Elsevier

The Lancet

Volume 382, Issue 9890, 3–9 August 2013, Pages 417-425
The Lancet

Articles
Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis

https://doi.org/10.1016/S0140-6736(13)60993-9Get rights and content

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.

Introduction

An estimated 20 million infants every year are born with low birthweight (LBW; <2500 g),1 and these infants have an increased risk mortality in the first year of life. The primary causes of LBW are preterm birth, intrauterine growth restriction (IUGR), or a combination of the two. Of 135 million children born in low-income and middle-income countries (LMICs) in 2010, an estimated 29·7 million were born both term and small-for-gestational-age (SGA), 10·9 million were born preterm and appropriate-for-gestational-age, and 2·8 million were born preterm and SGA.2 Risk factors and interventions to reduce the number of babies born SGA might differ from those to reduce the number of babies born preterm. The survival and growth patterns of preterm or growth-restricted newborn babies are not well described in LMICs and the contribution to mortality of non-LBW babies (≥2500 g) who are preterm or those with IUGR in such settings is unknown.

Few studies in LMICs have investigated differences in mortality by extent of prematurity, IUGR, or the two in combination,3, 4 or mortality risk in infants who are SGA stratified by gestational age.5, 6, 7, 8, 9, 10 Examination of the mortality risk by degree of prematurity and SGA as a proxy for IUGR might be crucial in understanding the attributable disease burden, especially because regions such as south Asia have a reported SGA prevalence of about 40%.11, 12 Such mortality risk estimates and attributable burden could enable the specific targeting of these disorders with appropriate interventions to more effectively save lives.

The Child Health Epidemiology Reference Group (CHERG) previously examined the risk of infant mortality associated with term-LBW as a proxy for IUGR.13 However, term-LBW excludes growth-restricted infants weighing more than 2500 g and high risk infants born both preterm and SGA, and such associations between mortality and SGA-non-LBW or SGA-preterm have not been well described in LMICs. With more population-based studies in LMICs now collecting data for gestational age in addition to birthweight, the CHERG identified an opportunity to assess the mortality risk of SGA and preterm on early neonatal, late neonatal, neonatal, post-neonatal, and infant mortality.

Section snippets

Dataset identification

We searched Medline, WHO regional databases (African Index Medicus, LILAS, EMRO), bibliographies of sentinel articles and reviews, and grey literature to identify potential datasets from low-income and middle-income countries that recorded data for gestational age and birthweight, and systematically recorded vital status from delivery through at least 28 days of life. The most recent search was done on Feb 22, 2010. We applied no no date or language restrictions. Search terms included “preterm

Results

We included 20 datasets with 2 015 019 livebirths from sub-Saharan Africa, Latin America, and south and southeast Asia, with gestational age available for 2 008 675 babies and both gestational age and birthweight available for 1 996 763 babies (table and appendix).4, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 Study dates ranged from 1982 through to 2010. The Chilean national birth registry35 provided much of these data. The prevalence of preterm birth

Discussion

We identified a large percentage of infants who were SGA but not LBW or preterm (21% in Asia, 16% in Africa, and 4% in Latin America), although their mortality rates were lower than preterm infants or SGA-LBW infants. Although most LBW was in term and SGA babies in Asia and Africa, the majority of babies with LBW in Latin America were preterm. Preterm mortality risk associations were generally higher at all gestational age categories (late, moderate, and early preterm) than SGA (3% to <10% or

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