Periconceptional intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further reduce the risk of neural tube defects in offspring: a United States population-based case-control study of women meeting the folic acid recommendations.

BACKGROUND: Neural tube defects (NTDs) still occur among some women who consume 400 µg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs. OBJECTIVES: To investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations. METHODS: Data were from the National Birth Defects Prevention Study (United States population-based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 µg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center. RESULTS: NTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake. CONCLUSIONS: Our findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.

Associations of Diet Quality, Socioeconomic Factors, and Nutritional Status with Gestational Weight Gain among Pregnant Women in Dar es Salaam, Tanzania.

Background: Gestational weight gain (GWG) is a modifiable factor associated with maternal and child health outcomes, but the relationship between diet quality and GWG has not been evaluated using metrics validated for low-income and middle-income countries (LMICs). Objective: This study aimed to investigate relationships between diet quality, socioeconomic characteristics, and GWG adequacy using the novel Global Diet Quality Score (GDQS), the first diet quality indicator validated for use across LMIC. Methods: Weights of pregnant women enrolled between 12 and 27 wk of gestation (N = 7577) were recorded in Dar es Salaam, Tanzania, from 2001 to 2005 during a prenatal micronutrient supplementation trial. GWG adequacy was the ratio of measured GWG to Institute of Medicine-recommended GWG, categorized into severely inadequate (<70%), inadequate (70 to <90%), adequate (90 to <125%), or excessive (≥125%). Dietary data were collected using 24-h recalls. Multinomial logit models were used to estimate relationships between GDQS tercile, macronutrient intake, nutritional status, and socioeconomic characteristics and GWG. Results: GDQS scores in the second [relative risk (RR): 0.82; 95% confidence interval (CI): 0.70, 0.97] tercile were associated with lower risk of inadequate weight gain than those in the first tercile. Increased protein intake was associated with higher risk of severely inadequate GWG (RR: 1.06; 95% CI: 1.02, 1.09). Nutritional status and socioeconomic factors were associated with GWG: underweight prepregnancy BMI (in kg/m2) with a higher risk of severely inadequate GWG (RR: 1.49; 95% CI: 1.12, 1.99), overweight or obese BMI with a higher risk of excessive GWG (RR: 6.80; 95% CI: 5.34, 8.66), and a higher education (RR: 0.61; 95% CI: 0.42, 0.89), wealth (RR: 0.68; 95% CI: 0.48, 0.80), and height (RR: 0.96; 95% CI: 0.95, 0.98) with a lower risk of severely inadequate GWG. Conclusions: Dietary indicators showed few associations with GWG. However, stronger relationships were revealed between GWG, nutritional status, and several socioeconomic factors.This trial was registered at clinicaltrials.gov as NCT00197548.

Gestational weight gain during the second and third trimesters and adverse pregnancy outcomes, results from a prospective pregnancy cohort in urban Tanzania.

BACKGROUND: Appropriate gestational weight gain (GWG) is important for optimal pregnancy outcomes. This study prospectively evaluated the associations between GWG during the second and third trimesters of pregnancy and adverse pregnancy outcomes in an urban Tanzanian pregnancy cohort. METHODS: We used data from a randomized clinical trial conducted among pregnant women recruited by 27 weeks of gestation in Dar es Salaam, Tanzania (N = 1230). Women's gestational weight was measured at baseline and at monthly antenatal visits. Weekly GWG rate during the second and third trimesters was calculated and characterized as inadequate, adequate, or excessive, in conjunction with measured or imputed early-pregnancy BMI status according to the 2009 Institute of Medicine (IOM) GWG guidelines. We used multivariable Poisson regression with a sandwich variance estimator to calculate risk ratios (RR) for associations of GWG with low birth weight, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). Degree of appropriate GWG defined using additional metrics (i.e., percentage of adequacy, z-score) and potential effect modification by maternal BMI were additionally evaluated. RESULTS: According to the IOM guidelines, 517 (42.0%), 270 (22.0%), and 443 (36.0%) women were characterized as having inadequate, adequate, and excessive GWG, respectively. Overall, compared to women with adequate GWG, women with inadequate GWG had a lower risk of LGA births (RR = 0.54, 95% CI: 0.36-0.80) and a higher risk of SGA births (RR = 1.32, 95% CI: 0.95-1.81). Women with inadequate GWG as defined by percentage of GWG adequacy had a higher risk of LBW (OR = 1.93, 95% CI: 1.03-3.63). In stratified analyses by early-pregnancy BMI, excessive GWG among women with normal BMI was associated with a higher risk of preterm birth (RR = 1.59, 95% CI: 1.03-2.44). CONCLUSIONS: A comparatively high percentage of excessive GWG was observed among healthy pregnant women in Tanzania. Both inadequate and excessive GWGs were associated with elevated risks of poor pregnancy outcomes. Future studies among diverse SSA populations are warranted to confirm our findings, and clinical recommendations on optimal GWG should be developed to promote healthy GWG in SSA settings. TRIAL REGISTRATION: This trial was registered as "Prenatal Iron Supplements: Safety and Efficacy in Tanzania" (NCT01119612; http://clinicaltrials.gov/show/NCT01119612 ).

