Trial Of Micronutrient Supplementation Research Articles

Micronutrients and Major Depression: A Mendelian Randomisation Study.

Various vitamins and minerals have been implicated in the aetiology of depression. To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomisation (MR), a method using genetic data to estimate causal effects given certain assumptions. We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566) and rMDD (cases = 17,451; controls = 62,482). None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g., cIVW) highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (ORcIVW 0.90 per SD increase; 95% CI 0.85-0.95; p = 0.0003); erythrocyte copper (ORcIVW 0.97; 95% CI 0.95-0.99; p = 0.0004); and 25(OH) vitamin D (ORcIVW 0.81; 0.66-0.99; p = 0.04). Apparent adverse effects of increased selenium on the risk of MDD (ORcIVW 1.03; 95% CI 1.02-1.05; p = 0.0003) and rMDD (ORcIVW 1.08; 95% CI 1.00-1.08; p = 0.06), and serum magnesium on rMDD (ORcIVW 1.21; 1.01-1.44; p = 0.04); were less consistent between methods and may be driven by pleiotropy. Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.

A Systematic Review of Multiple Micronutrient Supplementation Trials Concerning Maternal Health

Background: Maternal nutrition is critically important for the well-being of both the mother and the developing fetus. Multiple micronutrient (MMN) supplements have the added advantage of addressing nutritional deficiencies. This study aimed to review the effects of MMN supplementation trials to prevent maternal and fetal complications from the preconception period to the post-natal phase by incorporating adequate micronutrients into the daily diet. Methodology: A comprehensive review of online literature was conducted following PRISMA guidelines. Three databases—PubMed, ScienceDirect, and Google Scholar—were searched for clinical trials from 2019 to 2023. MeSH terms such as "maternal," "micronutrient supplementation," "Pakistan," "trials," "clinical trials," and "micro-element supplementation" were used with Boolean operators "AND" and "OR." Titles and abstracts of the articles were screened initially, followed by full-text reviews in the second round. A total of seven articles meeting the inclusion criteria and diagnostic accuracy (STARD) were selected. Results: Risk of bias and quality assessment of clinical trials were evaluated using a 23-item questionnaire, with scores ranging from 0 to 2. Conclusion: Nutritional supplements were found to be most effective when taken daily for three months before conception and continued throughout the first trimester of pregnancy.

Oral Antioxidant and Lutein/Zeaxanthin Supplements Slow Geographic Atrophy Progression to the Fovea in Age-Related Macular Degeneration

PurposeThe only treatments approved to slow geographic atrophy (GA) progression in age-related macular degeneration (AMD) require frequent intraocular injection and suffer from modest efficacy, important risks, and high costs. The purpose of this study was to determine whether oral supplements slow GA progression in AMD. DesignPost hoc analysis of the Age-Related Eye Diseases Study (AREDS) and AREDS2, multi-center randomized placebo-controlled trials of oral micronutrient supplementation, each with 2x2 factorial design. Participants392 eyes (318 participants) with GA in AREDS; 1210 eyes (891 participants) with GA in AREDS2. MethodsAREDS participants were randomly assigned to oral antioxidants (500 mg vitamin C; 400 IU vitamin E; 15 mg β-carotene); 80 mg zinc; combination; or placebo. AREDS2 participants were randomly assigned to 10 mg lutein/2 mg zeaxanthin; 350 mg docosahexaenoic acid/650 mg eicosapentaenoic acid; combination; or placebo. Consenting AREDS2 participants were also randomly assigned to alternative AREDS formulations: original; no beta-carotene; 25 mg zinc instead of 80 mg; both. Main outcome measures(1) Change in GA proximity to central macula over time, and (2) change in square root GA area over time, each measured from color fundus photographs at annual visits and analyzed by mixed-model regression according to randomized assignments. ResultsIn AREDS eyes with non-central GA (n=208), proximity-based progression towards the central macula was significantly slower with randomization to antioxidants versus none, at 50.7 μm/year (95% CI 38.0-63.4 μm/year) versus 72.9 μm/year (95% CI 61.3-84.5 μm/year; p=0.012), respectively. In AREDS2 eyes with non-central GA, in participants assigned to AREDS antioxidants without β-carotene (n=325 eyes), proximity-based progression was significantly slower with randomization to lutein/zeaxanthin versus none, at 80.1 μm/year (95% CI 60.9-99.3 μm/year) versus 114.4 μm/year (95% CI 96.2-132.7 μm/year; p=0.011), respectively. In AREDS eyes with any GA (n=392), area-based progression was not significantly different with randomization to antioxidants versus none (p=0.63). In AREDS2 eyes with any GA, in participants assigned to AREDS antioxidants without β-carotene (n=505 eyes), area-based progression was not significantly different with randomization to lutein/zeaxanthin versus none (p=0.64). ConclusionsOral micronutrient supplementation slowed GA progression towards the central macula, likely by augmenting the natural phenomenon of foveal sparing.

