Prenatal Multiple Micronutrient Supplementation Research Articles

A Prenatal Multiple Micronutrient Supplement Produces Higher Maternal Vitamin B-12 Concentrations and Similar Folate, Ferritin, and Zinc Concentrations as the Standard 60-mg Iron Plus 400-μg Folic Acid Supplement in Rural Bangladeshi Women

Background: The effects of prenatal food and micronutrient supplementation on maternal micronutrient status are not well known.Objective: We compared the efficacy and effectiveness of 3 different micronutrient supplements on maternal micronutrient status when combined with food supplementation.Methods: In the MINIMat (Maternal and Infant Nutrition Intervention, Matlab) trial in Bangladesh, 4436 pregnant women were randomly assigned to daily intake of 3 types of micronutrient capsules: 30 mg Fe and 400 μg folic acid (Fe30F), 60 mg Fe and 400 μg folic acid (Fe60F), or multiple micronutrient supplements (MMNs) combined with early (week 9 of pregnancy) or usual (week 20 of pregnancy) food supplementation in a 2 by 3 factorial design. Plasma concentrations of vitamin B-12, folate, ferritin, and zinc were analyzed before the start of micronutrient supplementation (week 14) and at week 30 of pregnancy in 641 randomly selected women. An electronic monitoring device was used to measure the number of capsules taken. The effectiveness of food and micronutrient regimens as well as efficacy per capsule in maternal micronutrient status were analyzed by ANOVA and general linear models.Results: At week 30 of pregnancy, women in the MMN group had higher geometric mean concentrations of vitamin B-12 than women in the Fe60F group (119 compared with 101 pmol/L, respectively); no other differences in effectiveness of micronutrient and food regimens were observed. A dose-response relation between the number of capsules taken and concentrations of folate and ferritin was observed for all micronutrient supplements. Fe30F had lower efficacy per capsule in increasing ferritin concentrations within the first tertile of capsule intake than did Fe60F and MMNs. Because ferritin reached a plateau for all types of micronutrient supplements, there was no difference between the regimens in their effectiveness.Conclusion: Compared with Fe60F, MMNs produced higher maternal vitamin B-12 and similar ferritin and folate concentrations in Bangladeshi women. The MINIMat trial was registered at isrctn.org as ISRCTN16581394.

Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial.

BackgroundIt is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials.Methods and findingsWe conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron–folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: −0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: −0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: −0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: −0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: −0.22, 0.44; p = 0.53) or motor scores (SMD: −0.04; 95% CI: −0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages.ConclusionsThere was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones.Trial registrationClinicalTrials.gov NCT02145000.

Associations Between Gestational Weight Gain Adequacy and Perinatal Outcomes in Tanzania

ObjectivesGestational weight gain (GWG) is associated with fetal and newborn health; however, data from sub-Saharan Africa are limited. We estimated the relationship between GWG and newborn outcomes in a cohort of pregnant women in Tanzania. MethodsWe used data from a prenatal multiple micronutrient supplementation trial among HIV-negative pregnant women enrolled between 12 to 27 weeks gestational age (GA) in Dar es Salaam. GWG adequacy was defined as the ratio of the total observed weight gain over the expected weight gain based on the Institute of Medicine pre-pregnancy body mass index (BMI)-specific guidelines, and categorized as follows: severely inadequate (< 70%), inadequate (70–90%), adequate (90–125%) or excessive (≥125%). Newborn outcomes assessed were: stillbirth, perinatal death, preterm birth (birth < 37 weeks GA), low birthweight (LBW; < 2500 grams), macrosomia (birthweight > 4000 grams), small- and large-for-GA (birthweight-for-GA < 10th percentile and > 90th percentile, respectively), short-for-GA (length-for-GA z-score < -2SD), and microcephaly (head circumference-for-GA z-score < -2SD). Modified Poisson regression with robust standard error was used to estimate the relative risk of newborn outcomes as a function of GWG adequacy, adjusting for confounders. ResultsOverall, 51% (n = 3866/7561) women had severely inadequate or inadequate GWG, 31% had adequate GWG, and 18% had excessive GWG by delivery. Compared to adequate GWG, severely inadequate GWG was associated with increased risk of LBW [Adjusted Relative Risk (95% CI): 1.63 (1.24, 2.14)], SGA [1.76 (1.50, 2.08)], short-for-GA [1.24 (1.04, 1.48)], and microcephaly [1.35 (1.05, 1.73)]; but a lower risk of LGA [0.72 (0.58, 0.89)] and macrosomia [0.31 (0.17, 0.56)]. Inadequate GWG was similarly associated with a higher risk of SGA, short-for-GA, and microcephaly, but lower risk of LGA. Excessive GWG was only associated with a higher risk of LGA and macrosomia. Severely inadequate GWG in the second trimester was associated with preterm birth. GWG adequacy was not associated with stillbirth or perinatal death. ConclusionsInadequate GWG was associated with several indicators of poor newborn size. Interventions to support maternal nutrition during pregnancy are needed and are likely to improve newborn outcomes. Funding SourcesBill and Melinda Gates Foundation; CIHR Fellowship.

