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
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.
Source: PLoS Medicine
Authors: Dongqing Wang, Uttara Partap, Enju Liu, Janaína Calu Costa, Ilana R. Cliffer, Molin Wang, Sudeer Kumar Nookala, Vishak Subramoney, Brittany Briggs, Imran Ahmed, Alemayehu Argaw, Shabina Ariff, Nita Bhandari, Ranadip Chowdhury, Trenton Dailey-Chwalibóg, Giles T. Hanley-Cook, Lieven Huybregts, Fyezah Jehan, Nancy F. Krebs, Carl Lachat, Dharma S. Manandhar, Elizabeth M. McClure, Sophie E. Moore, Ameer Muhammad, Muhammad Imran Nisar, Andrew M. Prentice, Dominique Roberfroid, Naomi M. Saville, Yasir Shafiq, Bhim P. Shrestha, Bakary Sonko, Sajid Soofi, Sunita Taneja, Laéticia Céline Toe, Wafaie W. Fawzi
Institutions: George Mason University, Harvard University, Boston Children's Hospital, Brigham and Women's Hospital, Gates Foundation, Aga Khan University, Ghent University, Society for Applied Studies, AFRICSanté, Food and Agriculture Organization of the United Nations, International Food Policy Research Institute, University of Colorado Anschutz, Mother and Infant Research Activities, RTI International, King's College London, MRC Unit the Gambia, Vital Pakistan Trust, University of Namur, Belgian Health Care Knowledge Centre (KCE), University College London, Institut de Recherche en Sciences de la Santé
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,460
Awards: Harvard T.H. Chan School of Public Health - to conduct secondary analyses of data to understand patterns of gestational weight gain, its predictors and risk of adverse pregnancy outcomes in t..., Harvard T.H. Chan School of Public Health - This grant will be used to conduct secondary analyses of data to better understand patterns of gestational weight gain in LMIC contexts and to deve..., Leveraging the Global Network to implement health interventions to improve maternal and child outcomes in a rapidly changing environment
OpenAlex ID: W7129725203