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ZUSAMMENFASSUNG Einleitung Das Geburtsgewicht ist u. a. durch die mütterliche Größe beeinflusst. Die SGA-Rate Neugeborener relativ kleiner und leichter Mütter ( 177 cm,>79 kg) werden überschätzt. Die LGA-Rate Neugeborener relativ kleiner und leichter Mütter und die SGA-Rate relativ großer und schwerer Mütter wird unterschätzt. Individualisierte Geburtsgewichtsperzentilen (IGGP) basierend auf 18 Müttergruppen (6 Körperhöhengruppen mit jeweils 3 Gewichtsgruppen), Geschlecht und Schwangerschaftswochen wurden publiziert. Das Ziel dieser Studie ist die Validierung der IGGP durch Evaluierung der SGA-, AGA- und LGA-Raten an einem unabhängigen Perinataldatensatz. Methoden Die Validierungsstudie vergleicht IGGP (1995 bis 2000, n=2,2 Mio Einlingsschwangerschaften) mit Perzentilwerten aus zwei gesamtdeutschen Kohorten (i: 1995 bis 2000; n=2,3 Mio und ii: 2007 bis 2011, n=3,2 Mio) anhand von Neugeborenen der niedersächsischen Perinatalerhebung (n=0,56 Mio Einlingsschwangerschaften von 2001 bis 2009). SGA-, AGA- und LGA-Raten werden berechnet mit dem Statistikprogramm R. Ergebnisse Die Perzentilwerte der Gesamtpopulation 1995–2000 bzw. 2007–2011 ergaben SGA-Raten bei relativ kleinen und leichten Müttern von 21,1 bis 21,6% und LGA-Raten von 2,0 bis 3,1%. Bei relativ großen und schweren Müttern waren die SGA-Raten von 3,3 bis 3,5% und die LGA-Raten von 26,6 bis 27,1%. Die IGGP erreichten SGA-Raten von 9,0% und LGA-Raten von 11,4 bis 11,6% bei relativ kleinen und leichten Müttern sowie SGA- und LGA-Raten von annähernd 10% bei relativ großen und schweren Müttern. Diskussion IGGP berücksichtigen das Wachstumspotential von Feten entsprechend der mütterlichen Größe und erreichen die erwarteten SGA- und LGA-Raten von 10%. Die Berücksichtigung des individuellen Wachstumspotential vermeidet ein Unter- und Überschätzen von SGA- und LGA-Raten. IT-unterstützte Analysen des Geburtsgewichtes mit IGGP vereinfachen die Anwendung.

To examine characteristics and outcomes of cesarean delivery (CD) in women with a history of vertical hysterotomy.This is a comparative study that retrospectively queried the National Inpatient Sample from October 2016 to December 2018. Pregnancy characteristics and surgical outcomes of CD among 18 575 women with prior vertical uterine incision were compared to 1 072 949 women with prior low-transverse incision, assessed by multivariable generalized estimating equation model and propensity score weighting.In a multivariable analysis, women who had prior vertical uterine incision were more likely to have placenta percreta (odds ratio [OR] 3.41, 95% confidence interval [CI] 1.87-6.20), pre-labor uterine rupture (OR 2.70, 95% CI 1.52-4.80), in-labor uterine rupture (OR 2.33, 95% CI 1.55-3.51), and extreme preterm delivery28 weeks (OR 17.8, 95% CI 15.2-20.7) in the current pregnancy, compared to those who had prior low-transverse uterine incision. In a weighted model, prior vertical hysterotomy was associated with increased surgical morbidity in current CD compared to prior low-transverse hysterotomy (10.6% vs. 4.8%, OR 2.02, 95% CI 1.81-2.26), including hemorrhage (OR 1.99, 95% CI 1.74-2.27) and hysterectomy (OR 3.67, 95% CI 2.97-4.53).Prior vertical uterine incision at CD was associated with increased risk of placenta percreta, uterine rupture, particularly before labor, and adverse outcomes in the subsequent pregnancy.

Purpose While the optimal delivery method of twin pregnancies is debated, the rate of cesarean deliveries is increasing. This retrospective study evaluates delivery methods and neonatal outcome of twin pregnancies during two time periods and aims to identify predictive factors for the delivery outcome. Methods 553 twin pregnancies were identified in the institutional database of the University Women’s Hospital Freiburg, Germany. 230 and 323 deliveries occurred in period I (2009–2014) and period II (2015–2021), respectively. Cesarean births due to non-vertex position of the first fetus were excluded. In period II, the management of twin pregnancies was reviewed; adjusted and systematic training with standardized procedures was implemented. Results Period II showed significantly lower rates of planned cesarean deliveries (44.0% vs. 63.5%, p p = 0.02). Independent risk factors for primary cesarean delivery were period I, maternal age > 40 years, nulliparity, a history with a previous cesarean, gestational age 20%). Predictive factors for successful vaginal delivery were previous vaginal delivery gestational age between 34 and 36 weeks and vertex/vertex presentation of the fetuses. The neonatal outcomes of period I and II were not significantly different, but planned cesareans in general were associated with increased admission rates to the neonatal intensive care units. Inter-twin interval had no significant impact on neonatal outcome. Conclusion Structured regular training of obstetrical procedures may significantly reduce high cesarean rates and increase the benefit–risk ratio of vaginal deliveries.

Introduction The most common sensorineural disorder in humans is hearing impairment and approximately 60% of prelingual hearing disorders are genetic. Especially parents with a congenital deaf child want to know as early as possible whether their second born child has the same genetic defect or not. The aim of this study is to demonstrate that postnatal genetic umbilical cord analysis is both the earliest detection possibility and sufficient. Methods We included first born children with severe hearing impairment that underwent cochlear implantation. All included patients were analyzed genetically and exhibited mutations of either DFNB1 loci or SLC26A4 gene. Additionally, the umbilical cord of the sibling underwent genetic analysis to detect hereditary genetic mutations as early as possible. Results 49 newborn children out of 22 families were included in this study. Genetic analysis revealed clinical relevant mutations in all first born children and in four siblings via umbilical cord analysis. All patients who have been diagnosed with a relevant genetic mutation that caused severe hearing impairment underwent hearing rehabilitation via cochlear implant surgery. Conclusion This study demonstrates the sufficient and early as possible detection of known genetically hearing disorders via umbilical cord analysis. In case of a known familial genetic hearing disorder, it is advisable to analyze newborn siblings for the corresponding genetic defect as soon as possible, to be able to plan and initiate clinical care for the patient as early as possible. It is also extremely important for the parents to obtain clear information about the auditory status of the newborn.