Gestational Age, Birth Weight, and Neurocognitive Development in Adolescents in Tanzania

ObjectivesTo investigate the association between gestational age, birthweight, and birthweight adjusted for gestational age, with domains of neurocognitive development and behavioral problems in adolescents in Tanzania.Study designData from a long-term follow-up of adolescents aged 11-15 years born to women previously enrolled in a randomized controlled trial of prenatal multiple micronutrient supplementation in Dar es Salaam, Tanzania, were used. A battery of neurodevelopmental tests were administered to measure adolescent general intelligence, executive function, and behavioral problems. The INTERGROWTH-21st newborn anthropometric standards were used to derive birthweight for gestational age z-scores. We assessed the shape of relationships using restricted cubic splines and estimated the associations of gestational age, birthweight, and birthweight for gestational age z-score with adolescent development using multivariable linear regressions.ResultsAmong adolescents studied (n = 421), higher gestational age (per week), birthweight (per 100 grams), and birthweight for gestational age z-score (per SD) were linearly associated with higher intelligence score (adjusted standardized mean difference, 0.05 SD [95% CI, 0.01-0.09], 0.04 SD [95% CI, 0.02-0.06], and 0.09 SD [95% CI, 0.01-0.17], respectively). Birthweight and birthweight for gestational age z-score, but not gestational age, were also associated with improved executive function. Low birthweight (<2500 g) was associated with lower intelligence and executive function scores. Associations between birthweight and executive function were stronger among adolescents born to women with higher education.ConclusionsThe duration of gestation and birthweight were positively associated with adolescent neurodevelopment in Tanzania. These findings suggest that interventions to improve birth outcomes may also benefit adolescent cognitive function.

Demographic variations and temporal trends in prenatal use of multiple micronutrient supplements in Beijing, 2013-2017.

To provide updated information about demographic variations and temporal trends in the prenatal use of multiple micronutrient (MMN) supplements in the metropolitan areas of China. Descriptive analysis of routine prenatal healthcare data between 2013 and 2017. Chaoyang District, Beijing, China. A total of 197 346 pregnant women who attended their first prenatal care visit and provided information about MMN supplementation during the periconceptional period. Of these pregnant women, 60·6 % reported consuming prenatal MMN supplements. In multivariate-adjusted models, there were significant gradients of age, education and parity in prenatal MMN supplementation, with the highest likelihood of MMN use among the oldest, the most highly educated and nulliparous women (Pfor trend < 0·001). Compared with that among unemployed women, prenatal MMN supplementation was more common among the employed, especially those engaged in business (adjusted relative risks (95 % CI): 1·08 (1·06, 1·10)) and management (1·10 (1·08, 1·12)). The proportion of prenatal MMN supplementation was 57·0 % in 2013, which increased to 63·5 % in 2017 (Pfor trend < 0·001). The trends varied by age, education and parity (Pfor heterogeneity < 0·001), whereas no significant difference was observed in trends across subgroups of ethnicity or occupation. The greatest magnitude increase in MMN supplement use occurred in women of age < 25 years (annual percent change: 5·7 %), less than high school education (9·6 %), parity ≥ 2 (6·8 %) or unemployment (6·1 %). Approximately two-thirds of women consumed prenatal MMN supplements during the periconceptional period in the central area of Beijing and the proportion increased over time, indicating a need to evaluate the effectiveness and safety and to develop a guideline for relatively well-nourished women.

