Neurodevelopmental Abnormalities in Children With In Utero Zika Virus Exposure Without Congenital Zika Syndrome

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.

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In utero Zika virus exposure and schizophrenia

The World Journal of Biological Psychiatry ◽

10.1080/15622975.2018.1533995 ◽

2019 ◽

Vol 21 (1) ◽

pp. 12-12 ◽

Cited By ~ 1

Author(s):

Beuy Joob ◽

Viroj Wiwanitkit

Keyword(s):

Zika Virus ◽

In Utero ◽

Virus Exposure

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Sequential Neuroimaging of the Fetus and Newborn With In Utero Zika Virus Exposure

JAMA Pediatrics ◽

10.1001/jamapediatrics.2018.4138 ◽

2019 ◽

Vol 173 (1) ◽

pp. 52 ◽

Cited By ~ 11

Author(s):

Sarah B. Mulkey ◽

Dorothy I. Bulas ◽

Gilbert Vezina ◽

Yamil Fourzali ◽

Armando Morales ◽

...

Keyword(s):

Zika Virus ◽

In Utero ◽

Virus Exposure

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Reply to ‘A critical analysis of neurodevelopmental and neurosensory outcomes after 2 years for children with in utero Zika virus exposure’

Nature Medicine ◽

10.1038/s41591-019-0631-z ◽

2019 ◽

Vol 25 (11) ◽

pp. 1642-1643

Author(s):

Karin Nielsen-Saines ◽

Patricia Brasil ◽

Tara Kerin ◽

Zilton Vasconcelos ◽

Claudia Raja Gabaglia ◽

...

Keyword(s):

Zika Virus ◽

Critical Analysis ◽

In Utero ◽

Virus Exposure

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Can in utero Zika virus exposure be a risk factor for schizophrenia in the offspring?

The World Journal of Biological Psychiatry ◽

10.1080/15622975.2018.1500027 ◽

2018 ◽

Vol 21 (1) ◽

pp. 2-11 ◽

Cited By ~ 1

Author(s):

Johnathan Pierson ◽

Rajashekar Reddy Yeruva ◽

Rif S. El-Mallakh

Keyword(s):

Risk Factor ◽

Zika Virus ◽

In Utero ◽

Virus Exposure

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Clinical Outcomes of a Zika Virus Mother–Child Pair Cohort in Spain

Pathogens ◽

10.3390/pathogens9050352 ◽

2020 ◽

Vol 9 (5) ◽

pp. 352 ◽

Cited By ~ 1

Author(s):

Antoni Soriano-Arandes ◽

Marie Antoinette Frick ◽

Milagros García López-Hortelano ◽

Elena Sulleiro ◽

Carlota Rodó ◽

...

Keyword(s):

Zika Virus ◽

Adverse Outcomes ◽

Zikv Infection ◽

Child Pair ◽

Referral Hospitals ◽

Congenital Zika Syndrome ◽

Endemic Areas ◽

Neurodevelopmental Abnormalities ◽

Congenital Microcephaly

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.

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A critical analysis of the neurodevelopmental and neurosensory outcomes after 2 years for children with in utero Zika virus exposure

Nature Medicine ◽

10.1038/s41591-019-0630-0 ◽

2019 ◽

Vol 25 (11) ◽

pp. 1641-1642 ◽

Cited By ~ 1

Author(s):

Manon Vouga ◽

Léo Pomar ◽

Alice Panchaud ◽

Didier Musso ◽

David Baud

Keyword(s):

Zika Virus ◽

Critical Analysis ◽

In Utero ◽

Virus Exposure

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1872. Neurodevelopment in Apparently Normal Infants from Zika Virus Positive Pregnancies

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz359.102 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S46-S47

Author(s):

Sarah B Mulkey ◽

Margarita Arroyave-Wessel ◽

Colleen Peyton ◽

Dorothy Bulas ◽

Gilbert Vezina ◽

...

Keyword(s):

Zika Virus ◽

Infant Development ◽

Brain Mri ◽

Fetal Brain ◽

In Utero ◽

Cranial Ultrasound ◽

Neurodevelopmental Delay ◽

Congenital Zika Syndrome ◽

Z Scores ◽

Us Findings

Abstract Background Congenital Zika syndrome (CZS) is seen in 5–12% of newborns from Zika virus (ZIKV)-infected pregnancies and includes severe neurologic abnormalities. However, the majority of ZIKV-exposed newborns do not have CZS. The risk for neurodevelopmental impairment for infants without CZS following in utero ZIKV is not well known. The objective was to determine whether infants without CZS exposed to ZIKV in utero, have normal neurodevelopment. Methods We performed a longitudinal study of neurodevelopment in Colombia for infants exposed to ZIKV in utero who had a normal fetal brain MRI (Mulkey et al, JAMA Peds 2019) and normal head circumference at birth. Infant development was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) and the Alberta Infant Motor Scale (AIMS) between 6 and 18 months of age. In-person training was done by a neurologist. The AIMS were video-recorded and scored centrally. Interrater reliability for the novel method of video-based AIMS was determined. WIDEA and AIMS scores were converted to Z-scores compared with normative samples. We also compared development between infants with normal and nonspecific findings on cranial ultrasound (US). Results Seventy-two non-CZS infants had neurodevelopmental tests; 40 were at a mean (SD) of 5.7 (0.9) months and 66 were at 13.5 (3.2) months of age. Thirty-four had two assessments. The total WIDEA, social cognition, and mobility domain scores became more abnormal with postnatal age (figure). The AIMS scores were similar to the normative sample. Three infants had an AIMS score < 2 SD’s below the norm. On cranial US, 19 infants (26%) had a nonspecific finding (lenticulostriate vasculopathy, choroid plexus cysts, subependymal cysts, and/or calcification). Infants with a US finding had a lower WIDEA mobility score than infants with normal US (P = .054). There was a trend toward lower AIMS scores in infants with US findings compared with infants with normal US (P = .26). AIMS Interrater agreement on video-based scoring was good (ICC = 0.73, 95% CI 0.42, 0.87). Conclusion ZIKV-exposed infants without CZS are at risk for neurodevelopmental delay. Nonspecific cranial US findings may represent mild ZIKV-related injury. Long-term neurodevelopmental follow-up is important for all ZIKV-exposed infants. Disclosures All Authors: No reported Disclosures.

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