(PTFS04-02-26) Dietary Total Fat and Polyunsaturated Fatty Acid Intake and Risk of Preterm Birth: A Systematic Review

Objectives: Polyunsaturated fatty acids (PUFA) are essential during pregnancy for maternal health and fetal brain and retinal development, and their intake is associated with reduced risk of preterm birth (PTB, < 34 and < 37 weeks gestation). Strong evidence has supported voluntary PUFA fortification of infant formulas and prenatal omega-3 (n-3) supplement use. As part of a broader review of dietary fat intake and child growth and developmental outcomes to inform forthcoming Dietary Reference Intake (DRI) updates, PUFA intake during pregnancy and risk of PTB was evaluated.

Methods: Databases were searched from 1990-August 2025, supplemented by reference list screening and Federal Register Notice responses. Using predefined criteria, two reviewers screened abstracts and full text articles. Risk of bias (ROB) and strength of evidence (SOE) were assessed, and eligible studies were synthesized. 

Results: Of the 86 included studies (126 publications), 23 (29 publications) evaluated prenatal PUFA intake and risk of PTB; the majority (90%) were RCTs and over half (55%) were rated high or moderate ROB. Interventions largely involved n-3 supplementation compared with control, differing amounts or other n-3s, or combined n-3/n-6 formulations. Overall, meta-analyses showed no difference in risk of PTB < 34 weeks (8 studies, low SOE) or < 37 weeks (12 studies, low SOE) in generally healthy populations. One trial of PUFA fortified milk powder reported reduced risk of PTB < 34 weeks versus unfortified milk; five trials reported reduced risk of PTB < 37 weeks with n-3 intake alone versus combined n-3/n-6 supplementation.

Conclusions: Studies assessing PUFA intake during pregnancy and risk of PTB generally reported similar rates at < 34 and < 37 weeks gestation. Of note, widespread use of prenatal n-3 supplements may have elevated baseline PUFA status among pregnant populations, potentially masking intervention effects. Recent landmark trials highlighted differential effects of prenatal supplementation by baseline n-3 status. Results underscore the need for targeted research to develop equitable approaches to identify populations most likely to benefit and evidence-based recommendations for these populations in future DRIs. 

Funding Sources: Agency for Healthcare Research and Quality, US Department of Health and Human Services.