Vitamin D deficiency in pregnancy and the risk of preterm birth: a nested case-control study.

BACKGROUND: Each year, an estimated 15 million babies are born preterm. Micronutrient deficiencies, including vitamin D deficiency (VDD), are common in many low- and middle-income countries (LMICs), and these conditions are often associated with adverse pregnancy outcomes. Bangladesh experiences a high prevalence of VDD. The country also has a high preterm birth (PTB) rate. Using data from a population-based pregnancy cohort, we estimated the burden of VDD during pregnancy and its association with PTB. METHODS: Pregnant women (N = 3,000) were enrolled after ultrasound confirmation of gestational age at 8-19 weeks of gestation. Trained health workers prospectively collected phenotypic and epidemiological data at scheduled home visits. Trained phlebotomists collected maternal blood samples at enrollment and 24 -28 weeks of gestation. Aliquots of serum were stored at -800 C. We conducted a nested case-control study with all PTB (n = 262) and a random sample of term births (n = 668). The outcome, PTB, was defined as live births < 37 weeks of gestation, based on ultrasound. The main exposure was vitamin D concentrations of 24-28 weeks maternal blood samples. The analysis was adjusted for other PTB risk factors. Women were categorized as VDD (lowest quartile of 25(OH)D; < = 30.25 nmol/L) or not deficient (upper-three quartiles of 25(OH)D; > 30.25 nmol/L). We used logistic regression to determine the association of VDD with PTB, adjusting for potential confounders. RESULTS: The median and interquartile range of serum 25(OH)D was 38.0 nmol/L; 30.18 to 48.52 (nmol/L). After adjusting for co-variates, VDD was significantly associated with PTB [adjusted odds ratio (aOR) = 1.53, 95% confidence interval (CI) = 1.10 - 2.12]. The risk of PTB was also higher among women who were shorter (aOR = 1.81, 95% CI: 1.27-2.57), primiparous (aOR = 1.55, 95% CI = 1.12 - 2.12), passive smokers (aOR = 1.60, 95% CI = 1.09 - 2.34), and those who received iron supplementation during pregnancy (aOR = 1.66, 95% CI: 1.17, 2.37). CONCLUSION: VDD is common in Bangladeshi pregnant women and is associated with an increased risk of PTB.

Prevalence and Risk Factors of Vitamin B12 Deficiency among Pregnant Women in Rural Bangladesh.

Vitamin B12 deficiency is associated with an increased risk of pregnancy complications and adverse birth outcomes. However, data on vitamin B12 deficiency in pregnant Bangladeshi women are limited. This study examines vitamin B12 deficiency and marginal deficiency in rural Bangladeshi women during early and late pregnancies. Some 522 women whose gestational age was <20 weeks were recruited. Serum vitamin B12 concentrations were measured at baseline and after 14 weeks of iron-folate supplementation. Logistic regression analysis examined the association of various socio-demographic, dietary, and pregnancy-related factors with vitamin B12 deficiency and marginal deficiency. Overall, 19% of the women during early pregnancy had vitamin B12 deficiency (serum vitamin B12 concentration < 203 pg/mL) and nearly 40% had marginal deficiency (serum vitamin B12 concentration 203 to <300 pg/mL). Vitamin B12 deficiency doubled to 38% during late pregnancy, while marginal deficiency slightly increased to 41.7%. The pregnant women with a gestational age of ≥27 weeks had a higher risk of developing vitamin B12 deficiency (OR = 2.61; 95% CI = 1.096−6.214) than those of a gestational age of <27 weeks. Vitamin B12 deficiency was significantly higher in pregnant women in rented accommodation (OR = 13.32; 95% CI = 1.55−114.25) than in those living in their own house. Vitamin B12 deficiency was significantly higher among women who consumed red or organ meat <3 times a week than in those who consumed it more often (OR = 2.327, 95% CI = 1.194−4.536). None of these factors were significantly associated with marginal vitamin B12 deficiency. In conclusion, vitamin B12 deficiency and marginal deficiency among pregnant rural Bangladeshi women increased as their pregnancies progressed. Increasing gestational age, living in a rented house, and the consumption of red or organ meat <3 times a week were identified as the independent risk factors of vitamin B12 deficiency in this population. Further research with more in-depth assessments of dietary vitamin B12 intakes is needed to develop an intervention program preventing vitamin B12 deficiency in this population.

