title: Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study.
abstract: BACKGROUND
  The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy.
  
  
  METHODS
  We did this case-control study in eight public hospitals in Recife, Brazil. Cases were neonates with microcephaly. Two controls (neonates without microcephaly), matched by expected date of delivery and area of residence, were selected for each case. Serum samples of cases and controls and cerebrospinal fluid samples of cases were tested for Zika virus-specific IgM and by quantitative RT-PCR. Laboratory-confirmed Zika virus infection during pregnancy was defined as detection of Zika virus-specific IgM or a positive RT-PCR result in neonates. Maternal serum samples were tested by plaque reduction neutralisation assay for Zika virus and dengue virus. We estimated crude odds ratios (ORs) and 95% CIs using a median unbiased estimator for binary data in an unconditional logistic regression model. We estimated ORs separately for cases with and without radiological evidence of brain abnormalities.
  
  
  RESULTS
  Between Jan 15, 2016, and May 2, 2016, we prospectively recruited 32 cases and 62 controls. 24 (80%) of 30 mothers of cases had Zika virus infection compared with 39 (64%) of 61 mothers of controls (p=0·12). 13 (41%) of 32 cases and none of 62 controls had laboratory-confirmed Zika virus infection; crude overall OR 55·5 (95% CI 8·6-∞); OR 113·3 (95% CI 14·5-∞) for seven cases with brain abnormalities; and OR 24·7 (95% CI 2·9-∞) for four cases without brain abnormalities.
  
  
  CONCLUSIONS
  Our data suggest that the microcephaly epidemic is a result of congenital Zika virus infection. We await further data from this ongoing study to assess other potential risk factors and to confirm the strength of association in a larger sample size.
  
  
  BACKGROUND
  Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations.
authors.affiliation: Department of Social Medicine, Federal University of Pernambuco, Recife, Brazil. Electronic address: thalia@ufpe.br.
authors.forename: Thalia Velho Barreto
authors.initials: TVB
authors.lastname: de Araújo
authors.affiliation: Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Laura Cunha
authors.initials: LC
authors.lastname: Rodrigues
authors.affiliation: Department of Tropical Medicine, Federal University of Pernambuco, Recife, Brazil; University of Pernambuco, Recife, Brazil.
authors.forename: Ricardo Arraes
authors.initials: RA
authors.lastname: de Alencar Ximenes
authors.affiliation: University of Pernambuco, Recife, Brazil.
authors.forename: Demócrito
authors.initials: D
authors.lastname: de Barros Miranda-Filho
authors.affiliation: University of Pernambuco, Recife, Brazil.
authors.forename: Ulisses Ramos
authors.initials: UR
authors.lastname: Montarroyos
authors.affiliation: Department of Community Health, Federal University of Pernambuco, Vitória de Santo Antão, Brazil.
authors.forename: Ana Paula Lopes
authors.initials: APL
authors.lastname: de Melo
authors.affiliation: Department of Social Medicine, Federal University of Pernambuco, Recife, Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Valongueiro
authors.affiliation: The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
authors.forename: Maria de Fátima Pessoa Militão
authors.initials: MFPM
authors.lastname: de Albuquerque
authors.affiliation: The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
authors.forename: Wayner Vieira
authors.initials: WV
authors.lastname: Souza
authors.affiliation: The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Braga
authors.affiliation: The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
authors.forename: Sinval Pinto Brandão
authors.initials: SPB
authors.lastname: Filho
authors.affiliation: The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
authors.forename: Marli Tenório
authors.initials: MT
authors.lastname: Cordeiro
authors.affiliation: Pan American Health Organization, Brasília, Brazil.
authors.forename: Enrique
authors.initials: E
authors.lastname: Vazquez
authors.affiliation: Instituto Materno Infantil Fernando Figueira, Recife, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Di Cavalcanti Souza Cruz
authors.affiliation: Fiocruz Brasília, Brasília, Brazil.
authors.forename: Cláudio Maierovitch Pessanha
authors.initials: CMP
authors.lastname: Henriques
authors.affiliation: Pernambuco State Health Department, Recife, Brazil.
authors.forename: Luciana Caroline Albuquerque
authors.initials: LCA
authors.lastname: Bezerra
authors.affiliation: The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
authors.forename: Priscila Mayrelle
authors.initials: PM
authors.lastname: da Silva Castanha
authors.affiliation: The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Dhalia
authors.affiliation: The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
authors.forename: Ernesto Torres Azevedo
authors.initials: ETA
authors.lastname: Marques-Júnior
authors.affiliation: The Research Center Aggeu Magalhães (CPqAM) and Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil; Department of Community Health, Federal University of Goiás, Goiânia, Brazil.
authors.forename: Celina Maria Turchi
authors.initials: CMT
authors.lastname: Martelli
mesh_terms: D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D008831:Microcephaly / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D059906:Neuroimaging; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D011446:Prospective Studies; D012307:Risk Factors; D000071244:Zika Virus / Q000302:isolation & purification*; D000071243:Zika Virus Infection / Q000151:congenital / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology