Giulia Masuelli

Vaginal and endocervical microorganisms in symptomatic and asymptomatic non-pregnant females: risk factors and rates of occurrence

Physiological or non-physiological factors may affect the vaginal flora. The occurrence of genital microorganisms in non-pregnant females of all ages was studied, as were the risk factors associated with each microorganism. A retrospective analysis of vaginal and endocervical cultures and wet smears from 27,172 non-pregnant women, between 1996 to 2005, was performed taking into consideration clinical and socio-demographic characteristics. No microorganisms were observed in 55.7% of the individuals studied and 44.3% had positive cultures. There was no microbiological aetiology in 49% of women with genital symptoms. Poor hygiene, chemical irritants, sexual behaviour, vaginal blood, birth control type, and/or the lack of an oestrogen effect may have caused the symptoms. The highest occurrence of Gram-negative bacteria (p<0.01), mainly Escherichia coli, was observed in prepubescent girls. The highest occurrence of Candida species (p<0.01) was in women of childbearing age, and of Gram-positive bacteria (p<0.01) in menopausal women. Adolescents, particularly asymptomatic girls, carried more frequently Ureaplasma urealyticum and Chlamydia trachomatis (p<0.01). Hormonal contraception and consistent condom use was protective against bacterial vaginosis and U. urealyticum colonization. Users of intrauterine devices had an increased risk of bacterial vaginosis or of contracting U. urealyticum, Mycoplasma hominis and Candida species. Genital complaints were an independent indicator of Candida species, Gram-negative and Gram-positive bacteria, Trichomonas vaginalis and bacterial vaginosis.Chlamydia trachomatis infections were often asymptomatic. It is concluded that the hormonal milieu and non-physiological factors are major determinants of the vaginal flora. If diagnosis of genital infections is based on symptoms alone and not on culture results, it may be erroneous. Sexual abuse should be investigated when a child presents with a sexually transmitted disease.

Prevention of Primary Cytomegalovirus Infection in Pregnancy.

Background Cytomegalovirus (CMV) is the leading infectious agent causing congenital sensorineural hearing loss and psychomotor retardation. CMV vaccine is currently unavailable and treatment options in pregnancy are limited. Susceptible pregnant women caring for children are at high risk for primary infection. CMV educational and hygienic measures have the potential to prevent primary maternal infection. Methods A mixed interventional and observational controlled study was conducted to investigate the effectiveness of hygiene information among pregnant women at risk for primary CMV infection for personal/occupational reasons. In the intervention arm, CMV-seronegative women, identified at the time of maternal serum screening for fetal aneuploidy at 11–12 weeks of gestation, were given hygiene information and prospectively tested for CMV until delivery. The comparison arm consisted of women enrolled at delivery who were neither tested for nor informed about CMV during pregnancy, and who had a serum sample stored at the screening for fetal aneuploidy. By design, groups were homogeneous for age, parity, education, and exposure to at least one risk factor. The primary outcome was CMV seroconversion. Acceptance of hygiene recommendations was a secondary objective and was measured by a self-report. Findings Four out of 331 (1.2%) women seroconverted in the intervention group compared to 24/315 (7.6%) in the comparison group (delta = 6.4%; 95% CI 3.2–9.6; P < 0.001). There were 3 newborns with congenital infection in the intervention group and 8 in the comparison group (1 with cerebral ultrasound abnormalities at birth). Ninety-three percent of women felt hygiene recommendations were worth suggesting to all pregnant women at risk for infection. Interpretation This controlled study provides evidence that an intervention based on the identification and hygiene counseling of CMV-seronegative pregnant women significantly prevents maternal infection. While waiting for CMV vaccine to become available, the intervention described may represent a responsible and acceptable primary prevention strategy to reduce congenital CMV.

Atazanavir and lopinavir profile in pregnant women with HIV: tolerability, activity and pregnancy outcomes in an observational national study

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.

Pregnancy Outcomes in HIV-Infected Women of Advanced Maternal Age

Abstract Background: There is limited information on pregnancy outcomes in women with HIV who are of a more advanced maternal age.Methods: Data from a national observational study in Italy were used to evaluate the risk of nonelective cesarean section, preterm delivery, low birthweight, major birth defects, and small gestational age-adjusted birthweight according to maternal age (<35 and ≥35 years, respectively).Results: Among 1,375 pregnancies with live births, 82.4% of deliveries were elective cesarean sections, 15.8% were nonelective cesarean sections, and 1.8% were vaginal deliveries. Rates of nonelective cesarean section were similar among mothers ≥35 and <35 years (odds ratio [OR], 1.22; 95% CI, 0.90–1.65;P = .19). Preterm delivery and low birthweight were significantly more common among women ≥35 years in univariate but not in multivariate analyses. Newborns from women ≥35 and <35 years showed no differences inZ scores of birthweight, with a similar occurrence of birthweight <10th percentile (12.1% vs 12.0%; OR, 1.02; 95% CI, 0.71–1.46;P = .93). The overall rate of birth defects was 3.4% (95% CI, 2.4–4.4), with no differences by maternal age (≥35 years, 3.5%; <35 years, 3.3%; OR, 1.05; 95% CI, 0.56–1.98;P = .88).Discussion: In this study of pregnant women with HIV, older women were at higher risk of some adverse pregnancy outcomes, such as preterm delivery and low birthweight. The association, however, did not persist in multivariable analyses, suggesting a role of some predisposing factors associated with older age.