Improving infant Neurocognitive Development and Growth Outcomes with micronutrients (INDiGO): A protocol for an efficacy trial in rural Gambia.

Undernutrition during the early years of life has a harmful and irreversible impact on child growth and cognitive development. Many of the interventions tested to improve outcomes across infancy have had disappointing or inconsistent impact, a common feature being the absence of any attempt to provide nutritional supplements to infants during the first six months. With increasing evidence of micronutrient deficiencies in this age group, alongside strong evidence that growth and developmental deficits begin before six months, a renewed focus on the micronutrient status of infants is required. This study is a five-arm, double-blind, placebo-controlled, randomised efficacy trial of micronutrient supplementation to mothers (during pregnancy or pregnancy and lactation) and infants (Day 8 to six months of age) in rural Gambia, where rates of micronutrient deficiencies are high. 600 pregnant women (<20 weeks gestation) will be enrolled into one of five trial arms and followed to 12 months post-partum. The primary outcome will be infant brain development at six months, with micronutrient status, growth and neurocognitive development to 12 months as secondary outcomes. This novel research will identify the most efficacious way of improving micronutrient status in infancy, and assess impact on infant developmental outcomes, providing an evidence base for future effectiveness trials and policy recommendations. ISRCTN registry ( ISRCTN15063705, 09/07/2021); Pan African Clinical Trials Registry ( PACTR202201552774601, 21/01/2022).

Fetal femur length and risk of diabetes in adolescence: a prospective cohort study

BackgroundDiabetes is more apparent in adulthood but may be dormant in childhood and originates during early fetal development. In fetal biometry, femur length (FL) is crucial for assessing fetal growth and development. This study aimed to assess potential associations between fetal femur growth and prediabetic biomarkers in Bangladeshi children.MethodsA cohort study embedded in a population-based maternal food and micronutrient supplementation (MINIMat) trial was conducted in Matlab, Bangladesh. The children in the cohort were followed up until 15 years of age. In the original trial, pregnancy was confirmed by ultrasound before 13 gestational weeks (GWs). Afterward, ultrasound assessments were performed at 14, 19, and 30 GWs. FL was measured from one end to the other, capturing a complete femoral image. The FL was standardized by GW, and a z-score was calculated. FBG and HbA1c levels were determined in plasma and whole blood, and the triglyceride–glucose index, a biomarker of insulin resistance, was calculated as Ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. Multivariable linear regression analysis using a generalized linear model was performed to estimate the effects of FL at 14, 19 and 30 GWs on prediabetic biomarkers at 9 and 15 years of age. Maternal micronutrient and food supplementation group, parity, child sex, and BMI at 9 years or 15 years were included as covariates.ResultsA total of 1.2% (6/515) of the participants had impaired fasting glucose during preadolescence, which increased to 3.5% (15/433) during adolescence. At 9 years, 6.3% (32/508) of the participants had elevated HbA1c%, which increased to 28% (120/431) at 15 years. Additionally, the TyG index increased from 9.5% (49/515) (during preadolescence) to 13% (56/433) (during adolescence). A one standard deviation decrease in FL at 14 and 19 GWs was associated with increased FBG (β = − 0.44 [− 0.88, − 0.004], P = 0.048; β = − 0.59 [− 1.12, − 0.05], P = 0.031) and HbA1c (β = − 0.01; [− 0.03, -0.005], P = 0.007; β = − 0.01 [− 0.03, − 0.003], P = 0.018) levels at 15 years. FL was not associated with diabetic biomarkers at 9 years.ConclusionMid-trimester impaired femur growth may be associated with elevated prediabetic biomarkers in Bangladeshi adolescents.

