Gestational diabetes mellitus (GDM) and pre-conceptional diabetes are linked to increased long-term risk of type 2 diabetes (T2D) and microvascular complications. However, the earliest signs of neurovascular damage during pregnancy remain elusive. Here, we report the first longitudinal analysis of circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using high-resolution 768-A-scan spectral-domain OCT in a population-based cohort of 591 pregnant women, including healthy pregnancies (HPC), diet-treated (dGDM) and insulin-treated GDM (iGDM), and pre-conceptional diabetes (T1D/T2D). We reveal divergent, treatment-specific neuroretinal trajectories: dGDM exhibited early thinning in the temporal-inferior sector (up to −20 µm), while iGDM showed progressive thickening in the temporal-superior sector (up to +22 µm), correlating with insulin exposure duration. Notably, women with pre-conceptional diabetes displayed profound and sustained thinning (up to −30 µm), exceeding levels seen in non-pregnant diabetic individuals. Using Euclidean nested case-control matching, these differences were confirmed after rigorous adjustment for confounders. Our findings demonstrate that glucose dysregulation during pregnancy induces measurable neuroretinal changes at an earlier stage than previously recognized, suggesting that the retina may serve as a non-invasive window into systemic metabolic vulnerability. These results position cpRNFLT as a potential biomarker for early detection of long-term diabetes risk, with implications for prenatal screening and preventive strategies.

Soluble Fms-like tyrosine kinase 1 (sFlt-1), a protein secreted by the placenta, plays a central role in the pathogenesis of preeclampsia-a life-threatening pregnancy complication for which no disease-specific treatment currently exists. We developed a strategy to selectively deplete circulating sFlt-1 and then conducted a single-arm, open-label trial to reduce circulating sFlt-1 in women with very preterm preeclampsia. The primary endpoints were safety and tolerability. Extracorporeal apheresis with an adsorber containing high-affinity IgG1 antibodies against sFlt-1 resulted in an approximately 50% reduction of circulating sFlt-1 levels in pregnant baboons. In women with preterm preeclampsia treated with single ascending doses (phase A, n = 7, preapheresis, mean ± s.d., sFlt-1: 15,120 ± 4,484 pg ml-1), maternal and fetal vital signs and umbilical artery pulsatility indices remained stable when comparing measures before, during and after apheresis. In women with very preterm preeclampsia treated with multiple doses (phase B, n = 9, median gestational age 30.3 (interquartile range, 29.3-30.9) weeks, systolic and diastolic blood pressures 146 ± 10 and 92 ± 5 mmHg, respectively, and preapheresis circulating sFlt-1 levels 11,960 ± 3,056 pg ml-1), each apheresis reduced sFlt-1 levels by 16.7 ± 7.6% and mean arterial pressures by 4.1 ± 7.8 mmHg. Reductions in mean arterial pressures after apheresis strongly correlated with reductions in circulating sFlt-1 (R = 0.63, Spearman's correlation). Pregnancy continued from admission for a median of 10 (range, 3-19) days. Compared to antenatal estimated birth weights, neonatal birth weights generally remained stable or increased among those with the longest extensions. Treatment-related adverse events included mild hypocalcemia (n = 3), skin hemorrhage at the puncture site (n = 1) and false labor (n = 1). Selective removal of sFlt-1 by apheresis appeared to be safe and well tolerated in women with very preterm preeclampsia. Controlled trials are needed to confirm the additional safety and efficacy of this approach. ClinicalTrials.gov registration: NCT02923206 .

