Endocrine Abstracts

Background: Pregnancy loss affects approximately 25% of pregnancies, of which 40% have no detectable chromosome abnormalities and are suspected to be caused by maternal comorbidity. Pregnancy loss has been associated with specific endocrine disorders, e.g. autoimmune thyroid disease (AITD), polycystic ovarian syndrome (PCOS) or diabetes mellitus (DM). Because of the well-described overlap between these endocrine disorders, we hypothesized that pregnancy loss is associated with any endocrine disorder and that having more than one endocrine disorder constitutes a more severe phenotype with a higher risk of pregnancy loss.

Methods: Danish nationwide cohort based on the Danish Health Registries containing information on ICD-8/ICD-10-diagnoses, all redeemed medicine prescriptions, and pregnancy outcomes. We identified women born from 1977-1993 with ≥1 pregnancy. Cases had a diagnosis of a non-iatrogenic endocrine disorder and controls had none. Logistics regression models, with the number of pregnancy losses as the outcome, adjusted for birth year provided odds ratios for endocrine disorders. Results are given as odds ratio with 95% confidence interval.

Results: The cohort consisted of 366,548 women of which 54,394 (15%) had an endocrine disorder. There was a highly significant association between endocrine disorders and pregnancy loss increasing with the number of pregnancy losses; one loss 1.15 (1.12-1.17), two losses 1.31 (1.24-1.38) and three losses 1.81 (1.70-1.93), P<0.001. The risk of pregnancy loss was also increased by AITD (1.21, 1.17-1.25), PCOS (1.32, 1.26-1.38), DM1 (1.38, 1.25-1.53), and DM2 (1.22, 1.09-1.35), respectively, and increased further with a higher number of pregnancy losses. When these disorders were included simultaneously in the model, the increased risk associated with each individual condition persisted, suggesting that each disorder contributes distinctly to the pregnancy loss risk. Lastly, compared to individuals with no endocrine disorders, those with one disorder had a higher risk of pregnancy loss (1.23, 1.19-2.6). This risk was further amplified in individuals with two disorders (1.60, 1.44-1.78), indicating a progressive elevation in risk correlating with the number of comorbid endocrine conditions.

Conclusion: In this nationwide register-based cohort study, there was a highly significant association between endocrine disorders and pregnancy loss. This was especially the case with an increasing number of pregnancy losses, and in women having more than one endocrine disorder. The observed additive effects indicates that each endocrine condition independently elevates the risk of pregnancy loss. This underscores the critical need for personalized intervention strategies including monitoring of each endocrine disorder to reduce the cumulative risk of pregnancy loss.