STUDY CLOSEOUT FOR THE INTERNATIONAL COHORT STUDY OF CHILDREN BORN TO WOMEN INFECTED WITH ZIKA VIRUS DURING PREGNANCY (ZIP 2.0)

对怀孕期间感染寨卡病毒的妇女所生儿童的国际队列研究即将结束 (ZIP 2.0)

• 批准号: 10701122
• 负责人: BARBARA DRIVER
• 金额: $ 50万
• 依托单位: WESTAT, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10701122
• 关键词: Address; Age-Months; Anatomy; Arboviruses; Auditory; Behavioral; Brain; Brazil; Child; Cognitive; Cohort Studies; Communication; Conflict (Psychology); Congenital Abnormality; Data; Data Analyses; Development; Developmental Delay Disorders; Ensure; Epidemic; Epidemiology; Evaluation; Exposure to; Eye; Flaviviridae; Frequencies; Growth and Development function; Head circumference; Impact evaluation; Infant; Infection; International; Life; Literature; Longitudinal Studies; Manuscripts; Microcephaly; Mothers; National Institute of Child Health and Human Development; Natural History; Newborn Infant; Observational Study; Outcome; Ownership; Pathogenesis; Patients; Population Study; Pregnancy; Pregnant Women; Protocols documentation; Registries; Reporting; Risk; Site; Specimen; United States National Institutes of Health; Virus; Visit; Woman; ZIKA; ZIKV infection; Zika Virus; adverse pregnancy outcome; congenital zika syndrome; data submission; follow-up; high risk; in utero; intrapartum; mortality risk; neurodevelopment; prenatal; prenatal exposure; vector-borne

Zika virus (ZIKV) is an arbovirus (vector-borne virus) of the genus Flaviviridae. Infections were thought to be mild and self-limiting until 2015, when an epidemic was observed initially in Brazil of microcephaly and other birth defects in newborns following infection of the mother during pregnancy with ZIKV. Increasing evidence now points to ZIKV as the agent responsible for a variety of birth defects in newborns of mothers who become infected during pregnancy. The relationship of ZIKV infections in pregnant women with adverse outcomes of pregnancy is the subject of ongoing evaluation. Studies to date of infants born to infected women have tended to focus on those born with serious birth defects that constitute the congenital Zika syndrome (CZS), which has been shown in a recent population-based study from Brazil to increase risk of death in the first three years of life more than 11-fold compared to children without CZS1. The U.S. Zika Pregnancy and Infant Registry reports that approximately 5% of infants born to women with ZIKV infection during pregnancy have Zika-associated brain or eye defects2 consistent with CZS. But whether there are latent effects on growth and development in the 95% of infants who are born without CZS to Zika-infected women, and what those effects may be, remains to be elucidated. Longitudinal studies of infants born to Zika-infected pregnant women are needed to assess the broader spectrum and natural history of a wider range of possible manifestations of intrauterine or intrapartum Zika exposure. In 2016, NIH initiated a large, multicenter, international observational study of the epidemiology, natural history, and pathogenesis of Zika in infants and pregnancy, the Zika Infections in Pregnancy (ZIP) Study. The ZIP Study followed infants born to women at risk for Zika infection during pregnancy through just the first 12 months of life and completed its last patient last visit December 2019. In 2018, NIH initiated the International Cohort Study of Children Born to Women Infected with Zika Virus During Pregnancy (ZIP 2.0) of Zika exposed children and unexposed control children from the ZIP Study or similar studies, following the children through 42 months of age to evaluate the effects of Zika on child growth and development. Recent studies have found that infants who had in utero ZIKV exposure without CZS appear to be at risk for abnormal neurodevelopmental outcomes in the first 18 months of life3 and similarly observed high frequencies of anatomical and neurodevelopmental abnormalities in children without microcephaly who were exposed to ZIKV in utero4. One study found a gradient of risk of development delay according to head circumference, with severely microcephalic children at highest risk for delays while normocephalic ZIKV-exposed children showed similar risk to unexposed control children5. However, several other studies have observed abnormal neurodevelopment in the absence of microcephaly among children with intrauterine ZIKV exposure6,7. Those reports indicate that nearly all such children presented at least one developmental delay and that a significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities. This task order addresses NIH’s requirement to conduct an evaluation of the impact of prenatal Zika exposure among ZIP 2.0 infants and children. Given the variable and sometimes conflicting findings reported to date in the scientific literature, this task order will help to determine whether, to what extent, and what types of longer-term follow-up is indicated.

