👤 Francesca Cirulli

The beneficial effects of omega-3 polyunsaturated fatty acids (PUFA) supplementation during pregnancy have been associated with reduced risk of preterm birth and low birthweight. However, inconsistent findings have been reported regarding their impact on children's neurodevelopmental trajectories. We performed a comprehensive systematic review with meta-analysis of preclinical studies to assess the effects of prenatal omega-3 supplementation on long-term outcomes in offspring and to identify key relevant neurodevelopmental domains to guide the design and prioritization of future clinical follow-up studies. The databases consulted included PubMed/Medline, Scopus and Web of Science. Thirty-five studies were included in the systematic review, and 19 studies were included in the meta-analysis. Relevant information such as characteristics of nutritional interventions, maternal conditions, offspring characteristics and article attributes were extracted. Sample sizes, means, and standard deviation or standard error for the outcome measures were also extracted. The search yielded 3198 articles; 35 met inclusion criteria, with 11 included in a random-effects meta-analysis of memory retention, and 8 in a meta-analysis of brain-derived neurotrophic factor (BDNF) levels. Our findings show that maternal omega-3 PUFA supplementation during pregnancy improves memory retention (SMD=0.671; CI 95 %: 0.163-1.179; p = 0.010) and increases levels of BDNF (SMD=0.838; CI 95 %: 0.369-1.307; p = 0.000) in the offspring. These effects are more pronounced in offspring exposed to prenatal adversities. Maternal omega-3 supplementation shows promise in mitigating oxidative stress and inflammation, although findings remain heterogeneous. Maternal omega-3 supplementation appears as a safe and effective means to improve offspring neurodevelopment, with stronger effects under adverse gestational conditions, highlighting its potential for at-risk populations. Show less

The Helix Research Network program is a large population genomics initiative that screens an all-comers population of patients for Centers for Disease Control and Prevention Tier 1 genetic conditions, including familial hypercholesterolemia (FH). We evaluated changes in clinical management and low-density lipoprotein cholesterol (LDL-C) levels among patients we identified to have FH. Participants across 9 US health systems provided samples that underwent clinical-grade exome sequencing. Individuals with a positive screening result for a Tier 1 condition were offered no-cost genetic counseling through their health system. Using medication and laboratory testing records, we evaluated changes in patients' lipid-lowering therapies and LDL-C levels. Among 228 602 adults enrolled between 2017 to 2025, 1155 (≈1/198) had a pathogenic FH variant in Following genetic screening, many patients with a pathogenic FH variant experienced improvements in clinical management and LDL-C levels. Electronic health record documentation of the diagnosis code was associated with a greater likelihood of therapeutic modifications, which, in turn, were associated with larger LDL-C reductions. Findings underscore the powerful potential of population genomic screening for supporting optimal lipid management in individuals with FH. Show less

Clinical conditions correlated with elevated triglyceride levels are well-known: coronary heart disease, hypertension, and diabetes. Underlying genetic and phenotypic mechanisms are not fully understood, partially due to lack of coordinated genotypic-phenotypic data. Here we use a subset of the Healthy Nevada Project, a population of 9,183 sequenced participants with longitudinal electronic health records to examine consequences of altered triglyceride levels. Specifically, Healthy Nevada Project participants sequenced by the Helix Exome+ platform were cross-referenced to their electronic medical records to identify: (1) rare and common single-variant genome-wide associations; (2) gene-based associations using a Sequence Kernel Association Test; (3) phenome-wide associations with triglyceride levels; and (4) pleiotropic variants linked to triglyceride levels. The study identified 549 significant single-variant associations ( Show less

Obesity is a heterogeneous phenotype that is crudely measured by body mass index (BMI). There is a need for a more precise yet portable method of phenotyping and categorizing risk in large numbers of people with obesity to advance clinical care and drug development. Here, we used non-targeted metabolomics and whole-genome sequencing to identify metabolic and genetic signatures of obesity. We find that obesity results in profound perturbation of the metabolome; nearly a third of the assayed metabolites associated with changes in BMI. A metabolome signature identifies the healthy obese and lean individuals with abnormal metabolomes-these groups differ in health outcomes and underlying genetic risk. Specifically, an abnormal metabolome associated with a 2- to 5-fold increase in cardiovascular events when comparing individuals who were matched for BMI but had opposing metabolome signatures. Because metabolome profiling identifies clinically meaningful heterogeneity in obesity, this approach could help select patients for clinical trials. Show less