Multiple Micronutrient Research Articles

Maternal Periconceptional Folic Acid Supplementation and Risk for Fetal Congenital Heart Defects

To determine the effects of maternal periconceptional supplementation with folic acid or multiple micronutrients containing folic acid on the prevention of fetal congenital heart defects (CHDs). Data were drawn from a Prenatal Health Care System and a Birth Defects Surveillance System in a district of Beijing, China. A total of 63 969 singleton births, live or stillborn, 308 CHDs among them, during 2013 to 2018 were included. Associations between different patterns of supplementation and risk for total CHDs or main types of CHDs were evaluated with risk ratios (RRs). For folic acid or multiple micronutrients containing folic acid users compared with nonusers, the adjusted RRs (ARRs) for total CHDs, critical CHD, and ventricular septal defect (VSD) were 0.60 (95% CI, 0.44-0.83), 0.41 (95% CI, 0.26-0.67), and 0.47 (95% CI, 0.30-0.74), respectively. When we compared multiple micronutrients containing folic acid users with folic acid users, the ARRs were 0.84 (95% CI, 0.66-1.09), 0.64 (95% CI, 0.41-1.00), and 0.94 (95% CI, 0.63-1.41) for total CHDs, critical CHD, and VSD, respectively. We also found that, compared with supplementation initiated after conception, supplementation initiated before conception was associated with a lower risk for CHDs: the ARRs were 0.68 (95% CI, 0.48-0.95) for total CHDs and 0.26 (95% CI, 0.10-0.71) for critical CHD, but 1.08 (95% CI, 0.63-1.83) for VSD. Maternal periconceptional supplementation with folic acid or multiple micronutrients containing folic acid seems to decrease the risk for CHDs, especially critical CHD, in offspring. Supplementation confers a greater protective effect when it is initiated before conception. We did not find any difference between folic acid and multiple micronutrients containing folic acid in terms of preventing CHDs.

Multiple micronutrient supplementation programme of Sri Lanka: does it deliver the goods? Experience from Central Province - A preliminary study

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

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

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

Maternal-focused interventions to improve infant growth and nutritional status in low-middle income countries: A systematic review of reviews.

BackgroundSmall and nutritionally at-risk infants under 6 months (<6m) are a vulnerable group at increased risk of mortality, morbidity, poor growth and sub-optimal development. Current national and international (World Health Organization) management guidelines focus mainly on infants’ needs, yet growing evidence suggests that maternal factors also influence infant outcomes. We aimed to inform future guidelines by exploring the impacts of maternal-focused interventions on infant feeding and growth.MethodsWe conducted a systematic review of reviews published since 2008 (PROSPERO, register number CRD 42019141724). We explored five databases and a wide variety of maternal-focused interventions based in low- and middle-income countries. Infant outcomes of interest included anthropometric status, birthweight, infant mortality, breastfeeding and complementary feeding practices. Given heterogenous interventions, we present a narrative synthesis of the extracted data.ResultsWe included a total of 55 systematic reviews. Numerous maternal interventions were effective in improving infant growth or feeding outcomes. These included breastfeeding promotion, education, support and counselling interventions. Maternal mental health, while under-researched, showed potential to positively impact infant growth. There was also some evidence for a positive impact of: women’s empowerment, m-health technologies, conditional cash transfers, water, sanitation and hygiene and agricultural interventions. Effectiveness was increased when implemented as part of a multi-sectoral program. Antenatal supplementation with macronutrient, multiple micronutrients, Vitamin D, zinc, iron folic acid and possibly calcium, iodine and B12 in deficient women, improved birth outcomes. In contrast, evidence for postnatal supplementation was limited as was evidence directly focusing on small and nutritionally at-risk infants; most reviews focused on the prevention of growth faltering.ConclusionOur findings suggest sufficient evidence to justify greater inclusion of mothers in more holistic packages of care for small and nutritionally at-risk infants aged <6m. Context specific approaches are likely needed to support mother-infant dyads and ensure infants survive and thrive.

Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

BackgroundNutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine.Methods and findingsWe nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron–folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6–8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear.ConclusionsThis study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings.Trial registrationClinicalTrials.gov NCT02145000.

Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01–2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844–868) at birth in terms of weight (β’ = 0.078 (0.024–0.133); p = 0.005), head circumference (β’ = 0.060 (0.012–0.107); p = 0.02), body mass index (β’ = 0.067 (0.014–0.119); p = 0.01), and various skinfold thicknesses (β’ = 0.067–0.094; p = 0.03–0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM.

English

BACKGROUND Multiple micronutrient deficiencies commonly coexist in pregnancy and may play a role in the pathogenesis of many high-risk events in pregnancy. Mineral estimation during the first and second trimester may help in the identification of high-risk pregnancies predisposed to pre-eclampsia, preterm birth or low birth weight. Body mass index (BMI) is an independent risk factor influencing the serum levels of micronutrients like iron, calcium, phosphorous and magnesium. The purpose of this study was to compare the serum levels of iron, magnesium, calcium and phosphorus during first &amp; second trimesters of pregnancy and their correlation with body mass index and adverse pregnancy outcomes. METHODS This was a longitudinal descriptive study, done over a period of twelve months, from April 2017 to March 2018. 94 low risk pregnant women were selected in the first trimester, and they were followed up for the entire duration of pregnancy. 2 ml of blood is collected at first and second trimester and analysed for the serum levels of iron (µg/dl), magnesium (mg/dl), calcium (mg/dl) and inorganic phosphorus (mg/dl). Mean values of these elements were noted and BMI was measured. Patients were followed up to observe the pregnancy outcome, especially development of hypertension, preterm birth and low birth weight. The data were subjected to suitable statistical analyses. P value less than 0.05 is considered as statistically significant. RESULTS Mean values of Ca, Mg, inorganic P and Fe were 9.3 mg/dl ± 0.52, 1.79 mg/dl ± 0.28, 3.59 mg/dl ± 0.54 and 83.7 µg/dl ± 25.36 respectively in first trimester and 8.9 mg/dl ± 0.47, 1.62 mg/dl ± 0.16, 3.17 mg/dl ± 0.44 and 76.17 µg/dl ± 21. 69 respectively in the second trimester. Hypocalcaemia was noted in 12.7 % and 38.3 % in the first and second trimester respectively. Hypomagnesaemia was seen in 51.1 % and 80.9 % in the first and second trimester respectively. Hypophosphatemia was seen in 3.2 % and 14.8 % in the first and second trimester respectively. These findings were statistically significant. There was no significant change in the iron levels in the present study. 19.1 % were underweight. 56.4 % had normal BMI. 19.2 % were overweight. 5.3 % were obese. CONCLUSIONS There is no correlation between serum values of trace elements and the BMI of study subjects. Even though significant hypocalcaemia, hypophosphatemia and hypomagnesaemia was noted in second trimester compared to first, there was no predisposition to the development of adverse outcomes like pre-eclampsia, preterm birth or low birth weight. This may be the effect of dietary and pharmacological supplementation during pregnancy. KEYWORDS Micronutrients, Pregnancy Complications, Calcium, Phosphorus, Magnesium, Iron

Efficacy of B12 Fortified Nutrient Bar and Yogurt in Improving Plasma B12 Concentrations—Results From 2 Double-Blind Randomized Placebo Controlled Trials

Dietary vitamin B12 (B12) deficiency is common in Indians. Long-term compliance to tablet supplementation is poor in asymptomatic individuals. To study efficacy of B12 fortified nutrient bar and yogurt in improving plasma B12 concentrations in children and adults. Two double-blind, placebo-controlled directly observed therapy randomized controlled trials were conducted for 120 days: (1) Healthy children (10-13 years) were fed nutrient bar fortified with B12 (2 μg), multiple micronutrients B12 (1.8 μg) or placebo. (2) Healthy adults (18-50 years) were fed yogurt fortified with B12 (2 μg) or Propionibacterium (1 × 108 cfu/g) or placebo. B12, folate, homocysteine, and hemoglobin concentrations were measured before and post intervention. We randomized 164 children and 118 adults; adherence was 96% and 82%, respectively. In children, B12 fortified bars increased B12 concentrations significantly above baseline (B12 alone +91 pmol/L, B12+ multiple micronutrients +82 pmol/L) compared to placebo. In adults, B12 fortified yogurt increased B12 significantly (+38 pmol/L) but Propionibacterium and placebo did not. In both trials, homocysteine fell significantly with B12 supplementation. Rise of B12 and fall of homocysteine were influenced by dose of B12 and folic acid. There was no significant difference in change of anthropometry and hemoglobin between groups. B12 fortified foods are effective in improving B12 status in Indian children and adults. They could be used to improve B12 status in the national programs for children, adolescents, and women of reproductive age. They could also be used as over-the-counter products.

