Pre-pregnancy overweight and obesity (OWOB) is associated with higher adiposity at birth, abnormal fetal growth (large and small for gestational age infants) and medically indicated and spontaneous preterm births.
Polyunsaturated fatty acids (PUFA) have been found to modulate inflammation, insulin sensitivity and lipid metabolism, and a recently published Cochrane review showed that n omega-3 supplementation was associated with reduced risk of preterm birth and low birthweight (BW).
Animal studies and post-hoc analyses from prior RCTs suggest women with higher baseline metabolic dysregulation and with low n-3 status may most benefit from dietary supplementation. However, studies evaluating the role of supplementation specifically in these higher risk cohorts are lacking.
The authors of the current study previously reported that in women with OWOB, higher n-6/n-3 PUFA ratio was associated with shorter length of gestation and impaired fetal growth. However, the effects of n-3 PUFA supplementation on length of gestation and neonatal outcomes, specifically in women with OWOB, are still unknown.
The current pilot double-blind RCT involved 48 healthy women (24 placebo and 24 supplemented) with body mass index (BMI) > 25 kg/m2 and was conducted to investigate the effects of n-3 supplementation starting in early gestation (<16 weeks).
The study was unique because it was comprised specifically of women with OWOB who have an increased risk of preterm birth and a unique metabolism characterised by chronic low-grade inflammation, oxidative stress, and an imbalance in pro-inflammatory n-6 vs. anti-inflammatory n-3 PUFA.
Blister packs were dispensed monthly at routine obstetrical visits checked for compliance and side effects. There were two visits in the clinical research unit (CRU) at MetroHealth Medical Center for each study participant: visit one between 8–16 weeks and visit 2 between 34–36 weeks
This study's researchers previously reported the primary findings from this study, that n-3 PUFA supplementation reduced systemic and placental inflammation, and in a secondary analysis of the trial they reported that n-3 PUFA supplementation reduced placental lipid storage.
The objective of the present report was to study the results to explore the preliminary efficacy of n-3 PUFA supplementation on neonatal adiposity, fetal growth and length of gestation.
Results suggest that supplementation with n-3 PUFA led to higher lean mass accrual at birth as well as improved fetal growth and longer gestation. However, the effects of supplementation were only evident in women with a high dietary n-6/n-3 ratio, suggesting that n-3 supplementation may be beneficial specifically in mothers with overall lower diet quality and high metabolic dysfunction.
The authors also note that supplementing women who are already replete in omega-3 PUFA may increase risk for preterm birth.
They also found n-3 supplementation had stronger effects in male babies, versus females, contrary to previous studies.
The report concludes: "This pilot study provides preliminary evidence that supplementation with n-3 PUFA during pregnancy in women with OWOB for ~25 weeks may increase fetal fatfree mass accrual, improve fetal growth, and increase length of gestation.
"Improving the n-3 status in pregnancy may have value as a prophylactic intervention in some women, particularly those with high-risk pregnancies such as women with obesity. Larger adequately powered trials of n-3 supplementation or dietary intervention specifically in women with OWOB starting before conception or early in pregnancy should be conducted to confirm these findings and explore the long-term impact on offspring adiposity and cardiometabolic health."
Maternal obesity-associated inflammation has been found to be associated with altered placental lipid metabolism and insulin signaling that are thought to lead to excessive nutrient transport, resulting in increased fetal fat accretion. Placental inflammation can also result in abnormal placentation and vasculature that may lead to placental insufficiency, resulting in intra-uterine growth restriction and preterm births. This adverse metabolic environment is associated with metabolic programming in the offspring with consequences throughout the lifespan.
Prospective cohort studies have shown associations of higher n-6 PUFA with lower birthweight (BW), higher fat mass (FM) and higher body fat, and associations of higher n-3 with higher lean mass (LM) and lower adiposity in childhood. Animal studies have shown that interventions to increase the antiinflammatory omega-3 (n-3) to pro-inflammatory n-6 ratio can reduce obesity-induced inflammation and insulin resistance and prevent offspring adverse metabolic programming.
Prior to the current study, several n-3 randomized controlled trials (RCTs) have reported mixed findings, and systematic reviews have not been conclusive on the effects of n-3 supplementation on neonatal outcomes, specifically offspring body composition.
Catalano. P. M., et al
"Effect of Omega-3 Supplementation in Pregnant Women with Obesity on Newborn Body Composition, Growth and Length of Gestation: A Randomized Controlled Pilot Study"
https://doi.org/10.3390/nu13020578 (registering DOI)