title: Systematic review and meta-analyses: fever in pregnancy and health impacts in the offspring.
abstract: OBJECTIVE
  Fever during pregnancy has been suspected to harm the developing fetus. However, until now, no systematic analysis of the available evidence has been undertaken to assess the impact of maternal fever on health outcomes in the child. The goal of this study was to systematically review evidence from epidemiologic studies on adverse health outcomes of the offspring in relation to exposure to maternal fever during pregnancy.
  
  
  METHODS
  Systematic searches in PubMed, Web of Science, and the Cochrane Library were performed by using Medical Subject Headings, Boolean operators, and truncation, and references of references were reviewed. Cohort and case-control studies addressing health outcomes of prenatal fever exposure in humans were eligible for inclusion. Studies with no direct reference to fever, studies in selected populations (eg, preterm births), and studies published before 1990 were excluded.
  
  
  RESULTS
  The available literature supported an increased risk of adverse offspring health in association with fever during pregnancy. The strongest evidence was available for neural tube defects, congenital heart defects, and oral clefts, in which meta-analyses suggested between a 1.5- and nearly 3-fold increased risk with fever exposure in the first trimester. We did not find strong evidence of a dose-response relationship, but there was some evidence that antipyretic medications may have a protective effect when used in relation to febrile episodes.
  
  
  CONCLUSIONS
  We found substantial evidence to support the contention that maternal fever during pregnancy may negatively affect offspring health. The harmful effects seemed to cover both short- and longer-term health outcomes; however, for several outcomes, the evidence was insufficient to judge any association.
authors.affiliation: Institute of Public Health, University of Southern Denmark, Esbjerg, Denmark; and.
authors.forename: Julie Werenberg
authors.initials: JW
authors.lastname: Dreier
authors.forename: Anne-Marie Nybo
authors.initials: AM
authors.lastname: Andersen
authors.forename: Gabriele
authors.initials: G
authors.lastname: Berg-Beckhoff
mesh_terms: D016022:Case-Control Studies; D002971:Cleft Lip / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D005334:Fever / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology*; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D009436:Neural Tube Defects / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis* / Q000453:epidemiology*; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis* / Q000453:epidemiology*
keywords: congenital abnormalities; developmental disabilities; fetal origins of disease; fever; hypersensitivity; meta-analysis; mortality; pregnancy; pregnant women; review; stillbirth