Effect of Fortification with Multiple Micronutrient Powder on the Prevention and Treatment of Iron Deficiency and Anaemia in Brazilian Children: A Randomized Clinical Trial.

Fortification with multiple micronutrient powder has been proposed as a public health intervention able to reduce micronutrient deficiencies in children. Our objective was to compare the effectiveness of fortification with multiple micronutrient powder with drug supplementation in the prevention and treatment of iron deficiency and anaemia. This was a cluster trial with anemic and non-anaemic children between six and 42 months old, in randomization data. Non anaemic children received fortification with multiple micronutrient powder or standard drug supplementation of ferrous sulfate associated with folic acid in a prevention dose. Anaemic children who were randomized to receive multiple micronutrient powder also received the recommended iron complementation for anaemia treatment. A total of 162 children were evaluated. The prevalence of anaemia decreased from 13.58 to 1.85%. Iron deficiency decreased from 21.74% to 7.89% (by serum ferritin) and iron deficiency decreased from 66.81 to 38.27% (by soluble transferrin receptor). No difference was identified between interventions for hemoglobin (p = 0.142), serum ferritin (p = 0.288), and soluble transferrin receptor (p = 0.156). Fortification with multiple micronutrient powder was effective in preventing iron deficiency and anaemia in children aged six to 48 months. In anaemic children; it was necessary to supplement the dose of multiple micronutrient powder with ferrous sulfate.

Physico-chemical and sensory acceptability of no added sugar chocolate spreads fortified with multiple micronutrients

Vitamin D and magnesium-calcium carbonate nanoparticles were used to fortify a newly developed healthy chocolate spread formulated with inulin and maltitol as sugar replacers and alternative to palm oil to reduce the concentration of saturated fatty acid. These samples were compared with well-known commercially available chocolate spreads in terms of rheology, polyphenols content and in vitro digestion, sensory attributes and willingness to buy. The fortified chocolate spreads showed comparable if not better acceptability than the current products on the market and over 80% of the participants were inclined to buy and 66% prepared to spend 10 to 15% more money on the product enriched with the three micronutrients. The results also demonstrate that the incorporation of nanoparticles could affect the rheological and physio-chemical properties of the formulations and an appropriate ratio between the fat phase and particles seems an important factor to consider.

Effects of vitamin and mineral supplementation during pregnancy on maternal, birth, child health and development outcomes in low- and middle-income countries: A systematic review.

Effects of vitamin and mineral supplementation during pregnancy on maternal, birth, child health and development outcomes in low- and middle-income countries: A systematic review.

Effects of Prenatal and Postnatal Maternal Multiple Micronutrient Supplementation on Child Growth and Morbidity in Tanzania: A Double-Blind, Randomized Controlled Trial

ObjectivesMaternal 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. The aim of this study was to determine the effects of prenatal and postnatal maternal MMS on child growth and morbidity in Tanzania. MethodsIn this double-blind, randomized controlled trial, 8,379 HIV-negative pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. From pregnancy (12 to 27 weeks of gestation) through 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 18 months postpartum, 3,100 women were re-randomized to MMS or placebo. Child growth measures, hemoglobin concentrations, and infectious morbidities were assessed longitudinally from birth to up to 18 months. Linear mixed-effects models were used to estimate the effects of prenatal and postnatal MMS on child growth z-scores and hemoglobin concentrations. Cox proportional hazards models were used to estimate the effects on undernutrition. Generalized estimating equations were used to estimate the effects on anemia and infectious morbidities. ResultsPrenatal MMS led to modest increases in weight-for-age z-score (mean difference: 0.050; 95% CI: 0.002, 0.099; p = 0.04) and length-for-age z-score (mean difference: 0.062; 95% CI: 0.013, 0.111; p = 0.01) during the first six months of life but not thereafter. Prenatal MMS did not have significant benefits for anemia, morbidity, or other child growth outcomes. Postnatal MMS did not have significant benefits for any child outcomes. ConclusionsWhile 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. Funding SourcesThis work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health.

