Prenatal Iron + Folate

OBJECTIVE: To characterize neonatal iron stores depending on gestational age (GA) at term. STUDY DESIGN: Participants were 751 mother-newborn pairs from the placebo arm of a randomized clinical trial of prenatal iron-folate supplementation in China. We compared mean cord serum ferritin (SF) by weeks GA and, following the general linear model, assessed whether maternal iron deficiency (ID) influenced relations between GA and cord SF. RESULTS: Controlling for covariates, cord SF increased between 37 and 41 weeks (ps < 0.05-0.01). Cord SF was lower in infants of ID vs. non-ID mothers (geometric mean 96.3 [95% CI: 91.3-101.6] µg/L vs. 115.9 [95% CI: 105.0-127.8] µg/L, effect size = 0.33 SD, p = 0.0012). There was no significant increase with GA among infants of ID mothers. For non-ID mothers, cord-blood SF increased sharply with GA until 38 5/7 weeks, after which it plateaued. CONCLUSIONS: The findings emphasize that neonates at 37-38 weeks, although considered term, are not fully mature.

BACKGROUND: Previous trials of prenatal iron supplementation had limited measures of maternal or neonatal iron status. OBJECTIVE: The purpose was to assess effects of prenatal iron-folate supplementation on maternal and neonatal iron status. METHODS: Enrollment occurred June 2009 through December 2011 in Hebei, China. Women with uncomplicated singleton pregnancies at ≤20 wk gestation, aged ≥18 y, and with hemoglobin ≥100 g/L were randomly assigned 1:1 to receive daily iron (300 mg ferrous sulfate) or placebo + 0.40 mg folate from enrollment to birth. Iron status was assessed in maternal venous blood (at enrollment and at or near term) and cord blood. Primary outcomes were as follows: 1) maternal iron deficiency (ID) defined in 2 ways as serum ferritin (SF) <15 μg/L and body iron (BI) <0 mg/kg; 2) maternal ID anemia [ID + anemia (IDA); hemoglobin <110 g/L]; and 3) neonatal ID (cord blood ferritin <75 μg/L or zinc protoporphyrin/heme >118 μmol/mol). RESULTS: A total of 2371 women were randomly assigned, with outcomes for 1632 women or neonates (809 placebo/folate, 823 iron/folate; 1579 mother-newborn pairs, 37 mothers, 16 neonates). Most infants (97%) were born at term. At or near term, maternal hemoglobin was significantly higher (+5.56 g/L) for iron vs. placebo groups. Anemia risk was reduced (RR: 0.53; 95% CI: 0.43, 0.66), as were risks of ID (RR: 0.74; 95% CI: 0.69, 0.79 by SF; RR: 0.65; 95% CI: 0.59, 0.71 by BI) and IDA (RR: 0.49; 95% CI: 0.38, 0.62 by SF; RR: 0.51; 95% CI: 0.40, 0.65 by BI). Most women still had ID (66.8% by SF, 54.7% by BI). Adverse effects, all minor, were similar by group. There were no differences in cord blood iron measures; >45% of neonates in each group had ID. However, dose-response analyses showed higher cord SF with more maternal iron capsules reported being consumed (β per 10 capsules = 2.60, P < 0.05). CONCLUSIONS: Prenatal iron supplementation reduced anemia, ID, and IDA in pregnant women in rural China, but most women and >45% of neonates had ID, regardless of supplementation. This trial was registered at clinicaltrials.gov as NCT02221752. © 2015 American Society for Nutrition.

INTRODUCTION: Iron and folate supplementation can effectively control and prevent anaemia in pregnancy. In Ethiopia, all pregnant women are prescribed iron folate during their ANC visit. However, limited adherence is thought to be a major reason for the low effectiveness of iron supplementation programs. Therefore this study was done to investigate factors associated with compliance of prenatal iron folate supplementation among women who gave birth in the last 12 months before the survey in Mecha district. METHODS: Community based cross sectional study design was employed in Mecha district from June 25 - July 15/2013. A sample of 634 women who gave birth 12 months before the survey was included in the study. Study participants were selected by systematic random sampling technique after allocating the total sample to each kebele proportionally. Data were collected using a pre-tested structured Amharic questionnaire. Collected data were edited, coded and entered to Epi info version 3.1 and exported to' SPSS version 16. Bivariate and multivariable analysis was computed. RESULTS: A total of 628 women who gave birth twelve months before the survey were enrolled. In this study only 20.4% of participants were compliant with iron foliate supplementation. In multivariable analysis, age of the mother, educational status of the mother, knowledge of anaemia and iron folate tablets, and history of anaemia during pregnancy were significantly associated with compliance to iron folate supplementation (P<.05). Belief that too many tablets would harm the baby and fear of side effects were the major reasons given for noncompliance. CONCLUSION: Compliance to iron folate supplementation is very low in the study area. Increasing female education and increasing knowledge of women about anaemia and iron folate tablets are recommended to increase compliance to iron folate supplementation.

