Evaluation of Maternal Dietary n-3 LCPUFA Supplementation as a Primary Strategy to Reduce Offspring Obesity: Lessons From the INFAT Trial and Implications for Future Research

Abstract

Preclinical research suggests that early exposure to LCPUFAs is associated with offspring health outcomes, although evidence in humans is rather unclear. In 2006, we established the Impact of Nutritional Fatty acids during pregnancy and lactation on early human Adipose Tissue development (INFAT) study, a prospective randomized controlled intervention trial that examined whether decreasing the n-6/n-3 LCPUFA ratio during pregnancy and lactation influences offspring adipose tissue development in children up to 5 years. Our results indicate that maternal supplementation with n-3 LCPUFAs does not reduce offspring obesity risk, which is in line with recent publications. This perspective describes the challenges and lessons learned from our clinical trial. We discuss key findings and critically evaluate differences in study design, methodology, and analyses across similar intervention trials that may partly explain heterogeneous results. Summarizing evidence from human trials, we conclude that n-3 LCPUFA supplementation should not be recommended as a primordial strategy to prevent childhood obesity. Instead, it remains unknown whether n-3 LCPUFA supplementation could benefit high-risk subgroups and some vulnerable maternal/child populations. The perspectives offered herein are derived largely from insights gained from ours and similar n-3 LCPUFA intervention trials and help to provide direction for future research that examines the impact of maternal nutritional exposure on offspring health and disease outcomes.

Fetal sex modulates placental microRNA expression, potential microRNA-mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition

“…The main clinical characteristics of INFAT study subpopulation mothers and offspring were presented previously [10] and in the present study in Additional file 1: Table S1. There were no significant differences between the groups in the investigated offspring growth parameters at birth and up to 5 years of age, consistent with the data for the respective whole INFAT cohort as previously reported [10,[31][32][33][34]84].…”

“…Since significant associations were often only observed either in the unadjusted or the adjusted model, it will be interesting to find out which of the various covariates are involved. It is important to note that offspring bodyweight in the intervention and control groups did not differ significantly from 1 year onwards, neither in the entire INFAT study population nor the INFAT subgroup in the present and previous studies [31][32][33][34]84]. The present data indicate that the observed sex-specific expression changes and Tau and Trp level alterations and their respective associations with offspring body composition need more detailed analyses to find out exactly which sex and sexgroup interactions significantly matter.…”

Long-chainn-3 PUFA given before and throughout gestation and lactation in rats prevent high-fat diet-induced insulin resistance in male offspring in a tissue-specific manner

“…A meta-analysis of 11 randomized controlled trials (RCTs) (34) and a recent review (35) concluded to no beneficial effect of LC n-3 PUFAs given during pregnancy on obesity in offspring. Another one concluded to no benefit towards IR but to a significant decrease in Creactive protein (36) .…”