Secondary prevention of congenital cytomegalovirus infection with valacyclovir following maternal primary infection in early pregnancy.

OBJECTIVE: Cytomegalovirus (CMV) maternal primary infection (MPI) in early pregnancy is the main risk factor for congenital CMV (cCMV) infection with long-term sequelae. Our aim was to evaluate, in a single center offering CMV serology screening at 11-14 gestational weeks, secondary prevention of cCMV by administration of high-dosage maternal oral valacyclovir (VACV) in the first trimester of pregnancy. METHODS: This was a case-control study in a longitudinal cohort of pregnancies with CMV-MPI diagnosed prior to 14 weeks of gestation by serology screening (immunoglobulin (Ig) M and IgG measurement and IgG avidity) between 2009 and 2020. From October 2019 onwards, all women presenting at our center with MPI before 14 weeks' gestation were offered treatment with high-dosage oral VACV (8 g/day, 4 g twice/day). We used propensity score matching to compare fetal infection rates in cases treated with maternal oral VACV (8 g/day) with those in untreated controls. Fetal infection was assessed following amniocentesis at 17-22 weeks of gestation, by polymerase chain reaction (PCR) analysis of amniotic fluid for viral DNA. RESULTS: Of 310 cases of CMV-MPI identified, 269 underwent amniocentesis for PCR. Of these, 66 were offered, and 65 accepted, treatment with VACV. From the remaining untreated cases, we selected 65 controls, matched for proportion of periconceptional infections and gestational age at amniocentesis. VACV was initiated at a median gestational age of 12.71 (interquartile range (IQR), 10.00-13.86) weeks and the median duration of treatment was 35 (IQR, 26-54) days. On multivariate logistic regression, fetal infection was lower in the treated group (odds ratio, 0.318 (95% CI, 0.120-0.841); P = 0.021). One treated patient developed acute renal failure 4 weeks after initiation of VACV therapy, but this resolved within 5 days after treatment was stopped. CONCLUSION: This study confirms the acceptability, tolerance and benefit of secondary prevention by VACV of cCMV infection in a clinical setting with a well-established routine maternal serum screening policy in the first trimester of pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

First-trimester diagnosis of congenital cytomegalovirus infection after maternal primary infection in early pregnancy: feasibility study of viral genome amplification by PCR on chorionic villi obtained by CVS.

OBJECTIVE: To evaluate the feasibility of amplification of the viral genome by polymerase chain reaction (PCR) analysis of trophoblast samples obtained by chorionic villus sampling (CVS) in cases of maternal primary infection (MPI) with cytomegalovirus (CMV) in early pregnancy. METHODS: This was a prospective study carried out at the Department of Obstetrics and Fetal Medicine, Hopital Necker-E.M., between October 2019 and October 2020. Following CMV serology screening in early pregnancy, CVS was offered to women at 11-14 weeks' gestation after CMV-MPI ≤ 10 weeks. Array-comparative genomic hybridization and amplification of the viral genome by PCR were performed on the trophoblasts obtained by CVS. All cases also underwent amniocentesis from 17 weeks onwards and PCR was performed on the amniotic fluid. Secondary prevention with valacyclovir was initiated as soon as MPI was diagnosed, to decrease the risk of vertical transmission. We evaluated the diagnostic performance of CMV-PCR of trophoblast obtained by CVS, using as the reference standard PCR of amniotic fluid obtained by amniocentesis. RESULTS: CVS was performed in 37 pregnancies, at a median (range) gestational age of 12.7 (11.3-14.4) weeks. CMV-PCR in chorionic villi was positive in three and negative in 34 cases. CMV-PCR following amniocentesis, performed at a median (range) gestational age of 17.6 (16.7-29.9) weeks, was positive for the three cases which were positive following CVS and, of the 34 patients with a negative finding following CVS, amniocentesis was negative in 31 and positive in three. The sensitivity of CMV-PCR analysis of trophoblast obtained by CVS for the diagnosis of CMV, using as the reference standard PCR analysis of amniotic fluid obtained by amniocentesis, was 50% (95% CI, 19-81%), specificity was 100% (95% CI, 89-100%), positive predictive value was 100% (95% CI, 44-100%) and negative predictive value was 91% (95% CI, 77-97%). CONCLUSIONS: Diagnosis of placental infection following MPI in early pregnancy can be achieved by PCR amplification of the CMV genome in chorionic villi. We propose that negative CMV-PCR in the trophoblast after 12 weeks could be used to exclude CMV-related embryopathy leading to sequelae. However, this needs to be confirmed through long-term follow-up evaluation. These findings could help to establish CVS as the diagnostic test of choice following maternal serology screening in early pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Severe and fatal forms of COVID-19 in children.

OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.