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Background Food allergy (FA) is a growing health problem worldwide. Effective strategies are advocated to limit the disease burden. Human milk (HM) could be considered as a protective factor against FA, but its mechanisms remain unclear. Butyrate is a gut microbiota‐derived metabolite able to exert several immunomodulatory functions. We aimed to define the butyrate concentration in HM, and to see whether the butyrate concentration detected in HM is able to modulate the mechanisms of immune tolerance. Methods HM butyrate concentration from 109 healthy women was assessed by GS‐MS. The effect of HM butyrate on tolerogenic mechanisms was assessed in in vivo and in vitro models. Results The median butyrate concentration in mature HM was 0.75 mM. This butyrate concentration was responsible for the maximum modulatory effects observed in all experimental models evaluated in this study. Data from mouse model show that in basal condition, butyrate up‐regulated the expression of several biomarkers of gut barrier integrity, and of tolerogenic cytokines. Pretreatment with butyrate significantly reduced allergic response in three animal models of FA, with a stimulation of tolerogenic cytokines, inhibition of Th2 cytokines production and a modulation of oxidative stress. Data from human cell models show that butyrate stimulated human beta defensin‐3, mucus components and tight junctions expression in human enterocytes, and IL‐10, IFN‐γ and FoxP3 expression through epigenetic mechanisms in PBMCs from FA children. Furthermore, it promoted the precursors of M2 macrophages, DCs and regulatory T cells. Conclusion The study's findings suggest the importance of butyrate as a pivotal HM compound able to protect against FA., Human milk contains a significant level of the short‐chain fatty acid butyrate. At concentration detectable in human milk, butyrate effectively modulates several tolerogenic mechanisms involved in the protection against food allergy. The protective role of human milk against food allergy could be related, at least in part, to the presence of an effective concentration of butyrate

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 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

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.

Introduction The aim of this study was to evaluate the incidence of toxoplasmosis infection during pregnancy and to describe the characteristics of the serological status, management, follow-up and treatment. Material and methods This is a population-based cohort study of women referred for suspected toxoplasmosis during pregnancy from January, 2001 to December, 2012. Suspected toxoplasmosis was defined as positive IgM antibody during pregnancy. Women with suspected toxoplasmosis during pregnancy were classified into three groups: seroconversion, suspected infection, or no infection in pregnancy. Women in the first and second group were treated according to local protocol, and amniocentesis with toxoplasmosis PCR detection and serial detailed ultrasound scans were offered. Neonates were investigated for congenital toxoplasmosis at birth and were monitored for at least one year after birth. Results During the study period, there were 738,588 deliveries in Campania. Of them 1159 (0.2%) were referred to our Institution for suspected toxoplasmosis during pregnancy: 183 (15.8%) women were classified as seroconversion, 381 (32.9%) were suspected infection, and 595 (51.3%) were not infected in pregnancy. Neonatal outcome was available for 476 pregnancies, including 479 neonates (3 twins, 473 singletons), out of the 564 pregnancies with seroconversion or suspected infection. 384 (80.2%) babies were not infected at birth and at follow-up, 67 (14.0%) had congenital toxoplasmosis, 10 (2.1%) were voluntary induced termination of pregnancy, 15 (3.1%) were spontaneous miscarriage, and 4 (0.8%) were stillbirth (of which one counted already in the infected cohort). Considering cases of congenital toxoplasmosis, the transmission rate in women with seroconversion was 32.9% (52/158), and in women with suspected infection was 4.7% (15/321). Conclusions Toxoplasmosis is uncommon in pregnancy with overall incidence of seroconversion and suspected infection in pregnancy of 0.8 per 1000 live births and incidence of congenital toxoplasmosis 0.1 per 1000 live births when applying a strict protocol of screening, follow-up, and treatment. 51.3% (595/1159) of women referred to our center for suspected infection were actually considered not infected.

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.

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.