Context:The intrauterine environment strongly influences children's health and development. Distinct cardiovascular biomarkers have been linked to birth weight and later weight gain, with correlations observed in maternal and umbilical cord serum. Objective:To describe (1) maternal cardiovascular biomarker patterns during the second and third trimesters and (2) potential associations between these biomarkers and offspring weight at birth and at 1 year of age. Design:Within the LIFE Child Study, serum samples from 86 healthy mothers at 24 and 36 gestational weeks and cord blood at birth were analyzed using the Olink® Target 96 Cardiovascular III panel. Statistical analyses (Wilcoxon test, Spearman correlation, multivariate regression) were performed in R. Setting:Community-based cohort, Leipzig, Germany. Patients or Other Participants:Eighty-six mother-child pairs from the LIFE Child cohort. Mothers had no pregnancy complications, and all newborns had birth weights between 2500 and 4500 g. Main Outcome Measure:Offspring body weight at 1 year of age. Results:Of 92 maternal serum biomarkers, 88 were detectable. Seventy biomarkers increased significantly from 24 to 36 weeks (P < .004). Several biomarkers measured at the 36th gestational week correlated with birth weight and 1-year weight. After adjustment for maternal age, body mass index, and offspring sex, no associations remained with birth weight. However, maternal paraoxonase 3 (PON3) [P = .037, 95% confidence interval (CI): -0.52, -0.02] and integrin subunit β 2 (ITGB2) (P = .038, 95% CI: 0.04, 1.12) were significantly associated with child weight at 1 year. Conclusion:In our cohort, maternal PON3 and ITGB2 were independently associated with early postnatal growth, potentially implicating these biomarkers in fetal programming.

OBJECTIVES:The safety and efficacy of peripartum transfusion support depends on a comprehensive risk analysis, the provision of substantiated criteria for ordering blood products, and surveillance of outcomes over time. We aimed to determine bleeding frequencies and volumes of blood loss, associated patient risk factors, and the effectiveness of our transfusion support scheme. METHODS:Birth records of 12,255 pregnant women who gave birth at our hospital were screened for haemorrhage volumes, mode of delivery, bleeding aetiology, accompanying risk factors as well as outcome. Transfusion related data was extracted from the electronic blood product database. RESULTS:A total of 204 (1.6 %) women who gave birth within the 5-year study period received at least one RBC transfusion within 48 h after delivery. Differences in haemorrhage volumes in all women compared to those receiving RBC transfusion confirmed an increased probability of RBC transfusion with larger haemorrhage volumes. Uterus atony bleeding (UAB) was the most common cause associated with transfusions. Six risk factors for RBC transfusion among transfused patients were identified that showed a probability of >10 %: Adherent placenta (31.4 %), preterm rupture of membranes (PROM) (25.5 %), age over 35 (25.0 %), a previous caesarean section (19.6 %), gestational diabetes mellitus (15.2 %), and a twin pregnancy (11.8 %). An overall crossmatch-to-transfusion (C/T) ratio of 2.75:1 was reached and no patient with major haemorrhage-related morbidity or mortality was recorded. CONCLUSIONS:Evaluation of peripartum haemorrhage and associated RBC transfusion using the described methodology revealed RBC transfusions in 1.6 % of all women who gave birth within the study period. The described blood ordering scheme demonstrates a safe and efficient utilisation of blood products.

BACKGROUND:Adaptive optics retinal imaging (rtx1e, Imagine Eyes, Orsay, France) enables high-resolution visualization of the retinal microvasculature, providing insights into systemic vascular health. Currently, no studies exist describing changes in wall-to-lumen ratio (WLR) during pregnancy, neither during the physiological course of pregnancy nor in pregnancy-associated complications. METHODS:This single-center, prospective study at the Leipzig University Hospital, Germany, examines changes in retinal microvasculature by employing adaptive optics to calculate the WLR of an arteriole within a few seconds. The study examined a well-phenotyped cohort of 460 primarily White healthy singleton pregnancies, with 543 measurements taken from the first to the third trimester. The WLR was automatically determined using the nnUNet deep learning model. RESULTS:Step-down selection mixed-effects modeling identified gestational week, maternal age, mean arterial pressure, and parity as significant contributors to WLR, whereas body mass index did not improve model fit. In the final model, advancing gestational week (P<0.001), higher maternal age (0.012), and higher mean arterial pressure (<0.001) were independently associated with increased WLR, whereas multiparous women showed significantly lower WLR values compared with nulliparous women, with negligible multicollinearity (variance inflation factor ≈1). CONCLUSIONS:We identify WLR as a sensitive marker for imaging microvascular remodeling, serving as an indicator of adaptation to physiological pregnancy. Normal pregnancy is associated with an instant change of the retinal microvasculature indicated by an increase of WLR. Further studies are required to investigate the postpartum course of WLR and establish whether these changes are reversible. REGISTRATION:URL: https://www.drks.de; Unique identifier: DRKS00032530.