The Relationship of Preterm and Small for Gestational Age with Child Cognition During School-Age Years

BackgroundChildren born preterm and/or small for gestational age (SGA) are at increased risk of poor cognitive outcomes, particularly in low and middle-income countries (LMICs). ObjectivesThis study aimed to examine the cognitive and academic deficits during the school-age years in children born preterm or SGA compared with those in children born term adequate for gestational age (AGA) in rural Vietnam. MethodsChildren born to women in a preconception micronutrient supplementation trial in Vietnam were classified into 3 groups: preterm AGA (n =138), term SGA (n =169), and term AGA (n = 1134). Cognitive abilities were assessed using the Wechsler Intelligence Scale for Children, measuring 4 domains [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI) scores] and full-scale intelligence quotient (FSIQ) at 6–7 and 10–11 y. Academic achievement was assessed with mathematic and language tests. Analysis of variance and multiple regression models were used to analyze differences in cognitive function and academic achievement at 6–7 and 10–11 y by birth phenotypes. ResultsCompared with term AGA children, those born SGA had lower cognitive scores at both 6–7 y (VCI, −2.3; PRI, −3.7; PSI −2.1; and FSIQ, −2.9) and 10–11 y (VCI, −3.7; PRI, −3.5; WMI, −2.7; PSI, −1.9; and FSIQ, −3.9). Children born SGA also had poorer academic achievement with lower language (5.3) and mathematic (2.5) scores. Adjustments for maternal factors and home environment attenuated the associations, but the differences in VCI, PRI, FSIQ, and language at 10–11 y remained significant. There were no differences in cognitive function and academic achievement between children born preterm and AGA. ConclusionsOur findings highlight the enduring association of birth phenotype on cognitive functioning and academic achievement during the school years, despite adjustments for maternal education and family environment. Further research is needed to implement effective interventions to improve birth outcomes and optimize child health and development in LMICs.The trial was registered at clinicaltrials.gov as NCT01665378 (URL: https://clinicaltrials.gov/ct2/show/NCT01665378).

Associations of parental age at pregnancy with adolescent cognitive development and emotional and behavioural problems: a birth cohort in rural Western China

BackgroundThe relationship between parental age at pregnancy and offspring development in low- and middle-income countries remains unclear. We aimed to examine the associations of parental age at pregnancy with adolescent development in rural China.MethodsWe conducted a prospective birth cohort study of offspring born to pregnant women who participated in an antenatal micronutrient supplementation trial in rural Western China. Adolescent cognitive development and emotional and behavioural problems were assessed by using the Wechsler Intelligence Scale for Children-IV and the Youth Self-Report-2001, respectively. After accounting for the possible nonlinear relationships, we examined the linear associations between parental age (in years) at pregnancy and scores of adolescent cognitive development and emotional and behavioural problems by performing generalized estimating equations.ResultsAmong 1897 adolescents followed from birth to early adolescence, 59.5% were male with a mean age of 11.8 (standard deviation (SD): 0.8) years. The mean ages of mothers and fathers at pregnancy were 24.6 (SD: 4.4) and 27.9 (SD: 4.1) years old, respectively. All the P values of the nonlinear terms between parental age and adolescent development in all domains were greater than 0.05. Each one-year increase in maternal age at pregnancy was associated with a 0.29-point (95% confidence interval (CI) 0.06, 0.52) increase in the full-scale intelligence quotient in early adolescence. After parental age was categorized into quartiles, the total behavioural problem scores of adolescents with fathers with an age in the fourth quartile (Q4) were 6.71 (95% CI 0.86, 12.57) points higher than those of adolescents with fathers with an age in the first quartile (Q1), with a linear trend P value of 0.01. Similarly, higher scores (worse behavioural problems) were observed for internalizing behavioural problems and other emotional and behavioural symptoms related to anxiety, withdrawal, social problems, thought problems and aggressive behaviour.ConclusionsAt conception, older maternal age was independently linked to better adolescent cognitive development, whereas advanced paternal age was independently associated with a greater risk of adolescent emotional and behavioral problems. These findings suggest that public health policies targeting an optimal parental age at pregnancy should be developed in the context of offspring developmental consequences.