BACKGROUND: Anemia is a global public health problem affecting both developing and developed countries. It is associated with increased morbidity and mortality in pregnant women and children. Nevertheless, information regarding the prevalence of anemia and associated factors among pregnant in the study area is limited. Therefore, this study was aimed to assess the prevalence of anemia and associated factors among pregnant women attending antenatal care clinic in Adare General Hospital, Southern Ethiopia. METHOD: A facility-based cross-sectional study was conducted from October 1, 2020, to December 15, 2020, among 340 pregnant women aged 15 to 49 years who came for focused antenatal care follow-up. Trained data collectors administered questionnaires, and collected capillary blood and stool samples. Data were coded and entered into EPI Info 7 and the analysis was done using SPSS version 20.0. Factors associated with anemia were assessed using binary logistic regression. Those variables that had a P-value less than .25 on bi-variable regression analysis were considered for multi-variable regression analysis. Statistical significance was declared with P < .05. RESULT: The prevalence of anemia among pregnant women was 24.1% (95% CI: 19.55%-28.69%). The majority of anemia cases were mildly anemic (62.2.0%). Increased odds of anemia was found among pregnant women with household monthly income ⩽2550 Ethiopian Birr (⩽69.67 United States Dollar) (AOR = 2.08; 95% CI: 1.15, 3.76), not attended formal education (AOR = 3.86; 95% CI: 1.42, 10.54), not using iron tablets (AOR = 2.64; 95% CI: 1.33, 5.27) and infected with Plasmodium vivax (AOR = 7.58; 95% CI: 3.11, 18.47). CONCLUSIONS: Anemia had moderate public health significance in the study. Low monthly family income, educational status, iron tablet consumption during pregnancy and Plasmodium vivax infection were found to be independent predictors for anemia in pregnancy. The burden of anemia should be alleviated through enhancing maternal socio-economic status, prevention of illnesses targeting pregnant women, and strengthening the expansion of prenatal iron-folate supplementation. © The Author(s) 2021.

OBJECTIVE: The determinants of anemia during both pregnancy and postpartum recovery remain incompletely understood in sub-Saharan African women. SUBJECTS/METHODS: In a prospective cohort study among pregnant women, we assessed dietary, biochemical, anthropometric, infectious and sociodemographic factors at baseline. In multivariate Cox proportional hazards models, we examined predictors of incident anemia (hemoglobin <11 g/dl) and iron deficiency anemia (anemia plus mean corpuscular volume <80fL), and recovery from anemia and iron deficiency anemia through 18 months postpartum at antenatal clinics in Dar es Salaam, Tanzania between 2001 and 2005. A total of 2364 non-anemic pregnant women and 4884 anemic women were enrolled between 12 and 27 weeks of gestation. RESULTS: In total, 292 women developed anemia during the postpartum period and 165 developed iron deficiency anemia, whereas 2982 recovered from baseline anemia and 2044 from iron deficiency anemia. Risk factors for postpartum anemia were delivery complications (RR 1.6, 95% confidence interval (CI) 1.13, 2.22) and low postpartum CD4 cell count (RR 1.73, 95% CI 0.96, 3.17). Iron/folate supplementation during pregnancy had a protective relationship with the incidence of iron deficiency anemia. Absence of delivery complications, education status and iron/folate supplementation were positively associated with time to recovery from iron deficiency. CONCLUSION: Maternal nutritional status during pregnancy, prenatal iron/folate supplementation, perinatal care, and prevention and management of infections, such as malaria, are modifiable risk factors for the occurrence of, and recovery from, anemia.

