Article record

意大利临床实践中引入伐昔洛韦后原发性CMV感染妊娠结局的改善：来自一项大型真实世界多中心研究的更新数据

Improvement of pregnancy outcome following primary CMV infection after the introduction of valacyclovir in the clinical practice in Italy, updated data from a large real-life multicenter study.

临床研究耳科IF 3.8Q1

文献信息

PMID	42874798
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Lorenzo Zammarchi 查看其他 49 位作者 Anna Beltrami；Giuseppina Liuzzi；Federica Ciccone；Filippo Lagi；Beatrice Borchi；Lucia Pasquini；Elisabetta Venturini；Luisa Galli；Nigritella Brianese；Lina Rachele Tomasoni；Sofia Lovatti；Vania Spinoni；Serena Messali；Antonella Vimercati；Francesco Di Gennaro；Sara Daleno；Maria Teresa Tassone；Daniele Lilleri；Milena Furione；Piera d'Angelo；Alessia Arossa；Giuseppe Maria Maruotti；Laura Letizia Mazzarelli；Serena Salomè；Francesco Raimondi；Sara Ornaghi；Francesca Arienti；Federica Fernicola；Mariateresa Sinelli；Carolina Saffioti；Erica Ricci；Alessio Mesini；Francesca Ippolita Calò Carducci；Leonardo Caforio；Giulia Lorenzetti；Carlo Torti；Maria Merelli；Paolo Fusco；Licia Bordi；Gabriella Rozera；Antonella Giancotti；Stefano Ghirardello；Maria Grazia Capretti；Alessandro Bartoloni；Anna Seidenari；Camilla Dionisi；Giuliana Simonazzi；Michele Trotta；Tiziana Lazzarotto
作者单位	Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Infectious and Tropical Disease Unit, Careggi University Hospital, Florence, Italy. Electronic address: lorenzo.zammarchi@unifi.it. 查看其他 33 条单位信息 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.；National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy.；National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy; Sapienza University of Rome, Rome, Italy.；Infectious and Tropical Disease Unit, Careggi University Hospital, Florence, Italy.；Fetal Medicine Unit, Department for Woman and Child Health, Careggi University Hospital, Florence, Italy.；Infectious Diseases Unit, Meyer Children's Hospital-IRCCS, Florence, Italy.；Infectious Diseases Unit, Meyer Children's Hospital-IRCCS, Florence, Italy; Department of Health Sciences, University of Florence, Florence, Italy.；Malattie Infettive, ASST Spedali Civili di Brescia, Brescia, Italy.；Malattie Infettive, Università degli Studi di Brescia, Brescia, Italy.；Neonatologia e Terapia Intensiva Neonatale, ASST Spedali Civili di Brescia, Brescia, Italy.；SMeL Microbiologia e Virologia, ASST Spedali Civili di Brescia, Brescia, Italy.；Dipartimento Interdisciplinare di Medicina, University of Bari, Bari, Italy.；Infectious Disease Unit, University of Bari, Bari, Italy.；Obstetrics and Gynecology Unit, University of Bari, Bari, Italy.；UOC Malattie Infettive e Tropicali, Università degli studi "Magna Graecia", Catanzaro, Italy.；Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.；Obstetrics and Gynecology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.；Department of Public Health, University of Naples Federico II, Naples, Italy.；Division of Neonatology, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.；Department of Obstetrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy; University of Milano-Bicocca, School of Medicine and Surgery, Monza, Italy.；Department of Obstetrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.；Department of Neonatology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.；Infectious Disease Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.；Bambino Gesù Children's Hospital, Rome, Italy.；Dipartimento di Sicurezza e Bioetica, Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.；Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.；UOC Malattie Infettive e Tropicali, AOU R. Dulbecco, Catanzaro, Italy.；Sapienza University of Rome, Rome, Italy.；Neonatology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.；IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.；Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Infectious and Tropical Disease Unit, Careggi University Hospital, Florence, Italy.；Obstetrics and Prenatal Medicine, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.；Microbiology, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy; Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
期刊	American journal of obstetrics & gynecology MFM
SCI 分区	Q1
IF	3.8
研究类型	临床研究 · 临床
所属专科	耳科

