Affiliation:
1. Department of Obstetrics and Gynecology, Ribeirão Preto Medical School University of São Paulo, Ribeirão Preto, SP, Brazil.
2. Department of Pediatrics, Ribeirão Preto Medical School University of São Paulo, Ribeirão Preto, SP, Brazil.
3. Epidemiology and Disease Control Division, Department of Public Health and Surveillance, Secretary of Health, Ribeirão Preto, SP, Brazil.
4. Department of Imaging, Hematology and Oncology, Ribeirão Preto Medical School University of São Paulo, Ribeirão Preto, SP, Brazil.
5. Rehabilitation Center of Clinics Hospital at the Ribeirão Preto School of Medicine, Ribeirão Preto, SP, Brazil.
6. Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, Brazil.
7. Division of Ophthalmology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Corresponding author: Conrado Milani Coutinho
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Campus Universitário s/no, CEP: 14048-900, Ribeirão Preto, SP, Brazil. Phone: +55 16 3602-2925. Fax: +55 16 3602-1549. Email: cmcoutinho@hotmail.com
Running title: Early maternal Zika infection and severe outcomes.
Word count of main text: 3435 words.
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
Keywords: ZIKA virus, pregnancy, infant, adverse outcomes, congenital Zika syndrome.