Smith Emily R, Gomes Filomena, Adu-Afarwuah Seth, Aguayo Victor M, El Arifeen Shams, Bhutta Zulfiqar A, Caniglia Ellen C, Christian Parul, Devakumar Delanjathan, Dewey Kathryn G, Fawzi Wafaie W, Friis Henrik, Gomo Exnevia, Guindo Ousmane, Hallamaa Lotta, Isanaka Sheila, Kæstel Pernille, Lachat Carl, Maleta Ken, Moore Sophie E, Oakley Erin M, Osrin David, Rahman Anisur, Rana Ziaul, Rizvi Arjumand, Roberfroid Dominique, Shaikh Saijuddin, Sonko Bakary, Soofi Sajid Bashir, Subarkah Inan, Sunawang Rahardjo, Wang Dongqing, West Keith P, Wu Lee Shu Fune, Zagre Noel, Bourassa Megan W, Sudfeld Christopher R
Department of Global Health, Exercise and Nutrition Sciences, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States.
Nutrition Science Program, The New York Academy of Science, New York, NY, United States; NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal; Healthy Mothers Healthy Babies Program, Micronutrient Forum, Washington, DC, United States.
Adv Nutr. 2025 Jul;16(7):100455. doi: 10.1016/j.advnut.2025.100455. Epub 2025 May 30.
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.
与单独补充铁和叶酸（IFA）相比，孕期补充多种微量营养素（MMS）可降低婴儿低出生体重（LBW）的风险，并改善其他母婴结局。然而，在实际项目中，开始补充的时间和依从性对MMS有效性的影响仍不明确。为解决这一问题，我们进行了一项两阶段的个体参与者数据荟萃分析，该分析纳入了15项随机试验（61204名孕妇），并评估了MMS的相对效果是否因以下因素而有所不同：单独的依从性；依从性与开始补充时的孕周相结合；以及服用的片剂总数。我们还评估了这些因素与接受MMS的参与者结局之间的观察性关联。与IFA补充剂相比，依从性越高，MMS对持续出生体重这一主要结局的相对效果越大（P交互作用<0.05）。在服用≥90%补充剂的女性中，MMS使出生体重增加了56克（95%CI：45，67克），而在服用<60%补充剂的女性中，MMS和IFA补充剂之间的出生体重没有差异[平均差异（MD）：9克；95%CI：-17，35克]。更高的依从性还与MMS对低出生体重和出生体重相对于胎龄百分位数的更大效果相关，与IFA补充剂相比，服用更多补充剂的女性，MMS对出生体重相对于胎龄百分位数和小于胎龄儿出生（SGA）的相对影响更大。对接受MMS的参与者的观察性分析表明，≥90%的依从性与出生体重增加（MD：44克；95%CI：31，56克）、低出生体重风险降低[相对风险（RR）：0.93克；95%CI：0.88，0.98克]和小于胎龄儿风险降低（RR：0.95；95%CI：0.93，0.98）相关，而<75%的依从性与死产风险增加（RR：1.43；95%CI：1.12，1.83）和母体贫血风险增加（RR：1.26；95%CI：1.11，1.43）相关，高于75%-90%的依从性。项目应投资于促进早期开始和高依从性服用MMS的策略。该试验在PROSPERO注册，注册号为CRD42022319207。
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