Pratibha Dwarkanath

Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban South Indians.

Objective:To assess the maternal sociodemographic, anthropometric, dietary and micronutrient status in apparently healthy pregnant women in order to determine their associations with intrauterine growth retardation (IUGR).Design:Prospective observational study.Setting:Bangalore City, India.Subjects:A total of 478 women were recruited at 12.9±3.3 weeks of gestation and followed up at the first, second and third trimesters of pregnancy and at delivery. The dropout rate was 8.5%.Interventions:None.Main outcome measures:Birth weight was measured at hospital delivery.Results:The mean birth weight was 2.85±0.45 kg. In all, 28.6% of newborns were IUGR. There was a strong inverse relationship between maternal educational level and risk of IUGR. A low body weight at baseline was also associated with a high risk of IUGR. Compared with women in the highest quartile for second trimester weight gain, those in the lowest quartile had a significantly higher adjusted odds ratio (AOR: 3.98; 95% CI: 1.83, 8.65) for IUGR. Women in the lowest tertile for serum vitamin B12 concentration during each of the three trimesters of pregnancy had significantly higher risk of IUGR (AOR: 5.98, 9.28 and 2.81 for trimesters 1–3, respectively).Conclusions:The present study demonstrates associations between educational status, maternal weight and gestational weight gain with IUGR. Importantly, in a subsample, there were strong associations of vitamin B12 status with IUGR, suggesting that better socioeconomic conditions, improved nutritional status and early detection of vitamin B12 deficiency in pregnancy combined with appropriate interventions are likely to play an important role in reducing IUGR.Sponsorship:This research was partly supported by the GlaxoSmithKline Consumer Healthcare Ltd, India.

High folate and low vitamin B-12 intakes during pregnancy are associated with small-for-gestational age infants in South Indian women: a prospective observational cohort study

BACKGROUND Folic acid supplementation in those with a low vitamin B-12 intake or status may have adverse effects. These effects are unknown with regard to birth outcome in pregnant Indian women who are routinely supplemented with high doses of folic acid. OBJECTIVE The objective was to examine the association of unbalanced vitamin B-12 and total folate (folic acid supplement + dietary folate) intakes during pregnancy with outcomes in small-for-gestational-age (SGA) infants. DESIGN This was a prospective observational cohort study of 1838 pregnant women in South India. Low intake of dietary vitamin B-12 in the presence of high total folate intake was examined as the ratio of vitamin B-12 intake to total folate intake. RESULTS The inadequacy of vitamin B-12 intake (<1.2 μg/d) assessed by a food-frequency questionnaire in the first, second, and third trimesters of pregnancy was 25%, 11%, and 10%, respectively. Multivariate log binomial regression showed that low vitamin B-12 and folate intakes in the first trimester were independently associated with a higher risk of SGA. In a subgroup of women with high supplemental folic acid intakes in the second trimester, those with the lowest tertile of vitamin B-12:folate ratio had a higher risk of SGA outcome than did those in the highest tertile (adjusted RR: 2.73; 95% CI: 1.17, 6.37). A similar trend was observed in the analysis of blood micronutrient status in a random subset (n = 316) of the sample. CONCLUSIONS These findings suggest that, in addition to vitamin B-12 and folate deficiencies alone, there may be adverse birth outcomes associated with unbalanced vitamin B-12 and folate intakes or status during pregnancy. These findings have important implications for the antenatal B vitamin supplementation policy in India. This trial was registered at the Clinical Trial Registry of India as 2013/07/005342.