BACKGROUND: Gestational weight gain (GWG) during pregnancy is a critical factor that affects maternal and child health outcomes. The considerable burden of inadequate GWG and the rising tide of excessive GWG are overlooked challenges in low and middle-income countries (LMICs). METHODS: This systematic review assessed the impact of antenatal interventions on GWG in LMICs. Randomised controlled trials (RCTs) on antenatal interventions on GWG in LMICs were included. These interventions included educational, behavioural, nutritional supplementation and pharmacological therapies. A systematic literature search was conducted using PubMed, Embase, Web of Science, CINAHL and the Cochrane Library from the start of each database through September 2025. RESULTS: Out of the 33 642 unique articles identified, 70 articles were included in our systematic review, with 59 individual RCTs and 11 cluster RCTs. Nutritional interventions (31 studies) included food and micronutrient supplementations. Micronutrient supplementation such as multiple micronutrient supplementations was found to reduce the risk of severely inadequate or inadequate GWG among pregnant women compared to iron only or iron and folic acid supplementation (Grading of Recommendations Assessment, Development and Evaluation [GRADE]: moderate certainty). Food supplementation showed mixed results, although most trials demonstrated higher mean GWG among undernourished pregnant women and a greater likelihood of achieving Institute of Medicine-recommended ranges (GRADE: moderate certainty). Behavioural (counselling/education) interventions (20 studies) were associated with significant reductions in excessive GWG among pregnant women with overweight or obesity and improved adequacy of GWG (GRADE: moderate certainty). Physical activity (seven studies) was found to reduce the risk of excessive GWG (GRADE: moderate certainty). Combined dietary and physical activity interventions (six studies) were found to reduce the risk of excessive GWG among pregnant women (GRADE: low certainty). CONCLUSIONS: Well-structured antenatal interventions, initiated before 20 weeks of gestation and continuing beyond this period, tailored to loca

BACKGROUND: Prenatal multiple micronutrient supplementation (MMS) including iron, folic acid, and other essential micronutrients, has shown potential to improve birth outcomes in controlled studies. We did an effectiveness study in Ethiopia to determine the effect on mean birthweight of MMS provided as part of routine antenatal care, relative to iron-folic acid supplementation (IFA). METHODS: A pragmatic, two-arm, facility-based, cluster-randomised controlled trial was conducted across 42 districts in five regions of Ethiopia to determine the effect on birthweight of MMS relative to IFA. Districts were randomly assigned to either retain IFA as part of routine antenatal care or switch to MMS. Randomisation was stratified by region and done using a random number generator within statistical software. All live singleton births at participating health facilities were eligible for inclusion and birthweights were recorded. Additionally, data were collected on maternal receipt and utilisation of MMS or IFA. The primary outcome was birthweight, analysed in the intention-to-treat population. This completed trial is registered at ClinicalTrials.gov, NCT05708183. FINDINGS: Between Jan 1, 2023, and Dec 31, 2024, birthweights were recorded for 47 325 babies in the 21 IFA districts and 36 473 babies in the 21 MMS districts. Mean age of mothers was 26·2 years (SD 5·3) and median gestational age of babies at birth was 38 weeks (IQR 38-39). The effect of MMS on birthweight was a mean increase of 38 g (95% CI 20-55) in the MMS arm relative to the IFA arm after adjustment for time, geographical region stratification factor, gestational age, sex of baby, and parity. Among women who reported taking at least 90 tablets of their assigned supplement, the increase in mean birthweight in the MMS arm relative to the IFA arm was 58 g (38-79). Stillbirth risk was 7·5 per 1000 births in the IFA arm and 6·9 per 1000 births in the MMS arm. INTERPRETATION: The findings of this trial are consistent with those from efficacy trials in other settings, indicating that the transition from IFA to MMS as part of routine antenatal care in Ethiopia could lead to a small but clear improvement in birthweig

BACKGROUND: Small vulnerable newborn (SVN) types, defined by combinations of being born too soon or too small, have distinct determinants, health consequences, and prevention strategies. The effects of prenatal balanced energy and protein (BEP) supplementation on SVN types remain unknown. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of individual participant data from eight randomized controlled trials of prenatal BEP supplements (N = 10,252, with 5,164 in the BEP arm and 5,088 in the control arm) in low- and middle-income countries were used. The control arms varied across studies and included context-specific standards of care, iron and folic acid supplements, or multiple micronutrient supplements. Newborns were classified into 10 groups through the combinations of preterm birth, small for gestational age (SGA) birth, and low birthweight (LBW), such as term-appropriate-for-gestational-age (AGA)-nonLBW, preterm-SGA-LBW, preterm-large-for-gestational-age-LBW, term-SGA-LBW, preterm-AGA-nonLBW, and other permutations. Newborns were also analyzed using a four-group categorization that included term-nonSGA, preterm-nonSGA, term-SGA, and preterm-SGA. Log-binomial models were used to estimate study-specific risk ratios (RRs), which were pooled using meta-analyses. Subgroup analyses were conducted by maternal age, parity, gestational age at enrollment, early pregnancy body mass index, and maternal anemia status. In the 10-group categorization of SVNs, on average, prenatal BEP supplementation led to a 30% lower risk of preterm-SGA-LBW (RR: 0.70; 95% CI [0.53, 0.91]; P = 0.009), a 25% lower risk of preterm-AGA-LBW (RR: 0.75; 95% CI [0.60, 0.93]; P = 0.009), and a 20% lower risk of term-SGA-LBW (RR: 0.80; 95% CI [0.72, 0.90]; P < 0.001). In the four-group categorization, prenatal BEP supplementation led to a 31% lower risk of preterm-SGA (RR: 0.69; 95% CI [0.52, 0.91]; P = 0.008) and a 12% lower risk of term-SGA (RR: 0.88; 95% CI [0.81, 0.96]; P = 0.005). The protective effect of prenatal BEP supplementation on preterm-SGA was stronger among multiparous women and women without anemia. The protective effects on all three SVN types under the four