Purpose While the optimal delivery method of twin pregnancies is heavily debated, the rate of cesarean deliveries is increasing. This retrospective study evaluates delivery methods and neonatal outcome of twin pregnancies during two time-periods and aims to identify predictive factors for the delivery outcome. Methods 553 twin pregnancies were identified in the institutional database of the University Women’s Hospital Freiburg, Germany. 230 and 323 deliveries occurred in period I (2009–2014) and period II (2015–2021) respectively. Cesarean births due to non-vertex position of the first fetus were excluded. In period II, the management of twin pregnancies was reviewed and adjusted and systematic training and standardized procedures were implemented. Results Period II showed significantly lower rates of planned cesarean deliveries (44.0% vs. 63.5%, p 40 years, nullipara, previous cesarean birth (HR:11.3, p

BACKGROUND: Pregnancy is a good time to motivate women to implement health-promoting behaviors in their everyday lives. There is no official German-language guideline for the counseling of pregnant women by professionals involved in their care. The goal of this review is, therefore, to discuss the links between exercise and gestational diabetes mellitus (GDM), low birth weight, and prematurity. METHODS: This review is based on pertinent articles retrieved by a systematic search of PubMed and the Web of Science. The articles included in the evaluation were reports of randomized controlled trials (RCTs) and meta-analyses of RCTs of exercise interventions in pregnant women that were published from 1 January 2011 to 15 November 2021. RESULTS: A structured exercise program during pregnancy can lower the risk of gestational diabetes by as much as 49%. A 25% risk reduction for GDM was achieved with 140 minutes of exercise per week. The mean birth weight was not affected but the rate of excessively heavy newborns was lowered by 32–59% in the normal-weight subgroup. This effect was not seen in the overweight subgroup, possibly because of poorer compliance. Exercise did not elevate the risk of preterm delivery. CONCLUSION: Regular exercise during pregnancy lessens gestationally induced weight gain and lowers the risk of excessive weight gain, as well as the risk of GDM, without elevating the risk of preterm delivery.

Birth weight is influenced by maternal anthropometry. The SGA-rate of newborns of short and light mothers (158 cm,53 kg) and the LGA-rate of tall and heavy mothers (177 cm,79 kg) are overestimated. The LGA-rate of newborns of shorter mothers and the SGA-rate of taller mothers are underestimated. Individualized birth weight percentiles (IBWP) based on 18 maternal groups (6 groups of height combined with 3 groups of weight), sex and weeks of gestation have been published. The aim of this study is to validate IBWP by evaluating SGA-, AGA-, and LGA-rates using perinatal data.The validation study compares IBWP (1995 to 2000, n=2.2 million singletons) with percentile values from two German cohorts (i: 1995 to 2000; n=2.3 million and ii: 2007 to 2011, n=3.2 million singletons) using newborns from the Lower Saxony Perinatal Survey (n=0.56 million singleton newborns, 2001 to 2009). SGA-, AGA-, and LGA-rates were calculated using R statistical analysis.Common percentile charts based on the total population 1995-2000 and 2007-2011 yielded SGA-rates among shorter mothers of 21.1 to 21.6% and LGA-rates of 2.0 to 3.1%. In taller mothers, SGA-rates were 3.3 to 3.5% and LGA-rates were 26.6 to 27.1%. IBWP achieved SGA-rates of 9.0% and LGA-rates of 11.4 to 11.6% in shorter mothers and SGA- and LGA-rates of 10% in taller mothers.IBWP consider the maternal size for estimation of the fetal growth potential and achieve expected SGA- and LGA-rates of 10%. Consideration of individual growth potential avoids underestimation and overestimation of SGA- and LGA-rates. It aided analyses of birth weight with IBWP simplify the assessment of the nutritional status.Das Geburtsgewicht ist u. a. durch die mütterliche Größe beeinflusst. Die SGA-Rate Neugeborener relativ kleiner und leichter Mütter (158 cm,53 kg) und die LGA-Rate relativ großer und schwerer Mütter (+ 177 cm,79 kg) werden überschätzt. Die LGA-Rate Neugeborener relativ kleiner und leichter Mütter und die SGA-Rate relativ großer und schwerer Mütter wird unterschätzt. Individualisierte Geburtsgewichtsperzentilen (IGGP) basierend auf 18 Müttergruppen (6 Körperhöhengruppen mit jeweils 3 Gewichtsgruppen), Geschlecht und Schwangerschaftswochen wurden publiziert. Das Ziel dieser Studie ist die Validierung der IGGP durch Evaluierung der SGA-, AGA- und LGA-Raten an einem unabhängigen Perinataldatensatz.Die Validierungsstudie vergleicht IGGP (1995 bis 2000, n=2,2 Mio Einlingsschwangerschaften) mit Perzentilwerten aus zwei gesamtdeutschen Kohorten (i: 1995 bis 2000; n=2,3 Mio und ii: 2007 bis 2011, n=3,2 Mio) anhand von Neugeborenen der niedersächsischen Perinatalerhebung (n=0,56 Mio Einlingsschwangerschaften von 2001 bis 2009). SGA-, AGA- und LGA-Raten werden berechnet mit dem Statistikprogramm R.Die Perzentilwerte der Gesamtpopulation 1995–2000 bzw. 2007–2011 ergaben SGA-Raten bei relativ kleinen und leichten Müttern von 21,1 bis 21,6% und LGA-Raten von 2,0 bis 3,1%. Bei relativ großen und schweren Müttern waren die SGA-Raten von 3,3 bis 3,5% und die LGA-Raten von 26,6 bis 27,1%. Die IGGP erreichten SGA-Raten von 9,0% und LGA-Raten von 11,4 bis 11,6% bei relativ kleinen und leichten Müttern sowie SGA- und LGA-Raten von annähernd 10% bei relativ großen und schweren Müttern.IGGP berücksichtigen das Wachstumspotential von Feten entsprechend der mütterlichen Größe und erreichen die erwarteten SGA- und LGA-Raten von 10%. Die Berücksichtigung des individuellen Wachstumspotential vermeidet ein Unter- und Überschätzen von SGA- und LGA-Raten. IT-unterstützte Analysen des Geburtsgewichtes mit IGGP vereinfachen die Anwendung.

