Hyperemesis gravidarum and risk of cancer in offspring, a Scandinavian registry-based nested case–control study

Kathrine F. Vandraas, Åse V. Vikanes, Nathalie C. Støer, Rebecca Troisi, Olof Stephansson, Henrik T. Sørensen, Siri Vangen, Per Magnus, Andrej M. Grjibovski, Tom Grotmol

Hyperemesis gravidarum is a serious condition affecting 0.8-2.3 % of pregnant women and can be regarded as a restricted period of famine. Research concerning potential long-term consequences of the condition for the offspring, is limited, but lack of nutrition in-utero has been associated with chronic disease in adulthood, including some cancers. There is growing evidence that several forms of cancer may originate during fetal life. We conducted a large study linking the high-quality population-based medical birth- and cancer registries in Norway, Sweden and Denmark, to explore whether hyperemesis is associated with increased cancer risk in offspring. A registry-based nested case-control study. Twelve types of childhood cancer were selected; leukemia, lymphoma, cancer of the central nervous system, testis, bone, ovary, breast, adrenal and thyroid gland, nephroblastoma, hepatoblastoma and retinoblastoma. Conditional logistic regression models were applied to study associations between hyperemesis and risk of childhood cancer, both all types combined and separately. Cancer types with five or more exposed cases were stratified by age at diagnosis. All analysis were adjusted for maternal age, ethnicity and smoking, in addition to the offspring's Apgar score, placental weight and birth weight. Relative risks with 95 % confidence intervals were calculated. In total 14,805 cases and approximately ten controls matched on time, country of birth, sex and year of birth per case (147,709) were identified. None of the cancer types, analyzed combined or separately, revealed significant association with hyperemesis. When stratified according to age at diagnosis, we observed a RR 2.13 for lymphoma among adolescents aged 11-20 years ((95 % CI 1.14-3.99), after adjustment for maternal ethnicity and maternal age, RR 2.08 (95 % CI 1.11-3.90)). The finding was not apparent when a stricter level of statistical significance was applied. The main finding of this paper is that hyperemesis does not seem to increase cancer risk in offspring. The positive association to lymphoma may be by chance and needs confirmation.