Assessment of high-risk human papillomavirus infections and associated cervical dysplasia in HIV-positive pregnant women in Germany: a prospective cross-sectional two-centre study.

PURPOSE: Invasive cervical cancer (ICC) is associated in nearly 100% with persistent high-risk Human Papillomavirus (HR-HPV) infection. ICC is still one of the leading causes for cancer mortality in women worldwide. The immunosuppressive influence of Human Immunodeficiency Virus (HIV) and the immunocompromised period of pregnancy due to tolerance induction against the hemiallogeneic fetus, are generally risk factors for acquisition and persistence of HR-HPV infections and their progression to precancerous lesions and HPV-associated carcinoma. METHODS: Overall, 81 pregnant women living with HIV (WLWH) were included. A medical history questionnaire was used to record clinical and HIV data. Participants received cervicovaginal cytological smear, colposcopy and HPV testing. HPV test was performed using BSGP5+/6+ PCR with Luminex read-out. The HR-HPV genotypes 16, 18, 31, 33, 45, 52, 58 were additionally grouped together as high-high-risk HPV (HHR-HPV) for the purpose of risk-adapted analysis. RESULTS: HR-HPV prevalence was 45.7%. Multiple HPV infections were detected in 27.2% of participants, of whom all had at least one HR-HPV genotype included. HR-HPV16 and HR-HPV52 were the most prevalent genotypes and found when high squamous intraepithelial lesion (HSIL) was detected by cytology. HIV viral load of ≥ 50 copies/ml was associated with higher prevalence of HR-HPV infections. Whereas, CD4 T cells < 350/µl showed association with occurrence of multiple HPV infections. Time since HIV diagnosis seemed to impact HPV prevalence. CONCLUSION: Pregnant WLWH require particularly attentive and extended HPV-, colposcopical- and cytological screening, whereby clinical and HIV-related risk factors should be taken into account.

Association of peripartum management and high maternal blood loss at cesarean delivery for placenta accreta spectrum (PAS): A multinational database study.

INTRODUCTION: Placenta accreta spectrum (PAS) carries a high burden of adverse maternal outcomes, especially significant blood loss, which can be life-threatening. Different management strategies have been proposed but the association of clinical risk factors and surgical management options during cesarean delivery with high blood loss is not clear. MATERIAL AND METHODS: In this international multicenter study, 338 women with PAS undergoing cesarean delivery were included. Fourteen European and one non-European center (USA) provided cases treated retrospectively between 2008 and 2014 and prospectively from 2014 to 2019. Peripartum blood loss was estimated visually and/or by weighing and measuring of volume. Participants were grouped based on blood loss above or below the 75th percentile (>3500 ml) and the 90th percentile (>5500 ml). RESULTS: Placenta percreta was found in 58% of cases. Median blood loss was 2000 ml (range: 150-20 000 ml). Unplanned hysterectomy was associated with an increased risk of blood loss >3500 ml when compared with planned hysterectomy (adjusted OR [aOR] 3.7 [1.5-9.4], p = 0.01). Focal resection was associated with blood loss comparable to that of planned hysterectomy (crude OR 0.7 [0.2-2.1], p = 0.49). Blood loss >3500 ml was less common in patients undergoing successful conservative management (placenta left in situ, aOR 0.1 [0.0-0.6], p = 0.02) but was more common in patients who required delayed hysterectomy (aOR 6.5 [1.7-24.4], p = 0.001). Arterial occlusion methods (uterine or iliac artery ligation, embolization or intravascular balloons), application of uterotonic medication or tranexamic acid showed no significant effect on blood loss >3500 ml. Patients delivered by surgeons without experience in PAS were more likely to experience blood loss >3500 ml (aOR 3.0 [1.4-6.4], p = 0.01). CONCLUSIONS: In pregnant women with PAS, the likelihood of blood loss >3500 ml was reduced in planned vs unplanned cesarean delivery, and when the surgery was performed by a specialist experienced in the management of PAS. This reinforces the necessity of delivery by an expert team. Conservative management was also associated with less blood loss, but only if successful. Therefore, careful patient selection is of great importance. Our study showed no consistent benefit of other adjunct measures such as arterial occlusion techniques, uterotonics or tranexamic acid.

Testing for HIV during pregnancy: 5 years after changing German pregnancy guidelines.

