Long term adverse health outcomes for women and children following SARS-CoV-2 infection during pregnancy

项目摘要 严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）感染，该病毒负责全球 规模空前的COVID-19大流行导致多器官疾病，影响广泛。增加 有证据表明，SARS-CoV-2感染对一些个体的长期影响长达一年， 初始感染，称为SARS-CoV-2急性后后遗症（PASC）。孕妇及其 胎儿可能特别容易受到SARS-CoV-2感染的长期影响。生物 来自人群中SARS-CoV-2感染的可解释性和新出现的流行病学证据强调了 迫切需要研究妊娠期间SARS-CoV-2感染对妇女 心脏代谢和神经精神健康结果以及儿童的生长和发育。局限性 目前对感染SARS-CoV-2的孕妇及其在子宫内暴露的子女的研究， 包括缺乏长期后续行动，缺乏关于先前存在状况数据，难以理清 感染的风险因素，从其后果，和有限的能力，检查协会的主要 SARS-CoV-2变异株和疫苗接种状况。拟议的研究利用Kaiser Permanente北方 加州（KPNC）关于SARS-CoV-2感染检测和 结果收集了> 195，000名孕妇的纵向妊娠队列（> 22，000名 怀孕期间感染SARS-CoV-2，2020年3月至 2022年12月我们将使用我们强大而全面的EHR来跟踪妇女及其子女， 年，并确定临床诊断数据。此外，我们将招募和调查2000名 当孩子3岁时，母亲-孩子二对，以确定妇女和孩子的自我/父母报告 亚临床健康结果在EHR中不可用，但可能表明需要监测和/或提供 早期干预。我们将随机确定1000对妊娠期间感染SARS-CoV-2的夫妇（1/3 早期变异体，1/3 Delta和1/3 Omicron变异体）和1000个无SARS-CoV-2感染的二联体， 怀孕我们的研究将评估以下内容：1）评估SARS-CoV-2感染的长期影响 妊娠期间对女性心脏代谢和神经精神结局的影响（EHR和自我报告），以及2） 评估宫内暴露于SARS-CoV-2感染对儿童生长轨迹的长期影响， 神经发育（EHR和父母报告）。我们将检查变异，感染的严重程度和胎龄 在感染与所有感兴趣的结果的关系，并探索通过疫苗接种状态的影响修改， 种族/民族和先前存在的合并症。最后，我们的分析将包括感染前， 以及在怀孕或出生后允许估计联合效应。该项目将填补一个重大空白 告知怀孕期间暴露于SARS-CoV-2感染的妇女和儿童、公众、临床医生， 卫生保健系统对感染的全方位健康后果的认识。

Project Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus responsible for the global COVID-19 pandemic of unprecedented scale causes a multi-organ disease with widespread effects. Increasing evidence suggests long-term effects of SARS-CoV-2 infection in some individuals present up to a year after initial infection, referred to as Post-Acute Sequelae of SARS-CoV-2 (PASC). Pregnant women and their fetuses may be particularly vulnerable to the long-term effects of SARS-CoV-2 infection. The biological plausibility and emerging epidemiological evidence from SARS-CoV-2 infections in the population highlight the urgent need for research on the long-term effects of SARS-CoV-2 infection during pregnancy on women’s cardiometabolic and neuropsychiatric health outcomes and children’s growth and development. Limitations of current studies of both pregnant women with SARS-CoV-2 infection and their children exposed in utero, include a lack of long-term follow-up, lack of data on pre-existing conditions making it difficult to disentangle risk factors for the infection from its consequences, and limited ability to examine associations by predominant SARS-CoV-2 variant and vaccination status. The proposed study leverages Kaiser Permanente Northern California’s (KPNC’s) high-quality electronic health records (EHR) data on SARS-CoV-2 infection testing and results to assemble a longitudinal pregnancy cohort of >195,000 pregnant women (>22,000 women with SARS-CoV-2 infection during pregnancy and approximately>173,000 without) between March 2020 and December 2022. We will use our robust and comprehensive EHR to follow women and their children for up to 5 years and ascertain clinical diagnoses data. Additionally, we will recruit and survey a subsample of 2000 of the mother-child dyads when the child is 3 years old to ascertain women’s and children’s self/parent-reported subclinical health outcomes not available in the EHR, but that may suggest a need to monitor and/or provide early interventions. We will randomly identify 1000 dyads with SARS-CoV-2 infection during pregnancy (1/3 early variants, 1/3 Delta and 1/3 Omicron variants) and 1000 dyads without SARS-CoV-2 infection during pregnancy. Our study will assess the following: 1) Evaluate the long-term effects of a SARS-CoV-2 infection during pregnancy on women’s cardiometabolic and neuropsychiatric outcomes (EHR and self-report), and 2) Evaluate the long-term effects of in utero exposure to SARS-CoV-2 infection on child growth trajectory and neurodevelopment (EHR and parent-report). We will examine variant, severity of infection and gestational age at infection in relation to all outcomes of interest and explore effect modification by vaccination status, race/ethnicity and pre-existing co-morbidities. Finally, our analyses will include infection status before, during and after pregnancy or birth allowing for estimation of joint effects. This project will fill a significant gap informing women and children exposed to SARS-CoV-2 infection during pregnancy, the public, clinicians, and health care systems of the full spectrum of health consequences of infection.