Prenatal ultrasound screening and pregnancy outcomes in HIV-positive women in Germany: results from a retrospective single-center study at the Charité-Universitätsmedizin Berlin.

OBJECTIVES: The aim of this study was to investigate the rate of Mother-to-child-transmission (MTCT) in women living with HIV (WLWH) in a tertiary care institution. Furthermore, we aimed to assess prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection." METHODS: In this single-center study, retrospective data related to pregnancy and childbirth were collected from 420 WLWH. All data were evaluated descriptively. RESULTS: From January 2014 to December 2020, a total number of 420 pregnant WLWH delivered 428 newborns. 415 (98.8%) were receiving antiretroviral therapy (ART) and 88.8% had a viral load of < 50 cop/ml prior delivery. 46 (11%) of the newborns were born prematurely. Low birth weight < 2500 g occurred in 38 (9.1%) of the children. 219 (52.1%) caesarean sections (CS) were performed. The most frequent indication for an elective CS was a previous CS (70.2%). 8 severe malformations were detected using first and second trimester ultrasound. In one child, MTCT was detected postpartum, resulting in an HIV transmission rate of 0.2% in the presented cohort. CONCLUSIONS: The low rate of vertical HIV-transmission in our cohort of 0.2% is the result of interdisciplinary prenatal care and high experience of healthcare providers in treatment of WLWH. Despite high ART coverage and adherence, good maternal immune system and very low vertical HIV transmission rate, maternal HIV infection remains a challenge in obstetric care. First and second ultrasound screening should be a part of prenatal care for HIV-infected women and should also be offered to HIV-negative women. A reduction of the rate of unnecessary elective caesarean deliveries in WLWH is necessary to reduce complications in subsequent pregnancies.

Genotype-specific high-risk human papillomavirus infections and risk factors for cervical dysplasia in women with human immunodeficiency virus in Germany: results from a single-center cross-sectional study.

OBJECTIVE: Women living with HIV have an increased risk of human papillomavirus (HPV) infection and cervical cancer. Little is known about genotype-specific HPV prevalence, the impact of antiretroviral therapy, immunological status, and additional risk factors in women living with HIV in Germany. The goal of this study was to characterize the risk profile for cervical dysplasia in these women. METHODS: Patients with HIV infection presenting at Charité-Universitätsmedizin Berlin from October 2017 to September 2020 were included and underwent gynecological examination, colposcopy, cervical cytology and HPV genotype testing. HPV genotypes were stratified by carcinogenicity. Atypical squamous cells of undetermined significance or higher were considered abnormal cytology. Data were analyzed by SPSS software (version 26, 2019). A two-tailed p-value ≤0.05 was considered statistically significant. RESULTS: A total of 84 women were evaluated. The majority (95.2%) received antiretroviral therapy. Median CD4 cell count was 564 cells/µl (range 20-1969). 95.2% were previously screened for cervical cancer. High-risk HPV prevalence was 44%. High-high-risk HPV subtypes (16, 18, 31, 33, 45, 52, 58) were significantly associated with abnormal cytology (p<0.001). HPV16 was the most common genotype (23%), was significantly associated with abnormal cytology (p=0.002) and was the main risk factor for abnormal cytology (OR 8.55, 95% CI 2.15 to 34.13, p=0.002), followed by age <35 years (OR 4.96, 95% CI 1.23 to 19.61, p=0.033) and cigarette smoking (OR 3.944, 95% CI 0.98 to 15.88, p=0.053). CONCLUSIONS: Antiretroviral therapy and adherence to cervical cancer screening was high. High-high-risk HPV, especially HPV16, coincided with high incidence of cytological abnormalities. Women living with HIV in Germany have adequate immune status and are often pre-screened for cervical cancer, and therefore have a different risk profile for cervical dysplasia than in low-income or medium-income countries. Adapted screening programs should be defined.

The Effect of Pregnancy on the Pharmacokinetics of Total and Unbound Dolutegravir and Its Main Metabolite in Women Living With Human Immunodeficiency Virus.