Increasing numbers of women in resource-rich settings are prescribed zidovudine (ZDV)-sparing highly active antiretroviral therapy (HAART) in pregnancy. We compare ZDV-sparing with ZDV-containing HAART in relation to maternal viral load at delivery, mother-to-child transmission (MTCT) of HIV, and congenital abnormality. This is an analysis of data from the National Study of HIV in Pregnancy and Childhood and the European Collaborative Study. Data on 7573 singleton births to diagnosed HIV-infected women between January 2000 and June 2009 were analyzed. Logistic regression models were fitted to estimate adjusted odds ratios (AORs). Overall, 15.8% (1199 of 7573) of women received ZDV-sparing HAART, with increasing use between 2000 and 2009 (P

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.

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.

The association between monozygotic twins and posterior urethral valves (PUV) in postnatal life has been thoroughly described. In the fetus, the prenatal recognition of PUV is feasible. However, it has been repeatedly reported in singletons but never in monochorionic twins. We describe two cases of early prenatal diagnosis of concordant PUVs in monochorionic twins. In one of the sets, the expression of the disease was different for each twin.

Objectives: To carry out an epidemiological analysis of the emerging epidemic in an Eastern European country and to compare the approach to prevention of mother-to-child transmission (MTCT) with that in Western Europe. Design: Prospective cohort study established in 1985 in Western Europe and extended to Ukraine in 2000. Methods: Data on 5967 HIV-infected pregnant women and their infants (1251 from Ukraine and 4716 from Western/Central Europe) was analysed. Factors associated with transmission were identified with logistic regression. Results: HIV-infection among pregnant women enrolled in Western European centres has shifted from being largely injecting drug use (IDU)-related to heterosexually-acquired; in Ukraine IDU also gradually declined with women increasingly identified without specific risk factors. In Ukraine in 2000-2004 most (80%) women received single dose nevirapine (sdNVP) and/or short-course zidovudine prophylaxis [MTCT rate 4.2%; 95% confidence interval (CI), 1.8-8.0 for sdNVP with short-course zidovudinel; 2% (n = 27) received antenatal HAART and 33% (n = 418) delivered by elective caesarean section (CS); in Western European centres 72% of women received HAART (MTCT rate 1.0%; 95% Cl, 0.4-1.9) and 66% delivered by elective CS during the same period. Conclusions: Our findings indicate distinct differences in the epidemics in pregnant women across Europe. The evolution of the MTCT epidemic in Ukraine does not appear to be following the same pattern as that in Western Europe in the 1980s and 1990s. Although uptake of preventive MTCT prophylaxis has been rapid in both Western Europe and Ukraine, substantial challenges remain in the more resource-constrained setting in Eastern Europe. (c) 2006 Lippincott Williams & Wilkins

Background. Despite the introduction of screening bases intrapartum prophylaxis,Streptococcus agalactiaeis still an important etiological agent of perinatal infections. The increasing rate of resistance and the differences in resistance pattern among countries suggest that a program of surveillance at the institutional level is important in determining optimal prophylaxis. In contrast, knowledge on GBS epidemiology in Italy is limited, and no data are available in the Southern region of the country. We sought to determine the occurrence of resistance to macrolides and clindamycin of GBS isolates in pregnant and nonpregnant women.Methods. Between 2005 and 2008, 1346 vaginal and 810 rectovaginal swabs were obtained from pregnant and not-pregnant women.Results. The occurrence of macrolides and clindamycin resistance was 16.5% in 2005 increasing up to 69.9% in 2008. A high percentage of isolates was resistant to tetracycline through all the study period with no statistically significant annual.Conclusions. In our cohort, an increase ofin vitroresistance of GBS to macrolides and clindamycin is clearly evident. The discordance with reports from different countries emphasize the crucial role of microbiological methods in setting possible therapeutic strategies.

