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Meta-Analysis
. 2025 Jul;16(7):100455.
doi: 10.1016/j.advnut.2025.100455. Epub 2025 May 30.

Contribution of Maternal Adherence to the Effect of Multiple Micronutrient Supplementation During Pregnancy: A Systematic Review and Individual Participant Data Meta-analysis

Emily R Smith  1 , Filomena Gomes  2 , Seth Adu-Afarwuah  3 , Victor M Aguayo  4 , Shams El Arifeen  5 , Zulfiqar A Bhutta  6 , Ellen C Caniglia  7 , Parul Christian  8 , Delanjathan Devakumar  9 , Kathryn G Dewey  10 , Wafaie W Fawzi  11 , Henrik Friis  12 , Exnevia Gomo  13 , Ousmane Guindo  14 , Lotta Hallamaa  15 , Sheila Isanaka  16 , Pernille Kæstel  12 , Carl Lachat  17 , Ken Maleta  18 , Sophie E Moore  19 , Erin M Oakley  20 , David Osrin  9 , Anisur Rahman  5 , Ziaul Rana  21 , Arjumand Rizvi  22 , Dominique Roberfroid  23 , Saijuddin Shaikh  24 , Bakary Sonko  25 , Sajid Bashir Soofi  26 , Inan Subarkah  27 , Rahardjo Sunawang  27 , Dongqing Wang  28 , Keith P West Jr  8 , Lee Shu Fune Wu  8 , Noel Zagre  29 , Megan W Bourassa  30 , Christopher R Sudfeld  11
Affiliations
Meta-Analysis

Contribution of Maternal Adherence to the Effect of Multiple Micronutrient Supplementation During Pregnancy: A Systematic Review and Individual Participant Data Meta-analysis

Emily R Smith et al. Adv Nutr. 2025 Jul.

Abstract

Multiple micronutrient supplements (MMS) in pregnancy reduces risk of infant low birthweight (LBW) and improves other maternal and infant outcomes compared with iron and folic acid (IFA) supplements alone. However, the impact of timing of initiation and adherence on the MMS effectiveness in real-world programs remains unclear. To address this, we conducted a 2-stage individual participant data meta-analysis that included 15 randomized trials (61,204 pregnant women) and assessed whether the relative effect of MMS differed by the following: adherence alone; adherence in combination with gestational age at initiation; and the total number of tablets taken. We also evaluated the observational association of these factors with outcomes among participants who received MMS. Compared with IFA supplements, the relative effect of MMS on the primary outcome of continuous birthweight was greater with higher adherence (P-interaction < 0.05). Among women who took ≥90% of supplements, MMS increased birthweight by 56 g (95% CI: 45, 67 g), whereas among women who took <60% of supplements, there was no difference in birthweight between MMS and IFA supplements [mean difference (MD): 9 g; 95% CI: -17, 35 g). Higher adherence was also associated with greater effect of MMS on LBW and birthweight-for-gestational age centile and women who took more supplements experienced a greater relative impact of MMS on birthweight-for-gestational age centile and small-for-gestational age births (SGA) as compared with IFA supplements. Observational analyses among participants who received MMS showed that ≥90% adherence was associated with increased birthweight (MD: 44 g; 95% CI: 31, 56 g) and lower risk of LBW [relative risk (RR): 0.93 g; 95% CI: 0.88, 0.98 g] and small-for-gestational age (RR: 0.95; 95% CI: 0.93, 0.98), whereas <75% adherence was associated with greater risk of stillbirth (RR: 1.43; 95% CI: 1.12, 1.83) and maternal anemia (RR: 1.26; 95% CI: 1.11, 1.43) than 75%-90% adherence. Programs should invest in strategies that promote early initiation and high adherence to MMS. This trial was registered at PROSPERO as CRD42022319207.

Keywords: antenatal care; individual participant data meta-analysis; multiple micronutrient supplements; pregnancy.

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Conflict of interest statement

Conflict of interest MWB reports financial support was provided by JBJ Foundation. ZAB is an Editorial Board Member for Advances in Nutrition and played no role in the Journal’s evaluation of the manuscript. The other authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of identified and included studies. IPD, individual participant data.
See this image and copyright information in PMC

References

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