Chronic Vitamin E Deficiency in Rural Bangladeshi Women

ObjectivesVitamin E deficiency (VED) appears to be common in rural areas of South Asia, with prevalence of ≥ 50% reported among women of reproductive age. Long term deficiency may impart neurological damage, but little information exists about persistence of VED. We provide initial estimates of chronic VED (CVED) in women of reproductive age living in Gaibandha District, a typical rural setting in NW Bangladesh. MethodsWe assessed α-tocopherol concentrations by HPLC in early pregnancy and 3-month postpartum (PP) plasma samples of women participating in biochemical sub-studies of JiVitA-1 (n = 2,319), a cluster-randomized, placebo-controlled, weekly vitamin A or β-carotene supplementation trial from 2001–7, and JiVitA-3 (N = 2,073), a cluster-randomized, daily multiple micronutrient (MMS) versus iron-folic acid (IFA) supplementation trial from 2008–12. VED was conventionally defined by an α-tocopherol concentration < 12 μmol/L and CVED as α-tocopherol < 12 μmol/L at both early pregnancy and postpartum assessments, an interval spanning a median (IQR) of 9.4 (2.8) months. ResultsAcross both trials combined (N = 4,392), the mean ± SD plasma α-tocopherol concentration and prevalence of VED in early pregnancy and at 3 months post-partum was 11.28 ± 4.07 and 10.86 ± 4.41 μmol/L, and 53.5% and 42.2%, respectively. In JiVitA-3, the post-partum prevalence of VED among women not previously receiving MMS (containing 15 mg of vitamin E as all-rac-α-tocopheryl acetate) was 57.5% (vs 42.5% among MMS recipients, p < 0.001). The prevalence of CVED among women in both trials combined was 32.0% (34.45% in JiVitA-1 and 26.65% in JiVitA-3, IFA group only). Across a maternal age range of 11–43 [median: 20 (IQR: 8) years, risk of CVED decreased comparably per year of age in the JiVitA-1 [OR = 0.94 (95% CI: 0.93–0.95)] and JiVitA-3 [OR = 0.93 (95% CI:0.92–0.95)] trials. ConclusionsIn rural NW Bangladesh, where over half of women enter pregnancy vitamin E-deficient, about one-third are also deficient postpartum, ∼10 months later, providing a provisional estimate of chronic maternal vitamin E deficiency in a South Asian setting. Funding SourcesBill & Melinda Gates Foundation (Grant GH614, OPP1141435) and US Agency for International Development (AID (HRN-A-00–97-00015–00).

Associations Between Gestational Weight Gain Adequacy and Perinatal Outcomes in Tanzania

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

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.

Antenatal Multiple Micronutrient Supplementation in the State of Palestine: A Protocol for Implementation and Evaluation

ObjectivesThe 2013 Palestinian Micronutrient Survey1 reported high and comparable 1st trimester prevalences of micronutrient deficiencies in the Gaza Strip and West Bank: 23.6% and 21.3% for iron, 67.9% and 49.6% for zinc, 11.4% and 8.8% for vitamin A, 27.9% and 19.1% for B12, 78.6% and 66.7% for vitamin D and 17.5% and 13.2% for vitamin E, respectively. Rates were generally higher among gravida in their 2nd-3rd trimesters. Interim, clinic-based, anemia rates2 in the Gaza Strip and West Bank of 32% and 19% in the first trimester and 71% and 38% in the 2nd and 3rd trimesters, respectively, coupled with food insecurity, dietary inadequacy, civil conflict and stresses from the COVID-19 pandemic, suggest micronutrient deficiencies persist as a public health burden in the State of Palestine. To replace current iron-folic acid (IFA) with a multiple micronutrient supplement (MMS) providing a Recommended Dietary Allowance of 15 essential vitamins and minerals as standard of antenatal care (ANC) in UNWRA clinics and hot spots serving pregnant women in the Gaza (n = 22) in 2021–2 and West Bank (n = 44) in 2022–3. MethodsMMS is planned to start in Gaza in the Fall of 2021, where UNRWA antenatal services reach ∼38,000 pregnant women with IFA each year; ∼97% of whom attended ANC ≥ 4 times2. Implementation will follow a randomized, step-wedge procedure whereby MMS will start in the 1st 11 clinics, and six months later, the 2nd group of 11 clinics, providing a design for monitoring and comparing the new MMS to existing IFA programs during an initial 6–8 month period. ResultsOutcomes will include indicators of adoption, acceptability, coverage, adherence, fidelity, cost-efficiencies and, as a routine clinical outcome, late pregnancy anemia. ConclusionsMaternal micronutrient deficiencies are common in Palestine3, meriting replacing IFA with MMS. This research protocol will evaluate implementation in the Gaza Strip to provide guidance for launching and improving antenatal MMS delivery throughout the UNRWA health system. Funding SourcesUNWRA, Sight and Life, Kirk Humanitarian, Vitamin Angels Alliance, Ministry of Foreign Affairs of Japan, Palestine Ministry of Health.