BACKGROUND: This study directly examined the effects of antenatal micronutrient supplementation on adolescent blood pressure (BP). METHODS: This study involved adolescents from two rural counties in western China. Their mothers had previously participated in a cluster-randomized trial of antenatal micronutrient supplementation. All pregnant women were randomized to take a daily capsule of folic acid (FA) as control, folic acid plus iron (IFA), or multiple micronutrients (MMNs) until delivery. Adolescent BP was assessed using a validated electronic sphygmomanometer and converted into percentiles by population reference. We examined the effects of antenatal micronutrient supplementation on adolescent BP and BP percentiles using generalized estimation equations. Multinomial logistic regression was employed to examine the associations between antenatal micronutrient supplementation and categorical BP outcomes, with relative risk reduction estimated. RESULTS: Among 4488 singleton births eligible for long-term follow-up, 1994 (44.4%) adolescents were followed, and among them, 59.2% were male, with a mean age of 11.73 (SD, 0.86) years old. After adjusting for a range of covariates, antenatal MMNs supplementation relative to FA alone was associated with a 1.13 (95% CI -2.09, -0.17) mmHg lower systolic blood pressure (SBP) and a 2.59 (95% CI -5.01, -0.17) points lower SBP percentile. The similar benefits of MMNs were observed for categorized adolescent high BP (SBP and/or diastolic blood pressure (DBP) ≥ the 95th percentile for age, sex, and height). CONCLUSIONS: Compared with folic acid alone, antenatal MMNs supplementation was associated with lower adolescent SBP. This finding suggests that comprehensive antenatal nutritional interventions may offer a potential strategy for the primordial prevention of hypertension in offspring. TRIAL REGISTRATION: ISRCTN08850194, retrospectively registered December 14, 2006. https://www.isrctn.com/ISRCTN08850194?q=ISRCTN08850194&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10 . © 2025. The Author(s).

BACKGROUND: Micronutrient deficiencies among pregnant women contribute to adverse maternal and neonatal outcomes. Multiple micronutrient supplementation (MMS) has proven its superiority when compared to the standard iron and folic acid (IFA) supplementation for maternal and infant morbidity and mortality. The Government of Nepal is exploring the scale-up of MMS, but first requires evidence such as on its adherence and acceptability. The objective of this study, thus, is to generate this needed evidence. METHODS: The Non-inferiority Assessment of Maternal Adherence to Supplements, a Trial on the Effects of Multiple Micronutrient Supplementation (NAMASTE-MMS) in Nepal study is a three-arm, parallel, non-inferiority cluster-randomized controlled trial (c-RCT) assessing how well pregnant women adhere to and accept different types of supplements: MMS in blister packs or bottles versus IFA in blister packs. In one of Nepal's seven provinces, Lumbini, the longitudinal NAMASTE-MMS study is being implemented across 120 health facilities (clusters), enrolling 2640 pregnant women into one of three arms: IFA-blister, MMS-blister, or MMS-bottle. The primary outcome is adherence to 180 supplements during pregnancy, measured by tablet counts with a non-inferiority margin of 13%. Secondary outcomes include comparisons of adherence between the two MMS arms and utilization of Antenatal Care (ANC), both potentially impacted by type of packaging. Exploratory outcomes include comparisons of adherence as well as the degree of acceptability to supplementation during early and mid pregnancy and post-partum. DISCUSSION: Evidence generated from this study and three related mixed-methods implementation research studies will help the government in its potential scale-up of MMS supplementation during pregnancy and lactation. TRIAL REGISTRATION: NCT06327646 (ClinicalTrials.gov, March 18, 2024 registered). © 2025. The Author(s).