BACKGROUND: Pharmacokinetic and efficacy data on dolutegravir in pregnant women living with human immunodeficiency virus (HIV) are still limited but needed to support its use as one of the preferred antiretroviral agents. METHODS: Within the multicenter Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) study, pregnant women living with HIV and using dolutegravir once daily (50 mg, with food) underwent 24-hour pharmacokinetic profiling in their third trimester and postpartum. Dolutegravir exposure in the third trimester was considered adequate if geometric mean unbound, pharmacologically active, minimal plasma concentrations (Cmin, unbound) and ≥90% of individual Cmin, unbound levels were >0.85 µg/L, the proposed 90% inhibitory concentration for unbound dolutegravir. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) for comparison of total and unbound pharmacokinetic parameters in the third trimester and postpartum were calculated, including the metabolic ratio for dolutegravir-glucuronide. Safety and virological data were collected. RESULTS: Seventeen women (76% black) were enrolled (25 evaluable pharmacokinetic profiles; 15 in the third trimester, 10 in postpartum). In the third trimester, geometric mean (coefficient of variation, %) Cmin, unbound was 2.87 (87) µg/L and 93% of individual Cmin, unbound levels were >0.85 µg/L. The GMR (90% CI) in the third trimester vs postpartum was 0.86 (.68-1.10) for area under the curve (AUC0-24h), and for Cmax, 0.93 (.77-1.13). GMR (90% CI) for the trough concentrations was 0.71 (.49-1.02), based on total dolutegravir concentrations. Four serious adverse events were reported, unlikely related to dolutegravir. The HIV polymerase chain reaction test was negative in 14/17 infants (result unknown for 3 infants). CONCLUSIONS: Pharmacokinetic changes for dolutegravir in late pregnancy are not clinically relevant and support the use of dolutegravir 50 mg once daily with food in pregnancy. CLINICAL TRIALS REGISTRATION: NCT00825929.

Fetal growth restriction in a cohort of migrants in Germany.

BACKGROUND: Migrant women may have an increased risk of adverse birth outcomes. This study analyses the occurrence of low birth weight, preterm birth and intrauterine growth restriction / fetal growth restriction (IUGR/FGR) in pregnant migrants. METHOD: Cross-sectional study of 82 mother-child pairs of pregnant migrants attending medical care in Germany. RESULTS: The Median age was 27 years, 49% of patients were of oriental-asian ethnicity and median year of migration was 2015. At least one previous pregnancy was reported in 76% of patients, in 40% the delivery mode was caesarian section. Median gestational age was 39.7 weeks. Preterm birth occurred in 6.1% of pregnancies. Median gestational age for preterm birth was 32.3 weeks. Low birth weight (< 2500 g) occurred in 6.1%. Birth weights below the 10th percentile of birth weight for gestational age were observed in 8.5% of the total cohort. CONCLUSIONS: Compared to German data no increased occurrence of low birth weight, preterm birth or IUGR/FGR was found. We note that the rate of caesarian section births was higher than in the general population for reasons yet to be identified. The authors propose stratification according to migration status for the national documentation of birth outcomes in Germany.

Safety of tenofovir during pregnancy: early growth outcomes and hematologic side effects in HIV-exposed uninfected infants.

Intrauterine exposure to zidovudine-based combination antiretroviral therapy (cART) can cause severe anemia within the first weeks of life. Tenofovir disoproxil fumarate (TDF)-based regimens may have less hematologic side effects but may affect growth parameters. This study aimed to assess the safety of TDF for prevention of mother-to-child transmission (PMTCT) in HIV-exposed uninfected infants regarding early growth outcomes and hematologic side effects. Our retrospective observational cohort study included children born (n = 232) to HIV-infected mothers (n = 228) on cART. Blood counts were compared at birth, 4-6 weeks, and 3, 12 and 18 months of age. Growth parameters were measured at birth and 12 and 18 months of age. Data were analyzed according to treatment group (TDF and non-TDF cART regimes). The median hemoglobin (Hgb) was significantly lower in the non-TDF-based group at birth (15.4 g/dl vs. 16.9 g/dl; **p = 0.002) and at 4-6 weeks of age (9.9 g/dl vs. 10.4 g/dl; **p = 0.004). The mean corpuscular volume was higher in the non-TDF-based group (109 fl vs. 105 fl; ***p < 0.001) as well at 4-6 weeks (102 fl vs. 95 fl; ***p < 0.001). In the TDF-based group, a higher proportion of neutropenia (grade 2 and higher) compared to the non-TDF-group (21.4% vs. 11%; *p = 0.015) was observed at three months of age. This effect was transient. There was no difference in growth.Conclusions: TDF appears to have no major side effects in our cohort. Transient anemia was observed more commonly with non-TDF regimens. However, our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age.What is Known:• TDF is suspected to affect the growth of HIV-exposed uninfected infants.• Non-TDF-based cART regimes for prevention of mother-to-child transmission of HIV often result in transient anemia in the infant.What is New:• TDF appears to have no major side effects regarding the growth of HIV-exposed uninfected infants.• Our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age in these infants.