OBJECTIVE: A known HIV status is the most important step in preventing mother-to-child transmission of HIV and screening for HIV is recommended by German prenatal guidelines. In our study, we wanted to ascertain the prevalence of HIV-testing in a pregnant inner-city cohort. METHODS: Prenatal records of 279 women were prospectively studied, and the testing confirmed with the prenatal care providers. RESULTS: 82.4 % of the patients had been tested for HIV during pregnancy. The test was refused by 4.0 % of the women. Contrary to current guidelines, in more than half of the cases documentation of the test or the result was found in the women's prenatal care papers. CONCLUSIONS: Even though a large majority of pregnant women are screened for HIV, the rates of testing need to be increased. Education of patients and providers as well as changing to the "opt-out" approach used in other countries may prevent unnecessary mother-to-child transmission of HIV.

Pyrosequencing allows the detection of emergent ganciclovir resistance mutations after HCMV infection.

Prenatally acquired human cytomegalovirus (HCMV) infection is the most frequent viral infection of newborns in developed countries. Virostatic therapy is accompanied by side effects and stepwise emergence of resistant virus variants. Different genotypic approaches show limited sensitivity in detecting on-growing minor resistant virus populations. Here, we demonstrate the superiority of pyrosequencing for the monitoring of mutant emergence. In a preterm baby born after 28 weeks of gestation and suffering from disseminated congenital HCMV infection, long-term control could not be achieved under ganciclovir/valganciclovir therapy and the infant died on the 113th day of life. Resistance-associated mutations in the HCMV UL97 gene were not detected by conventional DNA sequencing but postmortem pyrosequencing. Four different CMV variants carrying resistance-associated mutations each representing 11-17% of the total CMV population were found.

Consultations of HIV-infected women who wish to become pregnant.

PURPOSE: The aim of this study was to determine the impact and outcome of consultations of HIV-infected women if a pregnancy is planned. METHODS: This study was performed retrospectively based on patient's records of HIV-infected women with the desire to become pregnant between 2000 and 2008. Relevant data regarding HIV infection, obstetrical history, diagnostic procedures and medical interventions related to conception, as well as pregnancy outcomes, were evaluated. RESULTS: A total of 57 HIV-infected women (and their partner) were included; 38% (n = 22) of the couples showed a reduced fertility and 24 women (42%) became pregnant once or several times during the study period. Conception resulted from unprotected intercourse (n = 11), self-insemination (n = 10), assisted insemination (n = 2) or in vitro fertilization (n = 1). The outcome of all pregnancies was: 26 live births, 1 intrauterine fetal demise (38 weeks), 1 miscarriage, 1 cervical pregnancy and 1 legal abortion. No horizontal transmission occurred in serodiscordant couples. Seven (12%) women were lost to follow-up, 12 couples (21%) abandoned the attempt to get pregnant, and 14 couples (25%) reported an ongoing wish for a child. CONCLUSIONS: In this group of HIV-affected couples, we showed a high rate of reduced fertility. In our study, consultations and interventions led to a pregnancy rate of 42% without horizontal transmission of HIV.

Protease inhibitor-based antiretroviral prophylaxis during pregnancy and the development of drug resistance.

BACKGROUND: The aim of this study was to determine the development of drug resistance among pregnant women receiving a protease inhibitor-based antiretroviral prophylaxis for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). METHODS: HIV-infected pregnant women without maternal indication for antiretroviral therapy were enrolled prospectively. Genotypic resistance testing was performed prior to initiation of antiretroviral prophylaxis and was repeated 4-8 weeks after cessation of antiretroviral therapy at the time of delivery. RESULTS: Forty pregnant women with HIV infection (Centers for Disease Control and Prevention stage A1 or A2) were included. All women received an antiretroviral regimen including either fixed-dose lopinavir/ritonavir (n = 33) or ritonavir-boosted saquinavir (n = 7) and a backbone consisting of 2 nucleoside reverse-transcriptase inhibitors. The mean duration of antiretroviral treatment was 8.4 weeks (range, 5-22 weeks). Primary resistance mutations were found in 2 patients (nonnucleoside reverse-transcriptase inhibitor resistance, K103N; protease inhibitor resistance, G48V). Postpartum genotypic resistance revealed no new relevant resistance mutations. CONCLUSIONS: In our study no clinically significant resistance mutations developed in pregnant women receiving a short-term protease inhibitor-based antiretroviral regimen for prophylaxis of mother-to-child transmission of HIV. Future therapeutic options are therefore preserved.