We examined the prevalence of magnesium supplementation among pregnant women in Germany and assessed whether risk factors for preterm birth might be associated with magnesium use. We explored the association between magnesium supplementation and pregnancy duration . The LIFE Child Study (Leipzig, Germany) recruited pregnant women and collected data in the 24th and 36th week of pregnancy from 2011 to 2019. In this prospective observational cohort study (n = 1078 participants), we analysed potential associations for magnesium supplementation with health-related factors using logistic regression models adjusted for age and socioeconomic status (SES). Using a generalised linear model, we explored whether magnesium supplementation potentially affects pregnancy duration. During their current pregnancy, 60.0

Aim This S2k guideline of the German Society of Gynecology and Obstetrics (DGGG) contains consensus-based recommendations for the care and treatment of women with hypertension in pregnancy. It aims to serve as a guide for all professions involved in the care of pregnant women and to improve interprofessional and interdisciplinary cooperation. A new focus was placed on patients' long-term health beyond the postpartum period. Methods The existing S2k guideline was revised and the relevant literature reviewed. Where new questions arose, they were formulated and developed in PICO format. A targeted systematic literature search was carried out using PubMed. Other international guidelines were also consulted. After summarizing and presenting the available data, recommendations and statements were developed, discussed, and agreed on by the guideline group. Recommendations The recommendations cover prediction, prevention, diagnosis, and treatment from the moment hypertensive disease is detected in pregnancy as well as postpartum, in the puerperium, and during breastfeeding. A major change from the previous version of the guideline is the reduction in blood pressure levels that should be achieved during pregnancy. Suggestions are made on how to proceed with regards to the long-term health of mother and child, which the guideline group believes is currently regulated inadequately in the German healthcare system.

PROBLEM/BACKGROUND:Depression and anxiety during the peripartum period affect maternal and infant well-being but remain understudied and undertreated. AIM:This study investigated the prevalence, longitudinal course, flow patterns, and risk and protective factors for depression and generalized anxiety during pregnancy and postpartum. METHODS:A longitudinal design with four assessment points (second trimester, third trimester, three and six months postpartum) was used, including 136 women from a German university hospital. Depression and anxiety were measured using the EPDS and GAD-7. Multiple regression analyses were conducted to identify predictors of postpartum mental health outcomes. FINDINGS:Prevalence rates for depression ranged from 14.7 % to 20.6 %, and for generalized anxiety from 9.6 % to 14.7 %, with no significant changes over time. Notably, 37.5 % of women recovered from antepartum depression postpartum, and 53.8 % recovered from antepartum anxiety postpartum. However, among women who reported postpartum depression or anxiety, 41.2 % experienced new-onset depression and 45.5 % new-onset anxiety. Pregnancy-related worries, depression during pregnancy, and Caesarean sections were significant risk factors for postpartum depression, whereas perceived social support was protective. Risk factors for postpartum generalized anxiety included antepartum anxiety, whereas exclusive breastfeeding was protective. DISCUSSION:The findings highlight the substantial prevalence and persistence of peripartum depression and anxiety, with a notable proportion of women experiencing new-onset postpartum symptoms. The identified risk and protective factors provide valuable targets for future interventions. CONCLUSIONS:Peripartal depression and anxiety are common and often persistent. Routine mental health screening and targeted interventions are crucial to improve outcomes for mothers and infants.

