Neurodevelopmental Outcomes in Children Vertically Exposed to Chikungunya Virus: A Two Years Follow-up Study.

Maria D S Quintans,Renata A de O Vianna,Luis G C Velarde,Solange A de Oliveira,Alexandre R Fernandes,Arnaldo C Bueno,Claudete A A Cardoso
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Abstract

OBJECTIVES To monitor by the first 24 months of life, children born to mothers with laboratory evidence of chikungunya virus (CHIKV) infection during pregnancy or up to 8 weeks before it, and to describe abnormalities in head circumference (HC), auditory and ophthalmological assessments and neuroimaging tests during the follow-up period. METHOD This is a observational, descriptive, longitudinal and prospective study of children born to mothers who had a rash and a positive test for CHIKV during pregnancy or up to 8 weeks before it. They were admitted between November 2015 and May 2019 in the outpatient multidisciplinary clinic to investigate acute exanthematous disease. The exposed children were followed up by a multidisciplinary team and underwent periodic measurements of the HC. The Denver II test was applied, in addition to transfontanellar ultrasound (TU) to evaluate neurodevelopmental outcomes during the study period. Ophthalmological and auditory examinations, echocardiography and laboratory tests were also included. RESULTS We included in the study 27 children vertically exposed to CHIKV. All children had a negative polymerase chain reaction test for the virus collected at the first outpatient visit (mean age of 16.8 days and standard deviation of 8 days). No clinical condition compatible with congenital infection at birth was reported. A change in HC characterized by macrocephaly and mild global delay development was observed in a 1-year-old child whose mother was infected in the peripartum, but with normal TU. Changes in the TU were observed in 2 other children with nonspecific subependymal cystic malformation that was not evident by the cranial computed tomography. The other children monitored showed normal results in the Denver II test, in the HC and TU. No changes were identified on ocular ophthalmoscopy or auditory brainstem response test. Two children had an increase in serum ferritin levels during the first year of life, with the others' inflammatory disease markers normal. CONCLUSIONS Our study added knowledge about the neurodevelopment of children exposed to CHIKV during pregnancy by a longitudinal and prospective follow-up, throughout their first 24 months of life. We did not observe a negative impact of exposure to the virus on the neurological examination, global developmental test or measurements of the HC of these children.
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垂直暴露于基孔肯雅病毒的儿童的神经发育结果:两年随访研究
方法 这是一项观察性、描述性、纵向和前瞻性研究,研究对象为母亲在怀孕期间或怀孕前8周内出疹且基孔肯雅病毒(CHIKV)检测呈阳性的新生儿。他们在2015年11月至2019年5月期间被多学科门诊收治,以调查急性出血性疾病。暴露儿童由一个多学科小组进行随访,并定期测量HC。在研究期间,除了经胼胝体超声波(TU)外,还采用了丹佛 II 测试来评估神经发育结果。研究还包括眼科和听力检查、超声心动图和实验室检测。所有患儿在首次门诊时的病毒聚合酶链反应检测结果均为阴性(平均年龄为 16.8 天,标准差为 8 天)。没有发现与出生时先天感染相符的临床症状。一名 1 岁儿童的母亲在围产期受到感染,但其 TU 正常,观察到其 HC 发生变化,表现为巨大颅畸形和轻度全身发育迟缓。另外 2 名患有非特异性腮腺下囊性畸形的儿童的 TU 也发生了变化,但头颅计算机断层扫描结果并不明显。接受监测的其他儿童在丹佛 II 测试、HC 和 TU 中均显示正常。眼底镜检查或听觉脑干反应测试均未发现异常。结论我们的研究通过纵向和前瞻性随访,增加了对孕期接触过 CHIKV 的儿童在出生后 24 个月内神经发育情况的了解。我们没有观察到接触病毒对这些儿童的神经系统检查、全面发育测试或HC测量产生负面影响。
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