This is a prospective cohort study developed to determine the prevalence and the incidence of common CVD conditions in a cohort of pregnant females in the Anuradhapura district.

The present study was carried out in the Anuradhapura district, the largest Sri Lanka district. According to 2017 Department of Census and Statistics data ¹⁷ , it covers 7,179 km ² with a total population of 917,748. The total fertility rate of the district is 2.4 births per woman, one of the highest values in Sri Lanka ¹⁸ .

In Sri Lanka, the field maternal and child health services are mainly provided by the public health administrative units named "Medical Officer of Health" (MOH) areas. In each MOH area, a Medical Officer of Health (MOH) is in charge and leads a team of ground-level health care workers, including public health midwives (PHM), public health nursing sisters (PNS), and public health inspectors. In Anuradhapura, this service for pregnant women is provided through 22 MOHs, and currently 17 PNS and more than 250 PHM are working in the area. Spatial distribution of those MOH areas is displayed in Figure 1.

Curative services are provided through 56 hospitals/primary care units, including one teaching hospital (tertiary care unit) and three base hospitals (secondary care units). Almost all deliveries (99.5%) take place in government hospitals ¹⁸ . The study was conducted in all 22 MOH areas covering all the antenatal clinics.

All pregnant females in Anuradhapura district.

All pregnant females visiting antenatal clinics in the Anuradhapura district from July to September 2019.

Pregnant women:

1. Registered by field midwives and visiting field antenatal clinics in the Anuradhapura district.

2. Period of amenorrhoea (POA) less than 12 weeks by the time of recruitment.

1. Pregnant women planning to leave the study area for childbirth or after childbirth.

2. Pregnant women who are not registered at field antenatal clinics.

All the pregnant females registered at field antenatal clinics in Anuradhapura within three months from the beginning of the study were screened ( Figure 2). The usual number of pregnant mothers registered in each quarter is around 4000. However, 15–20% are registered after a POA of 10 weeks. Around 3000 pregnant women were recruited as the sample size. We hypothesized that the incidence of CVD complicating pregnancy among those who were without risk factors would be around 5% compared to 2% among those who did not have risk factors. With a conservative estimate of unexposed to exposed ratio 5:1, power of 80%- and two-sided confidence at 95% a sample of at least 1529 pregnant women (Kelsey formula) were required for the study. With around 15% early pregnancy miscarriages and 10% expected attrition, a minimum of 1911 pregnant women were required, and the number was well within the number recruited. Based on the actual rate of CVD, we will calculate the power of the study to detect the expected outcomes retrospectively.

Following registration to the antenatal care, pregnant women fulfilling the eligibility criteria were invited to attend a special clinic in their relevant MOH area. This invitation was given by way of a leaflet provided to the antenatal women through the PHM. At the special clinic, potential participants were recruited by the data collectors who visit these special antenatal clinics (ANC) in the field. Data collectors visited each field antenatal clinic in all 22 MOH areas on the pre-planned special clinic day. Eligible pregnant mothers were educated about the research purpose and written informed consent was obtained before recruitment. Participants were informed that they might need to visit the Teaching Hospital, Anuradhapura, if the study suggested an echocardiogram. All the other data collection and follow-up was done at the routine antenatal clinics. Recruitment was carried out until the data collection period was over.

We carried out the risk assessment through a specific interviewer-administered questionnaire, including clinical features of present cardiovascular diseases ¹⁹ and a clinical examination. The examination included a baseline physical examination and referral checklist, including a specific set of variables/signs, each defined previously, to improve the validity and reliability of data ¹⁹ . Measurement of blood pressure and CVS examination auscultation was done using standard protocols given to all medical officers doing the clinical assessment ¹⁹ . Specially trained medical graduates carried out data collection to use the above equipment using standard guidelines, which was issued in print for each procedure ¹⁹ .

According to the baseline data, every recruited mother was classified according to the New York Heart Association (NYHA) classification. Based on that data and cardiac examination screening, suspected/probable cases with cardiovascular conditions were referred to the Professorial Unit, Teaching Hospital, Anuradhapura, for an echocardiogram and consultant cardiologist's opinion ( Figure 2).

We developed this checklist with less stringent criteria to improve the sensitivity with low threshold values to develop a more refined screening checklist based on the results of the study. The development of the screening checklist was done after a literature review and expert opinions. We incorporated this checklist into the examination sheet to minimize the duplication of work.

As the objective was to determine the prevalence of common cardiac conditions in the first trimester of the pregnant female, the referral method was developed to have a low threshold. If any of the above signs or symptoms were positive, the participants were referred to the consultant cardiologist at the Professorial Unit, Teaching Hospital, Anuradhapura.

All screening positive patients were subject to a two-dimensional (2D) echocardiogram and an electrocardiogram (ECG) to evaluate cardiac electrical activity and rhythm. The ECG was taken using the Zonecare, iMAC 300 Three channel ECG machine, and the 2D echocardiogram using a Philips EPIQ 7.