Human Capital and Wage Income Gains of Scaling-Up Maternal Prenatal Nutrition Interventions in Low- and Middle-Income Countries

Abstract Objectives Scaling-up nutrition interventions during pregnancy may provide human capital gains by lowering the risk of adverse birth outcomes associated with reduced long-term socioeconomic outcomes. We estimated gains in years of schooling and lifetime wages of scaling up prenatal maternal nutrition interventions for a 137 low- and middle-income countries. Methods Through a comprehensive review of the literature, we identified four prenatal maternal nutrition interventions with convincing-level of evidence for improving birth outcomes: prenatal multiple micronutrient supplements (MMS), calcium supplements, iron-folic acid supplements (IFA), and balanced protein energy supplements (BEP) among underweight pregnant women (BMI &amp;lt; 18.5 kg/m2). Effect sizes for intervention impact were derived from systematic reviews and random-effects meta-analysis. We focused on low birthweight (LBW) and preterm birth (PTB) as primary birth outcomes. We used the 2015 LBW and PTB prevalence estimates to calculate country-specific absolute reductions attributable to scaling-up a given prenatal nutrition invention. We then used an effect size based on a de novo review of the economics literature to quantify gains in schooling and lifetime wages due to reductions in LBW/PTB under two hypothetical scale-up scenarios of 50% and 90% coverage. Results For each country, returns on schooling and lifetime wages were estimated for scaling-up each prenatal nutrition intervention. For example, in Bangladesh, scaling-up IFA supplements from current coverage of 26% to 90% was estimated to reduce LBW prevalence by 3.2% contributing to a predicted increase of 0.11 million school years and US$153 million in wages per birth cohort. Similarly, scaling-up MMS, calcium supplements, and BEP to 90% coverage was predicted to increase schooling by 0.25, 0.17, and 0.07 million years, and wages by US$338, US$223, and US$97 million, respectively, per birth cohort. Global, regional, and national-level estimates for schooling and wage gains for each nutrition intervention will be presented. Conclusions Our findings indicate that scaling-up prenatal maternal nutrition interventions will contribute to substantial population-level increases in human capital, particularly in countries with a high burden of low birthweight or preterm birth. Funding Sources Bill and Melinda Gates Foundation.

Prenatal early food and multiple micronutrient supplementation trial reduced infant mortality in Bangladesh, but did not influence morbidity.

A previous maternal and infant nutrition intervention in rural Matlab, Bangladesh, showed that prenatal nutrient supplements improved child survival, but had no effect on size at birth. This secondary analysis examined whether prenatal multiple micronutrient supplements (MMS), on their own or combined with an early invitation to receive prenatal food supplements, affected child morbidity. This randomised trial enrolled 4436 pregnant women from November 2001 to October 2003 and allocated them to early or standard invitations to food supplements, in the ninth and 20th weeks of pregnancy, respectively, and supplements of either the standard 60 mg iron with 400 μg folic acid, 30 mg iron with 400 μg folic acid or MMS. Quasi-Poisson regression was used to analyse morbidity. There were 3560 single live births and 3516 had morbidity data. The incidence rates of fever, diarrhoea and acute lower respiratory tract infection were 15.3, 3.6 and 2.3 episodes per person-year, respectively. The separate or combined interventions had no effect on morbidity up to 24 months. Early invitations to prenatal food supplements or prenatal MMS had no effect on common infections in rural Bangladesh, suggesting that earlier findings on improved child survival were not mediated by an effect on child morbidity.

