National and International Comparisons of Gynecological Research in Germany Based on a Bibliometric Analysis of Publications.

Background: Recent years have seen a considerable shift from male doctors to female doctors in the field of gynecology. Female doctors are traditionally more involved with planning and maintaining their family. For gynecology, this could be associated with a risk that research activities will decrease, particularly if results are published in scientific journals. Methods: In view of this shift, a comparative observational study was carried for 2022 in which 1306 publications were matched to 1786 female and male doctors reported on the websites of the 44 locations of university gynecology departments in Germany. In addition, the volume of publications issued between 2014 and 2022 was compared for Germany, France, the United Kingdom, and the United States. In Germany, the volume of publications in Gynecology was additionally compared with the publication outputs of the specialties Urology and Trauma Surgery. Results: Since 2014, the increase in the numbers of publications in the field of Gynecology in Germany was lower (225%) than that of the countries with which it was compared (238%/252%/260% for F/UK/USA). When Gynecology was compared with other medical specialties in Germany, the number of publications in Urology were found to have increased at a lower rate (196%) while the number of publications in the field of Trauma Surgery increased by more (286%) than that of Gynecology. At the start of 2023, the percentage of women who were working as doctors at the lowest hierarchical level (junior doctor) was 81%. The publication output per capita of female doctors working at lower levels in the medical hierarchy, i.e., working as junior doctors and senior physicians, was between 40% and 80% lower than that of male doctors working at the same level. However, female directors published as much as male directors did. In the lower hierarchy levels, men were up to 14% more likely to be without an academic title. Predictors for more extensive publication activities by young female and male doctors include the extent and quality of publications by doctors in senior positions, the presence of a comprehensive cancer center or an institute for human genetics at the location where the young doctors were working, and joint publications with foreign authors. Conclusion: For the German Society of Gynecology and Obstetrics, the results suggest a number of approaches to promote young researchers. The support provided to young female doctors is especially important as this should help to retain them as junior researchers over the long term.

Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Prevalence of genital Mycoplasma in pregnancies with shortened cervix.

OBJECTIVE: To determine whether colonisation with genital Mycoplasma species (spp.) in patients presenting with a shortened cervix before 34th week of pregnancy is associated with preterm birth. METHODS: The collection of this retrospective study consisted of 100 pregnant women who presented to a German Tertiary Perinatal Center between 2017 and 2020 due to a shortened cervix defined as a cervical length of 25 mm or shorter measured by transvaginal ultrasound before 34 weeks of gestation. At the time of admission, gestational age ranged from 18 + 4 to 33 + 3 weeks (+ days) of pregnancy. All patients underwent urine polymerase chain reaction (PCR) for genital Mycoplasma [Ureaplasma (U.) urealyticum, U. parvum, M. hominis or M. genitalium]. Patients who were tested positive underwent a therapy with macrolides (azithromycin or clarithromycin). RESULTS: 37% of the patients were positive for Ureaplasma spp., whereas 5% (5 patients) were Mycoplasma spp.-positive. All the latter were simultaneously colonised with Ureaplasma spp. Ureaplasma-positive patients were significantly younger than those who were tested negative. Median maternal age at examination was 30 years (a) versus 31a (p = 0.04). There was no difference between Ureaplasma-positive and -negative patients regarding median maternal body mass index (BMI) (kg/m2) (23.4 versus 22.3, p = 0.41), cervical length at admission (mm) (15 versus 17, p = 0.17), gestational age at examination (days, d) (198 versus 197, p = 0.97) or gestational age at birth (d) (250 versus 257, p = 0.33), respectively. Comparing U. parvum-positive and U. urealyticum-positive patients, there was some weak indication that U. parvum-positive patients may get a shortening of the cervix earlier in pregnancy, as the median gestational age at examination was 196d versus 215d (p = 0.06). Regarding Mycoplasma-positive and -negative patients, there was no difference in all examined parameters. CONCLUSIONS: Overall, one-third of all women in our study with a shortened cervix before 34th week of pregnancy were colonised with genital Mycoplasma spp. We were able to show that pregnant women, who were treated with antibiotics when tested positive for genital Mycoplasma, gave birth at the same gestational age as patients with a shortened cervix without detected Mycoplasma. This raises the question of whether routine testing and early antibiotic treatment should be established in prenatal care.

