Prenatal micronutrient supplements cumulatively increase fetal growth

Prenatal multiple micronutrients (UNIMMAP) improve fetal growth only moderately compared to iron and folic acid alone (IFA). Whether this is due to insufficient amounts of UNIMMAP or to IFA being in reality an active control is unknown. We assessed the association between cumulative micronutrient intake (CMI) and fetal growth by secondary analysis of a randomized controlled trial in Burkina Faso where tablet intake was directly observed. We applied 2-part residual regression models adjusted for main confounders. Among the 1056 single pregnancies included, the mean CMI (± SD) was 124 ± 54 tablets. The odds of delivering a small-for-gestational-age baby was reduced by 21% [(95%CI: 5, 35); P = 0.013] for each additional tertile of CMI. The association between CMI and birth weight was positively modified by gestational age at enrollment (P-interaction = 0.001). Each unit of CMI was associated with a 1.6-g [(95%CI: 0.3, 3.1); P = 0.019] higher birth weight at a mean-centered gestational age at enrollment, with a higher gradient observed later in pregnancy. Maternal BMI at enrollment was also a positive modifying factor (P-interaction = 0.02), with no association of CMI with birth weight for low BMI. There was no evidence of an effect modification by group allocation; i.e., we observed the same change in birth weight per unit of CMI with either IFA or UNIMMAP. Yet UNIMMAP increased birth weight by 69 g [(95%CI: 58, 81); P < 0.001] relative to IFA. We found similar results for thoracic and cephalic circumferences. In conclusion, for both IFA and UNIMMAP, the effect on fetal growth is cumulative. The supplementation should therefore begin as early as possible in pregnancy, even if the growth increment per CMI is higher in late than in early pregnancy. Women with a low BMI should also receive extra energy.