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）是一种黄病毒科（Flaviviridae）的虫媒病毒。感染被认为是温和的和自限性的，直到2015年，当在巴西最初观察到在母亲怀孕期间感染ZIKV后新生儿的小头畸形和其他出生缺陷的流行病。越来越多的证据表明，ZIKV是导致怀孕期间感染的母亲的新生儿出现各种出生缺陷的原因。孕妇中ZIKV感染与妊娠不良结局的关系是正在进行评估的主题。 迄今为止，对受感染妇女所生婴儿的研究往往集中在那些患有严重出生缺陷的婴儿身上，这些缺陷构成了先天性寨卡综合征（CZS），巴西最近的一项基于人群的研究表明，与没有CZ1的儿童相比，这会增加生命前三年的死亡风险超过11倍。美国Zika妊娠和婴儿登记处报告说，在妊娠期间感染ZIKV的妇女所生的婴儿中，约有5%患有与CZS一致的Zika相关的大脑或眼睛缺陷2。 但是，对于95%出生时没有CZS的婴儿的生长和发育是否存在潜在影响，以及这些影响可能是什么，仍有待阐明。需要对感染寨卡病毒的孕妇所生婴儿进行纵向研究，以评估宫内或分娩时寨卡病毒暴露的更广泛可能表现的更广泛范围和自然史。 2016年，NIH启动了一项大型、多中心、国际观察性研究，研究婴儿和妊娠期寨卡病毒的流行病学、自然史和发病机制，即妊娠期寨卡病毒感染（ZIP）研究。ZIP研究跟踪了怀孕期间有寨卡感染风险的妇女所生的婴儿，直到生命的前12个月，并于2019年12月完成了最后一次患者访视。2018年，美国国立卫生研究院启动了妊娠期间感染寨卡病毒的妇女所生儿童的国际队列研究（ZIP 2.0），对来自ZIP研究或类似研究的寨卡暴露儿童和未暴露对照儿童进行了42个月的随访，以评估寨卡对儿童生长和发育的影响。 最近的研究发现，在子宫内暴露于ZIKV而没有CZS的婴儿似乎在生命的前18个月内有异常神经发育结果的风险3，并且在子宫内暴露于ZIKV的没有小头畸形的儿童中类似地观察到解剖和神经发育异常的高频率4。一项研究发现，根据头围，发育延迟的风险存在梯度，严重小头症儿童的发育延迟风险最高，而头部正常的ZIKV暴露儿童与未暴露的对照儿童显示出相似的风险。然而，其他几项研究已经观察到患有宫内ZIKV感染的儿童在没有小头畸形的情况下神经发育异常6，7。这些报告表明，几乎所有这些儿童都表现出至少一种发育迟缓，并且在子宫内暴露于ZIKV的儿童中有很大一部分发展为轻度认知迟缓和听觉行为异常。 该任务令满足了NIH的要求，即对ZIP 2.0婴儿和儿童产前接触寨卡病毒的影响进行评估。考虑到科学文献中迄今为止报告的各种结果，有时相互矛盾，该任务顺序将有助于确定是否需要长期随访，随访的程度和类型。