A Prenatal Multiple Micronutrient Supplement Produces Higher Maternal Vitamin B-12 Concentrations and Similar Folate, Ferritin, and Zinc Concentrations as the Standard 60-mg Iron Plus 400-μg Folic Acid Supplement in Rural Bangladeshi Women.

Background: The effects of prenatal food and micronutrient supplementation on maternal micronutrient status are not well known.Objective: We compared the efficacy and effectiveness of 3 different micronutrient supplements on maternal micronutrient status when combined with food supplementation.Methods: In the MINIMat (Maternal and Infant Nutrition Intervention, Matlab) trial in Bangladesh, 4436 pregnant women were randomly assigned to daily intake of 3 types of micronutrient capsules: 30 mg Fe and 400 μg folic acid (Fe30F), 60 mg Fe and 400 μg folic acid (Fe60F), or multiple micronutrient supplements (MMNs) combined with early (week 9 of pregnancy) or usual (week 20 of pregnancy) food supplementation in a 2 by 3 factorial design. Plasma concentrations of vitamin B-12, folate, ferritin, and zinc were analyzed before the start of micronutrient supplementation (week 14) and at week 30 of pregnancy in 641 randomly selected women. An electronic monitoring device was used to measure the number of capsules taken. The effectiveness of food and micronutrient regimens as well as efficacy per capsule in maternal micronutrient status were analyzed by ANOVA and general linear models.Results: At week 30 of pregnancy, women in the MMN group had higher geometric mean concentrations of vitamin B-12 than women in the Fe60F group (119 compared with 101 pmol/L, respectively); no other differences in effectiveness of micronutrient and food regimens were observed. A dose-response relation between the number of capsules taken and concentrations of folate and ferritin was observed for all micronutrient supplements. Fe30F had lower efficacy per capsule in increasing ferritin concentrations within the first tertile of capsule intake than did Fe60F and MMNs. Because ferritin reached a plateau for all types of micronutrient supplements, there was no difference between the regimens in their effectiveness.Conclusion: Compared with Fe60F, MMNs produced higher maternal vitamin B-12 and similar ferritin and folate concentrations in Bangladeshi women. The MINIMat trial was registered at isrctn.org as ISRCTN16581394.

Effects of prenatal multiple micronutrient supplementation on growth and cognition through 2 y of age in rural Bangladesh: the JiVitA-3 Trial

Background: Childhood undernutrition may have prenatal origins, and the impact of prenatal interventions on postnatal growth is not well known.Objective: We assessed the effects of prenatal multiple micronutrient (MM) supplementation on child growth and cognitive development.Design: In a cluster-randomized controlled trial in rural Bangladesh, prenatal MM supplementation compared with iron-folic acid (IFA) supplementation was examined for its impact on growth assessed longitudinally from birth up to 24 mo of age (n = 8529) and, in a subsample (n = 734), on cognitive function at 24 mo of age by use of the Bayley scales of infant and toddler development–third edition test.Results: Prevalence of stunting at birth [length for age z score (LAZ): <−2] was 31.9% in the MM and 35.7% in the IFA groups (P < 0.001); however, LAZ increased during the first 3–4 mo in both groups. With the use of a linear random-effects model, prenatal MM-exposed children sustained a higher mean predicted LAZ of ∼0.10 at 1 and 3 mo and 0.06 at 6 mo of age compared with children in the IFA group. Supplementation reduced the prevalence of stunting at 1 (RR: 0.95; 95% CI: 0.92, 0.98) and 3 (RR: 0.91; 95% CI: 0.88, 0.94) mo of age. Differences between groups were absent by 6, 12, and 24 mo of age, when nearly 50% of children had stunted growth. Ponderal and linear growth velocities were somewhat slower from 3 to 12 mo of age in the MM group than in the IFA group, but not from 12 to 24 mo of age. There was no difference between groups on composite scores of cognition, language, and motor performance at 24 mo of age.Conclusions: In this Bangladeshi trial, maternal pre- and postnatal MM supplementation resulted in improvements in LAZ and reduction in stunting through 3 mo of age, but not thereafter and had no impact on cognitive and motor function at 2 y. This trial was registered at clinicaltrials.gov as NCT000860470.

Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh.

Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies.Trial RegistrationClinicalTrials.gov NCT00860470

The Long‐Term Impact of Water and Sanitation on Childhood Cognition

Unsafe water and poor sanitation may negatively affect brain development, however few studies have examined the long‐term impact on children's cognitive function.Our objective was to assess the relationship between household access to safe water and toilet facilities during the prenatal period with childhood cognition 9‐12 years later.The Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), conducted in 2001‐2004 In Indonesia, compared the health effects of a prenatal multiple micronutrient supplement to an iron and folic acid supplement. At baseline, information collected included water supply, sanitation, and maternal education. We assessed cognition in 3687 children of SUMMIT participants at 9‐12 years of age. Children of mothers who had access to safe toilet facilities during pregnancy had higher scores in Digit Span Forward (95%CI 0.008‐0.17, P&lt;0.03), Information (95%CI 0.08‐0.2, P&lt;0.001), Block Design (95%CI 0.01‐0.1, P&lt;0.02), and Word List Memory (95%CI 0.006‐0.17, P&lt;0.03) tests after adjusting for cluster randomization, data collector, maternal education, socio‐economic status and home environment score. Children of mothers with access to safe water during pregnancy had higher Word List Memory scores (95%CI 0.01‐0.19, P&lt;0.02).The finding that safe water and toilet facilities were associated with child cognition even after adjustment for socio‐economic status and maternal education suggests that interventions to improve water and sanitation in early life may have long‐term benefits on child cognitive abilities.

Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood: follow-up of a double-blind randomised controlled trial in Nepal.

A randomised trial of prenatal multiple micronutrient supplementation in Nepalese women increased birthweight and weight at 2 years of age in offspring, compared to those born to mothers who only received iron and folic acid supplements. Further follow-up of this cohort provided an opportunity to investigate the effect of antenatal multiple micronutrients on subsequent lung function by measuring spirometry at 7-9 years of age in C: hildren born during the trial. 841 children (80% of the cohort) were seen at mean±sd 8.5±0.4 years. Technically successful spirometry results were obtained in 793 (94.3%) children, 50% of whom had been randomised to micronutrient supplementation. Background characteristics, including anthropometry, were similar in the two allocation groups. Lung function was also similar, mean (95% CI) difference in z-scores (supplementation minus control) was -0.08 (-0.19-0.04), -0.05 (-0.17-0.06) and -0.04 (-0.15-0.07) for forced expiratory volume in 1 s (FEV1), forced vital capacity and FEV1/FVC, respectively. Compared with healthy white children, FEV1 and FVC in the "healthy" Nepalese children were ∼1 (∼13%) z-score lower, with no difference in FEV1/FVC. We conclude that, compared with routine iron and folic acid, multiple micronutrient supplementation during pregnancy has no effect on spirometric lung function in Nepalese children at 8.5 years of age.

Effects of Prenatal Multiple Micronutrient Supplementation on Miscarriage in Developing Countries: A Meta-analysis of Randomized Controlled Trials

Effects of Prenatal Multiple Micronutrient Supplementation on Miscarriage in Developing Countries: A Meta-analysis of Randomized Controlled Trials

The effect of prenatal multiple micronutrient supplementation on biomarkers of placental angiogenesis in rural Bangladesh (804.2)

Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased gestational age, yet it is unknown if improved placental function contributes to this effect. We assessed the effects of prenatal MM vs. iron and folic acid (IFA) on placental angiogenesis (the formation of blood vessels from existing ones) in a subset of women (n=395) participating in a double blinded, cluster‐randomized trial in rural Bangladesh. Angiogenic factors assessed in maternal plasma at 10 and 32 weeks gestation were placental growth factor (PlGF), angiopoietin 2 (Ang‐2), vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR‐1). Concentrations were similar at baseline (10 weeks); PlGF, VEGF and VEGFR‐1 increased from the first to third trimester, whereas Ang‐2 decreased in both groups (p&lt;0.01). At 32 weeks, PlGF and Ang‐2 were positively associated with gestational age and placental weight at birth and VEGFR‐1 was positively associated with placental weight (all p&lt;0.05). Ang‐2 was 3.1 (95% CI: 0.20, 6.0) ng/mL higher at 32 weeks in mothers taking MM vs. IFA. There was no difference between MM and IFA groups in other angiogenic factors at 32 weeks, or their change from 10 to 32 weeks. MM supplementation improved angiogenic Ang‐2, reflective of enhanced placental vascular remodeling that may explain part of the MM impact on birth size through increased gestational age.Grant Funding Source: Supported by The Thrasher Research Fund, NIH (T32HD046405), The Gates Foundation, and USAID

Effects of exclusive breastfeeding intervention on child growth and body composition: theMINIMat trial,Bangladesh

Exclusive breastfeeding (EBF) for 6months is recommended for optimal infant health, but the evidence for longer-term impacts is weak. We examined whether randomization to receive EBF counselling (BFC) in rural Bangladeshi women had an impact on childhood growth trajectories and body composition. In the Maternal and Infant Nutrition Interventions in Matlab trial, 4436 pregnant women were randomized to six equally sized, food and micronutrient groups. Of these, 3214 were randomized during the last trimester of pregnancy to receive either BFC or the usual/standard health message (UHM). Their infants were extensively followed up, with anthropometric measurements between 0 and 54months and assessment of body composition at 54months. The mean duration of EBF in the BFC group was 111days compared to 76days in the UHM group (mean difference: 35.0days, 95% CI 30.6-39.5, p<0.001). There was no difference in growth trajectories between the BFC and UHM groups and no difference in body composition at 54months. Children exposed to prenatal multiple micronutrients (vs 60mg iron and folate) combined with BFC (vs UHM), however, had slower linear growth (mean difference -0.17 SD score, p<0.01). Exclusive breastfeeding counselling resulted in neither differential growth trajectories in infancy and childhood, nor body composition differences at 54months. The combination of prenatal multiple micronutrient supplementation (MMS) and BFC was unfavourable for linear growth during 0-54months, which raises questions about possible negative effects of MMS.

Effects of Prenatal Micronutrient and Early Food Supplementation on Maternal Hemoglobin, Birth Weight, and Infant Mortality Among Children in Bangladesh

Nutritional insult in fetal life and small size at birth are common in low-income countries and are associated with serious health consequences. To test the hypothesis that prenatal multiple micronutrient supplementation (MMS) and an early invitation to food supplementation would increase maternal hemoglobin level and birth weight and decrease infant mortality, and to assess whether a combination of these interventions would further enhance these outcomes. A randomized trial with a factorial design in Matlab, Bangladesh, of 4436 pregnant women, recruited between November 11, 2001, and October 30, 2003, with follow-up until June 23, 2009. Participants were randomized into 6 groups; a double-masked supplementation with capsules of 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, including 30 mg of iron and 400 μg of folic acid, was combined with food supplementation (608 kcal 6 days per week) randomized to either early invitation (9 weeks' gestation) or usual invitation (20 weeks' gestation). Maternal hemoglobin level at 30 weeks' gestation, birth weight, and infant mortality. Under 5-year mortality was also assessed. Adjusted maternal hemoglobin level at 30 weeks' gestation was 115.0 g/L (95% CI, 114.4-115.5 g/L), with no significant differences among micronutrient groups. Mean maternal hemoglobin level was lower in the early vs usual invitation groups (114.5 vs 115.4 g/L; difference, -0.9 g/L; 95% CI, -1.7 to -0.1; P = .04). There were 3625 live births out of 4436 pregnancies. Mean birth weight among 3267 singletons was 2694 g (95% CI, 2680-2708 g), with no significant differences among groups. The early invitation with MMS group had an infant mortality rate of 16.8 per 1000 live births vs 44.1 per 1000 live births for usual invitation with 60 mg of iron and 400 μg of folic acid (hazard ratio [HR], 0.38; 95% CI, 0.18-0.78). Early invitation with MMS group had an under 5-year mortality rate of 18 per 1000 live births (54 per 1000 live births for usual invitation with 60 mg of iron and 400 μg of folic acid; HR, 0.34; 95% CI, 0.18-0.65). Usual invitation with MMS group had the highest incidence of spontaneous abortions and the highest infant mortality rate. Among pregnant women in poor communities in Bangladesh, treatment with multiple micronutrients, including iron and folic acid combined with early food supplementation, vs a standard program that included treatment with iron and folic acid and usual food supplementation, resulted in decreased childhood mortality. isrctn.org Identifier: ISRCTN16581394.

