Omega-3 supplementation in addition to prenatal vitamins during pregnancy is associated with lower rates of preterm birth and small for gestational age

Omega-3 fatty acids and prenatal vitamins support fetal growth, but most studies assess omega-3 supplementation without accounting for baseline prenatal vitamin use during pregnancy. In this secondary analysis, we obtained data from the large, prospective Nulliparous Mother-to-be (nuMoM2b) cohort study of 9,461 nulliparous individuals. Participants were enrolled through eight clinical sites across the United States. We compared adverse birth outcomes between those taking additional omega-3 supplements beyond standard prenatal vitamin intake (PNV-OM) vs. prenatal vitamins alone (PNV). PNV-OM intake was associated with significantly lower rates of preterm birth (5.04 vs. 8.41%, <i>P</i> < 0.001) and SGA (2.84 vs. 4.48%, <i>P</i> = 0.004). After adjustment for demographic and clinical differences, PNV-OM use remained associated with reduced odds of preterm birth (aOR 0.64, 95% CI: 0.47-0.86, <i>P</i> = 0.004) and SGA (aOR 0.64, 95% CI: 0.42-0.95, <i>P</i> = 0.03). However, given substantial socioeconomic differences between groups and the potential for residual confounding, these findings should be interpreted with caution. Supplemental omega-3 intake during pregnancy may provide an additive benefit beyond prenatal vitamins alone, but randomized trials are needed to determine whether this relationship is causal.