Das subgaleale Hamatom (SGH) ist eine seltene Geburtskomplikation des Neugeborenen und kann aufgrund des erheblichen Blutverlustes in den subgalealen Raum zu einem hamorrhagischen Schock fuhren. Wir berichten von zwei Neugeborenen, die ein subgaleales Hamatom mit schwerem hamorrhagischem Schock und Enzephalopathie entwickelten. Im ersten Fall eines reifen weiblichen Neugeborenen wurde die Entstehung des subgalealen Hamatoms durch eine Neugeboreneninfektion und die Geburt mittels Vakuumextraktion begunstigt. Der zweite Fall eines mannlichen Fruhgeborenen wurde durch eine schwierige Kindsentwicklung mittels sekundarer Sectio caesarea kompliziert. Neben der raschen Behandlung des Schocks ist vor allem die Therapie der Gerinnungsstorung essentiell. Beide Falle verdeutlichen, dass das subgaleale Hamatom ein neonatologischer Notfall ist. Subgaleal hematoma (SGH) is a rare complication in neonates that may lead to hemorrhagic shock due to significant blood loss into the subgaleal space. We report of two neonates who developed subgaleal hematoma with severe hemorrhagic shock and encephalopathy. In the first case of a mature female neonate, the development of the subgaleal hematoma was promoted by early-onset sepsis and delivery by vacuum extraction. The second case, of a male preterm neonate, was a complicated fetal development followed by secondary cesarean section. Both cases highlight that a subgaleal hematoma is a severe neonatal emergency. In addition to prompt treatment of the shock, therapy of the coagulopathy is essential.

Purpose Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis and meningitis, in infants 30% of LOD. The study revealed that 59% of mothers of EOD cases had not received antenatal screening, whilst GBS was detected in 48.5% of screened cases. Meningitis was associated with an adverse outcome in LOD cases, while prematurity and the presence of cardiocirculatory symptoms were associated with an adverse outcome in EOD cases. Capsular-polysaccharide type III was the most frequent in both EOD and LOD cases with regional differences in the clonal complex distribution. Conclusions Standardizing recommendations related to neonatal GBS disease and increasing compliance might improve clinical care and the prevention of GBS EOD. But even full adherence to antenatal screening would miss a relevant number of EOD cases, thus, the most promising prophylactic approach against GBS EOD and LOD would be a vaccine for maternal immunization.

Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis and meningitis, in infants 3 months of age and of mortality among neonates. This study, a major component of the European DEVANI project (Design of a Vaccine Against Neonatal Infections) describes clinical and important microbiological characteristics of neonatal GBS diseases. It quantifies the rate of antenatal screening and intrapartum antibiotic prophylaxis among cases and identifies risk factors associated with an adverse outcome.Clinical and microbiological data from 153 invasive neonatal cases (82 early-onset [EOD], 71 late-onset disease [LOD] cases) were collected in eight European countries from mid-2008 to end-2010.Respiratory distress was the most frequent clinical sign at onset of EOD, while meningitis is found in 30% of LOD. The study revealed that 59% of mothers of EOD cases had not received antenatal screening, whilst GBS was detected in 48.5% of screened cases. Meningitis was associated with an adverse outcome in LOD cases, while prematurity and the presence of cardiocirculatory symptoms were associated with an adverse outcome in EOD cases. Capsular-polysaccharide type III was the most frequent in both EOD and LOD cases with regional differences in the clonal complex distribution.Standardizing recommendations related to neonatal GBS disease and increasing compliance might improve clinical care and the prevention of GBS EOD. But even full adherence to antenatal screening would miss a relevant number of EOD cases, thus, the most promising prophylactic approach against GBS EOD and LOD would be a vaccine for maternal immunization.

Bei ca. 3 % der Schwangerschaften kommt es zu einem frühen vorzeitigen Blasensprung („preterm premature rupture of the membranes“, PPROM). Da bei PPROM mit hoher Wahrscheinlichkeit mit einer MIAC („microbial invasion of the amniotic cavity“) – bereits vorbestehend oder sekundär nach Blasensprung – zu rechnen ist, ist auch die Wahrscheinlichkeit für eine intraamniale Inflammation (IAI) signifikant erhöht. Eine IAI ist mit kurzer Latenz bis zur Geburt des Kindes und mit ungünstigen Verläufen mit kurz- und langfristig erhöhter Morbidität des Neugeborenen assoziiert, besonders bei Entwicklung eines FIRS („fetal inflammatory response syndrome“). Die Vorhersage einer IAI anhand mütterlicher Parameter ist nur schwer möglich. Die neu eingeführte Definition Triple I („infection, inflammation, or both“) fokussiert auf den Parameter maternale Körpertemperatur, der bei gesichertem Anstieg auf ≥ 38,0 °C und fehlendem Anhalt für eine andere Fieberursache sowie durch mindestens einen weiteren Parameter (fetale Tachykardie > 160 bpm („beats per minute“) für mindestens 10 min, maternale Leukozyten > 15.000/µl ohne Gabe von Kortikosteroiden, purulenter Fluor aus dem Muttermund) bestätigt werden soll. Die Bestätigung der Diagnose Triple I ist zuverlässig nur durch eine Plazentahistologie („histologically confirmed chorioamnionitis“, HCA) möglich. Eine Bestätigung durch Amniozentese (positive Gram-Färbung, Glukosekonzentration 30 Zellen/mm3, positive Bakterienkultur) dauert zu lange und ist unzuverlässig. Auch serielle CRP(C-reaktives Protein)-Bestimmungen ermöglichen keine zuverlässige Diagnose einer IAI. Studien zur Bestimmung von IL(Interleukin)-6 aus dem Zervikalkanal und dem hinteren Scheidengewölbe sind vielversprechende Verfahren, deren Validierung abgewartet werden muss.

