<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.134720.2</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Research Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Study of anaemia in pregnancy and low birth weight in fluoride endemic area of Western Rajasthan: a cohort study</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 2; peer review: 3 approved]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Bhardwaj</surname>
                        <given-names>Pankaj</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Mantri</surname>
                        <given-names>Neha</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Joshi</surname>
                        <given-names>Nitin Kumar</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Suthar</surname>
                        <given-names>Praveen</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Funding Acquisition</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
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                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Sharma</surname>
                        <given-names>Praveen</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <xref ref-type="aff" rid="a3">3</xref>
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                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Purohit</surname>
                        <given-names>Purvi</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-8559-2911</uri>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Singh</surname>
                        <given-names>Pratibha</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Funding Acquisition</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <xref ref-type="aff" rid="a4">4</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Shekhar</surname>
                        <given-names>Shashank</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Funding Acquisition</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <xref ref-type="aff" rid="a4">4</xref>
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                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Khandelwal</surname>
                        <given-names>Shweta</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <xref ref-type="aff" rid="a5">5</xref>
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                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Dandabathula</surname>
                        <given-names>Giribabu</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-3245-8094</uri>
                    <xref ref-type="aff" rid="a5">5</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Raghav</surname>
                        <given-names>Pankaja Ravi</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Ramawat</surname>
                        <given-names>Nikky</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Funding Acquisition</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Jain</surname>
                        <given-names>Sanjeev</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Funding Acquisition</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <uri content-type="orcid">https://orcid.org/0009-0004-3523-4541</uri>
                    <xref ref-type="aff" rid="a6">6</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Patil</surname>
                        <given-names>Manoj</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-7126-5810</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a7">7</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Gaidhane</surname>
                        <given-names>Abhay</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a7">7</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Quazi Syed</surname>
                        <given-names>Zahiruddin</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-5875-8277</uri>
                    <xref ref-type="aff" rid="a7">7</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Saxena</surname>
                        <given-names>Deepak</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <xref ref-type="aff" rid="a8">8</xref>
                    <xref ref-type="aff" rid="a9">9</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>School of Public Health, All India Institute of Medical Sciences,, Jodhpur, Rajasthan, India</aff>
                <aff id="a2">
                    <label>2</label>Department of Community Medicine and Family Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India</aff>
                <aff id="a3">
                    <label>3</label>Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India</aff>
                <aff id="a4">
                    <label>4</label>Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India</aff>
                <aff id="a5">
                    <label>5</label>Regional Remote Sensing Centre &#x2013; West, National Remote Sensing Centre,, Indian Space Research Organization, Jodhpur, Rajasthan, India</aff>
                <aff id="a6">
                    <label>6</label>State Health Department, Government of Rajasthan, Jaipur, Rajasthan, India</aff>
                <aff id="a7">
                    <label>7</label>Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, India</aff>
                <aff id="a8">
                    <label>8</label>Adjunct Faculty, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, India</aff>
                <aff id="a9">
                    <label>9</label>Epidemiology, Indian Institute of Public Health, Gandhinagar, Gujarat, India</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:mpatil98dent@gmail.com">mpatil98dent@gmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>19</day>
                <month>3</month>
                <year>2024</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2023</year>
            </pub-date>
            <volume>12</volume>
            <elocation-id>602</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>14</day>
                    <month>3</month>
                    <year>2024</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Bhardwaj P et al.</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/12-602/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>Fluoride is a noxious element known to destroy gastrointestinal mucosa, leading to erythrocytes&#x2019; destruction and causing anaemia. The birth weight of newborn babies is a significant indicator of a child&#x2019;s vulnerability to the risk of childhood diseases and chances of existence.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>This prospective cohort study was planned to find linkages between fluorosis and the low-birth weight of newborn babies with anaemic mothers. Antenatal mothers until the 20th week of gestation were followed up till delivery in the Antenatal Clinic of a District Hospital in one of the known fluoride-endemic districts (Nagaur) and the other not-so-endemic district (Jodhpur) of Western Rajasthan.</p>
                </sec>
                <sec>
                    <title>Results</title>
                    <p>Around 19% of the newborn in Jodhpur and around 22% in Nagaur had low birth weight. Mean fluoride values in water samples were measured to be 0.57 (range from 0.0 to 2.7 PPM) in Jodhpur and 0.7 (range from 0.0 to 3.4 PPM) in Nagaur.</p>
                </sec>
                <sec>
                    <title>Conclusions</title>
                    <p>Thus, in fluoride endemic areas, other factors should be included besides iron and folic acid supplementation for improving anaemia in pregnant women. This calls for assessing the effectiveness of de-fluoridation activities along with the area&#x2019;s most common indigenous food practices.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Newborns</kwd>
                <kwd>Infant</kwd>
                <kwd>Pregnancy</kwd>
                <kwd>Fluoride</kwd>
                <kwd>Low Birth Weight</kwd>
                <kwd>Anemia</kwd>
                <kwd>Geographic Information System</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1">
                    <funding-source>Public Health Research Initiative- Department of Science and Technology</funding-source>
                </award-group>
                <funding-statement>The study was funded by the Public Health Research Initiative- Department of Science and Technology.  </funding-statement>
                <funding-statement>
                    <italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic>
                </funding-statement>
            </funding-group>
        </article-meta>
        <notes>
            <sec sec-type="version-changes">
                <label>Revised</label>
                <title>Amendments from Version 1</title>
                <p>The revised version of the manuscript incorporates the corrections suggested by the reviewers. The Introduction was expanded, incorporating evidences from recent bibliographic references. Evidences from related studies about impact of fluoride on adolescents, impact on elderly and impact on children were added. In results section, the mean hemoglobin percentage in pregnant women of study districts was added, and the text on mean weight of newborns in both districts was updated with comment on significant difference between the two districts. Text regarding confounding factors, sample size and bias of the other risk factors causing anemia was added as limitations at the end of discussion section. The related references were updated in the bibliography section.</p>
            </sec>
        </notes>
    </front>
    <body>
        <sec id="sec1" sec-type="intro">
            <title>Introduction</title>
            <p>Maternal and neonatal mortality rates are high in developing countries (
                <xref ref-type="bibr" rid="ref9">Beck 
                    <italic toggle="yes">et al.</italic>, 2010</xref>). Low birth weight (LBW) is the most common cause of neonatal mortality (
                <xref ref-type="bibr" rid="ref17">Eshete 
                    <italic toggle="yes">et al.</italic>, 2019</xref>; 
                <xref ref-type="bibr" rid="ref66">Watkins 
                    <italic toggle="yes">et al.</italic>, 2016</xref>). The birth weight of newborn babies is a significant indicator of a child&#x2019;s vulnerability to the risk of childhood diseases and chances of existence (
                <xref ref-type="bibr" rid="ref1">Alemayehu 
                    <italic toggle="yes">et al.</italic>, 2020</xref>). The World Health Organization (WHO) defines LBW as weight at birth less than 2.5 kg 
                <xref ref-type="bibr" rid="ref67">(&#x201c;WHA Global Nutrition Targets 2025: Low Birth Weight Policy Brief,&#x201d; n.d.</xref>). LBW may be an outcome of either preterm birth or retarded fetal growth. According to a report by UNICEF on &#x201c;The State of the World&#x2019;s Children 2008&#x201d;, the highest percentage (43%) of LBW babies below five years of age are in India. The prevalence of LBW babies in South Asia is 42%, in developed countries 35%, in developing countries 26% and 25% in the rest of the world (
                <xref ref-type="bibr" rid="ref55">Sachdev, 2001</xref>).</p>
            <p>India has been documenting the serious problem of anaemia in pregnancy, resulting in LBW (
                <xref ref-type="bibr" rid="ref7">Batista Filho 
                    <italic toggle="yes">et al.</italic>, 2008</xref>; 
                <xref ref-type="bibr" rid="ref51">Rahman 
                    <italic toggle="yes">et al.</italic>, 2016</xref>; 
                <xref ref-type="bibr" rid="ref68">World Health Organization, 2015</xref>). The Ministry of Health and Family Welfare, Government of India, has launched the National Anaemia Prophylaxis Programme to combat anaemia. The decision to supplement iron along with folic acid (iron (60 mg) and folic acid (500 &#x03bc;g) orally for 90 days) to pregnant women visiting antenatal clinics (ANCs) during the first and second trimesters was implemented across the country. The Indian Council of Medical Research (ICMR) conducted a study in 11 Indian states in 1985&#x2013;86 and discovered that the intervention did not affect pregnant women&#x2019;s haemoglobin (Hb) levels. This resulted in the power of iron and folic acid tablets increasing to 100 mg and 500 mg, respectively, which has been popular since 1992 (
                <xref ref-type="bibr" rid="ref60">Susheela 
                    <italic toggle="yes">et al.</italic>, 2010</xref>).</p>
            <p>However, despite so many interventions to reduce anaemia during pregnancy, expected results have not so far been obtained (
                <xref ref-type="bibr" rid="ref8">Beard, 2000</xref>; 
                <xref ref-type="bibr" rid="ref36">Kapil 
                    <italic toggle="yes">et al.</italic>, 2019</xref>; 
                <xref ref-type="bibr" rid="ref65">Vijayaraghavan 
                    <italic toggle="yes">et al.</italic>, 1990</xref>). So, another factor needs to be investigated, and one such factor is fluoride intake. Fluorosis, an underestimated and sometimes debilitating condition, is being caused by high levels of fluoride in food and contaminated groundwater in India (
                <xref ref-type="bibr" rid="ref69">Bello, 2020</xref>). Fluoride causes serious destruction to the gastrointestinal mucosa by destroying microvilli resulting in non-absorption of nutrients from the regimen (
                <xref ref-type="bibr" rid="ref11">Das 
                    <italic toggle="yes">et al.</italic>, 1994</xref>; 
                <xref ref-type="bibr" rid="ref15">Dhar and Bhatnagar, 2009</xref>; 
                <xref ref-type="bibr" rid="ref62">Susheela 
                    <italic toggle="yes">et al.</italic>, 2018</xref>). Fluoride also destroys erythrocytes, thereby contributing to the loss of Hb and anaemia. Interestingly, fluoride exposure during pregnancy was not significantly associated with fertility or birth outcomes, especially among women living in areas with levels of fluoride consistent with water fluoridation (
                <xref ref-type="bibr" rid="ref70">Goodman 
                    <italic toggle="yes">et al.</italic>, 2022</xref>). A study conducted in the United States discovered that greater water fluoride concentrations were connected with a 3.3-month earlier age of menarche (
                <xref ref-type="bibr" rid="ref71">Malin 
                    <italic toggle="yes">et al.</italic>, 2022</xref>). Further, cognitive skills in older adults living in high fluoride drinking water locations may be compromised (
                <xref ref-type="bibr" rid="ref72">Ren 
                    <italic toggle="yes">et al.</italic>, 2021</xref>). A south Indian researcher discovered that nutritional status has an effect on the severity of fluorosis, with impoverished children being more affected by severe fluorosis (
                <xref ref-type="bibr" rid="ref42">Mahantesha 
                    <italic toggle="yes">et al.</italic>, 2016</xref>).</p>
            <p>Fagin&#x2019;s report on fluoride&#x2019;s second thoughts in 2008 is a warning to all concerned, as he exposed the possibility of fluoride-producing diseases in the teeth, bone, brain, and thyroid gland (
                <xref ref-type="bibr" rid="ref18">Fagin, 2008</xref>). Fluoride is a toxic substance that promotes thyroid hormone production in children when it is consumed during the intrauterine growth stage (
                <xref ref-type="bibr" rid="ref22">Gedalia 
                    <italic toggle="yes">et al.</italic>, 1964</xref>). As a result, the thyroid hormone status of married women before conception may need to be examined (
                <xref ref-type="bibr" rid="ref43">McNeil and Stanford, n.d.</xref>).</p>
            <p>Fluorides, like other elements, have both good and harmful properties that have a substantial impact on public health. Even though it is noted that an optimal dose of 1mg of fluoride per litre in drinking water is beneficial for the prevention of tooth decay, extended exposure to greater concentrations can lead to adverse effects on teeth and bones (
                <xref ref-type="bibr" rid="ref5">Azami-Aghdash 
                    <italic toggle="yes">et al.</italic>, 2013</xref>). A concentration of fluoride higher than 2 mg/l causes teeth corrosion to increase with fluoride intake, and this can occur in conjunction with other conditions or might increase certain risks (
                <xref ref-type="bibr" rid="ref59">Susheela, 2013</xref>). In pregnant women, placental carriage of fluorides happens as early as the 19
                <sup>th</sup> week of gestation (
                <xref ref-type="bibr" rid="ref22">Gedalia 
                    <italic toggle="yes">et al.</italic>, 1964</xref>). Studies in a few countries have demonstrated linkages between dental fluorosis and LBW. Contrastingly, other literatures have found increased risk of adverse birth outcomes in areas where fluoride levels in drinking water are high (&gt; 1.5 mg/L) (
                <xref ref-type="bibr" rid="ref24">Goyal 
                    <italic toggle="yes">et al.</italic>, 2020</xref>). However, there is a paucity of studies in the Indian context correlating exposure to fluoride and anaemia in mothers resulting in LBW infants (
                <xref ref-type="bibr" rid="ref28">Guth 
                    <italic toggle="yes">et al.</italic>, 2020</xref>). Therefore, this study was planned to find linkages between fluorosis, anaemia during pregnancy, and outcome regarding the birth weight of newborn babies.</p>
        </sec>
        <sec id="sec2" sec-type="methods">
            <title>Methods</title>
            <sec id="sec3">
                <title>Study design and study setting</title>
                <p>For years, Rajasthan has been one of the worst states impacted by fluorosis, which has had a significant impact on the health of the native people. According to assessment from the State Institute of Health and Family Welfare in 2004, all 32 districts of Rajasthan are fluoride endemic areas. From June 2017 to September 2018, a prospective cohort study was done in the Antenatal Clinics of a District Hospital in one of the known fluoride-endemic areas (Nagaur) and one not so endemic district (Jodhpur) in Western Rajasthan. The reporting was done in accordance with the checklist for Strengthening the Reporting of Observational Studies (STROBE) (
                    <xref ref-type="bibr" rid="ref45">Patil, 2023a</xref>).</p>
            </sec>
            <sec id="sec4">
                <title>Study participants</title>
                <p>All pregnant women until the 20
                    <sup>th</sup> week of gestational age attending the ANC clinics from the month of initiation of study were enrolled for the study. Participants were enrolled based on consecutive sampling as they appear in the Out Patient Department (OPD). All participants were given a brief about the objectives of the study and were given choices for participation. After obtaining written informed consent, pregnant women were followed-up till delivery for estimating the birth weight of the new-born. For new-borns, consent was obtained from the parent/guardian. Those who did not give consent were excluded from the cohort. All participants were recruited till January 2018 and a ticket with the unique line listing number was provided to them with the dates for their next visit. The follow-up for each participant was conducted in the 2
                    <sup>nd</sup> and 3
                    <sup>rd</sup> trimester during their routine ANC check-up at the hospital and repeat test (Hb test, test for water fluoride and urinary fluoride) was conducted. To minimize loss-to-follow up, telephonic reminder was made to the enrolled participants and visits were planned according to their convenience. After the delivery, the new-born was enrolled and birth weight was estimated.</p>
            </sec>
            <sec id="sec5">
                <title>Ethical considerations</title>
                <p>Ethical approval was obtained from the Institutional Ethics Committee of All India Institute of Medical Sciences, Jodhpur, Rajasthan, India on 20
                    <sup>th</sup> August 2016 (Ref. AIIMS/RES (04)/2017/169). All participants were asked to sign an informed consent before enrolment.</p>
            </sec>
            <sec id="sec6">
                <title>Study tool</title>
                <p>Data was captured using a semi-structured questionnaire designed to elicit information on socio-demographic details, medical history, obstetric history, vital parameters, 24-hour diet, source of drinking water, medication history, dental and skeletal fluorosis (
                    <xref ref-type="bibr" rid="ref46">Patil, 2023b</xref>). The tool was pilot tested and refined based on experiences of the 20 participants who were not the part of the study. Appropriate measures were followed to minimize the potential bias at recruitment by providing a unique line listing number and concealing the identification details from the samples.</p>
                <p>
                    <bold>
                        <italic toggle="yes">Haemoglobin test</italic>
                    </bold> &#x2013; For the purpose of the study, we used the WHO Criteria for Anaemia as reference for pregnant women (pregnant women with haemoglobin levels less than 11.0 g/dl in the first and third trimesters and less than 10.5 g/dl in the second trimester were considered anaemic). A point-of-care instrument Haemocue 201+ analyser (Manufactured at HeamoCue AB, Sweden, Catalogue no. 1627013065)was used to measure haemoglobin level at three times &#x2013; at enrolment, second visit and third visit. The trained research staff were appointed for conducting the procedure. All necessary PPE measures were used to avoid contamination during the procedure. After cleaning the puncture site with an alcohol swab (middle finger or ring finger of the either hand), a prick was made on the fingertip using a needle and 2&#x2013;3 drops of blood was taken on a microcuvette and loaded in the analyser. The haemoglobin concentration was then displayed as a digital reading, in either g/dl or mmol/l in 15&#x2013;45 seconds. Results were also mentioned in the patient summary sheet and necessary consultation with obstetrician was arranged if any intervention was required.</p>
                <p>
                    <bold>
                        <italic toggle="yes">Fluoride test</italic>
                    </bold> (water and urine) &#x2013; All participants were given a 500 ml water sample sterile high-density polyethylene bottle for collecting water from their residence at the time of enrolment in the study. All enrolled participants were given a sterile polyethylene urine container (50 ml) by adding 0.2% Etheylenediaminetetraacetic acid (EDTA) [Orion Manufacturer] to bottles before collection during the visit to collect urine and were stored in refrigerator at 4&#x00b0;C to avoid bacterial contamination. The patient identification was concealed and all samples were labelled with unique line listing number and transported to the central laboratory for a test within 48 hours. Water and urine analysis was carried out in the biochemistry research unit, according to analytical protocol (
                    <ext-link ext-link-type="uri" xlink:href="https://www.cdc.gov/niosh/docs/2003-154/pdfs/8308.pdf">NIOSH Manual of Analytical Methods, P&amp;CAM, 2
                        <sup>ND</sup> edition</ext-link>) using a Thermo Scientific Fluoride Ion Meter Model (Ion 85 Analyser Radiometer Copenhagen). As per NIOSH manual, Fluoride Ion is used as an analyte in Ion selective electrode (ISE) technique. A Fluoride standard was prepared and an electrode (Orion, 9609BNWP) was setup using TISAB III (Orion, 940911). Then, the urine sample was diluted with equal volume of TISAB III. The electrode was dipped in the sample and the reading was displayed on the screen. The instrument was calibrated with the reference electrode each time before running samples in a batch of 60&#x2013;70 samples. The results were noted in the log book simultaneously with the line listing number.</p>
            </sec>
            <sec id="sec7">
                <title>Sample size calculation</title>
                <p>We enrolled a total of 1440 pregnant women in the study. As per the reference article by Aditya 
                    <italic toggle="yes">et al.</italic> (
                    <xref ref-type="bibr" rid="ref4">Arun 
                        <italic toggle="yes">et al.</italic>, 2022</xref>), Mean &#x00b1; Std. Deviation of Water Fluoride (mg/L) in Low-birth-weight population = 0.54 &#x00b1; 0.36.</p>
                <p>Using the formula for minimal Sample size required-
                    <disp-formula id="e1">
                        <mml:math display="block">
                            <mml:mspace width="0.25em"/>
                            <mml:mi>N</mml:mi>
                            <mml:mo>=</mml:mo>
                            <mml:mfrac>
                                <mml:mrow>
                                    <mml:msup>
                                        <mml:mfenced close=")" open="(">
                                            <mml:msub>
                                                <mml:mi>Z</mml:mi>
                                                <mml:mrow>
                                                    <mml:mn>1</mml:mn>
                                                    <mml:mo>&#x2212;</mml:mo>
                                                    <mml:mi>&#x03b1;</mml:mi>
                                                    <mml:mo>/</mml:mo>
                                                    <mml:mn>2</mml:mn>
                                                </mml:mrow>
                                            </mml:msub>
                                        </mml:mfenced>
                                        <mml:mn>2</mml:mn>
                                    </mml:msup>
                                    <mml:mspace width="0.25em"/>
