Kinase-inactivated CDK6 preserves the long-term functionality of adult hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are characterized by the ability to self-renew and to replenish the hematopoietic system. The cell-cycle kinase cyclin dependent-kinase 6 (CDK6) regulates transcription, whereby it has both kinase-dependent and kinase-independent functions. We here describe the complex role of CDK6, balancing quiescence, proliferation, self-renewal and differentiation in activated HSCs. Mouse HSCs expressing kinase-inactivated CDK6 show enhanced long-term repopulation and homing, whereas HSCs lacking CDK6 have impaired functionality. The transcriptomes of basal and serially transplanted HSCs expressing kinase-inactivated CDK6 exhibit an expression pattern dominated by HSC quiescence and self-renewal, proposing a concept where MAZ and NFY-A are critical CDK6 interactors. Pharmacologic kinase inhibition with a clinically used CDK4/6 inhibitor in murine and human HSCs validated our findings and resulted in increased repopulation capability and enhanced stemness. Our findings highlight a kinase-independent role of CDK6 in long-term HSC functionality. CDK6 kinase inhibition represents a possible strategy to improve HSC fitness.

Trends in caesarean section rates in Europe from 2015 to 2019 using Robson's Ten Group Classification System: A Euro-Peristat study.

OBJECTIVE: To assess changes in caesarean section (CS) rates in Europe from 2015 to 2019 and utilise the Robson Ten Group Classification System (TGCS) to evaluate the contribution of different obstetric populations to overall CS rates and trends. DESIGN: Observational study utilising routine birth registry data. SETTING: A total of 28 European countries. POPULATION: Births at ≥22 weeks of gestation in 2015 and 2019. METHODS: Using a federated model, individual-level data from routine sources in each country were formatted to a common data model and transformed into anonymised, aggregated data. MAIN OUTCOME MEASURES: By country: overall CS rate. For TGCS groups (by country): CS rate, relative size, relative and absolute contribution to overall CS rate. RESULTS: Among the 28 European countries, both the CS rates (2015, 16.0%-55.9%; 2019, 16.0%-52.2%) and the trends varied (from -3.7% to +4.7%, with decreased rates in nine countries, maintained rates in seven countries (≤ ± 0.2) and with increasing rates in 12 countries). Using the TGCS (for 17 countries), in most countries labour induction increased (groups 2a and 4a), whereas multiple pregnancies (group 8) decreased. In countries with decreasing overall CS rates, CS tended to decrease across all TGCS groups, whereas in countries with increasing rates, CS tended to increase in most groups. In countries with the greatest increase in CS rates (>1%), the absolute contributions of groups 1 (nulliparous term cephalic singletons, spontaneous labour), 2a and 4a (induction of labour), 2b and 4b (prelabour CS) and 10 (preterm cephalic singletons) to the overall CS rate tended to increase. CONCLUSIONS: The TGCS shows varying CS trends and rates among countries of Europe. Comparisons between European countries, particularly those with differing trends, could provide insight into strategies to reduce CS without clinical indication.

The maternal microbiome in pregnancy, delivery, and early-stage development of neonatal microbiome after cesarean section: A prospective longitudinal study.

INTRODUCTION: Changes within the maternal microbiome during the last trimester of pregnancy and the determinants of the subsequent neonatal microbiome establishment after delivery by elective cesarean section are described. MATERIAL AND METHODS: Maternal vaginal and rectal microbiome samples were collected in the last trimester and before cesarean section; intrauterine cavity, placenta, neonatal buccal mucosa, skin, and meconium samples were obtained at birth; neonatal sample collection was repeated 2-3 days postnatally. Microbial community composition was analyzed by 16S rRNA gene amplicon sequencing. Relative abundance measurements of amplicon sequencing variants and sum counts at higher taxonomic levels were compared to test for significant overlap or differences in microbial community compositions. CLINICALTRIALS: gov ID: NCT04489056. RESULTS: A total of 30 mothers and their neonates were included with available microbiome samples for all maternal, intrauterine cavity and placenta samples, as well as for 18 of 30 neonates. The composition of maternal vaginal and rectal microbiomes during the last trimester of healthy pregnancies did not significantly change (permutational multivariate analysis of variance [PERMANOVA], p > 0.05). No robust microbial signature was detected in the intrauterine cavity, placenta, neonatal buccal mucosa, skin swabs, or meconium samples collected at birth. After birth, the neonatal microbiome was rapidly established, and significantly different microbial communities were detectable 2-3 days postnatally in neonate buccal mucosa and stool samples (PERMANOVA, p < 0.01). CONCLUSIONS: Maternal vaginal and rectal microbiomes in healthy pregnancies remain stable during the third trimester. No microbial colonization of the neonate was observed before birth in healthy pregnancies. Neonatal microbiomes in infants delivered by cesarean section displayed a taxonomic composition distinct from maternal vaginal and rectal microbiomes at birth, indicating that postnatal exposure to the extrauterine environment is the driving source of initial neonatal microbiome development in this cohort.