Pregnancy is a critical lifetime event for both mother and the offspring, with implications in short-term and long-term health consequences. Gestational weight gain (GWG) is an important modifiable factor for pregnancy outcomes related to infant body size and weight and prematurity. Countries in sub-Saharan Africa (SSA) have long had poor rates of insufficient GWG and pregnancy complications associated with insufficient GWG. Nevertheless, some SSA countries are experiencing economic transitions accompanied with changes in lifestyle and nutrition, which might impact pregnancy experiences, including GWG and pregnancy outcomes. This study aimed to characterize recent GWG patterns and the associations of both inadequate and excessive GWG with adverse pregnancy outcomes, using an urban pregnancy cohort in Tanzania. This study found that 42.0%. 22.0%, and 36.0% of women had insufficient, adequate, and excessive GWG, respectively. Insufficient GWG was associated with higher risks of small infant size and low infant body weight, and excessive GWG was associated with higher risk of preterm birth, particularly among women with body mass index 18.5­25.0 kg/m². Results from the present study highlight that both insufficient and excessive GWG are of potential public health concerns in urban centers of SSA, concerning upward trends in obesity and possibly obesity-related pregnancy consequences. Local public health practitioners should continue to advocate longitudinal GWG monitoring and care among African pregnant women, and optimal GWG with feasible and effective clinical guidelines should be developed to prevent both over- and under-gaining of maternal weight during pregnancy.

Associations between Gestational Weight Gain Adequacy and Neonatal Outcomes in Tanzania.

INTRODUCTION: Gestational weight gain (GWG) is associated with fetal and newborn health; however, data from sub-Saharan Africa are limited. METHODS: We used data from a prenatal micronutrient supplementation trial among a cohort of human immunodeficiency virus-negative pregnant women in Dar es Salaam, Tanzania to estimate the relationships between GWG and neonatal outcomes. GWG adequacy was defined as the ratio of the total observed weight gain over the recommended weight gain based on the Institute of Medicine body mass index-specific guidelines. Neonatal outcomes assessed were stillbirth, perinatal death, preterm birth, low birthweight, macrosomia, small-for-gestational age (SGA), large-for-gestational age (LGA), stunting at birth, and microcephaly. Modified Poisson regressions with robust standard error were used to estimate the relative risk of newborn outcomes as a function of GWG adequacy. RESULTS: Of 7,561 women included in this study, 51% had severely inadequate (<70%) or inadequate GWG (70 to <90%), 31% had adequate GWG (90 to <125%), and 18% had excessive GWG (≥125%). Compared to adequate GWG, severely inadequate GWG was associated with a higher risk of low birthweight, SGA, stunting at birth, and microcephaly, whereas excessive GWG was associated with a higher risk of LGA and macrosomia. CONCLUSION: Interventions to support optimal GWG are needed and may contribute to preventing adverse neonatal outcomes.