                                    <mml:msup>
                                        <mml:mi>&#x03c3;</mml:mi>
                                        <mml:mn>2</mml:mn>
                                    </mml:msup>
                                </mml:mrow>
                                <mml:msup>
                                    <mml:mi>d</mml:mi>
                                    <mml:mn>2</mml:mn>
                                </mml:msup>
                            </mml:mfrac>
                        </mml:math>
                    </disp-formula>
                </p>
                <p>Where 
                    <inline-formula>
                        <mml:math display="inline">
                            <mml:msub>
                                <mml:mi>Z</mml:mi>
                                <mml:mi>&#x03b1;</mml:mi>
                            </mml:msub>
                        </mml:math>
                    </inline-formula> = 1.96 at a 5% level of significance
                    <disp-formula id="e2">
                        <mml:math display="block">
                            <mml:mtext>Estimated Error</mml:mtext>
                            <mml:mo>=</mml:mo>
                            <mml:mn>4</mml:mn>
                            <mml:mo>%</mml:mo>
                            <mml:mspace width="0.35em"/>
                            <mml:mtext>of Mean</mml:mtext>
                            <mml:mo>=</mml:mo>
                            <mml:msup>
                                <mml:mfenced close=")" open="(">
                                    <mml:mrow>
                                        <mml:mn>0.54</mml:mn>
                                        <mml:mo>/</mml:mo>
                                        <mml:mn>100</mml:mn>
                                    </mml:mrow>
                                </mml:mfenced>
                                <mml:mo>&#x2217;</mml:mo>
                            </mml:msup>
                            <mml:mn>5</mml:mn>
                            <mml:mo>=</mml:mo>
                            <mml:mn>0.02</mml:mn>
                            <mml:mo>.</mml:mo>
                        </mml:math>
                    </disp-formula>
                    <disp-formula id="e3">
                        <mml:math display="block">
                            <mml:mtext>Minimum sample size required was</mml:mtext>
                            <mml:mo>=</mml:mo>
                            <mml:mi>N</mml:mi>
                            <mml:mo>=</mml:mo>
                            <mml:mfrac>
                                <mml:mrow>
                                    <mml:msup>
                                        <mml:mfenced close=")" open="(">
                                            <mml:mn>1.96</mml:mn>
                                        </mml:mfenced>
                                        <mml:mn>2</mml:mn>
                                    </mml:msup>
                                    <mml:mspace width="0.25em"/>
                                    <mml:msup>
                                        <mml:mfenced close=")" open="(">
                                            <mml:mn>0.36</mml:mn>
                                        </mml:mfenced>
                                        <mml:mn>2</mml:mn>
                                    </mml:msup>
                                </mml:mrow>
                                <mml:msup>
                                    <mml:mfenced close=")" open="(">
                                        <mml:mn>0.0216</mml:mn>
                                    </mml:mfenced>
                                    <mml:mn>2</mml:mn>
                                </mml:msup>
                            </mml:mfrac>
                            <mml:mo>=</mml:mo>
                            <mml:mn>1245</mml:mn>
                        </mml:math>
                    </disp-formula>
                </p>
                <p>Assuming a non-response of 10% and rounding off, the sample size was finalized to 1440.</p>
            </sec>
            <sec id="sec8">
                <title>Statistical analysis</title>
                <p>Microsoft Excel v.2016 (Microsoft
                    <sup>&#x00ae;</sup> Corp., Redmond, WA) was used to enter the data and was analysed using Statistical Packages for Social Sciences (SPSS) version 23 software (IBM Corp., Armonk, NY). The descriptive statistics (mean, percentages) were used to summarize quantitative data for the study outcomes. Chi-squared test was used to examine the differences between categorical variables and was considered significant when a p-value &lt; 0.05. Further, to provide the graphical presentation, spatial mapping of the various variable like level of fluoride in urine and low birth weight in both the district was done using Arc GIS v 10.3(
                    <xref ref-type="bibr" rid="ref3">&#x201c;ArcGIS 10.3,&#x201d; n.d.</xref>).</p>
            </sec>
        </sec>
        <sec id="sec9" sec-type="results">
            <title>Results</title>
            <p>Out of 1440 pregnant women enrolled, 50% (n = 720) were from the Jodhpur district, and 50% (n = 720) were from the Nagaur district of western Rajasthan (
                <xref ref-type="bibr" rid="ref47">Patil, 2023c</xref>, 
                <xref ref-type="bibr" rid="ref48">2023d</xref>). The mean age of women from Jodhpur was 25.51 (&#x00b1;3.87) years, and from Nagaur were, 23.74 (&#x00b1;3.85) years. The mean Hb (gm%) level in pregnant women in the Jodhpur district was 10.4 gm% as compared to the Nagaur district (9.1 gm%).</p>
            <sec id="sec10">
                <title>Fluoride content in water and urine samples of Nagaur and Jodhpur district</title>
                <p>Mean fluoride values in water samples were measured to be 0.57 (range from 0.0 to 2.7 PPM) in Jodhpur and 0.7 (range from 0.0 to 3.4 PPM) in Nagaur.</p>
                <p>The excretion of mean fluoride value in the urine of pregnant females was found to be 1.4 (range from 0.0 to 12.7 mg/L) in the Jodhpur district and 2.2 (range from 0.1 to 13.7 mg/L) in the Nagaur district. 
                    <xref ref-type="fig" rid="f1">Figure 1</xref> depicts the urinary fluoride content in the Nagaur district, which is very high on the northern side. 
                    <xref ref-type="fig" rid="f2">Figure 2</xref> describes the level of urinary fluoride in the Jodhpur district. The level of fluoride is low compared to the Nagaur district. However, in the district&#x2019;s central and southern regions, fluoride content is high in the urine as it is excessive in the groundwater.</p>
                <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                    <label>Figure 1. </label>
                    <caption>
                        <title>Fluoride content in urine samples of Nagaur District.</title>
                    </caption>
                    <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/163694/34a2a1e8-2c95-4c68-af8f-9d58ef516d66_figure1.gif"/>
                </fig>
                <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                    <label>Figure 2. </label>
                    <caption>
                        <title>Fluoride content in urine samples of Jodhpur District.</title>
                    </caption>
                    <graphic id="gr2" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/163694/34a2a1e8-2c95-4c68-af8f-9d58ef516d66_figure2.gif"/>
                </fig>
            </sec>
            <sec id="sec11">
                <title>Low birth weight babies in Nagaur and Jodhpur district</title>
                <p>The mean weight of newborns from the Jodhpur district was 2.8 kg (&#x00b1;0.56), and from Nagaur was 2.8 kg (&#x00b1;0.44). Around 19% of the newborns in Jodhpur and around 22% in Nagaur had LBW. However, there was no significant difference in LBW babies in both districts (p=0.151).</p>
                <p>As shown in 
                    <xref ref-type="fig" rid="f3">Figure 3</xref>, the LBW babies were seen in the regions of the Nagaur district where the groundwater fluoride level was very high. However, in the context of the Jodhpur district (
                    <xref ref-type="fig" rid="f4">Figure 4</xref>), the low weight babies were seen in the southern part of the district where the groundwater fluoride level is low. This might be because of the consumption of the fluoride from the other sources.</p>
                <fig fig-type="figure" id="f3" orientation="portrait" position="float">
                    <label>Figure 3. </label>
                    <caption>
                        <title>Low birth weight babies in Nagaur District.</title>
                    </caption>
                    <graphic id="gr3" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/163694/34a2a1e8-2c95-4c68-af8f-9d58ef516d66_figure3.gif"/>
                </fig>
                <fig fig-type="figure" id="f4" orientation="portrait" position="float">
                    <label>Figure 4. </label>
                    <caption>
                        <title>Low birth weight babies in Jodhpur District.</title>
                    </caption>
                    <graphic id="gr4" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/163694/34a2a1e8-2c95-4c68-af8f-9d58ef516d66_figure4.gif"/>
                </fig>
                <p>
                    <xref ref-type="table" rid="T1">Table 1</xref> illustrates the socio-demographic characteristics of western Rajasthan&#x2019;s Jodhpur and Nagaur fluoride endemic districts. A significant association was seen between fluoride level in the water (p = 0.00001), Body Mass Index (BMI) (p = 0.00001), anaemia (p = 0.00001), and dental fluorosis (p = 0.00001). 
                    <xref ref-type="table" rid="T2">Table 2</xref> illustrate the association of fluoride in water with BMI, anaemia and dental fluorosis among pregnant women.</p>
                <table-wrap id="T1" orientation="portrait" position="float">
                    <label>Table 1. </label>
                    <caption>
                        <title>Socio-demographic and selected characteristics of fluoride endemic districts.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="2" valign="top">Characteristics</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Jodhpur District</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Nagaur District</th>
                            </tr>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">(n = 720)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">(n = 720)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Mean age of pregnant women (years)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">25.51 (+3.87)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">23.74 (+3.85)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Mean weight of pregnant women (kg)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">62.7 (+11.53)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">58.6 (+10)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Mean height of pregnant women (cm)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">161.9 (+7.52)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">163.1 (+3.62)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="middle">
                                    <bold>Socio-economic Status (%)</bold>
                                </td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Upper Class</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">17.92</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">0.69</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Upper Middle Class</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">55.56</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1.67</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Middle Class</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">12.22</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">4.87</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Lower Middle Class</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">11.94</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">87.64</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Lower Class</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">2.36</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">5.13</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="middle">
                                    <bold>Literacy Status (%)</bold>
                                </td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">No Schooling</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">2.8</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">16.4</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Primary Education</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">27.5</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">58.2</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Secondary Education</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">21.1</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">19.4</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Graduation</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">28.2</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">5.6</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Post-Graduation</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">20.4</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">0.4</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="middle">
                                    <bold>Birth Weight (%)</bold>
                                </td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Low Birth Weight</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">18.89</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">22.08</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Normal Birth Weight</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">81.11</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">77.92</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Water Fluoride (%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1.67</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">7.08</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Dental Fluorosis (%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">9.02</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">23.33</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Chin Test (%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">5.13</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">12.63</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Stretch Test (%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">4.16</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">7.5</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Muscular Weakness (%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">20.14</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">38.33</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Tingling Sensation (%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">12.5</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">37.22</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <table-wrap id="T2" orientation="portrait" position="float">
                    <label>Table 2. </label>
                    <caption>
                        <title>Association of fluoride level in water with BMI, anemia, and dental fluorosis.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="2" rowspan="2" valign="top">Variables</th>
                                <th align="left" colspan="3" rowspan="1" valign="top">Water Fluorosis</th>
                                <th align="left" colspan="1" rowspan="2" valign="top">&#x03c7;
                                    <sup>2</sup>
                                </th>
                                <th align="left" colspan="1" rowspan="2" valign="top">p-value</th>
                            </tr>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Optimal n = 939 (%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Sub-Optimal n = 438 (%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">High n = 63 (%)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="middle">Birth Weight</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Low</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">207</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">80</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">8</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">5.0727</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">0.07915</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Normal</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">732</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">358</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">55</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="middle">Anaemia</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">No</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">191</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">152</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">9</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">37.0404</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">0.00001</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Yes</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">748</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">286</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">54</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="middle">Dental Fluorosis</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">No</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">417</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">247</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">17</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">28.1077</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">0.00001</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Yes</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">522</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">191</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">46</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="middle">Chin Test</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">No</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">860</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">401</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">51</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">8.3956</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">0.01502</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Yes</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">79</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">37</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">12</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <p>A significant association was also seen in dental fluorosis with birth weight and anaemia (p &lt; 0.005). 
                    <xref ref-type="table" rid="T3">Table 3</xref> illustrates dental fluorosis&#x2019;s association with baby birth weight (normal birth weight (NBW) and LBW) and anaemia in pregnant women (no anaemia and anaemia). The excretion of fluoride in pregnant women&#x2019;s urine and haemoglobin (Hb) has a statistically significant linear relationship. The direction of the relationship is negative, i.e., urine fluorosis and haemoglobin of pregnant women are negatively correlated. This illustrated that greater fluoride excretion is associated with lower haemoglobin levels (r = -0.2).</p>
                <table-wrap id="T3" orientation="portrait" position="float">
                    <label>Table 3. </label>
                    <caption>
                        <title>Association of dental fluorosis across baby birth weight and anemia status of pregnant women.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="2" rowspan="2" valign="top">Variables</th>
                                <th align="left" colspan="2" rowspan="1" valign="top">Dental Fluorosis</th>
                                <th align="left" colspan="1" rowspan="2" valign="top">&#x03c7;
                                    <sup>2</sup>
                                </th>
                                <th align="left" colspan="1" rowspan="2" valign="top">p-value</th>
                                <th align="left" colspan="1" rowspan="2" valign="top">Relative Risk (RR)</th>
                            </tr>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">No Fluorosis (%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Fluorosis (%)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="middle">Birth Weight</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">Normal Birth Weight</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">754 (46.31)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">874 (53.69)</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">19.1402</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">0.000012</td>
                                <td align="left" colspan="1" rowspan="2" valign="top">RR = 1.63 (CI 1.27-2.09)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Low Birth Weight</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">46 (28.40)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">116 (71.60)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="middle">Anaemia</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">No anemia</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">160 (34.26)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">307 (65.74)</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">74.1282</td>
                                <td align="left" colspan="1" rowspan="2" valign="middle">0.00001</td>
                                <td align="left" colspan="1" rowspan="2" valign="top">RR = 2.2 (CI 1.84-2.63)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Anaemia</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">206 (15.57)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1117 (84.43)</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <p>Urine fluoride and newborn birth weight have a statistically significant linear relationship. The direction of the relationship is negative, i.e., urinary fluoride and newborn birth weight are negatively correlated. This illustrated that greater urinary fluoride is associated with birth weight (r = -0.01). The relative risk of LBW was 1.63 times more in high fluorosis cases. Also, the relative risk of anaemia among pregnant women was 2.2 times in high fluoride endemic areas.</p>
                <p>Tea consumption was high in both districts, whereas tobacco/areca nut usage was high (55%) in the Nagaur district. It was observed that the consumption of black salt was around 38% in Nagaur and 28% in the Jodhpur district, and the consumption of churan/chat masala was 35.4% and 14.6% in Nagaur and Jodhpur districts, respectively. 
                    <xref ref-type="table" rid="T4">Table 4</xref> shows drug consumption and selected dietary habits of pregnant women.</p>
                <table-wrap id="T4" orientation="portrait" position="float">
                    <label>Table 4. </label>
                    <caption>
                        <title>Drug consumption and dietary habits of pregnant women.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Drug/Diet</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Nagaur (%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Jodhpur (%)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="middle">
                                    <bold>Drugs</bold>
                                </td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Anti-Depressant</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">3 (0.4)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">28 (3.9)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Anti-infective</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">16 (2.2)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">37 (5.1)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">NSAID</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">23 (2.2)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">25 (3.5)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Corticosteroids</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1 (0.1)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">0 (0)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Sedative</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">6 (0.8)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">10 (1.4)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Ani-Emetic</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">159 (22.1)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">54 (7.5)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Other like thyroid, DM</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">51 (7.1)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">42 (5.8)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Iron tab</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">376 (52.2)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">134 (18.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Calcium</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">376 (52.2)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">131 (18.2)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Multivitamin</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">37 (5.1)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">48 (6.7)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Homoeopathic</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">13 (1.8)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">38 (5.3)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Ayurvedic</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">4 (0.6)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">38 (5.3)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Albendazole</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">6 (0.8)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">38 (5.3)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Vaccine T1 T2</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">376 (52.2)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">40 (5.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Others Drugs</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">28 (3.9)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">76 (10.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="middle">
