title: Fertility Treatment and Childhood Epilepsy: A Nationwide Cohort Study.
abstract: Fertility treatment includes hormonal stimulation of the woman and in vitro manipulation of gametes and embryos that may influence prenatal brain development. We aimed to investigate the association between fertility treatment and childhood epilepsy, including specific types of treatment and indications, as well as subtypes of epilepsy.
  
  
  
  In this nationwide birth cohort study, we included all pregnancies in Denmark resulting in live-born singletons, 1995-2003. Children conceived by fertility treatment and children developing epilepsy (until 2013) were identified from Danish national registers.
  
  
  
  A total of 565,116 pregnancies were included; 8,071 children (1.4%) developed epilepsy. Children conceived after ovulation induction or intrauterine insemination had a slightly higher risk of childhood epilepsy (hazard ratio [HR]: 1.15; 95% confidence interval [CI]: 1.00, 1.31). The association was more pronounced for the subtypes idiopathic generalized and focal epilepsy. Regarding the specific hormonal treatments, only clomiphene citrate was associated with an increased risk of childhood epilepsy, also in a sibling analysis (HR: 2.07; 95% CI: 1.05, 4.08). In vitro fertilization or intracytoplasmic sperm injection was not associated with an overall increased risk of childhood epilepsy but with idiopathic generalized epilepsy (HR: 1.43; 95% CI: 0.99, 2.05). No clear associations were seen regarding other treatment types or indications.
  
  
  
  Children conceived by ovulation induction or intrauterine insemination with clomiphene citrate may be at slightly increased risk of childhood epilepsy. Furthermore, children conceived by in vitro fertilization or intracytoplasmic sperm injection may be at slightly increased risk of idiopathic generalized epilepsy.
authors.affiliation: From the aPerinatal Epidemiology Research Unit and Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark; bThe Fertility Clinic, Department of Obstetrics and Gynecology, Herlev University Hospital, Herlev, Denmark; cDepartment of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark; dThe Fertility Clinic, Department of Obstetrics and Gynecology, Aarhus University, Regions Hospital Horsens, Denmark; and eDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA.
authors.forename: Laura Ozer
authors.initials: LO
authors.lastname: Kettner
authors.forename: Ulrik Schiøler
authors.initials: US
authors.lastname: Kesmodel
authors.forename: Cecilia Høst
authors.initials: CH
authors.lastname: Ramlau-Hansen
authors.forename: Bjørn
authors.initials: B
authors.lastname: Bay
authors.forename: Beate
authors.initials: B
authors.lastname: Ritz
authors.forename: Niels Bjerregaard
authors.initials: NB
authors.lastname: Matthiesen
authors.forename: Tine Brink
authors.initials: TB
authors.lastname: Henriksen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002996:Clomiphene / Q000627:therapeutic use; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004827:Epilepsy / Q000453:epidemiology*; D005260:Female; D005307:Fertilization in Vitro / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007246:Infertility / Q000628:therapy*; D007315:Insemination, Artificial / Q000706:statistics & numerical data; D008297:Male; D010062:Ovulation Induction / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D012042:Registries; D027724:Reproductive Techniques, Assisted / Q000706:statistics & numerical data*; D020554:Sperm Injections, Intracytoplasmic / Q000706:statistics & numerical data
chemical_list: D002996:Clomiphene