TY - JOUR
T1 - The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis
AU - Chatzakis, Christos
AU - Shahar-Nissan, Karen
AU - Faure-Bardon, Valentine
AU - Picone, Olivier
AU - Hadar, Eran
AU - Amir, Jacob
AU - Egloff, Charles
AU - Vivanti, Alexandre
AU - Sotiriadis, Alexandros
AU - Leruez-Ville, Marianne
AU - Ville, Yves
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024/2
Y1 - 2024/2
N2 - Objective: Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection. Data Sources: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www.clinicaltrials.gov), and gray literature sources were searched from inception to March 2023. Study Eligibility Criteria: Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included. Methods: All corresponding authors of the eligible studies were contacted. Cochrane's Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy. Results: Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18–0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12–0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16–0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19–0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14–0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17–0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22–0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%. Conclusion: A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.
AB - Objective: Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection. Data Sources: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www.clinicaltrials.gov), and gray literature sources were searched from inception to March 2023. Study Eligibility Criteria: Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included. Methods: All corresponding authors of the eligible studies were contacted. Cochrane's Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy. Results: Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18–0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12–0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16–0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19–0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14–0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17–0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22–0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%. Conclusion: A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.
KW - amniocentesis
KW - congenital cytomegalovirus infection
KW - first trimester
KW - neonates
KW - periconceptional period
KW - prevention
KW - primary infection
KW - side effects
KW - valacyclovir
KW - vertical transmission
UR - http://www.scopus.com/inward/record.url?scp=85167831827&partnerID=8YFLogxK
U2 - 10.1016/j.ajog.2023.07.022
DO - 10.1016/j.ajog.2023.07.022
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C2 - 37473793
AN - SCOPUS:85167831827
SN - 0002-9378
VL - 230
SP - 109-117.e2
JO - American Journal of Obstetrics and Gynecology
JF - American Journal of Obstetrics and Gynecology
IS - 2
ER -