title: Viral infections: contributions to late fetal death, stillbirth, and infant death.
abstract: OBJECTIVE
  To determine the role of viral infections in causing fetal and infant death.
  
  
  METHODS
  We assessed a well-validated population database of fetal (≥20 weeks gestation) and infant death for infective deaths and deaths from viruses over a 21-year period (1988-2008). We analyzed by specific viral cause, timing (late fetal loss [20-23 weeks], stillbirth [≥24 weeks], neonatal death [0-27 days], and post-neonatal infant death [28-364 days]) and across time.
  
  
  RESULTS
  Of the 989 total infective deaths, 108 were attributable to viral causes (6.5% of late fetal losses, 14.5% of stillbirths, 6.5% of neonatal deaths, and 19.4% of postneonatal infant deaths). Global loss (combined fetal and infant losses per 100,000 registerable births) was 139.6 (95% CI, 130.9-148.3) for any infective cause and 15.2 (95% CI, 12.3-18.1) for viral infections. More than one-third (37%) of viral-attributed deaths were before live birth, from parvovirus (63%) or cytomegalovirus (33%). Parvovirus accounted for 26% (28 of 108) of all viral deaths. Cytomegalovirus was associated with a global loss rate of 3.1 (95% CI, 1.8-4.4) and an infant mortality rate of 1.3 (95% CI, 0.4-2.1) per 100,000 live births; 91% of cases were congenital infections. Herpes simplex virus caused death only after live births (infant mortality rate, 1.4; 95% CI, 0.5-2.3). No changes in rates were seen over time.
  
  
  CONCLUSIONS
  We have identified a substantial contribution of viral infections to global fetal and infant losses. More than one-third of these losses occurred before live births. Considering our methodology, our estimates represent the minimum contribution of viral illness. Strategies to reduce this burden are needed.
authors.affiliation: Newcastle Neonatal Service, Royal Victoria Infirmary, Newcastle Upon Tyne Hospitals National Health Service Foundation Trust, Newcastle-Upon-Tyne, United Kingdom.
authors.forename: Eleri J
authors.initials: EJ
authors.lastname: Williams
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Embleton
authors.forename: Julia E
authors.initials: JE
authors.lastname: Clark
authors.forename: Mary
authors.initials: M
authors.lastname: Bythell
authors.forename: Martin P
authors.initials: MP
authors.lastname: Ward Platt
authors.forename: Janet E
authors.initials: JE
authors.lastname: Berrington
mesh_terms: D005313:Fetal Death / Q000453:epidemiology* / Q000821:virology*; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D012189:Retrospective Studies; D050497:Stillbirth / Q000453:epidemiology*; D014777:Virus Diseases / Q000401:mortality*
keywords: CMV; Congenital cytomegalovirus; Cytomegalovirus; HSV; Herpes simplex virus; IMR; Infant mortality rate; PMS; Perinatal Mortality Survey; TOP; Termination of pregnancy; cCMV