Review Quality Rating: 8 (strong) - View Quality Assessment Citation: Saccone G, Saccone I, & Berghella V. (2016). Omega-3 long-chain polyunsaturated fatty acids and fish oil supplementation during pregnancy: Which evidence? Journal of Maternal-Fetal and Neonatal Medicine, 29(15). Abstract OBJECTIVE: The aim of this study was to provide evidence-based recommendations for omega-3 supplementation during pregnancy through a systematic review of level-1 data published on this topic.METHODS: We reviewed all randomized-controlled trials (RCTs) including women who were randomized to treatment with either omega-3 supplementation or control (placebo or no treatment) during pregnancy and analyzed all the outcomes reported in the trials, separately. We planned to evaluate the effect of omega-3 on: preterm birth (PTB); pre-eclampsia (PE) and intrauterine growth restriction (IUGR); gestational diabetes; perinatal mortality; small for gestational age (SGA) and birth weight; infant eye and brain development; and postpartum depression.RESULTS: We identified 34 RCTs including 14 106 singletons and 2578 twins. These level-1 data showed that omega-3 was not associated with prevention of PTB, PE, IUGR, gestational diabetes, SGA, post-partum depression or better children development. Data about birth weight, perinatal mortality and childhood cognitive outcome were limited. Women with gestational diabetes who received omega-3 had significantly lower serum C-reactive protein concentrations, low incidence of hyperbilirubinemia in newborns and decreased newborns hospitalization rate.CONCLUSIONS:There was not enough evidence to support the routine use of omega-3 supplementation during pregnancy. Given the 73% significant decrease in perinatal death in the singleton gestations who started omega-3 supplementation < 20 weeks, further research is needed. Large RCTs in multiple gestations and longer follow-up are also required. Keywords: Adults, Behaviour Modification, Diabetes, Food & Nutrition, Home, Meta-analysis, Primary Health Care Provider Office (e.g., Public health nurse, dietitian, social worker), Reproductive Health & Healthy Families, Women