                                    <bold>Diet</bold>
                                </td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Black salt</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">204 (28.3)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">273 (37.9)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Churan/chat masala</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">105 (14.6)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">255 (35.4)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Tea</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">495 (68.8)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">628 (87.2)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Coca/coffee</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">39 (5.4)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">40 (5.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Preserved fruits juice</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">48 (6.7)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">48 (6.7)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Meat/canned fish</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">38 (5.3)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">207 (28.7)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Dry fruits/walnut</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">61 (8.5)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">41 (5.7)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Tobacco/Arecanut</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">43 (6)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">396 (55.0)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Milk product</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">663 (92.1)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">305 (42.4)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Eggs</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">46 (6.4)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">90 (12.5)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Pickle</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">126 (17.5)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">199 (27.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Fruits</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">622 (86.4)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">427 (59.3)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Vegetable</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">699 (97.1)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">676 (93.9)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Cereals</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">704 (97.8)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">688 (95.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Pulses</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">688 (95.6)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">677 (94.0)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Fat oils</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">692 (96.1)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">667 (92.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Sugar/honey/Jaggery</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">664 (92.2)</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">77 (10.7)</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
            </sec>
        </sec>
        <sec id="sec12" sec-type="discussion">
            <title>Discussion</title>
            <p>Fluorosis is an endemic disease caused by excessive fluoride exposure from various sources. The element fluorine is a potent enzyme inhibitor, hormone disruptor, and neurotoxic, making it a double-edged sword that causes metabolic derangements (
                <xref ref-type="bibr" rid="ref62">Susheela 
                    <italic toggle="yes">et al.</italic>, 2018</xref>). Fluorosis manifests as a &#x201c;linked disease&#x201d; in many emerging Asian and African countries (
                <xref ref-type="bibr" rid="ref63">Susheela and Toteja, 2018</xref>). In many countries throughout the world, high fluoride level in groundwater has become one of the most serious health-related geo-environmental challenges (
                <xref ref-type="bibr" rid="ref13">Demelash 
                    <italic toggle="yes">et al.</italic>, 2019</xref>; 
                <xref ref-type="bibr" rid="ref34">Johnston and Strobel, 2020</xref>). Fluorosis has affected 21 Indian states. The Fluorosis Research and Rural Development Foundation, India survey mentioned that more than 66 million people are affected by fluorosis in India (
                <xref ref-type="bibr" rid="ref63">Susheela and Toteja, 2018</xref>).</p>
            <p>The Bureau of Indian Standards (BIS) has specified fluoride levels in drinking water standards, with a maximum acceptable limit of 1.0 mg/L and an allowed limit of 1.5 mg/L in the absence of an alternative source (
                <xref ref-type="bibr" rid="ref49">Puri and Kumar, 2012</xref>). In some areas of Rajasthan, people drink water with fluoride levels as high as 24 mg/l (
                <xref ref-type="bibr" rid="ref14">Department of Environmental Engineering, Delhi Technological University, India 
                    <italic toggle="yes">et al.</italic>, 2014</xref>). In our study, mean fluoride values in water samples were 0.57 (range 0.0 to 2.7 PPM) in Jodhpur and 0.7 (range 0.0 to 3.4 PPM) in Nagaur. A similar study was carried out in the Punjab district of Faridkot, India. The mean value of water fluoride content was discovered to be 2.4 mg/L, which was higher than the allowable limits (
                <xref ref-type="bibr" rid="ref24">Goyal 
                    <italic toggle="yes">et al.</italic>, 2020</xref>). Hence, this region&#x2019;s exposure to fluoride from drinking water is of considerable concern.</p>
            <p>Even though low haemoglobin levels are frequently detected in clinical settings, they are rarely considered significant unless they are associated with the detection of a serious blood disease (
                <xref ref-type="bibr" rid="ref2">Andezhath, 2010</xref>). The greatest concern is that ingesting fluoride (F&#x2013;) through water and food could result in serious health consequences. In our research, there was a significant association between fluoride levels in water and anaemia (p = 0.00001). The highly detrimental F&#x2013; damages the lining of the intestine and hinders nutritional absorption when it enters the body through food, water, habit-forming chemicals, and dental products (
                <xref ref-type="bibr" rid="ref62">Susheela 
                    <italic toggle="yes">et al.</italic>, 2018</xref>). Hillman 
                <italic toggle="yes">et al.</italic> discovered anaemia in cattle due to F&#x2013; poisoning and fluorosis in the 1980s (
                <xref ref-type="bibr" rid="ref32">Hillman 
                    <italic toggle="yes">et al.</italic>, 1979</xref>). Excessive fluoride may affect brain development 
                <italic toggle="yes">in utero</italic> and lead to neurological abnormalities, according to evidence from several human studies (
                <xref ref-type="bibr" rid="ref27">Grandjean, 2019</xref>; 
                <xref ref-type="bibr" rid="ref28">Guth 
                    <italic toggle="yes">et al.</italic>, 2020</xref>).</p>
            <p>Urine has long been recognized as a significant diagnostic marker for fluoride intake since it is widely used, relatively easy to collect, and non-invasive (
                <xref ref-type="bibr" rid="ref33">Idowu 
                    <italic toggle="yes">et al.</italic>, 2019</xref>; 
                <xref ref-type="bibr" rid="ref39">Kumar 
                    <italic toggle="yes">et al.</italic>, 2017</xref>). In our study, pregnant women&#x2019;s excretion of fluoride in urine and haemoglobin (Hb) had a statistically significant linear relationship. The direction of the relationship is negative, i.e., urine fluorosis and haemoglobin of pregnant women are negatively correlated. Excretion of mean fluoride value in the urine of pregnant females was found to be 1.4 (range from 0.0 to 12.7 mg/L) in Jodhpur district and 2.2 (range from 0.1 to 13.7 mg/L) in Nagaur district. Females with high urine fluoride levels have a higher risk of pregnancy difficulties such as anaemia and poor fetal outcomes, according to a study by 
                <xref ref-type="bibr" rid="ref24">Goyal 
                    <italic toggle="yes">et al.</italic> (2020)</xref>.</p>
            <p>According to AK Susheela 
                <italic toggle="yes">et al.</italic>, drinking fluoride-free water and eating fluoride-free food reduced preterm births by four times and LBW babies by two times (
                <xref ref-type="bibr" rid="ref63">Susheela and Toteja, 2018</xref>).</p>
            <p>In industrialized and developing countries, the burden of poor pregnancy outcomes (APOs), including preterm deliveries and LBWs, is significant (
                <xref ref-type="bibr" rid="ref10">Blencowe 
                    <italic toggle="yes">et al.</italic>, 2012</xref>; 
                <xref ref-type="bibr" rid="ref40">Lawn 
                    <italic toggle="yes">et al.</italic>, 2006</xref>; 
                <xref ref-type="bibr" rid="ref41">Lee 
                    <italic toggle="yes">et al.</italic>, 2013</xref>). Maternal anaemia was identified as a risk factor for low/insufficient birth weight in the current study, which was similar to findings from a prior study by 
                <xref ref-type="bibr" rid="ref52">R&#x00e4;is&#x00e4;nen 
                    <italic toggle="yes">et al.</italic> (2014)</xref>.</p>
            <p>In India, anaemia affects 55.3 per cent of women aged 15 to 49 years old (
                <xref ref-type="bibr" rid="ref38">Kulasekaran, 2012</xref>). Anaemia in women during pregnancy has been linked to underweight children. Mother and newborn mortality rates in India are still high due to poor haemoglobin levels. Furthermore, anaemic mothers frequently give birth to low-weight newborns (as low as 1.0 to 1.2 kg), with a high risk of developmental problems or infant mortality later in life (
                <xref ref-type="bibr" rid="ref2">Andezhath, 2010</xref>).</p>
            <p>A study finds that maternal haemoglobin (Hb &gt; 110 g/l) protects against the risk of APOs in the study populations, which is consistent with prior findings (
                <xref ref-type="bibr" rid="ref44">Padhi 
                    <italic toggle="yes">et al.</italic>, 2015</xref>). With anaemia in the first or second trimester, a recent systematic review and meta-analysis found a significantly greater risk of LBW (OR: 1.29; 95 percent CI: 1.09&#x2013;1.53) and preterm birth (OR: 1.21; 95 percent CI: 1.13&#x2013;1.30) (
                <xref ref-type="bibr" rid="ref29">Haider 
                    <italic toggle="yes">et al.</italic>, 2013</xref>). Preterm delivery and LBW are important factors of child survival, impairments, stunting, and long-term negative implications for the beginning of non-communicable diseases later in life. They necessitate effective public health interventions.</p>
            <p>The precise mechanism that links maternal anaemia to LBW remains unknown. Only a few prospective cohort studies have examined the relationships between maternal anaemia and LBW (
                <xref ref-type="bibr" rid="ref6">Bakacak 
                    <italic toggle="yes">et al.</italic>, 2015</xref>; 
                <xref ref-type="bibr" rid="ref20">Figueiredo 
                    <italic toggle="yes">et al.</italic>, 2019</xref>; 
                <xref ref-type="bibr" rid="ref29">Haider 
                    <italic toggle="yes">et al.</italic>, 2013</xref>; 
                <xref ref-type="bibr" rid="ref51">Rahman 
                    <italic toggle="yes">et al.</italic>, 2016</xref>). In Jodhpur, around 19 percent of newborns had a LBW, whereas, in Nagaur, nearly 22 percent had a LBW. According to another study, the relative risk of giving birth to LBW babies is 37% among the women with low haemoglobin levels (
                <xref ref-type="bibr" rid="ref20">Figueiredo 
                    <italic toggle="yes">et al.</italic>, 2019</xref>).</p>
            <p>According to other studies, factors such as diet, excessive tea consumption, other associated nutritional deficiencies, and the use of fluoridated toothpaste have also been linked to the occurrence and severity of fluorosis (
                <xref ref-type="bibr" rid="ref53">Rao and Mahajan, 1990</xref>; 
                <xref ref-type="bibr" rid="ref56">Shruthi and Anil, 2018</xref>). The participants in our study mostly ate locally grown vegetarian cuisine daily and had a history of drinking tea and brushing their teeth with fluoridated toothpaste. In our study, there was a significant link between dental fluorosis and birth weight and anaemia (p &gt; 0.005). Tea consumption was high in both districts, whereas tobacco/areca nut consumption was high (55 percent) in Nagaur. Black salt consumption was found to be roughly 38 percent in Nagaur and 28 percent in the Jodhpur district. In comparison, churan/chat masala consumption was found to be 35.4 percent and 14.6 percent in Nagaur and Jodhpur districts, respectively.</p>
            <p>The prevalence of dental fluorosis was 13.17 percent in the study by Shruti 
                <italic toggle="yes">et al.</italic>, with a high fluoride level (
                <xref ref-type="bibr" rid="ref56">Shruthi and Anil, 2018</xref>). Fluorosis is irreversible and only develops when the enamel is growing and exposed to fluoride. Fluoridated enamel is porous (objectionable secondary staining is common) and opaque rather than being a standard creamy-white translucent tint (
                <xref ref-type="bibr" rid="ref42">Mahantesha 
                    <italic toggle="yes">et al.</italic>, 2016</xref>). In our study, a significant association was also seen between fluoride level in the water and dental fluorosis (p = 0.00001) and baby birth weight (p = 0.000012) and LBW (p = 0.00001).</p>
            <p>The presence of more than eight ppm of fluoride in drinking water over a long period might cause skeletal fluorosis (
                <xref ref-type="bibr" rid="ref54">Reddy, 2009</xref>). As a result of the persistent poisoning, bone density gradually increases, and joints stiffen and become painful.</p>
            <p>Susheela 
                <italic toggle="yes">et al.</italic>&#x2019;s findings support the notion that iron and folic acid at current levels is beneficial in reducing the risk of LBW when combined with proper nutrition and reduced F&#x2013; intake (
                <xref ref-type="bibr" rid="ref60">Susheela 
                    <italic toggle="yes">et al.</italic>, 2010</xref>). According to one study, efforts to raise Hb by iron and folic acid (IFA) supplementation through State and National Programs have yet to provide desired outcomes (
                <xref ref-type="bibr" rid="ref8">Beard, 2000</xref>; 
                <xref ref-type="bibr" rid="ref65">Vijayaraghavan 
                    <italic toggle="yes">et al.</italic>, 1990</xref>).</p>
            <p>The use of validated instruments by previously trained researchers strengthens the internal validity of this study. A large sample size aids in extrapolating study findings to populations with similar geographies. In terms of the study&#x2019;s weaknesses, the self-reported data may have resulted in calibration bias. Also, sample losses owing to missed follow-ups are a possibility.</p>
            <p>With a coordinated effort to implement proper rules and procedures, the Millennium Development Goal of reducing early childhood mortality by two-thirds will be easier to attain (
                <xref ref-type="bibr" rid="ref23">&#x201c;Global nutrition targets 2025,&#x201d; n.d.</xref>). Here are a few solutions that have been presented for better implementation.</p>
            <p>In every policy design, Behavior Change Communication (BCC) intervention must be an integral part that focuses on each stakeholder (
                <xref ref-type="bibr" rid="ref64">&#x201c;tagged_ifas_participants_manual_for_healthcare_providers.pdf,&#x201d; n.d.</xref>). Information, Education and Communication (IEC) initiatives must include educating pregnant women on the role of Hb and LBW children, as well as the do&#x2019;s and don&#x2019;ts of fluoride consumption in the diet, through media campaigns (
                <xref ref-type="bibr" rid="ref16">&#x201c;Dietary guidelines for Indians.pdf,&#x201d; n.d.</xref>; 
                <xref ref-type="bibr" rid="ref24">Goyal 
                    <italic toggle="yes">et al.</italic>, 2020</xref>). The role of dieticians and nutritionists must be escalated during ANC visits (
                <xref ref-type="bibr" rid="ref37">Kominiarek and Rajan, 2016</xref>). Ascorbic acid improves iron absorption (vitamin C). This should be stressed throughout the diet counselling session, which includes a list of vital fruits and vegetables that contain vitamin C that should be consumed (
                <xref ref-type="bibr" rid="ref31">Hallberg 
                    <italic toggle="yes">et al.</italic>, 1989</xref>). Iron absorption is inhibited by phytic acid/sodium phytate in brown bread and tannin in tea. The resulting vitamin B12 and folic acid deficiencies may cause anaemias. Vitamin B12 is not often investigated but is a key constituent for Hb biosynthesis (
                <xref ref-type="bibr" rid="ref12">Delimont 
                    <italic toggle="yes">et al.</italic>, 2017</xref>). Withdrawing fluoride from the diet may have repaired damage to the gastrointestinal mucosa/loss of microvilli, allowing nutrients to be absorbed, resulting in increased Hb and correction of anaemias (
                <xref ref-type="bibr" rid="ref34">Johnston and Strobel, 2020</xref>). This calls for assessing the effectiveness of de-fluoridation activities along with the most common food practices leading to high fluoride levels in pregnant women.</p>
            <p>Fluoride assessment in body fluids is the primary criterion to know how much fluoride has entered the body. Regular monitoring of 24-hour urine samples and plasma samples may help researchers better understand the harmful effects of excessive fluoride exposure during pregnancy (
                <xref ref-type="bibr" rid="ref24">Goyal 
                    <italic toggle="yes">et al.</italic>, 2020</xref>). Thus, a monitoring and impact assessment must be part and parcel of future research related to fluoride and anaemic mothers.</p>
            <p>In addressing the potential impact of various risk factors on anemia in the studied areas, we took measures to mitigate bias. Although the mean fluoride levels were not exceptionally high in both regions, we conducted a comprehensive assessment of potential contributors to anemia in pregnant women. This included the measurement of fluoride levels in both water and urine, acknowledging their role as risk factors.</p>
            <p>Additionally, we investigated other factors such as dietary patterns, excessive consumption of tea and black salt, concomitant nutritional deficiencies, and the use of fluoridated toothpaste. We also considered the source of drinking water, aiming to account for any potential effects on hemoglobin levels in pregnant women. The study also delved into iron and folate supplementation for pregnant women, exploring the correlation with the risk of low birth weight in both districts. However, there was no significant difference in LBW babies in both districts (p=0.151).</p>
            <p>It&#x2019;s important to note that the study has its limitations, and while we addressed a few risk factors, there may be several area-specific that were not thoroughly explored, contributing to potential bias in the assessment of anemia in pregnant women.</p>
        </sec>
        <sec id="sec15">
            <title>Limitations</title>
            <p>The confounding factors included the exposure time to fluoride in drinking water, as well as the exposure to fluoride in age, obstetric history, supplements, diet, air, medication, water sources, cooking vessel etc. To minimize the confounding factors, we could have applied regression analysis to observe the impact of fluoride on maternal and child health. Further, recruitment of larger sample participants in a randomized manner could help in getting the impact of Fluoride on pregnant women.</p>
            <p>However, we have collected data on variables like 24-hr diet recall to track nutrition aspects, past obstetric history, cooking vessels, medication, water sources and other co-morbidity like blood pressure, diabetes etc. But we could not perform analysis to see their impact on MCH in fluoride endemic areas.</p>
        </sec>
        <sec id="sec13" sec-type="conclusion">
            <title>Conclusion</title>
            <p>In fluoride endemic areas, other factors should be included besides iron and folic acid supplementation for improving anaemia in pregnant women. This calls for an assessment of the effectiveness of de-fluoridation activities along with the most common indigenous food practices in the area. In India, the role of fluoride as a risk factor in pregnancy has not been documented. In this context, the current study has added a significant body of knowledge that can be further scaled up.</p>
        </sec>
    </body>
    <back>
        <sec id="sec17" sec-type="data-availability">
            <title>Data availability</title>
            <sec id="sec18">
                <title>Underlying data</title>
                <p>Zenodo: Jodhpur_Data File_anemia in Pregnancy_CSV.csv (Data of study participants from Jodhpur district on sociodemographic details, dietary habits and food consumption, addictions, drugs and medications consumed, drinking water sources, diseases, health parameters and anthropometric details) 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.7928263">https://doi.org/10.5281/zenodo.7928263</ext-link> (
                    <xref ref-type="bibr" rid="ref47">Patil, 2023c</xref>).</p>
                <p>Zenodo: Nagaur_Data File_Anemia in Pregnancy_CSV.csv (Data of study participants from Nagaur district on sociodemographic details, dietary habits and food consumption, addictions, drugs and medications consumed, drinking water sources, diseases, health parameters and anthropometric details) 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.7928230">https://doi.org/10.5281/zenodo.7928230</ext-link> (
                    <xref ref-type="bibr" rid="ref48">Patil, 2023d</xref>).</p>
                <p>Zenodo: Fluoride_studyQuestionnaire.pdf (Copy of blank Questionnaire used for data collection) 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.7962221">https://doi.org/10.5281/zenodo.7962221</ext-link> (
                    <xref ref-type="bibr" rid="ref46">Patil, 2023b</xref>).</p>
            </sec>
            <sec id="sec19">
                <title>Reporting guidelines</title>
                <p>Zenodo: STROBE checklist for &#x2018;Study of anaemia in pregnancy and low birth weight in fluoride endemic area of Western Rajasthan: A cohort study&#x2019;. 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.7780105">https://doi.org/10.5281/zenodo.7780105</ext-link> (
                    <xref ref-type="bibr" rid="ref45">Patil, 2023a</xref>).</p>
                <p>Data are available under the terms of the 
                    <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link> (CC-BY 4.0).</p>
            </sec>
        </sec>
        <sec id="sec14">
            <title>Software availability</title>
            <p>ArcGIS is a licensed online geographic information system software developed and maintained by Esri ( 
                <ext-link ext-link-type="uri" xlink:href="https://www.arcgis.com/index.html">https://www.arcgis.com/index.html</ext-link>). The alternative software with the similar function is QGIS (QGIS is a free and open-source cross-platform desktop geographic information system application that supports viewing, editing, printing, and analysis of geospatial data. It can be downloaded through the link: 
                <ext-link ext-link-type="uri" xlink:href="https://qgis.org/">https://qgis.org/</ext-link>).</p>
        </sec>
        <ack>
            <title>Acknowledgements</title>
            <p>We acknowledge the support of study participants and all those who contributed directly and indirectly.</p>
        </ack>
        <ref-list>
            <title>References</title>
            <ref id="ref1">
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Alemayehu</surname>
                            <given-names>GM</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Chernet</surname>
                            <given-names>AG</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Dumga</surname>
                            <given-names>KT</given-names>
                        </name>
</person-group>:
                    <article-title>Determinants of Child Size at Birth and Associated Maternal Factor in Gurage Zone.</article-title>
                    <year>2020</year>;<volume>21</volume>:<fpage>8</fpage>.</mixed-citation>
            </ref>
            <ref id="ref2">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Andezhath</surname>
                            <given-names>S</given-names>
                        </name>
</person-group>:
                    <article-title>Anemia in pregnancy: An easily rectifiable problem.</article-title>
                    <source>

