In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study

Rebecca Grant, Olivier Fléchelles, Benoît Tressières, Mama Dialo, Narcisse Elenga, Nicolas Mediamolle, Adeline Mallard, Jean-Christophe Hebert, Noémie Lachaume, Elvire Couchy, Bruno Hoen, Arnaud Fontanet, Rebecca Grant, Olivier Fléchelles, Benoît Tressières, Mama Dialo, Narcisse Elenga, Nicolas Mediamolle, Adeline Mallard, Jean-Christophe Hebert, Noémie Lachaume, Elvire Couchy, Bruno Hoen, Arnaud Fontanet

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.

Keywords: Emerging infectious diseases; Epidemiology; Neurodevelopment; Pediatrics; Zika virus.

Conflict of interest statement

The authors declare that they have no financial or non-financial competing interests.

Figures

Fig. 1
Fig. 1
Toddlers from the ZIKA-DFA-BB prospective cohort study in Guadeloupe, Martinique, and French Guiana included in the analysis

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