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Purpose: To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV. Methods: We evaluated, in a national study of pregnant women with HIV receiving antiretroviral treatment (ART), values of CD4/CD8 ratio at entry in pregnancy, changes between first and third trimester, and possible associations with preterm delivery, low birthweight, and HIV-RNA < 50 copies/ml at third trimester in univariate and multivariate analyses. Results: Among 934 women, 536 (57.4%) were already on ART at conception. CD4/CD8 ratio (baseline value 0.570) increased significantly between the first and third trimesters, particularly in women who started ART in pregnancy (+ 0.163, vs. + 0.036 in women already on treatment). The rate of CD4/CD8 ratio normalization, defined by achieving a ratio ≥ 1 at the third trimester, was 13.2%. In multivariable analyses, women who entered pregnancy with a CD4/CD8 ratio < 0.3, compared to women with ratio ≥ 1, were almost four-times less likely to have third-trimester HIV-RNA < 50 copies/ml (AOR 0.258, 95%CI 0.111–0.601), and more than twice as likely to have preterm delivery (AOR 2.379, 95%CI 1.082–5.232). For preterm delivery, also a baseline CD4/CD8 ratio between 0.3 and 0.45 was significantly associated with an increased risk (AOR: 3.415, 95%CI 1.690–6.900). Conclusion: We described for the first time independent associations of low CD4/CD8 ratio with preterm delivery and HIV-RNA suppression.

Background No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. Methods Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses. Results Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+ T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65). Conclusions No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

Background Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P

Objectives To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures. Design Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. Setting University and hospital clinics. Population Pregnant women with HIV. Methods Temporal trends were analysed by analysis of variance and by the Chi-square test for trend. Quantitative variables were compared by Student's t-test and categorical data by the Chi-square test, with odds ratios and 95% confidence intervals calculated. Main outcome measures Rate of invasive testing, intrauterine death, HIV transmission. Results Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011–2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005. Conclusions The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment. Tweetable abstract No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti-HIV regimens.

PURPOSE: To evaluate the maternal and neonatal safety of vaginal delivery in women with HIV following the implementation of a national protocol in Italy. METHODS: Vaginal delivery was offered to all eligible women who presented antenatally at twelve participating clinical sites. Data collection and definition of outcomes followed the procedures of the National Program on Surveillance on Antiretroviral Treatment in Pregnancy. Pregnancy outcomes were compared according to the mode of delivery, classified as vaginal, elective cesarean (ECS) and non-elective cesarean section (NECS). RESULTS: Among 580 women who delivered between January 2012 and September 2017, 142 (24.5%) had a vaginal delivery, 323 (55.7%) had an ECS and 115 (19.8%) had an NECS. The proportion of vaginal deliveries increased significantly over time, from 18.9% in 2012 to 35.3% in 2017 (p

Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study.Laboratory measures (CD4, HIV-RNA, lipid profile, glucose, hemoglobin, and alanine transferase) and pregnancy outcomes (preterm delivery, low birthweight, nonelective cesarean section, birthweight Z-score, congenital defects, HIV transmission, maternal weight gain, and pregnancy complications) were compared after prenatal exposure to ABC/3TC or TDF/FTC.The study evaluated 913 pregnancies (ABC/3TC: 252; TDF/FTC: 661). At entry in pregnancy, women on TDF/FTC were older (33.6 vs. 32.4 years, P = 0.005), less frequently on treatment (66.9% vs. 80.2%, P0.001), and had lower CD4 counts (475/mm vs. 533/mm, P = 0.003) and higher plasma HIV-RNA levels (2.48 vs. 2.22 log10 copies/mL, P = 0.003). Women on ABC/3TC had more commonly hypertension/nephropathy (5.2% vs. 2.0%, P = 0.013). No major differences were observed in the main pregnancy outcomes and in rates of undetectable HIV-RNA at third trimester. In a subgroup analysis that evaluated at third trimester only cases with regular 3-drug treatment during pregnancy, women on TDF/FTC had lower hemoglobin levels (median: 11.1 vs. 11.8 g/dL, P = 0.002) and women on ABC/3TC had higher levels of total cholesterol (median: 230 vs. 216 mg/dL, P = 0.023) and low-density lipoprotein-cholesterol (133 vs. 111 mg/dL, P = 0.030).In this study, use of TDF/FTC and ABC/3TC in pregnancy was associated with similar pregnancy outcomes and with some differences in laboratory measures that might guide physicians' prescriptions in mothers with hematologic or metabolic risk factors.

