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The effect of universal maternal antenatal iron supplementation on neurodevelopment in offspring: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Although antenatal iron supplementation is beneficial to mothers, its impact on the neurodevelopment of offspring is controversial. A systematic review and meta-analysis was undertaken to assess whether routine maternal antenatal iron supplementation confers later neurodevelopmental benefit to offspring. METHODS:Electronic databases were searched using MESH terms or key words and identified papers were reviewed by two independent reviewers. The study quality was assessed using the Cochrane risk of bias assessment tool. The review was registered in the PROSPERO CRD data base. RESULTS:Seven publications were identified, based on four randomised trials published between 2006 and 2016. Three of the trials were in the Asian sub-continent. A range of tools were used to evaluate neurodevelopment. Meta-analysis of outcomes from the three RCTs meeting our inclusion criteria showed minimal effect of antenatal iron supplementation on the neurodevelopment of offspring, which was not statistically significant: weighted mean difference of 0.54 (95% CI: -0.67 to 1.75); test for overall effect Z?=?0.87; p?=?0.38; and heterogeneity 48%. Meta-analysis of outcomes of these RCTs at later stages of development produced similar results. CONCLUSIONS:The benefit of routine antenatal iron supplementation on neurodevelopment in offspring was not statistically significant in this relatively limited set of trials, and some benefit cannot be excluded in areas with a high prevalence of maternal anaemia. A large randomized controlled trial showing significant benefit would be required to modify our conclusions.

SUBMITTER: Jayasinghe C

PROVIDER: S-EPMC5936025 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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The effect of universal maternal antenatal iron supplementation on neurodevelopment in offspring: a systematic review and meta-analysis.

Jayasinghe C C Polson R R van Woerden H C HC Wilson P P

BMC pediatrics 20180504 1

<h4>Background</h4>Although antenatal iron supplementation is beneficial to mothers, its impact on the neurodevelopment of offspring is controversial. A systematic review and meta-analysis was undertaken to assess whether routine maternal antenatal iron supplementation confers later neurodevelopmental benefit to offspring.<h4>Methods</h4>Electronic databases were searched using MESH terms or key words and identified papers were reviewed by two independent reviewers. The study quality was assesse ...[more]

PMID: 29728086

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Project description:BackgroundAnemia affects over 500 million women, and in pregnancy is associated with impaired maternal and infant outcomes. Intermittent antenatal iron supplementation is an attractive alternative to daily dosing; however, the impact of this strategy on infant outcomes remains unclear. We compared the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Viet Nam.Methods and findingsThis cluster randomised trial was conducted in Ha Nam province, Viet Nam. 1,258 pregnant women (< 16 wk gestation) in 104 communes were assigned to daily iron-folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Mean birth weight was 3,148 g (standard deviation 416). There was no difference in the birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference [MD] 28 g; 95% CI -22 to 78), or twice weekly MMN compared to daily IFA (MD -36.8 g; 95% CI -82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (geometric mean ratio 0.62; 95% CI 0.57 to 0.68), but there was no difference in hemoglobin levels. Infants of mothers who received twice weekly IFA had higher cognitive scores at 6 mo of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56).ConclusionsTwice weekly antenatal IFA or MMN did not produce a clinically important difference in birth weight, when compared to daily IFA supplementation. The significant improvement in infant cognitive outcomes at 6 mo of age following twice weekly antenatal IFA requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal IFA in populations with low rates of iron deficiency.Trial registrationAustralia New Zealand Clinical Trials Registry 12610000944033.

