婴儿与孕期寨卡病毒研究（ZIP）：一项关于产前寨卡病毒感染及不良胎儿和婴儿结局的前瞻性国际队列研究结果

Zika in Infants and Pregnancy (ZIP) study: results from a prospective international cohort study of prenatal Zika virus infection and adverse fetal and infant outcomes.

作者信息

Lebov Jill Farnell, Nason Martha, Stolka Kristen B, Ximenes Ricardo, Mussi-Pinhata Marisa M, Moye Jack, Zorrilla Carmen D, Velez Vega Carmen M, Cordero José F, Scalabrin Deolinda M F, Ko Albert I, Moreira Maria Elisabeth Lopes, Galvão Luiz Augusto, Britt William, Marques Ernesto T A, Balmaseda Angel, Harris Eva, Arias Juan F, Schultz-Cherry Stacey, Garces Ana Lucía, Krebs Nancy F, Ochoa Theresa J, Ugarte-Gil César Augusto, Fogleman Elizabeth, Gabriel Erin, Welton Michael, Irizarry Carmen M, de Moura Negrini Silvia Biason, Coutinho Conrado Milani, de Barros Miranda-Filho Demócrito, Montarroyos Ulisses Ramos, Cordeiro Marli Tenorio, Gajewski Anna, Osorio Jorge E, Figueroa Lester

机构信息

Social, Statistical and Environmental Health Sciences RTI International, Durham, NC, England.

Center for Vaccine Innovation and Access, PATH, Washington, DC, USA.

出版信息

BMC Pregnancy Childbirth. 2025 Aug 30;25(1):903. doi: 10.1186/s12884-025-07774-y.

DOI:10.1186/s12884-025-07774-y

PMID:40885911

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12399002/

Abstract

BACKGROUND

Before Zika virus (ZIKV) infections were observed in the Americas, an association between ZIKV and microcephaly or other congenital malformations was not well documented. Initial reports suggested strong associations between ZIKV and congenital malformations, but plausible estimates of causal effects from prospective studies with adequate sample size and covariate data were few.

METHODS

From 2016-2018, the Zika in Infants and Pregnancy (ZIP) study enrolled pregnant people before 18 weeks gestation or with confirmed symptomatic ZIKV in a prospective cohort across 10 sites in South and Central America, and in Puerto Rico. Pregnancies were followed monthly through delivery and 6 weeks postpartum. Infants were followed quarterly to age 12 months. Prespecified co-primary analyses evaluated the associations between a composite endpoint of adverse fetal, neonatal, and infant outcomes with intrauterine ZIKV exposure overall and with symptomatic intrauterine ZIKV exposure. Secondary analyses separately evaluated the association of intrauterine ZIKV exposure with individual components of the primary endpoint.

RESULTS

Six thousand one hundred pregnant participants were included in the primary analysis, including 61 with ZIKV infection during pregnancy confirmed by a ZIKV-specific RNA test. For the primary analyses, the relative risk (RR) for the composite endpoint associated with any ZIKV exposure was 1.64 (95% CI: 0.65, 4.13) and with symptomatic ZIKV exposure 1.08 (95% CI: 0.15, 7.64). Sensitivity analyses provided similar results. Secondary analyses showed significant adjusted RRs [95% CI] for stillbirth (4.28 [1.39, 13.21]), infant death within six weeks (6.20 [1.08, 35.60], and fetal loss before 20 weeks (3.72 [1.82, 7.59]).

CONCLUSIONS

The ZIP study identified an elevated but not statistically significant risk of the primary composite outcome with intrauterine ZIKV exposure, and a significantly increased risk of some adverse fetal and infant outcomes with intrauterine ZIKV exposure in secondary analyses. Fewer than expected infections observed during pregnancy, coincident with a waning epidemic, limited study power to evaluate risk. Combining data from multiple cohorts for future meta-analysis may better define the risks of intrauterine ZIKV exposure.

TRIAL REGISTRATION

NCT02856984. Registered August 5, 2016. Retrospectively registered.

摘要

背景

在美洲地区观察到寨卡病毒（ZIKV）感染之前，ZIKV与小头畸形或其他先天性畸形之间的关联尚无充分记录。初步报告表明ZIKV与先天性畸形之间存在密切关联，但样本量充足且有协变量数据的前瞻性研究对因果效应的合理估计却很少。

方法

2016年至2018年，婴儿与孕期寨卡病毒（ZIP）研究在南美洲、中美洲的10个地点以及波多黎各的一个前瞻性队列中，招募了妊娠18周前或确诊有症状性ZIKV感染的孕妇。孕期每月随访直至分娩及产后6周。婴儿每季度随访至12个月龄。预先设定的共同主要分析评估了不良胎儿、新生儿和婴儿结局的综合终点与宫内ZIKV总体暴露以及有症状的宫内ZIKV暴露之间的关联。次要分析分别评估了宫内ZIKV暴露与主要终点各个组成部分之间的关联。

结果

6100名孕妇纳入了主要分析，其中61名孕妇孕期ZIKV感染经ZIKV特异性RNA检测确诊。对于主要分析，与任何ZIKV暴露相关的综合终点的相对风险（RR）为1.64（95%可信区间：0.65，4.13），与有症状的ZIKV暴露相关的RR为1.08（95%可信区间：0.15，7.64）。敏感性分析提供了类似结果。次要分析显示，死产（4.28 [1.39，13.21]）、六周内婴儿死亡（6.20 [1.08，35.60]）以及20周前胎儿丢失（3.72 [1.82，7.59]）的调整后RR [95%可信区间]具有统计学意义。