SUMMARYYoung pregnant women with HIV may be at significant risk of unplanned pregnancy, lower treatment coverage, and other adverse pregnancy outcomes. In a large cohort of pregnant women with HIV in Italy, among 2979 pregnancies followed in 2001–2016, 9·0% were in women P< 0·001). Younger women had a lower rate of planned pregnancy (23·2%vs.37·7%, odds ratio (OR) 0·50, 95% confidence interval (CI) 0·36–0·69), were more frequently diagnosed with HIV in pregnancy (46·5%vs.20·9%, OR 3·29, 95% CI 2·54–4·25), and, if already diagnosed with HIV before pregnancy, were less frequently on antiretroviral treatment at conception (vs.99·3%), with no differences in rate of HIV viral suppression at third trimester and adverse pregnancy outcomes. The data show that young women represent a growing proportion of pregnant women with HIV, and are significantly more likely to have unplanned pregnancy, undiagnosed HIV infection, and lower treatment coverage at conception. During pregnancy, antiretroviral treatment, HIV suppression, and pregnancy outcomes are similar compared with older women. Earlier intervention strategies may provide additional benefits in the quality of care for women with HIV.

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.

BACKGROUND: Atazanavir and lopinavir represent the main HIV protease inhibitors recommended in pregnancy, but comparative data in pregnant women are limited. METHODS: Women from a national observational study, exposed in pregnancy to either atazanavir or lopinavir, were compared for glucose and lipid profiles, liver function tests, CD4 count, HIV RNA and main pregnancy outcomes. Statistical methods included univariate and multivariable analyses. RESULTS: The study population included 428 pregnancies (lopinavir, 322; atazanavir, 106). The lopinavir group was characterized by higher rates of HIV diagnosis in pregnancy and treatment indication for maternal health, lower CD4 counts, higher HIV RNA levels, less frequent antiretroviral treatment at conception and shorter duration of drug exposure during pregnancy. No differences in pregnancy outcomes, glucose metabolism and weight gain were observed. The two groups also showed in a multivariable analysis similar odds for detectable HIV RNA in the third trimester (adjusted OR 0.85, 95% CI 0.35-2.10, P = 0.730). Total lipid levels were significantly higher in the lopinavir group (median values in the third trimester 239 versus 221 mg/dL for total cholesterol and 226 versus 181 mg/dL for triglycerides; P < 0.001 for both comparisons) and bilirubin levels were significantly higher in the atazanavir group (1.53 versus 0.46 mg/dL, P < 0.001). CONCLUSIONS: In this observational study atazanavir and lopinavir showed similar safety and activity in pregnancy, with no differences in the main pregnancy outcomes. Atazanavir use was associated with a better lipid profile and with higher bilirubin levels. Overall, the study findings confirm that these two HIV protease inhibitors represent equally valid alternative options.

Objectives The aim of the study was to assess the rate, determinants, and outcomes of repeat pregnancies in women with HIV infection. Methods Data from a national study of pregnant women with HIV infection were used. Main outcomes were preterm delivery, low birth weight, CD4 cell count and HIV plasma viral load. Results The rate of repeat pregnancy among 3007 women was 16.2%. Women with a repeat pregnancy were on average younger than those with a single pregnancy (median age 30 vs. 33 years, respectively), more recently diagnosed with HIV infection (median time since diagnosis 25 vs. 51 months, respectively), and more frequently of foreign origin [odds ratio (OR) 1.36; 95% confidence interval (CI) 1.10–1.68], diagnosed with HIV infection in the current pregnancy (OR: 1.69; 95% CI: 1.35–2.11), and at their first pregnancy (OR: 1.33; 95% CI: 1.06–1.66). In women with sequential pregnancies, compared with the first pregnancy, several outcomes showed a significant improvement in the second pregnancy, with a higher rate of antiretroviral treatment at conception (39.0 vs. 65.4%, respectively), better median maternal weight at the start of pregnancy (60 vs. 61 kg, respectively), a higher rate of end-of-pregnancy undetectable HIV RNA (60.7 vs. 71.6%, respectively), a higher median birth weight (2815 vs. 2885 g, respectively), lower rates of preterm delivery (23.0 vs. 17.7%, respectively) and of low birth weight (23.4 vs. 15.4%, respectively), and a higher median CD4 cell count (+47 cells/μL), with almost no clinical progression to Centers for Disease Control and Prevention stage C (CDC-C) HIV disease (0.3%). The second pregnancy was significantly more likely to end in voluntary termination than the first pregnancy (11.4 vs. 6.1%, respectively). Conclusions Younger and foreign women were more likely to have a repeat pregnancy; in women with sequential pregnancies, the second pregnancy was characterized by a significant improvement in several outcomes, suggesting that women with HIV infection who desire multiple children may proceed safely and confidently with subsequent pregnancies.

Objectives: Congenital Toxoplasmosis (CT) in newborns results from primary maternal infection with Toxoplasma gondii (TG). Many infected children are asymptomatic at birth but at high risk of neurological sequelae during early childhood. In case of missed diagnosis at birth, retrospective testing of neonatal Guthrie cards for TG DNA or specific IgM anti-TG detection could help to distinguish congenital from acquired Toxoplasmosis. The aim of the this study was to investigate the sensitivity and specificity of IgM testing by Western Blot (WB) and DNA amplification in dried blood samples (DBS) of infants born from mothers infected by TG during pregnancy. Methods: A retrospective study was performed in 18 infants born from mothers who acquired toxoplasmosis during the second or third trimester of pregnancy. At birth, all mother-child serum pairs were tested by conventional assays (Enzygnost Toxoplasmosis-Siemens; Vidas Toxo-bioMérieux) and by comparative WB (Toxoplasma WB IgG/IgM-LDBio Diagnostics). We collected Guthrie cards of every child (informed consensus was obtained from parents); one DBS was used for TG DNA detection and another one for antibodies elution. Nucleic acids were extracted from DBS with Versant kPCR Sample Preparation system (Siemens) and Toxoplasma Q-PCR Alert Kit (Nanogen) was used for amplification. Specific IgM anti-TG were detected in eluates from DBS by using LDBio Toxoplasma WB IgM. Results: At birth CT was diagnosed in 8 of the 18 newborns, because of IgM/IgA positivity and/or different IgG WB pattern in infant’s serum compared to the corresponding mother’s one. CT was excluded in the remaining 10 children because of their sera were IgM/IgA negative and their IgG titres decreased during the follow-up period; at 1 year of age all these 10 babies were IgG negative. In the present study, we confirmed CT in 4 out of the 8 CT cases. In particular, we were able to amplify TG DNA from one of the cards, while in other 3 cases we found specific IgM anti-TG. Specificity of DBS examination was 100%, since no TG DNA or IgM was found in the group of 10 non-infected babies. Serological test at birth and Guthrie card results of the 8 CT cases are shown in detail in table 1. Conclusions: Although serological evaluation at birth and during the first year remains basic for the laboratory diagnosis ofCT, examination of Guthrie cards could be considered a retrospective method to evaluate infants (>1 year ofage) with clinical signs suggestive of CT.