Maternal biomarkers in predicting neonatal sepsis after preterm premature rupture of membranes in preterm infants.

AIM: This retrospective cohort study aimed to assess the utility of maternal C-reactive protein (CRP) and leukocyte levels in predicting neonatal sepsis after preterm premature rupture of membranes (pPROM). METHODS: We conducted a retrospective cohort study (2009-2021), encompassing preterm infants born ≤29 + 6 weeks of gestation following pPROM. The primary outcome was early-onset neonatal sepsis within the initial 72 h of life. RESULTS: We analysed data from 706 patients with a median gestational age at pPROM of 25.1 weeks and a median gestational age at birth of 26.4 weeks. Overall survival rate was 86.1%, with 65.7% survival without severe morbidities. These rates were significantly worse in preterm infants with sepsis. Maternal CRP and leukocyte levels correlated significantly with neonatal infection markers and sepsis. However, their predictive values, correlation coefficients, and area under the curve values were generally low. Using maternal CRP ≥2 mg/dL to predict neonatal sepsis yielded a positive predictive value of 18.5%, negative predictive value of 91.5%, AUC of 0.589, 45.5% sensitivity, and 74.5% specificity. CONCLUSION: Maternal CRP and leukocyte levels were ineffective as a tool for predicting early-onset neonatal sepsis following early pPROM. Consequently, these biomarkers lack the reliability required for clinical decision-making in this context.

Dequalinium Chloride for the Treatment of Vulvovaginal Infections: A Systematic Review and Meta-Analysis.

OBJECTIVE/PURPOSE: Women at reproductive age frequently experience vulvovaginal infections and vaginitis. The most common etiologies are vulvovaginal candidiasis (VVC), bacterial vaginosis (BV), desquamative inflammatory vaginitis/aerobic vaginitis, and trichomoniasis. Various treatment options are available for these infections, such as specific antimicrobial or antiseptic agents. Dequalinium chloride (DQC) is a local antiseptic agent with a broad antimicrobial and antifungal spectrum. Multiple studies suggest that DQC is an efficient treatment for vaginal infections; however, it is not widely recommended as a first-line treatment. This systematic review and meta-analysis aims to evaluate the efficacy of DQC compared with that of standard treatment. METHODS: Our systematic review was conducted according to the PRISMA guidelines. PubMed/MEDLINE, EMBASE, CENTRAL, and clinicaltrials.org were searched to retrieve relevant reports up to October 2022. RESULTS: Four randomized controlled studies and 1 observational study were included in this review. Overall, DQC showed noninferiority to the reference treatments for BV and VVC, and to the evaluated treatment options for desquamative inflammatory vaginitis/aerobic vaginitis. For BV and VVC, this could also be confirmed in a meta-analysis including 3 randomized controlled studies. No serious adverse events were reported in any of these studies. CONCLUSIONS: Dequalinium chloride offers a safe, well-tolerated, and efficient treatment option for vulvovaginal infections of different etiologies. However, further studies are needed to confirm our findings and allow inclusion of DQC as a first-line treatment into guidelines.

The impact of pandemic restrictive visiting policies on infant wellbeing in a NICU.