BH3-mimetics inhibiting anti-apoptotic BCL-2 proteins represent a novel and promising class of antitumor drugs. While the BCL-2 inhibitor venetoclax is already approved by the Food and Drug Administration, BCL-XL and MCL-1 inhibitors are currently in early clinical trials. To predict side effects of therapeutic MCL-1 inhibition on the human hematopoietic system, we used RNA interference and the small molecule inhibitor S63845 on cord blood-derived CD34+ cells. Both approaches resulted in almost complete depletion of human hematopoietic stem and progenitor cells. As a consequence, maturation into the different hematopoietic lineages was severely restricted and CD34+ cells expressing MCL-1 shRNA showed a very limited engraftment potential upon xenotransplantation. In contrast, mature blood cells survived normally in the absence of MCL-1. Combined inhibition of MCL-1 and BCL-XL resulted in synergistic effects with relevant loss of colony-forming hematopoietic stem and progenitor cells already at inhibitor concentrations of 0.1 mM each, indicating “synthetic lethality” of the two BH3- mimetics in the hematopoietic system.

ObjectivesMeasurement of birth length and birth head circumference is part of the newborn assessment. Both measurements aid in distinguishing between proportionate and disproportionate small and large for gestational age newborns. It had been shown that birth weight is related to maternal height and weight. This study aims to analyze birth length and birth head circumference percentiles based on maternal stature.MethodsThis observational study analyzed birth length and birth head circumference percentiles of 2.3 million newborns stratified by maternal height and weight from the first obstetric assessment. Percentiles were calculated for sex and 22–43 gestational weeks for all infants. Eighteen subgroups based on six maternal height and three weight strata were defined and percentiles calculated from 32 to 42 gestational weeks using GAMLSS package for R.ResultsNewborns of mothers with height 177 cm, weight >79 kg). Small stature mothers were 1.7 years younger. Birth length differed by several centimeters for the same percentiles between groups of short and tall stature mothers, whereas birth head circumference differed up to 1.2 cm. The largest deviation of birth length was between the 97th percentiles. For male newborns born at term, birth length at the 97th percentile differed by 3.2 cm, at the 50th percentile by 2.7 cm and at the third percentile by 2.5 cm.ConclusionsBirth length and birth head circumference are related to maternal height and weight. To more completely assess newborns, the maternal size should be considered.

Based on 190,000 applications for asylum, Germany remains a top destination for refugees and asylum seekers in Europe. The updated recommendations are considered evidence-based and targeted guidelines for the diagnosis and prevention of infectious diseases in underage refugees and asylum seekers.The objective of these recommendations is to guide medical staff in the care of minor refugees, in particular to:1. assure early recognition and completion of incomplete vaccination status,2. diagnose and treat common infectious diseases,3. recognize and treat imported infectious diseases that are considered uncommon to the German healthcare system.The recommendations have been formally written to be published as AWMF S1 guidelines.This includes a representative expert panel appointed by several professional societies, and formal adoption of the recommendations by the board of directors of all societies concerned.Recommendations are given for the medical evaluation of minor refugees, including medical history and physical examination. A blood count as well as screening for tuberculosis and hepatitis B should be offered to all minor refugees. In addition, screening for other infectious diseases like hepatitis C, HIV or schistosomiasis should be considered depending on age and country of origin. Vaccinations are recommended based on both age and country of origin.As thousands of minor refugees continue to seek shelter in Germany every year, professional health care with adequate financial support needs to be established to ensure an appropriate medical treatment of this particularly vulnerable population.

Objectives Establishing immediate intravenous access to a newborn is challenging even for trained neonatologists in an emergency situation. Correct placement of umbilical catheter or an intraosseous needle needs consistent training. We evaluated the time required to correctly place an emergency umbilical button cannula (EUC) or an umbilical catheter (UC) using the standard intersection (S-EUC or S-UC, respectively) or lateral umbilical cord incision (L-EUC) by untrained medical personnel. Methods Single-center cross-over pilot-study using a model with fresh umbilical cords. Video-based teaching of medical students before probands performed all three techniques after assignment to one of three cycles with different sequence, using a single umbilical cord divided in three pieces for each proband. Results Mean time required to establish L-EUC was 89.3 s, for S-EUC 82.2 s and for S-UC 115.1 s. Both application routes using the EUC were significantly faster than the UC technique. There was no significant difference between both application routes using EUC (p=0.54). Conclusions Using an umbilical cannula is faster than an umbilical catheter, using a lateral incision of the umbilical vein is an appropriate alternative.

