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Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach

Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach
Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach
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.
2041-1723
Huang, Jonathan Y.
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Cai, Shirong
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Huang, Zhongwei
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Mya, Tint
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Yuan, Wen Lun
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Aris, Izzuddin M.
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Godfrey, Keith
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Karmani, Neerja
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Lee, Yung Seng
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Chan, Jerry Kok Yen
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Chong, Yap-Seng
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Eriksson, Johan G.
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Chan, Shiao-Yng
3c9d8970-2cc4-430a-86a7-96f6029a5293
Huang, Jonathan Y.
35e14404-4a04-49f6-822a-65ec0ac4f50c
Cai, Shirong
6e4e2d93-9910-4fc8-91a1-07d445f868a4
Huang, Zhongwei
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Mya, Tint
6f8cd9a6-2667-4495-b1c9-40c7ff3ffb28
Yuan, Wen Lun
bd1a80dc-c82a-4387-b754-72e30dd603a7
Aris, Izzuddin M.
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Godfrey, Keith
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Karmani, Neerja
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Lee, Yung Seng
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Chan, Jerry Kok Yen
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Chong, Yap-Seng
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Eriksson, Johan G.
eb96b1c5-af07-4a52-8a73-7541451d32cd
Chan, Shiao-Yng
3c9d8970-2cc4-430a-86a7-96f6029a5293

Huang, Jonathan Y., Cai, Shirong, Huang, Zhongwei, Mya, Tint, Yuan, Wen Lun, Aris, Izzuddin M., Godfrey, Keith, Karmani, Neerja, Lee, Yung Seng, Chan, Jerry Kok Yen, Chong, Yap-Seng, Eriksson, Johan G. and Chan, Shiao-Yng (2021) Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach. Nature Communications, 12 (1), [5613]. (doi:10.1038/s41467-021-25899-4).

Record 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.

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Accepted/In Press date: 6 August 2021
e-pub ahead of print date: 23 September 2021

Identifiers

Local EPrints ID: 450870
URI: http://eprints.soton.ac.uk/id/eprint/450870
ISSN: 2041-1723
PURE UUID: 300292ad-5a3e-4197-a32a-6932e6e2db76
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

Catalogue record

Date deposited: 17 Aug 2021 16:32
Last modified: 26 Nov 2021 06:58

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Contributors

Author: Jonathan Y. Huang
Author: Shirong Cai
Author: Zhongwei Huang
Author: Tint Mya
Author: Wen Lun Yuan
Author: Izzuddin M. Aris
Author: Keith Godfrey ORCID iD
Author: Neerja Karmani
Author: Yung Seng Lee
Author: Jerry Kok Yen Chan
Author: Yap-Seng Chong
Author: Johan G. Eriksson
Author: Shiao-Yng Chan

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