University of Oulu

Xinxia Chen, Emilia Koivuaho, Terhi T Piltonen, Mika Gissler, Catharina Lavebratt, Association of maternal polycystic ovary syndrome or anovulatory infertility with obesity and diabetes in offspring: a population-based cohort study, Human Reproduction, Volume 36, Issue 8, August 2021, Pages 2345–2357, https://doi.org/10.1093/humrep/deab112

Association of maternal polycystic ovary syndrome or anovulatory infertility with obesity and diabetes in offspring : a population-based cohort study

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Author: Chen, Xinxia1,2,3; Koivuaho, Emilia4; Piltonen, Terhi T.4;
Organizations: 1School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
3Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
4Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
5Department of Information Services, Finnish Institute for Health and Welfare, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2022022220359
Language: English
Published: Oxford University Press, 2021
Publish Date: 2022-02-22
Description:

Abstract

STUDY QUESTION: Are children of mothers with polycystic ovary syndrome (PCOS) or anovulatory infertility at increased risks of obesity or diabetes?

SUMMARY ANSWER: Maternal PCOS/anovulatory infertility is associated with an increased risk of offspring obesity from early age and diabetes in female offspring from late adolescence.

WHAT IS KNOWN ALREADY: Women with PCOS often have comorbid metabolic disorders such as obesity and diabetes, and children of mothers with PCOS have an increased risk of subtle signs of cardiometabolic alterations.

STUDY DESIGN, SIZE, DURATION: This was a nationwide cohort study of all live births (n = 1 105 997) during 1996–2014 in Finland, excluding those with maternal diagnoses sharing signs and symptoms with PCOS (n = 8244). A total of 1 097 753 births were included and followed up until 31 December 2018.

PARTICIPANTS/MATERIALS, SETTING, METHODS: National registries were linked to identify births with maternal PCOS or anovulatory infertility (n = 24 682). The primary outcomes were diagnoses of obesity (ICD-10: E65, E66) and diabetes (ICD-10: E10–E14) in offspring recorded in the Finnish Care Register for Health Care. Cox proportional hazards regression was modeled to analyze the risk of offspring obesity and diabetes in relation to prenatal exposure to maternal PCOS/anovulatory infertility. Differently adjusted models and stratified analyses were used to assess whether the risk was modified by maternal obesity or diabetes diagnoses, pre-pregnancy BMI, fertility treatment or perinatal problems.

MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to maternal PCOS/anovulatory infertility was associated with a higher cumulative incidence of obesity in the children (exposed: 1.83%; 95% CI 1.66–2.00% vs unexposed: 1.24%; 95% CI 1.22–1.26%). Accounting for birth factors and maternal characteristics such as obesity and diabetes diagnoses, the hazard ratio (HR) for obesity was increased in offspring below 9 years of age (HR 1.58; 95% CI 1.30–1.81), and in those 10–16 years of age (HR 1.37; 95% CI 1.19–1.57), but not in those aged 17–22 years (HR 1.24; 95% CI 0.73–2.11). Sex-stratified analyses revealed similar risk estimates for boys (HR 1.48; 95% CI 1.31–1.68) and girls (HR 1.45; 95% CI 1.26–1.68). Notably, the joint effect of PCOS/anovulatory infertility and BMI-based pre-pregnancy obesity on offspring obesity (HR 8.89; 95% CI 7.06–11.20) was larger than that of either PCOS/anovulatory infertility or obesity alone. Furthermore, PCOS/anovulatory infertility was associated with offspring obesity in children without perinatal problems (HR 1.27; 95% CI 1.17–1.39), with larger effect size for maternal PCOS/anovulatory infertility and joint perinatal problems (HR 1.61; 95% CI 1.35–1.91). However, the risk estimates were comparable between maternal PCOS/anovulatory infertility with (HR 1.54; 95% CI 1.17–2.03) and without fertility treatment (HR 1.46; 95% CI 1.32–1.61). For offspring diabetes, the HR was increased only between 17 and 22 years of age (HR 2.06; 95% CI 1.23–3.46), and specifically for Type 1 diabetes in females (HR 3.23; 95% CI 1.41–7.40).

LIMITATIONS, REASONS FOR CAUTION: The prevalence of PCOS/anovulatory infertility in this study was 2.2%, lower than that reported in previous studies. In addition, the incidence of obesity in offspring was lower than that reported in studies based on measured or self-reported weight and height and may include mainly moderate and severe obesity cases who needed and/or actively sought medical care. Moreover, mothers with PCOS/anovulatory infertility were identified based on ICD codes, with no information on PCOS phenotypes. Furthermore, maternal pre-pregnancy BMI was available only from 2004. The PCOS/anovulatory infertility association with female offspring diabetes was based on only a few cases. Mothers’ weight gain during pregnancy, use of fertility treatment other than fresh or frozen IVF/ICSI, offspring lifestyle, as well as fathers’ age, medical disorders or medication prescriptions were not available for this study.

WIDER IMPLICATIONS OF THE FINDINGS: These findings support that prenatal PCOS/anovulatory infertility exposure influences metabolic health in the offspring from early age.

STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Shandong Provincial Natural Science Foundation, China [ZR2020MH064 to X.C.], Shandong Province Medical and Health Technology Development Plan [2018WS338 to X.C.], the joint research funding of Shandong University and Karolinska Institute [SDU-KI-2019-08 to X.C. and C.L.], the Finnish Institute for Health and Welfare: Drug and Pregnancy Project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 and SLL20190589 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. received grants from the China Scholarship Council at the beginning of the study. The authors have no competing interests to disclose.

TRIAL REGISTRATION NUMBER: N/A.

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Series: Human reproduction
ISSN: 0268-1161
ISSN-E: 1460-2350
ISSN-L: 0268-1161
Volume: 36
Issue: 8
Pages: 2345 - 2357
DOI: 10.1093/humrep/deab112
OADOI: https://oadoi.org/10.1093/humrep/deab112
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Subjects:
Funding: This study was supported by Shandong Provincial Natural Science Foundation, China [ZR2020MH064 to X.C.], Shandong Province Medical and Health Technology Development Plan [2018WS338 to X.C.], the joint research funding of Shandong University and Karolinska Institute [SDU-KI-2019-08 to X.C. and C.L.], the Finnish Institute for Health and Welfare: Drug and pregnancy project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 and SLL20190589 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. received grants from the China Scholarship Council at the beginning of the study. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Copyright information: © The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
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