Effects of prenatal and postnatal maternal multiple micronutrient supplementation on child growth and morbidity in Tanzania: a double-blind, randomized-controlled trial.

BACKGROUND: Maternal micronutrient status is critical for child growth and nutrition. It is unclear whether maternal multiple micronutrient supplementation (MMS) during pregnancy and lactation improves child growth and prevents child morbidity. METHODS: This study aimed to determine the effects of prenatal and postnatal maternal MMS on child growth and morbidity. In this double-blind, randomized-controlled trial, 8428 HIV-negative pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. From pregnancy (12-27 weeks of gestation) through to 6 weeks postpartum, participants were randomized to receive daily oral MMS or placebo. All women received daily iron and folic acid during pregnancy. From 6 weeks postpartum through to 18 months postpartum, 3100 women were re-randomized to MMS or placebo. Child-growth measures, haemoglobin concentrations and infectious morbidities were assessed longitudinally from birth to ≤18 months. RESULTS: Prenatal MMS led to modest increases in weight-for-age z-scores (mean difference: 0.050; 95% confidence interval: 0.002, 0.099; p = 0.04) and length-for-age z-score (mean difference: 0.062; 95% confidence interval: 0.013, 0.111; p = 0.01) during the first 6 months of life but not thereafter. Prenatal or postnatal MMS did not have benefits for other child outcomes. CONCLUSIONS: Whereas maternal MMS is a proven strategy to prevent adverse birth outcomes, other approaches may also need to be considered to curb the high burdens of child morbidity and growth faltering.

Multivitamin Supplementation Is Associated with Greater Adequacy of Gestational Weight Gain among Pregnant Women in Tanzania.

BACKGROUND: Gestational weight gain (GWG) is a modifiable risk factor associated with adverse birth outcomes. Studies have shown that the provision of multiple micronutrient supplements to pregnant women reduces the risk of low birth weight. However, the effect of multiple micronutrient supplements on GWG has been understudied. OBJECTIVES: We examined the effect of daily supplementation of pregnant women with multivitamins on GWG in relation to the GWG recommendation by the Institute of Medicine (IOM). METHODS: Pregnant women with gestational age between 12 and 27 wk were randomly assigned to receive daily multivitamins or placebo until delivery. Weight was measured at enrollment and every follow-up visit. Percentage adequacy of GWG was calculated as actual GWG divided by the recommended GWG according to the IOM recommendation. Binary outcomes included severely inadequate (<70%), inadequate (<90%), and excessive GWG (≥125%). The analysis included 7573 women with singleton pregnancies. Multiple linear regression models were used to examine the association between multivitamin supplementation and percentage adequacy of GWG, and log-binomial models were used for binary outcomes. RESULTS: The mean percentage adequacy of GWG was 96.7% in the multivitamin arm and 94.4% in the placebo arm, with a mean difference of 2.3% (95% CI: 0.3%, 4.2%; P = 0.022). Compared with women in the placebo arm, those who received multivitamins had a lower risk of severely inadequate GWG (RR: 0.90; 95% CI: 0.83, 0.97; P = 0.008) and inadequate GWG (RR: 0.95; 95% CI: 0.91, 0.99; P = 0.018). No significant difference was found in excessive GWG. CONCLUSIONS: Multivitamin supplementation increased GWG and reduced the risk of severely inadequate and inadequate GWG among pregnant women in Tanzania. Together with previously reported beneficial effects of the supplements on birth outcomes in low- and middle-income countries, our findings support scaling up the use of prenatal supplements that include multivitamins in addition to iron and folic acid.This trial was registered at clinicaltrials.gov as NCT00197548.

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

OBJECTIVES: To 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 DESIGN: Data 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. RESULTS: Among 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. CONCLUSIONS: The 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.

Breast milk vitamin B12 concentration and incidence of diarrhea and respiratory infections among infants in urban Tanzania: a prospective cohort study.