                        <italic toggle="yes">Fluoride.</italic>
</source>
                    <year>2010</year>;<volume>43</volume>:<fpage>104</fpage>&#x2013;<lpage>107</lpage>.</mixed-citation>
            </ref>
            <ref id="ref3">
                <mixed-citation publication-type="other">
                    <collab>ArcGIS 10.3</collab>:
                    <article-title>The Next Generation of GIS Is Here.</article-title>
                    <year>n.d.</year>(accessed 5.25.23). ArcGIS Blog.
                    <ext-link ext-link-type="uri" xlink:href="https://www.esri.com/arcgis-blog/products/3d-gis/3d-gis/arcgis-10-3-the-next-generation-of-gis-is-here/">Reference Source</ext-link>
                </mixed-citation>
            </ref>
            <ref id="ref4">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Arun</surname>
                            <given-names>AK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Rustveld</surname>
                            <given-names>L</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Sunny</surname>
                            <given-names>A</given-names>
                        </name>
</person-group>:
                    <article-title>Association between Water Fluoride Levels and Low Birth Weight: National Health and Nutrition Examination Survey (NHANES) 2013&#x2013;2016.</article-title>
                    <source>

                        <italic toggle="yes">IJERPH.</italic>
</source>
                    <year>2022</year>;<volume>19</volume>:<fpage>8956</fpage>.
                    <pub-id pub-id-type="pmid">35897326</pub-id>
                    <pub-id pub-id-type="doi">10.3390/ijerph19158956</pub-id>
                    <pub-id pub-id-type="pmcid">PMC9332356</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref5">
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Azami-Aghdash</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Ghojazadeh</surname>
                            <given-names>M</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Azar</surname>
                            <given-names>FP</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Fluoride Concentration of Drinking Waters and Prevalence of Fluorosis in Iran: A Systematic Review.</article-title>
                    <year>2013</year>;<volume>7</volume>:<fpage>7</fpage>.</mixed-citation>
            </ref>
            <ref id="ref6">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Bakacak</surname>
                            <given-names>M</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Avci</surname>
                            <given-names>F</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Ercan</surname>
                            <given-names>O</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>The effect of maternal hemoglobin concentration on fetal birth weight according to trimesters.</article-title>
                    <source>