BACKGROUND: Given the countrywide lockdown in the first pandemic period and the respective Hospital restrictive policies, we aimed to investigate if the SARS-COV-2 pandemic was associated to a reduced parental presence in the NICU and in which form this had an impact on infant wellbeing. METHODS: Retrospective cohort study about altered NICUs parental presence (measured by number of visits and kangaroo care time) due to pandemic restrictive policies and its impact on infant wellbeing (measured through The Neonatal Pain Agitation and Sedation scale and nurses' descriptive documentation). RESULTS: Presence of both parents at the same time was significantly lower during pandemic. Contrary, maternal presence only and total kangaroo-care time were higher within the pandemic (163.36 ± 94.07 vs 122.71 ± 64.03; p = 0.000). Lower NPASS values were documented during the lookdown (1.28 ± 1.7 vs 1.78 ± 2.2; p = 0.000). CONCLUSION: Data collected through the pandemic confirm the importance of parental presence for infants' wellbeing in a NICU setting. IMPACT: Parental support is an extremely important aspect for infants hospitalized in an intensive care unit. Their presence was limited in many NICUs worldwide during the SARS-COV-2 pandemic. This study confirm the importance of parental presence for infants' wellbeing also in a pandemic situation. Our results support a family-centered newborn individualized developmental care approach in the NICU.

Quality of life in women with chronic recurrent vulvovaginal candidosis: A sub-analysis of the prospective multicentre phase IIb/III Prof-001 study.

BACKGROUND: Chronic recurrent vulvovaginal candidosis (RVVC), defined as three or more episodes of vulvovaginal candidosis per year, significantly impairs quality of life (QoL) and sexual health. OBJECTIVES: The primary objective of this study was to assess health-related QoL in women with RVVC using validated questionnaires before and after treatment. The secondary objective was to analyse the effect of RVVC on women's sexual health. PATIENTS/METHODS: This was a sub-analysis of a randomised, controlled, double-blinded study titled 'A phase IIb/III, parallel-arm, randomized, active-controlled, double-blind, double-dummy, multicenter, non-inferiority study in patients with recurrent vulvovaginal candidosis to compare the clinical efficacy, safety and tolerability of topically administered ProF-001 (Candiplus®) to oral fluconazole, which was conducted at 35 study sites in Austria, Poland and Slovakia. QoL was assessed using the European Quality of Life (EQ) five-dimension five-level scale (EQ-5D-5L) and visual analogue scale (EQ-VAS) questionnaires, followed by specific questions regarding sexuality. RESULTS: From 2019 to 2021, 360 of 432 (83.3%) women with RVVC had accomplished a 6-months maintenance treatment and were enrolled in this sub-analysis. The EQ-5D-5L and EQ-VAS scores demonstrated improved QoL in 137 (65.2%) and 159 (75.4%) women after 6 months of maintenance treatment. Each individual aspect of sexual health significantly improved (all p < .05). A reduction in pain frequency during or after sexual intercourse in the 6-month period occurred in 124 (66.3%) women. CONCLUSIONS: Women with RVVC had high QoL and sexual health impairment; however, a 6-months maintenance treatment resulted in effective improvement in QoL and sexual health.

Perinatal and postpartum care during the COVID-19 pandemic: A nationwide cohort study.

BACKGROUND: This study aimed to analyze perinatal outcomes and adverse events during the COVID-19 pandemic's first wave to help direct decision making in future waves. METHODS: This study was an epidemiological cohort study analyzing comprehensive birth registry data among all 80 obstetric departments in Austria. Out of 469 771 records, 468 348 were considered eligible, whereof those with preterm delivery, birthweight <500 g, multiple fetuses, fetal malformations and chromosomal anomalies, intrauterine fetal death, maternal cancer, HIV infection, and/or inter-hospital transfers were excluded. Women who delivered between January and June 2020 were then classified as cases, whereas those who delivered between January and June 2015-2019 were classified as controls. Perinatal outcomes, postpartum hospitalization, and adverse events served as outcome measures. RESULTS: Of 33 198 cases and 188 225 controls, data analysis showed significantly increased rates of labor induction, instrumental delivery, obstetric anesthesia, NICU transfer, and 5-min Apgar score below 7 during the COVID-19 period. There was a significantly shorter length of postpartum hospitalization during the COVID-19 period compared with the non-COVID-19 period (3.1 ± 1.4 vs 3.5 ± 1.5 days; P < .001). Significantly more women opted for short-stay delivery during the COVID-19 period (3.7% vs 2.4%; P < .001). Those who delivered during the COVID-19 period were also more likely to experience postpartum adverse events (3.0% vs 2.6%; P < .001), which was confirmed in the logistic regression model (odds ratio, 2.137; 95% confidence interval, 1.805-2.530; P < .001). CONCLUSIONS: Perinatal and postpartum care during the first wave of the COVID-19 pandemic differed significantly from that provided before. Increased rates of adverse events underline the need to ensure access to high-quality obstetric care to prevent collateral damage.