INTRODUCTION: The risk of adverse birth outcomes, such as low birth weight (<2500 g, LBW), is associated with poor maternal nutrition and weight gain in pregnancy and can increase the risk of infant mortality. We evaluated the effect of three prenatal nutritional supplementation strategies to improve maternal nutrition and adverse pregnancy and birth outcomes. METHODS: A cluster-randomised trial of three prenatal nutritional supplements was conducted in rural Niger. Villages (n=53) were randomised to receive either daily prenatal multiple micronutrient supplementation with 20 micronutrients and 30 mg iron (MMN), medium-quantity lipid-based micronutrient supplementation with 30 mg iron and 237 kcal (MQ-LNS), or routine iron folic acid supplementation with 60 mg of iron (IFA). Pregnant women were identified through monthly, community-based pregnancy surveillance. Study outcomes included infant birth weight, maternal weight gain during pregnancy (including total weight gain, rate of weight gain and adequacy of weight gain) and maternal haemoglobin (Hb) concentration and anaemia (Hb <110 g/L) in the second and third trimesters. RESULTS: A total of 3332 pregnant women were enrolled between September 2015 and February 2017. Birth weight did not significantly differ by supplementation group (mean difference MMN vs IFA=39 g, 95% CI -55, 134; mean difference MQ-LNS vs IFA=50 g, 95% CI -55, 156). There was also no statistically significant effect of MMN or MQ-LNS compared with IFA on total weight gain in pregnancy, the rate of weight gain per week during the second and third trimesters or adequacy of gestational weight gain (p values >0.05). We found no effect of MMN or MQ-LNS on maternal haemoglobin concentration or anaemia in the second and third trimesters (p values >0.05). CONCLUSION: There was no statistically significant difference in birth weight, maternal weight gain or anaemia by prenatal nutritional supplementation strategy. However, statistical power in the trial was limited. A combination of strategies may be required to make large improvements in birth and pregnancy outcomes in rural Niger. © Author(s) (or their employer(s)) 2025. Re-use permitted under CC B

OBJECTIVE: Nutrition education plays a crucial role in improving the nutritional status of pregnant women, yet evidence of its impact in low-income settings like Ethiopia is limited. This study evaluated the effectiveness of facility-based nutrition education and counseling on pregnant women's knowledge, dietary practices, and Fe-folic acid supplement use. DESIGN: A cluster randomised controlled trial was conducted in Addis Ababa, Ethiopia, involving 683 pregnant women across twenty health centres assigned to intervention or control groups. Antenatal care providers in the intervention group received training on pregnancy nutrition and counseling, while the control group continued standard care per national guidelines. A total of 683 pregnant women were enrolled during their first and second antenatal care (ANC) visits. Mixed-effects linear regression was used to evaluate outcomes. STUDY SETTING: The study was conducted in Addis Ababa, Ethiopia, from August to December 2017. PARTICIPANTS: Pregnant women attending ANC follow-ups and healthcare providers working in ANC units. RESULTS: The intervention group demonstrated significant improvements in knowledge, including iodised salt use (difference-in-differences (DID) 23 %), correct Fe-folic acid supplementation duration (DID 68 %) and the need for additional meals during pregnancy (DID 49·9 %). Dietary practices improved with higher dietary diversity (DID 32·3 %), increased dairy consumption (MD 1·2 v. -0·1; DID 1·2 per week) and higher Fe-folic acid supplementation (MD 4·9 v. 1·6; DID 3·2 per week). CONCLUSION: Nutrition education and counseling during ANC visits significantly improved pregnant women's knowledge and dietary practices. Integrating and strengthening these interventions into routine ANC services could effectively enhance dietary intake and health outcomes.

BACKGROUND: A few studies examined behavioral difficulties among children in low-income countries or the influence of early life nutrition interventions. OBJECTIVES: We examined the effect of micronutrient supplementation done as part of 2 randomized trials during pregnancy or in early preschool age on behavioral outcomes among school-aged children in rural Nepal. METHODS: Children between 7 and 9 y of age were enrolled in a cohort follow-up study in which the Conners Rating Scale-Revised was administered to their parents and teachers. These children were offspring of participants in a cluster-randomized trial during pregnancy receiving daily iron-folic acid, iron-folic acid + zinc, or multiple micronutrients, compared with a control (all groups received vitamin A). These children between 12 and 35 mo of age also received daily placebo, iron-folic acid, zinc alone, or iron-folic acid + zinc in a separate randomized trial. Factor analysis identified 2 attention-deficit hyperactivity disorder-related behaviors for parent scores (hyperactivity/oppositional and inattention) and 2 for teacher scores (hyperactivity and inattention). Using mixed-effects linear regression analysis, we analyzed the effect of early life supplementation on these behavioral domains in school children (n = 1255). RESULTS: Exposure to prenatal iron-folic acid resulted in lower oppositionality/hyperactivity and inattention scores in children assessed via parental ratings in both unadjusted and adjusted analyses. Iron-folic acid with zinc reversed the positive effect seen with iron-folic acid. Multiple micronutrient supplementation resulted in a lower oppositionality and/or hyperactivity score, using parent and teacher ratings in the adjusted analysis. All 3 supplement groups in the preschool trial reduced child inattention when assessed by parents. Based on teacher ratings, groups that had received iron-folic acid alone or with zinc during preschool had reduced scores of hyperactivity in both unadjusted and adjusted analyses. CONCLUSIONS: Our study shows potential benefit of early life exposure to micronutrient supplementation for child-related behavior outcomes in a South Asian setting where