Cervical ectopic pregnancy - the first case of live birth and uterus-conserving management.

A 37-old III gravida II para with two previous cesarean sections (CS) presented in 7 + 3 weeks of pregnancy with cervical ectopic pregnancy (CEP). At 12th week of pregnancy, a cerclage was performed to avoid cervical distention by the expanding placenta. Due to missing experience in CEP management and to avoid emergency operation, we recommended CS in 30th week of pregnancy due to unspecific pain of the patient. Vaginal bleeding never occured.After transverse laparotomy, the urinary bladder was sharply dissected from the anterior uterine and cervical wall. The baby was delivered by transverse cervicotomy caudally of the placenta. The placenta was left in situ. The patient then got prophylactic embolization of the uterine arteries to prevent further severe hemorrhage. 48 h later, ultrasound showed a floating, avascular placenta within a poor echogenic fluid-filled cervical space as well as macrohematuria. After re-laparotomy and cervicotomy at the same day, the placenta was completely and easily evacuated. A bladder injury was recognized and closed. We performed a cervical internal os plasty by inverting the cervical lips and suturing their distal ends on the proximal cervical tissue, resulting in complete bleeding cessation. Although, the patient got 8 erythrocyte concentrates at all, she was always in a stable condition without hemorrhagic shock.This case demonstrates for the first time a live-birth with uterus-conserving management in CEP.

Effect of QT interval-prolonging drugs taken in pregnancy on the neonatal QT interval.

Introduction: Acquired QT interval prolongations due to drug side effects can result in detrimental arrhythmia. Maternal use of placenta-permeable drugs may lead to fetal exposure, thus leading to an increased risk of neonatal QT prolongation and arrhythmia. Objectives: This study aimed to evaluate the influence of maternal QT-prolonging medication on the neonatal QT interval. Methods: In the prospective KUNO-Kids health study, an ongoing population-based birth cohort, we classified maternal medications according to the known risk of QT interval prolongation. Effects on the neonatal QT interval were tested by linear regression analyses, correcting for perinatal confounders (birth weight, gestational age, birth mode, and age at ECG recording). Subgroup analyses were performed for selective serotonin reuptake inhibitors, proton pump inhibitors, and antihistamine dimenhydrinate. Logistic regression analysis was performed using a QTc of 450 ms as the cut-off value. Results: A total of 2,550 pregnant women received a total of 3,990 medications, of which 315 were known to increase the risk of QT prolongation, resulting in 105 (4.1%) neonates exposed in the last month of pregnancy. Overall, the mean age of the neonates at ECG was 1.9 days and the mean QTc (Bazett) was 414 ms. Univariate (regression coefficient -2.62, p = 0.288) and multivariate (regression coefficient -3.55, p = 0.146) regression analyses showed no significant effect of fetal medication exposure on the neonatal QT interval, neither in the overall nor in the subgroup analysis. Logistic regression analysis showed no association of exposure to maternal medication with an increased risk of neonatal QT interval prolongation (OR (odds ratio) 0.34, p = 0.14). Conclusion: The currently used maternal medication results in a relevant number of fetuses exposed to QT interval-prolonging drugs. In our cohort, exposure was found to have no effect on the neonatal QT interval.

Therapeutic Plasma Exchange in Early-Onset Preeclampsia: A 7-Year Monocentric Experience.

