# The effect of prenatal balanced energy and protein supplementation on small vulnerable newborn types in low- and middle-income countries: A systematic review and meta-analysis of individual participant data

## TL;DR

Prenatal balanced energy and protein supplements reduce risks of small vulnerable newborns in low- and middle-income countries.

## Contribution

First systematic review and meta-analysis of individual data on prenatal BEP supplements and small vulnerable newborn types.

## Key findings

- Prenatal BEP reduced preterm-SGA-LBW risk by 30% and term-SGA-LBW risk by 20%.
- BEP showed stronger effects in multiparous women and those without anemia.
- Supplementation was most effective when started before 20 weeks of gestation.

## Abstract

Small vulnerable newborn (SVN) types, defined by combinations of being born too soon or too small, have distinct determinants, health consequences, and prevention strategies. The effects of prenatal balanced energy and protein (BEP) supplementation on SVN types remain unknown.

We conducted a systematic review and meta-analysis of individual participant data from eight randomized controlled trials of prenatal BEP supplements (N = 10,252, with 5,164 in the BEP arm and 5,088 in the control arm) in low- and middle-income countries were used. The control arms varied across studies and included context-specific standards of care, iron and folic acid supplements, or multiple micronutrient supplements. Newborns were classified into 10 groups through the combinations of preterm birth, small for gestational age (SGA) birth, and low birthweight (LBW), such as term-appropriate-for-gestational-age (AGA)-nonLBW, preterm-SGA-LBW, preterm-large-for-gestational-age-LBW, term-SGA-LBW, preterm-AGA-nonLBW, and other permutations. Newborns were also analyzed using a four-group categorization that included term-nonSGA, preterm-nonSGA, term-SGA, and preterm-SGA. Log-binomial models were used to estimate study-specific risk ratios (RRs), which were pooled using meta-analyses. Subgroup analyses were conducted by maternal age, parity, gestational age at enrollment, early pregnancy body mass index, and maternal anemia status. In the 10-group categorization of SVNs, on average, prenatal BEP supplementation led to a 30% lower risk of preterm-SGA-LBW (RR: 0.70; 95% CI [0.53, 0.91]; P = 0.009), a 25% lower risk of preterm-AGA-LBW (RR: 0.75; 95% CI [0.60, 0.93]; P = 0.009), and a 20% lower risk of term-SGA-LBW (RR: 0.80; 95% CI [0.72, 0.90]; P < 0.001). In the four-group categorization, prenatal BEP supplementation led to a 31% lower risk of preterm-SGA (RR: 0.69; 95% CI [0.52, 0.91]; P = 0.008) and a 12% lower risk of term-SGA (RR: 0.88; 95% CI [0.81, 0.96]; P = 0.005). The protective effect of prenatal BEP supplementation on preterm-SGA was stronger among multiparous women and women without anemia. The protective effects on all three SVN types under the four-group categorization were stronger among women enrolled before 20 weeks of gestation. The main limitations of the study included the absence of some BEP trials and the small event numbers for some SVN types.

Prenatal BEP supplementation reduces the risk of SVNs to varying extents. Further research is needed to determine the optimal targeting approach for providing BEP supplements to vulnerable pregnant women who are most likely to benefit from the supplementation.

Small vulnerable newborn (SVN) types, defined by combinations of being born too soon or too small, have distinct determinants, health consequences, and prevention strategies.

The effects of prenatal balanced energy and protein (BEP) supplementation on SVN types are unclear.

Individual participant data from eight randomized controlled trials of prenatal BEP supplements in low- and middle-income countries were used, including data from 10,252 pregnant women.

The consumption of BEP supplements during pregnancy reduced the risks of numerous SVN types, particularly the types that involve small-for-gestational-age births and the types previously shown to confer a greater risk of neonatal mortality.

This work underscores the public health benefits of BEP in antenatal care in low- and middle-income countries.

Further work is warranted to determine the effectiveness, cost-effectiveness, and implementation strategies of prenatal BEP supplementation.

The main limitations included the absence of some BEP trials and the small event numbers for some SVN types.

In a systematic review and individual participant meta-analysis, Dongqing Wang and colleagues investigate the effect of prenatal nutritional supplements on small vulnerable newborns in low- and middle-income countries.Image: https://unsplash.com/photos/person-in-teal-long-sleeve-shirt-lying-on-bed-Jf5WbV0uVpgCredit: Solen Feyissa via unsplash