Adherence and Costs of Micronutrient Supplementation in Pregnancy in a Double-Blind, Randomized, Controlled Trial in Rural Western China

Efforts to determine the impact of prenatal multivitamin supplementation on birth outcome have been carried out in several developing countries. A review of factors that would impact the effectiveness of prenatal supplementation under normal field conditions is currently lacking and will be required for expanded supplementation programs. An efficacy trial of a multiple micronutrient supplement for pregnant women was conducted in rural western China, and additional information on side effects, rates of adherence, program inputs, and cost was also gathered. To examine reports of side effects and rates of adherence to prenatal multiple micronutrient supplementation in comparison with supplementation with folic acid and with iron-folic acid, and to describe inputs and costs associated with prenatal supplementation in China. A cluster-randomized, double-blind, controlled trial was conducted in two rural counties in northwest China. All pregnant women in villages were randomly assigned to take daily supplements of folic acid, iron-folic acid, or a recommended daily allowance of 15 vitamins and minerals from enrollment until delivery. Information was collected from the women on side effects and adherence. Program inputs and costs of supplementation were tracked. Descriptive statistics were used for the analysis. The biological effectiveness of prenatal multiple micronutrient supplements is reported elsewhere. Less than 4% of women withdrew from the study because of side effects. Adherence to supplementation was high: the supplements were consumed on more than 90% of the days on which they were available for consumption. The mean number of supplements consumed was high at 165 capsules, and about 40% consumed the recommended 180 supplements during pregnancy. High adherence to a prenatal supplement schedule can be achieved when mothers have frequent contact with trained health workers and a reliable supply of supplements.

Preventing low Birthweight through Maternal Multiple Micronutrient Supplementation: A Cluster-Randomized, Controlled Trial in Indramayu, West Java

Micronutrient deficiencies may contribute to a higher incidence of low birthweight (LBW). UNICEF/United Nations University/World Health Organization jointly proposed a formulation for a multiple micronutrient supplement for pregnant women, and several effectiveness trials were conducted to assess its impact. To evaluate the efficacy of prenatal multiple micronutrient supplementation for improving birth size, pregnancy outcome, and maternal micronutrient status in comparison with iron-folic acid supplementation. We carried out a cluster-randomized, controlled trial in Indramayu, Indonesia, involving 843 pregnant women. Of these, 432 received multiple micronutrients and 411 received iron-folic acid. Fieldworkers visited the women daily to observe supplement consumption and record fetal loss and mortality. The mean number of supplements consumed during pregnancy and 30 days postpartum was high (136 in the group receiving multiple micronutrients and 140 in the iron-folic acid group). The women consumed the supplements on average 5 days per week. Although there were no significant differences between the groups in the percentage of infants with LBW there was a trend toward a lower incidence of LBW in the group receiving multiple micronutrients (6.3% vs. 7.3%), and the mean birthweight was 40 g higher in the group receiving multiple micronutrients than in the iron-folic acid group, although the difference was not significant. Among those who consumed 90 or more supplements during pregnancy, women taking multiple micronutrients had a 3.3% combined rate of miscarriage, stillbirth, or neonatal death, as compared with 6.9% for those taking iron-folic acid only (p < .049). The anemia rates in the two groups were similar after supplementation, even though the amount of iron in the multiple micronutrient supplement was half that in the iron-folic acid supplement. Serum retinol was higher in the group receiving multiple micronutrients. Multivitamin supplementation use among pregnant women is as effective as iron-folic acid in improving anemia status and appears to have other benefits for maternal and child nutritional status.

