Effects of prenatal alcohol exposition on cognitive outcomes in childhood and youth: a longitudinal analysis based on meconium ethyl glucuronide.

BACKGROUND: Prenatal alcohol exposure (PAE) has been linked to severe, adverse child outcomes. However, little is known regarding subclinical outcomes of low/moderate PAE and its longitudinal consequences, especially regarding neurophysiological and neurocognitive development. A newborn biomarker of PAE, meconium ethyl glucuronide (EtG), has been shown to predict cognitive impairments in primary-school-aged children. The current study investigated the ongoing effects of subclinical PAE in adolescence. METHODS: A sample of n = 96 mother-child dyads of the FRAMES/FRANCES cohort were classified into PAE/no PAE using EtG with a 10 ng/g cutoff. Mothers were recruited during pregnancy and children were assessed during primary-school age (M = 7.57, SD = 0.65, range: 6.00-9.92 years) and adolescence (M = 13.26, SD = 0.31, range: 12.79-14.20 years) on three levels: clinical (ADHD rating), neuropsychological (IQ score and performance in a go/nogo task), and neurophysiological (analysis of P3 event-related potentials (ERP) during said go/nogo task). Developmental outcomes and courses following PAE were assessed using rmANCOVAs, controlling for relevant confounders (socioeconomic status (SES), birth weight, and maternal psychopathology). RESULTS: Neurophysiological impairments emerged for exposed children in the form of diminished attentional resource recruiting in childhood and adolescence (reduced go-P3 amplitudes) with no differences in performance. Neuropsychological testing showed a reduced IQ score for both time points with dose-dependent effects in childhood. Clinical ADHD symptoms were not significantly affected. CONCLUSION: Subclinical PAE, as determined by meconium EtG, has negative developmental consequences on cognitive function that persist from childhood to adolescence. These findings suggest that there is no safe limit for alcohol consumption during pregnancy and that more thorough screening of alcohol consumption during pregnancy is necessary for early identification and treatment of at-risk children.

Cerebroplacental versus Umbilicocerebral Ratio-Analyzing the Predictive Value Regarding Adverse Perinatal Outcomes in Low- and High-Risk Fetuses at Term.

Background and Objectives: The aim of this study was to investigate the prediction of adverse perinatal outcomes using the cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in different cohorts of singleton pregnancies. Materials and Methods: In this retrospective cohort study, we established our own Multiple of Median (MoM) for CPR and UCR. The predictive value for both ratios was studied in the following outcome parameters: emergency cesarean delivery, operative intervention (OI), OI due to fetal distress, 5-min Apgar < 7, admission to neonatal intensive care unit, and composite adverse perinatal outcome. The performance of the ratios was assessed in the following cohorts: total cohort (delivery ≥ 37 + 0 weeks gestation, all birth weight centiles), low-risk cohort (delivery ≥ 37 + 0 weeks gestation, birth weight ≥ 10. centile), prolonged pregnancy cohort (delivery ≥ 41 + 0 weeks gestation, birth weight ≥ 10. centile) and small-for-gestational-age fetuses (delivery ≥ 37 + 0 weeks gestation, birth weight < 10. centile). The underlying reference values for MoM were estimated using quantile regression depending on gestational age. Prediction performance was evaluated using logistic regression models assessing the corresponding Brier score, combining discriminatory power and calibration. Results: Overall, 3326 cases were included. Across all cohorts, in the case of a significant association between a studied outcome parameter and CPR, there was an association with UCR, respectively. The Brier score showed only minimal differences for both ratios. Conclusions: Our study provides further evidence regarding predictive values of CPR and UCR. The results of our study suggest that reversal of CPR to UCR does not improve the prediction of adverse perinatal outcomes.

Longitudinal Course of Short-Term Variation and Doppler Parameters in Early Onset Growth Restricted Fetuses.