中文摘要

背景： 先天性巨细胞病毒（CMV）感染（cCMV）是神经发育障碍和先天性感音神经性听力损失（SNHL）的主要原因。自2020年12月起，伐昔洛韦（VCV）被意大利国家卫生系统报销，用于减少母体原发性CMV感染后的母胎CMV传播。
目的： 本研究旨在评估VCV在预防胎儿CMV感染、终止妊娠、流产、出生时先天性CMV感染以及新生儿中cCMV体征/症状方面的有效性。
研究设计： 本研究提供了先前发表的一项大型多中心观察性意大利研究的更新数据，该研究纳入了2010年1月至2025年6月期间在围受孕期至妊娠24周内获得原发性CMV感染的女性。主要结局是羊膜穿刺术时的CMV传播、终止妊娠、流产、出生时传播（新生儿尿液中CMV DNA阳性）、症状性cCMV，以及一个复合结局（羊膜穿刺术时或出生时传播、终止妊娠或流产的发生）。
结果： 共纳入832名女性（826例单胎和8组双胎妊娠，共842个胎儿）；588个胎儿接受了产前VCV治疗（576例单胎和6例双胎），254个未治疗（248例单胎和4例双胎）。CMV阳性羊膜穿刺术在VCV治疗胎儿中发生率为17.2%（64/373），而未治疗胎儿为27.9%（38/136）（p=0.007，aOR 0.53 [95%CI 0.34, 0.85]）。终止妊娠和流产在治疗胎儿中分别发生率为4.7%（26/555）和0.7%（4/555），而未治疗胎儿分别为10.0%（25/250）和1.6%（4/250）（p=0.004，aOR 0.46 [95%CI 0.25, 0.78] 和 p=0.24，aOR 0.45 [95%CI 0.11, 1.80]）。新生儿尿液中检测到CMV DNA在治疗和未治疗妊娠的新生儿中分别为23.7%（124/525）和27.1%（60/221）（p=0.31，aOR 0.83 [95%CI 0.58, 1.19]）。出生时症状性先天性感染的患病率在VCV组显著较低（3.6% 19/525 vs. 9.9% 22/221，p=0.001，aOR 0.34 [95%CI 0.18, 0.64]）。复合结局在治疗妊娠中发生频率较低（27.2% vs. 35.8%，p=0.012，aOR 0.67 [95%CI 0.49, 0.91]）。VCV相关不良事件报告率为6.7%，且为轻度或中度。羊膜穿刺术阴性后出生时诊断cCMV感染在治疗和未治疗妊娠之间无显著差异（12.9%，36/280 vs. 7.3%，7/96；p=0.139）。在羊膜穿刺术阴性的治疗妊娠组中，出生时诊断cCMV的新生儿比例在血清转化、IgG-IgM阳性且IgG亲和力低、IgG-IgM阳性且IgG亲和力中等以及分子检测阳性者中分别为23.2%（63例中19例）、10.9%（90例中11例）和6.3%（90例中6例）（p=0.003）。
结论： 大规模真实世界数据证实，VCV改善了原发性CMV感染妊娠的结局，且具有良好的安全性。

英文摘要

BACKGROUND: Congenital cytomegalovirus infection (cCMV) is a leading cause of neurodevelopmental impairment and congenital sensorineural hearing loss (SNHL). Since December 2020, valacyclovir (VCV) is reimbursed by the Italian National Health System to reduce maternal-fetal CMV transmission following primary CMV maternal infection.
OBJECTIVE: The aim of this study is to evaluate the effectiveness of VCV in preventing fetal CMV infection, termination of pregnancy, miscarriage, congenital CMV infection at birth and presence of signs/symptoms of cCMV in newborns.
STUDY DESIGN: The current study provides an update on previously published data from a large multicenter observational Italian study including women with primary CMV infection acquired during the periconceptional period and up to 24 gestational weeks between January 2010 and June 2025. Primary outcomes are CMV transmission at amniocentesis, termination of pregnancy, miscarriage, transmission at birth (positive CMV DNA on newborn's urine), symptomatic cCMV, and a composite outcome (occurrence of transmission at amniocentesis or at birth or termination of pregnancy or miscarriage).
RESULTS: Overall, 832 women were included (826 singletons and 8 sets of twin pregnancies, total 842 fetuses); 588 fetuses received prenatal VCV (576 singletons and 6 twins) and 254 were untreated (248 singletons and 4 twins). CMV-positive amniocentesis occurred in 17.2% (64/373) of VCV-treated fetuses compared with 27.9% (38/136) of untreated one (p=0.007, aOR 0.53 [95%CI 0.34, 0.85]).Termination of pregnancy and miscarriage occurred in 4.7% (26/555) and 0.7% (4/555) of treated fetuses versus 10.0% (25/250) and 1.6% (4/250) of untreated one, respectively (p=0.004, aOR 0.46 [95%CI 0.25, 0.78] and p=0.24, aOR 0.45 [95%CI 0.11, 1.80]). Neonatal CMV DNA in urine was detected in 23.7% (124/525) and 27.1% (60/221) of newborns from treated and untreated pregnancies, respectively (p=0.31, aOR 0.83 [95%CI 0.58, 1.19]). The prevalence of symptomatic congenital infection at birth was significantly less frequent in the VCV group (3.6% 19/525 vs. 9.9% 22/221, p=0.001, aOR 0.34 [95%CI 0.18, 0.64]). The composite outcome occurred less frequently in treated pregnancies (27.2% vs. 35.8%, p = 0.012, aOR 0.67 [95%CI 0.49, 0.91]). VCV-related adverse events were reported in 6.7% of cases and were mild or moderate. The diagnosis of cCMV infection at birth following a negative amniocentesis was not significantly different among treated and untreated pregnancies (12.9%, 36/280 versus 7.3%, 7/96; p = 0.139). In the group of treated pregnancies with negative amniocentesis the proportion of newborn with cCMV diagnosed at birth was 23.2% (19 of 63), 10.9% (11 of 90) and 6.3% (6 of 90) among those with seroconversion, positive lgG-IgM and low IgG avidity and positive lgG-IgM and intermediate IgG avidity and positive molecular test respectively (p=0.003).
CONCLUSIONS: Large scale real-life data confirm that VCV improves the outcome of pregnancy with CMV primary infection with a good safety profile.