Treatment with valacyclovir during pregnancy for prevention of congenital cytomegalovirus infection: a real-life multicenter Italian observational study

被引：27

作者：

Zammarchi, Lorenzo ^{[1
,2
,3
]}

Tomasoni, Lina Rachele ^{[4
]}

Liuzzi, Giuseppina ^{[5
]}

Simonazzi, Giuliana ^{[6
,7
]}

Dionisi, Camilla ^{[6
,7
]}

Mazzarelli, Laura Letizia ^{[8
]}

Seidenari, Anna ^{[6
,7
]}

Maruotti, Giuseppe Maria ^{[8
]}

Ornaghi, Sara ^{[9
,10
]}

Castelli, Francesco ^{[11
]}

Abbate, Isabella ^{[5
]}

Bordi, Licia ^{[5
]}

Mazzotta, Stefania ^{[5
]}

Fusco, Paolo ^{[12
]}

Torti, Carlo ^{[12
]}

Carducci, Francesca Ippolita Calo ^{[13
]}

Baccini, Michela ^{[14
]}

Modi, Giulia ^{[1
]}

Galli, Luisa ^{[15
,16
]}

Lilleri, Daniele ^{[17
]}

Furione, Milena ^{[17
]}

Zavattoni, Maurizio ^{[17
]}

Ricciardi, Alessandra ^{[18
]}

Arossa, Alessia ^{[19
]}

Vimercati, Antonella ^{[20
]}

Lovatti, Sofia ^{[4
]}

Salome, Serena ^{[21
]}

Raimondi, Francesco ^{[21
]}

Sarno, Laura ^{[21
]}

Sforza, Anita ^{[4
]}

Fichera, Anna ^{[22
]}

Caforio, Leonardo ^{[23
]}

Trotta, Michele ^{[2
,3
]}

MEGAL ITALI Working Grp ^{[7
,24
]}

机构：

[1] Univ Florence, Dept Expt & Clin Med, Florence, Italy

[2] Careggi Univ Hosp, Infect & Trop Dis Unit, Florence, Italy

[3] Tuscany Reg Referral Ctr Infect Dis Pregnancy, Florence, Italy

[4] Univ Brescia, Dept Infect & Trop Dis, Azienda Socio Sanit Territoriale ASST Spedali Civ, Brescia, Italy

[5] IRCCS, Natl Inst Infect Dis Lazzaro Spallanzani, Rome, Italy

[6] Azienda Osped Univ Bologna, Ist Ricovero & Cura Carattere Sci IRCCS, Obstet Unit, Bologna, Italy

[7] Alma Mater Studiorum Univ Bologna, Dept Med & Surg Sci, Bologna, Italy

[8] Univ Naples Federico II, Dept Publ Hlth, Naples, Italy

[9] Fdn IRCCS San Gerardo Tintori, Dept Obstet, Monza, Italy

[10] Univ Milano Bicocca, Sch Med & Surg, Monza, Italy

[11] Univ Brescia, Dept Clin & Expt Sci, Infect & Trop Dis Unit, Brescia, Italy

[12] Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, Infect & Trop Dis Unit, Catanzaro, Italy

[13] Bambino Gesu Pediat Hosp, Infect Dis Unit, Rome, Italy

[14] Univ Florence, Dept Stat Comp Sci, Applicat G Parenti, Florence, Italy

[15] Meyer Childrens Hosp IRCCS, Infect Dis Unit, Florence, Italy

[16] Univ Florence, Dept Hlth Sci, Florence, Italy

[17] Fdn IRCCS Policlin San Matteo, Microbiol & Virol Unit, Pavia, Italy

[18] Fdn IRCCS Policlin San Matteo, Infect Dis Unit, Pavia, Italy

[19] Fdn IRCCS Policlin San Matteo, Dept Obstet & Gynecol, Pavia, Italy

[20] Univ Bari Aldo Moro, Dept Precis & Regenerat Med & Ionian Area, Bari, Italy

[21] Univ Naples Federico II, Dept Translat Med Sci, Div Neonatol, Naples, Italy

[22] Univ Brescia, Dept Clin & Expt Sci, Div Obstet & Gynecol, ASST Spedali Civili, Brescia, Italy

[23] Bambino Gesu Pediat Hosp, Fetal & Perinatal Med & Surg Unit, Rome, Italy

[24] Microbiol Unit, IRCCS Azienda Ospeda liero Universitaria Bologna, Bologna, Italy

来源：

AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM | 2023年 / 5卷 / 10期

关键词：

congenital; cytomegalovirus; fetal; immunoglobulin; preg-nant; screening; valaciclovir; women; HYPERIMMUNE GLOBULIN; LONG-TERM; DIAGNOSIS; SEQUELAE; RISK;

D O I：

10.1016/j.ajogmf.2023.101101

中图分类号：

R71 [妇产科学];

学科分类号：

100211 ;

摘要：

BACKGROUND: 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.OBJECTIVE: 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.STUDY DESIGN: 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).RESULTS: 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.CONCLUSION: 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.

引用

页数：10

共 41 条

[1]

Ahlfors K, 1999, SCAND J INFECT DIS, V31, P443, DOI 10.1080/00365549950163969

[2] Revised Protocol for Secondary Prevention of Congenital Cytomegalovirus Infection With Valaciclovir Following Infection in Early Pregnancy [J].