An Effectiveness Trial of Multiple Micronutrient Supplementation during Pregnancy in Vietnam: Impact on Birthweight and on Stunting in Children at around 2 Years of Age

Multiple micronutrient deficiencies during pregnancy in Vietnam may contribute to poor fetal growth and stunting, which are major determinants of the health and development offuture generations. We assessed the effects of prenatal multiple micronutrient supplementation on maternal weight gain during pregnancy, infant birthweight, and height of the child at around 2 years of age. We conducted a nonrandomized, non-blinded, side-by-side effectiveness trial in a normal program setting in three districts in the Red River Delta in the north of Vietnam. Women in one district received the standard iron-folic acid supplement during prenatal care; women in the second district received the multiple micronutrient supplement; in the third district, gender training was provided in addition to the multiple micronutrient supplement. Cluster surveys were carried out in the three districts at the end of the trial to verify low birthweight (LBW) and at around 2 years after the trial to measure children's height and weight, as well as to collect demographic data on the mothers. Mean birthweight was higher in the districts receiving multiple micronutrient supplements than in the district receiving iron-folic acid tablets. The mean birthweight was 166 g higher in the district receiving multiple micronutrients and 105 g higher in the district receiving multiple micronutrients with gender training than in the district receiving iron-folic acid (p < .05). The prevalence of LBW children (< 2500 g) was lower in the district receiving multiple micronutrients (4.0%) and the district receiving multiple micronutrients plus gender training (5.8%) than in the district receiving iron-folic acid (10.6%) (p < .05). Children at around 2 years of age were taller in the district receiving multiple micronutrients (82.66 cm) and the district receiving multiple micronutrients plus gender training (83.61 cm) than in the district receiving iron-folic acid (81.64 cm), and the stunting rates were about 10% lower than in the district receiving iron-folic acid. Multiple micronutrient supplementation during pregnancy could be an important intervention to help reduce stunting rates in Vietnam.

Prenatal multiple micronutrient supplementation impact on biochemical indicators during pregnancy and postpartum

The objective of this analysis was to test the impact of daily supplementation with multiple micronutrients (MM) during pregnancy on Zn, vitamin A and folate status compared to iron only (Fe). The study was carried out during 1997-2000 in a semi-urban community in Morelos state, Mexico. Women were randomly assigned to MM (n= 249) or Fe (n= 258) and received supplements daily (6 d/wk) under supervision by the field team from recruitment (approximately 9 weeks pregnancy) until delivery. Blood samples were collected on a sub-sample of women at baseline, 32 weeks pregnancy and one month postpartum (1PP) and assessed for serum zinc, retinol and whole blood folate (baseline and 1PP only). A breast milk sample was extracted at 1PP and assessed for retinol content. At baseline there was no significant difference between supplementation groups in mean Zn, retinol or folate concentrations or the prevalence of deficiencies (Zn 12.2%, vitamin A 2.8%, folate 5.3%). Mean change in Zn and retinol concentrations from baseline to 32 weeks pregnancy did not differ between groups or between baseline and 1PP for Zn, retinol or folate. At 1PP, there was a tendency (p= 0.09) towards a lower prevalence of folate deficiency/depletion in the MM group (10.0%) than the Fe group (18.5%). MM supplementation during pregnancy did not improve zinc or vitamin A status compared to Fe only. There is some indication that folate status may have improved with MM supplementation despite low prevalence of deficiency. While lack of response in serum retinol may be explained by generally adequate status, the lack of impact on zinc status requires further exploration.