Mismatch between poor fetal growth and rapid postnatal weight gain in the first 2 years of life is associated with higher blood pressure and insulin resistance without increased adiposity in childhood: the GUSTO cohort study

Author:

Ong Yi Ying1,Sadananthan Suresh Anand2,Aris Izzuddin M3ORCID,Tint Mya Thway24,Yuan Wen Lun1,Huang Jonathan Y2ORCID,Chan Yiong Huak5,Ng Sharon4,Loy See Ling267,Velan Sendhil S28,Fortier Marielle V29,Godfrey Keith M10,Shek Lynette1211,Tan Kok Hian712,Gluckman Peter D213,Yap Fabian714,Choo Jonathan Tze Liang14,Ling Lieng Hsi15,Tan Karen216,Chen Li2,Karnani Neerja2,Chong Yap-Seng24,Eriksson Johan G24,Wlodek Mary E217,Chan Shiao-Yng24,Lee Yung Seng1211ORCID,Michael Navin2ORCID

Affiliation:

1. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

2. Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research, Singapore, Singapore

3. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA

4. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

5. Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

6. Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore

7. Duke-NUS Medical School, Singapore, Singapore

8. Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore, Singapore

9. Department of Diagnostic and Interventional Imaging, KK Women's and Children's Hospital, Singapore, Singapore

10. MRC Lifecourse Epidemiology Unit and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK

11. Department of Pediatrics, Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, National University Health System, Singapore, Singapore

12. Department of Maternal Fetal Medicine, KK Women's and Children's Hospital, Singapore, Singapore

13. Liggins Institute, University of Auckland, Auckland, New Zealand

14. Department of Pediatrics, KK Women's and Children's Hospital, Singapore, Singapore

15. Department of Cardiology, National University Heart Centre, Singapore, Singapore

16. Molecular Diagnosis Centre, Department of Laboratory Medicine, National University Health System, Singapore, Singapore

17. Department of Physiology, University of Melbourne, Melbourne, VIC, Australia

Abstract

Abstract Background Using longitudinal ultrasounds as an improved fetal growth marker, we aimed to investigate if fetal growth deceleration followed by rapid postnatal weight gain is associated with childhood cardiometabolic risk biomarkers in a contemporary well-nourished population. Methods We defined fetal growth deceleration (FGD) as ultrasound-measured 2nd-3rd-trimester abdominal circumference decrease by ≥0.67 standard deviation score (SDS) and rapid postnatal weight gain (RPWG) as 0–2-year-old weight increase by ≥0.67 SDS. In the GUSTO mother-offspring cohort, we grouped 797 children into four groups of FGD-only (14.2%), RPWG-only (23.3%), both (mismatch, 10.7%) or neither (reference, 51.8%). Adjusting for confounders and comparing with the reference group, we tested associations of these growth groups with childhood cardiometabolic biomarkers: magnetic resonance imaging (MRI)-measured abdominal fat (n = 262), liver fat (n = 216), intramyocellular lipids (n = 227), quantitative magnetic resonance-measured overall body fat % (BF%) (n = 310), homeostasis model assessment of insulin resistance (HOMA-IR) (n = 323), arterial wall thickness (n = 422) and stiffness (n = 443), and blood pressure trajectories (ages 3–6 years). Results Mean±SD birthweights were: FGD-only (3.11 ± 0.38 kg), RPWG-only (3.03 ± 0.37 kg), mismatch (2.87 ± 0.31 kg), reference (3.30 ± 0.36 kg). FGD-only children had elevated blood pressure trajectories without correspondingly increased BF%. RPWG-only children had altered body fat partitioning, higher BF% [BF = 4.26%, 95% confidence interval (CI) (2.34, 6.19)], HOMA-IR 0.28 units (0.11, 0.45)] and elevated blood pressure trajectories. Mismatch children did not have increased adiposity, but had elevated ectopic fat, elevated HOMA-IR [0.29 units (0.04,0.55)] and the highest blood pressure trajectories. Associations remained even after excluding small-for-gestational-age infants from analyses. Conclusions Fetal growth deceleration coupled with rapid postnatal weight gain was associated with elevated childhood cardiometabolic risk biomarkers without correspondingly increased BF%.

Funder

Singapore National Research Foundation

Translational and Clinical Research

(TCR) Flagship Programme

Singapore Ministry of Health’s National Medical Research Council

NMRC

Singapore Institute for Clinical Sciences, Agency for Science Technology and Research

UK Medical Research Council

National Institute for Health Research

NIHR Southampton Biomedical Research Centre

European Union

Erasmus+ Programme Early Nutrition eAcademy Southeast Asia

Publisher

Oxford University Press (OUP)

Subject

General Medicine,Epidemiology

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