In resource-rich settings, advances in antiretroviral therapy have reduced the morbidity and increased the life expectancy of patients infected with HIV and consequently increased the likelihood of observing other non-HIV-related diseases in this group of patients. We report a high-risk pregnancy in a 26-year-old woman infected with HIV with complicated insulin-dependent diabetes mellitus. Because of maternal concomitant disease and concerns regarding potential antiretroviral toxicity on maternal disease, an abbreviated regimen of zidovudine prophylaxis was offered to prevent neonatal infection. After the iatrogenic preterm delivery of a healthy and uninfected baby, the patient experienced vulvar oedema and she is now waiting for renal transplantation. In conclusion, our case is one of a range of possible scenarios that may develop in pregnant women who are infected with HIV, reflecting the highly active antiretroviral therapy (HAART)-associated improvements in survival and health.

lbright-Hodes syndrome, or limb reduction defects and renal dysplasia, is an unusual lethal congenital malformation that consists of mesomelia, radiohumeral fusion, and renal dysplasia. We report the successful prenatal diagnosis of the condition at 21 weeks’ gestation in a family with a negative history, which to our knowledge has not been reported previously. Sonographic findings, new and atypical features, the differential diagnosis, and counseling of the couple are reported.

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.

To analyze the changes over two decades in HIV-infected pregnant women followed at a highly specialized regional center for antenatal care in southern Italy.Since 1985, all HIV-infected pregnant women attending our center have been monitored using progressively updated protocols.By December 2006, 230 deliveries in 159 women had been monitored. Deliveries in HIV-infected women increased from 0.16% (4/2,499) of all deliveries in 1985 to 0.73% (15/2,042) in 2006. The sociodemographic profile of the women changed greatly over the study period, and there was a shift from injecting drug use to heterosexual contact as the main transmission route and an increased proportion of foreign women. Subsequent to improvements in clinical care, the proportion of infected pregnant women receiving antiretroviral treatment increased from 27% (17/63) before 1996 to 81% (63/78) in 2006, with a corresponding decrease in the mother-to-child transmission rate from 36% (16/44) to 0.6% (1/157).The increasing number of HIV-infected pregnant women can be attributed to nonselective antenatal HIV screening, the spread of HIV infection through heterosexual contacts, and the desire of HIV-infected women to have children. In this context, highly specialized reference centers can play an important role in providing HIV-infected pregnant women with optimal care and in reducing mother-to-child transmission rates to very low levels.

Objective To assess the relationship between congenital heart disease (CHD) and Down syndrome (DS) in utero. Design Retrospective case series. Subjects Fifty-two fetuses with a cytogenetic diagnosis of DS managed at our Fetal Cardiology Unit in the study period. In particular, two populations of fetuses with DS were studied: a group of 41 DS fetuses referred to our unit for fetal echocardiography due to the chromosomal anomaly and a second group of 274 fetuses referred because of suspected CHD, 11 of which were found to have DS. Methods All fetuses were submitted to detailed ultrasound evaluation of fetal anatomy. Associated extracardiac anomalies, and presence and type of CHD, were recorded for all fetuses. Karyotyping was obtained by means of cordocentesis or amniocentesis. Necropsy or neonatal echocardiograms were sought for confirmation of the prenatal diagnosis. Results In the group of 41 fetuses with known DS, the incidence of CHD was 56% ([atrioventricular septal defect (AVSD) 44%, ventricular septal defect (VSD) 48%], the remainder having other heart defects). Conversely, considering the incidence of DS in fetuses with CHD, 43% of all AVSDs (53% of AVSD with normal visceral situs) were associated with DS, whereas none of the 39 cases of VSD was associated with trisomy 21. Ventricular septal defects were diagnosed only in fetuses referred to our center with a known diagnosis of aneuploidy. Conclusions We have confined that more than half of the fetuses with DS bear a CHD, which is an AVSD in 44% of cases. Conversely, 43% of fetuses with an AVSD have trisomy 21. For VSDS, the situation is controversial, due to the relatively low detection level of this heart defect at the routine mid-trimester obstetric scan.

