Sophono in Pediatric Patients: The Experience of an Italian Tertiary Care Center.

OBJECTIVE: Since 2011, a transcutaneous bone-anchored auditory implant (Sophono) has been available for patients affected by bilateral, conductive hearing loss that cannot be corrected by surgery. To date, very few cases of device application in the pediatric population have been described. The aim of the present study is to report on complications, functional outcome, and health-related quality of life of the first pediatric cases in Italy. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary care pediatric center. SUBJECTS AND METHODS: Of 25 candidates with bilateral, conductive hearing loss screened between January 2012 and July 2013, 6 were included in the study (3 male and 3 female; median age, 9 years; age range, 5-17 years). Data concerning surgery, complications, functional outcome, and health-related quality of life were gathered prospectively. RESULTS: No major intraoperative complications occurred. Postoperative complications included 1 patient developing a skin ulceration below the external magnet and 1 patient reporting pain from using the device for more than 4 hours a day consecutively. Median free-field pure tone average (0.5-3 kHz) with the device was 32.5 dB HL, and median functional gain was 33 dB HL. Median Glasgow Children's Benefit Inventory score was +42. CONCLUSION: Sophono implants can be a valuable alternative to percutaneous implants in patients with bilateral, conductive hearing loss. To ensure the success of the treatment, several precautions should be taken, including a careful preoperative assessment of skull bone thickness and a close postoperative follow-up of the skin under the external processor, especially over the first months.

Decreased mitochondrial DNA content in subcutaneous fat from HIV-infected women taking antiretroviral therapy as measured at delivery.

BACKGROUND: Increasing numbers of pregnant HIV-positive women are receiving combination antiretroviral regimens for preventing mother-to-child virus transmission or for treating the infection itself. Several studies have demonstrated that nucleoside reverse transcriptase inhibitors (NRTIs) induce mitochondrial toxicity by several mechanisms, including depletion of mitochondrial DNA (mtDNA). By the quantification of mtDNA levels, we studied mitochondrial toxicity in HIV-positive women at delivery and the possible correlations with antiretroviral regimens, viroimmunological and metabolic parameters. METHODS: We analysed 68 HIV-positive women enrolled in the Italian Prospective Cohort Study on Efficacy and Toxicity of Antiretroviral in Pregnancy (TARGET Study); all were taking ≥1 NRTI. We quantified mtDNA copies per cell in subcutaneous fat samples collected during delivery. At the 3rd, 6th and 9th month of pregnancy, we collected data concerning CD4(+) T-cell count, plasma HIV RNA, total and high-density lipoprotein (HDL) cholesterol, fasting plasma glucose and triglycerides. As a control, we analysed mtDNA levels in abdominal subcutaneous fat samples from 23 HIV-seronegative women at delivery. RESULTS: mtDNA content was significantly lower in HIV-infected women when compared with HIV-negative controls. mtDNA content varied independently from viroimmunological, lipid and glucose parameters at the different months, with the exceptions of triglycerides at the 9th month and of HDL at the 6th month of pregnancy. CONCLUSIONS: In subcutaneous tissue from women taking NRTI-based antiretroviral regimens, we observed a significant decrease of mtDNA content, compared with uninfected women not on antiviral treatment. Moreover, a significant correlation was noted between mtDNA content and HDL cholesterol and triglycerides.

Treatment of viral hepatitis in pregnancy.

Viral hepatitis can be caused by the hepatitis A, B, C, D and E viruses. In the Western world, hepatitis A, B or C do not seem to influence the course of pregnancy, whereas hepatitis E infection, when contracted during the second or third trimester, seems to have a higher risk of developing into a fulminant hepatitis. Mother-to-infant transmission of hepatitis A seems to be very uncommon. The majority of HBsAg-positive and HBeAg-positive mothers can transmit the disease vertically. The timing of transmission is predominantly peripartum, and newborns of HBsAg-positive mothers should receive hepatitis B immunoglobulins within 12 h of birth, with HBV vaccine at birth and 1 and 6 months later. Hepatitis C is more often a chronic disease. Vertical transmission of hepatitis C is considered to be relatively rare but high viraemia or coinfection with HIV can increase this risk. There is currently no treatment to prevent this vertical transmission and pregnancies among HCV-positive mothers should not be discouraged. Infants should be tested for anti-HCV at 1 year and followed for the development of hepatitis. Breast feeding does not seem to play an important role in the transmission of hepatitis B and C.