Project description:Abstract Objectives Vitamin D may have an adjunctive role in the prevention and treatment of iron deficiency (ID) through its proposed role in the regulation of erythropoiesis and circulating hepcidin concentrations. Observational studies have shown associations between low vitamin D and iron status; however, there are few data from intervention trials. In participants of the Maternal Vitamin D for Infant Growth Trial (MDIG; NCT01924013), among whom the baseline prevalence of vitamin D deficiency was 64%, we examined the effect of prenatal vitamin D supplementation on iron status during pregnancy by testing the effect of vitamin D supplementation on serum ferritin concentrations. Methods In this double-blind, dose-response, randomized trial in Dhaka, Bangladesh, women were recruited at 17–24 weeks’ gestation and randomly assigned to receive a prenatal vitamin D3 dose of 4200, 16,800, 28,000 IU/week or placebo. Serum ferritin was quantified using an electro-chemiluminescence immunoassay. Plasma C-reactive protein (CRP) was analysed by enzyme-linked immunoassay. Linear regression was used to test the hypothesized effect of vitamin D supplementation on serum ferritin (n = 1011 of 1300 enrolled). In a sensitivity analysis, we adjusted for concurrent CRP to correct for inflammation (n = 920). Regression correction was used to generate an inflammation-corrected estimate of the prevalence of ID (n = 920). Results Prevalence of ID (serum ferritin <15 µg/L) was high overall (27% corrected for inflammation; 12% uncorrected). Geometric mean (95% confidence interval) serum ferritin concentrations were lower in each of the vitamin D supplementation groups [43.1 (38.1, 48.7), 44.8 (40.4, 49.7) and 45.1 (41.5, 49.1) µg/L in the 4200, 16,800 and 28,000 IU/week groups, respectively] compared to the placebo group [50.3 µg/L (45.0, 56.2)], although none of the pairwise differences between each vitamin D group and placebo were statistically significant at the P < 0.05 threshold. Adjusting for CRP did not change the inferences. Conclusions In a population with concurrently high prevalence rates of iron and vitamin D deficiency, prenatal vitamin D supplementation did not lead to improvements in iron status by late gestation. The possibility of a negative effect of vitamin D supplementation on iron status should be further explored. Funding Sources The Bill and Melinda Gates Foundation.

Project description:Zinc deficiency is widespread, and preventive supplementation may have benefits in young children. Effects for children over 5?years of age, and effects when coadministered with other micronutrients are uncertain. These are obstacles to scale-up. This review seeks to determine if preventive supplementation reduces mortality and morbidity for children aged 6?months to 12?years.Systematic review conducted with the Cochrane Developmental, Psychosocial and Learning Problems Group. Two reviewers independently assessed studies. Meta-analyses were performed for mortality, illness and side effects.We searched multiple databases, including CENTRAL and MEDLINE in January 2013. Authors were contacted for missing information.Randomised trials of preventive zinc supplementation. Hospitalised children and children with chronic diseases were excluded.80 randomised trials with 205?401 participants were included. There was a small but non-significant effect on all-cause mortality (risk ratio (RR) 0.95 (95% CI 0.86 to 1.05)). Supplementation may reduce incidence of all-cause diarrhoea (RR 0.87 (0.85 to 0.89)), but there was evidence of reporting bias. There was no evidence of an effect of incidence or prevalence of respiratory infections or malaria. There was moderate quality evidence of a very small effect on linear growth (standardised mean difference 0.09 (0.06 to 0.13)) and an increase in vomiting (RR 1.29 (1.14 to 1.46)). There was no evidence of an effect on iron status. Comparing zinc with and without iron cosupplementation and direct comparisons of zinc plus iron versus zinc administered alone favoured cointervention for some outcomes and zinc alone for other outcomes. Effects may be larger for children over 1?year of age, but most differences were not significant.Benefits of preventive zinc supplementation may outweigh any potentially adverse effects in areas where risk of zinc deficiency is high. Further research should determine optimal intervention characteristics and delivery strategies.