Screening for Third-Generation Cephalosporin-Resistant Bacteria Reduces the Incidence on Late-Onset Sepsis and Antibiotic use in Neonates.

BACKGROUND: The extensive use of antibiotics is reflected by an increasing prevalence of infections with multidrug-resistant bacteria, including third-generation cephalosporin-resistant bacteria (3GCRB). For neonatal intensive care units screening and enhanced barrier precautions are recommended to control the spread of multidrug-resistant Gram-negative bacteria, while evidence for efficacy of barrier precautions remains scarce in a non-outbreak setting. OBJECTIVE: To determine the impact of a screening program for maternal 3GCRB colonization and the effects of contact precautions and cohort nursing, concerning the risk of neonatal late-onset sepsis (LOS) and antibiotic use rates (AURs). STUDY DESIGN: In a retrospective matched-pair cohort study, data of neonates exposed to maternal 3GCRB colonization were compared with findings in non-exposed neonates. RESULTS: Of 3,144 neonates admitted, 184 neonates born to 3GCRB-positive mothers were eligible. Among them, 37 (20%) became 3GCRB positive during hospital stay. 3GCRB-exposed infants had a lower rate of LOS (6.5 vs. 14.1%, p=0.03) and lower AURs in that time period compared to controls (mean 0.009 vs. 0.025, p=0.006). When started within the first 72h after birth, days of therapy with meropenem were significantly lower in non-exposed vs. 3GCRB-exposed infants (mean 0.13 vs. 0.42; p=0.002). No invasive infections with 3GCRB occurred. CONCLUSIONS: Neonates of 3GCRB-positive mothers do not have an increased a priori risk for invasive 3GCRB infection and may benefit from enhanced contact precautions measures. HINTERGRUND: Der zunehmende Einsatz von Antibiotika führt zu einem Anstieg von Infektionen mit multiresistenten Erregern wie z. B. Drittgeneration Cephalosporin-resistenten Bakterien (3GCRB). Empfehlungen zu Screening- und Kohortierungsmaßnahmen auf neonatologischen Intensivstationen zielen auf die Prävention von horizontaler Transmission und invasiven Infektionen ab. Für Nicht-Ausbruchssituationen ist die Evidenz für Hygienemaßnahmen und Screeningprogrammen unzureichend. ZIEL: Evaluation eines Screening für mütterliche 3GCRB-Besiedlung mit nachfolgender Isolation bzw. Kohortenpflege des Neugeborenen (NG) unter Bezug auf das Risiko einer Late-Onset-Sepsis (LOS) und die Anzahl der Antibiotika-Tage (AUR). STUDIENDESIGN: In einer retrospektiven Fall-Kontroll-Kohortenstudie wurden Daten von NG mit maternaler 3GCRB-Besiedelung im Vergleich zu einer Kontrollgruppe mit unauffälligem Screening analysiert. ERGEBNISSE: In einer Kohorte von 3144 NG fanden sich 184 NG von 3GCRB-besiedelten Müttern. Bei 37 (20%) wurde im Verlauf eine Besiedelung mit 3GCRB nachgewiesen. In der Gruppe der 3GCRB-exponierten NG kam es seltener zu einer LOS (6,5 vs. 14,1%, p=0,03). Zwischen dem 4. Lebenstag und der Entlassung hatten 3GCRB-exponierte NG eine niedrigere AUR (Mittelwert 0,009 vs. 0,025, p=0,006) als die Kontrollgruppe. Die Behandlungstage mit Meropenem (Start in den ersten 3 Lebenstagen), war in der Kontrollgruppe signifikant geringer als in der 3GCRB-exponierten Gruppe (Mittelwert 0,13 vs. 0,43 Tage; p=0,002). In beiden Gruppen trat keine invasive Infektion mit 3GCRB auf. SCHLUSSFOLGERUNG: Neugeborene, deren Mütter 3GCRB besiedelt sind, haben kein erhöhtes a priori Risiko für eine invasive Infektion mit 3GCRB Erregern und profitieren wahrscheinlich von erweiterten Kohortierungs- und Isolationsmaßnahmen.