                        <italic toggle="yes">J. Matern. Fetal Neonatal Med.</italic>
</source>
                    <year>2015</year>;<volume>28</volume>:<fpage>2106</fpage>&#x2013;<lpage>2110</lpage>.
                    <pub-id pub-id-type="pmid">25338012</pub-id>
                    <pub-id pub-id-type="doi">10.3109/14767058.2014.979149</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref7">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Batista Filho</surname>
                            <given-names>M</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Souza</surname>
                            <given-names>AI</given-names>
                            <prefix>de</prefix>
                        </name>

                        <name name-style="western">
                            <surname>Bresani</surname>
                            <given-names>CC</given-names>
                        </name>
</person-group>:
                    <article-title>Anemia como problema de sa&#x00fa;de p&#x00fa;blica: uma realidade atual.</article-title>
                    <source>

                        <italic toggle="yes">Ci&#x00ea;nc. Sa&#x00fa;de Coletiva.</italic>
</source>
                    <year>2008</year>;<volume>13</volume>:<fpage>1917</fpage>&#x2013;<lpage>1922</lpage>.
                    <pub-id pub-id-type="pmid">18833369</pub-id>
                    <pub-id pub-id-type="doi">10.1590/S1413-81232008000600027</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref8">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Beard</surname>
                            <given-names>JL</given-names>
                        </name>
</person-group>:
                    <article-title>Effectiveness and strategies of iron supplementation during pregnancy.</article-title>
                    <source>

                        <italic toggle="yes">Am. J. Clin. Nutr.</italic>
</source>
                    <year>2000</year>;<volume>71</volume>:<fpage>1288S</fpage>&#x2013;<lpage>1294S</lpage>.
                    <pub-id pub-id-type="doi">10.1093/ajcn/71.5.1288s</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref9">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Beck</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Wojdyla</surname>
                            <given-names>D</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Say</surname>
                            <given-names>L</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity.</article-title>
                    <source>

                        <italic toggle="yes">Bull. World Health Org.</italic>
</source>
                    <year>2010</year>;<volume>88</volume>:<fpage>31</fpage>&#x2013;<lpage>38</lpage>.
                    <pub-id pub-id-type="pmid">20428351</pub-id>
                    <pub-id pub-id-type="doi">10.2471/BLT.08.062554</pub-id>
                    <pub-id pub-id-type="pmcid">PMC2802437</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref69">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Bello</surname>
                            <given-names>LD</given-names>
                        </name>
</person-group>:
                    <article-title>Fluorosis: an ongoing challenge for India.</article-title>
                    <source>Lancet Planet. Health.</source>
                    <year>2020</year>;<volume>4</volume>:<fpage>e94</fpage>&#x2013;<lpage>e95</lpage>.
                    <pub-id pub-id-type="doi">10.1016/S2542-5196(20)30060-7</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref10">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Blencowe</surname>
                            <given-names>H</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Cousens</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Oestergaard</surname>
                            <given-names>MZ</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications.</article-title>
                    <source>

                        <italic toggle="yes">Lancet.</italic>
</source>
                    <year>2012</year>;<volume>379</volume>:<fpage>2162</fpage>&#x2013;<lpage>2172</lpage>.
                    <pub-id pub-id-type="pmid">22682464</pub-id>
                    <pub-id pub-id-type="doi">10.1016/S0140-6736(12)60820-4</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref11">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Das</surname>
                            <given-names>TK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Susheela</surname>
                            <given-names>AK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Gupta</surname>
                            <given-names>IP</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Toxic Effects of Chronic Fluoride Ingestion on the Upper Gastrointestinal Tract.</article-title>
                    <source>

                        <italic toggle="yes">J. Clin. Gastroenterol.</italic>
</source>
                    <year>1994</year>;<volume>18</volume>:<fpage>194</fpage>&#x2013;<lpage>199</lpage>.
                    <pub-id pub-id-type="pmid">8034913</pub-id>
                    <pub-id pub-id-type="doi">10.1097/00004836-199404000-00004</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref12">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Delimont</surname>
                            <given-names>NM</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Haub</surname>
                            <given-names>MD</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Lindshield</surname>
                            <given-names>BL</given-names>
                        </name>
</person-group>:
                    <article-title>The Impact of Tannin Consumption on Iron Bioavailability and Status: A Narrative Review.</article-title>
                    <source>

                        <italic toggle="yes">Curr. Dev. Nutr.</italic>
</source>
                    <year>2017</year>;<volume>1</volume>:<fpage>1</fpage>&#x2013;<lpage>12</lpage>.
                    <pub-id pub-id-type="pmid">29955693</pub-id>
                    <pub-id pub-id-type="doi">10.3945/cdn.116.000042</pub-id>
                    <pub-id pub-id-type="pmcid">PMC5998341</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref13">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Demelash</surname>
                            <given-names>H</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Beyene</surname>
                            <given-names>A</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Abebe</surname>
                            <given-names>Z</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Fluoride concentration in ground water and prevalence of dental fluorosis in Ethiopian Rift Valley: systematic review and meta-analysis.</article-title>
                    <source>

                        <italic toggle="yes">BMC Public Health.</italic>
</source>
                    <year>2019</year>;<volume>19</volume>:<fpage>1298</fpage>.
                    <pub-id pub-id-type="pmid">31619212</pub-id>
                    <pub-id pub-id-type="doi">10.1186/s12889-019-7646-8</pub-id>
                    <pub-id pub-id-type="pmcid">PMC6794803</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref14">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <collab>Department of Environmental Engineering, Delhi Technological University, India</collab>:

                        <name name-style="western">
                            <surname>Jain</surname>
                            <given-names>A</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Singh</surname>
                            <given-names>S</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Prevalence of Fluoride in Ground Water in Rajasthan State: Extent, Contamination Levels And Mitigation.</article-title>
                    <source>

