Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-021-25899-4
Title: Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach
Authors: Huang, Jonathan Yinhao
Cai, Shirong 
Huang, Zhongwei
Tint, Mya Thway 
Yuan, Wen Lun 
Aris, Izzuddin M 
Godfrey, Keith M
Karnani, Neerja 
Lee, Yung Seng 
Chan, Jerry Kok Yen 
Chong, Yap Seng 
Eriksson, Johan Gunnar
Chan, Shiao-Yng
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
IN-VITRO FERTILIZATION
DNA METHYLATION
PERINATAL OUTCOMES
UNITED-STATES
ASSOCIATION
CONCEPTION
HEALTH
IVF
BORN
EPIGENETICS
Issue Date: 23-Sep-2021
Publisher: NATURE PORTFOLIO
Citation: Huang, Jonathan Yinhao, Cai, Shirong, Huang, Zhongwei, Tint, Mya Thway, Yuan, Wen Lun, Aris, Izzuddin M, Godfrey, Keith M, Karnani, Neerja, Lee, Yung Seng, Chan, Jerry Kok Yen, Chong, Yap Seng, Eriksson, Johan Gunnar, Chan, Shiao-Yng (2021-09-23). Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach. NATURE COMMUNICATIONS 12 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-021-25899-4
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 Title: NATURE COMMUNICATIONS
URI: https://scholarbank.nus.edu.sg/handle/10635/208537
ISSN: 20411723
DOI: 10.1038/s41467-021-25899-4
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