Evidence-based guidelines for the management of abnormally invasive placenta: recommendations from the International Society for Abnormally Invasive Placenta.

The worldwide incidence of abnormally invasive placenta is rapidly rising, following the trend of increasing cesarean delivery. It is a heterogeneous condition and has a high maternal morbidity and mortality rate, presenting specific intrapartum challenges. Its rarity makes developing individual expertise difficult for the majority of clinicians. The International Society for Abnormally Invasive Placenta aims to improve clinicians' understanding and skills in managing this difficult condition. By pooling knowledge, experience, and expertise gained within a variety of different healthcare systems, the Society seeks to improve the outcomes for women with abnormally invasive placenta globally. The recommendations presented herewith were reached using a modified Delphi technique and are based on the best available evidence. The evidence base for each is presented using a formal grading system. The topics chosen address the most pertinent questions regarding intrapartum management of abnormally invasive placenta with respect to clinically relevant outcomes, including the following: definition of a center of excellence; requirement for antenatal hospitalization; antenatal optimization of hemoglobin; gestational age for delivery; antenatal corticosteroid administration; use of preoperative cystoscopy, ureteric stents, and prophylactic pelvic arterial balloon catheters; maternal position for surgery; type of skin incision; position of the uterine incision; use of interoperative ultrasound; prophylactic administration of oxytocin; optimal method for intraoperative diagnosis; use of expectant management; adjuvant therapies for expectant management; use of local surgical resection; type of hysterectomy; use of delayed hysterectomy; intraoperative measures to treat life-threatening hemorrhage; and fertility after conservative management.

Abnormally invasive placenta (AIP): pre-cesarean amnion drainage to facilitate exteriorization of the gravid uterus through a transverse skin incision.

The number of pregnant women with abnormally invasive placenta (AIP) including clinical relevant placenta increta and percreta has markedly increased with a reported incidence of as high as one in 731, By 2020 in the United States, there will be an estimated 4504 new cases of AIP and 130 AIP-associated maternal deaths annually. The preoperative diagnosis and operative management of AIP is challenging. In a planned cesarean delivery, a vertical lower abdominal skin incision is widely used in order to have enough space to perform a hysterotomy above the cranial edge of the placenta to avoid significant fetal and/or maternal hemorrhage. We have used preoperative drainage of the amniotic fluid after epidural anesthesia and immediately before a planned cesarean delivery through a transverse skin incision in five patients with AIP of the anterior uterine wall. With less uterine volume, exteriorization of the gravid uterus is easily performed through a transverse laparotomy. The combination of amnion drainage, transverse laparotomy and exteriorization of the gravid uterus facilitates identification of the exact site of placental implantation, provides adequate space for performing fundal or high anterior or even posterior uterine wall incisions and to deliver the fetus safely while minimizing the risk of placental separation and subsequent uncontrolled blood loss. Furthermore, this technique provides the chance to leave the untouched placenta in situ or to remove the placenta in toto with a uterine wall segment.

Intrauterine therapy of cytomegalovirus infection with valganciclovir: review of the literature.

Congenital cytomegalovirus (CMV) infection is the leading cause for sensorineural hearing loss and mental retardation in children without genetic diseases worldwide. There is little evidence guiding therapeutic strategies during pregnancy when intrauterine fetal CMV infection is confirmed. We provide a systematic review of the use of ganciclovir (GCV) or VGCV during pregnancy discussing safety of its use for mother and fetus and describe two cases of intrauterine therapy of fetal CMV infection with valganciclovir (VGCV). A PubMed database search was done up to November 16, 2016 without any restrictions of publication date or journal, using the following keywords: "valganciclovir" or "ganciclovir" and "pregnan*". Furthermore, citations were searched and expert references were obtained. Reported cases were considered if therapy was in humans and initiation of treatment of the CMV infection was during pregnancy. In total, seven case reports were retrieved which described GCV or VGCV use during pregnancy for fetal or maternal CMV infection. In the four cases of treatment for maternal CMV infection, no negative effects on the fetus were reported. Three cases of GCV administration to pregnant woman with the intention of fetal treatment after proven fetal infection were found. We additionally present two cases of VGCV treatment in pregnancy from our center of tertiary care. VGCV seems to be a safe treatment for congenital CMV infection for the mother and the fetus. Therapeutic concentrations can be achieved in the fetus by oral intake of the mother and CMV replication can be suppressed. Larger studies are needed to evaluate this therapeutic intervention and the long-term effects.