Growth patterns of preterm and small for gestational age children during the first 10 years of life.

Preterm and small for gestational age (SGA) remain significant public health concerns worldwide. Yet limited evidence exists on their growth patterns during childhood from low-or middle-income countries. We investigated the postnatal growth patterns of preterm and SGA compared to term appropriate for gestational age (AGA) children from birth to 10-11y, and examined the impact of birth status on child nutritional status during the school age years. Children born to women who participated in a double-blinded randomized controlled trial of preconception micronutrient supplementation in Vietnam were classified into three groups: preterm AGA (n = 130), full-term SGA (n = 165) and full-term AGA (n = 1,072). Anthropometric data (weight and height) were collected prospectively at birth, 3, 6, 12, 18, 24 months and at 6-7 and 10-11y. We used ANOVA and multiple regression models to examine the differences in growth patterns from birth to 10-11y as well as child undernutrition and overnutrition by birth status. Children who were born preterm exhibited rapid postnatal growth, but still had lower HAZ at 1y and 2y and showed catch up to the AGA group at 6y. Compared to those born AGA, SGA infants had higher risk of thinness (BMIZ < -2) at 2y and 6y (adjusted Odds Ratio, AOR [95% CI] 2.5 [1.0, 6.1] and 2.6 [1.4, 4.6], respectively); this risk reduced at 10-11y (1.6 [0.9, 2.8]). The risk of stunting (HAZ < -2) was also 2.4 [1.5, 3.8] and 2.3 times [1.2, 4.1] higher in SGA than AGA group at ages 2y and 6-7y, respectively, with no differences at 10y. Although preterm children had higher rates of thinness and stunting at 2y compared to AGA children, these differences were not statistically significant. No associations were found between preterm or SGA and overweight /obesity at age 10-11y. Children who were born term-SGA continued to demonstrate deficits in weight and height during childhood whereas those born preterm showed catch-up growth by age 6-7y. Additional efforts to reduce the burden of these conditions are needed, particularly during school-age and early adolescents when children are exposed to challenging environments and have higher demands for nutrition.

Associations between gestational weight gain under different guidelines and adverse birth outcomes: A secondary analysis of a randomized controlled trial in rural western China.

Several gestational weight gain (GWG) guidelines have been established based on monocenter or multicenter researches. We aimed to examine the associations between categories of GWG under the Institute of Medicine (IOM) recommendation guideline, the Chinese National Health Commission (NHC) guideline, and weight-gain-for-gestational-age z-scores derived from the INTERGROWTH-21st Project and adverse birth outcomes. We used data from an antenatal micronutrient supplementation trial in rural western China between 2002 and 2006. Maternal weekly average GWG during the second and third trimesters was calculated and classified into inadequate, adequate and excessive GWG according to the IOM and NHC, respectively. Weight-gain-for-gestational-age z-scores derived from the INTERGROWTH-21st Project were grouped into three subgroups using two approaches: z-score percentile<25th, 25th to 75th, >75th and z-score <-1, -1 to 1, >1 SD. Infant birth weight and gestational age were measured using standard approaches. Generalized linear model with binomial family and logit link was applied to estimate the odds ratio (OR) and 95% confidential intervals (CI) for GWG categories and adverse birth outcomes. Among 1,239 women with normal weight (18.5 kg/m2 to 23.9 kg/m2) during early pregnancy, 18.0% and 34.2% were classified as adequate GWG according to IOM and NHC, respectively. Less than half of Chinese women reached optimal GWG by any recommendation guideline. According to NHC, excessive GWG showed a significant association with macrosomia (OR 3.75, 95% CI 1.03, 13.74), large-for-gestation-age (LGA) (OR 2.12, 95% CI 1.01, 4.45), and inadequate GWG was associated with post-term birth (OR 2.25, 95% CI 1.21, 4.16), compared with adequate GWG. Inappropriate GWG was associated with adverse birth outcomes even among women with normal weight during early pregnancy. The monitoring and interventions of weight status during pregnancy, especially for the second and third trimesters, are of great public health importance for optimal birth outcomes. Additionally, developing guideline of appropriate GWG ranges should account for the traits of regional population.