OBJECTIVE: A recent trial of vitamin B12 supplementation among Indian children 6-30 months found no effect on the incidence of diarrhea and respiratory infections. These results differ with studies in adults that showed improvement of the immune response following treatment with vitamin B12. We sought to determine how the adequacy of vitamin B12 concentrations in breast milk could act as immune modulator and protect against the incidence of diarrhea and respiratory infections of children up to 18 months in urban Tanzania. RESULTS: A prospective cohort study was undertaken to determine the association of breast milk vitamin B12 concentration with the incidence of acute respiratory infection and diarrhea among infants in urban Tanzania. A random sample of 491 women enrolled in a trial of multivitamins provided milk for B12 analysis at or around 6 weeks postpartum. Of 491 women, 345 had breast milk vitamin B12 inadequacy (< 310 pmol/L). Using generalized estimating equations, we found no overall association of milk vitamin B12 concentration with incident diarrhea and acute respiratory infections in infants. Studies measuring longitudinal changes of breast milk B12 concentration over time are needed to clarify the role of breast milk vitamin B12 in childhood infections.

Prenatal Zinc and Vitamin A Reduce the Benefit of Iron on Maternal Hematologic and Micronutrient Status at Delivery in Tanzania.

BACKGROUND: Zinc and vitamin A supplementation have both been shown to affect iron status, hemoglobin (Hb) concentration, and anemia in animal and human studies. However, evidence on their combined use in pregnancy, in the context of iron-folic acid (IFA) supplementation, remains limited. OBJECTIVE: This study determined the effects of prenatal zinc, vitamin A, and iron supplementation on maternal hematologic and micronutrient status at delivery in Tanzania. METHODS: We analyzed 2 large randomized controlled trials, using generalized estimating equations, and examined the effect of daily zinc (25 mg) and vitamin A (2500 IU) supplementation starting in the first trimester of pregnancy compared with placebo (n = 2500), and separately evaluated the safety and efficacy of daily iron (60 mg) supplementation among iron-replete pregnant women (n = 1500). Blood samples from baseline and delivery were tested for Hb, serum ferritin, soluble transferrin receptor, plasma zinc, and zinc protoporphyrin. RESULTS: Zinc and vitamin A supplementation were associated with lower Hb concentrations at delivery of  -0.26 g/dL (95% CI: -0.50, -0.02 g/dL) and -0.25 g/dL (95% CI: -0.49, -0.01 g/dL), respectively. Vitamin A increased mean ferritin concentrations at delivery (14.3 µg/L, 95% CI: 1.84, 29.11 µg/L), but was associated with increased risk of severe anemia (RR: 1.41; 95% CI: 1.06, 1.88). Among women who were iron replete at baseline, iron supplementation reduced the risk of iron depletion at delivery by 47% (RR: 0.53; 95% CI: 0.43, 0.65). There was no effect of zinc or iron supplements on plasma zinc concentrations. CONCLUSIONS: Our findings support existing WHO guidelines on prenatal iron, vitamin A, and zinc supplementation among pregnant women. In this setting, scaling uptake of prenatal iron supplements is warranted, but prenatal zinc and vitamin A supplementation did not benefit maternal hematologic status at delivery. In settings where vitamin A deficiency is endemic, the efficacy and safety of the WHO recommended prenatal vitamin A supplementation require further evaluation.

Are out-of-school adolescents at higher risk of adverse health outcomes? Evidence from 9 diverse settings in sub-Saharan Africa.

OBJECTIVES: We analysed mutually comparable surveys on adolescent attitudes and behaviours from nine sites in seven sub-Saharan African countries, to determine the relationship between school enrolment and adolescent health outcomes. METHODS: Data from the Africa Research, Implementation Science, and Education Network cross-sectional adolescent health surveys were used to examine the associations of current school enrolment, self-reported general health and four major adolescent health domains: (i) sexual and reproductive health; (ii) nutrition and non-communicable diseases; (iii) mental health, violence and injury; and (iv) healthcare utilisation. We used multivariable Poisson regression models to calculate relative risk ratios with 95% confidence intervals (CI), controlling for demographic and socio-economic characteristics. We assessed heterogeneity by gender and study site. RESULTS: Across 7829 adolescents aged 10-19, 70.5% were in school at the time of interview. In-school adolescents were 14.3% more likely (95% CI: 6-22) to report that their life is going well; 51.2% less likely (95% CI: 45-67) to report ever having had sexual intercourse; 32.6% more likely (95% CI: 9-61) to report unmet need for health care; and 30.1% less likely (95% CI: 15-43) to report having visited a traditional healer. School enrolment was not significantly associated with malnutrition, low mood, violence or injury. Substantial heterogeneity was identified between genders for sexual and reproductive health, and in-school adolescents were particularly less likely to report adverse health outcomes in settings with high average school enrolment. CONCLUSIONS: School enrolment is strongly associated with sexual and reproductive health and healthcare utilisation outcomes across nine sites in sub-Saharan Africa. Keeping adolescents in school may improve key health outcomes, something that can be explored through future longitudinal, mixed-methods, and (quasi-)experimental studies.

