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Abstract: Although the diagnosis of congenital CMV infection is still complex, important goals have been achieved in recent years, among which are: the availability of more reliable IgM tests for screening pregnant women whose pre-pregnancy serological status for CMV is unknown, tests to determine the avidity index of anti-CMV IgG, allowing the diagnosis of a primary CMV infection and innovative and traditional virological tests to detect the virus in amniotic fluid. When a woman is found to be IgM-positive, further diagnostic evaluation focused on determining whether this is due to a primary infection should be carried out. Maternal primary infections that were difficult to determine until a few years ago unless documented by seroconversions can now be readily diagnosed from the presence of low/moderate avidity anti-CMV antibody which persists for approximately 18–20 weeks after primary infection. In mothers at risk of transmitting the virus prenatal diagnosis can be performed between 21 and 22 weeks of gestation, and the amniotic fluid represents the pathological material of choice to determine intrauterine virus transmission. At birth or in the first 2/3 weeks of life, it is essential to use appropriate tests for diagnosis of CMV congenital infection. [Copyright &y& Elsevier]

Abstract: Objective: To assess if detecting bacterial vaginosis either in early pregnancy or at midtrimester may predict adverse pregnancy outcome in women at risk for preterm delivery. Study design: 242 pregnant women with a previous preterm delivery were evaluated for bacterial vaginosis either in the first trimester (prior to 10+0 weeks) or in the second one (24–26 weeks). Adverse outcome was intended as miscarriage (≤25 weeks), or premature delivery (≤36+6). Results: The risk of adverse pregnancy outcome was significantly increased in women diagnosed at first trimester with bacterial vaginosis (OR: 4.56; 95% CI: 2.54–8.93); the same finding at midtrimester did not increase significantly the risk of preterm delivery. Conclusions: Early screening for bacterial vaginosis in pregnant women who experienced a preterm delivery may help in predicting the risk of adverse outcome. [Copyright &y& Elsevier]

Congenital cytomegalovirus (CMV) infection is the leading non-genetic cause of sensori-neural hearing loss and neuro-developmental 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 anti bodies, 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. [ABSTRACT FROM AUTHOR]

The article discusses a randomized clinical trial which examined the effectiveness of hyperimmune globulin in preventing the transmission of congenital cytomegalovirus (CMV) infection during pregnancy. Topics discussed include the administration of hyperimmune globulin to pregnant women, congenital CMV infection in fetuses and infants, and comparison of T-cell-mediated immune response, virus-specific antibodies and viral DNA between the placebo group and hyperimmune globulin group.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To assess the diagnostic and prognostic value of cerebral magnetic resonance imaging (cMRI) in comparison with that of cerebral ultrasound (cUS) in predicting neurodevelopmental outcome in newborns with congenital cytomegalovirus (CMV) infection. Methods: Forty CMV-congenitally infected newborns underwent cUS and cMRI within the first month of life. Clinical course, laboratory findings, visual/hearing function and neurodevelopmental outcome were documented. Results: Thirty newborns showed normal cMRI, cUS and hearing/visual function in the first month of life; none showed CMV-related abnormalities at follow-up. Six newborns showed pathological cMRI and cUS findings (pseudocystis, ventriculomegaly, calcifications, cerebellar hypoplasia) but cMRI provided additional information (white matter abnormalities in three cases, lissencephaly/polymicrogyria in one and a cyst of the temporal lobe in another one); cerebral calcifications were detected in 3/6 infants by cUS but only in 2/6 by cMRI. Four of these 6 infants showed severe neurodevelopmental impairment and five showed deafness during follow-up. Three newborns had a normal cUS, but cMRI documented white matter abnormalities and in one case also cerebellar hypoplasia; all showed neurodevelopmental impairment and two were deaf at follow-up. One more newborn showed normal cUS and cMRI, but brainstem auditory evoked responses were abnormal; psychomotor development was normal at follow-up. Conclusions: Compared with cUS, cMRI disclosed additional pathological findings in CMV-congenitally infected newborns. cUS is a readily available screening tool useful in the identification of infected newborns with major cerebral involvement. Further studies with a larger sample size are needed to determine the prognostic role of MRI, particularly regarding isolated white matter lesions. [Copyright &y& Elsevier]