The study objective was to assess the feasibility and the efficacy of bilateral uterine artery embolization (BUAE) for the treatment of cervical pregnancy. The design was a series of 3 cases of viable cervical pregnancy diagnosed by transvaginal ultrasonography and treated by means of BUAE and subsequent uterine curettage. Three women with viable cervical pregnancy underwent BUAE and subsequent uterine curettage in the department of obstetrics and gynecology, High Risk Pregnancy Center, University "Federico II" of Naples. Measurements included surgical outcomes and preservation of fertility. The treatment was effective in all cases. Two patients resumed normal menstruation about 1 month after the procedure, whereas 1 patient underwent a hysterectomy 2 weeks after embolization because of acute ischemic degeneration of a concomitant myoma. The conservative management of cervical pregnancy with angiographic BUAE is a feasible and effective option, even if subsequent hysterectomy may be required. Counseling is necessary.

Spilt notochord syndrome is an extremely rare form of spinal dysraphism characterized by a complete cleft of the spine and a persistent communication between endoderm and ectoderm. A variant of split notochord syndrome was diagnosed in a 25-week-old fetus showing a prolapsed congenital colostomy and a spinal cystic lesion. The final diagnosis included protruding colon segment, imperforate anus with a rectourethral fistula and lipomyelomeningocele. The ultrasound features of the condition and the post-natal management are discussed. The neonate was successfully treated with a posterior sagittal anorectoplasty, while the lipomyelomeningocele was resected at a later stage.

Objectives In the past essential thrombocythemia was considered a disease of the elderly. At present, the number of young people suffering from this disease is growing, with a slightly higher frequency in females. We investigated the effects of interferon alfa therapy in these patients. Study design We describe 9 pregnancies in 4 women affected by essential thrombocythemia. Results Four pregnancies were carried out without interferon alfa therapy, and resulted in 2 intrauterine deaths, 1 spontaneous abortion, and 1 neonatal death. Interferon alfa was given during another 5 pregnancies; among them, 2 ended in preterm deliveries with normal infants, and 3 in full-term deliveries. The literature is reviewed. Conclusion Our cases and published series suggest that fetal outcome is improved by therapy, and that interferon alfa may be the best therapeutic option.

INTRODUCTION: Most national guidelines for the prevention of mother-to-child transmission of HIV in Europe updated between 2001 and 2010 recommend vaginal deliveries for women with undetectable or very low viral load (VL). Our aim was to explore the impact of these new guidelines on the rates of vaginal deliveries among HIV-positive women in Europe. METHODS: In a pooled analysis of data on HIV-positive pregnant women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study 2000 to 2010, deliveries were classified as occurring pre- or postpublication of national guidelines recommending vaginal delivery. RESULTS: Overall, 2663 women with 3013 deliveries were included from 10 countries; 28% women were diagnosed with HIV during pregnancy. Combination antiretroviral therapy was used in most pregnancies (2020, 73%), starting during the first or second trimester in 78% and during the third trimester in 22%; in 25% pregnancies, the woman conceived on combination antiretroviral therapy. Overall, in 86% pregnancies, a VL < 400 copies per milliliter was achieved before delivery. The proportion of vaginal deliveries increased from 17% (414/2377) before the change in guidelines to 52% (313/600) after; elective Caesarean section rates decreased from 65% to 27%. The proportion of women with undetectable VL having a Caesarean section was 55% after implementation of new guidelines. We observed a decrease of late preterm deliveries from 16% (377/2354) before to 7% (42/599) after the change in guidelines (P < 0.001). CONCLUSION: There are still missed opportunities for women with HIV to fully suppress their VL and to deliver vaginally in Europe.

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.

We report a case of prenatal ultrasound diagnosis of frontonasal dysplasia. This represents a very rare disorder involving the face (hypertelorism, median cleft lip, absence of the nasal tip) and often the central nervous system (CNS) (cranium bifidum occultum, ethmoidal cephalocele, agenesis of the corpus callosum). Although several of the typical anomalies are diagnosable by ultrasound in utero (hypertelorism, median cleft lip, anterior cephalocele), very few cases have been reported prenatally, the present being only the third. In the present case, hemimegalencephaly is first reported among the anomalies possibly associated with frontonasal dysplasia. The diagnosis was made at 22 weeks' gestation and was confirmed by necropsy following termination of pregnancy.

Oculoauriculovertebral spectrum, or Goldenhar syndrome, is characterized by varying degrees of prevalently unilateral underdevelopment of craniofacial structures (orbit, ear, mandible) and spinal anomalies. We report the prenatal ultrasonographic diagnosis made at 24 weeks' gestation in a family with a negative history. The prenatal diagnosis was suspected due to the presence of marked hemifacial microsomia and moderate ipsilateral cerebellar hemisphere hypoplasia in the absence of facial clefting.

The trend to have children even if one or both parents suffer from chronic diseases is influenced by personal, psycho-organic and social factors. The Authors face the moral and professional dilemma of honouring a woman's intentions, or persuading her to interrupt her pregnancy to prevent damage to her health.

Background Although mother-to-child transmission (MTCT) rates are at an all-time low in Western Europe, potentially preventable transmissions continue to occur. Duration of antenatal combination antiretroviral therapy (ART) is strongly associated with MTCT risk. Methods Data on pregnant HIV-infected women enrolled in the Western and Central European sites of the European Collaborative Study between January 2000 and July 2009 were analysed. The proportion of women receiving no antenatal ART or 1–13 days of treatment was investigated, and associated factors explored using logistic regression models. Results Of 2,148 women, 142 (7%) received no antenatal ART, decreasing from 8% in 2000–2003 to 5% in 2004– 2009 (χ2=8.73; PConclusions Over the last 10 years, around one in 11 women in this study received insufficient antenatal ART, accounting for 40% of MTCTs. One-half of these women were diagnosed before conception, suggesting disengagement from care.

The Pena-Shokeir phenotype represents an autosomal recessive syndrome characterized by neurogenic arthrogryposis, facial anomalies and pulmonary hypoplasia. Prenatal diagnosis of this disease has been reported prospectively and in cases with positive family history. We describe here a patient who has had three consecutive pregnancies affected by the Pena-Shokeir syndrome. In these pregnancies, the onset of the arthrogryposis varied between the 12th and the 18th week of gestation. Therefore, the possibility of a variable chronological development of the main diagnostic feature of the syndrome, arthrogryposis, has to be taken into proper consideration while counseling families with a positive history for the Pena-Shokeir phenotype.

HIV-positive women with pelvic inflammatory disease have been reported to have an increased prevalence of tuboovarian masses (TOMs). The aim of this study was to assess the prevalence of asymptomatic ultrasonographic TOMs in women with HIV and to identify associated factors in order to formulate a selective ultrasonographic screening strategy. Two-hundred and four HIV outpatients underwent transvaginal ultrasonography. Eight (3.9%) had a diagnosis of TOM (5 were asymptomatic). Two profiles of patients at risk for TOM were identified who could be considered for selective screening strategies: the ‘long-term infected’ (age>35 years, diagnosis of HIV infection more than 5 years ago, HIV clinical category C, CD4 counts below 200/mm3, >5 lifetime partners and on antiretroviral therapy) and the ‘recently diagnosed with HIV’ (African ethnicity, age 25–35, HIV diagnosis in the previous year, >5 lifetime partners, HIV clinical category C and not on antiretroviral therapy).

Objectives The aim of the study was to examine temporal and geographical patterns of mode of delivery in the European Collaborative Study (ECS), identify factors associated with elective caesarean section (CS) delivery in the highly active antiretroviral therapy (HAART) era and explore associations between mode of delivery and mother-to-child transmission (MTCT). Methods The ECS is a cohort study in which HIV-infected pregnant women are enrolled and their infants prospectively followed. Data on 5238 mother-child pairs (MCPs) enrolled in Western European ECS sites between 1985 and 2007 were analysed. Results The elective CS rate increased from 16% in 1985-1993 to 67% in 1999-2001, declining to 51% by 2005-2007. In 2002-2004, 10% of infants were delivered vaginally, increasing to 34% by 2005-2007. During the HAART era, women in Belgium, the United Kingdom and the Netherlands were less likely to deliver by elective CS than those in Italy and Spain [adjusted odds ratio (AOR) 0.07; 95% confidence interval (CI) 0.04-0.12]. The MTCT rate in 2005-2007 was 1%. Among MCPs with maternal HIV RNA

To the Editor: Since the ACTG076 trial results were published in 1994 [1], antiretroviral prophylaxis for the neonate as well as during pregnancy and delivery has been the cornerstone of prevention of mother-to-child transmission (MTCT) of HIV. In the second decade of the combination antiretroviral therapy (cART) era, around 90% of pregnant HIV-infected women in Western Europe receive antenatal cART, for their own health and/or for prevention of MTCT (PMTCT) [2-4]. The rationale for including neonatal prophylaxis in the ACTG076 trial included uncertainty regarding timing of MTCT and the desire to boost the infant’s in utero and intrapartum antiretroviral drug exposure with 6 weeks zidovudine prophylaxis, as a post-exposure prophylaxis (PEP) for newborns not infected with HIV in utero. Observational studies and trials subsequently demonstrated effectiveness of neonatal PEP for infants whose mothers received no antiretroviral drugs [5-7]. No trial data exist comparing the efficacy of different neonatal prophylaxis regimens for infants of women on cART. We investigated trends in neonatal prophylaxis use in the cART era in Western European sites of the European Collaborative Study, a cohort of HIV-infected pregnant women and their children; full methods are described elsewhere [4]. Logistic regression was used to investigate factors associated with receipt of neonatal prophylaxis. Variables considered in the multivariable model were antenatal antiretroviral use, mode of delivery, country and year of delivery, prematurity (

Pregnancy in a woman with a history of Budd-Chiari syndrome treated by porto-systemic shunt, protein C deficiency and bicornuate uterus

The comfort-care is an innovative practice introduced recently by the neonatologist Dr. Elvira Parravicini, from Columbia University Medical Center [1]. This practice in a Neonatal Intensive Care Unit (NICU) is a compassionate response that provides families with clear and relevant information and that focuses on the needs of the parents as well as the baby. On the baby side, the need to be kept warm, to be free from hunger, thirst or pain are the cornerstones of the program. On the family side, it is a viable option of care for fetus/neonates who are suffering from life-limiting conditions which takes in to account the emotional needs of the family at this difficult time [2]. When we are not able to ensure medical treatments aimed at curing the disease, we can help in a different way. Palliative care planning involves multidisciplinary team planning with professionals from (1) gynecologist (2) midwife, (3) neonatologist, (4)pediatric nurse, (5) psychologist. The multidisciplinary approach is pointed on the satisfaction of “essential needs” of both the family and the baby starting from the pre birth care to the post death care. The team's goals cover practical aspects of infant care, including pain relief, symptom relief, comfort and dignity, the management of prognostic uncertainties, but also the provision of support to families during the pregnancy, their baby's illness and afterwards when coming to terms with his loss. The target population is all infants with a life-limiting conditions (trisomy 13, trisomy 18, bilateral renal agenesis or anencephaly, etc.) for whom a decision has been made to not interrupt the pregnancy [1]. The care planning is very flexible and continuously consideres parents’ personal and/or spiritual wishes, moreover it is continuously reviewed in the best interests of the baby. Multidisciplinary discussions and decision making involving the parents and the team to plan the management are essential. At least also the staff is provided with informal and formal support during the period of providing palliative care [3,4].

Results: Ultrasound examination of a 30-year-old Caucasian female, pregnant for the first time, showed a monozygotic pregnancy with: scalp cystic hygromata, polycystic kidney, bilateral clubhand, varusequin foot and polyhydramnios. These anomalies indicated possibility of chromosomal abnormality and suggested to perform the amniocentesis; fetal chromosomal analysis showed abnormal karyotype 47, XY, +21. The parents opted for termination of this pregnancy. Conclusions: The necessity of routine ultrasound examination for the prenatal detection of chromosomal abnormalities to all pregnancies.