OBJECTIVE: To evaluate zinc supplementation's efficacy in pregnancy, addressing gaps in previous reviews regarding high-risk subgroups and combination therapies. METHODS: Systematic review of six databases through March 27, 2025 for randomized controlled trials (RCTs) on prenatal zinc supplementation. Risk of bias was assessed using the Cochrane Risk of Bias 2. Stratified analyses was conducted by participant or intervention characteristics, with meta-analysis or qualitative synthesis when appropriate. Sensitivity analyses was conducted by excluding studies with high risk of bias. The systematic review was registered in PROSPERO (CRD42023440314). RESULTS: 77 RCTs were included. Compared with no zinc, zinc monotherapy among healthy pregnant women resulted in higher serum zinc level (standard mean difference (SMD) the second trimester = 0.32, 95% confidence interval (CI) 0.20 to 0.44; SMDthe third trimester = 0.51, 95% CI 0.27 to 0.76), lower fetal intrauterine retardation rate (risk ratio = 0.23, 95% CI 0.16 to 0.35), longer neonatal birth length (SMD = 0.66, 95% CI 0.21 to 1.12), bigger birth head circumference (SMD = 0.58, 95% CI 0.08 to 1.09), higher 1-min Apgar score (SMD = 0.28, 95% CI 0.06 to 0.49) and cord blood zinc level (SMD = 0.36, 95% CI 0.17 to 0.56). No additional benefits observed with zinc-iron-folate combinations versus iron-folate alone. Qualitative synthesis of limited evidence suggested potential benefits for high-risk groups (anemia, gestational diabetes, zinc deficiency or impaired intravenous glucose tolerance test). CONCLUSIONS: Zinc monotherapy may benefit healthy pregnancies and high-risk groups, but combination regimens show no additional advantages. Further research should confirm these findings. © 2025 The Author(s). Journal of Evidence‐Based Medicine published by Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

INTRODUCTION: We aimed to determine the impact of antenatal interventions to optimise maternal nutrition and infection management on birth outcomes in Ethiopia. METHODS: We conducted a pragmatic, open-label, 2×2 factorial randomised clinical effectiveness study among pregnant women enrolled <24 weeks gestation in 12 rural health centres in Amhara, Ethiopia. Eligible health centres were randomised to deliver an enhanced nutrition package (ENP) (iron-folic acid, iodised salt and targeted micronutrient fortified balanced energy protein (BEP) supplementation for undernourished women) or routine nutrition care (iron-folic acid only). Individual women were randomised to receive an enhanced infection management package (EIMP) (genitourinary tract infection screening-treatment and enhanced deworming) or routine infection care (syndromic management). The primary outcomes were birth weight and length; secondary outcomes were gestational age, preterm delivery, small-for-gestational-age, low birth weight, stillbirth, newborn weight-for-age and length-for-age z-scores, newborn head circumference, and maternal anemia. Analysis was intention to treat. RESULTS: From August 2020 to December 2021, 2392 women were randomised (604 ENP+EIMP, 600 ENP alone, 593 EIMP alone and 595 neither package) and followed until June 2022, with 2170 pregnancy outcomes analysed (565 ENP+EIMP, 549 ENP, 525 EIMP, 531 neither). In the ENP arm, 427 (36%) women were eligible for BEP and consumed on average 74 days. The prevalence of genitourinary tract infection was low (4.9%), while parasitic stool infections were common (31%). There was no difference in birth weight (ENP vs not-ENP: adjusted mean difference -4 g (-83 to 75); EIMP vs not-EIMP: 18 g (-35 to 70); ENP+EIMP vs neither: 14 g (-81 to 109)) or birth length (ENP: -0.3 cm (-1.1 to 0.5); EIMP: 0.2 cm (-0.1 to 0.5); ENP+EIMP: -0.1 cm (-1.2 to 1.1)) between study arms. In the ENP+EIMP group, the stillbirth rate was lower compared with the arm receiving neither package (7.1/1000 vs 24.7/1000 births; adjusted relative risk: 0.29 (0.09 to 0.94)). The packages did not significantly affect other secondary outcomes. CONCLUSIONS: In this pragmatic study