The effect of fish and ω-3 LCPUFA intake on low birth weight in Indian pregnant women

Background:Inadequate consumption of fish could be a risk factor for low birth weight (LBW). This study assessed fish intake and ω-3 LCPUFA intake and status for their association with LBW in a cohort of urban, south Indian pregnant women.Subjects/methods:In a prospective cohort study, data on maternal fish intake and ω-3 LCPUFA intake and status of 676 women were obtained at baseline (first trimester), the second and third trimesters of pregnancy. Infant birth weight was measured immediately following hospital delivery. The dropout rate was 7.6%.Results:Fifty-six percent of the study women consumed fish with low daily median intakes (3.4, 4.1 and 3.8 g day−1 at the three trimesters, respectively). Consequently, the median intakes of EPA and DHA during pregnancy were also low at 2.1 and 10.1 mg day−1, respectively. EPA and DHA intakes were associated with their status in erythrocyte membrane phospholipids during pregnancy (r=0.40 and 0.36, r=0.34 and 0.32 and r=0.37 and 0.41, at the three trimesters, respectively, all P<0.001). Women who did not eat fish during the third trimester had a significantly higher risk of LBW (OR: 2.49, P=0.019). Similarly, low EPA intake during the third trimester had an association with a higher risk of LBW (OR: 2.75, P=0.011).Conclusions:Among low fish-eating pregnant women, fish intake in the third trimester was closely associated with birth weight. Supplementation with ω-3 LCPUFA during pregnancy may have important implications for fetal development in India.

Anthropometry and body composition of south Indian babies at birth

OBJECTIVES To assess the consequences on body composition of increasing birth weight in Indian babies in relation to reported values in Western babies, and to assess the relationship between maternal and neonatal anthropometry and body composition. DESIGN Prospective observational study. SETTING Bangalore City, India. SUBJECTS A total of 712 women were recruited at 12.5+/-3.1 weeks of gestation (mean+/-standard deviation, SD) and followed up until delivery; 14.5% were lost to follow-up. Maternal body weight, height, mid upper-arm circumference and skinfold thicknesses were measured at recruitment. Weight and body composition of the baby (skinfold thicknesses, mid upper-arm circumference, derived arm fat index and arm muscle index; AFI and AMI, respectively) were measured at birth in hospital. RESULTS The mean+/-SD birth weight of all newborns was 2.80+/-0.44 kg. Birth weight was significantly related to the triceps and subscapular skinfold thickness of the baby. In a small number of babies with large birth weight for gestational age, there was a relatively higher normalised AFI relative to AMI than for babies with lower or appropriate birth weight for gestational age. Maternal height and fat-free mass were significantly associated with the babys length at birth. CONCLUSIONS Skinfold thicknesses in Indian babies were similar to those reported in a Western population with comparable birth weights, and the relationship of AFI to birth weight appeared to be steeper in Indian babies. Thus, measures to increase birth weight in Indian babies should take into account possible adverse consequences on body composition. There were no significant relationships between maternal anthropometry and body composition at birth on multivariate analysis, except for sum of the babys skinfold thicknesses and maternal fat-free mass (P<0.02).

Low maternal vitamin B12 status during pregnancy is associated with reduced heart rate variability indices in young children

Vitamin B12 plays a vital role in neuronal development, particularly in myelinogenesis. Demyelination of the autonomic nervous system occurs early in vitamin B12 deficiency. However, the impact of maternal vitamin B12 deficiency during pregnancy on neuronal function in the offspring is poorly documented. The objective of this study was to assess cardiac autonomic nervous activity in children born to mothers with low vitamin B12 status during pregnancy using heart rate variability (HRV) indices in the frequency domain. Seventy-nine healthy children between 3 and 8 years of age were evaluated from an ongoing birth cohort. The blood sample of the mother had been stored and was analysed for plasma vitamin B12 following enrolment of the child. Subjects were divided, based on the median maternal first trimester vitamin B12 status (114 pmol L(-1)), into lower (n = 40) and higher (n = 39) vitamin B12 status groups. A lead II electrocardiogram was recorded in the supine posture and subjected to HRV analysis. Low-frequency HRV in absolute units was reduced significantly in children of the lower vitamin B12 status group (P = 0.03) and was 53% that of the higher vitamin B12 status group. There was a significant association between low-frequency and total power HRV with cord blood vitamin B12 levels (ρ = 0.31 and 0.30, both P = 0.03). In summary, children born to mothers with a lower vitamin B12 status have a reduced cardiac sympathetic activity. The long-term implication of this needs to be evaluated by follow-up studies.

