Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach
Year: 2021
Type: article
Abstract: Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum metabolic biomarkers, and cord tissue DNA methylation by emulating a pragmatic trial supported by machine learning-based estimators. We find ART-conceived children to be shorter (-0.5 SD [95% CI: -0.7, -0.2]), lighter (-0.6 SD [-0.9, -0.3]) and have lower skinfold thicknesses (e.g. -14% [-24%, -3%] suprailiac), and blood pressure (-3 mmHg [-6, -0.5] systolic) at 6-6.5 years, with no strong differences in metabolic biomarkers. Differences are not explained by parental anthropometry or comorbidities, polygenic risk score, breastfeeding, or illnesses. Our simulations demonstrate ART is strongly associated with lower NECAB3 DNA methylation, with negative control analyses suggesting these estimates are unbiased. However, methylation changes do not appear to mediate observed differences in child phenotype.
Source: Nature Communications
Institutions: Agency for Science, Technology and Research, Singapore Institute for Clinical Sciences, National University of Singapore, Institute of Molecular and Cell Biology, Inserm, Université Paris Cité, Centre de Recherche Épidémiologie et Statistique, Harvard University, Harvard Pilgrim Health Care, University Hospital Southampton NHS Foundation Trust, NIHR Southampton Biomedical Research Centre, University of Southampton, SingHealth Duke-NUS Academic Medical Centre, KK Women's and Children's Hospital, Duke-NUS Medical School, University of Helsinki, Helsinki University Hospital, Folkhälsans Forskningscentrum
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: National Institute for Health and Care Research, British Heart Foundation, European Commission, National Research Foundation, Singapore Institute for Clinical Sciences, National Research Foundation Singapore, National University Health System, National Institute for Health Research Southampton Biomedical Research Centre, Medical Research Council, National Medical Research Council, Erasmus+
Awards: Programme 1: Musculoskeletal health in later life, G1917706474, G1956390128, G2693923786, G2780654756, G3210728687, G3424013768, NIHR Senior Investigator Award, G3778457340, G3873828540, G389277099, G427574963, NIHR Senior Investigator Award, Capacity Building to Improve Early Nutrition and Health in South Africa, Programme 3: Early development and risk of adult musculoskeletal disease, G524590474, Epigenetic biomarkers and determinants of cardiovascular risk in children, G5755632036, G606602278, G6206044308, G7388601084, MRC Lifecourse Epidemiology Centre - Core Support, G8346907872, Nutrition, Development and Lifelong Health: Studies in European Populations, G8831649822
OpenAlex ID: W3199459791