PMID- 31904798 OWN - NLM STAT- MEDLINE DCOM- 20201123 LR - 20220531 IS - 2168-6211 (Electronic) IS - 2168-6203 (Print) IS - 2168-6203 (Linking) VI - 174 IP - 3 DP - 2020 Mar 1 TI - Neurodevelopmental Abnormalities in Children With In Utero Zika Virus Exposure Without Congenital Zika Syndrome. PG - 269-276 LID - 10.1001/jamapediatrics.2019.5204 [doi] AB - IMPORTANCE: The number of children who were born to mothers with Zika virus (ZIKV) infection during pregnancy but who did not have apparent disability at birth is large, warranting the study of the risk for neurodevelopmental impairment in this population without congenital Zika syndrome (CZS). OBJECTIVE: To investigate whether infants without CZS but who were exposed to ZIKV in utero have normal neurodevelopmental outcomes until 18 months of age. DESIGN, SETTING, AND PARTICIPANTS: This cohort study prospectively enrolled a group of pregnant women with ZIKV in Atlantico Department, Colombia, and in Washington, DC. With this cohort, we performed a longitudinal study of infant neurodevelopment. Infants born between August 1, 2016, and November 30, 2017, were included if they were live born, had normal fetal brain findings on magnetic resonance imaging and ultrasonography, were normocephalic at birth, and had normal examination results without clinical evidence of CZS. Seventy-seven infants born in Colombia, but 0 infants born in the United States, met the inclusion criteria. EXPOSURES: Prenatal ZIKV exposure. MAIN OUTCOMES AND MEASURES: Infant development was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) and the Alberta Infant Motor Scale (AIMS) at 1 or 2 time points between 4 and 18 months of age. The WIDEA and AIMS scores were converted to z scores compared with normative samples. Longitudinal mixed-effects regression models based on bootstrap resampling methods estimated scores over time, accounting for gestational age at maternal ZIKV infection and infant age at assessment. Results were presented as slope coefficients with 2-tailed P values based on z statistics that tested whether the coefficient differed from 0 (no change). RESULTS: Of the 77 Colombian infants included in this cohort study, 70 (91%) had no CZS and underwent neurodevelopmental assessments. Forty infants (57%) were evaluated between 4 and 8 months of age at a median (interquartile range [IQR]) age of 5.9 (5.3-6.5) months, and 60 (86%) underwent assessment between 9 and 18 months of age at a median (IQR) age of 13.0 (11.2-16.4) months. The WIDEA total score (coefficients: age = -0.227 vs age2 = 0.006; P < .003) and self-care domain score (coefficients: age = -0.238 vs age2 = 0.01; P < .008) showed curvilinear associations with age. Other domain scores showed linear declines with increasing age based on coefficients for communication (-0.036; P = .001), social cognition (-0.10; P < .001), and mobility (-0.14; P < .001). The AIMS scores were similar to the normative sample over time (95% CI, -0.107 to 0.037; P = .34). Nineteen of 57 infants (33%) who underwent postnatal cranial ultrasonography had a nonspecific, mild finding. No difference was found in the decline of WIDEA z scores between infants with and those without cranial ultrasonography findings except for a complex interactive relationship involving the social cognition domain (P < .049). The AIMS z scores were lower in infants with nonspecific cranial ultrasonography findings (-0.49; P = .07). CONCLUSIONS AND RELEVANCE: This study found that infants with in utero ZIKV exposure without CZS appeared at risk for abnormal neurodevelopmental outcomes in the first 18 months of life. Long-term neurodevelopmental surveillance of all newborns with ZIKV exposure is recommended. FAU - Mulkey, Sarah B AU - Mulkey SB AD - Children's National Hospital, Washington, DC. AD - Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC. AD - Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Arroyave-Wessel, Margarita AU - Arroyave-Wessel M AD - Children's National Hospital, Washington, DC. FAU - Peyton, Colleen AU - Peyton C AD - Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, Illinois. FAU - Bulas, Dorothy I AU - Bulas DI AD - Children's National Hospital, Washington, DC. AD - Department of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Fourzali, Yamil AU - Fourzali Y AD - Sabbag Radiologos, Barranquilla, Colombia. FAU - Jiang, JiJi AU - Jiang J AD - Children's National Hospital, Washington, DC. FAU - Russo, Stephanie AU - Russo S AD - Children's National Hospital, Washington, DC. FAU - McCarter, Robert AU - McCarter R AD - Children's National Hospital, Washington, DC. FAU - Msall, Michael E AU - Msall ME AD - Kennedy Research Center on Neurodevelopmental Disabilities, University of Chicago Comer Children's Hospital, Chicago, Illinois. FAU - du Plessis, Adre J AU - du Plessis AJ AD - Children's National Hospital, Washington, DC. AD - Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC. AD - Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - DeBiasi, Roberta L AU - DeBiasi RL AD - Children's National Hospital, Washington, DC. AD - Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC. AD - Department of Tropical Medicine and Infectious Disease, The George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Cure, Carlos AU - Cure C AD - BIOMELAB, Barranquilla, Colombia. LA - eng GR - U54 HD090257/HD/NICHD NIH HHS/United States GR - UL1 TR001876/TR/NCATS NIH HHS/United States GR - KL2 TR001877/TR/NCATS NIH HHS/United States PT - Editorial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - JAMA Pediatr JT - JAMA pediatrics JID - 101589544 SB - IM CIN - JAMA Pediatr. 2020 Mar 1;174(3):237-238. PMID: 31904764 EIN - JAMA Pediatr. 2020 Mar 1;174(3):305. PMID: 32119038 MH - Alberta MH - Child MH - Cohort Studies MH - Colombia MH - Female MH - Humans MH - Infant MH - Infant, Newborn MH - Longitudinal Studies MH - *Nervous System/embryology/growth & development MH - Nervous System Malformations MH - Pregnancy MH - *Pregnancy Complications, Infectious MH - *Zika Virus MH - *Zika Virus Infection PMC - PMC6990858 COIS- Conflict of Interest Disclosures: Dr Mulkey reported receiving grants from the Thrasher Research Fund during the conduct of the study. Drs Mulkey and DeBiasi reported providing technical expertise to the Zika studies by the Centers for Disease Control and Prevention outside the submitted work. Dr Fourzali reported receiving other compensation from the Children's National Hospital outside the submitted work. No other disclosures were reported. EDAT- 2020/01/07 06:00 MHDA- 2020/11/24 06:00 PMCR- 2021/01/06 CRDT- 2020/01/07 06:00 PHST- 2020/01/07 06:00 [pubmed] PHST- 2020/11/24 06:00 [medline] PHST- 2020/01/07 06:00 [entrez] PHST- 2021/01/06 00:00 [pmc-release] AID - 2758105 [pii] AID - poi190092 [pii] AID - 10.1001/jamapediatrics.2019.5204 [doi] PST - ppublish SO - JAMA Pediatr. 2020 Mar 1;174(3):269-276. doi: 10.1001/jamapediatrics.2019.5204.