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

Friday 30 May 2025

Smith ER Gomes F Adu-Afarwuah S Aguayo VM El Arifeen S Bhutta ZA Caniglia EC Christian P Devakumar D Dewey KG Fawzi WW Friis H Gomo E Guindo O Hallamaa L Isanaka S Kæstel P Lachat C Maleta K Moore SE Oakley EM Osrin D Rahman A Rana Z Rizvi A Roberfroid D Shaikh S Sonko B Soofi SB Subarkah I Sunawang R Wang D West KP Wu LSF Zagre N Bourassa MW Sudfeld CR

Advances in nutrition (Bethesda, Md.) 2025 May 30; . doi: 10.1016/j.advnut.2025.100455. Epub 2025 05 30

antenatal care individual participant data meta-analysis multiple micronutrient supplements pregnancy

Abstract

Multiple micronutrient supplements (MMSs) 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.

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