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Summary Background Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries. Methods For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2 015 019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations. Findings Pooled overall RRs for preterm were 6·82 (95% CI 3·56–13·07) for neonatal mortality and 2·50 (1·48–4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34–2·50) for neonatal mortality and 1·90 (1·32–2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11–26·12). Interpretation Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4—the reduction of child mortality. Funding Bill & Melinda Gates Foundation.

SummaryBackgroundNational estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010.MethodsSmall for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses.FindingsIn 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of term-SGA babies ranged from 5·3% of livebirths in east Asia to 41·5% in south Asia, and the prevalence of preterm-SGA infants ranged from 1·2% in north Africa to 3·0% in southeast Asia. Of 18 million low-birthweight babies, 59% were term-SGA and 41% were preterm. Two-thirds of small-for-gestational-age infants were born in Asia (17·4 million in south Asia). Preterm-SGA babies totalled 2·8 million births in low-income and middle-income countries. Most small-for-gestational-age infants were born in India, Pakistan, Nigeria, and Bangladesh.InterpretationThe burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases.FundingBill & Melinda Gates Foundation by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group (CHERG).

Micronutrients, vitamins and minerals accessible from the diet, are essential for biologic activity. Micronutrient status varies widely throughout pregnancy and across populations. Women in low-income countries often enter pregnancy malnourished, and the demands of gestation can exacerbate micronutrient deficiencies with health consequences to the fetus. Examples of efficacious single micronutrient interventions include folic acid to prevent neural tube defects, iodine to prevent cretinism, zinc to reduce of preterm birth, and iron to reduce the risk of low birth weight. Folic acid and vitamin D might also increase birth weight. While extensive mechanism and association research links antenatal multiple micronutrients to plausible materno-fetal health advantages, hypothesized benefits have often been absent, minimal or unexpected in trials. These findings suggest a role for population context in determining health responses and extensive gaps in knowledge. Multiple micronutrient supplements reduce risks of being born low birth weight, small for gestational age or stillborn in undernourished settings, and justify micronutrient interventions with antenatal care. Measurable health effects of gestational micronutrient exposure may persist into childhood but few data exists on potential long-term benefits. In this Review, we discuss micronutrient intake recommendations, risks and consequences of deficiencies, and the effects of interventions with a particular emphasis on offspring.

Objective To assess the impact on birth size and risk of low birth weight of alternative combinations of micronutrients given to pregnant women. Design Double blind cluster randomised controlled trial.

Background Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30–40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain. Methods Using extant longitudinal birth cohorts (n = 19) with data on birth-weight, gestational age and child anthropometry (12–60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth. Results We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5–3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively. Conclusions This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.

Objective To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as carotene. Design Double blind, cluster randomised, placebo controlled field trial. Setting Rural southeast central plains of Nepal (Sarlahi district). Subjects 44 646 married women, of whom 20 119 became pregnant 22 189 times. Intervention 270 wards randomised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo, vitamin A (7000 g retinol equivalents) or carotene (42 mg, or 7000 g retinol equivalents) for over 3 1 ⁄2 years. Main outcome measures All cause mortality in women during pregnancy up to 12 weeks post partum (pregnancy related mortality) and mortality during pregnancy to 6 weeks postpartum, excluding deaths apparently related to injury (maternal mortality). Results Mortality related to pregnancy in the placebo, vitamin A, and carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yielding relative risks (95% confidence intervals) of 0.60 (0.37 to 0.97) and 0.51 (0.30 to 0.86). This represented reductions of 40% (P < 0.04) and 49% (P < 0.01) among those who received vitamin A and carotene. Combined, vitamin A or carotene lowered mortality by 44% (0.56 (0.37 to 0.84), P < 0.005) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births, or by 40% (P < 0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups. Conclusion Supplementation of women with either vitamin A or carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia.