Association of maternal and cord vitamin B12 levels with anthropometry in term neonates born to malnourished mothers in coastal South India

Introduction

Vitamin B12, also known as cobalamin, is a micronutrient essential for cell growth and differentiation.¹ This essential vitamin plays a crucial role in various biochemical processes, particularly in the synthesis of DNA, in conjunction with folic acid.² Adequate levels of vitamin B12 during early childhood promote growth and prevent cognitive impairment. Vitamin B12 is commonly found in animal-based food products such as dairy, fish, eggs, and poultry. Consuming these foods is an effective way to acquire vitamin B12 from the diet.³

While the vegetarian population is at a heightened risk of deficiency, it is also prevalent among non-vegetarians.³ Vitamin B12 deficiency is a major health concern worldwide. Pregnant women and young children are at an increased risk of facing this deficiency.⁴ Regional disparities in the occurrence of vitamin B12 deficiency throughout pregnancy have been observed, indicating varying levels of risks across different regions.⁵

Inadequacy of vitamin B12 in pregnancy has been linked to unfavourable pregnancy outcomes, including spontaneous abortions, stillbirth, neural tube defects, intrauterine growth restriction, low birth weight, and premature delivery.^6–10 Deficiency of vitamin B12 is also implicated in increased risk of gestational diabetes mellitus.¹¹ Vitamin B12 levels in expectant mothers are thought to influence the vitamin B12 status of the fetus and infant. Vitamin B12 deficient mothers may produce breast milk with insufficient levels of vitamin B12, and their exclusively breast-fed infants may develop symptoms in the postnatal period. These infants may have apathy, anorexia, irritability, failure to thrive, delayed or regression of milestones, pancytopenia, hypotonia, and seizures. Early symptoms may be nonspecific and pose challenges for identification.^12–16 A systematic review by Rogne et al. reported no clear linear relationship between birth weight and maternal vitamin B12 levels during pregnancy. However, deficiency was linked to a higher number of neonates born with low birth weight.¹⁷ The association between maternal, neonatal, and infant vitamin B12 levels has been heterogenous.^12–16

Pregnant women experiencing malnutrition face a heightened risk of micronutrient deficiencies, pregnancy complications, and perinatal outcomes.¹⁸ There are limited data regarding the occurrence of vitamin B12 deficiency in malnourished expectant mothers and its impact on neonatal outcomes. We aimed to assess the vitamin B12 status in malnourished and normally nourished pregnant women and to study the association between maternal B12 levels and cord B12 levels and neonatal anthropometry.

Methods

Results

Of the 126 pregnant women enrolled, 63 were malnourished and 63 were normal nourished. The mean age of the study subject was 26.58 (± 3.79) years. The mean pre-pregnancy weight was 48.68 (± 6.17) kg. Among these women, 75 (59.5%) were primigravidas. mixed diet was followed by 117 (92.9%) women, and all women consumed milk. Among the neonates, 64 (50.8%) were male and 62 (49.2) were female. The mean gestational age of the neonates was 38.39 (± 1.19) weeks. Mean birth weight was 2.77 (± 0.35) kg and 22 (17.5%) neonates belonged to small for gestation age (SGA) category. Maternal and neonatal characteristics are shown in Table 1.

Comparison of maternal anthropometric measurements among malnourished and normal nourished mothers is depicted in Table 2. Birth weight, length, and head circumference of neonates born to malnourished mothers were lower than those of neonates born to mothers with normal nourishment. Sixteen (25.4%) neonates of malnourished mother group were SGA. A comparison of the anthropometric parameters of neonates born to malnourished and normal-nourished mothers is shown in Table 2.

The median cord B12 value was considerably lower than the maternal B12 value, as shown in Table 3. There was a strong positive correlation between maternal and cord B12 levels (rho 0.829, p <0.001). Spearman correlation test for maternal BMI and vitamin B12 levels showed a positive correlation between the two measures (rho 0.590, p <0.001). Both maternal and cord B12 levels were significantly lower in the malnourished group than in the normal-nourished group (Table 4). In malnourished group, 66.8% mothers and 95.2% neonates were vitamin B12 deficient. In normal nourished group, only 1.5% mothers and 4.7% neonates were deficient. The maternal and cord B12 levels in both groups are shown in Table 4. Odd’s ratio for malnourished mothers to have vitamin B12 deficiency was 160 (95% CI 39.43, 649.27). In the malnourished group, the maternal B12 level showed a positive correlation with birth weight (rho 0.363, p = 0.003) and length (rho 0.330, p = 0.008), whereas in the normally nourished group, the cord B12 level was positively correlated with birth weight (rho 0.277 p = 0.028) (Table 5), respectively.