Project description:BackgroundFibroblast growth factor-23 (FGF23) regulates body phosphate homeostasis primarily by increasing phosphaturia. It also acts as a vitamin D-regulating hormone. Maternal iron deficiency is associated with perturbed expression and/or regulation of FGF23 and hence might be implicated in the pathogenesis of hypophosphatemia-driven rickets in their offspring.ObjectivesWe aimed to determine the effect of antenatal oral iron supplementation on FGF23 concentration and maternal and infant markers of bone-mineral regulation.MethodsWe performed a secondary analysis of a trial in which 470 rural Kenyan women with singleton pregnancies and hemoglobin concentrations ≥ 90 g/L were randomly allocated to daily, supervised supplementation with 60 mg elemental iron as ferrous fumarate or placebo from 13-23 weeks of gestation until 1 mo postpartum. As previously reported, iron supplementation improved iron status in mothers and neonates. For the present study, we reanalyzed all available plasma samples collected in mothers and neonates at birth, with primary outcomes being concentrations of FGF23, measured by 2 assays: 1 that detects intact hormone and C-terminal cleavage products (total-FGF23) and another that detects the intact hormone only (intact-FGF23).ResultsAnalysis was performed on 433 women (n = 216, iron group; n = 217, placebo group) and 414 neonates (n = 207, iron group; n = 207, placebo group). Antenatal iron supplementation reduced geometric mean total-FGF23 concentrations in mothers and neonates by 62.6% (95% CI: 53.0%, 70.3%) and 15.2% (95% CI: -0.3%, 28.4%, P = 0.06), respectively. In addition, it increased geometric mean neonatal intact-FGF23 concentrations by 21.6% (95% CI: 1.2%, 46.1%), increased geometric mean maternal hepcidin concentrations by 136.4% (95% CI: 86.1%, 200.3%), and decreased mean maternal 25-hydroxyvitamin D concentrations by 6.1 nmol/L (95% CI: -11.0, -1.2 nmol/L).ConclusionsAnalysis of this randomized trial confirms that iron supplementation can reverse elevated FGF23 production caused by iron deficiency in iron-deficient mothers and their neonates. Further investigations are warranted to assess to what extent iron supplementation can prevent FGF23-mediated hypophosphatemic rickets or osteomalacia.

Project description:BackgroundCoverage of iron-folic acid (IFA) supplementation is a key indicator for tracking programmatic progress within and across countries. However, the validity of maternal report of this information during household surveys has yet to be determined.ObjectivesThis study aimed to examine the validity of maternal recall of receipt of IFA supplementation during antenatal care (ANC) and factors associated with accuracy of maternal recall.MethodsA longitudinal cohort design was employed. The direct observation of the IFA received during all ANC visits at the 5 study health posts served as the "gold standard" to the maternal report of IFA received during the postpartum interview. Individual-level validity was assessed by calculating indicator sensitivity, specificity, and AUC. The inflation factor (IF) measured population-level bias. A multivariable log-binomial model was used to assess factors associated with accurate recall.ResultsThe majority (95.8%) of women were observed receiving IFA during pregnancy. Women overreported the number of IFA tablets received compared with what was observed during ANC visits (mean difference: 45 tablets). Maternal report of any IFA receipt was moderate (AUC = 0.60; 95% CI: 0.50, 0.71), and population bias was low (IF = 1.01). However, the individual-level validity was poor across the 7 IFA tablet count categories; the AUC for categories ranged from misleading to moderate. Driven by the trend of maternal overreport, the IF indicated that maternal report drastically underestimated the coverage of lower tablet categories and overestimated the coverage of higher tablet counts. Accuracy of maternal report was not associated with months since last ANC observation nor any maternal characteristics.ConclusionsMaternal report of the amount of IFA supplementation received during pregnancy produced extremely biased population coverage and performed poorly to moderately for individual-level validity. It is imperative to improve this indicator because it is used in global frameworks and national program planning.

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The effect of universal maternal antenatal iron supplementation on neurodevelopment in offspring: a systematic review and meta-analysis.

Publications

The effect of universal maternal antenatal iron supplementation on neurodevelopment in offspring: a systematic review and meta-analysis.

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