ImportanceAmniotic fluid embolism (AFE) is an uncommon pregnancy complication but is associated with high maternal mortality. Because of the rarity of AFE, associated risks factors and maternal outcomes have been relatively understudied.ObjectiveTo examine the clinical, pregnancy, and delivery characteristics and the maternal outcomes related to AFE in a recent period in the US.Design, Setting, and ParticipantsThis retrospective cohort study examined hospital deliveries from January 1, 2016, to December 31, 2019, from the Healthcare Cost and Utilization Project’s National Inpatient Sample.Main Outcomes and MeasuresThe primary outcome was clinical, pregnancy, and delivery characteristics of AFE, assessed with a multivariable binary logistic regression model. The coprimary outcome was failure to rescue, defined as maternal mortality after AFE. Associations with other severe maternal morbidity indicators and failure to rescue per clinical and pregnancy characteristics were also assessed.ResultsA total of 14 684 135 deliveries were examined, with AFE diagnosed in 880 women, corresponding to an incidence rate of 6.0 per 100 000 deliveries. The cohort-level median patient age was 29 years (IQR, 25-33 years). In a multivariable analysis, (1) patient factors of older age, Asian and Black race, Western US region, pregestational hypertension, asthma, illicit substance use, and grand multiparity; (2) pregnancy factors of placental accreta spectrum (PAS), placental abruption, uterine rupture, polyhydramnios, chorioamnionitis, preeclampsia, fetal growth restriction, and fetal demise; and (3) delivery factors of early gestational age, cervical ripening, cesarean delivery, operative delivery, and manual removal were associated with AFE. Among these characteristics, PAS had the largest association with AFE (adjusted odds ratio [aOR], 10.01; 95% CI, 7.03-14.24). When stratified by the PAS subtypes, more severe forms of PAS had a greater association with AFE (aOR for increta and percreta, 17.35; 95% CI, 10.21-28.48; and aOR for accreta, 7.62; 95% CI, 4.83-12.01). Patients who had AFE were more likely to have coagulopathy (aOR, 24.68; 95% CI, 19.38-31.44), cardiac arrest (aOR, 24.56; 95% CI, 17.84-33.81), and adult respiratory distress syndrome (aOR, 10.72; 95% CI, 8.09-14.20). The failure-to-rescue rate after AFE was 17.0% overall. However, the failure-to-rescue rate exceeded 30% when AFE co-occurred with other severe maternal morbidity indicators: 45.8% for AFE, cardiac arrest, and coagulopathy; 43.2% for AFE, shock, and cardiac rhythm conversion; and 38.6% for AFE, cardiac arrest, coagulopathy, and shock. The failure-to-rescue rate after AFE also exceeded 30% when AFE occurred in the setting of placental pathology: 42.9% for AFE and PAS and 31.3% for AFE and placental abruption.Conclusions and RelevanceThis contemporaneous, national-level analysis validated previously known risk factors for AFE and confirmed the dismal outcomes of pregnancy complicated by AFE. The association between PAS and AFE, which was not previously reported, warrants further investigation.

Background: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking. Objective: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19. Study Design: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19–associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints. Results: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88–2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43–5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38–6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P

Subgaleal hematoma (SGH) is a rare complication in neonates that may lead to hemorrhagic shock due to significant blood loss into the subgaleal space. We report of two neonates who developed subgaleal hematoma with severe hemorrhagic shock and encephalopathy. In the first case of a mature female neonate, the development of the subgaleal hematoma was promoted by early-onset sepsis and delivery by vacuum extraction. The second case, of a male preterm neonate, was a complicated fetal development followed by secondary cesarean section. Both cases highlight that a subgaleal hematoma is a severe neonatal emergency. In addition to prompt treatment of the shock, therapy of the coagulopathy is essential.Das subgaleale Hämatom (SGH) ist eine seltene Geburtskomplikation des Neugeborenen und kann aufgrund des erheblichen Blutverlustes in den subgalealen Raum zu einem hämorrhagischen Schock führen. Wir berichten von zwei Neugeborenen, die ein subgaleales Hämatom mit schwerem hämorrhagischem Schock und Enzephalopathie entwickelten. Im ersten Fall eines reifen weiblichen Neugeborenen wurde die Entstehung des subgalealen Hämatoms durch eine Neugeboreneninfektion und die Geburt mittels Vakuumextraktion begünstigt. Der zweite Fall eines männlichen Frühgeborenen wurde durch eine schwierige Kindsentwicklung mittels sekundärer Sectio caesarea kompliziert. Neben der raschen Behandlung des Schocks ist vor allem die Therapie der Gerinnungsstörung essentiell. Beide Fälle verdeutlichen, dass das subgaleale Hämatom ein neonatologischer Notfall ist.

Background/objectiveTo investigate the longitudinal development of maternal body weight and analyze the influence of obesity on obstetrics during more than two decades in Germany.Subjects/methodsData collected from the Federal state of Schleswig-Holstein (German Perinatal Survey) were analyzed with regard to the dynamics of maternal anthropometric variables (body weight, BMI) between 1995–7 and 2004–17. In total 335,511 mothers substantiated the presented study-collective. The statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY.ResultsMaternal BMI advanced significantly over the study period. Among a rise in mean periconceptional body weight (67.6–72.0 kg), the segment of obese women increased disproportionately (in average 9.4–19.2%). Despite the observed trend to late giving birth (mean maternal age 1995: 29.3 vs. 30.7 years in 2017), it was not advanced maternal age but parity that influenced the continuous increase in maternal weight (mean maternal body weight 1995–7: primi- bi-, multiparae 67.4, 68.3 and 69.0 kg vs. 2004–17: primi- bi-, multiparae 70.0, 71.5 and 73.2 kg respectively).ConclusionObesity is a major problem on health issues in obstetrics. Advancing maternal BMI, increasing mother’s age and derived prenatal risks considerably complicate pregnancy and delivery. It has to be emphasized that its consequences do not end with delivery or childbed, but represent a livelong burden to the mother and their offspring. Hence, multimodal strategies to reduce/control periconceptional body weight are mandatory.