Discussion

Vitamin B12 deficiency is widespread globally, and affects various populations. A study by Ramírez-Vélez et al in a sample representative of pregnant Colombian women, revealed that 18.6% of the population was deficient in vitamin B12 and 41.3% exhibited insufficient vitamin B12.²⁵ In a nutritional intervention study, that enrolled moderately malnourished Malawian mothers, 20.9% of the participants were deficient in vitamin B12.²⁶A study by Yildizdas et al in Turkey reported high rate of maternal vitamin deficiency of 96.3%.²⁷

There is a significant occurrence of vitamin B12 deficiency in Indian women during pregnancy. Studies from western and northern parts of India have reported the highest occurrence of vitamin B12 deficiency during pregnancy, ranging from 70–74%.⁵ A community based cross sectional study by Barney et al., enrolling pregnant women in rural South India, reported an extent of 55% vitamin B12 deficiency. They found obesity and being in the first trimester of pregnancy to be independent risk factors.²⁸ A study conducted by Katre et al. in Pune, which recruited pregnant women at 17 weeks of gestation, indicated that approximately 80% of rural and 65% of urban women exhibited low Vitamin B12 status.²⁹ A prospective cohort study involving pregnant women aged 18-45 years from urban hospitals in Bangalore reported low plasma vitamin B12 levels in 48.6% of women.³⁰ In the present study, 66.8% of women and 95.2% of neonates in the malnourished group exhibited vitamin B12 deficiency.

Despite general assumption that non-vegetarian diet provides sufficient vitamin B12, recent research has reported vitamin B12 deficiency in non-vegetarian population.

A review by Sukumaran et al. suggested that even within non-vegetarian populations, vitamin B12 insufficiency during pregnancy is frequently observed.³¹ Similar results were observed in our study, where there was a high prevalence of maternal vitamin B12 deficiency in a coastal community with high fish consumption. Food taboos targeting pregnant and postpartum women are widely prevalent in India and Southeast Asian countries which may contribute to this deficiency.^32,33

Vitamin B12 levels change during pregnancy across the trimesters. Concentrations of vitamin B12 decreased from the first trimester to the third trimester, as reported by Sukumaran et al.³¹ Similar observations were reported by Sobowale et al. from Bangladesh.³⁴ A cohort study involving healthy pregnant adolescent women from New York revealed decreasing levels of maternal serum cobalamin levels from mid gestation to delivery.³⁵ Hence cord B12 levels may not reflect maternal levels across the trimesters.

Low maternal vitamin B12 levels have resulted in lower neonatal B12 status as reported by previous studies. A study by Adaikalakoteswari et al. found that the offspring of mothers with low B12 levels exhibited significantly lower levels of vitamin B12 than did those of mothers with normal B12 levels.¹² A Study by Finkelstein e t al., who recruited pregnant women at approximately 12 weeks gestation from South India, revealed that vitamin B12 deficiency was prevalent in approximately 63% of women during early pregnancy.³⁵ This deficiency serves as predictor of neonatal vitamin B12 status. Specifically, lower maternal serum vitamin B12 levels were associated with a two-fold increased risk of neonatal vitamin B12 deficiency at birth.³⁶ The present study also reported a positive correlation between maternal and cord vitamin B12 levels, with cord B12 levels being lower than maternal B12 levels. In contrast, a study by Yildizdas et al. involving Turkish mothers and neonates, reported that micronutrient levels in the cord blood surpassed maternal levels.²⁷

The relationships between maternal vitamin B12 and, cord B12 and neonatal anthropometry are heterogenous. In a study by Yildizdas et al., there was a negative correlation between birth weight, head circumference, and cord blood Cbl levels. Interestingly, maternal Cbl levels did not show any correlation with neonatal anthropometry.²⁷ In a retrospective study by Yuan et al. in Eastern China involving 11,549 pregnant women, it was found that elevated maternal serum vitamin B12 levels were correlated with higher birth weight and an increased risk of new born being large.⁷ Sukumar et al. reported that there is no consistent relationship between vitamin B12 sufficiency and LBW.³¹ MAASTHI birth cohort study by Deepa et al. in South India revealed no association between vitamin B12 status and birth weight.³⁰

Hay et al. reported a negative association between cord Cbl and birth weight. The heaviest babies had lower cord Cbl levels. A similar negative association was also observed between birth length and head circumference.³⁷ A secondary analysis of 709 Canadian mother newborn dyads by Tan et al. revealed that maternal serum vitamin B12 biomarkers did not show any association with birth weight or head circumference.³⁸ In the present study, maternal B12 levels in malnourished women showed a positive correlation with birth weight (rho 0.363, p = 0.003) and length (rho 0.330, p = 0.008) but not with head circumference.

Limitations: This study was conducted in a tertiary care hospital, which may restrict the generalizability of its findings to a broader community. Maternal vitamin B12 levels measured only at the time of delivery may not reflect fluctuations throughout pregnancy. A smaller sample size raises concerns regarding the applicability of the results. The presence of coexisting micronutrient deficiencies in malnourished women poses a risk of confounding bias in the interpretation of results.

In conclusion, the present study revealed high rates of vitamin B12 deficiency in malnourished mothers and their neonates. Additionally, there was a positive correlation between birth weight, length, and maternal vitamin B12 levels in malnourished mothers. These findings emphasize the need to address maternal malnutrition and vitamin B12 deficiency to improve neonatal health.