Multiple endocrine neoplasia 2A (MEN 2A) is an inherited dominant syndrome characterised by medullary thyroid carcinoma, adrenal pheochromocytoma and hyperparathyroidism due to specific RET proto-oncogene mutations. Fertile MEN 2A women are at risk of complicated pregnancy because of unrecognised pheochromocytoma and transmission of RET mutation to the progeny. This condition may cause psychological distress in affected pregnant patients and their families. Here we describe the genetic prenatal testing, the pregnancy management and obstetric outcome in a MEN 2A patient with a right side adrenal hyperplasia and elevated calcitonin levels, a condition suspicious for possible recurrence of pheochromocytoma. We confirm that maternal or fetal complications are rare when MEN 2A diagnosis is made before pregnancy and an accurate monitoring is instituted. Furthermore, our results indicate that prenatal testing for RET mutations is highly recommended in making decisions and assuring parents on the lifelong risk of tumors. This will avoid the psychological distress that can further complicate the pregnancy of affected women.

Objective: To assess pregnancy levels and patterns of HIV RNA in the absence of antiretroviral therapy, while appropriately adjusting for potential confounders, including maternal immune status and race. Methods: Data on >= 1 antenatal HIV RNA measurements were available for 333 untreated HIV-infected pregnant women enrolled in the European Collaborative Study. CD4 counts and HIV RNA measurements were routinely collected from 1992 and 1998, respectively. Linear mixed effects models based on 246 women for whom complete data were available examined changes in HIV RNA levels over pregnancy, with a nested random effects term accounting for measurement variability within women and period of sample collection. Results: The change in HIV RNA over pregnancy varied significantly by race (p = 0.005): from the second trimester until delivery, HIV RNA decreased significantly by an estimated 0.019 log(10) copies/ml/week in white women (95% Cl -0.03, -0.007); in black women the estimated 0.016 log(10) copies/ml/week increase (95% Cl -0.005, 0.037) was not statistically significant. At delivery, HIV RNA levels in black women were 0.45 log(10) copies/ml higher (95% Cl 0.08, 0.83) than in white women. Conclusions: Our findings suggest that HIV RNA dynamics over pregnancy differ by race, although other interpretations cannot be excluded, due to potential for unmeasured confounding. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Recombinant factor VIIa in a patient with Glanzmann’s thrombasthenia undergoing gynecological surgery: open issues in light of successful treatment

OBJECTIVE To examine how the subsequent childbearing of HIV-infected mothers enrolled in the European Collaborative Study (ECS) has changed over time and identify factors predictive of further childbearing. DESIGN Prospective cohort study. SETTING Centres in nine European countries included in the ECS, enrolled between end 1986 and November 2003. POPULATION HIV-infected women (3911): 3693 with only one and 218 with subsequent live births. METHODS Univariable and multivariable logistic regression analyses to obtain odds ratios (OR) and 95% confidence intervals (CI). Kaplan-Meier (KM) analyses to estimate cumulative proportions of women having a subsequent live birth. MAIN OUTCOME MEASURES Subsequent live birth. RESULTS In multivariable analysis adjusting for time period, ethnicity, maternal age and parity, black women were more likely [adjusted odds ratio (AOR) 2.45; 95% CI, 1.75-3.43], and women >30 years less likely (AOR 0.54, 0.37-0.80), to have a subsequent live birth. Time to subsequent live birth significantly shortened over time, with an estimated 2% of women having a subsequent live birth within 24 months of enrollment pre-1989 versus 14% in 2000-2003 (P < 0.001). Estimated time to subsequent live birth was shorter for black than for white women (P < 0.001). CONCLUSIONS The likelihood of subsequent live births substantially increased after 1995 and birth intervals were shorter in women on HAART and among black women. Numbers are currently too small to address the issue of advantages and disadvantages in the management of subsequent deliveries.