In vivo arginine production and nitric oxide synthesis in pregnant Indian women with normal and low body mass indices

Background/Objectives:Nitric oxide (NO) has been proposed as a mediator of vascular expansion during pregnancy. Inability to increase NO synthesis and/or production of its precursor, arginine, may be a contributor to pregnancy-induced hypertension or preeclampsia. Because maternal weight is associated with blood pressure and risk of preeclampsia during pregnancy, it may also influence arginine and/or NO production. The purpose of this study was to determine the in vivo arginine production and NO synthesis rate in pregnant women with normal (n=10) and low (n=10) body mass indices (BMIs).Subjects/Methods:Arginine flux and NO synthesis rate were measured in the postabsorptive state with constant infusions of 15N2-arginine and 13C,2H4-citrulline. Plasma concentrations of arginine and NO metabolites were also measured. Kinetic parameters were correlated to maternal variables, gestational age, birth weight and blood pressure.Results:Endogenous arginine flux was significantly faster in the low-BMI compared with normal-BMI women in the first trimester (63.1±3.4 vs 50.2±2.0 μmol/kg per h, P<0.01), but not in the second. Plasma NO concentration was higher (44.7±5.3 vs 30.4±1.9 μmol/l, P=0.03) and its rate of synthesis trended faster in the low-BMI compared with normal-BMI group in the second trimester. Maternal weight and BMI were negatively correlated with arginine flux in both trimesters and NO synthesis in the second trimester.Conclusions:These findings suggest, but do not prove, that maternal BMI may be a factor in the ability to produce NO during pregnancy and may be one way by which BMI influences blood pressure during pregnancy.

Whole body methionine kinetics, transmethylation, transulfuration and remethylation during pregnancy

BACKGROUND & AIMS There is evidence from a study of pregnant American women that methionine transmethylation (TM) and remethylation (RM) rates increases and transulfuration (TS) decreases as pregnancy progresses from trimester 1 to 3. To determine whether pregnant Indian women can make this adaptation successfully, methionine kinetics, TS, TM, and RM were measured in Indian women in early and late pregnancy. METHODS Measurements were made in the postabsorptive and fed states in the 1st and 3rd trimesters of pregnancy by infusing 1-(13)C,(2)H3-methionine in 24 women, 12 with low (≤150 pmol L(-1)) and 12 with normal (≥200 pmol L(-1)) vitamin B12 status at recruitment. RESULTS From trimester 1 to 3, except RM which decreased significantly, there was no change in any weight-specific methionine kinetic parameter. When expressed per whole body, methionine flux from protein breakdown increased significantly from trimester 1 to 3 in the fed and postabsorptive states. Flux to protein synthesis also increased significantly in the fed state. Rates of TM, TS and RM did not change, regardless of vitamin B12 status at recruitment. Protein and methionine intakes correlated with TM and RM rates and the change in RM from trimester 1 to 3 correlated with the change in dietary protein intake. CONCLUSION These results suggest that methionine flux and its utilization for protein synthesis increases in Indian women as pregnancy progresses from trimester 1 to 3. TM and RM rates do not increase however, possibly because of inadequate protein intake and not because of vitamin B12 deficiency at trimester 1.

