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

congenital cytomegalovirus fetal immunoglobulin pregnant screening valaciclovir women

Journal

American journal of obstetrics & gynecology MFM
ISSN: 2589-9333
Titre abrégé: Am J Obstet Gynecol MFM
Pays: United States
ID NLM: 101746609

Informations de publication

Date de publication:
Oct 2023
Historique:
received: 20 04 2023
revised: 30 06 2023
accepted: 14 07 2023
pubmed: 30 7 2023
medline: 30 7 2023
entrez: 29 7 2023
Statut: ppublish

Résumé

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.

Sections du résumé

BACKGROUND 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 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 METHODS
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 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 CONCLUSIONS
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.

Identifiants

DOI: 10.1016/j.ajogmf.2023.101101 PMID: 37516151
pubmed: 37516151
pii: S2589-9333(23)00243-4
doi: 10.1016/j.ajogmf.2023.101101
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101101

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Lorenzo Zammarchi (L)

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). Electronic address: lorenzo.zammarchi@unifi.it.

Lina Rachele Tomasoni (LR)

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).

Giuseppina Liuzzi (G)

National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy (Dr Liuzzi, Dr Abbate, Dr Bordi, and Dr Mazzotta).

Giuliana Simonazzi (G)

Obstetric Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy (Dr Simonazzi, Dr Dionisi, and Dr Seidenari); Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy (Dr Simonazzi, Dr Dionisi, Dr Seidenari, and Dr Lazzarotto).

Camilla Dionisi (C)

Obstetric Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy (Dr Simonazzi, Dr Dionisi, and Dr Seidenari); Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy (Dr Simonazzi, Dr Dionisi, Dr Seidenari, and Dr Lazzarotto).

Laura Letizia Mazzarelli (LL)

Department of Public Health, University of Naples Federico II, Naples, Italy (Dr Mazzarelli and Dr Maruotti).

Anna Seidenari (A)

Obstetric Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy (Dr Simonazzi, Dr Dionisi, and Dr Seidenari); Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy (Dr Simonazzi, Dr Dionisi, Dr Seidenari, and Dr Lazzarotto).

Giuseppe Maria Maruotti (GM)

Department of Public Health, University of Naples Federico II, Naples, Italy (Dr Mazzarelli and Dr Maruotti).

Sara Ornaghi (S)

Department of Obstetrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy (Dr Ornaghi); University of Milano-Bicocca School of Medicine and Surgery, Monza, Italy (Dr Ornaghi).

Francesco Castelli (F)

Infectious and Tropical Diseases Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (Dr Castelli).

Isabella Abbate (I)

National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy (Dr Liuzzi, Dr Abbate, Dr Bordi, and Dr Mazzotta).

Licia Bordi (L)

National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy (Dr Liuzzi, Dr Abbate, Dr Bordi, and Dr Mazzotta).

Stefania Mazzotta (S)

National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy (Dr Liuzzi, Dr Abbate, Dr Bordi, and Dr Mazzotta).

Paolo Fusco (P)

Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy (Dr Fusco and Dr Torti).

Carlo Torti (C)

Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy (Dr Fusco and Dr Torti).

Francesca Ippolita Calò Carducci (FI)

Infectious Disease Unit, Bambino Gesù Children's Hospital, Rome, Italy (Dr Calò Carducci).

Michela Baccini (M)

Department of Statistics, Computer Science, Applications "G. Parenti," University of Florence, Florence, Italy (Dr Baccini).

Giulia Modi (G)

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy (Dr Zammarchi and Dr Modi).

Luisa Galli (L)

Infectious Diseases Unit, Meyer Children's Hospital IRCCS, Florence, Italy (Dr Galli); Department of Health Sciences, University of Florence, Florence, Italy (Dr Galli).

Daniele Lilleri (D)

Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (Dr Lilleri, Dr Furione, and Dr Zavattoni).

Milena Furione (M)

Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (Dr Lilleri, Dr Furione, and Dr Zavattoni).

Maurizio Zavattoni (M)

Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (Dr Lilleri, Dr Furione, and Dr Zavattoni).

Alessandra Ricciardi (A)

Infectious Diseases Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (Dr Ricciardi).

Alessia Arossa (A)

Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (Dr Arossa).

Antonella Vimercati (A)

Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Bari, Italy (Dr Vimercati).

Sofia Lovatti (S)

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).

Serena Salomè (S)

Division of Neonatology, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy (Dr Salomè and Dr Raimondi, and Dr Sarno).

Francesco Raimondi (F)

Division of Neonatology, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy (Dr Salomè and Dr Raimondi, and Dr Sarno).

Laura Sarno (L)

Division of Neonatology, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy (Dr Salomè and Dr Raimondi, and Dr Sarno).

Anita Sforza (A)

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).

Anna Fichera (A)

Division of Obstetrics and Gynecology, Department of Clinical and Experimental Sciences, ASST Spedali Civili, University of Brescia, Brescia, Italy (Dr Fichera).

Leonardo Caforio (L)

Fetal and Perinatal Medicine and Surgery Unit, Bambino Gesù Children's Hospital, Rome, Italy (Dr Caforio).

Michele Trotta (M)

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).

Tiziana Lazzarotto (T)

Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy (Dr Simonazzi, Dr Dionisi, Dr Seidenari, and Dr Lazzarotto); Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy (Dr Lazzarotto).

Classifications MeSH