Home environment and nutritional status mitigate the wealth gap in child development: a longitudinal study in Vietnam

BackgroundInequity in child development is found at early age, but limited evidence exists on whether these gaps change over time and what are the mediators.ObjectiveWe aim to (1) quantify wealth related gaps in cognitive and socio-emotional development in early and middle childhood; (2) examine how these gaps were mitigated by maternal, child factors and home environment.MethodsWe assessed the offspring of women who participated in a randomized controlled trial of preconception micronutrient supplementation in Vietnam (n = 1599). Child development was measured by the Bayley Scales of Infant Development-III (at 1-2y) and the Wechsler Intelligence Scale for Children®—IV (at 6-7y). We used multivariable regression to estimate the changes in wealth gaps for child development over time, adjusting for potential factors that potentially influence cognitive development.ResultsWe found significant wealth gaps in cognitive development during early childhood (gaps between top and bottom quintiles: 0.5 SD); these gaps increased substantially in middle childhood (0.9 SD). Wealth disparity in social emotion did not change over time (0.26–0.28 SD). Maternal factors, quality of home environment, and child nutritional status mitigated the wealth gap in cognitive development (7-42%) in early childhood. The contribution of these mitigating factors was smaller in middle childhood (2- 15%). Wealth gap in social emotion reduced by 13% and 43% among children with better nutritional status at 2y and higher quality of home environment at 6-7y, respectively.ConclusionInterventions focusing on improving quality of home environment, maternal education, wellbeing, and child nutrition status may help reduce developmental deficits associated with poverty.

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

BackgroundGestational 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). ObjectiveThis 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. MethodsWeights 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. ResultsGDQS 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. ConclusionsDietary 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.

Effects of antenatal micronutrient supplementation regimens on adolescent emotional and behavioral problems: A 14-year follow-up of a double-blind, cluster-randomized controlled trial

Antenatal multiple micronutrient supplementation has been shown to have beneficial effects on birth outcomes and may improve child development. However, whether there is an effect of antenatal micronutrient supplementation strategies on offspring socioemotional outcomes remains unknown. We aimed to examine the effect of antenatal folic acid (FA), iron-folic acid (IFA), and multiple micronutrient (MMN) supplementation on adolescent emotional and behavioral outcomes. We conducted a double-blind, cluster-randomized trial of antenatal micronutrient supplementation in rural western China between 2002 and 2006. Pregnant females were randomized by village to receive either daily (i) 400μg FA, (ii) IFA containing 60mg iron and 400μg FA or (iii) MMN supplementation containing 30mg iron, 400μg FA plus 13 additional vitamins and minerals. A 14-year follow-up of their offspring was conducted in 2016. Adolescents were administered the locally adapted Youth Self-Report-2001 (YSR-2001) which produced internalizing, externalizing, and total behavior problem scores. We applied generalized estimating equations to assess the effect of the randomized regimens on YSR-2001 scores and explored the potential effect modification by household wealth and initial timing and duration of supplementation. A total of 1920 adolescents were included in the analysis, 1130 (58.9%) were male, and the mean (SD) age was 11.8 (0.78) years. Adolescents in IFA group had lower total (mean difference (MD):-2.89; 95% CI -5.73,-0.04) and externalizing (MD:-0.97; 95% CI -1.79,-0.15) problem scores as compared to those in FA group. There was no effect of MMN on behavior problem scores as compared to IFA and FA alone. Although, in effect modification analyses, MMN appeared to have greater beneficial effects in wealthier households than IFA and FA alone. Iron supplementation during pregnancy reduced adolescent emotional and behavioral problem scores which provides additional support for expanding coverage of iron-containing prenatal supplements in resource-limited settings. isrctn. org Identifier: ISRCTN08850194.

