Measures of fetal growth and preterm birth and risk of endometriosis and adenomyosis in adult life: a systematic review and meta-analysis.

INTRODUCTION: Exposures in utero are suggested to play a role in the etiology of endometriosis and adenomyosis, although the current evidence is inconclusive. Knowledge about potential prenatal programming and early life exposures that may affect this risk is of high importance, to focus potential preventive strategies for the diseases already during pregnancy. The aim of this study was to review systematically the literature of the association between measures of fetal growth and preterm birth and endometriosis and adenomyosis in adult life. MATERIAL AND METHODS: A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and by search on PubMed and EMBASE was carried out. We included published case-control and cohort studies. We excluded studies without a reference group, eg case series, case reports as well as commentaries, letters and editorials. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Meta-analyses using a random-effect inverse variance weighted model were performed. PROSPERO registration number is CRD42021249322. RESULTS: A total of 11 studies were included. In general, the quality scores of the studies were moderate. We found that the risk of endometriosis was 26% higher in women born with a birthweight <2.5 kg (pooled odds ratio [pOR] 1.26, 95% confidence interval [CI] 1.05-1.52) and 32% higher in women born preterm (pOR 1.32, 95% CI 1.01-1.72) than in the reference groups. The studies on adenomyosis pointed towards no association, but a meta-analysis was unfeasible due to the small number of studies. CONCLUSIONS: This systematic review and meta-analysis found that low birthweight and being born preterm were associated with endometriosis in adult life, but the results must be interpreted cautiously. No solid conclusion could be made regarding adenomyosis due to a limited number of published studies, but the studies included found no association. The results support the hypothesis of a potential early programming effect of endometriosis. However, the body of evidence is sparse and this hypothesis needs to be investigated further.

Endometriosis and preterm birth: A Danish cohort study.

INTRODUCTION: Emerging evidence shows that women with endometriosis face a higher risk of preterm birth. However, the pathways are unclear. The objective of this study is to further investigate at different gestational ages the association between endometriosis and different pathways of preterm birth including, medically indicated preterm birth, premature pre-labor rupture of membranes (PPROM), and spontaneous labor contractions. MATERIAL AND METHODS: In this population-based cohort study we linked singleton pregnancies from the Aarhus Birth Cohort to the Danish National Patient Registry, the Danish Medical Birth Registry, the Danish National Pathology Registry and Data Bank, and the Danish in vitro fertilization registry to gather information on endometriosis status, outcomes and maternal characteristics. We investigated preterm birth before 37 completed weeks of gestation and very preterm birth before 32 completed weeks of gestation. We explored different pathways including medically indicated preterm birth defined as induction of labor with intact membranes and no prior labor contractions, PPROM defined as rupture of membranes, and spontaneous labor contractions defined as contractions with intact membranes resulting in labor. RESULTS: We found that women with endometriosis had an increased risk of preterm birth before 37 gestational weeks overall (adjusted hazard rate [aHR] 1.6, 95% confidence interval [CI] 1.3-1.9) and very preterm birth before 32 gestational weeks (aHR 1.8, 95% CI 1.1-2.9) compared with women without endometriosis. Medically indicated preterm birth was more prominent in women with endometriosis in deliveries before 37 gestational weeks (aHR 2.4, 95% CI 1.8-3.2) whereas spontaneous labor contractions were more common before 32 gestational weeks (aHR 2.2, 95% CI 1.1-4.5) in women with endometriosis compared with women without endometriosis. Further, in the analyses restricted to women with a histologically verified diagnosis of endometriosis, the results were strengthened overall and showed that women with endometriosis had an increased risk of PPROM before 32 gestational weeks (aHR 3.49, 95% CI1.36-8.98). CONCLUSIONS: Endometriosis was associated with both preterm and very preterm birth; however, apparently through different pathways. Women with endometriosis were more prone to have medically indicated preterm births before 37 gestational weeks and spontaneous preterm births before 32 gestational weeks compared with women without endometriosis.

Endometriosis and Risk of Adverse Pregnancy Outcome: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis summarizes the evidence for the association between endometriosis and adverse pregnancy outcome, including gestational hypertension, pre-eclampsia, low birth weight, and small for gestational age, preterm birth, placenta previa, placental abruption, cesarean section, stillbirth, postpartum hemorrhage, spontaneous hemoperitoneum in pregnancy, and spontaneous bowel perforation in pregnancy. METHODS: We performed the literature review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), by searches in PubMed and EMBASE, until 1 November 2020 (PROSPERO ID CRD42020213999). We included peer-reviewed observational cohort studies and case-control studies and scored them according to the Newcastle-Ottawa Scale, to assess the risk of bias and confounding. RESULTS: 39 studies were included. Women with endometriosis had an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth, compared to women without endometriosis. These results remained unchanged in sub-analyses, including studies on spontaneous pregnancies only. Spontaneous hemoperitoneum in pregnancy and bowel perforation seemed to be associated with endometriosis; however, the studies were few and did not meet the inclusion criteria. CONCLUSIONS: The literature shows that endometriosis is associated with an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth.