ObjectivesThe 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).MethodsThe 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.ResultsThe 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 < 400 HIV-1 RNA copies/mL (n=960), elective CS was associated with 80% decreased MTCT risk (AOR 0.20; 95% CI 0.05-0.65) adjusting for HAART and prematurity. Two infants born to 559 women with viral loads < 50 copies/mL were infected, one of whom was delivered by elective CS (MTCT rate 0.4%; 95% CI 0.04-1.29).ConclusionsOur findings suggest that elective CS prevents MTCT even at low maternal viral loads, but the study was insufficiently powered to enable a conclusion to be drawn as to whether this applies for viral loads < 50 copies/mL. Diverging mode of delivery patterns in Europe reflect uncertainties regarding the risk-benefit balance of elective CS for women on successful HAART.

The objective of this document is to identify and reinforce current recommendations concerning the management of HIV infection in infants and children in the context of good resource availability. All recommendations were graded according to the strength and quality of the evidence and were voted on by the 57 participants attending the first Italian Consensus on Paediatric HIV, held in Siracusa in 2008. Paediatricians and HIV/AIDS care specialists were requested to agree on different statements summarizing key issues in the management of paediatric HIV. The comprehensive approach on preventing mother-to-child transmission (PMTCT) has clearly reduced the number of children acquiring the infection in Italy. Although further reduction of MTCT should be attempted, efforts to personalize intervention to specific cases are now required in order to optimise the treatment and care of HIV-infected children. The prompt initiation of treatment and careful selection of first-line regimen, taking into consideration potency and tolerance, remain central. In addition, opportunistic infection prevention, adherence to treatment, and long-term psychosocial consequences are becoming increasingly relevant in the era of effective antiretroviral combination therapies (ART). The increasing proportion of infected children achieving adulthood highlights the need for multidisciplinary strategies to facilitate transition to adult care and maintain strategies specific to perinatally acquired HIV infection.

The aim of the study was to adjust and improve the accuracy of ultrasound two-dimensional estimation of fetal weight based on fetal standard biometry, by taking into account maternal data and additional fetal variables. We examined in a retrospective cross-sectional study 594 singleton uncomplicated pregnancies between 37 and 42 weeks. Each case underwent a 2D ultrasonography to obtain fetal standard biometric measurements (biparietal diameter, head circumference, abdominal circumference and femur length). The following variables, related with birth weight, were registered: maternal features (parity, maternal age, height, weight, BMI, weight increase, first child birth weight) and fetal variables (birth weight, gestational age at US examination and delivery, gender). An univariate analysis was performed in order to define the specific-weight of each variable in this series. We fitted linear regression equations and determined by the Box–Cox method that the square root of BW was the optimal transformation to define the variances and achieve normality. The new formula for estimating fetal weight was compared with commonly used weight estimation models. A new fetal weight estimation formula including HC, AC, FL, maternal BMI, gestational age at US examination, and fetal gender proved to be more precise in estimating fetal weight compared with established equations. We estimated on the basis of these results that 87.9% of the predicted birth weight fell between ± 10% of the observed birth weight (32–69% in reference models) and the mean absolute percent error in fetal weight prediction was 5.77% (versus a range of MA% error in published studies of 8.1–16.5%). This new formula showed that the accuracy of fetal weight estimation near term by traditional models based only on routine fetal biometry may be improved by using maternal (BMI) and fetal variables (gender, gestational age at US examination).

A panel of leading Italian specialists in infectious diseases, obstetrics and gynaecology met in a national consensus workshop on women facing HIV to review critical aspects and discuss recommendations for selected key questions on four issues: (1) women and highly active antiretroviral therapy (HAART): access to care and adherence to therapy, side effects and drug–drug interaction; (2) HIV-infected pregnant women: prevention of mother to child transmission; (3) desire for children among women living with HIV: assisted reproduction; (4) sexually transmitted diseases and genital disturbances. The method of a nominal group meeting was used, and recommendations were graded for their strength and quality of evidence using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed, and some of the most recent data supporting recommendations are provided.