寨卡病毒 (ZIKV) 是黄病毒科的一种虫媒病毒（媒介传播病毒）。直到 2015 年，最初在巴西观察到感染后新生儿出现小头畸形和其他出生缺陷的流行病之前，人们一直认为感染是轻微的、具有自限性。现在越来越多的证据表明，ZIKV 是导致怀孕期间感染 ZIKV 的母亲新生儿出现各种出生缺陷的病原体。妊娠中寨卡病毒感染与妊娠不良结局的关系是持续评估的主题。 迄今为止，对受感染妇女所生婴儿的研究往往集中在那些出生时患有严重先天缺陷的婴儿，这些缺陷构成先天性寨卡综合征（CZS），巴西最近的一项基于人群的研究表明，这种缺陷会增加婴儿的死亡风险。与未感染 CZS1 的儿童相比，生命前三年的感染率高出 11 倍以上。美国寨卡病毒妊娠和婴儿登记处报告称，怀孕期间感染 ZIKV 的妇女所生婴儿中约有 5% 患有寨卡病毒感染。寨卡相关的大脑或眼睛缺陷2与 CZS 一致。 但是，对于 95% 感染寨卡病毒的妇女所生的未患有 CZS 的婴儿，其生长和发育是否存在潜在影响，以及这些影响可能是什么，仍有待对感染寨卡病毒的孕妇所生的婴儿进行纵向研究来阐明。需要评估宫内或产时寨卡暴露的更广泛可能表现的更广泛谱和自然史。 2016 年，NIH 启动了一项针对婴儿和妊娠期寨卡病毒流行病学、自然史和发病机制的大型、多中心、国际观察性研究，即妊娠期寨卡病毒感染 (ZIP) 研究，该研究对有寨卡病毒风险的妇女所生的婴儿进行了跟踪。妊娠期至出生后前 12 个月内感染寨卡病毒，并于 2019 年 12 月完成最后一位患者的最后一次访视。2018 年，NIH 启动了国际队列研究怀孕期间感染寨卡病毒的妇女所生的孩子 (ZIP 2.0) 对 ZIP 研究或类似研究中暴露于寨卡病毒的儿童和未暴露于寨卡病毒的对照儿童进行跟踪，跟踪儿童至 42 个月大，以评估寨卡病毒对儿童生长和发育的影响。 最近的研究发现，在没有 CZS 的情况下在子宫内接触过 ZIKV 的婴儿似乎在生命的前 18 个月内存在神经发育结果异常的风险3，并且在没有小头畸形的儿童中也观察到了相似的解剖和神经发育异常的高频率。一项研究发现，根据圆周头参考，发育迟缓的风险存在梯度，患有严重小头畸形的儿童，而正常头畸形的儿童，发育迟缓的风险最高。暴露于 ZIKV 的儿童与未暴露于 ZIKV 的对照儿童表现出相似的风险 5 然而，其他几项研究观察到宫内 ZIKV 暴露的儿童在没有小头畸形的情况下出现神经发育异常 6,7。很大一部分在子宫内接触寨卡病毒的儿童出现了轻度认知迟缓和听觉行为异常。 该任务指令满足了 NIH 的要求，即对 ZIP 2.0 婴儿和儿童的产前寨卡病毒暴露影响进行评估。鉴于科学文献中迄今为止报告的结果存在差异且有时相互矛盾，该任务指令将有助于确定是否、何种情况。程度，以及表明了哪些类型的长期随访。