Zusammenfassung Anamnese und klinischer Befund Wir berichten über drei Schwangere: zwei in verschiedenen Stadien der Niereninsuffizienz und eine Nierentransplantierte. Pat. 1 ist eine 32-Jährige I/0 in der 20. SSW mit akutem Nierenversagen, nephrotischem Syndrom und familiärem Mittelmeerfieber in der Anamnese. Pat. 2 ist eine 23-Jährige mit Schrumpfnieren bds. und Niereninsuffizienz Stad. V unter Dialyse 3 × wöchentlich, die Schwangerschaft war eine Zufallsdiagnose. Pat. 3 ist eine 29-Jährige im Z. n. Nierentransplantation vor mehreren Jahren. Diagnose, Therapie und Verlauf Bei Pat. 1 wurde die Verdachtsdiagnose einer AA-Amyloidose durch Nierenbiopsie bestätigt. Im Verlauf wurde sie zunehmend dialysepflichtig. Bei Pat. 2 musste die Dialyse ebenfalls eskaliert werden. Beide Schwangerschaften wurden vorzeitig beendet. Die transplantierte Pat. 3 wurde am Termin ohne Komplikationen im Verlauf entbunden. Folgerung Die Verbesserung des fetalen Outcomes ist v. a. auf die interdisziplinäre Zusammenarbeit zurückzuführen. Ziel sollte sein, junge nierenkranke Frauen bereits vor einer Schwangerschaft umfassend über Risiken und Erfolgsaussichten zu beraten und zu betreuen.

Objectives The maternal body size affects birth weight. The impact on birth weight percentiles is unknown. The objective of the study was to develop birth weight percentiles based on maternal height and weight. Methods This observational study analyzed 2.2 million singletons from the German Perinatal Survey. Data were stratified into 18 maternal height and weight groups. Sex-specific birth weight percentiles were calculated from 31 to 42 weeks and compared to percentiles from the complete dataset using the GAMLSS package for R statistics. Results Birth weight percentiles not considering maternal size showed 22% incidence of small for gestational age (SGA) and 2% incidence of large for gestational age (LGA) for the subgroup of newborns from petite mothers, compared to a 4% SGA and 26% LGA newborns from big mothers. The novel percentiles based on 18 groups stratified by maternal height and weight for both sexes showed significant differences between identical original percentiles. The differences were up to almost 800 g between identical percentiles for petite and big mothers. The 97th and 50th percentile from the group of petite mothers almost overlap with the 50th and 3rd percentile from the group of big mothers. Conclusions There is a clinically significant difference in birth weight percentiles when stratified by maternal height and weight. It could be hypothesized that birth weight charts stratified by maternal anthropometry could provide higher specificity and more individual prediction of perinatal risks. The new percentiles may be used to evaluate estimated fetal as well as birth weight.

Objective To investigate the variability in the prevalences of selected birth risks in women of different heights and weights. Methods Data from the German Perinatal Survey of 1998–2000 were analyzed: 503,468 cases contributed to our analysis of the prevalences of selected birth risks specified according to maternal weight groups, 502,562 cases contributed to our analysis according to maternal height groups and 43,928 cases contributed to our analysis of birth risks in women with a body mass index (BMI) of 21–23 kg/m2 but different heights and weights. Data analysis was performed using SPSS version 22. Results Some birth risks varied substantially by maternal height in women with a “normal” BMI of 21–23 kg/m2: the prevalence of post-term birth increased from 8.7% in women with a height of 150 cm to 13.5% in 185 cm tall women, the prevalence of preterm birth decreased from 5.9% (150 cm tall women) to 3.1% (185 cm tall women), a pathologic cardiotocography (CTG) or poor fetal heart sounds on auscultation occurred in 19.4% of the 150 cm tall women but only in 9.2% of 185 cm tall women and cephalopelvic disproportion decreased from 12.3% (150 cm tall women) to 1.2% (185 cm tall women). Analyses of women in different body height and weight groups (without restriction of BMI) likewise showed differences in the prevalences of some birth risks. Conclusion Birth risks may vary by height and weight in women with the same, “normal” BMI. BMI should not be the only way by which the impact of maternal height and weight is assessed with regard to perinatal outcomes such as birth risks.

Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as cure to allow prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1.Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30-41 years) with very preterm PE (24+4 to 27+0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission (28 GW; n = 6). Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1 and PlGF were monitored.In apheresis patients (2-6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels throughout treatments, with sFlt-1/PLGF ratio remaining unaffected.H.E.L.P.-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.

Objectives: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, ­EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: We provide 75 recommendations and 68 statements in the updated evidence- and consensus-based national clinical guideline. The diagnostics part covers practical recommendations on cystitis and pyelonephritis for each defined patient group. Clinical examinations, as well as laboratory testing and microbiological pathogen assessment, are addressed. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.

The objective of this study was to investigate clinical and microbiological gingival changes during pregnancy in women without periodontal disease. Additionally, these parameters were to be compared in women with high risk for preterm birth and women with a normal course of pregnancy. Group I consisted of 40 subjects at high risk for preterm birth, while group II involved 49 subjects with a normal course of pregnancy. The control group (III) was made up of 50 non-pregnant women. Clinical parameters (plaque index, gingival index, probing pocket depths, gingival swelling, bleeding on probing) and microbiological changes were monitored during pregnancy and 2–4 weeks after parturition. In the high-risk preterm group (I), 19 women could be included in data analysis. This group was compared to 41 women in the normal pregnancy group (II) and 50 non-pregnant women (III). Gingival inflammation was significantly higher in women with high risk for preterm birth (I) compared to non-risk pregnant women (II, p 105) were found to be significantly higher after childbirth compared to non-pregnant women (p

Kollek et al. show that transient inhibition of apoptosis by short-term BCL-XL overexpression increases the viability of hematopoietic stem cells (HSCs) during engraftment and improves the outcome of HSC transplantation without signs of adverse pathologies. This strategy represents a promising and novel therapeutic approach, particularly under conditions of limited donor stem cell availability., During hematopoietic stem cell transplantation, a substantial number of donor cells are lost because of apoptotic cell death. Transplantation-associated apoptosis is mediated mainly by the proapoptotic BCL-2 family proteins BIM and BMF, and their proapoptotic function is conserved between mouse and human stem and progenitor cells. Permanent inhibition of apoptosis in donor cells caused by the loss of these BH3-only proteins improves transplantation outcome, but recipients might be exposed to increased risk of lymphomagenesis or autoimmunity. Here, we address whether transient inhibition of apoptosis can serve as a safe but efficient alternative to improve the outcome of stem cell transplantation. We show that transient apoptosis inhibition by short-term overexpression of prosurvival BCL-XL, known to block BIM and BMF, is not only sufficient to increase the viability of hematopoietic stem and progenitor cells during engraftment but also improves transplantation outcome without signs of adverse pathologies. Hence, this strategy represents a promising and novel therapeutic approach, particularly under conditions of limited donor stem cell availability.