Association of Antenatal Micronutrient Supplementation With Adolescent Emotional and Behavioral Health: A 14-Year Follow-Up of a Double-Blind Randomized Controlled Trial

Abstract Objectives To examine the impact of antenatal micronutrient supplementation on adolescent emotional and behavioral health, and to identify the modifying effect of household wealth. Methods We conducted a double-blind cluster-randomized trial of antenatal micronutrient supplementation in rural western China between 2002 and 2008. Pregnant women in every village were randomized to daily take one capsule of folic acid (as control), folic acid plus 60 mg iron (IFA), and multiple micronutrients (MMNs) including 30 mg iron. Singleton births were prospectively followed at early adolescence in 2016. Adolescents actively completed the localized and qualified Youth Self-Report. Scores of Internalizing Behavior Problems (constituting by Anxious/Depressed, Withdrawn and Somatic Complaints), Externalizing Behavior Problems (constituting by Delinquent/Rule-Breaking Behavior and Aggressive Behavior) and Total Behavior Problems, were derived. As priorly specified, we examined the modifying effect of household wealth on the response to antenatal IFA and MMNs vs. folic acid supplementation on adolescent emotional and behavioral health. Results Of 1920 adolescents included in the final analysis, 1130 (58.9%) were male, with a mean (SD) age of 11.8 (0.78) years. As compared to folic acid, adolescents born to mothers who consumed IFA had lower scores of total behavioral problems, externalizing, rule-breaking and aggressive behavior. The adjusted mean differences were −2.94 (95% CI −5.78, −0.11), −1.00 (95% CI −1.82, −0.18), −0.39 (95% CI −0.73, −0.05) and −0.61 (95% CI −1.15, −0.07), respectively. Similar associations were observed among medium-wealth households, while null associations in low-wealth households (all interaction P values &amp;lt; 0.05). Further, among high-wealth households, MMNs show benefits on reducing the risk of adolescent behavioral problems as compared to IFA or folic acid. Conclusions Sufficient iron intake in pregnancy has long-term benefits on reducing the risk of adolescent behavioral problems. Multiple micronutrients including 60 mg iron are recommended in rural areas with micronutrients deficiencies widely prevalent given the benefits of MMNs on improving birth outcomes. Funding Sources National Natural Science Foundation of China and China Postdoctoral Science Foundation.

Characteristics and birth outcomes of pregnant adolescents compared to older women: An analysis of individual level data from 140,000 mothers from 20 RCTs.

SummaryBackgroundAdolescence is a critical period of maturation when nutrient needs are high, especially among adolescents entering pregnancy. Using individual-level data from 140,000 participants, we examined socioeconomic, nutrition, and pregnancy and birth outcomes for adolescent mothers (10–19 years) compared to older mothers in low and middle-income countries.MethodsThis study was conducted between March 16, 2018 and May 25, 2021. Data were obtained from 20 randomised controlled trials of micronutrient supplementation in pregnancy. Stratified analyses were conducted by age (10–14 years, 15–17 years, 18–19 years, 20–29 years, 30–39 years, 40+ years) and geographical region (Africa, Asia). Crude and confounder-adjusted means, prevalence and relative risks of pregnancy, nutrition and birth outcomes were estimated using multivariable linear and log-binomial regression models with 95% confidence intervals.FindingsAdolescent mothers comprised 31.6% of our data. Preterm birth, small-for-gestational age (SGA), low birthweight (LBW) and newborn mortality followed a U-shaped trend in which prevalence was highest among the youngest mothers (10–14 years) and then reduced gradually, but increased again for older mothers (40+ years). When compared to mothers aged 20–29 years, there was a 23% increased risk of preterm birth, a 60% increased risk of perinatal mortality, a 63% increased risk of neonatal mortality, a 28% increased risk of LBW, and a 22% increased risk of SGA among mothers 10–14 years. Mothers 40+ years experienced a 22% increased risk of preterm birth and a 103% increased risk of stillbirth when compared to the 20–29 year group.InterpretationThe youngest and oldest mothers suffer most from adverse pregnancy and birth outcomes. Policy and programming agendas should consider both biological and socioeconomic/environmental factors when targeting these populations.FundingBill and Melinda Gates Foundation (Grant No: OP1137750).

