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

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Neurodevelopmental Abnormalities in Children With In Utero Zika Virus Exposure Without Congenital Zika Syndrome
JAMA Pediatrics ( IF 24.7 ) Pub Date : 2020-03-01 , DOI: 10.1001/jamapediatrics.2019.5204
Sarah B Mulkey _{1,

2,

3} , Margarita Arroyave-Wessel ₁ , Colleen Peyton ₄ , Dorothy I Bulas _{1,

5} , Yamil Fourzali ₆ , JiJi Jiang ₁ , Stephanie Russo ₁ , Robert McCarter ₁ , Michael E Msall ₇ , Adre J du Plessis _{1,

2,

3} , Roberta L DeBiasi _{1,

2,

8} , Carlos Cure ₉

Affiliation

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 Atlántico 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.

中文翻译：

宫内感染寨卡病毒但无先天性寨卡综合征的儿童的神经发育异常

重要性怀孕期间感染寨卡病毒 (ZIKV) 的母亲所生但在出生时没有明显残疾的儿童数量很大，值得研究该人群中没有先天性寨卡综合征 (CZS) 的神经发育障碍风险. 目的探讨宫内暴露于 ZIKV 的无 CZS 的婴儿是否在 18 个月大之前具有正常的神经发育结果。设计、环境和参与者本队列研究前瞻性地在哥伦比亚大西洋省和华盛顿特区招募了一组患有 ZIKV 的孕妇。通过这个队列，我们对婴儿神经发育进行了纵向研究。2016 年 8 月 1 日至 2017 年 11 月 30 日期间出生的婴儿，如果他们是活产的，则包括在内，磁共振成像和超声检查胎儿脑部检查结果正常，出生时头颅正常，检查结果正常，无 CZS 临床证据。77 名出生在哥伦比亚的婴儿，但 0 名出生在美国的婴儿符合纳入标准。暴露产前 ZIKV 暴露。主要成果和措施婴儿发育通过华纳适应性和功能技能初始发育评估 (WIDEA) 和阿尔伯塔婴儿运动量表 (AIMS) 在 4 至 18 个月大的 1 或 2 个时间点进行评估。与标准样本相比，WIDEA 和 AIMS 分数转换为 z 分数。基于自举重采样方法的纵向混合效应回归模型估计了一段时间内的分数，考虑了母体 ZIKV 感染时的胎龄和评估时的婴儿年龄。结果表示为基于 z 统计的具有 2 尾 P 值的斜率系数，该 z 统计测试系数是否不同于 0（无变化）。结果在该队列研究中包括的 77 名哥伦比亚婴儿中，70 名 (91%) 没有 CZS 并接受了神经发育评估。40 名婴儿 (57%) 在 4 至 8 个月大时接受了评估，中位数（四分位距 [IQR]）年龄为 5.9 (5.3-6.5) 个月，60 名婴儿 (86%) 在 9 至 18 个月大时接受了评估中位 (IQR) 年龄为 13.0 (11.2-16.4) 个月。WIDEA 总分（系数：age = -0.227 vs age2 = 0.006；P < .003）和自理领域得分（系数：age = -0.238 vs age2 = 0.01；P < .008）显示出与年龄的曲线关联。根据交流系数（-0.036；-0.036；P = .001)、社会认知 (-0.10; P < .001) 和流动性 (-0.14; P < .001)。随着时间的推移，AIMS 分数与标准样本相似（95% CI，-0.107 至 0.037；P = .34）。接受产后头颅超声检查的 57 名婴儿中有 19 名（33%）有非特异性、轻微的发现。除了涉及社会认知领域的复杂交互关系外，有和没有颅超声检查结果的婴儿之间的 WIDEA z 评分下降没有差异（P < .049）。具有非特异性颅超声检查结果的婴儿的 AIMS z 评分较低（-0.49；P = .07）。结论和相关性本研究发现，在没有 CZS 的情况下宫内暴露于 ZIKV 的婴儿在出生后 18 个月内出现神经发育异常的风险。

更新日期：2020-03-01

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