AIMS Congenital Toxoplasmosis (CT) in newborns results from primary maternal infection with T. gondii (TG). Most infected children show no symptoms at birth but are at great risk of sequelae during the first year of life or in early childhood [1]. Polymerase chain reaction (PCR) analysis of dried blood samples on the Guthrie card has been proposed as a sensitive method to screen for congenital CMV infection, but there are no data about the use for TG screening. The aim of present study was to assess the utility of PCR analysis of dried blood samples for the retrospective diagnosis of CT. METHODS A retrospective study was performed with 18 infants born between January 2010 and June 2012. Transmitters mothers seroconverted in the second trimester of pregnancy (mean 23.5 ± 7.9 weeks). At birth, serological tests (Enzygnost Toxoplasmosis IgG, IgM, IgA-Siemens Healthcare Diagnostics; Vidas Toxo IgMbioMerieux) as well as IgM-IgG WB (LDBio Toxoplasma WB IgG/IgM-LDBio Diagnostics) were performed in all mother-child pairs.Nucleic acids were extracted from Guthrie cards with VERSANT kPCR Sample Preparation system (Siemens) and Toxoplasma Q-PCR Alert Kit (Nanogen) was used for the amplification of TG target region AF 146527. RESULTS In 7/18 (38.9%) infants, CT was diagnosed by IgM-WB positivity at birth. The remaining 11 were considered non-infected (61.1%) and became IgG negative within 12 months of life. Infected infants received one-year therapy (pyrimethamine/sulfadiazine) and were followed according to our protocol. Four of these had a pathological neuroimaging (4/4 calcifications, 2/4 ventriculomegaly). None had hearing loss. TG DNA was detected in only one of the Guthrie cards of the infected newborns, while all the others were negative. CONCLUSIONS Although serological methods remain basic in the diagnosis of CT, TG DNA detection in Guthrie cards could be considered a retrospective method to evaluate infants (> 1 year of age) with clinical signs suggestive of CT. More studies with a larger number of infected cases are needed to assess the sensitivity of this method.

Introduzione. I nati da madri con infezione da Chlamydia trachomatis (CT) sono a rischio di infezioni oculari e polmonari. Nel presente studio riportiamo i casi di due neonati, entrambi nati da madri con infezioni asintomatiche da CT, che nella seconda settimana di vita hanno sviluppato una congiuntivite follicolare. Metodi. I tamponi congiuntivali dei neonati e i campioni di urina delle madri sono stati analizzati in Real-Time PCR con il kit commerciale Versant CT/GC DNA 1.0 (Siemens). E’ stata successivamente eseguita la genotipizzazione, con metodica RFLP per il gene omp1. Risultati. Entrambi i neonati, normali per età gestazionale, sono nati con parto spontaneo e sono stati dimessi in terza giornata in buone condizioni cliniche. Il successivo ricorso alle cure dell’U.O. Neonatologia è avvenuto in un caso per presenza di ittero neonatale e controlli per sospetta infezione congenita da Toxoplasma gondii, e nell’altro per presenza di difficoltà alimentari, scarso accrescimento ponderale ed edema palpebrale. La consulenza oculistica richiesta ha permesso in entrambi i casi di diagnosticare una congiuntivite follicolare. I tamponi congiuntivali effettuati sono risultati positivi per CT e la tipizzazione ha evidenziato rispettivamente il genotipo F ed E. In entrambi i neonati è stata instaurata una terapia con Claritromicina, 10 mg/kg/die in due somministrazioni, proseguita per 2 settimane; in un caso si è aggiunta una terapia topica con Ofloxacina collirio 0.3%, 1 goccia per occhio, 4 volte/die. La visita oculistica di controllo ha dimostrato per entrambi completa risoluzione della congiuntivite. Le madri sono state inviate presso l’ambulatorio MTS per ulteriori accertamenti e terapia. Conclusioni. L’infezione da CT nelle donne decorre spesso in maniera asintomatica: da qui deriva la necessità di effettuare in gravidanza uno screening per CT, almeno nelle donne più giovani o con fattori di rischio (numero elevato di partner, nuovo partner) per prevenire infezioni, anche gravi, nei neonati.