Prenatal nutrition supplementation and growth biomarkers in preadolescent Bangladeshi children: A birth cohort study.

Little is known about the usefulness of biomarkers to study the influence of prenatal nutrition supplementation in improving child growth. Anthropometry is not always straightforward to understand how nutrition might impact growth, especially in settings with high rates of malnutrition and infections. We examined the effects of prenatal supplementation on growth and growth biomarkers and the relationship between anthropometric measures and growth biomarkers of children at 4.5 and 9 years of age. Children were enrolled from a longitudinal cohort, where mothers were randomized into daily supplementation with either early-food (≤9 gestation week [GW]) or usual-food (~20 GW) (608 kcal 6 days/week); they were further randomized to receive 30-mg or 60-mg iron with 400-µg folic acid, or multiple micronutrients (MM) in rural Bangladesh. Anthropometric data were collected from mothers at GW8 and children at 4.5 (n = 640) and 9 years (n = 536). Fasting blood was collected from children at each age. Early-food supplementation showed reduced stunting and underweight at 4.5 and 9 years age respectively compared to usual-food. Prenatal supplementations did not have any effect on growth biomarkers except for STAT5b expression which was lower in the early-food compared to the usual-food group (ß = -0.21; 95 CI% = -0.36, -0.07). Plasma concentrations of 25-hydroxy vitamin D and calcium were both inversely associated with weight-for-age and body mass index-for-age Z-scores at 9 years, particularly in early-food and MM groups. Although there was minimal effect on child growth by prenatal supplementations, the associations of biomarkers with anthropometric indices were predominantly driven by timing of food or MM supplementations.

Effect of routine iron-folic acid supplementation among rural pregnant women living in low- and high-groundwater-iron areas in Bangladesh.

OBJECTIVE: The present study investigated the risks and benefits of routine Fe-folic acid (IFA) supplementation in pregnant women living in low- and high-groundwater-Fe areas in Bangladesh. DESIGN: A case-controlled prospective longitudinal study design was used to compare the effect of daily Fe (60 mg) and folic acid (400 µg) supplementation for 3·5 months. SETTING: A rural community in Bangladesh. PARTICIPANTS: Pregnant women living in low-groundwater-Fe areas (n 260) and high-groundwater-Fe areas (n 262). RESULTS: Mean Hb and serum ferritin concentrations at baseline were significantly higher in pregnant women in the high-groundwater-Fe areas. After supplementation, the mean change in Hb concentration in the women in the low-groundwater-Fe areas (0·10 g/dl) was higher than that in the pregnant women in the high-groundwater-Fe areas (-0·08 g/dl; P = 0·052). No significant changes in the prevalence of anaemia or Fe deficiency (ID) in either group were observed after IFA supplementation; however, the prevalence of Fe-deficiency anaemia (IDA) decreased significantly in the women in the low-groundwater-Fe areas. The risk of anaemia, ID and IDA after supplementation did not differ significantly between the groups. None of the participants had Fe overload. However, a significant proportion of the women in the high- and low-groundwater-Fe areas remained anaemic and Fe-deficient after supplementation. CONCLUSION: IFA supplementation significantly increased the Hb concentration in pregnant women living in the low-groundwater-Fe areas. Routine supplementation with 60 mg Fe and 400 µg folic acid does not pose any significant risk of haemoconcentration or Fe overload. Further research to identify other nutritional and non-nutritional contributors to anaemia is warranted to prevent and treat anaemia.