                        <italic toggle="yes">WPT.</italic>
</source>
                    <year>2014</year>;<volume>2014</volume>:<fpage>50</fpage>&#x2013;<lpage>57</lpage>.
                    <pub-id pub-id-type="doi">10.15764/WPT.2014.02006</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref15">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Dhar</surname>
                            <given-names>V</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Bhatnagar</surname>
                            <given-names>M</given-names>
                        </name>
</person-group>:
                    <article-title>Physiology and toxicity of fluoride.</article-title>
                    <source>

                        <italic toggle="yes">Indian J. Dent. Res.</italic>
</source>
                    <year>2009</year>;<volume>20</volume>:<fpage>350</fpage>.
                    <pub-id pub-id-type="doi">10.4103/0970-9290.57379</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref16">
                <mixed-citation publication-type="other">
                    <collab>Dietary guidelines for Indians.pdf</collab>:<year>n.d.</year>
                </mixed-citation>
            </ref>
            <ref id="ref17">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Eshete</surname>
                            <given-names>A</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Alemu</surname>
                            <given-names>A</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Zerfu</surname>
                            <given-names>TA</given-names>
                        </name>
</person-group>:
                    <article-title>Magnitude and Risk of Dying among Low Birth Weight Neonates in Rural Ethiopia: 
                        <italic toggle="yes">A Community-Based Cross-Sectional Study.</italic>
                    </article-title>
                    <source>

                        <italic toggle="yes">Int. J. Pediatr.</italic>
</source>
                    <year>2019</year>;<volume>2019</volume>:<fpage>1</fpage>&#x2013;<lpage>8</lpage>.
                    <pub-id pub-id-type="pmid">31223314</pub-id>
                    <pub-id pub-id-type="doi">10.1155/2019/9034952</pub-id>
                    <pub-id pub-id-type="pmcid">PMC6541952</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref18">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Fagin</surname>
                            <given-names>D</given-names>
                        </name>
</person-group>:
                    <article-title>Second thoughts about fluoride.</article-title>
                    <source>

                        <italic toggle="yes">Sci. Am.</italic>
</source>
                    <year>2008</year>;<volume>298</volume>:<fpage>74</fpage>&#x2013;<lpage>81</lpage>.
                    <pub-id pub-id-type="pmid">18225698</pub-id>
                    <pub-id pub-id-type="doi">10.1038/scientificamerican0108-74</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref20">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Figueiredo</surname>
                            <given-names>ACMG</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Gomes-Filho</surname>
                            <given-names>IS</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Batista</surname>
                            <given-names>JET</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Maternal anemia and birth weight: A prospective cohort study.</article-title>
                    <source>

                        <italic toggle="yes">PLoS One.</italic>
</source>
                    <year>2019</year>;<volume>14</volume>:<fpage>e0212817</fpage>.
                    <pub-id pub-id-type="pmid">30884493</pub-id>
                    <pub-id pub-id-type="doi">10.1371/journal.pone.0212817</pub-id>
                    <pub-id pub-id-type="pmcid">PMC6422668</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref22">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Gedalia</surname>
                            <given-names>I</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Brzezinski</surname>
                            <given-names>A</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Zukerman</surname>
                            <given-names>H</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Placental Transfer of Fluoride in the Human Fetus at Low and High F-Intake.</article-title>
                    <source>

                        <italic toggle="yes">J. Dent. Res.</italic>
</source>
                    <year>1964</year>;<volume>43</volume>:<fpage>669</fpage>&#x2013;<lpage>671</lpage>.
                    <pub-id pub-id-type="pmid">14197051</pub-id>
                    <pub-id pub-id-type="doi">10.1177/00220345640430050801</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref70">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Goodman</surname>
                            <given-names>C</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Hall</surname>
                            <given-names>M</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Green</surname>
                            <given-names>R</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Maternal fluoride exposure, fertility and birth outcomes: The MIREC cohort.</article-title>
                    <source>Environ. Adv.</source>
                    <year>2022</year>;<volume>7</volume>: 100135.
                    <pub-id pub-id-type="doi">10.1016/j.envadv.2021.100135</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref23">
                <mixed-citation publication-type="other">
                    <collab>Global nutrition targets 2025: low birth weight policy brief [WWW Document]</collab>:<year>n.d.</year>(accessed 11.23.22).
                    <ext-link ext-link-type="uri" xlink:href="https://www.who.int/publications-detail-redirect/WHO-NMH-NHD-14.5">Reference Source</ext-link>
                </mixed-citation>
            </ref>
            <ref id="ref24">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Goyal</surname>
                            <given-names>L</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Bakshi</surname>
                            <given-names>D</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Arora</surname>
                            <given-names>J</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Assessment of fluoride levels during pregnancy and its association with early adverse pregnancy outcomes.</article-title>
                    <source>

                        <italic toggle="yes">J. Family Med. Prim. Care.</italic>
</source>
                    <year>2020</year>;<volume>9</volume>:<fpage>2693</fpage>&#x2013;<lpage>2698</lpage>.
                    <pub-id pub-id-type="pmid">32984109</pub-id>
                    <pub-id pub-id-type="doi">10.4103/jfmpc.jfmpc_213_20</pub-id>
                    <pub-id pub-id-type="pmcid">PMC7491833</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref27">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Grandjean</surname>
                            <given-names>P</given-names>
                        </name>
</person-group>:
                    <article-title>Developmental fluoride neurotoxicity: an updated review.</article-title>
                    <source>

                        <italic toggle="yes">Environ. Health.</italic>
</source>
                    <year>2019</year>;<volume>18</volume>:<fpage>110</fpage>.
                    <pub-id pub-id-type="pmid">31856837</pub-id>
                    <pub-id pub-id-type="doi">10.1186/s12940-019-0551-x</pub-id>
                    <pub-id pub-id-type="pmcid">PMC6923889</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref28">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Guth</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>H&#x00fc;ser</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Roth</surname>
                            <given-names>A</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Toxicity of fluoride: critical evaluation of evidence for human developmental neurotoxicity in epidemiological studies, animal experiments and in vitro analyses.</article-title>
                    <source>

                        <italic toggle="yes">Arch. Toxicol.</italic>
</source>
                    <year>2020</year>;<volume>94</volume>:<fpage>1375</fpage>&#x2013;<lpage>1415</lpage>.
                    <pub-id pub-id-type="pmid">32382957</pub-id>
                    <pub-id pub-id-type="doi">10.1007/s00204-020-02725-2</pub-id>
                    <pub-id pub-id-type="pmcid">PMC7261729</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref29">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Haider</surname>
                            <given-names>BA</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Olofin</surname>
                            <given-names>I</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Wang</surname>
                            <given-names>M</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis.</article-title>
                    <source>

                        <italic toggle="yes">BMJ.</italic>
</source>
                    <year>2013</year>;<volume>346</volume>:<fpage>f3443</fpage>&#x2013;<lpage>f3443</lpage>.
                    <pub-id pub-id-type="pmid">23794316</pub-id>
                    <pub-id pub-id-type="doi">10.1136/bmj.f3443</pub-id>
                    <pub-id pub-id-type="pmcid">PMC3689887</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref31">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Hallberg</surname>
                            <given-names>L</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Brune</surname>
                            <given-names>M</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Rossander</surname>
                            <given-names>L</given-names>
                        </name>
</person-group>:
                    <article-title>The role of vitamin C in iron absorption.</article-title>
                    <source>

                        <italic toggle="yes">Int. J. Vitam. Nutr. Res.</italic>
</source>
                    <year>1989</year>;<volume>Suppl 30</volume>:<fpage>103</fpage>&#x2013;<lpage>108</lpage>.</mixed-citation>
            </ref>
            <ref id="ref32">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Hillman</surname>
                            <given-names>D</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Bolenbaugh</surname>
                            <given-names>DL</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Convey</surname>
                            <given-names>EM</given-names>
                        </name>
</person-group>:
                    <article-title>Hypothyroidism and Anemia Related to Fluoride in Dairy Cattle.</article-title>
                    <source>

                        <italic toggle="yes">J. Dairy Sci.</italic>
</source>
                    <year>1979</year>;<volume>62</volume>:<fpage>416</fpage>&#x2013;<lpage>423</lpage>.
                    <pub-id pub-id-type="pmid">447892</pub-id>
                    <pub-id pub-id-type="doi">10.3168/jds. S0022-0302(79)83261-0</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref33">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Idowu</surname>
                            <given-names>OS</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Azevedo</surname>
                            <given-names>LB</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Valentine</surname>
                            <given-names>RA</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>The use of urinary fluoride excretion to facilitate monitoring fluoride intake: A systematic scoping review.</article-title>
                    <source>

                        <italic toggle="yes">PLoS One.</italic>
</source>
                    <year>2019</year>;<volume>14</volume>:<fpage>e0222260</fpage>.
                    <pub-id pub-id-type="pmid">31509581</pub-id>
                    <pub-id pub-id-type="doi">10.1371/journal.pone.0222260</pub-id>
                    <pub-id pub-id-type="pmcid">PMC6738609</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref34">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Johnston</surname>
                            <given-names>NR</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Strobel</surname>
                            <given-names>SA</given-names>
                        </name>
</person-group>:
                    <article-title>Principles of fluoride toxicity and the cellular response: a review.</article-title>
                    <source>

                        <italic toggle="yes">Arch. Toxicol.</italic>
</source>
                    <year>2020</year>;<volume>94</volume>:<fpage>1051</fpage>&#x2013;<lpage>1069</lpage>.
                    <pub-id pub-id-type="pmid">32152649</pub-id>
                    <pub-id pub-id-type="doi">10.1007/s00204-020-02687-5</pub-id>
                    <pub-id pub-id-type="pmcid">PMC7230026</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref36">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Kapil</surname>
                            <given-names>U</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Kapil</surname>
                            <given-names>R</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Gupta</surname>
                            <given-names>A</given-names>
                        </name>
</person-group>:
                    <article-title>National Iron Plus Initiative: Current status &amp; future strategy.</article-title>
                    <source>

                        <italic toggle="yes">Indian J. Med. Res.</italic>
</source>
                    <year>2019</year>;<volume>150</volume>:<fpage>239</fpage>&#x2013;<lpage>247</lpage>.
                    <pub-id pub-id-type="pmid">31719294</pub-id>
                    <pub-id pub-id-type="doi">10.4103/ijmr. IJMR_1782_18</pub-id>
                    <pub-id pub-id-type="pmcid">PMC6886130</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref37">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Kominiarek</surname>
                            <given-names>MA</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Rajan</surname>
                            <given-names>P</given-names>
                        </name>
</person-group>:
                    <article-title>Nutrition Recommendations in Pregnancy and Lactation.</article-title>
                    <source>

                        <italic toggle="yes">Med. Clin. North Am.</italic>
</source>
                    <year>2016</year>;<volume>100</volume>:<fpage>1199</fpage>&#x2013;<lpage>1215</lpage>.
                    <pub-id pub-id-type="doi">10.1016/j.mcna.2016.06.004</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref38">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Kulasekaran</surname>
                            <given-names>R</given-names>
                        </name>
</person-group>:
                    <article-title>Influence of mothers&#x2019; chronic energy deficiency on the nutritional status of preschool children in Empowered Action Group states in India.</article-title>
                    <source>

                        <italic toggle="yes">Int J Nutr Pharmacol Neurol Dis.</italic>
</source>
                    <year>2012</year>;<volume>2</volume>:<fpage>198</fpage>.
                    <pub-id pub-id-type="doi">10.4103/2231-0738.99471</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref39">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Kumar</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Lata</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Yadav</surname>
                            <given-names>J</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Relationship between water, urine and serum fluoride and fluorosis in school children of Jhajjar District, Haryana, India.</article-title>
                    <source>

                        <italic toggle="yes">Appl Water Sci.</italic>
</source>
                    <year>2017</year>;<volume>7</volume>:<fpage>3377</fpage>&#x2013;<lpage>3384</lpage>.
                    <pub-id pub-id-type="doi">10.1007/s13201-016-0492-2</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref40">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Lawn</surname>
                            <given-names>JE</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Wilczynska-Ketende</surname>
                            <given-names>K</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Cousens</surname>
                            <given-names>SN</given-names>
                        </name>
</person-group>:
                    <article-title>Estimating the causes of 4 million neonatal deaths in the year 2000.</article-title>
                    <source>

                        <italic toggle="yes">Int. J. Epidemiol.</italic>
</source>
                    <year>2006</year>;<volume>35</volume>:<fpage>706</fpage>&#x2013;<lpage>718</lpage>.
                    <pub-id pub-id-type="pmid">16556647</pub-id>
                    <pub-id pub-id-type="doi">10.1093/ije/dyl043</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref41">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Lee</surname>
                            <given-names>AC</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Katz</surname>
                            <given-names>J</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Blencowe</surname>
                            <given-names>H</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010.</article-title>
                    <source>

                        <italic toggle="yes">Lancet Glob. Health.</italic>
</source>
                    <year>2013</year>;<volume>1</volume>:<fpage>e26</fpage>&#x2013;<lpage>e36</lpage>.
                    <pub-id pub-id-type="pmid">25103583</pub-id>
                    <pub-id pub-id-type="doi">10.1016/S2214-109X(13)70006-8</pub-id>
                    <pub-id pub-id-type="pmcid">PMC4221634</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref42">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Mahantesha</surname>
                            <given-names>T</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Dixit</surname>
                            <given-names>UB</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Nayakar</surname>
                            <given-names>RP</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Prevalence of Dental Fluorosis and associated Risk Factors in Bagalkot District, Karnataka, India.</article-title>
                    <source>

