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BACKGROUND: The effectiveness of Toxoplasma gondii (Tg) screening during pregnancy in areas with a low prevalence of the infection is debated. We investigate the Tg serological status, the rate of primary infection in a cohort of pregnant women and the rate of congenital toxoplasmosis among their infants during a 3-year period in an urban area with low Tg prevalence. METHODS: Demographic and Tg serological data for all pregnant women delivering from January 2009 to December 2011 were collected. All pregnant women with primary Tg infection during pregnancy and their infants were included in the study. RESULTS: In early pregnancy, 10,347 women underwent prenatal screening and 2308 (22.3%) had anti-Tg. The seroprevalence among non-native women was significantly higher than that among native women [32.8% vs. 19.1%, relative risk: 1.71, P < 0.001]. The incidence rate of primary Tg infection during pregnancy was 0.77%. Immigrant women were more likely to be infected during pregnancy than Italian women (relative risk: 4.88, P < 0.001). Tg infection was more frequent in women coming from Africa, Asia, Eastern Europe and South America. The CT incidence rate was 0.06%. All congenitally infected infants were born to immigrant mothers. CONCLUSIONS: Tg infection during pregnancy and congenital disease are more frequent in non-native mothers and their infants. Measures to prevent Tg exposition must be carefully explained to pregnant women, with a focus on specific habits in non-native women. Prenatal screening is still effective to select women for prenatal therapy aiming to decrease vertical transmission and to identify foetuses/newborns with congenital disease that could benefit from pre/postnatal antiparasitic therapy.

Human cytomegalovirus (CMV) is the most common cause of intrauterine infection, occurring in 0.2% to 2.2% of all live births, and congenital infection is a common cause of sensorineural hearing loss and mental retardation. Transmission to fetus may occur through primary or secondary maternal infection with a probability of 30% to 40%, intrauterine transmission following primary infection during pregnancy compared with 0.5% to 2.2 % following secondary infection. Approximately 10-15% of congenitally infected babies are symptomatic at birth and these infants have a perinatal mortality rate of around 10% with 70-80% of surviving babies presenting major neurological sequelae. Despite infection, 85-90% of babies have no symptoms at birth however 8-15% of them will suffer from psychomotor and sensory-neural disabilities. The management of congenital CMV infections varies considerably in different centers and often there are unequal methods used between practitioners, which can lead to substantial discrepancies between the indications suggested by the literature and what is actually performed. A multidisciplinary group of 30 experts and/or qualified representatives of the six Italian Scientific Societies of Clinical Microbiologists (AMCLI), Gynaecology and Obstetrics (SIGO), Sexually Transmitted Diseases (SIMaST), Infectious and Tropical Diseases (SIMIT), Neonatology (SIN) and Pediatrics (SIP) developed evidence and expert opinion-20 based consensus guidelines on CMV congenital infection management including mechanism of pathogenesis, clinical and epidemiological aspects, prevention, diagnostics, and treatments. Each section used a scoring system to rate the quality of evidence on which recommendations are based.The document was prepared, discussed and validated by multidisciplinary committee through a consensus conference

Background. Human cytomegalovirus (HCMV) is a major cause of congenital infection as well as sensorineural hearing loss and neurodevelopmental delay. Prenatal diagnosis is based mainly on the detection of HCMV infection in amniotic fluid and on ultrasound (US) examination. The major limitation of these techniques is that US identifies prenatally only up to 15-20% of infected babies and positive results of amniotic fluids tests do not discriminate between the infants who will have symptoms at birth and those who will not. Objectives. The aims of this study are to evaluate the usefulness of fetal cerebral magnetic resonance (MR) and biological parameters in fetal blood when a high HCMV load is detected in amniotic fluid. The results of MR and fetal blood testing were correlated with the fetal histological examination or neonatal outcome. Methods. We enrolled 17 women at 20-21 weeks gestation with documented intrauterine transmission of HCMV (amniotic fluid with a viral load more than 10^5 copies/ml) with or without abnormal ultrasound findings. All pregnant women performed cerebral MR at 21 weeks gestation. Twelve women elected to terminate the pregnancy and fetal blood was collected from the umbilical cord. Immunological, haematological, biochemical and virological examinations were performed in fetal blood. HCMV antigen expression and inflammatory response were studied in all fetal tissues including inner ears using immunohistochemical staining procedures. Five pregnancies continued up to term and fetal MR was repeated at 32 weeks of gestation. Results. We found no evidence of brain HCMV infection by immunohistochemistry in 4 out of 12 foetuses and US and MR brain imaging were both normal in these cases. Eight fetal brains were HCMV positive and a brain histological damage was observed. Among these, 4 HCMV positive inner ears were observed. Viral infection always involved the stria vascularis, the most vascularised area of the cochlea, and less the Reissner's membrane, the Organ of Corti and the vestibular apparatus. Considering the 8 fetuses with histological brain damage, US was pathological in 4 cases (50%) and MR imaging only in 3 (38%). The most prevalent finding were periventricular hyperechogenicity (US) and microcephaly (MR). In fetal blood only platelet count and the % of natural killer cells were associated significantly .

