Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study

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  • Ahmed Elhakeem
  • Justiina Ronkainen
  • Toby Mansell
  • Katherine Lange
  • Tuija M. Mikkola
  • Binisha H. Mishra
  • Rama J. Wahab
  • Tiffany Yang
  • David Burgner
  • Johan G. Eriksson
  • Marjo Riitta Järvelin
  • Romy Gaillard
  • Vincent W.V. Jaddoe
  • Terho Lehtimäki
  • Olli T. Raitakari
  • Richard Saffery
  • Melissa Wake
  • John Wright
  • Sylvain Sebert
  • Deborah A. Lawlor
Background
Common pregnancy and perinatal complications are associated with offspring cardiometabolic risk factors. These complications may influence multiple metabolic traits in the offspring and these associations might differ with offspring age.

Methods
We used data from eight population-based cohort studies to examine and compare associations of pre-eclampsia (PE), gestational hypertension (GH), gestational diabetes (GD), preterm birth (PTB), small (SGA) and large (LGA) for gestational age (vs. appropriate size for gestational age (AGA)) with up to 167 plasma/serum-based nuclear magnetic resonance-derived metabolic traits encompassing lipids, lipoproteins, fatty acids, amino acids, ketones, glycerides/phospholipids, glycolysis, fluid balance, and inflammation. Confounder-adjusted regression models were used to examine associations (adjusted for maternal education, parity age at pregnancy, ethnicity, pre/early pregnancy body mass index and smoking, and offspring sex and age at metabolic trait assessment), and results were combined using meta-analysis by five age categories representing different periods of the offspring life course: neonates (cord blood), infancy (mean ages: 1.1–1.6 years), childhood (4.2–7.5 years); adolescence (12.0–16.0 years), and adulthood (22.0–67.8 years).

Results
Offspring numbers for each age category/analysis varied from 8925 adults (441 PTB) to 1181 infants (135 GD); 48.4% to 60.0% were females. Pregnancy complications (PE, GH, GD) were each associated with up to three metabolic traits in neonates (P≤0.001) with some evidence of persistence to older ages. PTB and SGA were associated with 32 and 12 metabolic traits in neonates respectively, which included an adjusted standardised mean difference of −0.89 standard deviation (SD) units for albumin with PTB (95% CI: −1.10 to −0.69, P=1.3×10−17) and −0.41 SD for total lipids in medium HDL with SGA (95% CI: −0.56 to −0.25, P=2.6×10−7), with some evidence of persistence to older ages. LGA was inversely associated with 19 metabolic traits including lower levels of cholesterol, lipoproteins, fatty acids, and amino acids, with associations emerging in adolescence, (e.g. −0.11 SD total fatty acids, 95% CI: −0.18 to −0.05, P=0.0009), and attenuating with older age across adulthood
OriginalsprogEngelsk
Artikelnummer23
TidsskriftBMC Medicine
Vol/bind21
Udgave nummer1
Antal sider14
ISSN1741-7015
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements No. 733206 (LifeCycle), No. 874739 (LongITools) and No. 101021566 (ART-HEALTH), and the British Heart Foundation (CH/F/20/90003 and AA/18/1/34219). AE and DAL work in a unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_00011/6). Cohort funders are listed in Additional file : Table S3. The funders had no role in the design and conduct of the study; management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. This research reflects only the authors’ view, and the European Commission is not responsible for any use that may be made of the information it contains.

Publisher Copyright:
© 2023, The Author(s).

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