Adaptive Optics retinal imaging (AO) enables high-resolution visualization of the retinal microvasculature providing insights into systemic vascular health. Currently, no studies exist describing changes in wall-to-lumen ratio (WLR) during pregnancy, neither during the physiological course of pregnancy nor in pregnancy-associated complications. This single-centre, prospective study at the Leipzig University Hospital, Germany, examines longitudinal changes in retinal microvasculature by employing AO (rtx1e, Imagine Eyes, Orsay, France) to calculate the WLR of an arteriole within few seconds. The study examined a well-phenotyped cohort of 495 primarily Caucasian healthy pregnant women, with 584 measurements taken from the first to the third trimester. The WLR was automatically determined using the nnUNet deep learning model. As demonstrated in the linear mixed-effects model, gestational age exhibited the most significant effect on WLR (p < 0.001). Changes in WLR were also significantly associated with maternal age (p = 0.04) and mean arterial blood pressure (p < 0.001). Primiparous women had significantly lower WLRs at baseline (p < 0.01) and exhibited significantly steeper increases in WLR throughout gestation (p = 0.01) than nulliparous women. We identify WLR as a sensitive marker for imaging microvascular remodeling, serving as an indicator of adaptation to physiological pregnancy. Normal pregnancy is associated with an instant change of the retinal microvasculature indicated by an increase of WLR. Further studies are required to investigate the postpartum course of WLR and establish whether these changes are reversible.

Die Omodysplasie Typ II (autosomal-dominant) ist eine sehr seltene Erkrankung, welche mit einer Skelettanomalie, fazialen Dysmorphie und urogenitalen Auffälligkeiten einhergeht. Kausal finden sich Alterationen im FZD2-Gen. Wir beschreiben einen pränatal detektierten Fall mit verkürzten oberen Extremitäten, Lippen-Kiefer-Gaumenspalte und Verdacht auf Genitalhypoplasie. Beim betroffenen Fetus wurde in der Literatur die noch nicht beschriebene de novo Mutation im Gen FZD2 nachgewiesen, die höchstwahrscheinlich ursächlich für die Symptomatik ist. Nach unserem Wissen, ist es die Erstpublikation der de novo Mutation im Gen FZD2.

Background: Preeclampsia is a vascular complication of pregnancy with limited therapeutic options. It is associated with hypertension and an increase in angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor. Based on its onset, preclampsia can be categorized into early-onset (E-PE) or late-onset (L-PE) preeclampsia. Thrombo-inflammation, hallmarked by maternal platelet activation and sterile inflammation, is associated with pathophysiology of preeclampsia. However, whether these mechanisms are differentially regulated in E-PE vs L-PE remains unknown. Objectives: We aim to study the role of maternal platelet activation, inflammation and endothelial dysfunction in E-PE vs L-PE. Methods: Flow-cytometry analysis of platelet activation (P-selectin and active αIIbβ3) was conducted in whole blood from pregnant women with E-PE, L-PE and gestational age-matched patients. Plasma was evaluated for interleukin (IL)-1β and soluble vascular cell adhesion molecule 1 (sVCAM-1). Results: An increase in P-selectin and active αIIbβ3 expressing platelets in both forms of preeclampsia (n = 22) was observed compared with their gestational age-matched controls (n = 18). Similarly, an increase in plasma IL-1β and sVCAM-1 was observed in both forms of preeclampsia, suggesting inflammation and endothelial dysfunction, respectively. Maternal platelet activation (P-selectin positive platelets) was linked with disease severity (sFlt-1/placental growth factor) and maternal plasma IL-1β and sVCAM-1 only in late-onset preeclampsia. A statistically significant correlation with αIIbβ3 expressing platelets and sFlt-1, IL-1β, and sVCAM-1 was not observed. Conclusions: These findings identify that thrombo-inflammation is regulated in L-PE and E-PE through likely disjunct mechanisms supporting a role of maternal factors (eg, maternal platelet activation) involved in L-PE. Further studies with a larger cohort of patients are required to fully elucidate the mechanistic relevance of these findings.

OBJECTIVES:Depending on risk profile, pregnant women can freely choose their preferred birthplace, especially in the case of a normal pregnancy. In addition to obstetric maternity units in a hospital, options may include out-of-hospital births (such as births at home or in a freestanding midwifery unit. To our knowledge, there is no study comparing the outcomes of peripartum transfers from different places. METHODS:Between 2020 and 2021, all births transferred internally from the AMU of the University Hospital of Leipzig (n=74) were retrospectively analyzed and compared with births transferred from external (home or an FMU; n=72). The main outcome measures were morbidity and interventions. RESULTS:86.1 % were transfers from an FMU and 13.9 % were transfers of planned home births. There were significantly less spontaneous vaginal births in planned OH births (55.6 %) compared to planned AMU births (73.7 %, p<0.001). For the FMU births, we found a significantly higher rate of caesarean section (20.8 %, to 6.6 %, p<0.001) and postpartum neonatal transfers (8.3-4.1 %, p=0.025). The duration of labor was significantly longer in transferred OH (p<0.001). CONCLUSIONS:In case of an intrapartum transfer, there was a decreased likelihood of spontaneous vaginal birth and increased likelihood of secondary caesarean section compared to internally transferred AMU births. Furthermore, OH transfers were associated with a higher morbidity. Hence, pregnant women should be given an informed choice of birthplace, including the likelihood of intrapartum transfer. Out-of-hospital deliveries are associated with a higher rate of adverse perinatal outcome.

Rupture of fetal membranes and subsequent full-term birth are prerequisites for neonatal health, and a preterm rupture can lead to life-threatening complications. Our study determines the mechanical properties of term fetal membranes to identify perinatal structural changes by a unique biophysical multiscale approach, including atomic force microscopy, shear rheology, tabletop magnetic resonance elastography (MRE), and high-resolution optical microscopy. Fetal membranes from term spontaneous vaginal deliveries were compared to those from primary cesarean sections, used as a control group for pre-labor membranes. Spontaneously delivered term fetal membranes are softer and easier to deform in MRE experiments (median stiffness: 1.9 kPa, IQR 1.6–2.4) compared to controls (4.7 kPa, IQR 3.8–5.6); p < 0.001) and show increased water diffusion (median: 1.78 × 10 −3 mm 2 /s, IQR: (1.65–1.84) × 10 −3 vs. 1.66 × 10 −3 mm 2 /s, IQR (1.60–1.73) × 10 −3 ; p = 0.047). Their intermediate connective tissue layer (i.e. the collagen-rich area enclosed by the amnion and chorion) exhibits less ordered fiber alignment (median order parameter: 0.52, IQR 0.44–0.58 vs. 0.55, IQR 0.47–0.62; p = 0.04) and a looser fiber structure, as indicated by a significantly lower fiber area fraction (median: 0.33, IQR 0.25–0.46 vs. 0.73, IQR 0.63–0.88; p < 0.001) compared to the control membranes. These layer-specific changes in both structure and viscoelasticity are evidence for the dominant role of the intermediate connective tissue in maintaining membrane stability and the onset of rupture. Our mechanical and histopathological findings highlight the potential of mechanics-based screening-methods to assess the risk of preterm rupture and preterm birth to reduce neonatal morbidity.

INTRODUCTION:Magnetic resonance (MR) pelvimetry is widely used in planning vaginal breech birth and may support women's informed decision-making regarding their preferred mode of birth. This feasibility study aimed to assess whether transperineal ultrasound (TPU) could measure the maternal pelvis as accurately as MR pelvimetry and thus predict the outcome of vaginal breech birth. MATERIAL AND METHODS:In this prospective cohort study, nulliparous women with a singleton fetus in breech presentation received TPU for the measurement of the anteroposterior mid-pelvic diameter (AMD). These measurements were compared with those in MR pelvimetry to assess agreement and reliability. In women choosing to attempt vaginal breech birth, we additionally examined the association between the AMD (adjusted for possible confounders) and intrapartum cesarean section. The predictive performance of the AMD and traditional pelvic diameters (i.e., obstetric conjugate, interspinous, and intertuberous distance) was compared by means of the area under the receiver operating characteristic curve (AUC). RESULTS:Overall, 67 nulliparous women with breech presentation received both TPU and MR pelvimetry, of which 47 chose a vaginal breech birth (30 successful vaginal births and 17 intrapartum cesarean sections). The repeatability coefficients and intraclass correlation coefficient for the AMD were 0.38 cm and 0.97 (95% CI 0.96-0.98), respectively. Bland-Altman analysis between the AMD measured in TPU and MR pelvimetry yielded a mean difference of -0.0052 cm (95% CI -0.066 to 0.056 cm) with upper and lower limits of agreement of 0.48 cm (95% CI 0.38-0.59 cm) and -0.49 cm (95% CI -0.6 cm to -0.39 cm), respectively. In the subgroup of women who attempted vaginal breech birth, AMD was significantly associated with intrapartum cesarean section (adjusted odds ratio 0.25; 95% CI 0.06-0.81; AUC 0.77), while the obstetric conjugate, interspinous, and intertuberous distances were not. CONCLUSIONS:TPU can accurately and reliably measure the AMD, a novel pelvic diameter in breech presentation. Importantly, a smaller AMD was associated with an increased risk of intrapartum cesarean section if vaginal breech birth was attempted. Consequently, TPU could represent an alternative to MR pelvimetry and support women in deciding their preferred mode of birth in breech presentation.