PURPOSE: To evaluate the longitudinal pattern of fetal heart rate short term variation (STV) and Doppler indices and their correlation to each other in severe growth restricted (IUGR) fetuses. MATERIALS AND METHODS: In this retrospective study, pregnancies with a birth weight below the 10th percentile, born between 24 and 34 gestational weeks with serial Doppler measurements in combination with a computerized CTG (cCTG) with calculated STV were included. Longitudinal changes of both Doppler indices and STV values were evaluated with generalized additive models, adjusted for gestational age and the individual. For all measurements the frequency of abnormal values with regard to the time interval before delivery and Pearson correlations between Doppler indices and STV values were calculated. RESULTS: 41 fetuses with a total of 1413 observations were included. Over the course of the whole study period, regression analyses showed no significant change of STV values (p = 0.38). Only on the day of delivery, a prominent decrease was observed (mean STV d28-22: 7.97 vs. mean STV on day 0: 6.8). Doppler indices of UA and MCA showed a continuous, significant deterioration starting about three weeks prior to delivery (p = 0.007; UA and p < 0.001, MCA). Correlation between any Doppler index and STV values was poor. CONCLUSION: Fetal heart rate STV does not deteriorate continuously. Therefore, cCTG monitoring should be performed at least daily in these high-risk fetuses. Doppler indices of umbilical artery (UA) and middle cerebral artery (MCA), however, showed continuous deterioration starting about 3 weeks prior to delivery.

N(1)-methylnicotinamide as an endogenous probe for drug interactions by renal cation transporters: studies on the metformin-trimethoprim interaction.

PURPOSE: N(1)-methylnicotinamide (NMN) was proposed as an in vivo probe for drug interactions involving renal cation transporters, which, for example, transport the oral antidiabetic drug metformin, based on a study with the inhibitor pyrimethamine. The role of NMN for predicting other interactions with involvement of renal cation transporters (organic cation transporter 2, OCT2; multidrug and toxin extrusion proteins 1 and 2-K, MATE1 and MATE2-K) is unclear. METHODS: We determined inhibition of metformin or NMN transport by trimethoprim using cell lines expressing OCT2, MATE1, or MATE2-K. Moreover, a randomized, open-label, two-phase crossover study was performed in 12 healthy volunteers. In each phase, 850 mg metformin hydrochloride was administered p.o. in the evening of day 4 and in the morning of day 5. In phase B, 200 mg trimethoprim was administered additionally p.o. twice daily for 5 days. Metformin pharmacokinetics and effects (measured by OGTT) and NMN pharmacokinetics were determined. RESULTS: Trimethoprim inhibited metformin transport with K i values of 27.2, 6.3, and 28.9 µM and NMN transport with IC50 values of 133.9, 29.1, and 0.61 µM for OCT2, MATE1, and MATE2-K, respectively. In the clinical study, trimethoprim increased metformin area under the plasma concentration-time curve (AUC) by 29.5 % and decreased metformin and NMN renal clearances by 26.4 and 19.9 %, respectively (p ≤ 0.01). Moreover, decreases of NMN and metformin renal clearances due to trimethoprim correlated significantly (r S=0.727, p=0.010). CONCLUSIONS: These data on the metformin-trimethoprim interaction support the potential utility of N(1)-methylnicotinamide as an endogenous probe for renal drug-drug interactions with involvement of renal cation transporters.

WebPPG: Feasibility and Usability of Self-Performed, Browser-Based Smartphone Photoplethysmography.

Smartphones enable and facilitate biomedical studies as they allow the recording of various biomedical signals, including photoplethysmograms (PPG). However, user engagement rates in mobile health studies are reduced when an application (app) needs to be installed. This could be alleviated by using installation-free web apps. We evaluate the feasibility of browser-based PPG recording, conducting the first usability study on smartphone-based PPG. We present an at-home study using a web app and library for PPG recording using the rear camera and flash. The underlying library is freely made available to researchers. 25 Android users participated, using their own smartphones. The study consisted of a demographic and anamnestic questionnaire, the signal recording itself (60 s), and a consecutive usability questionnaire. After filtering, heart rate was extracted (14/17 successful), signal-to-noise ratios assessed (0.64 ± 0.50 dB, mean ± standard deviation), and quality was visually inspected (12/17 usable for diagnosis). Recording was not supported in 9 cases. This was due to the browser's insufficient support for the flash light API. The app received a System Usability Scale score of 82 ± 9, which is above the 90th percentile. Overall, browser flash light support is the main limiting factor for broad device support. Thus, browser-based PPG is not yet widely applicable, although most participants feel comfortable with the recording itself. The utilization of the user-facing camera might represent a more promising approach. This study contributes to the development of low-barrier, user-friendly, installation-free smartphone signal acquisition. This enables profound, comprehensive data collection for research and clinical practice.Clinical relevance- WebPPG offers low-barrier remote diagnostic capabilities without the need for app installation.

Feasibility and Acceptance of Self-Guided Mobile Ultrasound among Pregnant Women in Routine Prenatal Care.