The role of vitamin D in pre-eclampsia: a systematic review

BackgroundThe etiology of pre-eclampsia (PE) is not yet fully understood, though current literature indicates an upregulation of inflammatory mediators produced by the placenta as a potential causal mechanism. Vitamin D is known to have anti-inflammatory properties and there is evidence of an inverse relationship between dietary calcium intake and the incidence of PE. Evidence of the role of vitamin D status and supplementation in the etiology and prevention of PE is reviewed in this article along with identification of research gaps to inform future studies.MethodsWe conducted a structured literature search using MEDLINE electronic databases to identify published studies until February 2015. These sources were retrieved, collected, indexed, and assessed for availability of pregnancy-related data on PE and vitamin D.ResultsSeveral case-control studies and cross-sectional studies have shown an association between vitamin D status and PE, although evidence has been inconsistent. Clinical trials to date have been unable to show an independent effect of vitamin D supplementation in preventing PE.ConclusionsThe included clinical trials do not show an independent effect of vitamin D supplementation in preventing PE; however, issues with dose, timing, and duration of supplementation have not been completely addressed.

Maternal fat and fatty acid intake and birth outcomes in a South Indian population

BACKGROUND The quantity and quality of dietary fat during pregnancy play a key role in the growth and development of the fetus. The aim of this study was to examine the association between fat and fatty acid intakes in early pregnancy and birth outcomes in an apparent healthy normal South Indian population. METHODS The study was a prospective observational cohort of 1838 pregnant women, conducted in South India. Intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fats (PUFA) were assessed by a validated food-frequency questionnaire, and correlated with birthweight and incidence of small for gestational age (SGA) infants. RESULTS This is a population that traditionally consumes diets that are low in SFA and n-3 PUFA, but high in linoleic acid (LA, 18:2 n-6). The data show that consumption of low SFA was associated with decreased birthweight and an increased risk of SGA [adjusted odds ratio (AOR) 1.45; 95% confidence interval (CI): 1.1, 2.1). Similar results were seen with n-3 PUFA: low intakes of alpha linolenic acid (ALNA, 18:3 n-3) as well as low intakes of long-chain (LC) n-3 PUFA were associated with increased risk of SGA (AOR 1.70; 95% CI: 1.1, 2.6, and AOR 1.27; 95% CI: 1.1, 2.1, respectively). Increased intakes of SFA and ALNA were predominantly associated with lower intakes of cereals and higher intakes of milk and milk products. CONCLUSIONS These findings show that higher intakes of SFA and n-3 PUFA in early stages of pregnancy are associated with increased birthweight and reduced incidence of SGA in a South Indian population.

Association of oral iron supplementation with birth outcomes in non-anaemic South Indian pregnant women.

Background/Objectives:Iron in high doses or when given to non-anaemic women may have adverse effects on pregnancy outcomes. This study aimed to estimate the supplemental iron intake in non-anaemic pregnant women attending an urban antenatal care setting in South India and examine the association of supplemental iron intake with birth outcomes.Subjects/Methods:A cohort of 1196 non-anaemic pregnant women was studied. Daily supplemental iron intake was calculated as total supplemental iron consumed (mg) during pregnancy divided by the total number of days the supplement was recommended. Association of tertiles of supplemental iron intake with term low birth weight (tLBW), preterm delivery and small for gestational age (SGA) was examined using log-binomial regression, adjusting for maternal age, height, body mass index at recruitment, parity, education and type of delivery.Results:Mean haemoglobin in trimester 1 was 12.4±0.9 g/dl and mean supplemental iron intake was 37.7±4.0 mg/day. Women in the highest tertile (>39.2 mg/day) of supplemental iron intake had an increased risk of tLBW as compared with the lowest tertile (⩽36.6 mg/day) (adjusted risk ratio: 1.89; 95% confidence interval: 1.26, 2.83). Although supplemental iron intake was negatively correlated with gestational age (r=−0.20, P<0.001) and birth weight (r=−0.07, P=0.011), there was no association between preterm delivery or SGA and supplemental iron intake.Conclusions:It appears that iron supplementation in non-anaemic pregnant women may not be beneficial, as we have observed the adverse effects with a prescribed dose of 45 mg/day. This may warrant the consideration of an individualized approach for antenatal iron supplementation, especially in non-anaemic women.