BACKGROUND: Antenatal multiple micronutrient supplementation (MMS) has been shown to be more effective than iron-folic acid (IFA) alone in reducing adverse pregnancy and birth outcomes. However, there is a concern that MMS containing 30 mg of iron may be less effective in reducing maternal anemia compared to IFA supplements containing 60 mg of iron. This poses a clinical and programmatic dilemma for countries with a high burden of maternal anemia (> 40% prevalence) where the World Health Organization (WHO) recommends using IFA with 60 mg of iron. METHODS/DESIGN: We will conduct an individually randomized, quadruple-blind superiority trial of daily antenatal MMS in Dar es Salaam, Tanzania (n = 6381 pregnant women). Participants will be randomized to receive a daily MMS regimen during pregnancy containing 60 mg iron, 45 mg iron, or 30 mg iron at a ratio of 1:1:1. The trial participants, outcome assessors (research staff and care providers), investigators, trial statistician, and data analysts will be blinded. Pregnant women will be enrolled in the trial before 20 weeks of gestation and will receive the randomized MMS regimen from enrollment until the time of pregnancy outcome/delivery. The primary outcome is maternal third-trimester moderate or severe anemia (Hb < 10.0 g/dL). The proportion of women who have moderate or severe anemia at 32 weeks of gestation will be compared between MMS containing 60 mg iron versus MMS containing 30 mg iron, as well as MMS containing 45 mg iron versus MMS containing 30 mg iron. Secondary outcomes include maternal hemoglobin concentration, anemia, maternal iron deficiency, and maternal iron deficiency anemia at 32 weeks gestation and 6 weeks postpartum; preeclampsia, antepartum bleeding, postpartum hemorrhage, maternal peripartum infection, pregnancy-related death, symptoms consistent with depression, fatigue, and maternal malaria during pregnancy and 42 days following; fetal death, stillbirth, birth weight, low birthweight, gestational age at birth, preterm birth, birthweight for gestational age, and small-for-gestational age birth; infant hemoglobin concentrations, infant iron status, neonatal death, and infant death at 6 weeks o

Erratum in Adv Nutr. 2025 Dec;16(12):100553. doi: 10.1016/j.advnut.2025.100553. Multiple micronutrient supplements (MMS) in pregnancy reduces risk of infant low birthweight (LBW) and improves other maternal and infant outcomes compared with iron and folic acid (IFA) supplements alone. However, the impact of timing of initiation and adherence on the MMS effectiveness in real-world programs remains unclear. To address this, we conducted a 2-stage individual participant data meta-analysis that included 15 randomized trials (61,204 pregnant women) and assessed whether the relative effect of MMS differed by the following: adherence alone; adherence in combination with gestational age at initiation; and the total number of tablets taken. We also evaluated the observational association of these factors with outcomes among participants who received MMS. Compared with IFA supplements, the relative effect of MMS on the primary outcome of continuous birthweight was greater with higher adherence (P-interaction < 0.05). Among women who took ≥90% of supplements, MMS increased birthweight by 56 g (95% CI: 45, 67 g), whereas among women who took <60% of supplements, there was no difference in birthweight between MMS and IFA supplements [mean difference (MD): 9 g; 95% CI: -17, 35 g). Higher adherence was also associated with greater effect of MMS on LBW and birthweight-for-gestational age centile and women who took more supplements experienced a greater relative impact of MMS on birthweight-for-gestational age centile and small-for-gestational age births (SGA) as compared with IFA supplements. Observational analyses among participants who received MMS showed that ≥90% adherence was associated with increased birthweight (MD: 44 g; 95% CI: 31, 56 g) and lower risk of LBW [relative risk (RR): 0.93 g; 95% CI: 0.88, 0.98 g] and small-for-gestational age (RR: 0.95; 95% CI: 0.93, 0.98), whereas <75% adherence was associated with greater risk of stillbirth (RR: 1.43; 95% CI: 1.12, 1.83) and maternal anemia (RR: 1.26; 95% CI: 1.11, 1.43) than 75%-90% adherence. Programs should invest in strategies that promote early initiation and high adherence to MMS. This trial was registered at PROS

