Hyperemesis Gravidarum and the Potential for Cancer: A Longitudinal Cohort Study over Three Decades.

Background: Our objective was to assess whether hyperemesis gravidarum is associated with the risk of endodermal, mesodermal, and ectodermal human chorionic gonadotropin (hCG) receptor+ cancer in women.

Methods: We performed a longitudinal cohort study of 1,343,040 women who were pregnant between 1989 and 2019 in Quebec, Canada. We identified women with and without hyperemesis gravidarum and followed them over time to capture incident cancers, grouped by embryonic germ cell layer of origin and organ hCG receptor positivity. We used time-varying Cox regression to model hazard ratios (HR) and 95% confidence intervals (CI) for the association between hyperemesis gravidarum and cancer onset, adjusted for maternal age, comorbidity, multiple gestation, fetal congenital anomaly, socioeconomic deprivation, and time period.

Results: Women with hyperemesis gravidarum had a greater risk of endodermal cancer compared with no hyperemesis gravidarum (5.8 vs. 4.8 per 10,000 person-years; HR, 1.36; 95% CI, 1.17-1.57), but not mesodermal or ectodermal cancer. Severe hyperemesis with metabolic disturbance was more strongly associated with cancer from the endodermal germ layer (HR, 1.97; 95% CI, 1.51-2.58). The association between hyperemesis gravidarum and endodermal cancer was driven by bladder (HR, 2.49; 95% CI, 1.37-4.53), colorectal (HR, 1.41; 95% CI, 1.08-1.84), and thyroid (HR, 1.43; 95% CI, 1.09-1.64) cancer.

Conclusions: Women with hyperemesis gravidarum have an increased risk of cancers arising from the endodermal germ cell layer, particularly bladder, colorectal, and thyroid cancers.

Impact: Future studies identifying the pathways linking hyperemesis gravidarum with endodermal tumors may help improve the detection and management of cancer in women.