OBJECTIFS: Nous avons analysé des enquêtes mutuellement comparables sur les attitudes et les comportements d'adolescents dans neuf sites dans sept pays d'Afrique subsaharienne, afin de déterminer la relation entre la scolarisation et les résultats de la santé des adolescents. MÉTHODES: Des données provenant d'enquêtes transversales sur la santé des adolescents menées par le Réseau Africain de Recherche, d'Implémentation, de Science et d'Education ont été utilisées pour examiner les associations existant entre la scolarisation, l'état de santé général autodéclaré et les quatre principaux domaines de la santé des adolescents: (i) santé sexuelle et reproductive ; (ii) nutrition et maladies non transmissibles; (iii) santé mentale, violence et blessures et (iv) utilisation des soins de santé. Nous avons utilisé des modèles de régression multivariée de Poisson pour calculer les rapports de risque relatifs avec des intervalles de confiance (IC) à 95%, en tenant compte des caractéristiques démographiques et socioéconomiques. Nous avons évalué l'hétérogénéité par sexe et par site d'étude. RÉSULTATS: Sur 7.829 adolescents âgés de 10 à 19 ans, 70,5% étaient à l'école au moment de l'enquête. Les adolescents scolarisés étaient 14,3% (IC95%: 6-22) plus susceptibles de déclarer que leur vie se passait bien, 51,2% (IC95%: 45-67) moins susceptibles de déclarer avoir déjà eu des rapports sexuels, 32,6% (IC95%: 39-91) plus susceptibles de signaler un besoin de soins de santé non satisfait et 30,1% (IC95%: 15-43) moins susceptibles de déclarer avoir rendu visite à un guérisseur traditionnel. La scolarisation n'était pas associée de manière significative à la malnutrition, à la mauvaise humeur, à la violence ou aux blessures. Une hétérogénéité substantielle a été identifiée entre les sexes pour la santé sexuelle et reproductive, et les adolescents scolarisés étaient particulièrement moins susceptibles de faire état de résultats défavorables pour la santé dans les milieux où la moyenne de scolarisation était élevée. CONCLUSIONS: La scolarisation est fortement associée aux résultats en matière de santé sexuelle et reproductive et d'utilisation des soins de santé dans neuf sites en Afrique subsaharienne. Garder les adolescents à l'école peut améliorer les principaux résultats de santé, ce qui peut être exploré dans le cadre de futures études longitudinales.

Effect of antenatal and infant micronutrient supplementation on middle childhood and early adolescent development outcomes in Tanzania.

BACKGROUND: There is growing evidence that nutritional interventions in the first 1000 days of life may influence long-term health and development outcomes. Few studies have examined the effect of maternal and infant micronutrient supplementation on development outcomes in sub-Saharan Africa. METHODS: We conducted a follow-up study of two randomized trials of antenatal and infant micronutrient supplementation conducted in Dar es Salaam, Tanzania. We assessed the effect of maternal multiple micronutrient (MMN) supplementation in pregnancy on development of children at 11-14 years of age. We also examined the effect of infant zinc and MMN supplementation on development at 6-8 years of age. We used generalized linear models to assess standardized mean differences (SMDs) in general intelligence, executive function, and mental health scores. RESULTS: We followed up 446 children whose mothers were enrolled in the maternal MMN supplementation trial and 365 children who were enrolled in the infant zinc and MMN supplementation trial. We found no effect of maternal MMN supplementation on general intelligence (SMD: -0.03; 95% CI: -0.15, 0.09), executive function (SMD: 0.00; 95% CI: -0.11, 0.11), and mental health scores (SMD: 0.06; 95% CI: 10.10, 0.22). We also found no effect of either infant zinc or MMN supplementation on any of the three development domains (p-values > 0.05). CONCLUSIONS: We found that antenatal MMN supplementation and infant zinc and MMN supplementation did not have a large effect on development outcomes in middle childhood and early adolescence in Tanzania.