All the recruited participants in the first trimester were followed up between 24–28 weeks of POA at the routine antenatal clinic visit. A separate short interviewer-administered questionnaire was used ¹⁹ . We also carried out a general and cardiac examination, and referrals were done using a checklist ¹⁹ .

Participants were followed up through the routine system, and all maternal morbidities and hospital admissions recorded through a specific hospital surveillance system. All antenatal ward admissions with cardiac disease complicating pregnancy were extracted and cross-matched with the initial cohort to determine whether there were conditions missed through the screening. This was done in two major hospitals with a consultant obstetrician where all pregnant mothers from Anuradhapura districts are transferred. To determine the near misses and severe complications, all intensive care unit admissions were also screened during the study period. We matched all pregnant admissions with the original cohort to identify any cardiac disease complicating pregnancy.

A telephone interview was conducted with all study participants to document all antenatal morbidities in addition to the hospital admission screening. The interviews were carried out between 6–12 weeks after the expected delivery date to cover postpartum morbidities. Records relating to those who reported any hospital admissions were extracted from relevant hospitals. This approach was proposed to minimize unnecessary in-person contacts during the COVID-19 pandemic.

To reduce the bias in sample selection and recruitment all the mothers who have registered at the field antenatal clinics were given an equal opportunity to participate in the study. All the participants who fulfilled the inclusion and exclusion criteria were recruited to the study.

When it comes to the examination to reduce the observer bias, digital blood pressure monitors were used with the same method in every clinic. Two readings are taken from both arms with a five-minute gap and the lower value recorded as the blood pressure. If a high blood pressure value is detected (SBP> 135mmHg or DBP >85mmHg), a third reading is taken after a rest period of five minutes. The same procedure is carried out in subsequent blood pressure measurements of the participants.

To reduce the bias when referring participants for further assessment, referrals were initiated based solely on screening positivity at the initial assessment.

The main focus of the study is to describe the actual disease burden of cardiovascular disease in pregnancy in Sri Lanka (prevalence and incidence). With a proper assessment of disease burden, we expect to propose strategies to be included in the national program.

A field model will be developed using the findings for early detection of cardiovascular conditions during pregnancy at field level. With the appropriate inputs from the stakeholder, this model will be used to propose the required changes in strategies related to control and prevention of CVD complicating pregnancy in Sri Lanka.

All the data collection will be done using the electronic data collection method using a unique barcode and serial number. The database will be automatically formulated through this data collection platform. Access to the databases will be under restricted access. Access will be granted to principal investigators only. Two-dimensional echocardiogram reports will also be formulated via database management software, and a copy of the report will be provided to the participant. This database will also be accessible by the researchers only, and the data will be stored under the unique serial number.

Data will be analysed using the Statistical Package for Social Sciences ( SPSS) version 26 (IBM SPSS Statistics, RRID:SCR_019096). An open-access alternative that can provide an equivalent function is the R stats package (R Project for Statistical Computing, RRID:SCR_001905).Point prevalence of cardiovascular diseases complicating pregnancy will be calculated with 95% confidence intervals (CI). The prevalence of each specific condition will also be presented as proportions. The cumulative incidence of heart disease incidence will be estimated, and the 95% CI will be calculated using a Poisson distribution. An analysis of factors associated with cardiovascular disease complicating pregnancy will be done, and relative risks will be calculated. A risk prediction model will be developed to identify the predictive factors of cardiac disease complicating pregnancy. This model will be used to develop a screening checklist for the public health system.

All study procedures were done following the Helsinki declaration. Research was carried out only after the informed written consent of the participant for participation and after agreeing to publication of data collected in an anonymized format. Participants have been provided with the opportunity to withdraw from the study at any time. Participant identification data will be kept under lock and key to protect confidentiality. All identified conditions will be managed and treated by the consultant cardiologists with appropriate investigations and referral without an additional cost to the participant. Ethical clearance for the "Rajarata Pregnancy Cohort" has been obtained from the Ethics Review Committee, Faculty of the Medicine & Allied Sciences, Rajarata University of Sri Lanka under the approval number ERC/2019/07.

All the recruited participants have been provided with a serial number and a unique bar code. All the material and data belonging to a participant will be labelled with the above serial number and bar code. All the consent forms will be stored separately under lock and key at the Maternal and Child Health Research Unit, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka. The participant has also received an identity card with basic details and a barcode.

Findings will be published as research articles, abstracts, and presentations. Generated knowledge will be communicated with the local health care authorities, and nationally important findings will be published as policy briefs.

Open Science Framework: Generating Evidence for Ending Preventable Maternal Deaths (GEEPMED) in Sri Lanka. Extended data for ‘Disease burden and adverse pregnancy outcomes due to cardiovascular conditions complicating pregnancy in Sri Lanka’, ‘Tools’. https://doi.org/10.17605/OSF.IO/RTDCG ¹⁹

This project contains the following extended data:

1. Baseline questionnaire

2. Baseline physical examination and referral checklist sheet

3. Definition of selected signs and symptoms

4. Guide for blood pressure measurement

5. Guide for CVS examination

6. Follow-up questionnaire

7. Follow-up examination and referral checklist sheet

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)