Omodysplasia type II (autosomal dominant) is a very rare skeletal dysplasia with facial dysmorphism and urogenital abnormalities. Causal are alterations in the FZD2 gene. We describe a prenatally detected case with shortened upper extremities, cleft lip and palate and suspected genital hypoplasia. The de novo mutation in the FZD2 gene in the affected fetus, which has not been described yet, was found in the literature and is most likely the cause of the symptoms. To our knowledge, it is the first publication of the de novo mutation in the FZD2 gene.

Introduction:CNS malformations are among the most common malformations diagnosed prenatally and one of the main reasons for late terminations of pregnancy. Making the correct diagnosis and prognostic counseling a33re complex. The aim of this study was to analyze pregnancy outcomes with regard to specific malformations, the factors which affect decision-making, and the time between diagnosis and termination as well as the causes of late diagnosis and late termination. Patients and Method:A retrospective examination was carried out of all pregnancies with fetal CNS malformations treated at a perinatal center between 2003 and 2014. Termination rates, type of malformation, and gestational age at initial diagnosis and at termination were recorded. The factors influencing decision-making and the time between diagnosis and termination were analyzed statistically. A case-by-case analysis was carried out of any terminations performed after week 26+0 of gestation. Results:In 139 of 251 cases (55.44%), the pregnancy was terminated between week 13+1 and week 38+2 of gestation (median: 22+4 GW). The median time from the initial diagnosis to the start of termination (Δtermination) was 10 days (range: 1 to 94 days). Relevant factors influencing the decision to terminate the pregnancy were the type of malformation compared to isolated ventriculomegaly (non-isolated ACC [aOR 17.5; p < 0.001], holoprosencephaly [aOR 24.4; p < 0.001], spina bifida [aOR 7.24; p < 0.001], other neural tube defects [aOR 62.5; p < 0.001]) and the presence of additional genetic anomalies (aOR 6.38; p = 0.014). The decision to terminate the pregnancy occurred less often when the diagnosis was made at or after week 22+0 of gestation (aOR 0.24; p < 0.001). Significant factors which affected the time between diagnosis and the start of termination (Δtermination) were: having a fetal MRI (HR 0.41; p = 0.003) and maternal age (HR 0.95 per additional year; p = 0.034). The interval between diagnosis and termination was significantly shorter if a destructive abnormality (HR 10.5; p = 0.004) or a (non-spina bifida) neural tube defect (HR 3.86; p = 0.002) was present. A known chromosomal aberration (p = 0.87), non-CNS anomalies (p = 0.58), or a diagnosis ≥ 22+0 GW (p = 0.74) affected the time between diagnosis and termination. The analysis of particularly late terminations from week 26+0 of gestation onwards found that avoidable delays in making the diagnosis or terminating the pregnancy only occurred in a few individual cases. Conclusion:The diagnostic and prognostic complexity of cerebral malformations means that delayed diagnosis and prolonged decision-making are common, even under optimal conditions of care. Early introduction of standardized prenatal diagnostic examinations is needed for to ensure that the pregnant woman receives open-ended, informed counseling as soon as possible. But late termination of pregnancy is not necessarily negative as, in most cases, this is due to the need for a differentiated prenatal diagnostic evaluation - for example, a fetal MRI - and the ethical requirement of sufficient time to provide informed, well-considered decision-making.