Novel Insights in Fetal Cardiomyopathy due to in utero Herpes Simplex Virus Infection.

This is a case report of fatal cardiomyopathy in a fetus following maternal intrauterine infection with herpes simplex virus (HSV), despite the mother having no symptoms of an infection. The fetus showed signs of a disseminated infection affecting the heart, brain, lungs, liver, adrenal glands, and skin. HSV cardiomyopathy, characterized by vast necrosis, extensive calcifications, and inflammatory infiltration, was found to be the cause of intrauterine fetal death. To our knowledge, this is a unique report of an asymptomatic maternal nonprimary or recurrent HSV infection that induced a transmission of HSV resulting in extensive and fatal changes in the fetal heart.

High seroprevalence of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) among HIV-1-infected children and adolescents in a non-endemic population.

Human herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS), which primarily affects human immunodeficiency virus (HIV)-infected adults with advanced immunodeficiency. Currently, only limited prevalence data for HHV-8 infection in HIV-infected children living in non-endemic areas are available. This multicenter cross-sectional study was conducted in four university hospitals in Germany specializing in pediatric HIV care. Stored serum specimens obtained from 207 vertically HIV-1-infected children and adolescents were tested for antibodies against lytic and latent HHV-8 antigens. Logistic regression was used to assess independent risk factors associated with HHV-8 seropositivity. The overall HHV-8 seroprevalence was 24.6 % (n = 51/207) without significant differences related to sex, age, or ethnicity. In univariate analysis, HHV-8 seropositivity was significantly associated with a child having being born outside Germany, maternal origin from sub-Saharan Africa, a history of breastfeeding, CDC immunologic category 3, and deferred initiation of antiretroviral therapy (>24 months of age). In multivariate analysis, a child's birth outside Germany was the only significant risk factor for HHV-8 seropositivity (odds ratio 3.98; 95 % confidence interval 1.27-12.42). HHV-8-associated malignancies were uncommon; only one patient had a history of KS. Serum specimen of vertically HIV-infected children and adolescents living in Germany showed a high HHV-8 seroprevalence. These findings suggest that primary HHV-8 infection-a risk factor for KS and other HHV-8-associated malignancies-occurs early in life. Thus, management of perinatally HIV-infected children should include testing for HHV-8 coinfection and should consider future risks of HHV-8-associated malignancies.

The rationale for third trimester testing of vertical HIV transmission in neonates with CMV infection.

We report on a late-preterm neonate with severe congenital cytomegalovirus (CMV) infection, refractory to antiviral therapy with ganciclovir. Subsequent immune diagnostics led to the finding of HIV infection at day 69, even though the mother tested negative for HIV in early pregnancy. Thus, in congenital CMV infection, HIV testing should be performed to elucidate maternal HIV seroconversion during late pregnancy. Our case strongly supports third trimester screening of HIV infection acquired during pregnancy, yet recommended only for women with traditional risk factors for HIV or living in an area of high HIV prevalence.

Clinical, Laboratory, and Placental Findings in Perinatal Listeriosis.

Clinical, laboratory, and placental manifestations of perinatal listeriosis are highly variable. Herein, we retrospectively analyzed all patients treated for neonatal listeriosis at the Charité University Medical Center in Berlin, Germany, 1999-2013. A total of 16 cases were identified. In 14 patients listeriosis was confirmed in neonatal specimens, while in two only the placenta tested positive. Elevated C-reactive protein and/or interleukin-6 levels were only inconsistently found, while a marked white blood cell left shift was present in all infants, if available. All but one infant manifested symptoms on the first day of life. Most patients required respiratory support, while none developed meningoencephalitis as evidenced by clinical or cerebrospinal fluid findings. Two patients died, all other patients survived without sequelae. In conclusion, perinatal listeriosis is still associated with significant morbidity and mortality. Clinical and laboratory findings are highly heterogeneous, but extreme leukocyte left shift seems to be a common feature.

Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy.

BACKGROUND: The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women. METHODS: An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated. RESULTS: Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (<50 copies/mL). None of the children were HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53-.96) for AUC0-12h and 0.64 (.34-1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02-2.17; n = 9). CONCLUSIONS: Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women. CLINICAL TRIALS REGISTRATION: NCT00825929.

Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women.

OBJECTIVES: To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum. PATIENTS AND METHODS: This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included. Pharmacokinetic curves were recorded in the third trimester and post-partum. A cord blood sample and maternal sample were collected. The study is registered at ClinicalTrials.gov under number NCT00825929. RESULTS: Twenty-four women were included in the analysis [darunavir/ritonavir: 600/100 mg twice daily (n=6); 800/100 mg once daily (n=17); and 600/100 mg once daily (n=1)]. Geometric mean ratios of third trimester versus post-partum (90% CI) were 0.78 (0.60-1.00) for total darunavir AUC0-tau after 600/100 mg twice-daily dosing and 0.67 (0.56-0.82) for total darunavir AUC0-tau after 800/100 mg once-daily dosing. The unbound fraction of darunavir was not different during pregnancy (12%) compared with post-partum (10%). The median (range) ratio of darunavir cord blood/maternal blood was 0.13 (0.08-0.35). Viral load close to delivery was <300 copies/mL in all but two patients. All children were tested HIV-negative and no congenital abnormalities were reported. CONCLUSIONS: Darunavir AUC and Cmax were substantially decreased in pregnancy for both darunavir/ritonavir regimens. This decrease in exposure did not result in mother-to-child transmission. For antiretroviral-naive patients, who are adherent, take darunavir with food and are not using concomitant medication reducing darunavir concentrations, 800/100 mg of darunavir/ritonavir once daily is adequate in pregnancy. For all other patients 600/100 mg of darunavir/ritonavir twice daily is recommended during pregnancy.

The mother as most important risk factor for colonization of very low birth weight (VLBW) infants with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E).

OBJECTIVES: This study aimed to determine the prevalence of and risk factors for colonization with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) and methicillin-resistant Staphylococcus aureus (MRSA) in very low birth weight (VLBW; <1500 g) infants and their mothers. METHODS: This investigation was conducted in the perinatal centre at the Charité Berlin between May 2012 and June 2013. VLBW infants and their mothers were screened for colonization with ESBL-E and MRSA. Demographic and clinical data were obtained from the German nationwide surveillance system for nosocomial infections in VLBW infants (NEO-KISS) and used to perform univariate and multivariate analyses. RESULTS: Of 209 VLBW infants, 12 (5.7%) were colonized with ESBL-E. Eighteen of 209 (8.6%) ESBL-E-tested neonates were related to an ESBL-E-positive mother. Univariate analysis, strain typing and multivariate analysis (OR 7.4, 95% CI 2.1-26.7, P = 0.002) identified an ESBL-E-positive mother and maternal-neonatal transmission as a main source of colonization. The prevalence of MRSA was 2.3% (5 of 221) among VLBW infants. One of the 221 (0.5%) MRSA-tested neonates was related to an MRSA-positive mother. No risk factors for transmission of MRSA could be detected in this study. CONCLUSIONS: Our study demonstrated that maternal-neonatal transmission of ESBL-E from mother to child is an important risk factor for colonization of VLBW infants. As a consequence, routine ESBL-E screening of neonates and mothers should be considered as a means of reducing neonatal morbidity and mortality.

Breastfeeding is natural but not always easy: intervention for common medical problems of breastfeeding mothers - a review of the scientific evidence.