Each year approximately 1–7% of pregnant women acquire a primary cytomegalovirus (CMV) infection. Of these, about 30–40% transmit infection to their fetuses. Up until some years ago it was not possible to precisely define the maternal immune status through laboratory testing. Recent development of advanced serological tests now allow us to identify, among pregnant women with suspected CMV, those with primary infection who are therefore at higher risk of transmitting CMV to their fetus. Given the high risk of mother–fetus transmission and fetal damage, prenatal diagnosis is recommended, between 20-21 weeks’ gestation, to women with primary CMV infection contracted in the first half of pregnancy and/or in case of fetal abnormalities suggestive of infection. CMV-DNA detection in amniotic fluid (AF) distinguish uninfected from infected fetuses in primarily infected mothers (positive predictive value =100%). However it is still very difficult to determine which are the infected foetuses at higher risk of developing severe CMV disease. In this work we studied a cohort of 790 pregnancies at risk of in utero CMV transmission; 796 amniotic fluid (AF) samples were tested by real time PCR assay (qPCR) and virus isolation. AF samples were collected at 20-21 weeks' gestation and at least 6-8 weeks after the onset of maternal CMV infection. Outcome was fully documented in 714 newborns and 82 foetuses. A total of 108 newborns were CMV infected; 25 were 119 symptomatic and 83 asymptomatic. Comparing symptomatic and asymptomatic newborns, the mean viral load in AF was significantly higher in symptomatic newborns (mean values 2x10^6 vs 9.4x10^5, P=0.009). The 82 infected foetuses were divided in two groups: those with histological damage in the brain and in 2 or more organs and those with histological damage in only 2 or more organs. When qPCR disclosed more than 10^6 copies/mL of AF, 62.5% of foetuses had disseminated infection and brain damage compared to 29.4% of foetuses with disseminated infection alone. Although the highest median values of CMV-DNA in AF tend to indicate an increased risk of severe infection, high viral loads may be associated with symptomatic or asymptomatic congenital infections leading to the conclusion that a correlation between a high CMV load in AF and foetal/neonatal compromission is uncertain. Recent studies suggest that the determination of multiple markers (haematological, biochemical and virological markers) in foetal blood following virus detection in AF, is predictive of perinatal outcome of CMV infected foetuses. However our results do not completely confirm this. Therefore, one of the major limitations of CMV prenatal diagnosis is that we are not able to discriminate between infants who will or will not have symptoms at birth. Prognosis factors for CMV disease are still being researched. In this regards, we found interesting results studying the HLA-G antigen, which is a tolerogenic HLA-Ib molecule expressed during pregnancy. HLA-G expression is modified by CMV infection, with functional consequences in immuno-regulation. Data indicates that this molecule could be a biomarker of both maternal and foetal infection and leading to disease progression

Genital herpes is a common sexually transmitted infection. In reproductive age it involves the additional risk of vertical transmission to the neonate. Rates of transmission are affected by the viral type and whether the infection around delivery is primary or recurrent. Neonatal herpes is a rare but very severe complication of genital herpes infection and is caused by contact with infected genital secretions at the time of labor. Maternal acquisition of herpes simplex virus (HSV) in the third trimester of pregnancy carries the highest risk of neonatal transmission. Prevention of neonatal herpes depends on preventing acquisition of genital HSV infection during late pregnancy and avoiding exposure of the infant to herpetic lesions during delivery. Uninfected woman should be counselled about the need of avoiding sexual contact during the third trimester. Elective caesarean section before the onset of labor is the choice mode of delivery for women with genital lesions or with prodromal symptoms near the term, even if it offers only a partial protection against neonatal infection. Antiviral suppressive therapy is used from 36 weeks of gestation until delivery in pregnant women with recurrences to prevent genital lesions at the time of labor so reducing the need of caesarean sections. Currently, routine maternal serologic screening is not yet recommended. Because most mothers of infants who acquire neonatal herpes lack histories of clinically evident genital herpes, researchers should focus on the recognition of asymptomatic primary genital HSV infections.