Exposure to night-time light pollution and risk of prolonged duration of labor: A nationwide cohort study.

BACKGROUND: Light pollution (LP) is a ubiquitous environmental agent that affects more than 80% of the world's population. This large nationwide cohort study evaluates whether exposure to LP can influence obstetric outcomes. METHODS: We analyzed Austrian birth registry data on 717 113 cases between 2008 and 2016 and excluded cases involving day-time delivery, <23 + 0 gestational weeks, and/or birthweight <500 g, induction of labor, elective cesarean, or cases with missing data. The independent variable, that is, degree of night-time LP, was categorized as low (0.174 to <0.688 mcd/m2 ), medium (0.688 to <3 mcd/m2 ), or high (3 to <10 mcd/m2 ). Duration of labor and adverse neonatal outcomes served as outcome measures. RESULTS: Cases in regions with high LP (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.30-1.57) and medium LP (OR, 1.22; 95% CI, 1.14-1.31) showed increased odds of prolonged labor (P < .0001 each). Newborns born in regions with high LP (OR, 1.12; 95% CI, 1.07-1.16) and medium LP (OR, 1.07; 95% CI, 1.04-1.10) showed increased odds of experiencing adverse outcomes (P < .0001 each). Preterm delivery <28 + 0 weeks was also associated with the degree of LP (P = .04). CONCLUSIONS: Night-time LP negatively interferes with obstetric outcomes. The perceived influence of LP as an environmental agent needs to be re-evaluated to minimize associated health risks.

Bilateral lung transplantation during pregnancy after ECMO for influenza-A caused ARDS.

Pregnant women with influenza-A have an increased risk of developing acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) can be used as salvage therapy, with lung transplantation as a therapeutic option. However, successful bilateral lung transplantation during pregnancy has never been reported before. We herein report the case of a 34-year-old primipara, who was diagnosed with ARDS caused by influenza-A-induced pneumonia at early gestation. After considering all possible therapeutic options and being fully dependent on VV-ECMO support, she underwent bilateral lung transplantation. The transplantation with intraoperative central VA-ECMO support was successfully performed with good recovery after an initial primary graft dysfunction. The pregnancy was prolonged until 29+5  gestational weeks. The newborn exhibited growth retardation and was initially stabilized, but later died due to severe, hypoxic respiratory failure and pulmonary hypertension. In conclusion, lung transplantation is a possible salvage therapy for patients with severe lung failure following ARDS during pregnancy. However, it places the mother and unborn child at risk. A multi-professional approach is warranted to diagnose and treat complications at an early stage.

Tissue Sodium Concentration Quantification at 7.0-T MRI as an Early Marker for Chemotherapy Response in Breast Cancer: A Feasibility Study.