AIMS Chlamydia trachomatis is one of the most common sexually transmitted agents. Infants born vaginally to infected mothers may present with conjunctivitis (20-50%) and/or pneumonia (5-20%) [1]. Chlamydia spp. is a frequent identifiable cause of neonatal conjunctivitis, in association with S. aureus, E. coli, N. gonorrhoeae. Topical eye drops such as silver nitrate 1% effectively prevent gonococcal neonatal conjunctivitis; however, antibiotic topical agents are commonly used in the clinical practice in the attempt to prevent also chlamydial infections. METHODS Topical ocular prophylaxis with fusidic acid was instituted early after birth. Data about new cases of chlamydial conjunctivitis from September 2011 to August 2012 were recorded. Data included length and course of pregnancy, maternal diseases, delivery method, newborn weight, postnatal course. RESULTS Two cases of isolated chlamydial conjunctivitis were recorded. Both infants (one male, one female) were born by vaginal delivery. They were full term, healthy infants,without ocular malformations, whose mothers were treated with neither systemic nor local antibiotics near delivery. Birth weight: 3,400 and 2,380 g respectively. Pregnancy courses are unknown. Both infants received antibiotic prophylaxis in each eye 20 minutes after delivery. The age of presentation for conjunctivitis was between day 10 and 12 of life. Infants presented with hyperemic conjunctiva, mucopurulent discharge and swollen eyelids. The male infant also had blood-stained eye discharge. Ophthalmological examinations showed follicular conjunctivitis. Definite diagnosis was made by detection of Chlamydia DNA by PCR on specimens obtained by swabbing the conjunctiva. Both infants were treated with systemic Clarithromycin at 10 mg/kg/day in 2 doses for 14 days, after an electrocardiogram was performed. No long-term ocular sequelae were found. CONCLUSIONS In addition to the typical features of chlamydial conjunctivitis, a follicular conjunctivitis was demonstrated at ophthalmological examination in both our neonates. Prophylaxis with fusidic acid did not prevent all cases of chlamydial neonatal conjunctivitis. In the absence of information about pregnancy, screening for Chlamydia spp. may be an effective practice to prevent neonatal infection and related complications.

Although most of the women (69.4%) had a normal BMI at start of pregnancy, only 37% had an adequate weight gain during pregnancy. Inadequate body weight gain was more common (44.8%) than excessive weight gain (18.2%), but 40% of overweight women and 50% of obese women had an excessive weight gain in pregnancy, with about 9% of the women in these categories gaining >18 kg during pregnancy (Table 1). Only 1.9% of the women had a vaginal delivery; elective and nonelective cesarean deliveries accounted for 81.3% and 16.7% of deliveries, respectively. Compared to underweight/normal women, overweight/obese women had similar occurrences of preterm delivery (23.4% vs 22.7%, P = .871), significantly lower rates of low birthweight (14.2% vs 24.2%, P = .007) and nonelective cesarean deliveries (11.7% vs 18.3%, P = .042), and a significantly higher occurrence of fasting plasma glucose >92 mg/dL at 20–28 weeks (12.1% vs 6.6%, P = .027), hypertension during pregnancy (6.4% vs 2.7%, P = .019), and gestational age–adjusted birthweight >90th percentile (15.5% vs 5.0%, P < .001). Complications of delivery, major birth defects, and HIV transmission were similar between the 2 groups (7.3% vs 7.6%, P = .881; 2.6% vs 3.5%, P = .589; and 0.8% vs 0.5%, P = .661, respectively). An inadequate weight gain during pregnancy was associated with an increased risk of nonelective cesarean delivery (OR, 1.589 [95% CI, 1.077–2.346], P = .020). Excessive weight gain during pregnancy was not associated with either hypertension (OR, 1.364 [95% CI, .537–3.465], P = .514) or 20–28 week glucose level of >92 mg/dL (OR, 0.841 [95% CI, .399–1.772], P = .648), but was significantly associated with birthweight >90th percentile (OR, 2.271 [95% CI, 1.229–4.195], P = .009), and appeared to be protective against low birthweight (OR, 0.544 [95% CI, .323–.918], P = .023) and birthweight

Objective We used data from a national study of pregnant women with HIV to evaluate the prevalence of congenital abnormalities in newborns from women with HIV infection. Design Observational study. Setting University and hospital clinics. Population Pregnant women with HIV exposed to antiretroviral treatment at any time during pregnancy. Methods The total prevalence of birth defects was assessed on live births, stillbirths, and elective terminations for fetal anomaly. The associations between potentially predictive variables and the occurrence of birth defects were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs) for exposed versus unexposed cases, calculated in univariate and multivariate logistic regression analyses. Main outcome measures Birth defects, defined according to the Antiretroviral Pregnancy Registry criteria. Results A total of 1257 pregnancies with exposure at any time to antiretroviral therapy were evaluated. Forty-two cases with major defects were observed. The total prevalence was 3.2% (95% CI 1.9–4.5) for exposure to any antiretroviral drug during the first trimester (23 cases with defects) and 3.4% (95% CI 1.9–4.9) for no antiretroviral exposure during the first trimester (19 cases). No associations were found between major birth defects and first-trimester exposure to any antiretroviral treatment (OR 0.94, 95% CI 0.51–1.75), main drug classes (nucleoside reverse transcriptase inhibitors, OR 0.95, 95% CI 0.51–1.76; non-nucleoside reverse transcriptase inhibitors, OR 1.20, 95% CI 0.56–2.55; protease inhibitors, OR 0.92, 95% CI 0.43–1.95), and individual drugs, including efavirenz (prevalence for efavirenz, 2.5%). Conclusions This study adds further support to the assumption that first-trimester exposure to antiretroviral treatment does not increase the risk of congenital abnormalities.

Use of cocaine, by inhalation, is currently increasing in Western Countries and its use is superseding heroin in the rising generation. Young people of the third millennium use narcotics to avoid the negative conditions of daily life and to escape on "unreal" trips, as happened in the '60s and '70s for the heroin-addicted. Today, on the contrary, people addicted to cocaine want to be more competitive and "winners" and believe that cocaine can help them to reach this goal. A series of 104 patients (75 male, 29 female), aged between 16 and 54 yrs, all habitual inhaling cocaine users (or = 10 times per month) have been observed for 2 years. Among them, 11 (10.5%) had nasal septal perforation, which is frequently related to cocaine use. Of these 11 patients, 8 (72.7%) had nasal septal perforation of the quadrangular cartilage, while in the other 3 (27.3%) the perforation involved also the bony tract (vomer-perpendicular ethmoidal lamina). Psychological analysis of these 104 patients is reported: 62 patients (59.6%) answered that they inhaled cocaine to improve endurance and to feel stronger and less tired; 34 patients (32.7%) in order to enjoy themselves more during parties and to communicate more effectively with other people; 5 patients (4.8%) to gain confidence and to overcome their shyness, 2 patients (1.9%) to improve their sexual performance and 1 patient (1%) to drink more alcoholic drinks for a longer time without feeling sleepy. All the patients underwent psychotherapeutic treatment, but the lack of compliance and constantly missing the scheduled follow-up visits resulted in complete therapy being performed in only 16 patients (15.3%). All the patients with nasal septal perforation underwent rhino-endoscopy, at T0, with 0 degrees, 45 degrees endoscopes, computed tomography scan of nose and paranasal sinuses and biopsy. At the time of the observational period, none of the 11 patients who presented nasal septal perforation agreed to stop cocaine abuse; therefore, a temporary solution has been offered to all the patients (accepted by 3 of them), i.e., the positioning of a silicone button to close the perforation and, thus, improve the air flow in the nose and reduce progression of local necrosis. Together with the button, the positioning is described, under local anaesthesia, of two layers per septal side of hyaluronic acid, at different levels of esterification, kept in site by the button as a "sandwich" in order to obtain better re-growth of the mucosa and fewer scabs and bleeding.