Background In developed countries the rate of vertical transmission of HIV has dramatically declined after the introduction of a combination of measures represented by antiretroviral treatment before and at delivery, elective caesarean section and elimination of breastfeeding. Such measures are strongly effective and COULD reduced vertical transmission in many cases close to 0%. However, they can only be applied if the woman with HIV infection is aware of being infected: although HIV testing is always recommended during pre-conception counselling, many pregnancies are not preceded by a counselling visit, and a substantial proportion of pregnancies are not planned at all; so it is not uncommon to have a first assessment for HIV and other infections once pregnancy is already established. National data about pregnancies of HIV-infected women reported rate of 26.6% pregnancies characterized by a previously undetected HIV infection. The objectives of the present study were to assess the rate of women arriving at the time of delivery with unknown HIV status and to register the timing of availability laboratory results of the screening, in order to detect the possibility of a dismissed diagnosis before delivery. Material and Methods Data were collected by informatics consultation of clinical documentation of pregnant women delivering at the S. Orsola Hospital, where more than 3000 deliveries take place every year. We evaluated deliveries occurred during 4 sample-monthes in the years 2008-2009. We registered the effective annotation in the patients charts of HIV testing occurred during pregnancy, determined by a review of prenatal care records, which women submit ad admission and we evaluated the timing of availability of laboratory results (enzyme immunoassay) versus timing of delivery, were testing was performed at admission in women with no documented HIV testing records. Results: HIV status was present in 1136 (99.5%) charts of 1142 women at delivery: in 1002 cases (87.7%) HIV testing was performed during pregnancy and it was absent in the remain 134 (11.7%) women, so laboratory analysis (EIA) was performed. Laboratory results were available prior to delivery in 74 cases (55.2% of women tested at admission), on useful time to carry out all known strategies to prevent vertical transmission of HIV infection. In 28 cases (20.8%) serological diagnosis was received after delivery, but on time for an eventually promptly starting of antiretroviral prophylaxis on the newborn. The receipt of test results after 12 hours from delivery occurred in 32 cases (23.9%) and they were very late to enactment the necessary prevention strategies. Conclusion We found an important percentage of pregnant women reach to delivery without a HIV screening performed during pregnancy. This underline the necessary close surveillance that nurses, midwives and obstetrician must keep and the importance of HIV testing suggestion during pregnancy in order to achieve a timely HIV assessment, performed in the early stages of pregnancy. The attention of maternity hospital personnel, registering prenatal records, show crucial importance for a complete preventive intervention against HIV transmission to the newborn. Our study emphasizes the importance of a promptly HIV testing results and suggest the possibility of presence of rapid testing in delivery rooms, in order to carry out the prevention strategies soon as possible during labour in positive cases. We want to underline the recent up-date of international guidelines, where HIV testing is simplified adopting an opt-out approach and the abolition of a specific written informed consent in order to permit a major efficiency of pre-natal care ad an better manage of high risk pregnancies.

Objective: The administration of highly active antiretroviral therapy (HAART) to HIV-infected pregnant women raised the question of the association with adverse pregnancy outcomes. There is limited information regarding use of HAART during pregnancy in resource-constrained settings, where an increasing number of women need HAART administration. Our aim was to explore the association between HAART administration and adverse pregnancy outcomes and low birth weight (LBW)in a resource-limited setting. Methods: A retrospective cohort of HIV-infected pregnant women enrolled in the programme of Prevention of Mother-to- Child Transmission between 2003 and 2007 in Ouagadougou, Burkina Faso, was considered. Age, CD4+ T lymphocyte count, type and timing of antiretroviral drugs administration, pregnancy outcome, paediatric infection and birth weight were evaluated. Data were analysed using univariate analysis and binary logistic regression. Results: 678 HIV-infected were enrolled: 395 women received prophylactic regimen and 283 HAART regimen (115 started prior to conception, 168 started after the first trimester). Statistical analysis raised CD4+ T cell count

