title: Hyperemesis gravidarum and risk of cancer in offspring, a Scandinavian registry-based nested case-control study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Genes and Environment, Norwegian Institute of Public Health, PO Box 4404, Nydalen, 0403, Oslo, Norway. kafv@fhi.no.|Norwegian National Advisory Unit on Women's Health, Oslo University Hospital, PO box 4950, Nydalen, Oslo, Norway. kafv@fhi.no.
authors.forename: Kathrine F
authors.initials: KF
authors.lastname: Vandraas
authors.affiliation: Department of Genes and Environment, Norwegian Institute of Public Health, PO Box 4404, Nydalen, 0403, Oslo, Norway. ase.vigdis.vikanes@fhi.no.|The Intervention Center, Oslo University Hospital, PO Box 4950, Nydalen, Oslo, Norway. ase.vigdis.vikanes@fhi.no.
authors.forename: Åse V
authors.initials: ÅV
authors.lastname: Vikanes
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. nathalcs@math.uio.no.
authors.forename: Nathalie C
authors.initials: NC
authors.lastname: Støer
authors.affiliation: Divisions of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 9000 Rockville Pike, Bethesda, MD, 20892, USA. troisir@mail.nih.gov.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Troisi
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital and Institute, SE-141 86, Stockholm, Sweden. olof.stephansson@ki.se.|Department of Women and Children's Health, Division of Obstetrics and Gynecology Karolinska University Hospital and Institute, SE-141 86, Stockholm, Sweden. olof.stephansson@ki.se.
authors.forename: Olof
authors.initials: O
authors.lastname: Stephansson
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, 44 Norrebrogade, 8000, Aarhus, Denmark. hts@clin.au.dk.
authors.forename: Henrik T
authors.initials: HT
authors.lastname: Sørensen
authors.affiliation: Norwegian National Advisory Unit on Women's Health, Oslo University Hospital, PO box 4950, Nydalen, Oslo, Norway. sirvan@ous-hf.no.
authors.forename: Siri
authors.initials: S
authors.lastname: Vangen
authors.affiliation: Department of Genes and Environment, Norwegian Institute of Public Health, PO Box 4404, Nydalen, 0403, Oslo, Norway. per.magnus@fhi.no.
authors.forename: Per
authors.initials: P
authors.lastname: Magnus
authors.affiliation: Department of International Public Health, Norwegian Institute of Public Health, PO Box 4404, Nydalen, 0403, Oslo, Norway. andrej.grjibovski@gmail.com.|International School of Public Health, Northern State Medical University, Troitsky av.51, Arkhangelsk, Russia, 163000. andrej.grjibovski@gmail.com.|Department of Preventive Medicine, International Kazakh-Turkish University, Esimkhan str.2, Turkestan, Kazakhstan. andrej.grjibovski@gmail.com.
authors.forename: Andrej M
authors.initials: AM
authors.lastname: Grjibovski
authors.affiliation: Cancer Registry of Norway, PO Box 5313, Majorstuen, N-0304, Oslo, Norway. tom.grotmol@kreftregisteret.no.
authors.forename: Tom
authors.initials: T
authors.lastname: Grotmol
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006939:Hyperemesis Gravidarum / Q000150:complications*; D007223:Infant; D007231:Infant, Newborn; D008223:Lymphoma / Q000209:etiology*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology*; D012307:Risk Factors; D055815:Young Adult