Die aktualisierte AWMF-S3-Leitlinie zu unkomplizierten Harnwegsinfektionen bei Erwachsenen enthalt uberarbeitete Empfehlungen unter anderem zur antibiotischen Therapie unkomplizierter Harnwegsinfektionen sowie zur asymptomatischen Bakteriurie bei Schwangeren. Wesentlichen Einfluss auf die Anderungen hatten neben den Ergebnissen neuester Studien die Grundprinzipien der rationalen Antiinfektivaverordnung.

The anti-apoptotic BCL-2 proteins (BCL-2, BCL-XL, MCL-1, A1, BCL-W) counteract apoptotic signals emerging during development and under stress conditions, and are thus essential for the survival of every cell. While the “BCL-2 addiction” of different cell types is well described in mouse models, there is only limited information available on the role of different anti-apoptotic BCL-2 proteins in a given human cell type. Here we characterize the role of BCL-XL for survival and function of human hematopoietic cells, with the aim to predict hematological side effects of novel BCL-XL-inhibiting BH3-mimetics and to identify hematological malignancies potentially responsive to such inhibitors. Earlier clinical studies have shown that the combined BCL-2/BCL-XL/BCL-W inhibitor, Navitoclax (ABT-263) induces severe thrombocytopenia caused by direct platelet demise and counteracted by increased megakaryopoiesis. In contrast, murine studies have reported important contribution of BCL-XL to survival of late erythroid cells and megakaryocytes. Using lentiviral knockdown, we show that the roles of BCL-XL for human hematopoietic cells are much more pronounced than expected from murine data and clinical trials. Efficient genetic or chemical BCL-XL inhibition resulted in significant loss of human erythroid cells beginning from very early stages of erythropoiesis, and in a reduction of megakaryocytes. Most importantly, BCL-XL deficient human hematopoietic stem cells and multipotent progenitors were reduced in numbers, and they showed a severely impaired capacity to engraft in mice during xenotransplantation. BCL-XL deficiency was fully compensated by BCL-2 overexpression, however, loss of its antagonist BIM did not result in any rescue of human erythroid or stem and progenitor cells. We thus conclude that novel and specific BCL-XL inhibitors might be efficient to treat malignancies of erythroid or megakaryocytic origin, such as polycythemia vera, acute erythroid leukemia, essential thrombocytosis or acute megakaryocytic leukemia. At the same time, it can be expected that they will have more severe hematological side effects than Navitoclax.

Sacrococcygeal teratoma is one of the most common congenital tumors. Its optimal management requires interdisciplinary care by obstetricians, radiologists, pediatric surgeons, and neonatologists. Early surgery entailing complete tumor excision is the main therapy aim, but a substantial risk of life-threatening complications remains, especially uncontrollable intraoperative hemorrhage. To reduce the risk of bleeding in a female neonate with a giant sacrococcygeal teratoma, we successfully coil-embolized the tumor's main feeding arteries. Her subsequent complete surgical resection was uneventful, and the child is well with favorable reconstructive and functional status of all involved and adjacent organ systems.

AIM Milk banks are advised to use Holder pasteurisation to inactivate the cytomegalovirus, but the process adversely affects the bioactive properties of human breastmilk. This study explored the antibacterial efficacy of an alternative high-temperature short-time (HTST) treatment of human breastmilk and its effect on marker proteins, compared with the Holder method. METHODS Breastmilk samples were obtained from 27 mothers with infants in a German neonatal intensive care unit. The samples were either heated to 62°C for five seconds using HTST or processed using Holder pasteurisation, at 63 ± 0.5°C for 30 minutes. Immunoglobulin A, lactoferrin, lysozyme, alkaline phosphatase and bile salt-stimulated lipase concentrations and bacterial colony-forming units/mL were measured before and after heating. RESULTS HTST-treated samples retained higher rates of immunoglobulin A (95% versus 83%), alkaline phosphatase (6% versus 0%) and bile salt-stimulated lipase (0.8% versus 0.4%) than Holder pasteurisation samples (all p < 0.01), but not lactoferrin (32% versus 20%, p = 0.18) and lysozyme (72% versus 65%, p = 1). No difference in antibacterial efficacy was noted between the two groups (p = 0.29). CONCLUSION Using the HTST treatment protocol retained some of the bioactive properties of human breastmilk and appeared to have similar antibacterial efficacy to Holder pasteurisation.

Zielstellung: Ziel dieser Arbeit war die Berechnung und Darstellung von Referenzwerten fur Drillingsgeborene fur Geburtsgewicht, -lange, -kopfumfang und langenbezogenes Geburtsgewicht. Grundlage dafur bildeten die Daten der deutschen Perinatalerhebung der Jahre 2007–2011. Material und Methoden: Daten von 3 690 Drillingsgeborenen aus allen Bundeslandern Deutschlands, die im Rahmen der deutschen Perinatalerhebung erfasst worden waren, wurden uns freundlicherweise vom AQUA-Institut in Gottingen zur Verfugung gestellt. Daten von 3 567 Fallen wurden in die Auswertungen einbezogen. Geschlechtsspezifische Perzentilwerte wurden uber die kumulativen Haufigkeiten fur die 3., 10., 25., 50., 75., 90. und 97. Perzentile fur 21–36 vollendete Schwangerschaftswochen berechnet. Ergebnisse und Schlussfolgerungen: Es werden erstmalig fur die Bundesrepublik Deutschland Normwerte (Tabellen und zugehorige Kurven) fur die Korpermase von Drillingskindern vorgestellt und ausgewahlte Geburtsgewichts- und Geburtslangenperzentilwerte (nach 32 und 34 vollendeten Schwangerschaftswochen) von Drillingen mit denen von Einlingen und Zwillingen verglichen. Die Differenzen in der 50. Geburtsgewichtsperzentile zwischen Einlingen und Drillingen nach 32 vollendeten Schwangerschaftswochen betrugen bei den Madchen 180 g und bei den Knaben 210 g; nach 34 Wochen waren 320 bzw. 325 g. Die Differenzen zwischen Zwillingen und Drillingen betrugen bei den Madchen nach 32 Schwangerschaftswochen 100 g und bei den Knaben 120 g, nach 34 Wochen waren es 130 bzw. 135 g. Durch die hier vorgestellten Daten gibt es jetzt auch fur Drillingskinder die Moglichkeit, sie unter Bezugnahme auf das deutsche Geburtengut nach somatischen Parametern zu klassifizieren.

