Objectives To summarise evidence on the associations of maternal anaemia and prenatal iron use with maternal haematological and adverse pregnancy outcomes; and to evaluate potential exposure-response relations of dose of iron, duration of use, and haemoglobin concentration in prenatal period with pregnancy outcomes. Design Systematic review and meta-analysisData sources Searches of PubMed and Embase for studies published up to May 2012 and references of review articles.Study selection criteria Randomised trials of prenatal iron use and prospective cohort studies of prenatal anaemia; cross sectional and case-control studies were excluded.Results 48 randomised trials (17 793 women) and 44 cohort studies (1 851 682 women) were included. Iron use increased maternal mean haemoglobin concentration by 4.59 (95% confidence interval 3.72 to 5.46) g/L compared with controls and significantly reduced the risk of anaemia (relative risk 0.50, 0.42 to 0.59), iron deficiency (0.59, 0.46 to 0.79), iron deficiency anaemia (0.40, 0.26 to 0.60), and low birth weight (0.81, 0.71 to 0.93). The effect of iron on preterm birth was not significant (relative risk 0.84, 0.68 to 1.03). Analysis of cohort studies showed a significantly higher risk of low birth weight (adjusted odds ratio 1.29, 1.09 to 1.53) and preterm birth (1.21, 1.13 to 1.30) with anaemia in the first or second trimester. Exposure-response analysis indicated that for every 10 mg increase in iron dose/day, up to 66 mg/day, the relative risk of maternal anaemia was 0.88 (0.84 to 0.92) (P for linear trend<0.001).Birth weight increased by 15.1 (6.0 to 24.2) g (P for linear trend=0.005) and risk of low birth weight decreased by 3% (relative risk 0.97, 0.95 to 0.98) for every 10 mg increase in dose/day (P for linear trend<0.001). Duration of use was not significantly associated with the outcomes after adjustment for dose. Furthermore, for each 1 g/L increase in mean haemoglobin, birth weight increased by 14.0 (6.8 to 21.8) g (P for linear trend=0.002); however, mean haemoglobin was not associated with the risk of low birth weight and preterm birth. No evidence of a significant effect on duration of gestation, small for gestational age births, and birth length was noted.Conclusions Daily prenatal use of iron substantially improved birth weight in a linear dose-response fashion, probably leading to a reduction in risk of low birth weight. An improvement in prenatal mean haemoglobin concentration linearly increased birth weight.

BackgroundChild undernutrition affects millions of children globally. We investigated associations between suboptimal growth and mortality by pooling large studies.MethodsPooled analysis involving children 1 week to 59 months old in 10 prospective studies in Africa, Asia and South America. Utilizing most recent measurements, we calculated weight-for-age, height/length-for-age and weight-for-height/length Z scores, applying 2006 WHO Standards and the 1977 NCHS/WHO Reference. We estimated all-cause and cause-specific mortality hazard ratios (HR) using proportional hazards models comparing children with mild (−2≤Z<−1), moderate (−3≤Z<−2), or severe (Z<−3) anthropometric deficits with the reference category (Z≥−1).Results53 809 children were eligible for this re-analysis and contributed a total of 55 359 person-years, during which 1315 deaths were observed. All degrees of underweight, stunting and wasting were associated with significantly higher mortality. The strength of association increased monotonically as Z scores decreased. Pooled mortality HR was 1.52 (95% Confidence Interval 1.28, 1.81) for mild underweight; 2.63 (2.20, 3.14) for moderate underweight; and 9.40 (8.02, 11.03) for severe underweight. Wasting was a stronger determinant of mortality than stunting or underweight. Mortality HR for severe wasting was 11.63 (9.84, 13.76) compared with 5.48 (4.62, 6.50) for severe stunting. Using older NCHS standards resulted in larger HRs compared with WHO standards. In cause-specific analyses, all degrees of anthropometric deficits increased the hazards of dying from respiratory tract infections and diarrheal diseases. The study had insufficient power to precisely estimate effects of undernutrition on malaria mortality.ConclusionsAll degrees of anthropometric deficits are associated with increased risk of under-five mortality using the 2006 WHO Standards. Even mild deficits substantially increase mortality, especially from infectious diseases.

Children with multiple deficits are at a heightened risk of mortality and may benefit most from nutrition and other child survival interventions.

Iron deficiency is commonly assumed to cause half of all cases of anemias, with hereditary blood disorders and infections such as hookworm and malaria being the other major causes. In countries ranked as low, medium, and high by the Human Development Index, we conducted a systematic review of nationally representative surveys that reported the prevalence of iron deficiency, iron deficiency anemia, and anemia among pre-school children and non-pregnant women of reproductive age. Using random effects meta-analyses techniques, data from 23 countries for pre-school children and non-pregnant women of reproductive age was pooled, and the proportion of anemia attributable to iron deficiency was estimated by region, inflammation exposure, anemia prevalence, and urban/rural setting. For pre-school children and non-pregnant women of reproductive age, the proportion of anemia associated with iron deficiency was 25.0% (95% CI: 18.0, 32.0) and 37.0% (95% CI: 28.0, 46.0), respectively. The proportion of anemia associated with iron deficiency was lower in countries where anemia prevalence was >40%, especially in rural populations (14% for pre-school children; 16% for non-pregnant women of reproductive age), and in countries with very high inflammation exposure (20% for pre-school children; 25% for non-pregnant women of reproductive age). Despite large heterogeneity, our analyses suggest that the proportion of anemia associated with iron deficiency is lower than the previously assumed 50% in countries with low, medium, or high Human Development Index ranking. Anemia-reduction strategies and programs should be based on an analysis of country-specific data, as iron deficiency may not always be the key determinant of anemia.

Adequate supply of micronutrients during the first 1000 days is essential for normal development and healthy life. We aimed to investigate if interventions administering dietary doses up to the recommended nutrient intake (RNI) of iron and zinc within the window from conception to age 2 years have the potential to influence nutritional status and development of children. To address this objective, a systematic review and meta-analysis of randomized and quasi-randomized fortification, biofortification, and supplementation trials in women (pregnant and lactating) and children (6–23 months) delivering iron or zinc in doses up to the recommended nutrient intake (RNI) levels was conducted. Supplying iron or zinc during pregnancy had no effects on birth outcomes. There were limited or no data on the effects of iron/zinc during pregnancy and lactation on child iron/zinc status, growth, morbidity, and psychomotor and mental development. Delivering up to 15 mg iron/day during infancy increased mean hemoglobin by 4 g/L (p < 0.001) and mean serum ferritin concentration by 17.6 µg/L (p < 0.001) and reduced the risk for anemia by 41% (p < 0.001), iron deficiency by 78% (ID; p < 0.001) and iron deficiency anemia by 80% (IDA; p < 0.001), but had no effect on growth or psychomotor development. Providing up to 10 mg of additional zinc during infancy increased plasma zinc concentration by 2.03 µmol/L (p < 0.001) and reduced the risk of zinc deficiency by 47% (p < 0.001). Further, we observed positive effects on child weight for age z-score (WAZ) (p < 0.05), weight for height z-score (WHZ) (p < 0.05), but not on height for age z-score (HAZ) or the risk for stunting, wasting, and underweight. There are no studies covering the full 1000 days window and the effects of iron and zinc delivered during pregnancy and lactation on child outcomes are ambiguous, but low dose daily iron and zinc use during 6–23 months of age has a positive effect on child iron and zinc status.