Background Tissue sodium concentration (TSC) is elevated in breast cancer and can determine chemotherapy response. Purpose To test the feasibility of using a sodium 23 (23Na) MRI protocol at 7.0 T for TSC quantification to predict early treatment outcomes of neoadjuvant chemotherapy in breast cancer and to determine whether those quantitative values provide additional information about efficacy. Materials and Methods Women with primary breast cancer were included in this prospective study. From July 2017 to June 2018, participants underwent 7.0-T 23Na MRI. Multichannel data sets were acquired with a density-adapted, three-dimensional radial projection reconstruction pulse sequence. Two-dimensional tumor size and TSC were evaluated before and after the first and second chemotherapy cycle, and statistical tests were performed based on the presence or absence of a pathologic complete response (pCR). Results Fifteen women with breast cancer and six healthy women were enrolled. The mean baseline tumor size in women with a pCR was 7.0 cm2 ± 5.0 (standard deviation), and the mean baseline tumor size in women without a pCR was 19.0 cm2 ± 12.0. After the first chemotherapy cycle, women with a pCR showed a reduced tumor size of 32.9% (2.3 cm2/7.0 cm2), compared with 15.3% (2.9 cm2/19.0 cm2) in those without a pCR. The areas under the receiver operating characteristic curve for tumor size reduction after the first and second chemotherapy cycle were 0.73 (95% CI: 0.09, 0.50; P = .12) and 0.93 (95% CI: 0.04, 0.60; P < .001), respectively. Women with a pCR had a mean baseline TSC of 69.4 mmol/L ± 6.1, with a reduction of 12.0% (8.3 mmol/L), whereas those without a pCR had a mean baseline TSC of 71.7 mmol/L ± 5.7, with a reduction of 4.7% (3.4 mmol/L) after the first cycle. The areas under the receiver operating characteristic curve for TSC after the first and second cycles were 0.96 (95% CI: 0.86, 1.00; P < .001) and 1.000 (95% CI: 1.00, P < .001), respectively. Conclusion Using 7.0-T MRI for tissue sodium concentration quantification to predict early treatment outcomes of neoadjuvant chemotherapy in breast cancer is feasible, with reduced tissue sodium concentration indicative of cancer response. © RSNA, 2021 Online supplemental material is available for this article.

Multiprofessional perinatal care in a pregnant patient with acute respiratory distress syndrome due to COVID-19.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has caused ongoing challenges in health services worldwide. Despite the growing body of literature on COVID-19, reports on perinatal care in COVID-19 cases are limited. CASE PRESENTATION: We describe a case of severe acute respiratory distress syndrome (ARDS) in a 36-year-old G5/P2 pregnant woman with morbid obesity, confirmed severe acute respiratory syndrome coronavirus 2 infection, and fulminant respiratory failure. At 28+ 1 gestational weeks, the patient delivered an uninfected newborn. Using ImmunoCAP ISAC® technology, we found no immunoglobulin (Ig) M antibodies, suggesting that no mother-to-child viral transmission occurred during pregnancy or delivery. The maternal respiratory state improved rapidly after delivery; both maternal and neonatal outcomes were encouraging given the early gestational age and fulminant course of respiratory failure in our patient. CONCLUSIONS: The management of ARDS in pregnant women with COVID-19 is complex and requires an individualized, multidisciplinary approach, while considering maternal and fetal outcomes.

HIV infection as a risk factor for vaginal dysbiosis, bacterial vaginosis, and candidosis in pregnancy: A matched case-control study.

BACKGROUND: This study aimed to evaluate the vaginal microbiota of HIV-positive pregnant women relative to HIV-negative controls, and to compare their risk of vaginal dysbiosis, bacterial vaginosis, and vulvovaginal candidosis (VVC). METHODS: This is a nested matched case-control study that analyzed data from women who received pregnancy care at our center from 2003 to 2014. Women routinely underwent screening for asymptomatic vaginal infections using phase microscopy on Gram-stained smears. HIV-positive women were assigned to the case group, and HIV-negative women were assigned to the control group. Cases and controls were matched in a 1:4 ratio. Logistic regression was used to test whether HIV infection was associated with vaginal dysbiosis (Nugent score 4-6), BV (Nugent score 7-10), or VVC. RESULTS: One hundred and twenty-seven women were assigned to the case group, and 4290 were assigned to the control group (including 508 matched controls). Dysbiosis or BV was found in 29.9% of the cases and 17.6% of the controls. Women in the case group had increased risk of vaginal dysbiosis or BV (odds ratio [OR] 2.09, 95% confidence interval [CI], 1.30-3.32, P = .002). The risk of VVC was also higher in the case group (OR 2.14, 95% CI, 1.22-3.77, P = .008). The incidence of preterm birth did not differ significantly between the groups (cases: 8.7%; controls: 10%, P = .887). CONCLUSIONS: HIV-positive women are at risk of vaginal dysbiosis, BV, and VVC during pregnancy. As imbalances of the vaginal microbiota can lead to preterm birth, screening and treatment of HIV-positive pregnant women are warranted.