We report of three pregnancies, two with renal insufficiency and one with a history of renal transplantation. Pat.1 is a 32y at 20 weeks of gestation with acute renal failure, nephrotic syndrome and history of familial Mediterranean fever. Case 2 is a 23y with cirrhotic kidneys, stage 5 of chronic kidney disease and dialysis treatment 3 × a week. The pregnancy was an incidental finding. Pat. 3 is a 29y I/0 with history of renal transplantation years ago.In pat. 1a renal biopsy confirmed the suspected diagnosis of AA amyloidosis. Due to deterioration of the kidney function, she required dialysis up to 6 × a week. In Case 2 the dialysis increased to 6 × a week as well. In both patients, we indicated delivery at 35 weeks of gestational age. Pat. 3 delivered at term without complications.A close interdisciplinary cooperation improves neonatal outcome in pregnant women with CKD. Counseling and risk assessment of these patients should be initiated before pregnancy. The care of these high-risk pregnancies needs to be performed at a tertiary care center with the above-mentioned specialists.Wir berichten über drei Schwangere: zwei in verschiedenen Stadien der Niereninsuffizienz und eine Nierentransplantierte. Pat. 1 ist eine 32-Jährige I/0 in der 20. SSW mit akutem Nierenversagen, nephrotischem Syndrom und familiärem Mittelmeerfieber in der Anamnese. Pat. 2 ist eine 23-Jährige mit Schrumpfnieren bds. und Niereninsuffizienz Stad. V unter Dialyse 3 × wöchentlich, die Schwangerschaft war eine Zufallsdiagnose. Pat. 3 ist eine 29-Jährige im Z. n. Nierentransplantation vor mehreren Jahren.Bei Pat. 1 wurde die Verdachtsdiagnose einer AA-Amyloidose durch Nierenbiopsie bestätigt. Im Verlauf wurde sie zunehmend dialysepflichtig. Bei Pat. 2 musste die Dialyse ebenfalls eskaliert werden. Beide Schwangerschaften wurden vorzeitig beendet. Die transplantierte Pat. 3 wurde am Termin ohne Komplikationen im Verlauf entbunden.Die Verbesserung des fetalen Outcomes ist v. a. auf die interdisziplinäre Zusammenarbeit zurückzuführen. Ziel sollte sein, junge nierenkranke Frauen bereits vor einer Schwangerschaft umfassend über Risiken und Erfolgsaussichten zu beraten und zu betreuen.

Objective The aim of the present study was to assess the influence of maternal age and maternal body mass index of early pregnancy on the risk of preterm delivery. Material and methods The study included 2.1 million liveborn single newborns with documented data at perinatal surveys. Statistical analyses were performed using the SPSS statistics program. Results The risk of preterm births increased in obese women and in women with advanced age. Conclusion Strategies should be developed to reduce preconceptional body mass index, and guidelines are required to help advise women who postponed childbearing.

Background Rheumatoid arthritis is an immune-mediated disease, in which immune cell activation leads to destructive inflammation of the joints. In this context the treatment with JAK inhibitor tofacitinib has been proven to be effective. In mice treatment with tofacitinib resulted in reduced specific antibody responses, failure to generate germinal centres, and partial block of B cell development in the bone marrow. Conversely in vivo treatment of psoriasis arthritis patients as well as of rheumatioid arthritis patients with tofacitinib results in an increase of relative and absolute numbers of B cells in the first 4–8 weeks from beginning of treatment. It is known that mouse early B cell development is strongly dependent on IL-7 signalling, while this is not essential in humans. Nevertheless other cytokines are important in determining the fate and development of B lymphocytes. Hence, the outcome of JAK inhibition in early B cell development remains to be studied Objectives To assess the impact of JAK inhibition on early B cell development in vitro Methods We used a in vitro model in which CD34+ cells isolated from cord blood are cultivated subsequently in SCF, Flt3-L and IL-6, then SCF, Flt3-L and IL-7 and finally in cytokine-free medium(.1 The culture reproduces all stages of development from common lymphocytes progenitors to immature B cells. Results With the addition of tofacitinib to the in vitro culture we observed an increase in the absolute numbers of lymphoid precursors developing in vitro especially at week 5 and 6 of culture. Specifically, JAK inhibition led to an increase of pre-B and immature B cells by week 5 and 6. These data are in contrast with the early B cell development block observed in the tofacitinib treated mouse, but are in line with the rapid increase of B cells in peripheral blood after 4–8 weeks of tofacitinib treatment in patients. Analysis of induction of fate determining genes (EBF, E2A, PAX-5) showed an earlier and stronger induction of fate determining genes. Conclusions Our data indicate that JAK inhibition may promote early B cell development by enhancing the commitment of lymphoid precursors to the B cell compartment, contributing to a temporary increase in relative and absolute numbers of B cell in peripheral blood of treated patients. These data contribute to our understanding of human B cell development, prompt us to further analyse the quality of B cell output from the bone marrow in JAK inhibited patients, and may provide cues to understand the outcome of JAK inhibition treatment in rheumatic diseases. Reference [1] Kraus H, et al. A feeder-free differentiation system identifies autonomously proliferating B cell precursors in human bone marrow. J Immunol. 2014Feb 1;192(3):1044–54. Disclosure of Interest None declared