Maxillary ameloblastoma is a rare odontogenic neoplasm that is histologically benign and originates from epithelial cells present in bone tissue. If excised through conservative surgery, this tumour has a high relapse rate and is locally aggressive. The risk, in particularly extensive forms, that the ameloblastoma will invade extra-maxillary structures such as the orbit, the pterygomaxillary fossa, the infratemporal fossa and the base of the skull, means that surgical treatment is difficult if it is to be oncologically radical while respecting function and aesthetics. Thus, in these cases a complete and in-depth diagnostic work-up and careful planning of surgical treatment are needed: surgery entails an ablative phase with en-bloc resection of the neoformation to margins free of neoplastic infiltration, and a reconstruction phase that, within a short time-frame, will re-establish functionality and provide a good aesthetic result. Our experience in treating 2 cases of maxillary ameloblastoma is reported.

Human parechovirus (HpeV) is an important emerging infection in young infants, able to cause sepsis-like disease and meningoencephalitis, especially in newborns. Among the 19 identified genotypes, HPeV1, 3 and 6 are the most common types involved in human infections; HPeV3 is the type mainly responsible for neonatal infections and for infections involving the central nervous system. Signs and symptoms overlap with those of a bacterial infection and patients are usually treated with broad spectrum antibiotics. In the majority of cases lumbar puncture shows absence of pleocytosis, even in the presence of signs of meningitis. In these cases, cerebrospinal fluid cultures are negative for bacteria but, in the absence of diagnosis of viral infection, a full and unnecessary antibiotic cycle is often continued. Moreover, high sensitivity neuroimaging, i.e., magnetic resonance, and follow-up are often missed, thus resulting in substandard care. Availability of a real time PCR assay for HPeV RNA allows rapid and sensitive diagnosis as long as the disease is suspected. In this case study, we present cases of HPeV infections in newborns requiring neonatal intensive care admission, discuss their optimal management, and highlight the most relevant findings in the literature.

Background Cytomegalovirus (CMV)-specific CD8 + T-cell responses can be detected early in fetal life, but their role in the manifestations of congenital CMV (cCMV) infection remains largely unknown. Methods CMV-specific CD8 + T-cell responses were assessed in neonates with cCMV using QuantiFERON®-CMV assay, within day 14 of life (T0) and during the second month of life (T1). Detection and quantification of CMV DNA in whole blood and urine samples were performed at both time points. QuantiFERON®-CMV results were evaluated in relation to timing of maternal infection, clinical manifestations of cCMV and CMV DNA levels. Results Thirty neonates were enrolled (10/30 [33%] symptomatic; 20/30 [67%] asymptomatic). At T0 16/30 (53%) subjects had a reactive QuantiFERON®-CMV result and 16/16 (100%) were asymptomatic, whereas 14/30 (47%) had a nonreactive or indeterminate QuantiFERON®-CMV result and 4/14 (29%) were asymptomatic. At T1, 17/29 (59%) subjects had a reactive QuantiFERON®-CMV result, and 17/17 (100%) were asymptomatic, whereas 12/29 (41%) had a nonreactive or indeterminate result and 3/12 (25%) were asymptomatic. At both T0 and T1 reactive QuantiFERON®-CMV results correlated with lack of symptoms (P = .0001). At T1 median CMV DNAemia was lower in subjects with reactive QuantiFERON®-CMV results as compared with subjects with nonreactive or indeterminate results (1.82 log IU/mL [1.82–2.89] vs 2.55 log IU/mL [1.82–4.42], P = .009). No correlation was found between QuantiFERON®-CMV results and gestational age at maternal infection nor with urine CMV DNA levels. Conclusions A detectable CMV-specific CD8 + T-cell response, evaluated using the QuantiFERON®-CMV assay, correlates with the lack of CMV-related symptoms and the control of CMV DNAemia.