Vaginal microbiota in pregnant women with inflammatory rheumatic and inflammatory bowel disease: A matched case-control study.

BACKGROUND: Rheumatic diseases and vaginal infections both increase the risk of preterm birth. It is unclear whether pregnant women with rheumatic disease are more likely to experience vaginal infections, which might potentially accumulate modifiable risk factors. OBJECTIVE: In this study, we sought to evaluate the vaginal microbiota of pregnant women with inflammatory rheumatic and inflammatory bowel disease. METHODS: A total of 539 asymptomatic women with singleton pregnancy were routinely screened for an abnormal vaginal microbiota between 10 + 0 and 16 + 0 gestational weeks. Vaginal smears were Gram-stained and microscopically analysed. Those with inflammatory diseases (with or without immunomodulatory therapy) were assigned to the case group and matched in a 1:3 ratio to healthy pregnant controls. RESULTS: Overall, an abnormal vaginal microbiota occurred more frequently among women of the case group, compared with those of the control group (33.8% vs 15.6%; 95% CI: 1.78-4.27, p < .001). In particular, Candida colonisation (22.3% vs 9.2%; 95% CI: 1.69-4.75, p < .001), but also bacterial vaginosis (14.9% vs 7.2%; 95% CI: 1.25-4.1, p = .006), occurred more often in the case than in the control group. No significant difference was found with regard to the occurrence of an abnormal vaginal microbiota between subgroups with and without immunomodulatory treatment (37.0% vs 27.1%; 95% CI: 0.29-1.35, p = .232). CONCLUSION: Pregnant women with inflammatory rheumatic and inflammatory bowel disease are at risk for bacterial vaginosis and Candida colonisation, which might pose a risk for preterm birth. Prospective studies are needed to further evaluate the influence of autoimmune conditions and immunosuppressive therapy on the vaginal microbiota.

Guideline: Vulvovaginal candidosis (AWMF 015/072, level S2k).

Approximately 70-75% of women will have vulvovaginal candidosis (VVC) at least once in their lifetime. In premenopausal, pregnant, asymptomatic and healthy women and women with acute VVC, Candida albicans is the predominant species. The diagnosis of VVC should be based on clinical symptoms and microscopic detection of pseudohyphae. Symptoms alone do not allow reliable differentiation of the causes of vaginitis. In recurrent or complicated cases, diagnostics should involve fungal culture with species identification. Serological determination of antibody titres has no role in VVC. Before the induction of therapy, VVC should always be medically confirmed. Acute VVC can be treated with local imidazoles, polyenes or ciclopirox olamine, using vaginal tablets, ovules or creams. Triazoles can also be prescribed orally, together with antifungal creams, for the treatment of the vulva. Commonly available antimycotics are generally well tolerated, and the different regimens show similarly good results. Antiseptics are potentially effective but act against the physiological vaginal flora. Neither a woman with asymptomatic colonisation nor an asymptomatic sexual partner should be treated. Women with chronic recurrent Candida albicans vulvovaginitis should undergo dose-reducing maintenance therapy with oral triazoles. Unnecessary antimycotic therapies should always be avoided, and non-albicans vaginitis should be treated with alternative antifungal agents. In the last 6 weeks of pregnancy, women should receive antifungal treatment to reduce the risk of vertical transmission, oral thrush and diaper dermatitis of the newborn. Local treatment is preferred during pregnancy.

Perinatal outcomes of infants with congenital limb malformations: an observational study from a tertiary referral center in Central Europe.

