title: Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study.
abstract: BACKGROUND
  The emergence of Zika virus in the Americas has coincided with increased reports of babies born with microcephaly. On Feb 1, 2016, WHO declared the suspected link between Zika virus and microcephaly to be a Public Health Emergency of International Concern. This association, however, has not been precisely quantified.
  
  
  METHODS
  We retrospectively analysed data from a Zika virus outbreak in French Polynesia, which was the largest documented outbreak before that in the Americas. We used serological and surveillance data to estimate the probability of infection with Zika virus for each week of the epidemic and searched medical records to identify all cases of microcephaly from September, 2013, to July, 2015. Simple models were used to assess periods of risk in pregnancy when Zika virus might increase the risk of microcephaly and estimate the associated risk.
  
  
  RESULTS
  The Zika virus outbreak began in October, 2013, and ended in April, 2014, and 66% (95% CI 62-70) of the general population were infected. Of the eight microcephaly cases identified during the 23-month study period, seven (88%) occurred in the 4-month period March 1 to July 10, 2014. The timing of these cases was best explained by a period of risk in the first trimester of pregnancy. In this model, the baseline prevalence of microcephaly was two cases (95% CI 0-8) per 10,000 neonates, and the risk of microcephaly associated with Zika virus infection was 95 cases (34-191) per 10,000 women infected in the first trimester. We could not rule out an increased risk of microcephaly from infection in other trimesters, but models that excluded the first trimester were not supported by the data.
  
  
  CONCLUSIONS
  Our findings provide a quantitative estimate of the risk of microcephaly in fetuses and neonates whose mothers are infected with Zika virus.
  
  
  BACKGROUND
  Labex-IBEID, NIH-MIDAS, AXA Research fund, EU-PREDEMICS.
authors.affiliation: Mathematical Modelling of Infectious Diseases, Institut Pasteur, Paris, France. Electronic address: simon.cauchemez@pasteur.fr.
authors.forename: Simon
authors.initials: S
authors.lastname: Cauchemez
authors.affiliation: Neonatal Care Department, French Polynesia Hospital Centre, Pirae, Tahiti, French Polynesia.
authors.forename: Marianne
authors.initials: M
authors.lastname: Besnard
authors.affiliation: Bureau de Veille Sanitaire, Direction de la Santé, Papeete, Tahiti, French Polynesia.
authors.forename: Priscillia
authors.initials: P
authors.lastname: Bompard
authors.affiliation: Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.
authors.forename: Timothée
authors.initials: T
authors.lastname: Dub
authors.affiliation: Medical Imaging Department, French Polynesia Hospital Centre, Pirae, Tahiti, French Polynesia.
authors.forename: Prisca
authors.initials: P
authors.lastname: Guillemette-Artur
authors.affiliation: Gynecology-Obstetrics Department, French Polynesia Hospital Centre, Pirae, Tahiti, French Polynesia.
authors.forename: Dominique
authors.initials: D
authors.lastname: Eyrolle-Guignot
authors.affiliation: Mathematical Modelling of Infectious Diseases, Institut Pasteur, Paris, France; Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Henrik
authors.initials: H
authors.lastname: Salje
authors.affiliation: Centre for Global Health, Institut Pasteur, Paris, France.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Van Kerkhove
authors.affiliation: General Paediatrics Department, Necker Hospital, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Abadie
authors.affiliation: Department of Paediatric Radiology, Hôpital d'Enfants Armand-Trousseau, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Garel
authors.affiliation: Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France; Centre for Global Health, Institut Pasteur, Paris, France; Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fontanet
authors.affiliation: Bureau de Veille Sanitaire, Direction de la Santé, Papeete, Tahiti, French Polynesia.
authors.forename: Henri-Pierre
authors.initials: HP
authors.lastname: Mallet
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008831:Microcephaly / Q000453:epidemiology*; D011114:Polynesia / Q000453:epidemiology; D011247:Pregnancy; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult; D000071244:Zika Virus; D000071243:Zika Virus Infection / Q000453:epidemiology*