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Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of ZIKA Virus Infection in Gestation (NATZIG) cohort study
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  • Conrado Coutinho,
  • Silvia Fabiana Negrini,
  • Daniel Araujo,
  • Sara Teixeira,
  • Fabiana Amaral,
  • Marília Carolina Moro,
  • Juliana Fernandes,
  • Márcia Motta,
  • Bento Negrini,
  • Carla Andréa Caldas,
  • Adriana Anastasio,
  • João Marcello Furtado,
  • Adriana Aparecida Bárbaro,
  • Aparecida Yamamoto,
  • Geraldo Duarte,
  • Marisa Márcia Mussi-Pinhata
Conrado Coutinho
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Silvia Fabiana Negrini
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Daniel Araujo
Secretary of Health, Ribeirão Preto
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Sara Teixeira
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Fabiana Amaral
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Marília Carolina Moro
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Juliana Fernandes
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Márcia Motta
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Bento Negrini
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Carla Andréa Caldas
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Adriana Anastasio
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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João Marcello Furtado
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Adriana Aparecida Bárbaro
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Aparecida Yamamoto
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Geraldo Duarte
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Marisa Márcia Mussi-Pinhata
Universidade de Sao Paulo Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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Abstract

Objective: To define the prevalence of adverse outcomes according to the gestational age of maternal infection in a large cohort of ZIKV-infected Brazilian women and their infants. Design: Prospective, population-based cohort study. Setting: Ribeirão Preto’s region private and public health facilities. Population: All pregnant women with confirmed ZIKV-infection and their infants. Methods: Prenatal/early neonatal data were obtained for all pairs. A subgroup of infants had cranial ultrasonography, eye fundoscopy, hearing, neurological exam, and Bayley III screening test within 3 months of age. Main Outcome Measures: Prevalence of pregnancy losses, anomalies detected at birth or within 3 months according to the gestational age of infection. Results: 511 women with ZIKV were identified from a total of 1116 women with flavivirus-type symptoms. Pregnancy losses 24/511(4.7%) and/or ZIKV-related anomalies occurred in 43/511(8.4%) mothers. Microcephaly or other CNS malformations were diagnosed in 1/4(25.0%) of the stillbirths and 19/489[3.9%;CI95%:2.5-5.9] of the live-born infants, with 13/513[2.5%;CI95%:1.5-4.3] neonates presenting major signs of CZS. Fetal abnormalities were 14.0(CI95%:7.6-26.0) times more likely with gestational infection <11 weeks. Among 280 asymptomatic evaluated infants, 2/155(1.3%) had eye abnormalities, 1/207(0.5%) CNS imaging significant findings, and 16/199(8%) neurological alert signs. Conclusions: This prospective, population-based study represents the largest Brazilian cohort of ZIKV in pregnancy. Congenital anomalies potentially associated with CZS are less frequent than previously thought. There is a strong relationship between the gestational age of infection (<11 weeks) and worse early infant prognosis. A notable proportion of apparently asymptomatic newborns can present with subclinical findings within 3 months of age. Funding: FAEPA/SES-SP

Peer review status:Published

30 May 2020Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
01 Jun 2020Submission Checks Completed
01 Jun 2020Assigned to Editor
10 Jun 2020Reviewer(s) Assigned
29 Jun 2020Review(s) Completed, Editorial Evaluation Pending
14 Jul 2020Editorial Decision: Revise Major
09 Aug 20201st Revision Received
11 Aug 2020Submission Checks Completed
11 Aug 2020Assigned to Editor
13 Aug 2020Review(s) Completed, Editorial Evaluation Pending
03 Sep 2020Editorial Decision: Accept
13 Sep 2020Published in BJOG: An International Journal of Obstetrics & Gynaecology. 10.1111/1471-0528.16490