Prenatal nutrition, stimulation, and exposure to punishment are associated with early child motor, cognitive, language, and socioemotional development in Dar es Salaam, Tanzania.

BACKGROUND: Despite growing evidence that early life experiences and exposures can impact child development, there is limited research on how prenatal and early life nutrition and early life parenting practices predict specific domains of child development in resource-limited settings. This study examines the association between prenatal factors, birth outcomes, and early life characteristics with motor, cognitive/language, and socioemotional development in Tanzania. METHODS: We assessed motor, cognitive/language, and socioemotional development among a cohort of 198 children aged 20-39 months in Dar es Salaam, Tanzania, whose mothers were previously enrolled in a randomized, placebo-controlled trial of prenatal vitamin A and zinc supplementation. Linear regression models were used to assess standardized mean differences in child development scores for randomized prenatal regimen and pregnancy, delivery, and early childhood factors. RESULTS: Children born to mothers randomized to prenatal vitamin A had significantly lower reported motor scores in minimally adjusted and multivariate analyses, -0.29 SD, 95% CI [-0.54, -0.04], p = 0.03, as compared with children whose mothers did not receive vitamin A. There was no significant effect of randomized prenatal zinc on any development domain. Greater caregiver-child stimulation was associated with 0.38 SD, 95% CI [0.14, 0.63], p < 0.01, better cognitive/language scores, whereas children who experienced both verbal and physical punishment had 0.29 SD, 95% CI [-0.52, -0.05], p = 0.02, lower scores in socioemotional development. Maternal completion of primary school was associated with higher reported motor and cognitive/language development. Further, children of mothers who were <155 cm tall had lower cognitive and language scores. CONCLUSION: Prenatal vitamin A supplements in a setting with low levels of vitamin A deficiency may not provide child development benefits. However, integrated environmental, educational, parenting, and stimulation interventions may have large positive effects across child development domains in resource-limited settings.

Does early vitamin B12 supplementation improve neurodevelopment and cognitive function in childhood and into school age: a study protocol for extended follow-ups from randomised controlled trials in India and Tanzania.

INTRODUCTION: As many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods of neurodevelopment. METHODS AND ANALYSIS: In this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12 supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12 supplementation in different periods during early life and measure the outcomes later in childhood. ETHICS AND DISSEMINATION: The study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access. TRIAL REGISTRATION NUMBER: NCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam).

Maternal Dietary L-Arginine and Adverse Birth Outcomes in Dar es Salaam, Tanzania.

The amino acid arginine is a physiological precursor to nitric oxide, which is a key mediator of embryonic survival, fetal growth, and pregnancy maintenance. We evaluated the association between consumption of the amino acid arginine and the rate of adverse birth outcomes using data from a double-blind, randomized, placebo-controlled micronutrient supplementation trial among pregnant women in Dar es Salaam, Tanzania (2001-2004). Dietary intakes of arginine were assessed using repeated 24-hour recalls that were administered throughout pregnancy. Participants (n = 7,591) were monitored by research midwives throughout follow-up to assess pregnancy outcomes. Cubic-restricted splines and multivariable log-Poisson regression with empirical standard errors were used to estimate the continuous and categorical associations between arginine intake and adverse birth outcomes. Compared with women within the lowest quintile of arginine intake, those within the highest quintile had 0.79 times the risk of preterm birth before 37 weeks (95% confidence interval: 0.63, 1.00; P = 0.03). The continuous associations of arginine intake with preterm birth before 37 weeks and with preterm birth before 34 weeks were characterized by an initial rapid decrease in risk with increasing intake (P for nonlinearity < 0.01). Arginine intake was not associated with fetal loss or giving birth to infants who were born small for their gestational ages. This data suggest that the association between dietary arginine intake and preterm birth warrants further investigation.