Child linear growth trajectories during the first three years of life in relation to infant iron status: a prospective cohort study in rural Vietnam

BackgroundEarly childhood growth patterns have long-term consequences for health and disease. Little is known about the interplay between growth and iron status during childhood. We explored the interplay between linear growth and iron status during early childhood, by assessing child growth trajectories between 6 and 36 months (m) of age in relation to infant iron status at 6 months of age.MethodsA cohort study of infants born to women who had previously participated in a cluster randomized controlled trial of antenatal micronutrient supplementation, conducted in rural Vietnam. The relationship between child linear growth trajectories and infant iron status (ferritin concentration) was examined using latent growth curve modeling. Primary outcomes were height for age z scores (HAZ) and growth trajectory between 6 and 36 m of age.ResultsA total of 1112 infants were included in the study. Mean [SD] HAZ scores decreased over time from –0·58 [0·94] at 6 m, to –0·97 [0·99] at 18 m, to –1·14 [0·89] at 36 m of age. There was a steep linear decline in the HAZ scores between 6 and 18 m of age, followed by a slower linear decline from 18 to 36 m of age. Ferritin concentration at 6 m of age was inversely associated with HAZ score at 6 m of age (-0·145, 95% CI [-0.189, -0.101]). There was no association between infant ferritin at 6 m of age and child growth trajectory between 6 and 36 m of age.ConclusionsIron status at six months of age did not influence a child’s later linear growth trajectory in this cohort of rural Vietnamese children. Longitudinal studies with repeated ferritin and height measurements are required to better delineate this relationship and inform public health interventions.

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.

Postnatal Stature Does Not Largely Mediate the Relation between Adverse Birth Outcomes and Cognitive Development in Mid-Childhood and Early Adolescence in Rural Western China

BackgroundPreterm birth and fetal growth restriction are associated with linear growth faltering and suboptimal cognitive development in childhood. ObjectivesWe aimed to investigate whether and to what extent the associations between adverse birth outcomes and cognitive development in mid-childhood and early adolescence are mediated by postnatal stature. MethodsWe used data from a prospective birth cohort of children born to women who participated in a large cluster-randomized trial of antenatal micronutrient supplementation in rural western China. Children were followed up for anthropometric assessments at 6, 12, and 24 mo of age and in mid-childhood (7–9 y). Cognitive development was assessed in mid-childhood (n = 669) and early adolescence (n = 735; 10–12 y) using the Wechsler Intelligence Scale for Children-IV. We conducted a causal mediation analysis to evaluate the proportion of the association of low birth weight (LBW; <2500 g), small-for-gestational age (SGA; <10th percentile), and preterm birth (<37 weeks of gestation) with cognitive development in mid-childhood and early adolescence that was mediated by postnatal length/height-for-age and -sex z score (LAZ/HAZ) during the first 2 y of life and in mid-childhood. ResultsLBW and SGA, but not preterm birth, were associated with lower cognitive test scores in mid-childhood and early adolescence. The proportion of the total association of SGA with adolescent cognitive development that was mediated by LAZ/HAZ at 6, 12, and 24 mo of age and in mid-childhood was 25%, 32%, 32%, and 27%, respectively. The corresponding proportions for LBW were 25%, 32%, 16%, and 24%, respectively. ConclusionsThe association of LBW and SGA with cognitive development in mid-childhood and adolescence is not largely mediated by postnatal stature during the first 2 y of life. Postnatal interventions that address the antecedent causes of poor child growth and development, rather than early childhood growth alone, are more likely to mitigate the risk of suboptimal development among SGA and LBW children. This trial was registered at www.isrctn.com as ISRCTN08850194.

Micronutrient supplements can promote disruptive protozoan and fungal communities in the developing infant gut

Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, association of gastrointestinal disorders with iron has led to ongoing debate over their administration. To better understand their impact on gut microbiota, we analyse the bacterial, protozoal, fungal and helminth communities of stool samples collected from a subset of 80 children at 12 and 24 months of age, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan (ClinicalTrials.gov identifier NCT00705445). We show that while bacterial diversity is reduced in supplemented children, vitamins and iron (as well as residence in a rural setting) may promote colonization with distinct protozoa and mucormycetes, whereas the addition of zinc appears to ameliorate this effect. We suggest that the risks and benefits of micronutrient interventions may depend on eukaryotic communities, potentially exacerbated by exposure to a rural setting. Larger studies are needed to evaluate the clinical significance of these findings and their impact on health outcomes.

