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评估母体和新生儿脐血 SARS-CoV-2 抗体和胎盘转移率。

Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios.

机构信息

Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

出版信息

JAMA Pediatr. 2021 Jun 1;175(6):594-600. doi: 10.1001/jamapediatrics.2021.0038.

Abstract

IMPORTANCE

Maternally derived antibodies are a key element of neonatal immunity. Understanding the dynamics of maternal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and subsequent transplacental antibody transfer can inform neonatal management as well as maternal vaccination strategies.

OBJECTIVE

To assess the association between maternal and neonatal SARS-CoV-2-specific antibody concentrations.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study took place at Pennsylvania Hospital in Philadelphia, Pennsylvania. A total of 1714 women delivered at the study site between April 9 and August 8, 2020. Maternal and cord blood sera were available for antibody measurement for 1471 mother/newborn dyads.

EXPOSURES

SARS-CoV-2.

MAIN OUTCOMES AND MEASURES

IgG and IgM antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed in combination with demographic and clinical data.

RESULTS

The study cohort consisted of 1714 parturient women, with median (interquartile range) age of 32 (28-35) years, of whom 450 (26.3%) identified as Black/non-Hispanic, 879 (51.3%) as White/non-Hispanic, 203 (11.8%) as Hispanic, 126 (7.3%) as Asian, and 56 (3.3%) as other race/ethnicity. Among 1471 mother/newborn dyads for which matched sera were available, SARS-CoV-2 IgG and/or IgM antibodies were detected in 83 of 1471 women (6%; 95% CI, 5%-7%) at the time of delivery, and IgG was detected in cord blood from 72 of 83 newborns (87%; 95% CI, 78%-93%). IgM was not detected in any cord blood specimen, and antibodies were not detected in any infant born to a seronegative mother. Eleven infants born to seropositive mothers were seronegative: 5 of 11 (45%) were born to mothers with IgM antibody only, and 6 of 11 (55%) were born to mothers with significantly lower IgG concentrations compared with those found among mothers of seropositive infants. Cord blood IgG concentrations were positively correlated with maternal IgG concentrations (r = 0.886; P < .001). Placental transfer ratios more than 1.0 were observed among women with asymptomatic SARS-CoV-2 infections as well as those with mild, moderate, and severe coronavirus disease 2019. Transfer ratios increased with increasing time between onset of maternal infection and delivery.

CONCLUSIONS AND RELEVANCE

In this cohort study, maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta after asymptomatic as well as symptomatic infection during pregnancy. Cord blood antibody concentrations correlated with maternal antibody concentrations and with duration between onset of infection and delivery. Our findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from coronavirus disease 2019.

摘要

重要性

母体来源的抗体是新生儿免疫力的关键因素。了解母体对严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染的抗体反应动态以及随后的胎盘抗体转移,可以为新生儿管理以及母体疫苗接种策略提供信息。

目的

评估母体和新生儿 SARS-CoV-2 特异性抗体浓度之间的关联。

设计、地点和参与者:这项队列研究在宾夕法尼亚州费城的宾夕法尼亚医院进行。共有 1714 名女性于 2020 年 4 月 9 日至 8 月 8 日在研究地点分娩。1471 对母婴对的母血和脐血血清可用于抗体测量。

暴露

SARS-CoV-2。

主要观察指标和方法

通过酶联免疫吸附试验测量 SARS-CoV-2 刺突蛋白受体结合域的 IgG 和 IgM 抗体。结合人口统计学和临床数据分析抗体浓度和胎盘转移比。

结果

研究队列包括 1714 名产妇,中位(四分位距)年龄为 32(28-35)岁,其中 450 名(26.3%)为黑人/非西班牙裔,879 名(51.3%)为白种人/非西班牙裔,203 名(11.8%)为西班牙裔,126 名(7.3%)为亚洲人,56 名(3.3%)为其他种族/民族。在 1471 对可提供匹配血清的母婴对中,在分娩时,83 名(6%;95%CI,5%-7%)女性检测到 SARS-CoV-2 IgG 和/或 IgM 抗体,83 名新生儿中有 72 名(87%;95%CI,78%-93%)的脐血中检测到 IgG。任何脐血标本均未检测到 IgM,任何血清学阴性母亲所生婴儿均未检测到抗体。11 名出生于血清学阳性母亲的婴儿为血清学阴性:5 名(45%)仅为 IgM 抗体阳性,6 名(55%)与血清学阳性婴儿的母亲相比,IgG 浓度明显较低。脐血 IgG 浓度与母体 IgG 浓度呈正相关(r=0.886;P<0.001)。无症状 SARS-CoV-2 感染以及轻度、中度和重度 2019 年冠状病毒病(COVID-19)母亲的胎盘转移比均大于 1.0。转移比随着母体感染和分娩之间时间的延长而增加。

结论和相关性

在这项队列研究中,母体对 SARS-CoV-2 的 IgG 抗体在怀孕期间无症状和有症状感染后穿过胎盘。脐血抗体浓度与母体抗体浓度以及感染发病和分娩之间的时间有关。我们的研究结果表明,母体来源的 SARS-CoV-2 特异性抗体具有为新生儿提供针对 COVID-19 的保护的潜力。

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