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.

During the past 15 years Assisted Reproduction has been facing a new demand from patients requiring ART: couples at risk of partner to partner, and mother to child transmission of viral infections, mainly HIV-1, HCV and HIV–HCV co-infected partners. The general conditions and life expectancy of many patients with HIV infection are very good, and three-quarters of these individuals are in their reproductive years. For these reasons, a large number of young couples are expected to make future plans to have children. This desire is not easy to realize for serodiscordant couples, if we consider that, in order to avoid HIV virus transmission, it is necessary to encourage the condom use in vaginal and anal contacts. On the other hand infertile discordant HCV couples need to be included in protocols of controlled assisted reproduction procedures to avoid any risk of HCV transmission to the partner. In this paper we consider assisted reproduction in discordant couples for HIV or HCV-positive men.

Objectives The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV‐infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use. Methods Information on HBV surface antigen (HBsAg) positivity and HCV antibody (anti‐HCV) was collected retrospectively from the antenatal records of HIV‐infected women enrolled in the European Collaborative Study and linked to prospectively collected data. Results Of 1050 women, 4.9% [95% confidence interval (CI) 3.6–6.3] were HBsAg positive and 12.3% (95% CI 10.4–14.4) had anti‐HCV antibody. Women with an injecting drug use(r) (IDU) history had the highest HCV‐seropositivity prevalence (28%; 95% CI 22.8–35.7). Risk factors for HCV seropositivity included IDU history [adjusted odds ratio (AOR) 2.92; 95% CI 1.86–4.58], age (for ≥35 years vs . <25 years, AOR 3.45; 95% CI 1.66–7.20) and HBsAg carriage (AOR 5.80; 95% CI 2.78–12.1). HBsAg positivity was associated with African origin (AOR 2.74; 95% CI 1.20–6.26) and HCV seropositivity (AOR 6.44; 95% CI 3.08–13.5). Highly active antiretroviral therapy (HAART) use was less likely in HIV/HCV‐seropositive than in HIV‐monoinfected women (AOR 0.34; 95% CI 0.20–0.58). HCV seropositivity was associated with a higher adjusted HIV RNA level (+0.28log 10 HIV‐1 RNA copies/mL vs . HIV‐monoinfected women; P =0.03). HIV/HCV‐seropositive women were twice as likely to have detectable HIV in the third trimester/delivery as HIV‐monoinfected women (AOR 1.95; P =0.049). Conclusions Although HCV serostatus impacted on HAART use, the association between HCV seropositivity and uncontrolled HIV viraemia in late pregnancy was independent of HAART.

1) to study uterine artery (UtA) flow volume, diameter and velocity across gestation in normal uncomplicated human pregnancies; 2) to correlate UtA flow to UtA Pulsatility Index (PI) and estimated fetal weight (EFW) across gestation. Seventy-nine ultrasound exams performed in 49 singleton uneventful pregnancies, with a normal mean UtA PI, were considered. Each UtA was evidenced by power-Doppler mode. UtA diameter assessment and Doppler sampling were performed 10–15 mm prior to bifurcation. UtA diameter was measured on a perpendicular B-mode view after removing power-Doppler. UtA PI and velocity measurements had a Doppler beam angle < 30°. The average of three consecutive diameters and velocities were considered. UtA flow was estimated as Q = hV · πD2/4; h coefficient (0.5) was obtained by an ad hoc mathematical model. Calculations to test for mean differences and Spearman's rank correlation were used allowing for repeated measurements (Stata Software). 1) Total UtA flow significantly increased along gestation from 138.8 ml/min at 15 weeks to 405.7 at 35 weeks (2.9 fold) (p < 0.0001). UtA diameter increased from 2.38 mm at 15 weeks to 3.02 mm at 35 weeks, but this trend did not reach any significance; UtA mean velocity significantly increased along gestation, from 52.2 cm/s at 15 weeks to 98.9 at 35 weeks (1.9 fold) (p 0.02); 2) UtA flow (ml/min) reduced with UtA PI growth, even not significantly. UtA flow per EFW did show a significant inverse correlation to gestational age, dropping from 780.6 ml/min/kg at 15 weeks to 138.1 at 35 weeks (5.6 fold) (p < 0.001). 1) UtA flow (ml/min) and mean velocity significantly increased across gestation in normal pregnancies, while UtA diameter showed a slight not significant increment; 2) UtA flow volume (ml/min) did not show a significant reduction in relation to UA PI increase; UtA flow per EFW significantly reduced along gestation.