Different therapeutic apheresis techniques have been clinically tested to delay preterm delivery in the case of eoPE (early-onset preeclampsia). Our study evaluated the feasibility of TPE (therapeutic plasma exchange) compared to standard-of-care treatment. Twenty patients treated with 95 TPE sessions were included in the final analysis and retrospectively matched with 21 patients with comparable placental dysfunction. Gestational age at admission was 23.75 ± 2.26 versus 27.57 ± 2.68 weeks of gestation (WoG) in the control group (p = < 0.001), mean sFlt-1/PlGF ratio was 1946.26 ± 2301.63 versus 2146.70 ± 3273.63 (p = 0.821) and mean sEng was 87.63 ± 108.2 ng/mL versus 114.48 ± 88.78 ng/mL (p = 0.445). Pregnancy was prolonged for 8.25 ± 5.97 days when TPE was started, compared to 3.14 ± 4.57 days (p = 0.004). The median sFlt-1/PlGF Ratio was 1430 before and 1153 after TPE (-18.02%). Median sEng fell from 55.96 ng/mL to 47.62 mg/mL (-27.73%). The fetal survival rate was higher in TPE-treated cases. NICU (Neonatal Intensive Center Unit) stay was in the median of 63 days in the TPE group versus 48 days in the standard-of-care group (p = 0.248). To date, this monocentric retrospective study, reports the largest experience with extracorporeal treatments in eoPE worldwide. TPE could improve pregnancy duration and reduce sFlt-1 and sEng in maternal serum without impairing neonatal outcomes.

Identification of altered miRNAs and their targets in placenta accreta.

Placenta accreta spectrum (PAS) is one of the major causes of maternal morbidity and mortality worldwide with increasing incidence. PAS refers to a group of pathological conditions ranging from the abnormal attachment of the placenta to the uterus wall to its perforation and, in extreme cases, invasion into surrounding organs. Among them, placenta accreta is characterized by a direct adhesion of the villi to the myometrium without invasion and remains the most common diagnosis of PAS. Here, we identify the potential regulatory miRNA and target networks contributing to placenta accreta development. Using small RNA-Seq followed by RT-PCR confirmation, altered miRNA expression, including that of members of placenta-specific miRNA clusters (e.g., C19MC and C14MC), was identified in placenta accreta samples compared to normal placental tissues. In situ hybridization (ISH) revealed expression of altered miRNAs mostly in trophoblast but also in endothelial cells and this profile was similar among all evaluated degrees of PAS. Kyoto encyclopedia of genes and genomes (KEGG) analyses showed enriched pathways dysregulated in PAS associated with cell cycle regulation, inflammation, and invasion. mRNAs of genes associated with cell cycle and inflammation were downregulated in PAS. At the protein level, NF-κB was upregulated while PTEN was downregulated in placenta accreta tissue. The identified miRNAs and their targets are associated with signaling pathways relevant to controlling trophoblast function. Therefore, this study provides miRNA:mRNA associations that could be useful for understanding PAS onset and progression.

Development of Mothers' Health Literacy: Findings From the KUNO-Kids Study.

BACKGROUND AND OBJECTIVE: The aim of this study was to analyze the longitudinal development of health literacy (HL) in a large cohort of new mothers in Germany and to investigate which determinants are associated with the initial HL level and with change over time. METHODS: Longitudinal data from 1,363 mothers participating with their child in the KUNO-Kids Health Study was used; data were collected at birth of the child (baseline), after 6 and 12 months, using interviews and self-report questionnaires. The HL of mothers was assessed with the health care scale of the European Health Literacy Survey Questionnaire, which has 16 items on accessing, understanding, appraising, and applying health information in the health care setting. Latent growth curve models were used to analyze average trajectories and predictors of HL in the total sample and in the subgroup of first-time mothers. KEY RESULTS: HL values increased from baseline (M = 35.46, standard deviation [SD] = 7.34) over 6 months (M = 37.31, SD = 7.31) to 12 months (M = 38.01, SD = 7.41). The increase was statistically significant in the total sample (1.188, standard error [SE] = 0.087, p < .001) and in the subgroup of first-time mothers (1.357, SE = 0.113, p <. 001), with a steeper trajectory for mothers with lower HL at baseline. Several personal and situational variables were associated with HL at baseline (e.g., education, child health) and with its development (e.g., number of children). CONCLUSION: Overall, new mothers became slightly more health literate during their child's first year of life. However, some groups of mothers could benefit from support in developing HL skills even before childbirth. [HLRP: Health Literacy Research and Practice. 2023;7(1):e39-e51.] Plain Language Summary: We investigated how health literacy (that is the ability to find, understand, and apply health information) develops in new mothers in Germany. Mothers told us that this ability slightly improved during the child's first year of life. Some mothers still have difficulties in dealing with health information; these mothers should be supported even before childbirth.