There is limited information about the determinants of voluntary pregnancy termination (VPT) among women with HIV in the current context of wide access to highly active antiretroviral therapy (HAART). To investigate this issue, we analysed the characteristics of a series of VPTs which occurred in an ongoing observational national study of pregnant women with HIV between 2002 and 2008. Sixty-three cases of VPT were compared with 334 pregnancies not ending in a VPT concurrently reported from the same centres. VPTs showed significant associations with unplanned pregnancy (odds ratio [OR]: 24.3; 95% confidence interval [CI]: 5.8-101.2), previous pregnancies reported to the study (OR: 2.5; 95% CI: 1.30-4.82), lower CD4 counts (270 vs. 420 cells/mm3), and HIV-infected current partner (OR: 1.88; 95% CI: 0.97-3.63). Our data indicate that there is still the need to improve pregnancy planning among women with HIV, and strongly suggest that interventions aimed at improving pregnancy planning might also reduce the occurrence of VPT. Women with low CD4 counts and those with an HIV-infected partner represent two groups that should receive particular attention in preventive strategies. [ABSTRACT FROM AUTHOR]

Limited information is currently available on the metabolic profile of nevirapine in pregnancy. We used data from a national observational study to evaluate plasma lipid profile in pregnant women receiving nevirapine. Lipid values were collected during routine clinical visits. Midpregnancy (second trimester) lipid values were analyzed according to use of nevirapine, calculating differences and 95% confidence intervals (CI) between women taking and not taking this drug. In order to adjust for possible confounders, multivariable models were constructed using as dependent variables levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) levels and TC/HDL-C ratio, and as independent variables age, body weight, previous treatment history, CD4 count, and presence of any antiretroviral therapy, use or nonuse of protease inhibitors, stavudine, and nevirapine at the time of blood sampling. Overall, 375 women had available data for analysis. Pregnant women on nevirapine, compared to women not taking this drug, had in univariate analyses higher levels of HDL-C (difference: +13.0 mg/dL [95%CI 7.4–18.6], p < 0.001), lower values of TC/HDL-C ratio (difference: −0.51 [0.23–0.80], p < 0.001) and a trend for lower levels of triglycerides (difference: −17.6 mg/dL [0.7–35.9], p = 0.06). Higher HDL-C levels were also associated with use of protease inhibitors and with no previous antiretroviral experience before pregnancy. The associations with higher HDL-C levels were confirmed in multivariable analyses. Our study indicates in pregnant women an association between nevirapine use and higher HDL-C levels. Further studies should assess whether this effect is due to an intrinsic activity of nevirapine and define the potential mechanisms involved. [ABSTRACT FROM AUTHOR]

In most European countries, pregnant women are tested for cytomegalovirus (CMV) during the first trimester of pregnancy. Within the last 5 years, European laboratories have made significant progress in solving diagnostic problems linked to infection in pregnancy. With advances in CMV serology, the presence of anti-CMV immunoglobulin (Ig)M detected by a screening test such as enzyme immunoassay, can be confirmed by blot, identifying pregnant women undergoing an active or recent infection. Furthermore, primary infections that were proven if a seroconversion was observed or suspected in the presence of IgM, can now be readily diagnosed by disclosing the presence of anti-CMV low avidity in IgM-positive mothers, greatly reducing the number of women who should be considered at risk of transmitting the virus. Virologic maternal tests are not enough to diagnose a recent primary maternal CMV infection and the detection or quantification of CMV in maternal blood does not seem to be associated with a higher risk for fetal infection. A cohort of 1520 pregnant women considered at risk of transmitting the virus were followed in a longitudinal study at the University of Bologna. Women were identified as part of routine CMV screening in several Italian regions and were IgM-positive for CMV. We documented IgG seroconversion in 83 women and 1437 were IgM-positive by commercial kit. [Copyright &y& Elsevier]

Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infection and fetal damage largely attributable to maternal primary infection. Most cases of congenital CMV infection in twins reported in the literature involved only 1 twin. We assessed the validity of polymerase chain reaction (PCR) and quantitative PCR on amniotic fluid (AF), at 21 to 22 weeks' gestation and at least 6 to 8 weeks after seroconversion, to predict the outcome of newborns in twin pregnancies. Two pregnant women with twin pregnancies and 1 woman with a triple pregnancy with primary CMV infection defined by the presence of immunoglobulin (Ig) M and low IgG avidity and/or by the presence of clinical symptoms and abnormal liver enzyme values were evaluated. CMV infection was found in 6 fetuses/ newborns, 3 of whom were symptomatic. In the first twin pregnancy with diamniotic-dichorionic separate placentas, CMV symptomatic infection of the female twin was demonstrated by positive virus isolation and high viral load in AF. The male fetus was not infected as demonstrated by negative CMV culture and DNA detection in AF. In the triple pregnancy, the woman had a placenta with 2 monozygotic twins (females) and a separate placenta with a heterozygotic twin (male). The quantitative PCR results were 103 genome equivalents (GE)/mL of females AF and 1.9 x 10[sup 5] GE/mL of male AF. Both female twins were asymptomatic at birth, whereas the male presented petechiae, thrombocytopenia, and cerebral ventriculomegaly. In the last twin pregnancy with fused dichorionic placentas, congenital CMV infection of both twins was diagnosed at birth in contrast with prenatal diagnosis. At time of... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is related to the susceptibility of rubella infection in human immunodeficiency virus-infected pregnant women.

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. [ABSTRACT FROM AUTHOR]

Presents an abstract of the study 'Neonatal Aortic Arch Thrombosis as a Result of Congenital Cytomegalovirus Infection,' by Marcello Lanari, Tiziana Lazzarotto et al., published in a 2001 issue of 'Pediatrics.'

Abstract: Background: Congenital cytomegalovirus (CMV) infection is a major cause of central nervous system damage leading to sensorineural hearing loss, mental retardation and cerebral palsy. Objectives: Identify the type of organ involvement and understand the histopathogenesis of damage in foetuses of women with a CMV-highly positive amniotic fluid. Study design: 34 foetuses with congenital CMV infection documented by prenatal diagnosis were studied. Three foetuses died in utero. The remaining pregnancies were electively terminated at 20–21 weeks gestation. Results: Foetal organs positive for CMV antigens were: placenta (100%), pancreas (100%), lung (87%), kidney (87%), liver (71%), brain (55%) and heart (44%). Inflammatory infiltrate was almost always present in CMV-infected foetal organs and the severity of the inflammatory response was correlated with the organ damage. Brain damage with necrosis was observed in 33% (9/27) and a mild telencephalic leukoencephalopathy in 22% (6/27) of foetuses studied. Conclusions: Focal necrosis was observed very frequently in organs such as pancreases, livers, hearts and kidneys. However the damage in these organs is likely to be resolved by parenchymal regeneration. Brain damage, which seems to be the results of a combined effect of viral infection, inflammatory infiltration and hypoxia due to severe placentitis, is less likely to be resolved because of the low regeneration ability of this organ. [Copyright &y& Elsevier]

Background:: Cytomegalovirus (CMV) is the major infectious cause of congenital abnormalities in the central nervous system due to intrauterine infection in humans. Design and population:: Twenty-seven fetuses with congenital CMV infection documented at 20–21 weeks'' gestation by invasive prenatal diagnosis (amniotic fluid culture and PCR positive with a viral load >105 copies/ml) underwent histological examination. We focused our attention on brain and placenta to understand the histopathogenesis of cerebral damage and to find a possible correlation between placental infection and ischemic brain damage. Material and methods:: Fetal sections were studied with haematoxylin and eosin staining, immunohistochemistry for CMV early (ppUL44) and leukocyte common antigen CD45 to detect the inflammatory cells. Results:: CMV-positivity was detected in all placentas and 55% (15/27) of brains. Six out of 15 CMV-positive brains showed mild inflammatory response without necrosis and only mild telencephalic leukencephalopathy. Four out of 15 CMV-positive brains showed a moderate CD45-positive inflammatory response associated with focal microglial nodules and telencephalic leukencephalopathy. The CD45-positive inflammatory response in the remaining five of the 15 CMV-positive brains was severe and associated with diffuse cerebral damage such as cortical necrosis, polymicrogyria and periventricular leukomalacia. No damage was observed in CMV-negative brains. Conclusions:: Diffuse chronic villitis with necrosis was found in all the placentas of fetuses with severe brain damage. In other placentas, chronic villitis and necrosis were only focal. Brain damage may be caused not only by CMV infection but also by inflammatory infiltration and hypoxia due to severe placentitis. [Copyright &y& Elsevier]