                        <italic toggle="yes">Int. J. Clin. Pediatr. Dent.</italic>
</source>
                    <year>2016</year>;<volume>9</volume>:<fpage>256</fpage>&#x2013;<lpage>263</lpage>.
                    <pub-id pub-id-type="pmid">27843259</pub-id>
                    <pub-id pub-id-type="doi">10.5005/jp-journals-10005-1373</pub-id>
                    <pub-id pub-id-type="pmcid">PMC5086015</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref71">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Malin</surname>
                            <given-names>AJ</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Busgang</surname>
                            <given-names>SA</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Garcia</surname>
                            <given-names>JC</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Fluoride Exposure and Age of Menarche: Potential Differences Among Adolescent Girls and Women in the United States.</article-title>
                    <source>Expo Health.</source>
                    <year>2022</year>;<volume>14</volume>:<fpage>733</fpage>&#x2013;<lpage>742</lpage>.
                    <pub-id pub-id-type="doi">10.1007/s12403-021-00448-y</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref43">
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>McNeil</surname>
                            <given-names>AR</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Stanford</surname>
                            <given-names>PE</given-names>
                        </name>
</person-group>:
                    <article-title>Reporting Thyroid Function Tests in Pregnancy 18.</article-title>
                    <year>n.d.</year>
                </mixed-citation>
            </ref>
            <ref id="ref44">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Padhi</surname>
                            <given-names>BK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Baker</surname>
                            <given-names>KK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Dutta</surname>
                            <given-names>A</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Risk of Adverse Pregnancy Outcomes among Women Practicing Poor Sanitation in Rural India: A Population-Based Prospective Cohort Study.</article-title>
                    <source>

                        <italic toggle="yes">PLoS Med.</italic>
</source>
                    <year>2015</year>;<volume>12</volume>:<fpage>e1001851</fpage>.
                    <pub-id pub-id-type="pmid">26151447</pub-id>
                    <pub-id pub-id-type="doi">10.1371/journal.pmed.1001851</pub-id>
                    <pub-id pub-id-type="pmcid">PMC4511257</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref45">
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Patil</surname>
                            <given-names>M</given-names>
                        </name>
</person-group>:
                    <article-title>STROBE-cohort_checklist_Anemia in Pregnancy.docx.</article-title>
                    <year>2023a</year>.
                    <pub-id pub-id-type="doi">10.5281/zenodo.7780105</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref46">
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Patil</surname>
                            <given-names>M</given-names>
                        </name>
</person-group>:
                    <article-title>Fluoride_studyQuestionnaire.pdf.</article-title>
                    <year>2023b</year>.
                    <pub-id pub-id-type="doi">10.5281/zenodo.7962221</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref47">
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Patil</surname>
                            <given-names>M</given-names>
                        </name>
</person-group>:
                    <article-title>Jodhpur_Data File_anemia in Pregnancy_CSV.csv.</article-title>
                    <year>2023c</year>.
                    <pub-id pub-id-type="doi">10.5281/zenodo.7928263</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref48">
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Patil</surname>
                            <given-names>M</given-names>
                        </name>
</person-group>:
                    <article-title>Nagaur_Data File_Anemia in Pregnancy_CSV.csv.</article-title>
                    <year>2023d</year>.
                    <pub-id pub-id-type="doi">10.5281/zenodo.7928230</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref49">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Puri</surname>
                            <given-names>A</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Kumar</surname>
                            <given-names>M</given-names>
                        </name>
</person-group>:
                    <article-title>A review of permissible limits of drinking water.</article-title>
                    <source>

                        <italic toggle="yes">Indian J. Occup. Environ. Med.</italic>
</source>
                    <year>2012</year>;<volume>16</volume>:<fpage>40</fpage>&#x2013;<lpage>44</lpage>.
                    <pub-id pub-id-type="pmid">23112507</pub-id>
                    <pub-id pub-id-type="doi">10.4103/0019-5278.99696</pub-id>
                    <pub-id pub-id-type="pmcid">PMC3482709</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref51">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Rahman</surname>
                            <given-names>MM</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Abe</surname>
                            <given-names>SK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Rahman</surname>
                            <given-names>MS</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: systematic review and meta-analysis.</article-title>
                    <source>

                        <italic toggle="yes">Am. J. Clin. Nutr.</italic>
</source>
                    <year>2016</year>;<volume>103</volume>:<fpage>495</fpage>&#x2013;<lpage>504</lpage>.
                    <pub-id pub-id-type="doi">10.3945/ajcn.115.107896</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref52">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>R&#x00e4;is&#x00e4;nen</surname>
                            <given-names>S</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Kancherla</surname>
                            <given-names>V</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Gissler</surname>
                            <given-names>M</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Adverse Perinatal Outcomes Associated with Moderate or Severe Maternal Anaemia Based on Parity in Finland during 2006-10: Anaemia and perinatal outcomes.</article-title>
                    <source>

                        <italic toggle="yes">Paediatr. Perinat. Epidemiol.</italic>
</source>
                    <year>2014</year>;<volume>28</volume>:<fpage>372</fpage>&#x2013;<lpage>380</lpage>.
                    <pub-id pub-id-type="doi">10.1111/ppe.12134</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref53">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Rao</surname>
                            <given-names>KV</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Mahajan</surname>
                            <given-names>CL</given-names>
                        </name>
</person-group>:
                    <article-title>Fluoride content of some common South Indian foods and their contribution to fluorosis.</article-title>
                    <source>

                        <italic toggle="yes">J. Sci. Food Agric.</italic>
</source>
                    <year>1990</year>;<volume>51</volume>:<fpage>275</fpage>&#x2013;<lpage>279</lpage>.
                    <pub-id pub-id-type="doi">10.1002/jsfa.2740510215</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref54">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Reddy</surname>
                            <given-names>D</given-names>
                        </name>
</person-group>:
                    <article-title>Neurology of endemic skeletal fluorosis.</article-title>
                    <source>

                        <italic toggle="yes">Neurol. India.</italic>
</source>
                    <year>2009</year>;<volume>57</volume>:<fpage>7</fpage>&#x2013;<lpage>12</lpage>.
                    <pub-id pub-id-type="pmid">19305069</pub-id>
                    <pub-id pub-id-type="doi">10.4103/0028-3886.48793</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref72">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Ren</surname>
                            <given-names>C</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Zhang</surname>
                            <given-names>P</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Yao</surname>
                            <given-names>X-Y</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>The cognitive impairment and risk factors of the older people living in high fluorosis areas: DKK1 need attention.</article-title>
                    <source>BMC Public Health.</source>
                    <year>2021</year>;<volume>21</volume>:<fpage>2237</fpage>.
                    <pub-id pub-id-type="doi">10.1186/s12889-021-12310-6</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref55">
                <mixed-citation publication-type="other">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Sachdev</surname>
                            <given-names>HPS</given-names>
                        </name>
</person-group>:
                    <article-title>LOW BIRTH WEIGHT IN SOUTH ASIA.</article-title>
                    <year>2001</year>;<volume>21</volume>:<fpage>19</fpage>.</mixed-citation>
            </ref>
            <ref id="ref56">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Shruthi</surname>
                            <given-names>M</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Anil</surname>
                            <given-names>N</given-names>
                        </name>
</person-group>:
                    <article-title>A comparative study of dental fluorosis and non-skeletal manifestations of fluorosis in areas with different water fluoride concentrations in rural Kolar.</article-title>
                    <source>

                        <italic toggle="yes">J Family Med Prim Care.</italic>
</source>
                    <year>2018</year>;<volume>7</volume>:<fpage>1222</fpage>&#x2013;<lpage>1228</lpage>.
                    <pub-id pub-id-type="pmid">30613501</pub-id>
                    <pub-id pub-id-type="doi">10.4103/jfmpc.jfmpc_72_18</pub-id>
                    <pub-id pub-id-type="pmcid">PMC6293885</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref59">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Susheela</surname>
                            <given-names>AK</given-names>
                        </name>
</person-group>:
                    <article-title>Dental Fluorosis and its Extended Effects.</article-title>
                    <source>

                        <italic toggle="yes">Indian J. Pediatr.</italic>
</source>
                    <year>2013</year>;<volume>80</volume>:<fpage>715</fpage>&#x2013;<lpage>717</lpage>.
                    <pub-id pub-id-type="pmid">23801348</pub-id>
                    <pub-id pub-id-type="doi">10.1007/s12098-013-1100-1</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref60">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Susheela</surname>
                            <given-names>AK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Mondal</surname>
                            <given-names>NK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Gupta</surname>
                            <given-names>R</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Effective interventional approach to control anaemia in pregnant women.</article-title>
                    <source>

                        <italic toggle="yes">Curr. Sci.</italic>
</source>
                    <year>2010</year>;<volume>98</volume>:<fpage>11</fpage>.</mixed-citation>
            </ref>
            <ref id="ref62">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Susheela</surname>
                            <given-names>AK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Mondal</surname>
                            <given-names>NK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Gupta</surname>
                            <given-names>R</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Fluorosis is Linked to Anaemia.</article-title>
                    <source>

                        <italic toggle="yes">Curr. Sci.</italic>
</source>
                    <year>2018</year>;<volume>115</volume>:<fpage>692</fpage>.
                    <pub-id pub-id-type="doi">10.18520/cs/v115/i4/692-700</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref63">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Susheela</surname>
                            <given-names>AK</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Toteja</surname>
                            <given-names>GS</given-names>
                        </name>
</person-group>:
                    <article-title>Prevention &amp; control of fluorosis &amp; linked disorders: Developments in the 21st Century - Reaching out to patients in the community &amp; hospital settings for recovery.</article-title>
                    <source>

                        <italic toggle="yes">Indian J. Med. Res.</italic>
</source>
                    <year>2018</year>;<volume>148</volume>:<fpage>539</fpage>&#x2013;<lpage>547</lpage>.
                    <pub-id pub-id-type="pmid">30666981</pub-id>
                    <pub-id pub-id-type="doi">10.4103/ijmr. IJMR_1775_18</pub-id>
                    <pub-id pub-id-type="pmcid">PMC6366265</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref64">
                <mixed-citation publication-type="other">
                    <collab>tagged_ifas_participants_manual_for_healthcare_providers.pdf</collab>:<year>n.d.</year>
                </mixed-citation>
            </ref>
            <ref id="ref65">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Vijayaraghavan</surname>
                            <given-names>K</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Brahmam</surname>
                            <given-names>GNV</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Nair</surname>
                            <given-names>KM</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Evaluation of national nutritional anemia prophylaxis programme.</article-title>
                    <source>

                        <italic toggle="yes">Indian J. Pediatr.</italic>
</source>
                    <year>1990</year>;<volume>57</volume>:<fpage>183</fpage>&#x2013;<lpage>190</lpage>.
                    <pub-id pub-id-type="doi">10.1007/BF02722084</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref66">
                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Watkins</surname>
                            <given-names>WJ</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Kotecha</surname>
                            <given-names>SJ</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Kotecha</surname>
                            <given-names>S</given-names>
                        </name>
</person-group>:
                    <article-title>All-Cause Mortality of Low Birthweight Infants in Infancy, Childhood, and Adolescence: Population Study of England and Wales.</article-title>
                    <source>

                        <italic toggle="yes">PLoS Med.</italic>
</source>
                    <year>2016</year>;<volume>13</volume>:<fpage>e1002018</fpage>.
                    <pub-id pub-id-type="pmid">27163787</pub-id>
                    <pub-id pub-id-type="doi">10.1371/journal.pmed.1002018</pub-id>
                    <pub-id pub-id-type="pmcid">PMC4862683</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref67">
                <mixed-citation publication-type="other">
                    <collab>WHA Global Nutrition Targets 2025: Low Birth Weight Policy Brief</collab>:<year>n.d.</year>
                </mixed-citation>
            </ref>
            <ref id="ref68">
                <mixed-citation publication-type="book">
                    <collab>World Health Organization</collab>:
                    <source>