BACKGROUND AND OBJECTIVES: Mobile and remote ultrasound devices are becoming increasingly available. The benefits and possible risks of self-guided ultrasound examinations conducted by pregnant women at home have not yet been well explored. This study investigated aspects of feasibility and acceptance, as well as the success rates of such examinations. METHODS: In this prospective, single-center, interventional study, forty-six women with singleton pregnancies between 17 + 0 and 29 + 6 weeks of gestation were included in two cohorts, using two different mobile ultrasound systems. The participants examined the fetal heartbeat, fetal profile and amniotic fluid. Aspects of feasibility and acceptance were evaluated using a questionnaire. Success rates in relation to image and video quality were evaluated by healthcare professionals. RESULTS: Two thirds of the women were able to imagine performing the self-guided examination at home, but 87.0% would prefer live support by a professional. Concerns about their own safety and that of the child were expressed by 23.9% of the women. Success rates for locating the target structure were 52.2% for videos of the fetal heartbeat, 52.2% for videos of the amniotic fluid in all four quadrants and 17.9% for videos of the fetal profile. CONCLUSION: These results show wide acceptance of self-examination using mobile systems for fetal ultrasonography during pregnancy. Image quality was adequate for assessing the amniotic fluid and fetal heartbeat in most participants. Further studies are needed to determine whether ultrasound self-examinations can be implemented in prenatal care and how this would affect the fetomaternal outcome.

Effects of an App-Based Mindfulness Intervention during Pregnancy on the Infant's Prenatal Androgen Exposure: A Randomized Controlled Pilot Trial.

Prenatal androgen exposure modulates the development of the brain, with lasting effects on its function and behavior over the infant's life span. Environmental factors during pregnancy, in particular maternal stress, have been shown to influence the androgen load of the unborn child. We here addressed the research gap on whether a mindfulness intervention or a pregnancy education administered to pregnant women more affects the androgen exposure of the unborn child (quantified by the proxies of second-to-fourth digit length ratio (2D:4D) and anogenital distance assessed one year after delivery and at delivery, respectively). Moreover, we tested the mindfulness intervention's effects on maternal perceived stress, anxiety, depressiveness, and mindfulness. Pregnant women (gestation weeks 8-14) were randomized to a 15-week app-based mindfulness-oriented intervention (N = 72) or a pregnancy education intervention (control condition; N = 74). The mindfulness-oriented group did not significantly differ from the pregnancy education group in infants' 2D:4D or anogenital distance (partial η2 ≤ 0.01) or in maternal stress, anxiety, depressiveness, or mindfulness. However, the descriptive results indicate that across pregnancy, stress and anxiety decreased and mindfulness increased in both groups. Overall, this study did not show that the mindfulness intervention (relative to the pregnancy education) reduced the prenatal androgen exposure of the unborn children or improved the maternal outcomes significantly.

Usability and Perception of a Wearable-Integrated Digital Maternity Record App in Germany: User Study.

Background: Although digital maternity records (DMRs) have been evaluated in the past, no previous work investigated usability or acceptance through an observational usability study. Objective: The primary objective was to assess the usability and perception of a DMR smartphone app for pregnant women. The secondary objective was to assess personal preferences and habits related to online information searching, wearable data presentation and interpretation, at-home examination, and sharing data for research purposes during pregnancy. Methods: A DMR smartphone app was developed. Key features such as wearable device integration, study functionalities (eg, questionnaires), and common pregnancy app functionalities (eg, mood tracker) were included. Women who had previously given birth were invited to participate. Participants completed 10 tasks while asked to think aloud. Sessions were conducted via Zoom. Video, audio, and the shared screen were recorded for analysis. Task completion times, task success, errors, and self-reported (free text) feedback were evaluated. Usability was measured through the System Usability Scale (SUS) and User Experience Questionnaire (UEQ). Semistructured interviews were conducted to explore the secondary objective. Results: A total of 11 participants (mean age 34.6, SD 2.2 years) were included in the study. A mean SUS score of 79.09 (SD 18.38) was achieved. The app was rated "above average" in 4 of 6 UEQ categories. Sixteen unique features were requested. We found that 5 of 11 participants would only use wearables during pregnancy if requested to by their physician, while 10 of 11 stated they would share their data for research purposes. Conclusions: Pregnant women rely on their medical caregivers for advice, including on the use of mobile and ubiquitous health technology. Clear benefits must be communicated if issuing wearable devices to pregnant women. Participants that experienced pregnancy complications in the past were overall more open toward the use of wearable devices in pregnancy. Pregnant women have different opinions regarding access to, interpretation of, and reactions to alerts based on wearable data. Future work should investigate personalized concepts covering these aspects.