BACKGROUND: Congenital limb malformations are rare, and their perinatal outcomes are not well described. This study analyzed the perinatal outcomes of infants with congenital limb malformations. METHODS: All infants with congenital limb malformations who underwent prenatal assessment and delivery at our tertiary referral center from 2004 through 2017 were retrospectively identified. Neonatal outcome parameters were assessed, and the predictors of worse perinatal outcomes were determined. RESULTS: One hundred twenty-four cases of congenital limb malformations were identified, of which 104 (83.9%) were analyzed. The upper limb was affected in 15 patients (14.4%), the lower limb in 49 (47.1%), and both limbs in 40 (38.5%) patients. A fetal syndrome was identified in 66 patients (63.5%); clubfoot and longitudinal reduction defects were the most frequent malformations. In total, 38 patients (36.5%) underwent termination, seven (6.7%) had stillbirth, and 59 (56.7%) had live-born delivery. Rates of preterm delivery and transfer to the Neonatal Intensive Care Unit were 42.4 and 25.4%, respectively. Localization of the malformation was a determinant of perinatal outcome (P = .006) and preterm delivery (P = .046). CONCLUSIONS: Congenital limb malformations frequently occur bilaterally and are associated with poor perinatal outcomes, including high rates of stillbirth and preterm delivery. Multidisciplinary care and referral to a perinatal center are warranted.

Working-hour phenomenon in obstetrics is an attainable target to improve neonatal outcomes.

BACKGROUND: Giving birth in a health care facility does not guarantee high-quality care or favorable outcomes. The working-hour phenomenon describes adverse outcomes of institutional births outside regular working hours. OBJECTIVES: The objectives of the study were to evaluate whether the time of birth is associated with adverse neonatal outcomes and to identify the riskiest time periods for obstetrical care. STUDY DESIGN: This nationwide retrospective cohort study analyzed data from 2008 to 2016 from all 82 obstetric departments in Austria. Births at ≥ 23+0 gestational weeks with ≥500 g birthweight were included. Independent variables were categorized by the time of day vs night as core time (morning, day) and off hours (evening, nighttime periods 1-4). The composite primary outcome was adverse neonatal outcome, defined as arterial umbilical cord blood pH <7.2, 5 minute Apgar score <7, and/or admission to the neonatal intensive care unit. Multivariate logistic regression was used to develop a model to predict these adverse neonatal outcomes. RESULTS: Of 462,947 births, 227,672 (49.2%) occurred during off hours and had a comparable distribution in all maternity units, regardless of volume (<500 births per year: 50.3% during core time vs 49.7% during off hours; ≥500 births per year: 50.7% core time vs 49.3% off hours; perinatal tertiary center: 51.2% core time vs 48.8% off hours). Furthermore, most women (35.8-35.9%) gave birth between 2:00 and 5:59 am (night periods 3 and 4). After adjustment for covariates, we found that adverse neonatal outcomes also occurred more frequently during these night periods 3 and 4, in addition to the early morning period (night 3: odds ratio, 1.05; 95% confidence interval, 1.03-1.08; P < .001; night 4: odds ratio, 1.08; 95% confidence interval, 1.05-1.10; P < .001; early morning period: odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P < .001). The adjusted odds for adverse outcomes were lowest for births between 6:00 and 7:59 pm (odds ratio, 0.96; 95% confidence interval, 0.93-0.99; P = .006). CONCLUSION: There is an increased risk of adverse neonatal outcomes when giving birth between 2:00 and 7:59 am. The so-called working-hour phenomenon is an attainable target to improve neonatal outcomes. Health care providers should ensure an optimal organizational framework during this time period.

Human placentophagy: a review.

