Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries

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Abstract

Micronutrient deficiencies are common among women in low-income and middle-income countries. Data from randomised trials suggest that maternal multiple micronutrient supplementation decreases the risk of low birthweight and potentially improves other infant health outcomes. However, heterogeneity across studies suggests influence from effect modifiers. We aimed to identify individual-level modifiers of the effect of multiple micronutrient supplements on stillbirth, birth outcomes, and infant mortality in low-income and middle-income countries.

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International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project.

Jose Villar, Leila Cheikh Ismail, Cesar Victora … (2014)

In 2006, WHO published international growth standards for children younger than 5 years, which are now accepted worldwide. In the INTERGROWTH-21(st) Project, our aim was to complement them by developing international standards for fetuses, newborn infants, and the postnatal growth period of preterm infants. INTERGROWTH-21(st) is a population-based project that assessed fetal growth and newborn size in eight geographically defined urban populations. These groups were selected because most of the health and nutrition needs of mothers were met, adequate antenatal care was provided, and there were no major environmental constraints on growth. As part of the Newborn Cross-Sectional Study (NCSS), a component of INTERGROWTH-21(st) Project, we measured weight, length, and head circumference in all newborn infants, in addition to collecting data prospectively for pregnancy and the perinatal period. To construct the newborn standards, we selected all pregnancies in women meeting (in addition to the underlying population characteristics) strict individual eligibility criteria for a population at low risk of impaired fetal growth (labelled the NCSS prescriptive subpopulation). Women had a reliable ultrasound estimate of gestational age using crown-rump length before 14 weeks of gestation or biparietal diameter if antenatal care started between 14 weeks and 24 weeks or less of gestation. Newborn anthropometric measures were obtained within 12 h of birth by identically trained anthropometric teams using the same equipment at all sites. Fractional polynomials assuming a skewed t distribution were used to estimate the fitted centiles. We identified 20,486 (35%) eligible women from the 59,137 pregnant women enrolled in NCSS between May 14, 2009, and Aug 2, 2013. We calculated sex-specific observed and smoothed centiles for weight, length, and head circumference for gestational age at birth. The observed and smoothed centiles were almost identical. We present the 3rd, 10th, 50th, 90th, and 97th centile curves according to gestational age and sex. We have developed, for routine clinical practice, international anthropometric standards to assess newborn size that are intended to complement the WHO Child Growth Standards and allow comparisons across multiethnic populations. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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A nearly continuous measure of birth weight for gestational age using a United States national reference

Emily Oken, Ken Kleinman, Janet W. Rich-Edwards … (2003)

Background Fully understanding the determinants and sequelae of fetal growth requires a continuous measure of birth weight adjusted for gestational age. Published United States reference data, however, provide estimates only of the median and lowest and highest 5th and 10th percentiles for birth weight at each gestational age. The purpose of our analysis was to create more continuous reference measures of birth weight for gestational age for use in epidemiologic analyses. Methods We used data from the most recent nationwide United States Natality datasets to generate multiple reference percentiles of birth weight at each completed week of gestation from 22 through 44 weeks. Gestational age was determined from last menstrual period. We analyzed data from 6,690,717 singleton infants with recorded birth weight and sex born to United States resident mothers in 1999 and 2000. Results Birth weight rose with greater gestational age, with increasing slopes during the third trimester and a leveling off beyond 40 weeks. Boys had higher birth weights than girls, later born children higher weights than firstborns, and infants born to non-Hispanic white mothers higher birth weights than those born to non-Hispanic black mothers. These results correspond well with previously published estimates reporting limited percentiles. Conclusions Our method provides comprehensive reference values of birth weight at 22 through 44 completed weeks of gestation, derived from broadly based nationwide data. Other approaches require assumptions of normality or of a functional relationship between gestational age and birth weight, which may not be appropriate. These data should prove useful for researchers investigating the predictors and outcomes of altered fetal growth.

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Micronutrient deficiencies in pregnancy worldwide: health effects and prevention.

Alison Gernand, Kerry Schulze, Christine Stewart … (2016)

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 for the fetus. Examples of efficacious single micronutrient interventions include folic acid to prevent neural tube defects, iodine to prevent cretinism, zinc to reduce risk 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 mechanistic and association research links multiple antenatal micronutrients with 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 filling extensive gaps in knowledge. Multiple micronutrient supplements reduce the risks of being born with 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 might 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.