Neurodevelopment outcomes in infants born to women with Zika virus infection during pregnancy in Mexico

Abstract

Background Few studies have assessed neurodevelopmental outcomes in normocephalic infants born to women with Zika virus (ZIKV) infection during pregnancy in Mexico. We sought to evaluate ZIKV exposed infants in Yucatan, Mexico, with performance‐based and eye‐gaze measures of neurodevelopment, removing observer bias. Methods We enrolled 60 infants about 6‐month old born to women with PCR + test for ZIKV during pregnancy. Infants were normocephalic and asymptomatic. Sixty infants born to women without a history of ZIKV infection were included as comparison. Children were assessed with the Mullen scales of early learning (MSEL), a test with scales in motor, language, and overall cognitive skills development, and the Fagan test of infant intelligence (FTII) using automated eye‐tracking instrumentation to evaluate infant visual preference of human faces, where longer gaze lengths to unfamiliar (i.e., new) faces are expected. Results All MSEL subscale scores, except expressive language, were significantly lower among ZIKV exposed children compared to controls, including the overall standard composite (80 ± 10 vs. 87 ± 7.4, respectively; p < 0.001). FTII eye‐tracking measures of fixation and gaze length were in the expected direction, with longer times recorded among infants in the control group (i.e., higher attention), but none reached statistical significance. In adjusted linear regressions, the FTII high novelty score (expected preference for a novel face) predicted fine motor (β = 3.61, p = 0.04) and receptive language (β = 2.55, p = 0.03) scores. Conclusions Nonmicrocephalic children born to women with ZIKV during pregnancy in Mexico merit early neurodevelopmental evaluation to allow for appropriate interventions and clinical follow‐up. It is possible that long‐term monitoring of cognitive deficits may need to be established for a proportion of affected cases.

Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project Vigilancia de Embarazadas con Zika (VEZ), Colombia, 2016–2018

“…However, there is inconsistency in the literature around the potential neurodevelopmental impacts of Zika virus infection in pregnancy among children without Zika-associated brain and eye defects. There is evidence of neurodevelopmental delay based on standardized assessments of cohorts of children in Brazil [22,[39][40][41], Colombia [11], Nicaragua [42], Mexico [43], and French Guiana [23] but in another Brazilian cohort, there was no evidence of cognitive, language or motor delay in 18-month-old children exposed to the Zika virus during pregnancy without Zika-associated birth defects [44].…”

Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects

“…However, one study found altered general movements at 9–20 weeks in 16% of the group exposed to the ZIKV without CZS; abnormal BSID-III in 18% at 12 months; 5% with a score below 70 in at least one domain ( Einspieler et al, 2019 ). In one recent study, ZIKV exposed children showed somewhat lower scores on each subscale of Mullen Scales of Early Learning, except expressive language, but no statistical differences was observed in Fagan test of infant intelligence using eye-tracking measures of fixation and gaze ( Familiar et al, 2021 ).…”

“…A major concern following the in utero ZIKV exposure is whether the infants born without obvious structural brain abnormalities and/or microcephaly have impairment in development. Only a few studies compared the outcomes of the normocephalic ZIKV-exposed children with those of a neurotypical control group, or with children without ZIKV infection ( Supplementary Table S3 ) ( Cardoso et al, 2019 ; Einspieler et al, 2019 ; Valdes et al, 2019 ; Gerzson et al, 2020 ; Sobral da Silva et al, 2020 ; Familiar et al, 2021 ; Grant et al, 2021 ). Six studies did not find differences between prenatal ZIKV exposure without microcephaly and the unexposed controls ( Cardoso et al, 2019 ; Einspieler et al, 2019 ; Valdes et al, 2019 ; Gerzson et al, 2020 ; Sobral da Silva et al, 2020 ; Grant et al, 2021 ).…”

Acute neurologic emerging flaviviruses

“…A study of children with intrauterine Zika infection who were normocephalic at birth performed worse in several neurodevelopmental domains than those without intrauterine infection at 6-month follow-up, in addition to having shorter attention spans and longer processing times of visual stimuli. 125 Data from the Dominican Republic outbreak found that children of women who had been infected during pregnancy developed post-natal developmental abnormalities, including post-natal microcephaly, hypotonia, hypertonia, hearing issues, and transient developmental delay. 105 A 18-month longitudinal study of Columbian mothers with ZIKV during pregnancy and their infants found that newborns without CZS showed declines over time in neurodevelopmental outcomes using two validated assessments of infant development.…”