title: Risk factors for congenital hydrocephalus: a nationwide, register-based, cohort study.
abstract: OBJECTIVE
  To investigate the associations between isolated congenital hydrocephalus (CHC) and maternal characteristics, maternal medical diseases, and medicine intake during pregnancy as well as birth characteristics of the child in a retrospective, register-based, nationwide cohort study. Furthermore, to identify the risk factors unique for isolated CHC as compared to syndromic CHC.
  
  
  METHODS
  We established a cohort of all children born in Denmark between 1978 and 2008. Information on CHC and maternal medical diseases were obtained from the National Patient Discharge Register, maternal intake of medicine during pregnancy from the National Prescription Drug Register, and birth characteristics of the child from the Danish National Birth Register. Rate ratios (RR) of isolated and syndromic CHC with 95% CI were estimated using log-linear Poisson regression.
  
  
  RESULTS
  In a cohort of 1928666 live-born children, we observed 1193 cases of isolated CHC (0.062/1000) born children. First-borns had an increased risk of isolated CHC compared to later-borns (1.32 95% CI 1.17 to 1.49) (0.72/1000 born children). First trimester exposure to maternal use of antidepressants was associated with a significantly increased risk of isolated CHC compared to unexposed children (RR 2.52, 95% CI 1.47 to 4.29) (1.5/1000 born children). Risk factors also found for syndromic CHC were: Male gender, multiples and maternal diabetes.
  
  
  CONCLUSIONS
  The higher risk for isolated CHC in first-born children as well as behavioural aspects and comorbidities associated with maternal use of antidepressants, should be the targets for future research. Potential biological pathways by which antidepressants may cause hydrocephalus remain to be elucidated.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark Department of Neurosurgery, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Tina Noergaard
authors.initials: TN
authors.lastname: Munch
authors.affiliation: Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: Marie-Louise Hee
authors.initials: ML
authors.lastname: Rasmussen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Wohlfahrt
authors.affiliation: Department of Neurosurgery, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Juhler
authors.affiliation: Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects; D001722:Birth Order; D001724:Birth Weight; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005865:Gestational Age; D006801:Humans; D006849:Hydrocephalus / Q000209:etiology*; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology; D011264:Pregnancy Trimesters / Q000187:drug effects; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology; D012042:Registries; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000928:Antidepressive Agents
keywords: CSF; NEUROEPIDEMIOLOGY; NEUROSURGERY; PAEDIATRIC NEUROSURGERY