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Developmental origins of endometriosis: a Swedish cohort study
  1. Menghan Gao1,
  2. Peter Allebeck1,
  3. Gita D Mishra2,
  4. Ilona Koupil1,3
  1. 1 Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
  2. 2 School of Population Health, University of Queensland, Brisbane, Queensland, Australia
  3. 3 Department of Public Health Sciences, Centre for Health Equity Studies, Stockholm University, Stockholm, Sweden
  1. Correspondence to Menghan Gao, Department of Public Health Sciences, Karolinska Institutet, 171 77 Stockholm, Sweden; menghan.gao{at}ki.se

Abstract

Background Endometriosis is a chronic condition affecting women of reproductive age and is associated with multiple health burdens. Yet, findings regarding its ‘developmental origins’ are inconsistent. We aimed to investigate the associations of birth characteristics with endometriosis. We also explored potential mediation by adult social and reproductive factors.

Methods This cohort study consisted of 3406 women born in Uppsala, Sweden, between 1933 and 1972. We used data from archived birth records and endometriosis diagnoses at ages 15–50 recorded in the national patient registers. Socioeconomic and reproductive characteristics were obtained from routine registers. HRs were estimated from Cox regression.

Results During the follow-up, 111 women have been diagnosed with endometriosis, and most cases are external endometriosis (ie, outside the uterus, n=91). Lower standardised birth weight for gestational age was associated with increased rate of endometriosis (HR 1.35 per standard deviation decrease; 95% CI 1.08 to 1.67). This increased rate was also detected among women with fewer number of live births (HR 2.38; 95% CI 1.40 to 4.07 for one child vs ≥2 children; HR 6.09; 95% CI 3.88 to 9.57 for no child vs ≥2 children) and diagnosed infertility problem (HR 2.00; 95% CI 1.10 to 3.61) prior to endometriosis diagnosis. All the observed associations were stronger for external endometriosis. However, no evidence was found that number of births was the mediator of the inverse association between standardised birth weight and endometriosis.

Conclusion This study supports the developmental origins theory and suggests that exposure to growth restriction during the fetal period is associated with increased risk of endometriosis during reproductive years.

  • birth weight
  • cohort studies
  • life course epidemiology
  • gynaecology

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors MG, PA and IK were involved in conception and design of the study. MG conducted the literature search and data analysis. MG, PA, GDM and IK interpreted the data and MG drafted the manuscript. All authors revised the manuscript critically for important intellectual content and gave final approval of the version to be published.

  • Funding This study was supported by grants from the European Union’s Horizon 2020 research and innovation programme under grant agreement no 635316 (ATHLOS project), the Swedish Research Council (project no: 2013-5474), the Swedish Research Council for Health, Working Life and Welfare (project no: 2013-1850 and 2016-7312), the China Scholarship Council (no: 201600160078) (MG) and the Australian NHMRC Principal Research Fellowship (no: APP1121844) (GDM).

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval This study was approved by the Regional Ethics Committee in Stockholm, Sweden (dnrs: 03-117, 04-944T, 2009/1115-32, 2009/1830-32 and 2014/2058-31/5).

  • Provenance and peer review Not commissioned; externally peer reviewed.