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.

Zika病毒（ZIKV）是Flaviviridae属的Arbovirus（载体传播病毒）。直到2015年，人们认为感染被认为是温和的，是自我限制的，当时在巴西的小头畸形中观察到流行病，而在ZIKV怀孕期间感染了母亲后，新生儿感染了新生儿的其他出生缺陷。现在，越来越多的证据表明ZIKV是负责怀孕期间被感染的母亲的各种出生出生的代理人。妊娠不良后果的孕妇ZIKV感染的关系是持续评估的主题。 迄今为止，受感染妇女出生的婴儿的研究倾向于专注于构成先天性寨卡病毒综合征（CZS）的严重先天缺陷的人，这在巴西的最新基于人群的研究中已显示出与没有CZS1的儿童相比，在前三年的前三年中增加了11倍以上的死亡风险。美国寨卡病毒妊娠和婴儿登记处报告说，在怀孕期间，约有5％的ZIKV感染的婴儿患有Zika相关的脑或眼缺陷2与CZS一致。 但是，在没有CZ对Zika感染的妇女的情况下出生的95％的婴儿是否对生长和发育产生潜在影响，而这些影响可能是什么，尚待阐明。需要对Zika感染的孕妇出生的婴儿进行纵向研究，以评估宫内或Zika Zika暴露的广泛表现的广泛谱和自然历史。 2016年，NIH对婴儿和妊娠的流行病学，自然史和发病机理进行了大型，多中心的国际观察研究，怀孕（ZIP）研究中的寨卡病毒感染。这项ZIP研究跟踪了妇女出生的婴儿在怀孕期间的最初12个月生命的前12个月，并完成了最后一次访问的上一次访问，并完成了2019年12月的上一次患者。2018年，NIH对妇女的国际同龄人进行了国际同伴研究，该儿童感染了Zika病毒在怀孕期间受到Zika病毒的妇女出生（ZIP 2.0）的Zika儿童对Zika的儿童的影响，以评估Zika对Zip的儿童的研究，从而通过42个月的ZIIP对儿童进行评估，该研究是通过42个月的Zip对儿童进行了研究，该儿童是对ZIP的妇女的研究。和发展。 最近的研究发现，在没有CZ的子宫ZIKV暴露的婴儿中，在Life3的头18个月内似乎有神经发育结果异常的风险，同样观察到没有小型儿童的解剖学和神经发育异常的高频，在Utero4中暴露于ZIKV的儿童中。一项研究发现，根据头部循环的发育延迟风险梯度，严重的小头脑儿童的延迟风险最高，而正常ZIKV暴露的儿童则与未暴露的对照儿童显示出相似的风险5。然而，其他几项研究观察到宫内ZIKV暴露儿童没有小头畸形的神经发育异常。6,7。这些报告表明，几乎所有这些儿童都至少呈现出一个发育迟缓，并且在ZIKV中暴露于子宫内的很大一部分儿童会出现轻度的认知延迟和听觉行为异常。 该任务订单解决了NIH的要求，以评估ZIP 2.0婴儿和儿童对产前寨卡病毒的影响。鉴于迄今为止在科学文献中报告的变量，有时甚至是冲突的发现，该任务顺序将有助于确定是否指示，在何种程度，以及哪种类型的长期随访。