Zammarchi Lorenzo, Tomasoni Lina Rachele, Liuzzi Giuseppina, Simonazzi Giuliana, Dionisi Camilla, Mazzarelli Laura Letizia, Seidenari Anna, Maruotti Giuseppe Maria, Ornaghi Sara, Castelli Francesco, Abbate Isabella, Bordi Licia, Mazzotta Stefania, Fusco Paolo, Torti Carlo, Calò Carducci Francesca Ippolita, Baccini Michela, Modi Giulia, Galli Luisa, Lilleri Daniele, Furione Milena, Zavattoni Maurizio, Ricciardi Alessandra, Arossa Alessia, Vimercati Antonella, Lovatti Sofia, Salomè Serena, Raimondi Francesco, Sarno Laura, Sforza Anita, Fichera Anna, Caforio Leonardo, Trotta Michele, Lazzarotto Tiziana
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy (Dr Zammarchi and Dr Modi); Infectious and Tropical Disease Unit, Careggi University Hospital, Florence, Italy (Dr Zammarchi and Dr Trotta); Tuscany Regional Referral Center for Infectious Diseases in Pregnancy, Florence, Italy (Dr Zammarchi and Dr Trotta).
Department of Infectious and Tropical Diseases, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili, University of Brescia, Brescia, Italy (Dr Tomasoni, Dr Lovatti, and Dr Sforza).
Am J Obstet Gynecol MFM. 2023 Oct;5(10):101101. doi: 10.1016/j.ajogmf.2023.101101. Epub 2023 Jul 27.
Valacyclovir is the only treatment demonstrated to be effective for the prevention of vertical transmission of cytomegalovirus within a clinical randomized, placebo-controlled trial and has been reimbursed by the Italian National Health System since December 2020.
This study reported the results of a real-life Italian multicenter observational study on cytomegalovirus infection in pregnancy evaluating the effect of the introduction of valacyclovir in the clinical practice for the prevention of vertical transmission of cytomegalovirus.
The outcomes of women who received valacyclovir treatment and their fetuses or newborns were compared with those of a retrospective cohort observed between 2010 and 2020 who did not receive the antiviral treatment. The inclusion criterion was the diagnosis of cytomegalovirus primary infection occurring in the periconceptional period or up to 24 weeks of gestation. The primary outcome was the transmission by the time of amniocentesis. The secondary outcomes were termination of pregnancy, transmission at birth, symptomatic infection at birth, and a composite outcome (termination of pregnancy or transmission at birth).
A total of 447 pregnant women from 10 centers were enrolled, 205 women treated with valacyclovir (called the valacyclovir group, including 1 twin pregnancy) and 242 women not treated with valacyclovir (called the no-valacyclovir group, including 2 twin pregnancies). Valacyclovir treatment was significantly associated with a reduction of the diagnosis of congenital cytomegalovirus infection by the time of amniocentesis (weighted odds ratio, 0.39; 90% confidence interval, 0.22-0.68; P=.005; relative reduction of 61%), termination of pregnancy (weighted odds ratio, 0.36; 90% confidence interval, 0.17-0.75; P=.0021; relative reduction of 64%), symptomatic congenital cytomegalovirus infection at birth (weighted odds ratio, 0.17; 90% confidence interval, 0.06-0.49; P=.006; relative reduction of 83%). The treatment had no significant effect on the rate of diagnosis of congenital cytomegalovirus infection at birth (weighted odds ratio, 0.85; 90% confidence interval, 0.57-1.26; P=.500), but the composite outcome (termination of pregnancy or diagnosis of congenital cytomegalovirus infection at birth) occurred more frequently in the no-valacyclovir group (weighted odds ratio, 0.62; 90% confidence interval, 0.44-0.88; P=.024). Of note, the only symptomatic newborns with congenital cytomegalovirus infection in the valacyclovir group (n=3) were among those with positive amniocentesis. Moreover, 19 women (9.3%) reported an adverse reaction to valacyclovir treatment, classified as mild in 17 cases and moderate in 2 cases. Lastly, 4 women (1.9%) presented renal toxicity with a slight increase in creatinine level, which was reversible after treatment suspension.
Our real-life data confirm that valacyclovir significantly reduces the rate of congenital cytomegalovirus diagnosis at the time of amniocentesis with a good tolerability profile and show that the treatment is associated with a reduction of termination of pregnancy and symptomatic congenital cytomegalovirus infection at birth.
在一项临床随机、安慰剂对照试验中，伐昔洛韦是唯一被证明对预防巨细胞病毒垂直传播有效的治疗方法，自2020年12月起已被意大利国家卫生系统报销。
本研究报告了一项意大利多中心关于孕期巨细胞病毒感染的真实观察性研究结果，评估在临床实践中引入伐昔洛韦预防巨细胞病毒垂直传播的效果。
将接受伐昔洛韦治疗的女性及其胎儿或新生儿的结局与2010年至2020年间未接受抗病毒治疗的回顾性队列的结局进行比较。纳入标准为受孕期间或妊娠24周内发生的巨细胞病毒原发性感染的诊断。主要结局是羊膜穿刺术时的传播情况。次要结局包括终止妊娠、出生时传播、出生时有症状感染以及复合结局（终止妊娠或出生时传播）。
来自10个中心的447名孕妇入组，205名接受伐昔洛韦治疗的女性（称为伐昔洛韦组，包括1例双胎妊娠）和242名未接受伐昔洛韦治疗的女性（称为无伐昔洛韦组，包括2例双胎妊娠）。伐昔洛韦治疗与羊膜穿刺术时先天性巨细胞病毒感染诊断的减少显著相关（加权比值比，0.39；90%置信区间，0.22 - 0.68；P = 0.005；相对减少61%），终止妊娠（加权比值比，0.36；90%置信区间，0.17 - 0.75；P = 0.0021；相对减少64%），出生时有症状的先天性巨细胞病毒感染（加权比值比，0.17；90%置信区间，0.06 - 0.49；P = 0.006；相对减少83%）。该治疗对出生时先天性巨细胞病毒感染的诊断率无显著影响（加权比值比，0.85；90%置信区间，0.57 - 1.26；P = 0.500），但复合结局（终止妊娠或出生时先天性巨细胞病毒感染诊断）在无伐昔洛韦组中更频繁出现（加权比值比，0.62；90%置信区间，0.44 - 0.88；P = 0.024）。值得注意的是，伐昔洛韦组中仅有的3例先天性巨细胞病毒感染有症状的新生儿均在羊膜穿刺术阳性者中。此外，19名女性（9.3%）报告了对伐昔洛韦治疗的不良反应，其中17例为轻度，2例为中度。最后，4名女性（1.9%）出现肾毒性，肌酐水平略有升高，治疗暂停后可逆转。
我们的真实数据证实，伐昔洛韦可显著降低羊膜穿刺术时先天性巨细胞病毒的诊断率，耐受性良好，并表明该治疗与减少终止妊娠和出生时有症状的先天性巨细胞病毒感染相关。
