Hyperemesis gravidarum and maternal cancer risk, a Scandinavian nested case-control study

Reproductive factors have been shown to influence cancer risk. Several pathological conditions during pregnancy have also been associated with subsequent altered cancer risk in the mother. Hyperemesis gravidarum (hyperemesis) is an early pregnancy condition characterized by severe nausea and vomiting resulting in weight loss and metabolic disturbances. Studies have reported associations between hyperemesis and cancer, but results are inconsistent. In this nested case-control study we linked the population-based medical birth registries and cancer registries in Norway, Sweden and Denmark in order to examine overall cancer risk and risk of specific cancer types in women with a history of hyperemesis, using conditional logistic regression. In total, 168,501 cases of cancer in addition to up to 10 cancer-free controls per case were randomly sampled, matched on year of birth and birth registry (n = 1,721,626). Hyperemesis was defined through the International Classification of Diseases. Analyses were adjusted for potential confounders. Hyperemesis was inversely associated with overall cancer risk with adjusted relative risk (aRR) of 0.93 (95% CI: 0.88-0.99), with cancer in the lungs (aRR: 0.60, 95% CI: 0.44-0.81), cervix (aRR: 0.66, 95% CI: 0.49-0.91) and rectum (aRR: 0.48, 95% CI: 0.29-0.78). Thyroid cancer was positively associated with hyperemesis (aRR 1.45, 95% CI: 1.06-1.99) and risk increased with more than one hyperemetic pregnancy (aRR 1.80, 95% CI: 1.23-2.63). Hormonal factors, in particular human chorionic gonadotropin, are likely to be involved in mediating these effects. This study is the first to systematically address these associations and provides valuable knowledge on potential long-term consequences of hyperemesis.