1) To study uterine artery (UtA) flow (ml/min) growth rate along gestation in normal human pregnancies; 2) to evaluate longitudinal changes of UtA flow expressed per unit estimated fetal weight (EFW) (ml/min/kg). A cohort of twelve singleton uneventful human pregnancies, with a normal mean UtA PI, was included in this longitudinal study. UtA was evidenced by power-Doppler mode and sampled 10–15 mm prior to bifurcation. UtA diameter was measured on a perpendicular view after removing power-Doppler. UtA PI and velocity were measured with a Doppler beam angle < 30°. The average of three consecutive diameters and velocities was considered. UtA flow was estimated by the formula Q = hV · πD2/4; h coefficient (0.5) was obtained by an ad hoc mathematical model. UtA total flow (ml/min) (right plus left UtA flow) was then expressed per EFW (ml/min/kg). Using linear interpolation, including random effects for the intercept and the slope of gestational age for each fetus, a linear mixed effects model was fitted. Forty-seven ultrasound examinations were performed. Ultrasound exams were performed at 14.3,b1.2 weeks and every 4 weeks until delivery. Each case was definitively included in the study after recording normal perinatal and neonatal outcomes. UtA total flow (ml/min) showed a significant correlation to gestational age (133.6 ml/min at 15 weeks; 415.9 ml/min at 35 weeks) (p < 0.001), with a linear increase of 14.1 ml/min per week (right UtA 5.4 vs. left UtA 8.7 ml/min per week, p NS). UtA flow per unit EFW (ml/min/kg) showed a significant reduction from 780.3 ml/min/kg at 15 weeks to 144.1 ml/min/kg at 35 weeks (reduction rate 40.3 ml/min/kg per week). UtA flow (ml/min) significantly increased along gestation in this longitudinal cohort of normal pregnancies. UtA flow per unit EFW (ml/min/kg) significantly decreased longitudinally, since UtA flow (ml/min) growth rate was lower than fetal weight gain rate along gestation.

The objective of the study was to evaluate the access to Papanicolau (Pap) tests of HIV-infected women in Italy. A cross-sectional survey on a cohort of HIV-infected women seen at 27 HIV clinics was performed. At each clinic a female physician involved in the care of HIV-infected women was asked questions on clinic and patients' characteristics and on access to Pap tests. The outcome of the study was to find the percentage of women who had not had a Pap test before coming to the HIV clinic and the percentage having had a Pap test in 2001. In the survey, 7,600 HIV-infected women were represented. Women who came to the clinic without having ever had a Pap test were 62+/-22%, while women who had had a Pap test in 2001 were 43+/-36%. Women who reported never having had a Pap test before coming to the HIV clinic were more often from the south than the north of Italy (17.9+/-49% from the north, 18+/-53% from the center and 9.3+/-83.9% from the south; p<0.001). This a difference disappeared when comparing the women who had had a Pap test in 2001 (28+/-39.6% from the north, 31.6+/-44.2% from the center and 25.6+/-45.7% from the south; p=0.88). Despite the published guidelines in Italy, only 38% of women had ever had a Pap test before coming to the HIV clinic and only 43% had had a Pap test in 2001. Strategies aimed to improve these proportions should be rapidly implemented at all levels of care organization.