Patterns and Determinants of the Double Burden of Malnutrition Among Adolescents: A 14-Year Follow-Up of a Birth Cohort in Rural China

To examine the prevalence of the double burden of malnutrition and its associated factors among adolescents in rural China. A birth cohort of adolescents born to women in northwestern China who participated in a double-blind, randomized, controlled trial of micronutrient supplementation during pregnancy from August 2002 to January 2006 was enrolled. Follow-up was conducted from June to December2016. A total of 2115 participants were analyzed (median age 12years; IQR±1), the majority of whom were male (59.7%). The nutritional status distribution was 17.72% underweight, 8.62% overweight, 0.96% obese, and 2.58% stunted. Girls were less likely to be overweight/obese (relative risk ratio [RRR] 0.67, 95% CI 0.48-0.92) but more likely to be underweight (RRR 1.65, 95% CI 1.25-2.17) or stunted (RRR 2.26, 95% CI 1.21-4.22). Children of underweight mothers (RRR 1.63, 95% CI 1.19-2.25) with a history of small for gestational age (RRR 1.64, 95% CI 1.14-2.36) or described as being a "picky eater" (RRR 1.53, 95% CI 1.18-1.99) had a greater risk of being underweight. Children whose fathers' education was primary or below (RRR 2.25, 95% CI 1.11-4.59), with maternal height <150.1cm (RRR 2.46, 95% CI 1.12-5.39), or who had mothers with underweight (RRR 2.80, 95% CI 1.37-5.72) had a greater likelihood of stunting. Overweight/obesity was associated with high and middle household wealth (RRR 1.62, 95% CI 1.14-2.32), mothers with overweight (RRR 1.86, 95% CI 1.25-2.78), and picky eating (RRR 0.62, 95% CI 0.46-0.84). Malnutrition (undernutrition and overweight/obesity) is common in rural Chinese adolescents and is associated with perinatal, genetic, and economic conditions.

Determinants of Plasma Ferritin at 3 Months of Age Among Rural Bangladeshi Infants From the JiVitA-3 Trial

ObjectivesFerritin, a biomarker of iron stores, is rarely reported in infants despite a known role for iron in growth and development. Iron stores accumulated in utero decline in infancy, although breastmilk iron supports infant status. In rural northwest Bangladesh, an iron-replete area, infants are small and prone to common illnesses despite prevalent breastfeeding. We explored determinants of ferritin in 3 mo old infants in this setting. MethodsIn a double-blind, cluster-randomized trial (JiVitA-3) of multiple micronutrient or iron-folic acid supplementation from pregnancy ascertainment to 3 mo postpartum, maternal and infant hemoglobin (Hb), anthropometry, and plasma were obtained 3 mo after birth. Growth was assessed as weight gain since birth. In a preliminary analysis (n = 378), infant plasma ferritin, maternal ferritin, and infant α1-acid glycoprotein (AGP), a biomarker of inflammation, were assessed. Distributions are shown as mean ± SD or median (IQR) if skewed; associations of infant ferritin with biomarkers and anthropometry were assessed with Spearman correlation (rs) or linear regression with log10-transformed variables, if skewed. ResultsAmong infants, plasma ferritin was 118 (70,182) μg/L, Hb 111 ± 11 g/L; and AGP 0.91 (0.68, 1.17) g/L, with 40.5% of infants inflamed (AGP > 1.00 g/L). Among mothers, ferritin was 60 (38, 88) μg/L and Hb 121 ± 10 g/L. Ferritin was lower in boys (n = 200) than girls (n = 178) [102 (58,159) vs 142 (87,212) μg/L], but weight (5.4 ± 0.6 vs 4.9 ± 0.8 kg) and weight gain since birth (2.8 ± 0.5 vs 2.4 ± 0.7) were higher (all p < 0.0001). When adjusted for sex, infant ferritin was positively associated with AGP (p = 0.025). Adjusted for AGP and low birth weight status, each 1 kg gain in weight from birth to 3 months was associated with 32.0% lower ferritin (95%CI: –45.7, –14.9; p = 0.001) in boys, but not girls [8.4% lower ferritin (95%CI: –21.6, 7.1; p = 0.269)]. Ferritin was not associated with infant Hb (rs = 0.02), or maternal ferritin (rs = –0.003) or Hb (rs = –0.001) (all p > 0.05). ConclusionsInfant ferritin was unassociated with aspects of maternal or infant iron status. It was associated positively with AGP, which was commonly elevated, and negatively with growth in boys, whose size and rate of growth exceeded that of girls. Funding SourcesBill and Melinda Gates Foundation.