TOPLINE:

Endometriosis in mothers is associated with a 16% increased risk for congenital anomalies in their infants, with 2120 cases among 33,619 births to patients with endometriosis compared with 77,094 cases among 1,426,835 births to patients without endometriosis. In vitro fertilization (IVF) or intracytoplasmic sperm injection mediates only 11% of this risk, suggesting endometriosis itself is an independent risk factor.

METHODOLOGY:

• Researchers conducted a population-based cohort study using Ontario administrative health records from April 7, 2006, to March 31, 2021, including all live births at ≥ 20 weeks’ gestation to patients aged 15 to 50 years in Ontario, Canada.
• A total of 1,460,564 eligible births were analyzed, including 33,619 (2.3%) infants born to patients with endometriosis and 1,426,835 (97.7%) born to patients without endometriosis.
• Endometriosis was defined using a validated algorithm requiring two or more medical consultations with International Statistical Classification of Diseases and Related Health Problems, 9th Revision (ICD-9) code 617 or hospital admission with ICD-9 code 617 or ICD-10 code N80 before the index pregnancy.
• Congenital anomalies were classified using ICD-10 codes (Q00-Q99) based on the Metropolitan Atlanta Congenital Defects Program algorithm and categorized as any congenital anomaly, organ system anomaly, or specific anomalies.
• Modified Poisson regression models with robust error variance were used to derive relative risks (RRs), adjusting for maternal age at delivery, income quintile, chronic diabetes, chronic hypertension, smoking, alcohol use, substance use, parity, obesity, and comorbidity score.

TAKEAWAY:

• Endometriosis in patients was independently associated with a higher risk for any congenital anomaly (adjusted RR, 1.16; 95% CI, 1.12-1.21; P value not reported).
• Specific anomalies with the highest associated risks included unspecified cleft palate (adjusted RR, 1.52; 95% CI, 1.03-2.25), hypospadias (adjusted RR, 1.47; 95% CI, 1.04-2.09), and pulmonary artery stenosis (adjusted RR, 1.41; 95% CI, 1.03-1.94).
• Endometriosis was associated with increased risk for cardiovascular anomalies (adjusted RR, 1.23; 95% CI, 1.12-1.35), gastrointestinal anomalies (adjusted RR, 1.13; 95% CI, 1.04-1.23), genital anomalies (adjusted RR, 1.27; 95% CI, 1.11-1.45), and musculoskeletal anomalies (adjusted RR, 1.17; 95% CI, 1.05-1.31).
• IVF or intracytoplasmic sperm injection mediated only 11.0% of the association between endometriosis and any congenital anomaly, while subfertility, ovulation induction, and intrauterine insemination did not mediate the association, according to the authors.

IN PRACTICE:

“Endometriosis in the patient is associated with small but significantly increased risks of congenital anomalies among offspring, partially mediated by fertility treatment. The potential mechanisms remain to be identified,” the authors of the study wrote.

SOURCE:

The study was led by Bailey Milne, MPH, Queen’s University in Kingston, Ontario. It was published online on May 11 in CMAJ.

LIMITATIONS:

The prevalence of endometriosis in this cohort was 2.3%, lower than the expected 10% in reproductive-aged women, possibly due to higher infertility rates and the cohort being limited to deliveries. Although the positive predictive value for endometriosis coding was relatively high at 75%, the low prevalence means modest false-positive fractions could result in meaningful misclassification, biasing the estimated association toward the null. The validation of outcome diagnosis codes showed a sensitivity of 87.8% and positive predictive value of 78.3%, meaning some defects would be missed and other conditions falsely classified, likely attenuating results toward the null. The study was limited by unavailable variables in administrative data, including stage of endometriosis and number of IVF cycles, which may be important for parameterization, creating potential for unmeasured confounding. Additionally, the study did not assess the mediating role of pain management on risk for congenital anomalies, despite patients with endometriosis being more likely to use opioid analgesics (adjusted odds ratio, 2.76; 95% CI, 3.57-4.06).

DISCLOSURES:

This study received support from grant MFM-146444 from the Canadian Institutes of Health Research Institute of Human Development, Child and Youth Health, Clinician-Investigator Teams in Obstetrics and Maternal-Fetal Medicine. Milne received funding through the Queen’s University Dean’s Doctoral Award. ICES provided support through an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. Milne disclosed receiving a stipend from Queen’s University and travel support from Empowering Next-Generation Researchers in Perinatal and Child Health and Queen’s University. Milne serves as a board member of the Winchester District Memorial Hospital. No other competing interests were declared.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.