[Parental intention to vaccinate their children against COVID-19]. / COVID-19-Impfintention von Eltern bezogen auf ihre Kinder.

BACKGROUND: With the start of the vaccination campaign, a new phase in the management of the coronavirus pandemic has begun. Approval and recommendation for COVID-19 vaccination of children followed gradually; to date (4 October 2022), vaccination for children under five years of age has not been approved in Germany. AIM OF THE STUDY: The aim was to investigate how parents' intention to vaccinate their children against COVID-19 developed from May 2020 to February 2021 (from the first to the second wave of the COVID-19 pandemic) and to analyse the determinants of the intention to vaccinate. METHODS: In May 2020, 612 families participating with their children aged 1.5-6 years in the KUNO Kids Health Study completed an online survey (participation rate 51%), and 507 completed the second survey in February 2021. Determinants of the intention to vaccinate were analysed for both time points using univariable and multivariable logistic regression models. RESULTS: While 51% of parents reported wanting their children vaccinated against COVID-19 in May 2020, this proportion decreased to 41% by February 2021. At least at one of the two time points, health literacy and perceived competence regarding protective measures against the virus were significantly positively associated with higher vaccination intentions, while belonging to a risk group and the perception that the political measures were exaggerated were associated with lower vaccination intentions. DISCUSSION: Parents' intention to have their children vaccinated against COVID-19 was low and decreased further from the first to the second wave of the coronavirus pandemic. Attitudinal and competence-related determinants were important at both time points and could be targeted in a future vaccination campaign addressing parents of younger children.

The Impact of Increased Maternal sFlt-1/PlGF Ratio on Motor Outcome of Preterm Infants.

Background: The sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio serves as a clinical biomarker to predict the hypertensive, placenta-derived pregnancy disorder pre-eclampsia which is often associated with placental dysfunction and fetal growth restriction. Additionally elevated levels also indicate an increased risk for prematurity. However, its predictive value for subsequent neonatal neurological outcome has not been studied. Objective: This study aimed to evaluate the correlation of maternal sFlt-1/PlGF ratio with early motor outcome of preterm infants. Design/Methods: 88 preterm infants (gestational age ≤ 34 + 0) born between February 2017 and August 2020 at the Department of Obstetrics and Gynecology, University Hospital Essen in Germany, were included, when the following variables were available: maternal sFlt-1/PlGF levels at parturition and general movement assessment of the infant at the corrected age of 3 to 5 months. The infants were stratified into high and low ratio groups according to maternal sFlt-1/PlGF cut-off values of 85. To investigate the early motor repertoire and quality of spontaneous movements of the infant, the Motor Optimality Score (MOS-R) based on antigravity movements and posture patterns, was applied. In the given age, special attention was paid to the presence of fidgety movements. Linear regressions were run to test differences in infants motor repertoire according to the maternal sFlt-1/PIGF ratio. Results: Linear regression analysis showed that the sFlt-1/PlGF ratio does not predict the MOS-R score (ß=≤0.001; p=0.282). However, children with birth weight below the 10th percentile scored significantly lower (mean 20.7 vs 22.7; p=0.035). These children were 91% in the group with an increased ratio, which in turn is a known predictor of low birth weight (ß= -0.315; p <0.001). In the group with a high sFlt-1/PLGF ratio above 85 the mothers of female infants had a lower average sFlt-1/PlGF ratio compared to a male infant (median: 438 in female vs. 603 in male infant, p=0.145). Conclusions: In our cohort, especially low birth weight, which correlated with an elevated sFlt-1/PlGF ratio, had a negative effect on the outcome in the MOS-R. A direct correlation between an increased ratio and a worse motor outcome was not demonstrated.

Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice.

With the gaining prevalence of obesity, related risks during pregnancy are rising. Inflammation and oxidative stress are considered key mechanisms arising in white adipose tissue (WAT) sparking obesity-associated complications and diseases. The established anti-diabetic drug metformin reduces both on a systemic level, but only little is known about such effects on WAT. Because inhibiting these mechanisms in WAT might prevent obesity-related adverse effects, we investigated metformin treatment during pregnancy using a mouse model of diet-induced maternal obesity. After mating, obese mice were randomised to metformin administration. On gestational day G15.5, phenotypic data were collected and perigonadal WAT (pgWAT) morphology and proteome were examined. Metformin treatment reduced weight gain and visceral fat accumulation. We detected downregulation of perilipin-1 as a correlate and observed indications of recovering respiratory capacity and adipocyte metabolism under metformin treatment. By regulating four newly discovered potential adipokines (alpha-1 antitrypsin, Apoa4, Lrg1 and Selenbp1), metformin could mediate anti-diabetic, anti-inflammatory and oxidative stress-modulating effects on local and systemic levels. Our study provides an insight into obesity-specific proteome alterations and shows novel modulating effects of metformin in pgWAT of obese dams. Accordingly, metformin therapy appears suitable to prevent some of obesity's key mechanisms in WAT.

Families' Worries during the First and Second COVID-19 Wave in Germany: Longitudinal Study in Two Population-Based Cohorts.

This study aimed to compare worries related to the Coronavirus disease 2019 (COVID-19) in families with young children in two regions in Germany differently affected by the pandemic (Regensburg in Southeast Germany, Leipzig in Eastern Germany) during the first and the second waves of the COVID-19 pandemic. 720 parents participating in the KUNO Kids health study in Regensburg (n = 507) or the LIFE Child study in Leipzig (n = 213) answered questions regarding COVID-19-related worries and trust in anti-pandemic policy measures during the first wave (spring 2020) and during the second wave (winter 2020/2021) of the pandemic. Ordinal mixed-effects models were performed to assess differences depending on region and time, adjusting for education and migration background. Participants worried most about the general economic situation and their family and least about their own health or financial situation. Worries about oneself, family, friends, hometown, and country were stronger during the second than during the first wave. In regional comparisons, worries about family, friends, and hometown increased more pronouncedly from wave 1 to wave 2 in Leipzig (OR ranging from 2.67 (95% CI 1.71−4.19) to 3.01 (95% CI 1.93−4.71), all p < 0.001) than in Regensburg (OR ranging from to 1.38 (95% CI 1.08−1.78) to 1.72 (95% CI 1.33−2.21), all p < 0.05), running parallel with the increase in SARS-CoV-2 infections. Trust in anti-pandemic policy measures, in contrast, decreased significantly between wave 1 and wave 2, with a stronger decrease in Regensburg (OR = 0.30 (95% CI 0.22−0.39), p < 0.001) than in Leipzig (OR = 0.91 (95% CI 0.59−1.41), n.s.). The degree of families' COVID-19-related worries differs by region and time, which might be related to differences in infection rates and public interest. Regional differences should be taken into account when developing communication strategies and policy measures during the COVID-19 pandemic.

Soluble PD-L1 and B7-H4 serum levels during the course of physiological pregnancy.

PROBLEM: The aim of this study was to evaluate the soluble programmed death-ligand (sPD-L1) and soluble B7-H4 (sB7-H4) serum concentration levels longitudinal throughout the three trimesters of uncomplicated pregnancies. METHOD OF THE STUDY: sPD-L1 and sB7-H4 levels were determined with enzyme-linked immunosorbent assay (ELISA). The patients (n = 26) were divided into three groups according to the pregnancy trimester. Among 26 women involved in the study 14 had longitudinal sB7-H4 and sPD-L1 measurements in each trimester of pregnancy. RESULTS: During the course of pregnancy, the sB7-H4 blood serum levels were significant higher in second trimester than in first and third trimester, whereas sPD-L1 levels increased significantly over the course of pregnancy. CONCLUSION: The highest serum levels of sPD-L1 in the third trimester suggest increasing suppression of maternal immunity throughout pregnancy, whereas elevated sB7-H4 concentration levels in second trimester suggests different profile of T-cell regulation in physiological pregnancy.

Latency duration of preterm premature rupture of membranes and neonatal outcome: a retrospective single-center experience.

In preterm premature rupture of membranes (PPROM), a decision between early delivery with prematurity complications and pregnancy prolongation bearing the risk of chorioamnionitis has to be made. To define disadvantages of delayed prolongation, latency duration of PPROM in expectantly managed pregnancies was investigated. We included those PPROMs > 48 h leading to preterm birth prior 37 weeks' gestation and retrospectively analyzed 84 preterm infants fulfilling these criteria. The association between latency duration/appearance of PPROM and respiratory outcome (primary outcomes) and neurological outcome (secondary outcomes) was investigated. The study showed that latency duration of PPROM is not associated with clinical or histological chorioamnionitis (p = 0.275; p = 0.332). As the numerous clinical parameters show multicollinearity between each other, we performed a multiple regression analysis to consider this fact. Respiratory distress syndrome is significantly associated with gestational age at PPROM (p < 0.001), and surfactant application is significantly associated with PPROM duration (p = 0.014). The other respiratory parameters including steroids and diuretics therapy, bronchopulmonary dysplasia, and the neurological parameters (intraventricular hemorrhage, Bayley II testing at a corrected age of 24 months) were not significantly associated with PPROM duration or gestational age at PPROM diagnosis.Conclusion: Latency duration of PPROM was not associated with adverse neonatal outcome in expectantly and carefully managed pregnancies, but respiratory distress syndrome was pronounced. The observed effect of pronounced respiratory distress syndrome can be treated with surfactant preparations and was not followed by increased rate of bronchopulmonary dysplasia. What is Known: • In case of preterm premature rupture of membranes, a decision between pregnancy prolongation with the risk of chorioamnionitis and early delivery with prematurity complications has to be made. • Chorioamnionitis is a dangerous situation for the pregnant woman and the fetus. • Impaired neurodevelopmental outcome is strongly correlated with pronounced prematurity due to the increased rate of serious complications. What is New: • Respiratory distress syndrome is significantly associated with gestational age at PPROM, and surfactant application is significantly associated with PPROM duration. • Latency duration of PPROM is not associated with adverse respiratory neonatal outcome (therapy with continuous positive airway pressure, therapy with diuretics and/or steroids, bronchopulmonary dysplasia) in expectantly and carefully managed pregnancies. • Intraventricular hemorrhage and Bayley II testing at a corrected age of 24 months are not associated with latency duration of PPROM when pregnancies are carefully observed.

Food allergy in infants assessed in two German birth cohorts 10 years after the EuroPrevall Study.