The aim of the study was to describe the recent trends in antiretroviral treatment in late pregnancy and the sociodemographic changes among pregnant women with HIV over the last 6 years. Data from the National Program on Surveillance on Antiretroviral Treatment in Pregnancy in Italy were grouped per calendar year, and changes in antiretroviral treatment, population characteristics, maternal immunovirologic status and newborn clinical parameters were analyzed. A total of 981 HIV-infected mothers who delivered between 2002 and 2008 were evaluated. The proportion of women receiving at least three antiretroviral drugs at delivery increased significantly from 63.0% in 2002 to 95.5% in 2007-2008, paralleled by a similar upward trend in the proportion of women who achieved complete viral suppression at third trimester (from 37.3 in 2002 to 80.9 in 2007-2008; p < 0.001). The co-formulation of zidovudine plus lamivudine remained the most common nucleoside backbone in pregnancy, even if a significant increase in the use of tenofovir plus emtricitabine was observed in more recent years. Starting from 2003, nevirapine prescription declined, paralleled by a significant rise in the use of protease inhibitors (PI), which were present in more than 60% of regimens administered in 2007-2008. Nelfinavir was progressively replaced by ritonavir-boosted PIs, mainly lopinavir. No significant changes in preterm delivery, Apgar score, birth weight, and birth defects were observed during the study period, and the rate of HIV transmission remained below 2%. These data demonstrate a significant evolution in the treatment of HIV in pregnancy. Constant improvements in the rates of HIV suppression were observed, probably driven by the adoption of stronger and more effective regimens and by the increasing options available for combination treatment

Intrauterine transmission of HHV-6 is well established in immunocompetent women while few data are available on infections in babies born to HIV-positive mothers. To assess the rate of HHV-6 vertical transmission in comparison to CMV, we analyzed cord blood spots dried on cards (Dried Blood Spots, DBS) collected during a multi-center study on HIV congenital infections in Italy. DBS were tested by PCR for HHV-6 and CMV footprints. HHV-6 amplimers were sequenced and characterized. As control group, cards taken from babies born to HIV-negative mothers were analyzed. DBS of 187 babies born to HIV-positive and 372 to HIV-negative mothers were analyzed. The prevalence of HHV-6 was 3.2% in babies born to HIV-positive mothers. CMV was found in the HIV-positive group with a prevalence rate of 1.6%. In newborns of control pregnant women, HHV-6 prevalence rate was 1.1% (p=0.09), while CMV was not detected (p=0.04). Sequence analysis could distinguish between HHV-6 A and B variant in both groups and one A/B coinfection was found in a baby born to a HIV-positive mother. HIV-infected mothers transmit HHV-6 and CMV viruses to their babies more frequently than uninfected women.

We analysed the characteristics of the pregnancies with a previously undetected HIV infection in a national observational study of pregnant women with HIV in Italy. In a total of 443 pregnancies with available date of HIV diagnosis, 118 were characterized by a previously undetected HIV infection (26·6%, 95% CI 22·5–30·8). The following factors were independently associated with this occurrence in a multivariate analysis (adjusted odds ratios; 95% CIs): foreign nationality (5·1, 2·8–9·3); no pre-conception counselling (35·9, 4·8–266·1); first pregnancy (2·1, 1·2–4·0); asymptomatic status (6·8, 1·5–30·6). Women with previously undetected infection started antiretroviral treatment significantly later during pregnancy (P

In our study we evaluated the frequency of three SNPs (-52 G/A, -44 C/G; -20 G/A) in the 5' UTR of DEFB-1 gene, in a cohort of 130 HIV-1 infected mothers and their children, collected by the Italian group SIGO in Obstetrics and Gynecology.The three SNPs (-52 G/A, -44 C/G; -20 G/A) in the 5' UTR of DEFB-1 gene were genotyped by direct sequencing of PCR products.The C allele at position -44 was shown to be significantly different in both HIV-1 positive mothers and their children when compared to the healthy controls. The odds ratio for -44 C allele in children born to HIV-1 infected mothers is 7.09 (confidence interval 3.38-15.3) while the odds ratio for this allele in HIV-1 infected mothers is 6.42 (confidence interval 3.14-13.4).Our results evidence a high frequency of the -44 CC allele in HIV-1 infected mothers and their children with augmented potential risk of maternal fetal transmission. This potential vertical transmission risk has been successfully prevented by antiretroviral drug treatment and cesarian section of the HIV-1 positive mothers.

Objective. We investigated genetic polymorphisms of MBL2 gene, in a cohort of 90 italian HIV-1 pregnant seropositive women and their children in order to understand whether the MBL2 genotype of HIV-1 positive mothers might be related to their ability to transmit the virus to their children.Materials and methods. DNA was extracted from Iso Code Stix cards, and MBL2 genoptyping was performed by Melting Temperature Assay.Results. The frequency of the MBL2 0/0 homozygotes was higher in HIV-1 positive mothers than in healthy controls, the MBL2 0/0 genotype was more frequent in children born from HIV positive mothers than healthy subjects.Conclusions. We have confirmed the association of polymorphisms involving a gene of the innate immunity with an increased risk of being infected by HIV. These polymorphisms were also evidenced in children born from HIV + mothers, but the risk of infection was strongly reduced by cesarean delivery and by antiretroviral treatment.