Effects of Supplementation With Iron Syrup or Iron-Containing Multiple Micronutrient Powders on Neural Indices of Cognitive Functioning in Bangladeshi Children

ObjectivesMicronutrients, especially iron, play a critical role in the developing infant brain. Yet, the causal effects of iron supplementation on neurocognitive functioning in a low-income anemic population of children have not been examined. This study sought to evaluate the effects of supplementation with iron syrup and iron-containing multiple micronutrient powders (MNPs) in Bangladeshi children on habituation to familiar sounds, a marker for healthy memory development, using auditory event-related brain potentials (ERPs). MethodsThis study was nested within the Benefits and Risks of Iron Supplementation in Children (BRISC) trial, a double blinded double dummy randomized controlled trial (RCT). At 8 months of age, 3300 children were randomized to receive 3 months of 1) iron syrup + placebo MNPs, or 2) MNPs (containing iron, retinol, zinc, and Vitamin C) + placebo iron syrup, or 3) placebo iron syrup and placebo MNPs. ERPs in response to an auditory roving oddball paradigm were measured in a random subset of 441 children at 3 months post-intervention (11 months of age) and 595 children after a further 9 months follow-up (20 months of age). ERP measures indexing aspects of habituation included the [deviant minus standard] difference waveform amplitude, N2 waveform amplitude, and the difference in deviant-evoked ERP amplitudes between the first and second half of the paradigm. Intention-to-treat analyses on ERP outcomes using linear models were used at 11 and 20 months of age separately. ResultsBaseline characteristics were balanced between treatment groups. Overall prevalence of anemia was 43.7% and iron deficiency was 28.4%. Intention-to-treat analyses indicated no significant treatment effects of iron or MNPs on the difference waveform amplitude at 11 months of age [mean difference (MD, 95% CI) iron vs placebo 0.24 (–1.03, 1.51); MNP vs placebo 0.59 (–0.70, 1.88)] and 20 months of age [(MD, 95% CI) iron vs placebo 0.50 (–0.62, 1.63); MNP vs placebo 0.24 (–0.89, 1.38)]. There were no differences by treatment arm for the other ERP measures. ConclusionsResults from a rigorous prospectively powered sub-study of an RCT in an iron deficient population indicated no significant effects of supplementation with iron or MNPs on neural indices of habituation. Funding SourcesNHMRC and The University of Melbourne.

Harnessing Participatory Formative Research to Inform Women’s Preferences on Multiple Micronutrient Supplement (MMS) Design Considerations Across Four Country Contexts

ObjectivesTo determine universally acceptable MMS box design inputs including preferred color scheme, logo, and slogan options to include in demonstration projects across four countries. MethodsDesign: This multi-phased, formative study was conducted between Oct. 2020 - Feb. 2021 in Burkina Faso, Bangladesh, Tanzania, and Madagascar. It was designed using a social marketing framework and employed Rapid Assessment Procedures (RAP). Data collection methods and sampling: Qualitative methods were used to inform MMS product design and promotional strategies, including 40 participatory workshops and 32 focus group discussions with pregnant women across four countries. In Burkina Faso, a survey was administered to pregnant women (n = 30) for further triangulation. During data collection, several mock MMS box designs, with design options based on local contexts, were used as stimulus prompts for discussion and voting on preferred MMS design color schemes, logos, and slogans. Analysis: Data across methods were synthesized to identify the most preferred MMS characteristics. ResultsColor scheme: Overall, a white/pink MMS box color scheme was the most preferred, universal packaging color across countries. Participants explained that white was “clean”, and in Burkina Faso, it reminded participants of a local paracetamol package “which has no side effects.” The pink was described as “soft and attractive.” In Madagascar, there was a stronger preference for an orange/green color scheme, with pink as a second choice. Box logo: Across countries, participants suggested an image of a pregnant woman on the box design to ensure it is recognizable for its intended purpose. In Burkina Faso, participants voted for a ‘healthy pregnant woman smiling, holding the supplement’ and in Madagascar, participants preferred a ‘healthy, pregnant woman taking the supplement.’ Promotional slogans: While there was variation in specific slogan recommendations to promote MMS by country, shared themes related to good health, strength, happiness, and God. The MMS box design was thus tailored to reflect a combination of preferences. ConclusionsEngaging pregnant women who will be end-users of MMS through participatory methods in four countries aided to inform programming that may improve supplement acceptability and compliance across contexts. Funding SourcesBill and Melinda Gates Foundation.