Maternal Micronutrient Supplementation and Long Term Health Impact in Children in Rural Bangladesh.

BACKGROUND: Limited data is available on the role of prenatal nutritional status on the health of school-age children. We aimed to determine the impact of maternal micronutrient supplementation on the health status of Bangladeshi children. METHODS: Children (8.6-9.6 years; n = 540) were enrolled from a longitudinal mother-child cohort, where mothers were supplemented daily with either 30mg iron and 400µg folic acid (Fe30F), or 60mg iron and 400µg folic acid (Fe60F), or Fe30F including 15 micronutrients (MM), in rural Matlab. Blood was collected from children to determine the concentration of hemoglobin (Hb) and several micronutrients. Anthropometric and Hb data from these children were also available at 4.5 years of age and mothers at gestational week (GW) 14 and 30. RESULTS: MM supplementation significantly improved (p≤0.05) body mass index-for-age z-score (BAZ), but not Hb levels, in 9 years old children compared to the Fe30F group. MM supplementation also reduced markers of inflammation (p≤0.05). About 28%, 35% and 23% of the women were found to be anemic at GW14, GW30 and both time points, respectively. The prevalence of anemia was 5% and 15% in 4.5 and 9 years old children, respectively. The adjusted odds of having anemia in 9 year old children was 3-fold higher if their mothers were anemic at both GW14 and GW30 [Odds Ratio (OR) = 3.05; 95% Confidence Interval (CI) 1.42, 6.14, P = 0.002] or even higher if they were also anemic at 4.5 years of age [OR = 5.92; 95% CI 2.64, 13.25; P<0.001]. CONCLUSION: Maternal micronutrient supplementation imparted beneficial effects on child health. Anemia during pregnancy and early childhood are important risk factors for the occurrence of anemia in school-age children.

Intestinal mucosal permeability of severely underweight and nonmalnourished Bangladeshi children and effects of nutritional rehabilitation.

OBJECTIVE: Lactulose/mannitol (L/M) intestinal permeability tests were completed to compare the intestinal function of severely underweight children recovering from diarrhea and other illnesses and of nonmalnourished children from the same communities, and to evaluate the effects of food supplementation, with or without psychosocial stimulation, on the changes in intestinal function among the underweight children. PATIENTS AND METHODS: Seventy-seven malnourished children completed intestinal permeability studies at baseline and 3 months after receiving 1 of the following randomly assigned treatment regimens: group-C--fortnightly follow-up at community-based follow-up units, including growth monitoring and promotion, health education, and micronutrient supplementation, n = 17; group-SF--same as group-C plus supplementary food (SF) to provide 150 to 300 kcal/day, n = 23; group-PS--same as group-C plus psychosocial stimulation (PS), n = 17; or group-SF + PS--same as group-C plus SF and PS, n = 20. Seventeen nonmalnourished children were included as comparison subjects. RESULTS: The malnourished children's mean ± SD initial age was 13.1 ± 4.0 months, their mean weight-for-age z score was -3.82 ± 0.61, and their median (interquartile range) urinary L/M recovery ratio was 0.16 (0.10-0.28). Eighty-four percent of the children had L/M ≥ 0.07, suggestive of impaired intestinal function. The median L/M of the malnourished children was significantly greater than that of 17 relatively well-nourished children (median 0.09; interquartile range 0.05-0.12; P = 0.001). There were no significant differences in baseline characteristics of the severely malnourished children by treatment group. Following treatment, the L/M ratio improved in all of the groups (P < 0.001), but there were no significant differences in these changes by treatment group. There was a significant positive association between weight gain and the magnitude of improvement in L/M ratio (r = 0.30, P = 0.012). CONCLUSIONS: Intestinal mucosal function, as measured by sugar permeability, is impaired among severely underweight children. Intestinal permeability improves in relation to weight gain, but intestinal mucosal recovery is not specifically related to the types or amount of food supplementation or PS provided in this trial.