Francesca Cervi

Parvovirus B19 in pregnancy: possible consequences of vertical transmission

The aim was to determine the outcome of pregnancies complicated by maternal Parvovirus B19 (B19) infection.

Diagnosis and prognosis of congenital CMV infection: A case report and review of the literature

Abstract Congenital cytomegalovirus (CMV) infection is the leading non-genetic cause of sensori-neural hearing loss and neurodevelopmental sequelae. Despite these alarming facts, the general public healthcare system is often not aware of CMV and not enough is done to prevent congenital CMV infection.We describe the clinical and laboratory monitoring of a case with primary CMV infection occurring before the first trimester of gestation. Specific literature review is included in order to point out major goals achieved in the diagnosis and prognosis of congenital CMV infection and the many questions still unanswered. Serological diagnosis of primary CMV infection was performed based on serum-CMV specific-IgM antibodies, combined with low avidity anti-CMV IgG antibodies. The maternal infection was asymptomatic, as it is for most infections in immunocompetent patients. Therefore, disclosing primary infection depended on specific serological tests during the initial period of pregnancy (before weeks 12–16 of gestation). The invasive (amniocentesis) and non-invasive (ultrasonographic examination) prenatal tests, carried out at 21 weeks gestation, revealed a severe CMV infection in a fetus small for gestational age with ventriculomegaly. The presence of overt ultrasound abnormalities combined with high viral load in the amniotic fluid sampled at the appropriate times was highly suggestive of an unfavourable prognosis. The autopsy performed on the fetus confirmed severe disseminated CMV infection with histological brain damage.

Perinatal Outcomes of Non-Primary Maternal Cytomegalovirus Infection: A 15-Year Experience

Objective: To evaluate perinatal outcomes in case of non-primary maternal cytomegalovirus (CMV) infection. Methods: We performed a retrospective cohort study of pregnant women with active CMV infection referred to our unit over a 15-year period (January 2000 to December 2014). Non-primary infection was diagnosed on the basis of the results of confirmatory serological and virological tests (avidity test, immunoblotting, real-time PCR-DNA). The vertical transmission rate and the percentage of symptomatic congenital infection were determined in this group of patients. Results: A total of 205 pregnant women were enrolled. Congenital infection occurred in 7 (3.4%) fetuses/neonates. Symptomatic disease was present at birth in 3 of the 7 congenitally infected neonates (1.5%). Two out of 3 symptomatic newborns presented a pathologic second-trimester ultrasound scan. Conclusion: Maternal immunity offers substantial protection against intrauterine transmission of CMV infection, but not against disease once the fetus is infected.

Study of Soluble HLA-G in Congenital Human Cytomegalovirus Infection

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be expressed as membrane-bound and soluble forms. HLA-G expression increases strongly during viral infections such as congenital human cytomegalovirus (HCMV) infections, with functional consequences in immunoregulation. In this work we investigated the expression of soluble (s)HLA-G and beta-2 microglobulin (component of HLA) molecules in correlation with the risk of transmission and severity of congenital HCMV infection. We analyzed 182 blood samples from 130 pregnant women and 52 nonpregnant women and 56 amniotic fluid samples from women experiencing primary HCMV infection. The median levels of sHLA-G in maternal serum of women with primary HCMV infection were higher in comparison with nonprimary and uninfected pregnant women (p < 0.001). AF from HCMV symptomatic fetuses presented higher sHLA-G levels in comparison with infected asymptomatic fetuses (p < 0.001), presence of HLA-G free-heavy chain, and a concentration gradient from amniotic fluid to maternal blood. No significant statistical difference of beta-2 microglobulin median levels was observed between all different groups. Our results suggest the determination of sHLA-G molecules in both maternal blood and amniotic fluid as a promising biomarker of diagnosis of maternal HCMV primary infection and fetal HCMV disease.

Congenital Cytomegalovirus Infection: Prognostic Value of Maternal DNAemia at Amniocentesis

Background. Human Cytomegalovirus (HCMV) is the most common cause of childhood hearing loss and can lead to neurodevelopmental delay. To date, few studies have examined the correlation between maternal viremia and congenital HCMV infection. The aim of our study was to ascertain if HCMV DNA in the peripheral blood of pregnant women with primary HCMV infection at the time of amniocentesis may have a prognostic value in terms of congenital infection and neonatal symptomatic disease. Methods. We performed a prospective observational study of pregnant women referred to our maternal-fetal medicine division with suspected HCMV infection. Primary infection was diagnosed based on seroconversion for HCMV and/or HCMV immunoglobulin M–positive and low or moderate HCMV immunoglobulin G avidity. At the time of amniocentesis, maternal blood samples were collected and analyzed by means of real-time polymerase chain reaction to determine the presence of viral DNAemia. Fetuses and newborns were evaluated for the presence of congenital infection and symptomatic disease. Results. A total of 239 pregnant women were enrolled; 32 blood samples (13.4%) were positive, and 207 (86.6%) were negative for HCMV DNA. The overall rate of transmission was 23.4%. Fifteen infected patients (26.8%) were symptomatic. Vertical transmission occurred in 14 women (43.8%) with positive and 42 (20.3%) with negative results for HCMV DNAemia (P = .006; odds ratio, 3.06; 95% confidence interval, 1.41–6.64). Symptomatic infection occurred in 6 (42.9%) infected fetuses or newborns from women with and in 9 (21.4%) from women without viral DNAemia (P = .16). Conclusion. Maternal viremia at amniocentesis is associated with a 3-fold greater chance of congenital infection, but it is not correlated with symptomatic disease.

Congenital cytomegalovirus infection and small for gestational age infants

To evaluate the incidence of infants with birth weight less than the 10th centile for small for gestational age (SGA) in primary maternal cytomegalovirus (CMV) infection and to determine whether SGA predicts poor neurodevelopmental outcome.

Evolving treatment implementation among HIV- infected pregnant women and their partners: Results from a national surveillance study in Italy, 2001-2015

Background The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre–exposure chemoprophylaxis (PrEP), and treatment of HIV–negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. Methods The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001–2005, 2006–2010, 2011–2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. Results The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV–negative, 28.6% HIV–positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001–2005 to 81.3% in 2011–2015, P < 0.001), and in the proportion of HIV–positive partners on antiretroviral treatment (from 73.3% in 2001–2005 to 95.8% in 2011–2015, P = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV–negative partners. Conclusions The results suggest good implementation of antiretroviral treatment among HIV–positive women and their HIV–positive partners, but no implementation, even in recent years, of Pre–Exposure Prophylaxis (PrEP) among uninfected male partners. Further studies should assess the determinants of this occurrence and clarify the attitudes and the potential barriers to PrEP use.