L’ipotesi che provo ad argomentare in questo saggio è che Plotino abbia un certo rispetto per il venerando Parmenide, anche quello storico e non solo quello platonico, e che ciò si faccia evidente quando lo cita per sottolineare l’unità dell’intera tradizione filosofica greca. L’obiettivo è quindi dimostrare che 1) secondo Plotino il Parmenide storico è colui che dà fondamento logico alla postulazione di un principio al di là dell’essere; 2) nel confronto col Parmenide di Platone emerge che l’accuratezza del Parmenide storico è numerica e non dialettica; e 3) l’immagine suggerita in un testo neoplatonico tardo – cioè di Platone come una sorta di analogo dell’Uno – non fa che confermare una tendenza già plotiniana a pensare anche la filosofia presocratica come un momento necessario per lo sviluppo del sistema metafisico-causale neoplatonico.

Silver–Russell syndrome (SRS) is a clinically and genetically heterogeneous syndrome characterized by severe intrauterine and postnatal growth retardation, facial dysmorphism and body asymmetry. One of the main molecular mechanisms leading to the syndrome involves methylation abnormalities of chromosome 11p15. In the last decades, an increase of imprinting disorders have been reported in children born from assisted reproductive technology (ART); however there is currently little evidence linking SRS and ART. Only few infants with SRS born using ART, supported by molecular analysis, have been described. We report on a twin-girl conceived using intracytoplasmic sperm injection (ICSI) diagnosed with SRS. Molecular studies revealed a hypomethylation of the paternal H19/IGF2 Imprinting Control Region. Her twin sister had a normal prenatal and postnatal growth and a normal methylation pattern of the chromosome 11p15. This is the second reported case of a twin infant with SRS conceived using ART with hypomethylation of H19/IGF2; it provides additional evidence of a possible relationship between ART procedures and methylation defects observed in SRS. Given the clinical heterogeneity of SRS, and the increased risk of multiple and preterm births in the ART-conceived children, it is possible that a number of cases of SRS remains undiagnosed in this population. Future studies should investigate the possible link between ART and SRS, in order to better understand the causes of epimutations in ART pregnancies, and to help clinicians to adequately counsel parents who approach to ART and to assess the opportunity of a long-term follow-up of children conceived using ART. © 2013 Wiley Periodicals, Inc.

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.

none 8 BACKGROUND: Respiratory Syncytial Virus (RSV) is the most important cause of severe respiratory infections in infants with seasonal epidemics. Environmental factors (temperature, humidity, air pollution) could influence RSV epidemics through their effects on virus activity and diffusion. METHODS: We conducted a retrospective study on a paediatric population who referred to our Paediatric Emergency Unit in order to analyze the correlation between weekly incidence of RSV positive cases during winter season in Bologna and meteorological factors and air pollutants concentration. RESULTS: We observed a significant correlation between the incidence of RSV infections and the mean minimum temperature registered during the same week and the previous weeks.The weekly number of RSV positive cases was also correlated to the mean PM10 concentration of the week before. CONCLUSIONS: RSV epidemic trend in Bologna (Italy) is related to the mean minimum temperature, and the mean PM10 concentration. Vandini S; Corvaglia L; Alessandroni R; Aquilano G; Marsico C; Spinelli M; Lanari M; Faldella G. Vandini S; Corvaglia L; Alessandroni R; Aquilano G; Marsico C; Spinelli M; Lanari M; Faldella G.