Vitamin A and Zinc Supplementation Among Pregnant Women to Prevent Placental Malaria: A Randomized, Double-Blind, Placebo-Controlled Trial in Tanzania.

AbstractVitamin A and zinc are important for immune function and may improve host defense against malaria and reduce the risk of adverse pregnancy outcomes. Our objective was to determine whether daily oral supplementation with either or both nutrients starting in the first trimester reduces the risk of placental malaria and adverse pregnancy outcomes. We undertook a randomized, double-blind placebo-controlled trial with a factorial design among 2,500 human immunodeficiency virus-negative primigravid or secundigravid pregnant women in their first trimester of pregnancy in Dar es Salaam, Tanzania. We randomly allocated equal numbers of participants to 2,500 IU of vitamin A, 25 mg of zinc, both 2,500 IU of vitamin A and 25 mg of zinc, or a placebo until delivery. A total of 625 participants were allocated to each treatment group. Our primary outcome, placental malaria infection (past or current), was assessed in all randomized participants for whom placental samples were obtained at delivery (N = 1,404), which represents 56% of total participants and 62% of all pregnancies lasting 28 weeks or longer (N = 2,266). Birth outcomes were obtained for 2,434 of the 2,500 randomized participants. Secondary outcomes included small for gestational age (SGA) births and prematurity. All analyses were intent to treat. Those who received zinc had a lower risk of histopathology-positive placental malaria compared with those who did not receive zinc (risk ratio = 0.64, 95% confidence interval = 0.44, 0.91), but neither nutrient had an effect on polymerase chain reaction-positive malaria, SGA, or prematurity. No safety concerns were identified. We recommend additional studies in other geographic locations to confirm these findings.

Preconceptional Iron Intake and Gestational Diabetes Mellitus.

Our objective was to assess the impact of preconceptional heme and non-heme iron on gestational diabetes mellitius (GDM) in the Boston University Slone Epidemiology Birth Defects Study (BDS). This retrospective cohort analysis included 7229 participants enrolled in the BDS between 1998 and 2008 who gave birth to non-malformed infants and were free of pre-existing diabetes. All data were collected through structured interviews conducted within 6 months of delivery. Calorie-adjusted and multivariable odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models. Preconceptional dietary heme iron was modestly associated with an elevated risk of GDM among those (multivariable OR comparing the fifth quintile to the first: 1.55; 95% CI 0.98, 2.46). Conversely, preconceptional dietary non-heme iron was associated with a decreased risk of GDM among those in the fifth quintile of intake compared to the first (multivariable OR: 0.48; 95% CI 0.28, 0.81). Women who consumed supplemental iron during preconception also had a decreased risk of GDM (multivariable OR: 0.78; 95% CI 0.60, 1.02). In conclusion, our data support a positive association between preconceptional heme iron intake and GDM and an inverse association between preconceptional non-heme iron intake from foods and preconceptional intake from supplements.

Iron Supplementation Affects Hematologic Biomarker Concentrations and Pregnancy Outcomes among Iron-Deficient Tanzanian Women.