                        <italic toggle="yes">The global prevalence of anaemia in 2011.</italic>
</source>
                    <publisher-loc>Geneva</publisher-loc>:
                    <publisher-name>World Health Organization</publisher-name>;<year>2015</year>.</mixed-citation>
            </ref>
        </ref-list>
    </back>
    <sub-article article-type="reviewer-report" id="report257331">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.163694.r257331</article-id>
            <title-group>
                <article-title>Reviewer response for version 2</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Natesirinilkul</surname>
                        <given-names>Rungrote</given-names>
                    </name>
                    <xref ref-type="aff" rid="r257331a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-9840-3443</uri>
                </contrib>
                <aff id="r257331a1">
                    <label>1</label>Chiang Mai University and Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>4</day>
                <month>4</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Natesirinilkul R</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport257331" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.134720.2"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>I am pleased with the responses of the authors. I have no more comment to add.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Yes</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Partly</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Partly</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Yes</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>anemia, bleeding disorders, thrombosis, blood transfusion</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
        </body>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report179723">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.147800.r179723</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Pandya</surname>
                        <given-names>Apurvakumar</given-names>
                    </name>
                    <xref ref-type="aff" rid="r179723a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-0178-3978</uri>
                </contrib>
                <aff id="r179723a1">
                    <label>1</label>Parul Institute of Public Health, Parul University, Vadodara, Gujarat, India</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>27</day>
                <month>1</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Pandya A</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport179723" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.134720.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>The study is well carried out and nicely written.</p>
            <p> This prospective cohort study attempted to identify linkages between fluorosis and the low-birth weight of newborn babies with anaemic mothers.&#x00a0; In this study, Antenatal mothers until the 20th week of gestation were followed up till delivery in the Antenatal Clinic of a&#x00a0; fluoride-endemic district&#x00a0; and not-so-endemic district of Western Rajasthan.</p>
            <p> </p>
            <p> Considering current scenario, this study provides important insights. As this manuscript is well written, I have no comments for improvement.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Yes</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Yes</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Yes</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Yes</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Yes</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>public health, anemia control, health behaviour change, public mental health, health technology assessment</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
        </body>
        <sub-article article-type="response" id="comment10961-179723">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>PATIL</surname>
                            <given-names>MANOJ</given-names>
                        </name>
                        <aff>Research and Development, Datta Meghe Institute of Higher Education and Research, Wardha, Wardha, Maharashtra, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No conflicts of interest.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>27</day>
                    <month>1</month>
                    <year>2024</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Thank you very much for your appreciation.&#x00a0;The authors are grateful for your timely response on this article and your valuable comments.</p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report232742">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.147800.r232742</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Natesirinilkul</surname>
                        <given-names>Rungrote</given-names>
                    </name>
                    <xref ref-type="aff" rid="r232742a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-9840-3443</uri>
                </contrib>
                <aff id="r232742a1">
                    <label>1</label>Chiang Mai University and Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>22</day>
                <month>1</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Natesirinilkul R</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport232742" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.134720.1"/>
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            <p>This paper is interesting. However, a few issues are needed to be clarified more.&#x00a0;</p>
            <p> 1.Please provide the exact mean number of hemoglobin level in each group apart from percentage of pregnant women with anemia.&#x00a0;</p>
            <p> 2.Please provide the explanation why LBW neonates were more commonly found in Jodhpur district.&#x00a0;</p>
            <p> 3.Several risk factors were different between both areas where this study was performed. How do we decrease the bias of the other risk factors causing anemia in this study as the mean levels of fluoride were not extremly high in both areas.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Yes</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Partly</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Partly</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Yes</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>anemia, bleeding disorders, thrombosis, blood transfusion</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment11258-232742">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>PATIL</surname>
                            <given-names>MANOJ</given-names>
                        </name>
                        <aff>Research and Development, Datta Meghe Institute of Higher Education and Research, Wardha, Wardha, Maharashtra, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>None</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>12</day>
                    <month>3</month>
                    <year>2024</year>
                </pub-date>
            </front-stub>
            <body>
                <p>We are extremely thankful to the Reviewer for bringing new insights for improving the</p>
                <p> manuscript.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comments </bold>
                </p>
                <p> 
                    <bold>Response </bold>
                </p>
                <p> </p>
                <p> 1. Please provide the exact mean number of hemoglobin levels in each group apart from the percentage of pregnant women with anemia.&#x00a0;</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>The mean Hb (gm%) level in pregnant women in the Jodhpur district was 10.4gm% as compared to the Nagaur district (9.1gm%).</bold>
                </p>
                <p> </p>
                <p> 2. Please provide an explanation why LBW neonates were more commonly found in the Jodhpur district</p>
                <p> 
                    <bold>In our study, the mean weight of newborns from the Jodhpur district was 2.8 &#x00b1; 0.56 kg, and from Nagaur was 2.8 &#x00b1; 0.44 kg.</bold>
                </p>
                <p>
                    <bold> Around 19% of newborns in Jodhpur and around 22% in Nagaur had LBW. However, there was no significant difference in LBW babies in both districts (p=0.151)</bold>
                </p>
                <p> </p>
                <p> </p>
                <p> 3. Several risk factors were different between both areas where this study was performed. How do we decrease the bias of the other risk factors causing anemia in this study as the mean levels of fluoride were not extremely high in both areas?</p>
                <p> 
                    <bold>In addressing the potential impact of various risk factors on anemia in the studied areas, we took measures to mitigate bias. Although the mean fluoride levels were not exceptionally high in both regions, we conducted a comprehensive assessment of potential contributors to anemia in pregnant women. This included the measurement of fluoride levels in both water and urine, acknowledging their role as risk factors.</bold>
                </p>
                <p>
                    <bold> Additionally, we investigated other factors such as dietary patterns, excessive consumption of tea and black salt, concomitant nutritional deficiencies, and the use of fluoridated toothpaste. We also considered the source of drinking water, aiming to account for any potential effects on hemoglobin levels in pregnant women. The study also delved into iron and folate supplementation for pregnant women, exploring the correlation with the risk of low birth weight in both districts. However, there was no significant difference in LBW babies in both districts (p=0.151)</bold>
                </p>
                <p>
                    <bold> </bold>
                </p>
                <p>
                    <bold> It's important to note that the study has its limitations, and while we addressed a few risk factors, there may be several area-specific that were not thoroughly explored, contributing to potential bias in the assessment of anemia in pregnant women.</bold>
                </p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report179725">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.147800.r179725</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Charantimath</surname>
                        <given-names>Umesh</given-names>
                    </name>
                    <xref ref-type="aff" rid="r179725a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-1726-2798</uri>
                </contrib>
                <aff id="r179725a1">
                    <label>1</label>Department of Community Medicine, KLE Academy of Higher Education and Research J N Medical College, Belagavi, Karnataka, India</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>5</day>
                <month>7</month>
                <year>2023</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2023 Charantimath U</copyright-statement>
                <copyright-year>2023</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport179725" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.134720.1"/>
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        <body>
            <p>It is one of the nicely written manuscript. It would be very nice if you add recent articles in the Introduction part rather than quoting a three decade old article. Low birth weight has multiple causes and in this article you have tried to enlist them, but how to minimize the confounding factors and prioritize fluoride still needs to be explained in detail.&#x00a0;</p>
            <p> </p>
            <p> Fluorosis is a very important public health problem in the LMICs. In this article the authors have clearly mentioned the importance of fluorosis&#x00a0;in relation to anemia in pregnancy and LBW. There are many other reasons for LBW and anemia in pregnant women. How the fluoride content in the drinking water will have an adverse impact on maternal and child health has tried to be explained by the authors. What the impact fluorosis has on other age groups has to be addressed.</p>
            <p> </p>
            <p> I feel larger sample size should be looked into and along with that the multiple variables also need to be collected such as nutrition, obstetric history, other comorbidities&#x00a0;etc. to come to a final consensus about at what level the fluorosis will have an adverse impact on maternal and child health.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Yes</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Yes</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Yes</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Yes</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Yes</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Maternal child health</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
        </body>
        <sub-article article-type="response" id="comment9872-179725">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>PATIL</surname>
                            <given-names>MANOJ</given-names>
                        </name>
                        <aff>Research and Development, Datta Meghe Institute of Higher Education and Research, Wardha, Wardha, Maharashtra, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing Interests.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>6</day>
                    <month>7</month>
                    <year>2023</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Respected Sir,</p>
                <p> Thank you very much for taking time out of your busy schedule for this review. Also we are obliged for your valuable comments and suggestions on this manuscript and for approving the article.&#x00a0;We are extremely thankful for bringing new insights for improving the manuscript.</p>
                <p> Please see below the reply to your comments for further perusal-</p>
                <p> </p>
                <p> 
                    <bold>Comment -&#x00a0;</bold>
                    <bold>Recent articles in the Introduction</bold>
                </p>
                <p> 
                    <bold>Response: Following are the recent references-</bold>
                </p>
                <p> 1.&#x00a0;Fluorosis, an underestimated and sometimes debilitating condition, is being caused by high levels of fluoride in food and contaminated groundwater in India.</p>
                <p> 
                    <bold>Reference:</bold>
                </p>
                <p> Del Bello, Lou. Fluorosis: an ongoing challenge for India</p>
                <p> The Lancet Planetary Health,2020. Volume 4, Issue 3, e94 - e95</p>
                <p> </p>
                <p> 2. Interestingly, fluoride exposure during pregnancy was not significantly associated with fertility or birth outcomes, especially among women living in areas with levels of fluoride consistent with water fluoridation.</p>
                <p> 
                    <bold>Reference:</bold>
                </p>
                <p> Goodman C, Hall M, Green R, Hornung R, Martinez-Mier EA, Lanphear B, Till C. Maternal fluoride exposure, fertility and birth outcomes: The MIREC cohort. Environ Adv. 2022 Apr;7:100135. doi: 10.1016/j.envadv.2021.100135. Epub 2021 Nov 2. PMID: 36644332; PMCID: PMC9837859.</p>
                <p> </p>
                <p> 3. Contrastingly, other literatures have found increased risk of adverse birth outcomes in areas where fluoride levels in drinking water are high (&gt; 1.5 mg/L)</p>
                <p> 
                    <bold>Reference:</bold>
                </p>
                <p> Goyal LD, Bakshi DK, Arora JK, Manchanda A, Singh P. Assessment of fluoride levels during pregnancy and its association with early adverse pregnancy outcomes. J Family Med Prim Care. 2020 Jun 30;9(6):2693-2698. doi: 10.4103/jfmpc.jfmpc_213_20. PMID: 32984109; PMCID: PMC7491833.</p>
                <p> </p>
                <p> 
                    <bold>Comment:&#x00a0;</bold>
                    <bold>How to minimize the confounding factors and prioritize fluoride still need to be explored.</bold>
                </p>
                <p>
                    <bold> Response:</bold>
                </p>
                <p> The confounding factors included the exposure time to fluoride in drinking water, as well as the exposure to fluoride in age, obstetric history, supplements, diet, air, medication, water sources, cooking vessel etc.</p>
                <p> To minimize the confounding factors, we could have applied regression analysis to observe the impact of fluoride on maternal and child health. Further, recruitment of larger sample participants in a randomized manner could help in getting the impact of Fluoride on pregnant women (Limitation of Study).</p>
                <p> </p>
                <p> 
                    <bold>Comment:</bold>&#x00a0;
                    <bold>Impact of Fluorosis on other age groups</bold>
                </p>
                <p> It would be interesting to explore the impact of Fluoride on different age groups.</p>
                <p> </p>
                <p> 
                    <bold>Responses:</bold>
                </p>
                <p> 
                    <bold>Adolescents-</bold>
                </p>
                <p> </p>
                <p> A study conducted in the United States discovered that greater water fluoride concentrations were connected with a 3.3-month earlier age of menarche.</p>
                <p> Malin, A.J., Busgang, S.A., Garcia, J.C.&#x00a0;et al.&#x00a0;Fluoride Exposure and Age of Menarche: Potential Differences Among Adolescent Girls and Women in the United States.&#x00a0;Expo Health&#x00a0;14, 733&#x2013;742 (2022). 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1007/s12403-021-00448-y">https://doi.org/10.1007/s12403-021-00448-y</ext-link>
                </p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>Elderly-</bold>
                </p>
                <p> </p>
                <p> Further, cognitive skills in older adults living in high fluoride drinking water locations may be compromised.</p>
                <p> Ren C, Zhang P, Yao XY, Li HH, Chen R, Zhang CY, Geng DQ. The cognitive impairment and risk factors of the older people living in high fluorosis areas: DKK1 need attention. BMC Public Health. 2021 Dec 9;21(1):2237. doi: 10.1186/s12889-021-12310-6. PMID: 34886821; PMCID: PMC8656079.</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>Children-</bold>
                </p>
                <p> </p>
                <p> A south Indian researcher discovered that nutritional status has an effect on the severity of fluorosis, with impoverished children being more affected by severe fluorosis.</p>
                <p> Mahantesha T, Dixit UB, Nayakar RP, Ashwin D, Ramagoni NK, Kamavaram Ellore VP. Prevalence of dental fluorosis and associated risk factors in Bagalkot District, Karnataka, India.&#x00a0;Int J Clin Pediatr Dent.&#x00a0;(2016) 9:256&#x2013;63. doi: 10.5005/jp-journals-10005-1373</p>
                <p> </p>
                <p> 
                    <bold>Comment: A larger sample size should be looked in and along with multiple variables such as nutrition, obstetric history, other co-morbidities to come to a final consensus to see the impact of fluoride on MCH.</bold>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> However, we have collected data on variables like 24-hr diet recall to track nutrition aspects, past obstetric history, cooking vessels, medication, water sources and other co-morbidity like Blood pressure, diabetes etc. but we could not perform analysis to see their impact on MCH in fluoride endemic areas (Limitation of the study).</p>
            </body>
        </sub-article>
    </sub-article>
</article>