BACKGROUND: The Cambodian Ministry of Health is exploring transitioning from iron and folic acid (IFA) to multiple micronutrient supplements (MMS) during pregnancy and is seeking rigorous evidence to inform this policy change. OBJECTIVE: We aimed to assess the adherence and acceptability of MMS compared with IFA supplementation during pregnancy. METHODS: We conducted an open-label cluster-randomized noninferiority trial across 48 health centers in Cambodia. A total of 1546 healthy pregnant individuals (18-45 y) were recruited at their first antenatal care (ANC) visit (<14 weeks of gestation) and randomized to 1 of 3 arms at the health center level: 1) IFA for 90 d (IFA-90, n = 515), the current standard of care; 2) MMS for 180 d via 1 180-tablet bottle (MMS-180, n = 516); or 3) MMS for 180 d via 2 90-tablet bottles (MMS-90, n = 515). Our primary outcome was the noninferiority of adherence rates of MMS-180 compared with IFA-90, assessed by tablet counts and compared against a predefined noninferiority margin of -15%. Mixed-effects linear regression models were used to estimate the mean difference (95% confidence interval [95% CI]) in adherence rates. Our secondary outcomes included the mean difference in ANC attendance between the MMS groups and the acceptability of MMS across 6 domains. RESULTS: Overall, 88% of participants completed the trial, with high mean adherence rates across arms (91% for IFA-90, 95% for MMS-180, and 95% for MMS-90). The adjusted mean (95% CI) difference in adherence rates between MMS-180 and IFA-90 groups was 3.9% (1.7, 6.2). The adjusted mean (95% CI) difference in ANC visits for MMS-180 and MMS-90 groups was 0.0 (-0.1, 0.2) visits. The acceptability of MMS was positive (90%-100% "agreement" across 6 domains). CONCLUSIONS: Both IFA and MMS were highly acceptable, yet adherence to MMS was superior to IFA. These findings support the transition from IFA to MMS in Cambodia. This trial was registered at Clinicaltrials.gov as NCT05867836.

INTRODUCTION: Maternal undernutrition and infections during pregnancy may influence birth and long-term child development outcomes. Characterising the micronutrient, metabolomic and microbiome profiles of pregnant women and infants may elucidate the underlying biology of adverse birth outcomes and early child development in the first 1000 days. METHODS AND ANALYSIS: The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study was a 2×2 factorial, randomised clinical effectiveness study conducted in Amhara, Ethiopia from August 2020 to June 2022. We cluster-randomised pregnant women (n=2399) to receive either a nutrition intervention (iron-folic acid (IFA), iodised salt and balanced energy-protein supplementation for women with mid-upper arm circumference <23 cm) or routine care (IFA only), and individually randomised women to an infection control intervention (genitourinary tract infection screening-treatment and screening-treatment of stool parasites) or routine care (syndromic approach). Participants were followed until 1 month postpartum. A subset of 532 women-infant dyads were consecutively enrolled in the biospecimen substudy from July 2021 to August 2022. Specimens were collected at enrolment (<24 weeks) and antenatal care follow-up (third trimester), and 1-6 months postdelivery. A subset of ENAT mother-infant dyads (n=462) was enrolled in the Longitudinal Infant Development and Growth study that followed infants until 24 months postpartum, from February 2023 to June 2024. We will determine the impact of ENAT interventions on micronutrient status, inflammation biomarkers and metabolomic and microbiome profiles. We will also determine the association of these profiles with birth outcomes and infant neurodevelopment. ETHICS AND DISSEMINATION: These studies were approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/IRB/002/2022) and Mass General Brigham (2023P000461). Results will be disseminated to international stakeholders via peer-reviewed journals and locally via strategic dissemination sessions. TRIAL REGISTRATION NUMBERS: ISRCTN15116516 and NCT06296238. © Author(s) (or their employer(s)) 2025. Re-

BACKGROUND: Antenatal care attendance is still low in sub-Saharan countries. While mobile phones have shown to improve outcomes in maternal health services, there are few published studies on the use of mobile phone calls in antenatal care. OBJECTIVE: To determine the influence of mobile phone calls on pregnant women's completion of the recommended 4 ANC visits in Kisii County, Kenya. METHODOLOGY: 16 sub county health facilities (clusters) were randomly assigned to either intervention or routine care. A total of 160 pregnant women were recruited in their first antenatal care visit and followed up until delivery. The intervention involved calling mothers through their mobile phones to give health education on antenatal care every month until delivery. The primary outcome measure was the completion of the 4 recommended antenatal care (ANC) visits while secondary outcome measures were; women receiving iron and folate supplements, and completion of all recommended laboratory tests. RESULTS: 50% of the women in the intervention group and 35% in the control group completed the four recommended ANC visits. The intervention was not a significant predictor of women receiving iron and folate supplements, RR, 1.07 (0.93 - 1.25), p - value = 0.412. However, the intervention was associated with a 46% increase in women completing all required antenatal care laboratory investigations. CONCLUSION: The use of mobile phone calls in antenatal health education show promise in improving antenatal care attendance among pregnant women. © 2024 Malachi ZM et al.