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Abstract Background In utero exposure to Zika virus (ZIKV) is known to be associated with birth defects. The impact of in utero ZIKV exposure on neurodevelopmental outcomes in early childhood remains unclear. The objective of this study was to determine the impact of in utero ZIKV exposure on neurodevelopment at 24 months of age among toddlers who were born normocephalic to women who were pregnant during the 2016 ZIKV outbreak in French territories in the Americas. Methods We conducted a population-based mother-child cohort study of women whose pregnancies overlapped with the 2016 ZIKV epidemic in Guadeloupe, Martinique, and French Guiana. Infants were included in this analysis if maternal ZIKV infection during pregnancy could be determined, the newborn had a gestational age ≥ 35 weeks, there were no abnormal transfontanelle cerebral ultrasound findings after delivery or no abnormal ultrasound findings on the last ultrasound performed during the third trimester of the mother’s pregnancy, there was an absence of microcephaly at birth, and the parent completed the 24-month neurodevelopment assessment of the infant at 24 months (± 1 month) of age. ZIKV exposure of the toddler was determined by evidence of maternal ZIKV infection during pregnancy. Neurodevelopment assessments included the Ages and Stages Questionnaire (ASQ) for five dimensions of general development—communication, gross motor, fine motor, problem solving, and personal-social skills; the Modified Checklist for Autism on Toddlers (M-CHAT) for behavior; and the French MacArthur Inventory Scales (IFDC) for French language acquisition. Results Between June 2018 and August 2019, 156 toddlers with and 79 toddlers without in utero ZIKV exposure completed neurodevelopment assessments. Twenty-four (15.4%) ZIKV-exposed toddlers and 20 (25.3%) ZIKV-unexposed toddlers had an ASQ result below the reference − 2SD cut-off (P = 0.10) for at least one of the five ASQ dimensions. Conclusion In one of the largest population-based cohorts of in utero ZIKV-exposed, normocephalic newborns to date, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age compared to ZIKV-unexposed toddlers at 24 months of age. Trial registration ClinicalTrials.gov, NCT02810210 . Registered 20 June 2016.

We aimed to describe adverse pregnancy outcomes among women who had symptomatic, RT-PCR-confirmed ZIKV infection and early childhood outcomes among their infants. We enrolled pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection in a prospective cohort study, and their infants in a prospective pediatric cohort study. We defined adverse pregnancy and early childhood outcomes based on selected neurologic, ophthalmologic, auditory, musculoskeletal, and anthropometric abnormalities. We used RT-PCR and serologic tests to determine the ZIKV infection status of the child. Between 10 March and 24 November 2016, we enrolled 546 pregnant women with RT-PCR-confirmed ZIKV infection. The overall risk of adverse pregnancy and early childhood outcomes possibly related to in utero ZIKV exposure was 15.7% (95% CI: 12.8–19.0), distributed as follows: 3.6% (95% CI: 2.3–5.6) severe sequelae or fatality; 2.7% (95% CI: 1.6–4.5) major abnormalities; 9.4% (95% CI:7.1–12.2) mild abnormalities. The risk of severe sequelae or fatality was higher when ZIKV infection occurred during the first trimester (7.0%), compared to the second (2.7%) or third trimester (1.4%) (p = 0.02). Among the infants for whom ZIKV infection status could be determined, the vertical transmission rate was 3.0% (5/167) (95% CI: 1.1–7.2). Among pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection, severe or major pregnancy or early childhood outcomes were present in 6.3% of fetuses and infants. Severe outcomes occurred more frequently in fetuses and infants whose mothers had been infected in the first trimester.