BACKGROUND: The prevalence of food allergies (FA) in children increased rapidly at the turn of the century. The EuroPrevall study identified Germany as a country with very high prevalence of FA at that time. Using two large German birth cohorts, we provide an update of the status quo 10 years later. METHODS: KUNO Kids and Ulm SPATZ Health studies are two ongoing prospective birth cohorts. Information on FA was obtained by questionnaires at birth and after 6, 12, and 24 months. Univariable and multivariable logistic regression analyses were performed to investigate risk factors during pregnancy, birth, and early childhood. RESULTS: In 1139 and 1006 children from KUNO Kids and SPATZ, the point prevalence of parent-reported FA symptoms at the ages of 1 and 2 years was 13.2% (95% CI: 11.2-15.2) and 13.9% (95% CI: 11.5-17.2) in KUNO Kids. Doctor's diagnosed FA at 1 and 2 years was 2.4% (95% CI: 1.6-3.4) and 2.7% (95% CI: 1.2-4.3) in KUNO Kids and 2.3% (95% CI: 1.3-3.6) and 3% (95% CI: 2.0-4.5) in SPATZ. Cow's milk and citrus fruits were most frequently suspected by parents to cause FA symptoms. Atopy in the child was associated with a higher frequency of FA at any time, whereas atopy in first-degree relatives was only associated with FA at year 1. Smoke exposure during pregnancy was a risk for FA at age 2. CONCLUSION: The prevalence of food allergy seems to have plateaued in the last 10 years in Germany. FA is often suspected by parents but only rarely diagnosed by oral food challenge. Risk factor analysis may help to establish personalized health approaches.

The New Old CD8+ T Cells in the Immune Paradox of Pregnancy.

CD8+ T cells are the most frequent T cell population in the immune cell compartment at the feto-maternal interface. Due to their cytotoxic potential, the presence of CD8+ T cells in the immune privileged pregnant uterus has raised considerable interest. Here, we review our current understanding of CD8+ T cell biology in the uterus of pregnant women and discuss this knowledge in relation to a recently published immune cell Atlas of human decidua. We describe how the expansion of CD8+ T cells with an effector memory phenotype often presenting markers of exhaustion is critical for a successful pregnancy, and host defense towards pathogens. Moreover, we review new evidence on the presence of long-lasting immunological memory to former pregnancies and discuss its impact on prospective pregnancy outcomes. The formation of fetal-specific memory CD8+ T cell subests in the uterus, in particular of tissue resident, and stem cell memory cells requires further investigation, but promises interesting results to come. Advancing the knowledge of CD8+ T cell biology in the pregnant uterus will be pivotal for understanding not only tissue-specific immune tolerance but also the etiology of complications during pregnancy, thus enabling preventive or therapeutic interventions in the future.

Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?

BACKGROUND: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. METHODS/RESULTS: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. CONCLUSION: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.

MFSD2A-associated primary microcephaly - Expanding the clinical and mutational spectrum of this ultra-rare disease.

MFSD2A, a member of the major facilitator superfamily (MFS), is a transmembrane transporter responsible for the uptake of specific essential fatty acids through the blood-brain barrier (BBB) to the brain. The transporter is crucial for early embryonic brain development and a major factor in the formation and maintenance of the BBB. Mfsd2a-knockout mice show a leakage of the BBB in early embryonic stages and develop a phenotype characterized by microcephaly, cognitive impairment, and anxiety. So far, homozygous or compound heterozygous MFSD2A mutations in humans have only been reported in 13 different families with a total of 28 affected individuals. The phenotypical spectrum of patients with MFSD2A variants is rather broad but all patients present with microcephaly and severe intellectual disability, absent or limited speech, and walking difficulties. Severely affected patients develop seizures and show brain malformations and have, above all, a profound developmental delay hardly reaching any developmental motor milestones. Here, we report on two unrelated individuals with novel homozygous variants in the MFSD2A gene, presenting with severe primary microcephaly, brain malformations, profound developmental delay, and epilepsy, including hypsarrhythmia. Our findings extend the mutational spectrum of the bi-allelic MFSD2A variants causing autosomal recessive primary microcephaly type 15 and broaden the phenotypic spectrum associated with these pathogenic variants emphasizing the role of MFSD2A in early brain development.

Circulating Maternal sFLT1 (Soluble fms-Like Tyrosine Kinase-1) Is Sufficient to Impair Spiral Arterial Remodeling in a Preeclampsia Mouse Model.

[Figure: see text].