1) to correlate uterine artery (UtA) flow volume, diameter and velocity with placental site in normal uncomplicated human pregnancies; 2) to correlate UtA blood flow to UtA Pulsatility Index (PI) in different placental insertions. Seventy-two singleton uneventful pregnancies, with a normal mean UtA PI, were included in the study. UtA was evidenced by power-Doppler mode and sampled 10–15 mm prior to bifurcation. UtA diameter was measured on a perpendicular view after removing power-Doppler. UtA PI and velocity were measured with a Doppler beam angle < 30°. The average of three consecutive diameters and velocities was considered. UtA flow was estimated by the formula Q = hV · πD2/4; h coefficient (0.5) was obtained by an ad hoc mathematical model. Placental site was registered. Forty-six central and 26 lateral placental sites (8/26 right, 18/26 left) were recorded. Gestational age at examination was 22.4 ± 4.8, 20.9 ± 0.6 and 21.2 ± 4.7 weeks, respectively (p NS). 1) With a central placental UtA flow was equally distributed between the two vessels (right UtA 49.7 ± 11.0%, left UtA 50.3 ± 11.0%). Lateral placental site results are shown in the table below. 2) A significant inverse correlation was observed between ipsilateral UtA flow and PI (p < 0.001), but not in the controlateral vessel and in central placenta vessels. 1) In lateral placental insertions UtA flow was higher in the ispilateral than in the controlateral vessel, even this difference not reach a statistical significance; UtA mean velocity was significantly higher in the ispilateral than in the controlateral UtA, while diameter did not differ. In central placentae UtA flow was equally distributed. 2) Ipsilateral UtA flow significantly inversely correlated with PI increase, while controlateral and central placenta vessel flow did not.

To improve ultrasonography- base prediction of fetal weight at term, accounting for routinely measurable maternal and pregnancy-specific variables. Data on 1208 single pregnancies were prospectively collected; to estimate term birth weight (BW). 594 uncomplicated pregnancies were analysed. (gestational age (GA) at delivery between 37 and 42 weeks) with complete information on: Fetal Abdominal Circumference, Head Circumference, Femur length, neonatal Gender and BW and GA at delivery; Maternal Body mass Index (BMI), GA at ultrasound exam, Maternal Weigh increase during pregnancy, Maternal Age Statistical methods We fitted linear regression models using the square root to stabilise the variances and achieve Normality for BW. An interaction term was included in order to reflect possible synergy between fat/bone growth and quadratic terms for fetal variables to allow for growth faster than linear in these measurements An optimal model was found using a predictive information criteria. (S-Plus 2000). Baseline data included 300 female and 294 male born to Caucasian women with median BW gr 3365 (range 1930–5000); median maternal age 31 (range 16–44); maternal BMI is 26 (range 19–37); median maternal weight increase12 kg (range 4–27). We found a significant association with maternal BMI (p < 0.001) and gender (p < 0.0001). The final model is (SexNeonate is 0 = girl or 1 = boy). Matching the observed BW vs our prediction, and calculating the difference as a %of the observed BW, we estimated that 86.7% of the predicted BW fell between, b 10% of the observed BW. The mean absolute percent (MA %)error in BW prediction was 5.37%, remaining constant also for BW > 3500 gr. (n157) Our results compare favorably with previous published results (Table)

PURPOSE OF REVIEW:Three quarters of individuals infected with HIV are in their reproductive years and can expect an almost normal life expectancy under antiretroviral treatment. Many of them want to have a child and reproductive counselling and care can offer a sharp reduction in both sexual and vertical transmission rates.RECENT FINDINGS:Most couples with HIV are formed by an infected man and an uninfected woman; in this setting, semen washing coupled with reproductive technology can be applied to eliminate the risk of sexual transmission of the virus. Semen washing is a processing method which reduces both HIV RNA and DNA to undetectable amounts. In couples in which only the woman is infected, self-insemination might be indicated. When both partners are carrying HIV, semen washing can be used in couples with different viral strains. HIV can be vertically transmitted and the risk of infection for the infant can be decreased to approximately 1% by reducing maternal viral load, elective caesarean section and avoidance of breastfeeding. In pregnancy the efficacy of antiretroviral treatment should be balanced against the possibility of embryonic or fetal toxicity. Caesarean section, performed electively, has proven its protective efficacy, without significant maternal morbidity. Its role should now be reassessed in mothers with undetectable viral load. Breastfeeding, discouraged to avoid postnatal transmission, might be possible in the future, with antiretroviral therapy capable of suppressing viral excretion in maternal milk.SUMMARY:Semen washing, reproductive technology, antiretroviral therapy and obstetrical care can work in sequence to allow safe reproduction in couples infected with HIV.