Maternal risk factors for abnormal vaginal flora during pregnancy.

To determine the prevalence of abnormal vaginal flora during pregnancy and associated maternal risk factors.

Glucose Plasma Levels and Pregnancy Outcomes in Women with HIV

Abstract Background: There is limited information on the relation between glucose levels in pregnancy and adverse perinatal outcomes in HIV-infected pregnant women. Objective: To evaluate the potential impact of fasting glucose levels on pregnancy outcomes in a large sample of pregnant women with HIV from a national study, adjusting for potential confounders. Methods: Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. The main outcomes evaluated in univariate and multivariable analyses were birthweight for gestational age >90th percentile (large for gestational age [LGA]), nonelective cesarean delivery, and preterm delivery. Glucose measurements were considered both as continuous and as categorical variables, following the HAPO study definition. Results: Overall, 1,032 cases were eligible for the analysis. In multivariable analyses, a birthweight >90th percentile was associated with increasing fasting plasma glucose levels (adjusted odds ratio [AOR] per unitary (mg/dL) increase, 1.04; 95% CI, 1.01–1.06; P = .005), a higher body mass index, and parity of 1 or higher. A lower risk of LGA was associated with smoking and African ethnicity. A higher fasting plasma glucose category was significantly associated with LGA occurrence, and AORs for the glucose categories of 90–94 mg/ dL and 95–99 mg/dL were 3.34 (95% CI, 1.09–10.22) and 6.26 (95% CI, 1.82–21.58), respectively. Fasting plasma glucose showed no association with nonelective cesar-ean section [OR per unitary increase, 1.00; 95% CI, 0.98–1.02] or preterm delivery [OR per unitary increase, 1.00; 95% CI, 0.99–1.02]. Conclusions: In pregnant women with HIV, glucose values below the threshold usually defining hyperglycemia are associated with an increased risk of delivering LGA infants. Other conditions may independently contribute to adverse perinatal outcomes in women with HIV and should be considered to identify pregnancies at risk.

Rate, correlates and outcomes of repeat pregnancy in HIV-infected women

The aim of the study was to assess the rate, determinants, and outcomes of repeat pregnancies in women with HIV infection.

Brief Report: Consequences of Presentation With Advanced HIV Disease in Pregnancy: Data From a National Study in Italy.

Abstract:Among 469 women with a diagnosis of HIV in pregnancy, 74 (15.8%) presented with less than 200 CD4 cells per cubic millimeter. The only variable significantly associated with this occurrence was African origin (odds ratio: 2.22, 95% confidence intervals: 1.32 to 3.75, P = 0.003). Four women with low CD4 (5.6%), compared with none with higher CD4 counts, had severe AIDS-defining conditions (P < 0.001) during pregnancy or soon after delivery, and one transmitted HIV to the newborn. Early preterm delivery (<32 weeks) was significantly more frequent with low CD4 (6.2% vs. 1.4%, P = 0.015). An earlier access to HIV testing, particularly among immigrants of African origin, can prevent severe HIV-related morbidity.

Body Mass Index and Weight Gain in Pregnant Women With HIV: A National Study in Italy

Despite the growing number of human immunodeficiency virus (HIV)–infected women who are pregnant or planning a pregnancy, there is limited information on body weight status and weight gain in pregnancy in this population. The issue is relevant, because inadequate or excessive body mass index (BMI) and weight gain in pregnancy are risk factors for adverse pregnancy outcomes in the general population [1, 2], and may increase the risk of some events commonly observed among pregnant women with HIV, such as preterm delivery or glucose

Evolving treatment implementation among HIV- infected pregnant women and their partners: Results from a national surveillance study in Italy, 2001-2015

Background The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre–exposure chemoprophylaxis (PrEP), and treatment of HIV–negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. Methods The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001–2005, 2006–2010, 2011–2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. Results The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV–negative, 28.6% HIV–positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001–2005 to 81.3% in 2011–2015, P < 0.001), and in the proportion of HIV–positive partners on antiretroviral treatment (from 73.3% in 2001–2005 to 95.8% in 2011–2015, P = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV–negative partners. Conclusions The results suggest good implementation of antiretroviral treatment among HIV–positive women and their HIV–positive partners, but no implementation, even in recent years, of Pre–Exposure Prophylaxis (PrEP) among uninfected male partners. Further studies should assess the determinants of this occurrence and clarify the attitudes and the potential barriers to PrEP use.