How often are endometrial polyps malignant in asymptomatic postmenopausal women? A multicenter study.

OBJECTIVE: The objective of the study was to evaluate the prevalence of cancer and premalignant lesions in polyps on atrophic endometrium in asymptomatic postmenopausal women to compare these findings with a similar cohort of patients with abnormal uterine bleeding. STUDY DESIGN: One thousand one hundred fifty-two asymptomatic and 770 consecutive postmenopausal women with abnormal uterine bleeding were included in a retrospective multicenter study. Recruited patients underwent hysteroscopic polypectomy based on a sonohysterographic or hysteroscopic diagnosis. The pathologic report was the main outcome measure. RESULTS: One single case of stage 1 grade 1 endometrial carcinoma on a polyp with a mean diameter of 40 mm (0.1%) was observed in asymptomatic women. This prevalence was 10 times lower than in symptomatic patients (P < .0001). The prevalence of atypical hyperplastic polyps was 1.2% in asymptomatic women (2.2% in symptomatic patients; P < .005). At multivariate analysis, polyps' diameter was the only variable significantly associated to an abnormal histology (cancer, polypoid cancer, and atypical hyperplasia) in asymptomatic women (odds ratio for polyps with mean diameter > 18 mm, 6.9; confidence interval, 2.2-21.4). CONCLUSION: Follow-up and/or treatment of endometrial polyps incidentally diagnosed in asymptomatic postmenopausal patients could be safely restricted to few selected cases based on polyp diameter.

Reproductive experience of HIV-infected women living in Europe.

BACKGROUND: The aim of this study was to describe the experience of pregnant and non-pregnant HIV-infected women regarding fertility and childbearing, with a view to inform policies and practices to improve reproductive outcome. METHODS: A cross-sectional survey collected information on socio-demographic and basic reproductive characteristics of HIV-infected women in Europe. A total of 403 women participated; 121 were pregnant. RESULTS: The median age was 29 years and 84% (228) of women were born in Europe. Overall 68% (275 of 403) had been pregnant at some time. At the time of the survey, 59% (n = 160) of women had no HIV symptoms; severe symptoms were more frequent among non-pregnant than pregnant respondents (36% (65 of 181) versus 5% (4 of 88)). Of the women, 80% reported being in a long-standing relationship; 39% (74 of 190) reported that they became infected by their current partner and, overall, heterosexual infection was reported as the mode of acquisition in 55% (190 of 344). Maternal well-being, no previous live birth and having an uninfected partner were strongly associated with the likelihood of being pregnant. To assess the problems relating to fertility, pregnant and non-pregnant women were considered separately. Overall, 46% of pregnant women reported not using condoms to protect against infection during pregnancy. Of the 60 pregnant women who planned their pregnancies, 10 reported the need for assistance in conceiving: five monitored their ovulation period and five became pregnant through in vitro fertilization. Of 34 non-pregnant women currently trying for a baby, 15 (44%) had done so for more than 18 months. Overall 25 (27%) of 94 women who planned to become pregnant needed reproductive care. CONCLUSIONS: Our results suggest that these days knowledge of HIV infection neither influences the desire for children nor the decisions regarding pregnancy in HIV-infected women living in Europe.

Prevalence of sexually transmitted infections in HIV-1 infected pregnant women in Europe.

