TY - JOUR
T1 - Contribution of Maternal Adherence to the Effect of Multiple Micronutrient Supplementation During Pregnancy
T2 - A Systematic Review and Individual Participant Data Meta-analysis
AU - Smith, Emily R.
AU - Gomes, Filomena
AU - Adu-Afarwuah, Seth
AU - Aguayo, Victor M.
AU - El Arifeen, Shams
AU - Bhutta, Zulfiqar A.
AU - Caniglia, Ellen C.
AU - Christian, Parul
AU - Devakumar, Delanjathan
AU - Dewey, Kathryn G.
AU - Fawzi, Wafaie W.
AU - Friis, Henrik
AU - Gomo, Exnevia
AU - Guindo, Ousmane
AU - Hallamaa, Lotta
AU - Isanaka, Sheila
AU - Kæstel, Pernille
AU - Lachat, Carl
AU - Maleta, Ken
AU - Moore, Sophie E.
AU - Oakley, Erin M.
AU - Osrin, David
AU - Rahman, Anisur
AU - Rana, Ziaul
AU - Rizvi, Arjumand
AU - Roberfroid, Dominique
AU - Shaikh, Saijuddin
AU - Sonko, Bakary
AU - Soofi, Sajid Bashir
AU - Subarkah, Inan
AU - Sunawang, Rahardjo
AU - Wang, Dongqing
AU - West, Keith P.
AU - Wu, Lee Shu Fune
AU - Zagre, Noel
AU - Bourassa, Megan W.
AU - Sudfeld, Christopher R.
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/7
Y1 - 2025/7
N2 - 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.
AB - 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.
KW - antenatal care
KW - individual participant data meta-analysis
KW - multiple micronutrient supplements
KW - pregnancy
UR - https://www.scopus.com/pages/publications/105008878384
U2 - 10.1016/j.advnut.2025.100455
DO - 10.1016/j.advnut.2025.100455
M3 - Review article
AN - SCOPUS:105008878384
SN - 2161-8313
VL - 16
JO - Advances in Nutrition
JF - Advances in Nutrition
IS - 7
M1 - 100455
ER -