Smartphone-Based Colorimetric Analysis of Urine Test Strips for At-Home Prenatal Care.

OBJECTIVE: Clinical urine tests are a key component of prenatal care. As of now, urine test strips are evaluated through a time consuming, often error-prone and operator-dependent visual color comparison of test strips and reference cards by medical staff. METHODS AND PROCEDURES: This work presents an automated pipeline for urinalysis with urine test strips using smartphone camera images in home environments, combining several image processing and color combination techniques. Our approach is applicable to off-the-shelf test strips in home conditions with no additional hardware required. For development and evaluation of our pipeline we collected image data from two sources: i) A user study (26 participants, 150 images) and ii) a lab study (135 images). RESULTS: We trained a region-based convolutional neural network that is able to detect the urine test strip location and orientation in images with a wide variety of light conditions, backgrounds and perspectives with an accuracy of 85.5%. The reference card can be robustly detected through a feature matching approach in 98.6% of the images. Color comparison by Hue channel (0.81 F1-Score), Matching factor (0.80 F1-Score) and Euclidean distance (0.70 F1-Score) were evaluated to determine the urinalysis results. CONCLUSION: We show that an automated smartphone-based colorimetric analysis of urine test strips in a home environment is feasible. It facilitates examinations and provides the possibility to shift care into an at-home environment. CLINICAL IMPACT: The findings demonstrate that routine urine examinations can be transferred into the home environment using a smartphone. Simultaneously, human error is avoided, accuracy is increased and medical staff is relieved.

Pregnant and Postpartum Women Requiring Intensive Care Treatment for COVID-19-First Data from the CRONOS-Registry.

(1) Background: Data on coronavirus 2 infection during pregnancy vary. We aimed to describe maternal characteristics and clinical presentation of SARS-CoV-2 positive women requiring intensive care treatment for COVID-19 during pregnancy and postpartum period based on data of a comprehensive German surveillance system in obstetric patients. (2) Methods: Data from COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS), a prospective multicenter registry for SARS-CoV-2 positive pregnant women, was analyzed with respect to ICU treatment. All women requiring intensive care treatment for COVID-19 were included and compared regarding maternal characteristics, course of disease, as well as maternal and neonatal outcomes. (3) Results: Of 2650 cases in CRONOS, 101 women (4%) had a documented ICU stay. Median maternal age was 33 (IQR, 30-36) years. COVID-19 was diagnosed at a median gestational age of 33 (IQR, 28-35) weeks. As the most invasive form of COVID-19 treatment interventions, patients received either continuous monitoring of vital signs without further treatment requirement (n = 6), insufflation of oxygen (n = 30), non-invasive ventilation (n = 22), invasive ventilation (n = 28), or escalation to extracorporeal membrane oxygenation (n = 15). No significant clinical differences were identified between patients receiving different forms of ventilatory support for COVID-19. Prevalence of preterm delivery was significantly higher in women receiving invasive respiratory treatments. Four women died of COVID-19 and six fetuses were stillborn. (4) Conclusions: Our cohort shows that progression of COVID-19 is rare in pregnant and postpartum women treated in the ICU. Preterm birth rate is high and COVID-19 requiring respiratory support increases the risk of poor maternal and neonatal outcome.

Update Breast Cancer 2019 Part 3 - Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel.

The treatment of breast cancer patients in a curative situation is special in many ways. The local therapy with surgery and radiation therapy is a central aspect of the treatment. The complete elimination of tumour cells at the site of the primary disease must be ensured while simultaneously striving to keep the long-term effects as minor as possible. There is still focus on the continued reduction of the invasiveness of local therapy. With regard to systemic therapy, chemotherapies with taxanes, anthracyclines and, in some cases, platinum-based chemotherapies have become established in the past couple of decades. The context for use is being continually further defined. Likewise, there are questions in the case of antihormonal therapy which also still need to be further defined following the introduction of aromatase inhibitors, such as the length of therapy or ovarian suppression in premenopausal patients. Finally, personalisation of the treatment of early breast cancer patients is also being increasingly used. Prognostic tests could potentially support therapeutic decisions. It must also be considered how the possible use of new therapies, such as checkpoint inhibitors and CDK4/6 inhibitors could look in practice once study results in this regard are available. This overview addresses the backgrounds on the current votes taken by the international St. Gallen panel of experts in Vienna in 2019 for current questions in the treatment of breast cancer patients in a curative situation.