We investigated prevalence of sexually transmitted infections (STI) in a cohort of HIV-1-infected pregnant women and described factors associated with STI diagnosis, as a nested study within the European Collaborative Study (ECS). The ECS is a cohort study in which HIV-infected pregnant women are enrolled and their children followed from birth, according to standard clinical and laboratory protocols. Information on STIs diagnosed during pregnancy was collected retrospectively from the antenatal records of women enrolling between January 1999 and October 2005; other variables were obtained from the ECS prospective database. A total of 1,050 women were included: 530 in Western Europe and 520 in Ukraine. Syphilis was the most common bacterial STI (2% prevalence, 95% CI 1.2-3.0). Prevalence of HPV-related genital lesions was 8.6% (95%CI 6.9-10.4) and prevalence of Trichomonas vaginalis was 12.1% (95%CI 10.2-14.2). Women in Ukraine (AOR 10.7, 95%CI 3.7-30.5), single women (AOR 3.9, 95%CI 1.2-12.7), sexual partners of injecting drug users (AOR 3.8, 95%CI 1.4-10.4) and women with CD4 counts <200 cells/mm(3) (AOR 5.4, 95%CI 1.0-28.1) were at increased risk of diagnosis with Chlamydia trachomatis, syphilis or Trichomonas vaginalis. African origin (AOR 1.9, 95%CI 1.1-3.3) and CD4 count <200 cells/mm(3) (AOR 3.4, 95%CI 1.5-7.8) were associated with HSV-2 and/or HPV-related genital lesions. Antenatal screening should be considered an effective tool for diagnosis, treatment and prevention of further transmission of STIs. HIV-infected women should receive adequate screening for STIs during pregnancy together with appropriate counseling and follow-up for treatment and prevention.

Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA.

BACKGROUND: Rates of mother-to-child transmission of HIV-1 (MTCT) have historically been lower in European than in American cohort studies, possibly due to differences in population characteristics. The Pediatric AIDS Clinical Trials Group Protocol (PACTG) 316 trial evaluated the effectiveness of the addition of intrapartum/neonatal nevirapine in reducing MTCT in women already receiving antiretroviral prophylaxis. Participation of large numbers of pregnant HIV-infected women from the US and Western Europe enrolling in the same clinical trial provided the opportunity to identify and explore differences in their characteristics and in the use of non-study interventions to reduce MTCT. METHODS: In this secondary analysis, 1350 women were categorized according to enrollment in centres in the USA (n = 978) or in Europe (n = 372). Factors associated with receipt of highly active antiretroviral therapy and with elective caesarean delivery were identified with logistic regression. RESULTS: In Europe, women enrolled were more likely to be white and those of black race were mainly born in Sub-Saharan Africa. Women in the US were younger and more likely to have previous pregnancies and miscarriages and a history of sexually transmitted infections. More than 90% of women did not report symptoms of their HIV infection; however, more women from the US had symptoms (8%), compared to women from Europe (4%). Women in the US were less likely to have HIV RNA levels <400 copies/ml at delivery than women enrolling in Europe, and more likely to receive highly active antiretroviral therapy, and to start therapy earlier in pregnancy. The elective caesarean delivery rate in Europe was 61%, significantly higher than that in the US (22%). Overall, 1.48% of infants were infected and there was no significant difference in the rate of transmission between Europe and the US despite the different approaches to treatment and delivery. CONCLUSION: These findings confirm that there are important historical differences between the HIV-infected pregnant populations in Western Europe and the USA, both in terms of the characteristics of the women and their obstetric and therapeutic management. Although highly active antiretroviral therapy predominates in pregnancy in both settings now, population differences are likely to remain. TRIAL REGISTRATION: NCT00000869.

Antiretroviral therapy-associated modulation of Th1 and Th2 immune responses in HIV-infected pregnant women.

A successful pregnancy is characterised by an increase in Th2 cytokines and suppression of Th1 cytokine production. A Th1 to Th2 cytokine shift is also observed in the disease progression of HIV infection. Highly active antiretroviral therapy (HAART) suppresses HIV viremia, increases CD4+ cell counts and counteracts the Th1 to Th2 shift. We hypothesised that the increased risk of premature delivery reported in HIV-infected, HAART-treated pregnant women is mediated through changes in the cytokine environment in pregnancy. Here, we present results relating to levels of interleukin (IL)-2 (Th1) and IL-10 (Th2) in peripheral blood mononuclear cells (PBMCs) measured three times during pregnancy in 49 HIV-infected women. Slope values representing the trend of repeated cytokine (IL-2-PHA, IL-2-Env, IL-10-PHA and IL-10-Env) measurements within women during pregnancy were estimated and median values compared by prematurity and HAART use. Multiple regression adjusted for HAART and cytokine slope clarified the additional and independent effect of HAART on prematurity risk. Results showed favourable immunomodulation induced by HAART with increased IL-2 and decreased IL-10. HAART use and IL-10-Env slopes were not significantly associated with prematurity risk, but each unit increase in IL-2-PHA slope was associated with an 8% increased risk of premature delivery (AOR, 1.08; 95% CI, 1.0-1.17; p=0.005). HAART use in pregnancy provides significant benefits in delaying HIV disease progression and reducing the risk of mother-to-child-transmission, but may be counterproductive in terms of successful pregnancy outcome.

