Public Health Takes an Important Baby Step Toward... Health

George Mason University meta-analysis finds that iron, zinc, Vitamins D, A, B12, B3, magnesium, selenium and iodine combined were far better than iron and zinc alone. Share with future moms!

A meta-analysis funded by the Bill and Melinda Gates Foundation entitled “The Effects of Prenatal Multiple Micronutrient Supplementation and Small-Quantity Lipid-Based Nutrient Supplementation on Small Vulnerable Newborn Types in Low-Income and Middle-Income Countries: A Meta-Analysis of Individual Participant Data” was published in The Lancet Global Health in February 2025. The research, conducted by Dongqing Wang, Enju Liu, Nandita Perumal, Uttara Partap, Ilana R. Cliffer, Janaína Calu Costa, Molin Wang, and Wafaie W. Fawzi, on behalf of the Gestational Weight Gain Pooling Project Consortium, assessed the effects of prenatal multiple micronutrient supplementation (MMS) and small-quantity lipid-based nutrient supplementation (SQ-LNS) on pregnancy outcomes in low- and middle-income countries​.

Background and Rationale

Low birth weight (LBW) is a leading cause of neonatal mortality and adverse child health outcomes, particularly in low- and middle-income countries, where an estimated 19.8 million live births were classified as LBW in 2020. This study sought to determine whether multiple micronutrient supplementation (MMS) and SQ-LNS (small-quantity lipid-based nutrient supplementation) could reduce the risk of giving birth to "small vulnerable newborns"—a category that includes infants born preterm, small for gestational age (SGA), or LBW. These newborns face significant health risks, including higher neonatal mortality, stunted growth, developmental delays, and increased susceptibility to chronic diseases later in life​.

Study Design and Methodology

The study was a meta-analysis of individual participant data from 14 randomized controlled trials (RCTs) on MMS (42,618 participants) and four RCTs on SQ-LNS (6,246 participants) conducted in low- and middle-income countries. The researchers systematically reviewed PubMed, Embase, and Web of Science to identify relevant RCTs published between January 1, 2000, and December 31, 2021. The control groups in most studies received iron and folic acid supplementation, which is the current standard of care in many low- and middle-income countries​.

Newborns were categorized into ten subtypes based on combinations of preterm birth, small for gestational age (SGA), and low birth weight (LBW). A secondary classification grouped newborns into four categories: preterm–SGA, term–SGA, preterm–non-SGA, and term–non-SGA. The study employed log-binomial models to estimate risk ratios (RRs) for each newborn type and used meta-analysis techniques to pool the data across studies​.

Findings: The Impact of Prenatal MMS on Pregnancy Outcomes

The study found that MMS significantly reduced the risk of multiple small vulnerable newborn types, particularly those associated with the highest neonatal mortality risk:

• Preterm–SGA–LBW: 27% lower risk (RR 0.73, 95% CI 0.64–0.84, p=0.0003).

• Preterm–AGA–LBW: 18% lower risk (RR 0.82, 95% CI 0.74–0.91, p=0.0010).

• Preterm–AGA–non-LBW: 11% lower risk (RR 0.89, 95% CI 0.80–0.98, p=0.019).

• Term–SGA–LBW: 9% lower risk (RR 0.91, 95% CI 0.85–0.96, p=0.0046).

• Term–SGA–non-LBW: 5% lower risk (RR 0.95, 95% CI 0.90–1.00, p=0.050)​.

In the secondary four-group classification:

• Preterm–SGA births were reduced by 29% (RR 0.71, 95% CI 0.62–0.82, p=0.0002).

• Term–SGA births were reduced by 7% (RR 0.93, 95% CI 0.89–0.98, p=0.0066)​.

These findings reinforce the benefits of MMS in reducing the most high-risk pregnancy outcomes, particularly preterm and growth-restricted newborns, which are associated with high neonatal mortality rates.

Findings: The Limited Effect of SQ-LNS

Unlike MMS, SQ-LNS did not significantly impact most categories of small vulnerable newborns. The only observed effect was a 22% reduction in preterm–large for gestational age (LGA)–non-LBW newborns (RR 0.78, 95% CI 0.65–0.94, p=0.023)​. This suggests that SQ-LNS may have some role in improving fetal growth but does not provide the same broad benefits as MMS in preventing LBW and preterm births.

Micronutrients in MMS That Likely Contributed to These Benefits

MMS contained multiple micronutrients known to support maternal health and fetal development:

• Iron and folic acid: Essential for reducing anemia, preventing neural tube defects, and supporting fetal growth.

• Zinc: Plays a crucial role in immune function and cellular development.

• Vitamin A: Important for fetal growth and immune system development.

• Vitamin D: Regulates calcium balance and supports bone formation.

• Vitamin B12 and Niacin (B3): Essential for neurological and metabolic development.

• Magnesium: Helps prevent pre-eclampsia and regulate blood pressure.

• Iodine and Selenium: Critical for thyroid function and fetal brain development​.

Implications for Prenatal Care and Public Health Policy

The study provides strong evidence that prenatal MMS should replace iron and folic acid as the standard for antenatal care, especially in low- and middle-income countries where malnutrition contributes to poor birth outcomes. MMS was most effective in reducing the risk of small vulnerable newborn types that have the highest neonatal mortality, underscoring the need for policy changes to improve prenatal supplementation programs​.

Conclusion

This large-scale meta-analysis confirms that prenatal MMS significantly reduces the risk of preterm, small for gestational age, and low birth weight newborns—particularly among those most vulnerable to neonatal mortality. By contrast, SQ-LNS showed only limited benefits. These findings support the transition from iron and folic acid supplementation alone to comprehensive MMS regimens in prenatal care. Expanding access to MMS in low-resource settings could have a substantial impact on reducing newborn mortality and improving early-life health outcomes​.

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Full Citation

Wang, D., Liu, E., Perumal, N., Partap, U., Cliffer, I. R., Costa, J. C., Wang, M., & Fawzi, W. W. (2025). The effects of prenatal multiple micronutrient supplementation and small-quantity lipid-based nutrient supplementation on small vulnerable newborn types in low-income and middle-income countries: A meta-analysis of individual participant data. The Lancet Global Health, 13, e298–308. DOI: 10.1016/S2214-109X(24)00449-2