Outcome of pregnancies with a very recent primary cytomegalovirus infection in the first trimester treated with hyperimmunoglobulin: an observational study

OBJECTIVE In this study we set out to examine the efficacy of the hyperimmunoglobulin (HIG treatment in women with a recent primary CMV infection up to 14 weeks' gestation. METHODS Ongoing observational study at the prenatal medicine departments of Tuebingen, Bonn, Cologne and Erlangen, Germany as well as the laboratory Prof. Gisela Enders and Colleagues in Stuttgart, Germany and the Institute for Medical Virology at the University of Tuebingen. Enrollment criteria were the presence of confirmed, very recent primary CMV infection in the first trimester and a gestational age at first HIG administration of ≤ 14 weeks. The following inclusion criteria indicated a recent primary infection: low anti-IgG levels, low anti-CMV-IgG avidity in the presence of a positive CMV IgM test and no or just seroconversion anti-gB2-IgG-reactivity. The HIG administration (Cytotect CP®, Biotest, Germany) was started as soon as possible within few days after the first visit in the four units. HIG was administered at 200 IU per kilogram bodyweight intravenously and repeated every two weeks until about 18 weeks' gestation. Maternal-fetal transmission at the time of amniocentesis was considered as relevant primary outcome measure. Multivariate logistic regression analysis was used to determine significant covariates that could be used for the prediction of maternal-fetal transmission. RESULTS 149 pregnant women and 153 fetuses were treated. Median maternal age and weight was 32.0 years and 65.0 kg, respectively. Median gestational age at the time of the first referral to one of the four centers was 9.4 weeks. Median anti-CMV-IgG levels, the anti-CMV-IgM index and the CMV IgG avidity was 5.7 U/ml, 2.5, and 22.3%, respectively. Treatment with HIG started at a median gestational age of 10.6 weeks and ended at 17.9 weeks. Within this time frame, HIGs were administered on average 4 times. Amniocentesis was carried out at a median gestational age of 20.4 weeks. In 143 (93.6%) of the 153 cases, the fetus was not infected. Maternal-fetal transmission occurred in 10 cases (6.5%, [95% CI 3.2 - 11.7]). In the uni- and multivariate logistic regression analysis, only the level of the anti-IgM index was significantly associated with maternal-fetal transmission at the time of the amniocentesis. However, only four (40.0%) of the 10 cases with maternal-fetal transmission had an anti-IgM level above 11.4 which corresponds to the 95th centile of the pregnancies without transmission. CONCLUSION HIG is a treatment option to prevent maternal-fetal transmission in a case of a primary CMV infection. However, treatment is only beneficial in women with a very recent primary infection in the first trimester or during the periconceptional period, a timely start and an appropriate treatment interval. This article is protected by copyright. All rights reserved.