Placentophagy or placentophagia, the postpartum ingestion of the placenta, is widespread among mammals; however, no contemporary human culture incorporates eating placenta postpartum as part of its traditions. At present, there is an increasing interest in placentophagy among postpartum women, especially in the United States. The placenta can be eaten raw, cooked, roasted, dehydrated, or encapsulated or through smoothies and tinctures. The most frequently used preparation appears to be placenta encapsulation after steaming and dehydration. Numerous companies offer to prepare the placenta for consumption, although the evidence for positive effects of human placentophagy is anecdotal and limited to self-reported surveys. Without any scientific evidence, individuals promoting placentophagy, especially in the form of placenta encapsulation, claim that it is associated with certain physical and psychosocial benefits. We found that there is no scientific evidence of any clinical benefit of placentophagy among humans, and no placental nutrients and hormones are retained in sufficient amounts after placenta encapsulation to be potentially helpful to the mother postpartum. In contrast to the belief of clinical benefits associated with human placentophagy, the Centers for Disease Control and Prevention recently issued a warning due to a case in which a newborn infant developed recurrent neonatal group B Streptococcus sepsis after the mother ingested contaminated placenta capsules containing Streptococcus agalactiae. The Centers for Disease Control and Prevention recommended that the intake of placenta capsules should be avoided owing to inadequate eradication of infectious pathogens during the encapsulation process. Therefore, in response to a woman who expresses an interest in placentophagy, physicians should inform her about the reported risks and the absence of clinical benefits associated with the ingestion. In addition, clinicians should inquire regarding a history of placenta ingestion in cases of postpartum maternal or neonatal infections such as group B Streptococcus sepsis. In conclusion, there is no professional responsibility on clinicians to offer placentophagy to pregnant women. Moreover, because placentophagy is potentially harmful with no documented benefit, counseling women should be directive: physicians should discourage this practice. Health care organizations should develop clear clinical guidelines to implement a scientific and professional approach to human placentophagy.

Quality of web-based family-building information for LGBTQ individuals.

OBJECTIVE: The number of patients who seek health information on the internet is increasing. Rates are particularly high among lesbian, gay, bisexual, transgender and queer (LGBTQ) individuals, due to health care barriers. The aim of this study was to evaluate the quality and inclusivity of web-based information pertaining to LGBTQ family building. METHODS: The first 100 US-based websites pertaining to LGBTQ family building were identified through a terminology-based internet search. After eliminating 45 websites, 55 websites were found to be eligible. The 2016 Website Information Reliability Evaluation Instrument (of the Office of Disease Prevention and Health Promotion, US Department of Health and Human Services) was used to analyse the quality of information on each website. Websites were analysed for inclusivity of important topics surrounding LGBTQ family building. RESULTS: A total of 46 websites (83.6%) belonged or were related to reproductive services and served as advertisements for their respective owners; nine websites (16.4%) belonged to third parties. No website met more than four of the six major reliability criteria, and 42 websites (76.4%) met only one or two of the six major reliability criteria. When inclusivity was considered, 29 websites (52.7%) mentioned options for transgender individuals and nine websites (16.4%) mentioned adoption. CONCLUSIONS: There is a lack of reliable web-based information for LGBTQ family building and a need for improvement in quality and scope. Improvements could lead to a shift in reproductive health care towards better inclusion of and catering to LGBTQ individuals.

The colonization with Candida species is more harmful in the second trimester of pregnancy.

PURPOSE: Vaginal colonization with Candida species (spp.) during pregnancy has been associated with impaired pregnancy outcomes. There is a reduction in spontaneous preterm birth among women with recurrent asymptomatic colonization of Candida who were treated with clotrimazole. This study aimed to evaluate the impact of the trimester of vulvovaginal colonization with Candida species. METHODS: Data from all women, who were tested positive for the vaginal colonization with Candida spp. during the first or second trimester of pregnancy, and who registered for a planned birth at our tertiary referral center between 2005 and 2014 were retrospectively analyzed. Their preterm birth rate served as the primary outcome variable. Secondary outcome variables were neonatal birthweight and Apgar score. RESULTS: Overall, 1066 women were eligible for the study. In 673 women (63%), who were diagnosed with Candida spp. during the first trimester of pregnancy, the rate of preterm birth was 10% (N = 64). In 393 women (37%), who were diagnosed with candidosis during the second trimester, the preterm birth rate was 18% (N = 71; p = 0.0002). Neonates of women, who presented with vulvovaginal candidosis during the first trimester, had a mean birthweight of 3243 g, compared to 2989 g in the group with a second trimester colonization (p < 0.0001). CONCLUSION: Women who are colonized with Candida spp. during the second trimester of pregnancy have higher rates of preterm birth and lower neonatal birthweight than those who are colonized during the first trimester of their pregnancy. Screening programs for asymptomatic Candida colonization should take this information into account.