Uterine packing with chitosan-covered gauze compared to balloon tamponade for managing postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage (PPH) is a major cause of maternal death worldwide. Management of PPH includes the administration of uterotonics, and intrauterine packing techniques. OBJECTIVE: In this study the effectiveness and safety of chitosan covered gauze versus a balloon tamponade for managing severe PPH should be assessed. STUDY DESIGN: This retrospective cohort study was conducted at the Department of Obstetrics, Charité, university hospital Berlin, between October 2016 and June 2018. Women with PPH were treated according to management guidelines. When bleeding persisted, we applied additional uterine packing with either chitosan covered gauze or a balloon tamponade. The primary outcome was uterine bleeding termination without additional surgical interventions. Secondary outcomes included the amount of blood loss, the amount of blood transfusions and maternal complications. RESULTS: Among the 78 patients included in this study, 47 (60.3%) received chitosan covered gauze tamponade and 31 (39.7%) received a balloon tamponade. The major reason for PPH was atonic bleeding, no statistically significant group differences were observed. With respect to the outcomes monitored, the groups were not significantly different in postpartum vital signs, hemoglobin levels, blood loss, admission to intensive care unit, or inflammation parameters. However, three patients in balloon tamponade group required a hysterectomy. No hysterectomy was required in gauze group. CONCLUSION: Chitosan covered gauze is an excellent option for treating PPH, it appeared to be at least equivalent to the balloon tamponade, in our experience particularly suitable for atony or placenta bed bleeding after spontaneous delivery or during cesarean sections, in cases of lower uterine segment atony, placenta previa bed bleeding, and/or coagulopathy.

Progressive multicystic encephalopathy: is there more than hypoxia-ischemia?

Progressive multicystic encephalopathy following prenatal or perinatal hypoxia-ischemia is a well-described phenomenon in the literature. The authors report on a term infant with a devastating encephalopathy and severe neuronal dysfunction immediately after delivery without a known antecedent of prenatal or perinatal hypoxia or distress. Clinical and paraclinical findings in the patient are compared with those described in the literature. The authors focus on the specific results guiding to the final diagnosis of progressive multicystic encephalopathy and the timing of morphologic changes. As in this case, if the criteria of an acute hypoxic event sufficient to cause neonatal encephalopathy are not met, then factors other than hypoxia-ischemia may be leading to progressive multicystic encephalopathy.

Hematologic effects of maternal antiretroviral therapy and transmission prophylaxis in HIV-1-exposed uninfected newborn infants.

OBJECTIVE: A prospective observational study to investigate hematologic alterations during the first 3 months of life in HIV-exposed uninfected infants subjected to antiretroviral medication before and after birth. METHODS: Two hundred twenty-one consecutive uninfected infants born to HIV-positive mothers on antiretroviral medication during pregnancy were included. Perinatal transmission prophylaxis comprised zidovudine (ZDV) administered intravenously intrapartum and 10 days after birth. Blood counts and differentials were determined at birth and at 2, 4, 6, and 12 weeks of age, and hematologic toxicity was graded according to pediatric toxicity scales. Data were analyzed according to the kind of prenatal medication (ZDV alone or with another nucleoside reverse transcriptase inhibitor [NRTI] vs. highly active antiretroviral therapy [HAART]). RESULTS: Median hemoglobin was significantly lower in HAART-exposed newborns from birth (P = 0.004) until day 28. During follow-up, 119 (53.8%) infants had anemia grade 2 or higher on at least 1 occasion; 16 (7.2%) received red blood cell transfusion at 23 (range: 1-56) days of age. Neutropenia grade 2 or higher occurred in 106 (48.0%) infants at least once; 8 infants had staphylococcal infections, and 2 infections were severe. After adjustment for possible confounders (prematurity, birth weight, ethnicity, gender, duration of maternal antiretroviral therapy, maternal Centers for Disease Control and Prevention stage, and maternal illicit drug use), HAART exposure was the only independent risk factor for anemia (odds ratio [OR] = 2.22, 95% confidence interval [CI]: 1.06 to 4.64; P = 0.034) and neutropenia (OR = 2.15, CI: 1.02 to 4.55; P = 0.045). CONCLUSIONS: Antiretroviral transmission prophylaxis is associated with significant anemia and neutropenia in HIV-uninfected infants during the first 3 months of life. Anemia was more profound in HAART-exposed infants.