BACKGROUND: Iron deficiency is a highly prevalent micronutrient abnormality and the most common cause of anemia globally, worsening the burden of adverse pregnancy and child outcomes. OBJECTIVE: We sought to evaluate the response of hematologic biomarkers to iron supplementation and to examine the predictors of the response to iron supplementation among iron-deficient pregnant women. METHODS: We identified 600 iron-deficient (serum ferritin ≤12 µg/L) pregnant women, aged 18-45 y, presenting to 2 antenatal clinics in Dar es Salaam, Tanzania using rapid ferritin screening tests, and prospectively followed them through delivery and postpartum. All women received 60 mg Fe and 0.25 mg folate daily from enrollment until delivery. Proportions meeting the thresholds representing deficient hematologic status including hemoglobin <110 g/L, ferritin ≤12 µg/L, serum soluble transferrin receptor (sTfR) >4.4 mg/L, zinc protoporphyrin (ZPP) >70 mmol/L, or hepcidin ≤13.3 µg/L at baseline and delivery were assessed. The prospective change in biomarker concentration and the influence of baseline hematologic status on the change in biomarker concentrations were assessed. Regression models were estimated to assess the relation of change in biomarker concentrations and pregnancy outcomes. RESULTS: There was significant improvement in maternal biomarker concentrations between baseline and delivery, with increases in the concentrations of hemoglobin (mean difference: 15.2 g/L; 95% CI: 13.2, 17.2 g/L), serum ferritin (51.6 µg/L; 95% CI: 49.5, 58.8 µg/L), and serum hepcidin (14.0 µg/L; 95% CI: 12.4, 15.6 µg/L) and decreases in sTfR (-1.7 mg/L; 95% CI: -2.0, -1.3 mg/L) and ZPP (-17.8 mmol/L; 95% CI: -32.1, 3.5 mmol/L). The proportions of participants with low hemoglobin, ferritin, and hepcidin were 73%, 93%, and 99%, respectively, at baseline and 34%, 12%, and 46%, respectively, at delivery. The improvements in biomarker concentrations were significantly greater among participants with poor hematologic status at baseline - up to 12.1 g/L and 14.5 µg/L for hemoglobin and ferritin concentrations, respectively. For every 10-g/L increase in hemoglobin concentration, there was a 24% reduced risk of perinatal mortality (RR = 0.76; 95% CI: 0.59, 0.99) and a 23% reduced risk of early infant mortality (RR = 0.77; 95% CI: 0.60, 0.99). The risk of anemia at delivery despite supplementation was predicted by baseline anemia (RR = 2.11; 95% CI: 1.39, 3.18) and improvements in ferritin concentration were more likely to be observed in participants who took iron supplements for up to 90 d (RR = 1.41; 95% CI: 1.13, 1.76). CONCLUSION: Iron supplementation decreases the risk of maternal anemia and increases the likelihood of infant survival among iron-deficient Tanzanian pregnant women. Interventions to promote increased duration and adherence to iron supplements may also provide greater health benefits.

A prospective cohort study of Vitamins B, C, E, and multivitamin intake and endometriosis.

PURPOSE: Diet is a potentially modifiable risk factor for endometriosis. It has been hypothesized that vitamins C, E, and the B vitamins may influence factors involved in the pathogenesis of endometriosis, such as oxidative stress and steroid hormone metabolism. In this large, prospective cohort study, we examined the relation between intake of vitamins C, E, the B vitamins, and the use of multivitamin supplements and diagnosis of endometriosis. METHODS: Data were collected from women in the Nurses' Health Study II between 1991 and 2005. Diet was assessed via food frequency questionnaire. Incidence rate ratios (RR) and 95% confidence intervals (CI) were estimated using time-varying Cox proportional hazards models. RESULTS: A total of 1383 incident cases of laparoscopically-confirmed endometriosis were observed among 70,617 women during 735,286 person years of follow-up. Intakes of thiamine (B1) (RR = 0.84, CI = 0.72-0.99; P-value, test for linear trend [P] = 0.04), folate (B9) (RR = 0.79, CI = 0.66-0.93; P = 0.003), vitamin C (RR = 0.81, CI = 0.68-0.95; P = 0.02), and vitamin E (RR = 0.70, CI = 0.59-0.83; P<0.0001) solely from food sources were inversely related to endometriosis diagnosis. However, intakes of these nutrients from supplements alone were unrelated to endometriosis. CONCLUSION: Thiamine, folate, vitamin C, and vitamin E from food sources are inversely related to endometriosis risk. Our results suggest that the protective mechanism may not be related to the nutrients themselves but rather other components of foods rich in these micronutrients or factors correlated with diets high in these vitamin-rich foods.