Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
Centre for Economic Demography & Department of Economic History, Lund University, Lund, Sweden.
Int J Epidemiol. 2020 Apr 1;49(2):537-547. doi: 10.1093/ije/dyz140.
Perinatal characteristics are associated with subsequent risk of several chronic diseases. Previous studies regarding endometriosis were based on small samples and retrospective data and were limited by unmeasured confounding bias, leading to conflicting and inconclusive findings. We investigated the associations of maternal and birth characteristics with risk of endometriosis among Swedish women of reproductive age.
This total-population register-based cohort study consisted of 628 312 singleton women born in Sweden between 1973 and 1987, who were followed for diagnosed endometriosis from age 15 years until the end of 2012. Multivariable Cox regression was applied to examine associations with perinatal characteristics. Residual unmeasured confounding was assessed through within-family and E-value analyses.
During follow-up, 8262 women received an endometriosis diagnosis. There were clear dose-response/linear associations of endometriosis with lower maternal education, endometriosis in the mother [adjusted hazard ratio (aHR): 2.24, 95% confidence interval (CI): 2.04-2.46], maternal smoking during pregnancy (aHR: 1.18, 95% CI: 1.04-1.33 for moderate smoker and aHR: 1.36, 95% CI: 1.18-1.57 for heavy smoker vs non-smoker), lower birthweight, and lower birthweight-for-gestational age (aHR: 0.93 per standard deviation increase, 95% CI: 0.91-0.95). Within-family and E-value analyses suggested that these perinatal characteristics are robust predictors of the incidence of endometriosis. We also found that an estimated 26% of the association between maternal smoking and early-onset endometriosis could be explained by birthweight-for-gestational age.
This study finds support for fetal origins of endometriosis, in that exposure to adverse environment or restricted development during the perinatal period may increase the risk. Further research is needed to provide an understanding of the underlying mechanisms.
围产期特征与多种慢性疾病的后续风险相关。之前关于子宫内膜异位症的研究基于小样本和回顾性数据，受到未测量混杂偏差的限制，导致结果存在冲突且不一致。我们研究了瑞典生育年龄女性的围产期特征与子宫内膜异位症风险之间的关联。
本项基于人群的队列研究共纳入了 1973 年至 1987 年期间在瑞典出生的 628312 名单胎女性，她们从 15 岁起被随访至 2012 年底以诊断是否患有子宫内膜异位症。多变量 Cox 回归用于检查与围产期特征的相关性。通过家庭内和 E 值分析评估残留的未测量混杂。
在随访期间，8262 名女性被诊断患有子宫内膜异位症。子宫内膜异位症与母亲受教育程度较低、母亲患有子宫内膜异位症[校正后的危险比 (aHR)：2.24，95%置信区间 (CI)：2.04-2.46]、母亲在怀孕期间吸烟（aHR：1.18，95%CI：1.04-1.33 中度吸烟者和 aHR：1.36，95%CI：1.18-1.57 重度吸烟者 vs 不吸烟者）、较低的出生体重和较低的出生体重-胎龄（aHR：每标准偏差增加 0.93，95%CI：0.91-0.95）存在明显的剂量反应/线性关系。家庭内和 E 值分析表明，这些围产期特征是子宫内膜异位症发病的可靠预测因素。我们还发现，母亲吸烟与早发性子宫内膜异位症之间的关联有 26%可以用出生体重-胎龄来解释。
本研究支持子宫内膜异位症的胎儿起源假说，即围产期暴露于不良环境或发育受限可能会增加患病风险。需要进一步的研究来提供对潜在机制的理解。
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