Maternal periconceptional folic acid supplements use and fetus risk for limb defects.

Associations between the periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and risk for limb defects are inconsistent. To explore the association between periconceptional folic acid supplements use and risk for limb defects, including clubfoot, polydactyly, syndactyly, and limb deficiencies. Data were derived from a cohort based on a pregnancy registry in a district of Beijing, China, from 2013 to 2018. Information on maternal periconceptional FAO and MMFA supplementation was collected via face-to-face interviews at first trimester. Pregnancy outcomes including limb defects were ascertained in livebirths, stillbirths, and elective pregnancy terminations and were recorded into the system. Propensity score methods were used to adjust for potential confounders. A total of 63969 women with a singleton delivery were included. The overall prevalence of limb defects was 47.5 per 10000 (n=63969) singleton deliveries. Decreased prevalence of limb defects was found among FAO/MMFA users compared with women who did not take supplements (nonusers) (46.1 vs. 61.9 per 10000 births, adjusted risk ratio [RR] 0.80, 95% confidence interval [CI] 0.56, 1.12). Compared with nonusers (n=6462, 10.2%), women who took either FAO (n=26567, 42.0%) or MMFA (n=30259, 47.8%) had a lower risk for total clubfoot (RR 0.40, 95% CI 0.20, 0.84), and for isolated clubfoot (RR 0.41, 95% CI 0.17, 0.97). For other limb defects except clubfoot, FAO supplementation did not appear to be associated with reduced risk, while MMFA supplementation group had 30%-50% reduced risks for other limb defects. A lower risk for limb defects or isolated limb defects was found with MMFA supplementation when FAO supplementation was used as a control. Maternal periconceptional supplements with either FAO or MMFA had inverse association with clubfoot in offspring, and MMFA was associated with lower risk for isolated limb defects compared with FAO.

A Mixed-Methods Study of Factors Influencing Access to and Use of Micronutrient Powders in Rwanda.

The World Health Organization recommends point-of-use fortification with multiple micronutrients powder (MNP) for foods consumed by children aged 6-23 months in populations where anemia prevalence among children under 2 years or under 5 years of age is 20% or higher. In Rwanda, anemia affects 37% of children under 5 years. The MNP program was implemented to address anemia, but research on factors affecting the implementation of the MNP program is limited. We conducted a mixed-methods study to examine the factors influencing access to and use of MNP among mothers (N=379) in Rutsiro district, northwest Rwanda. Inductive content analysis was used for qualitative data. Logistic regression analysis was used to determine factors associated with the use of MNP. Qualitative results indicated that the unavailability of MNP supplies and distribution issues were major barriers to accessing MNP. Factors influencing the use of MNP included mothers' perceptions of side effects and health benefits of MNP, as well as inappropriate complementary feeding practices. Mothers of older children (aged 12-23 months) were more likely to use MNP than those of younger children (aged 6-11 months) (adjusted odds ratio [aOR]=3.63, P<.001). Mothers whose children participated in the supplementary food program were nearly 3 times more likely to use MNP than those whose children had never participated in the program (aOR=2.84, P=.001). Increasing household hunger score was significantly associated with lower odds of using MNP (aOR=0.80, P=.038). Mechanisms to monitor MNP supply and program implementation need to be strengthened to ensure mothers have access to the product. MNP program implementers should address gaps in complementary feeding practices and ensure mothers have access to adequate complementary foods.