HIV and pregnancy: is the outlook for mother and baby transformed?

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.

HIV and reproduction.

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.

Higher rates of post-partum complications in HIV-infected than in uninfected women irrespective of mode of delivery.

OBJECTIVE: To inform the debate on the use of elective caesarean section (CS) delivery in HIV-infected women, we investigated the occurrence of clinical events in the immediate post-partum period in women delivering in 13 European centres. DESIGN: Two separate matched case-control studies (vaginal and elective CS deliveries) among infected women (cases) and uninfected controls delivering between 1992 and 2002. METHODS: The prevalence of minor and major post-partum complications was assessed overall for infected and uninfected women; within mode of delivery group (vaginal/CS) the complication rates of infected cases were compared with uninfected controls in a matched analysis. RESULTS: Overall complication rates were 29.2% (119 of 408) for HIV-infected women, 19.4% (79 of 408) for uninfected women, 42.7% (135 of 316) for CS deliveries and 12.6% (63 of 500) for vaginal deliveries. There were no major complications in women delivering vaginally; but, compared with controls, HIV-infected cases were at increased risk of puerperal fever [odds ratio (OR), 4.5; 95% confidence interval (CI), 1.55-13.07), especially after medio-lateral episiotomy. In the CS group, there were six major complications (five among cases, one control) (OR, 5.1; 95% CI, 0.58-45) and cases had an increased risk of minor complications (OR, 1.51; 95% CI, 1.22-2.41) compared with controls, mainly anaemia not requiring blood transfusion. CONCLUSION: HIV-infected pregnant women are at increased risk of post-partum complications regardless of mode of delivery, but modification of clinical practice, particularly use of prophylactic antibiotics, would reduce this risk. Infected women should be informed about risks of vertical transmission and post-partum complications, and be involved in mode of delivery decisions.

European participation in an international perinatal trial.

OBJECTIVES: To identify factors affecting recruitment into a randomised trial involving HIV infected pregnant women. To compare the population enrolled in a Phase III trial to that enrolled during the same period in a parallel longitudinal cohort, and to assess the generalisability of the trial results. MATERIAL AND METHODS: The PACTG 316 trial was initiated in the USA and subsequently extended to Europe. Based on their involvement in an ongoing European cohort study, clinicians in 27 antenatal HIV reference centres in Italy, Spain, Sweden, UK, Belgium, Germany, Switzerland, Netherlands and Denmark were asked to participate. In centres with local, national and American approval, eligible women attending antenatal clinics were offered the chance to take part in the trial, which aimed to evaluate the additional use of nevirapine during labour and neonatally to reduce HIV mother-to-child transmission (MTCT). HIV-infected women who did not enrol in the trial were enrolled in the European Collaborative Study (ECS). Reasons for non-randomisation were recorded. Clinical and laboratory information on mother-child pairs were collected according to a standard protocol. RESULTS: Between February 1999 and June 2000, 247 women were enrolled in the ECS cohort and 118 were randomised in the 316 trial. Reasons for non-randomisation included the presence of the placebo arm, randomisation procedures and delays in obtaining approval from the various regulatory bodies. Women in the trial were younger, and their HIV disease was less advanced than those included in the ECS. The MTCT rate in the ECS was higher than in the trial. CONCLUSIONS: Differences between women who participated in the trial and those who did not had an effect on the absolute vertical transmission rate, but not on the relative effectiveness of the intervention assessed within the trial. Extrapolation of the trial MTCT rates to the general HIV infected population may be inappropriate.