Purpose of review Advances in antiretroviral regimens and specific obstetrical procedures have enabled HIV-positive women to have children, with a very low risk of transmitting the infection to the infant and with improved chances of seeing their children reach adulthood. New studies have given providers of care better information on how to assist women with HIV who want to have a child in the safest possible way. Recent findings Highly active antiretroviral therapy can effectively control viral replication and reduce the risk of vertical transmission. The benefit of treatment for the mother and the infant must be balanced against any negative effects on pregnancy, the embryo and the fetus. Potential long-term consequences of prenatal exposure to potent compounds should also be considered and monitored. The evidence suggests that even in women with undetectable viral load, Caesarean section reduces vertical transmission to the same degree as documented previously for all women. Although the absolute risk reduction is very low, no study can show whether or not this is statistically significant and therefore women should be helped to make their individual choice. Mothers with HIV should not breastfeed in countries where formula milk is easily available, however highly active antiretroviral therapy administered to mothers or infants may reduce the risk of postnatal HIV transmission. Summary Counselling and assistance to conceive, modification of the therapeutic regimens and options about delivery have changed dramatically since the beginning of the HIV epidemic. Nowadays, women with HIV, similarly to uninfected women, can discuss with their doctors which therapeutic and treatment options would best fit their expectations of care.

Data from the United States (US) were presented recently suggesting antiretroviral therapy (ART) during pregnancy in HIV women was not associated with an increased risk of prematurity (1). These findings contradict earlier findings from Europe which demonstrated a small but significant increased risk of premature delivery with use of combination therapy, especially when including a protease inhibitor (PI), and in particular when started before or in early pregnancy (2). But differences in populations and methodology applied could explain much of this apparent contradiction. Clinicians caring for HIV infected women should be aware of these findings.

ObjectiveTo describe changes over a 15-year period in characteristics and management of HIV-infected pregnant women in Europe. DesignProspective study. MethodsAnalysis of prospective data on 2876 pregnant HIV-infected women and their 3076 infants. Factors examined included maternal socio-demographic, immunological and virological characteristics, antiretroviral therapy and pregnancy outcome. ResultsAmong women enrolled, the proportion with heterosexual acquisition of infection has increased significantly from 59% (201/342) in 1985–1987 to 69% (327/471) after 1997 while the proportion acquiring HIV through injecting drug use has declined. Overall median CD4 cell count was 440 × 106/l and 41% of women had undetectable viral load at delivery. In 1995 28% (72/256) of mother–child pairs received the full 076 regimen to reduce risk of vertical transmission, rising significantly to 89% (116/130) by 1999. Use of triple therapy started in pregnancy has increased significantly from < 1% (1/153) in 1997 to 44% (47/107) in 1999. Exposure to antiretroviral therapy was not associated with prevalence or pattern of congenital abnormalities (P = 0.88) but was associated with reversible anaemia in the infant (P < 0.002). The elective cesarean section rate has increased from 10% in 1992 to 71% in 1999/2000. The vertical transmission rate declined from 15.5% by 1994 to 2.6% after 1998. In multivariate analysis, adjusting for maternal CD4 cell count, risk of vertical transmission was reduced by 66% (95% confidence interval, 37–82%) with the full 076 regimen and by 60% (95% confidence interval, 33–73%) with elective cesarean section delivery. ConclusionsChanges in treatment of adult HIV disease have affected the management of infected pregnant women. Despite therapeutic and surgical interventions, vertical transmission still occurs.