Natural processes do not always function perfectly. In breastfeeding, problems are encountered in up to 80% of mother-infant dyads. Altogether, in Western societies, the difficulties reduce the breastfeeding rate within the first months drastically. To deal with the problems of breastfeeding efficiently requires a profound understanding of its physiology, as well as of its psychological and social determinants. This review focuses on the current knowledge of breastfeeding physiology, only touching the psychosocial factors, which are included in the promotion strategies. Subsequently, it scrutinizes definitions, incidences, prevention, and treatment of breastfeeding problems faced most frequently by nursing mothers and their consultants. Not all measures used in counseling mothers and not all treatments for the most common medical problems withstand a careful evaluation on the basis of current scientific data. However, applying proven prevention strategies will significantly improve the well being of mothers and their infants, and may contribute to an affective attitude that increases the success, frequency, and duration of breastfeeding.

Are international guideline recommendations for the management of placenta accreta spectrum applicable in low- and middle-income countries?

OBJECTIVE: The aim of this study was to explore how obstetricians-gynecologists in low- and middle-income countries (LMICs) can apply current international clinical practice guidelines (CPGs) for the management of placenta accreta spectrum (PAS) in limited resource settings. METHODS: This was an observational, survey-based study. Clinicians with expertise in managing patients with PAS in LMICs were contacted for their evaluation of the recommendations included in four PAS clinical practice guidelines. RESULTS: Out of the 158 clinicians contacted, we obtained responses from 65 (41.1%), representing 27 middle income countries (MICs). The results of this survey suggest that the care of PAS patients in middle income countries is very different from what is recommended by international CPGs. Participants in the survey identified that their practice was limited by insufficient availability of hospital infrastructure, low resources of local health systems and lack of trained multidisciplinary teams (MDTs) and this did not enable them to follow CPG recommendations. Two-thirds of the participants surveyed describe the absence of centers of excellence in their country. In over half of the referral hospitals with expertise in managing PAS, there are no MDTs. One-third of patients with intraoperative findings of PAS are managed by the team initially performing the surgery (without additional assistance). CONCLUSION: The care of patients with PAS in middle income countries frequently deviates from established CPG recommendations largely due to limitations in local resources and infrastructure. New practical guidelines and training programs designed for low resource settings are needed.

Is telehealth useful in the management of placenta accreta spectrum in low-resource settings? Results of an exploratory survey.

OBJECTIVE: The optimal management of placenta accreta spectrum (PAS) requires the participation of multidisciplinary teams that are often not locally available in low-resource settings. Telehealth has been increasingly used to manage complex obstetric conditions. Few studies have explored the use of telehealth for PAS management, and we aimed evaluate the usage of telehealth in the management of PAS patients in low-resource settings. METHODS: Between March and April 2023, an observational, survey-based study was conducted, and obstetricians-gynecologists with expertise in PAS management in low- and middle-income countries were contacted to share their opinion on the potential use of telehealth for the diagnosis and management of patients at high-risk of PAS at birth. Participants were identified based on their authorship of at least one published clinical study on PAS in the last 5 years and contacted by email. This is a secondary analysis of the results of that survey. RESULTS: From 158 authors contacted we obtained 65 responses from participants in 27 middle-income countries. A third of the participants reported the use of telehealth during the management obstetric emergencies (38.5%, n = 25) and PAS (36.9%, n = 24). Over 70% of those surveyed indicated that they had used "informal" telemedicine (phone call, email, or text message) during PAS management. Fifty-nine participants (90.8%) reported that recommendations given remotely by expert colleagues were useful for management of patients with PAS in their setting. CONCLUSION: Telehealth has been successfully used for the management of PAS in middle-income countries, and our survey indicates that it could support the development of specialist care in other low resource settings.

[Emergency caesarean section and interdisciplinary emergency concepts for the delivery room - "What to do if it is urgent?"]. / Notsectio und interdisziplinäre Notfallkonzepte im Kreißsaal - "Und wenn es schnell gehen soll?"

Resolute and rapid action in obstetric emergencies is essential for the child and/or maternal survival. Therefore emergency caesarean section and the emergency actions for peripartal haemorrhage, shoulder dystocia, fetal bradycardia, hypertension and embolism should be interdisciplinarily coordinated. Interdisciplinary emergency concepts for the major complications could help to optimise their therapy taking structural conditions and legal requirements into account. Emergency concepts should include the alarm- procedure, communication, logistics, the priority steps in therapy as well as the analysis of the passed obstetric emergency. A regular interdisciplinary training of the major obstetric emergencies may help to avoid unnecessary loss of time.