University of Oulu

Elhakeem, A., Ronkainen, J., Mansell, T. et al. Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study. BMC Med 21, 23 (2023).

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

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Author: Elhakeem, Ahmed1,2; Ronkainen, Justiina3; Mansell, Toby4,5;
Organizations: 1MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
2Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
3Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland
4Murdoch Children’s Research Institute, Parkville, VIC, Australia
5Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
6Folkhälsan Research Center, Helsinki, Finland
7Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
8Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
9Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
10Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
11Department of Paediatrics, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, Netherlands
12The Generation R Study Group, Erasmus MC, University Medical Centre, Rotterdam, Netherlands
13Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
14Bradford Institute for Health Research, Bradford Teaching Hospitals National Health Service Foundation Trust, Bradford, UK
15Department of Paediatrics, Monash University, Clayton, VIC, Australia
16Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
17Obstetrics & Gynecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
18Singapore Institute for Clinical Sciences (SICS), Agency for Science and Technology (A*STAR), Singapore, Singapore
19Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
20Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
21Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
22Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
23Liggins Institute, University of Auckland, Auckland, New Zealand
24NIHR Bristol Biomedical Research Centre, Bristol, UK
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.4 MB)
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Language: English
Published: Springer Nature, 2023
Publish Date: 2023-09-21


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.

Conclusions: These reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for newborns rather than older ages, and for perinatal rather than pregnancy complications.

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Series: BMC medicine
ISSN: 1741-7015
ISSN-E: 1741-7015
ISSN-L: 1741-7015
Volume: 21
Issue: 1
Article number: 23
DOI: 10.1186/s12916-022-02711-8
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
Funding: 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 8: 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.
EU Grant Number: (733206) LIFECYCLE - Early-life stressors and LifeCycle health
(874739) LONGITOOLS - Dynamic longitudinal exposome trajectories in cardiovascular and metabolic non-communicable diseases
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