Examining Feeding and Cardiorespiratory Patterning in Zika-Exposed Infants in Puerto Rico

项目总结 寨卡病毒是一种单链RNA病毒，主要通过感染病毒传播给人类。 伊蚊。寨卡病毒病在大约20%的感染者中很明显。有越来越多的 表明寨卡病毒对孕妇及其婴儿有害影响的证据。事实上，世界 卫生组织此前宣布寨卡病毒为突发公共卫生事件，但我们仍然不明白为什么 这种疾病会影响婴儿茁壮成长所必需的早期临床结果，如吮吸和 喂食。吮吸和喂食行为是极其重要的临床标志，因为这些行为需要 跨多个系统(神经/心脏/呼吸系统)的大量集成，包括五个以上 脑神经，以及26对肌肉之间的协调(8，9)。事实上，吸吮和喂食的异常 早期婴儿期被认为是新生儿脑损伤的潜在标志(17，18，19)。那里仍然有一个 关于宫内暴露于寨卡病毒如何影响哺乳、哺乳和 婴儿的心肺模式。因此，这个项目的目的是定量检查非营养性 吸吮(NNS；AIM 1)、口服喂养(AIM 2)和心肺模式(心率、呼吸频率、心跳 比率变异性；目的3)在波多黎各出生的以下婴儿组(n=200)中发生：对照婴儿 孕期未接触寨卡病毒的婴儿(第1组)，孕期接触寨卡病毒的婴儿 无先天性ZIKV综合征证据的妊娠(CZS；定义如下：严重 小头畸形、脑畸形、眼睛发现、先天性痉挛和神经损伤(10)) (2)和孕期接触ZIKV且有CZS证据的婴儿(3组)。我们的 假设孕期接触ZIKV且有cZv证据的婴儿(第3组)将表现出 与第1组和第2组婴儿相比，他们在神经网络、口服喂养和心肺功能方面的结果更差 第二组婴儿表现较对照婴儿差(第一组)。我们将利用正在进行的ZIKV 波多黎各的一个项目，题为“婴儿和怀孕中的寨卡病毒(ZIP)”，已经在进行中，从 他们在为期两年的研究中的队列(见支持信)。本研究的几个特点提供了 识别ZIKV暴露与早期哺乳、喂养之间的联系的能力达到前所未有的水平 和心肺行为，包括对这些措施的量化评估 出生时对三个婴儿组进行了比较。这项工作的发现可能会对 促进我们对ZIKV的了解，并对临床治疗产生立竿见影的影响。更具体地说， 拟议的研究可能会：(1)提供有关ZIKV暴露如何影响吸吮、喂养、 和心肺发育；(2)检查使用这些行为作为早期生物标记物的效用 暴露于ZIKV的婴儿的发育，以及(3)改变研究人员和临床医生评估和治疗这些疾病的方式 旨在改善这些结果的行为，使这些婴儿能够生长、发育和茁壮成长。

PROJECT SUMMARY The Zika virus (ZIKV) is a single-stranded RNA virus that is mainly transmitted to humans through infected Aedes mosquitos. The ZIKV disease is evident in approximately 20% of infected people. There is growing evidence suggesting the deleterious effects of ZIKV on pregnant women and their infants. In fact, the World Health Organization previously declared ZIKV a public health emergency, yet we still do not understand how this disease impacts early clinical outcomes necessary for an infant to thrive and develop, like sucking and feeding. Sucking and feeding behaviors are extremely important clinical markers, as these behaviors require a tremendous amount of integration across multiple systems (neural/cardio/respiratory), including more than five cranial nerves, and coordination among 26 muscle pairs (8, 9). In fact, sucking and feeding abnormalities in early infancy have been viewed as potential markers of neonatal brain injury (17,18,19). There remains a significant gap in knowledge as to how exposure to ZIKV in utero influences sucking, feeding and cardiorespiratory patterning in infants. Therefore, this project aims to quantitatively examine how non-nutritive sucking (NNS; AIM 1), oral feeding (AIM 2), and cardiorespiratory patterning (heart-rate, respiratory rate, heart- rate variability; AIM 3) develop in the following groups of infants (n=200) born in Puerto-Rico: control infants who were not exposed to ZIKV during pregnancy (Group 1), infants who were exposed to ZIKV during pregnancy without evidence of congenital ZIKV syndrome (CZS; defined by the following: severe microcephaly, brain anomalies, ocular findings, congenital contractures, and neurological impairments (10)) (Group 2), and infants who were exposed to ZIKV during pregnancy with evidence of CZS (Group 3). Our hypothesis is that infants exposed to ZIKV during pregnancy with evidence of CZV (Group 3) will perform worse on their NNS, oral feeding and cardiorespiratory outcomes compared to infants in Groups 1 and 2—with infants in Group 2 performing worse than the control infants (Group 1). We will leverage the ongoing ZIKV project in Puerto Rico, entitled “Zika in Infants and Pregnancy (ZIP)”, already underway, to recruit infants from their cohort over the two-year study (see letter of support). Several features of this study provide an unprecedented level of power for identifying the connection between ZIKV exposure and early sucking, feeding and cardiorespiratory behaviors, including quantitative assessments of these measures sampled soon after birth with comparisons across three infant groups. Findings from this work could have broad implications for advancing our knowledge of ZIKV, and an immediate impact on clinical therapies. More specifically, the proposed studies are likely to (1) provide essential data on how ZIKV exposure influences sucking, feeding, and cardiorespiratory development; (2) examine the utility of using these behaviors as an early biomarker of development in infants exposed to ZIKV, and (3) shift how researchers and clinicians assess and treat these behaviors with the goal of improving these outcomes allowing these infants to grow, develop, and thrive.