The growth factor EPIREGULIN promotes basal progenitor cell proliferation in the developing neocortex.

Neocortex expansion during evolution is linked to higher numbers of neurons, which are thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells during development. Here, we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex and in gorilla cerebral organoids, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of basal progenitor cells, whereas EREG ablation in human cortical organoids reduces proliferation in the subventricular zone. Treatment of cortical organoids with EPIREGULIN promotes a further increase in proliferation of gorilla but not of human basal progenitor cells. EPIREGULIN competes with the epidermal growth factor (EGF) to promote proliferation, and inhibition of the EGF receptor abrogates the EPIREGULIN-mediated increase in basal progenitor cells. Finally, we identify putative cis-regulatory elements that may contribute to the observed inter-species differences in EREG expression. Our findings suggest that species-specific regulation of EPIREGULIN expression may contribute to the increased neocortex size of primates by providing a tunable pro-proliferative signal to basal progenitor cells in the subventricular zone.

Smelling of the mothers' diet in amniotic fluid by adult noses.

In this study, the transfer of odorants, namely vanilla, and garlic, into the amniotic fluid (AF) during the second trimester was investigated by examination of collected AF samples through healthy adults. Eleven AF samples were collected from pregnant women (aged 32.9 ±â€…4.9 yr, 16-25 wk of gestation) undergoing diagnostic amniocentesis after eating garlic oil or vanilla powder in high-fat yogurt. The control group did not receive food before amniocentesis. Two vanilla, 3 garlic, and 6 control samples were collected through amniocentesis 60-120 min after ingestion. Samples were collected at -80 °C and carefully defrosted over 12 h at the same time point. Sixteen healthy volunteers (8 males, aged 26.5 ±â€…5.0 yr) were asked to judge AF samples with potential garlic or vanilla odors from controls in a 2-alternative forced choice (2AFC) paradigm. Judges were able to identify vanilla in the AF samples with an estimated probability of 50%, resulting in a significant P-value of < 0.001. In contrast, the identification of garlic was unsuccessful with a P-value of 0.86, and only 2 judges were able to identify both vanilla and garlic. According to the results of this study, the vanilla odor probably passes into the amniotic fluid.

[Perinatal Networks: Ensuring Regional Care of Pregnant Woman and Newborns]. / Perinatologische Kompetenznetzwerke: Die Versorgung von Schwangeren und Neugeborenen in einer Region.

Health care of pregnant women and their newborns is facing major challenges due to the decline in birth rate and shortage of specialists. In the current discussion about future concepts, the centralization associated with minimum quantities and the necessary safeguarding of care in the area are often construed as conflicting goals. Instead, concepts are needed to guarantee that pregnant women and their children will continue to receive care close to home. The example of the saxony center for feto/neonatal health is used to show how partners in a region can jointly ensure care during pregnancy, birth and the neonatal period on a supra-local and cross-hospital basis. The close cooperation of maximum care providers with regional partners enables comprehensive health care. At the same time, this cooperation enables hospitals to remain attractive employers in structurally weak regions and to provide comprehensive care for young families in need of medical services related to pregnancy and birth through good family and social integration close to home and work. The overriding goals of the saxony center for feto/neonatal health are optimal, guideline-based, interdisciplinary and intersectoral care of pregnant women and premature or sick newborns in the region.

Evaluation of the telemedical health care network "SAFE BIRTH" for pregnant women at risk, premature and sick newborns and their families: study protocol of a cluster-randomized controlled stepped-wedge trial.

BACKGROUND: The Perinatal Center of the University Hospital Carl Gustav Carus Dresden has initiated the telemedical healthcare network "SAFE BIRTH" to coordinate and improve specialized care in non-metropolitan regions for pregnant women and newborns. The network incorporates five intervention bundles (IB): (1) Multi-professional, inter-disciplinary prenatal care plan; (2) Neonatal resuscitation; (3) Neonatal antibiotic stewardship; (4) Inter-facility transfer of premature and sick newborns; (5) Psycho-social support for parents. We evaluate if the network improves care close to home for pregnant women, premature and sick newborns. METHODS: To evaluate the complex healthcare intervention "SAFE BIRTH" we will conduct a cluster-randomized controlled stepped-wedge trial in five prenatal medical outpatient offices and eight non-metropolitan hospitals in Saxony, Germany. The offices and hospitals will be randomly allocated to five respectively eight sequential steps over a 30-month period to implement the telemedical IB. We define one specific primary process outcome for each IB (for instance IB#1: "Proportion of patients with inclusion criterion IB#1 who have a prenatal care plan and psychosocial counseling within one week"). We estimated a separate multilevel logistic regression model for each primary process outcome using the intervention status as a regressor (control or intervention group). Across all IB, a total of 1,541 and 1,417 pregnant women or newborns need to be included in the intervention and control group, respectively, for a power above 80% for small to medium intervention effects for all five hypothesis tests. Additionally, we will assess job satisfaction and sense of safety of health professionals caring for newborns (questionnaire survey) and we will assess families' satisfaction, resilience, quality of life and depressive, anxiety and stress symptoms (questionnaire surveys). We will also evaluate the cost-effectiveness of "SAFE BIRTH" (statutory health insurance routine data, process data) and barriers to its implementation (semi-structured interviews). We use multilevel regression models adjusting for relevant confounders (e.g. socioeconomic status, age, place of residence), as well as descriptive analyses and qualitative content analyses. DISCUSSION: If the telemedical healthcare network "SAFE BIRTH" proves to be effective and cost-efficient, strategies for its translation into routine care should be developed. TRIAL REGISTRATION: German clinical trials register. DRKS-ID: DRKS00031482.

[Cleft lip and palate : One of the most frequent congenital malformations]. / Lippen-Kiefer-Gaumen-Spalte : Eine der häufigsten angeborenen Fehlbildungen.

With a frequency of 1 per 500 live births, a cleft lip and palate is one of the most frequent congenital malformations. Untreated, it leads to disturbances in feeding, speech, hearing, tooth position and esthetics. A multifactorial genesis is assumed. The fusion of the different facial processes takes place in the first 3 months of pregnancy and a cleft can develop during this time. Surgical treatment includes the early anatomical and functional restoration of the affected structures within the first year of life in order to enable normal intake of food, articulation, nasal breathing and middle ear ventilation. Breastfeeding is possible in children with a cleft formation but alternative feeding methods, such as finger feeding, often have to be used. In addition to the surgery for primary closure of the cleft, otorhinolaryngological (ENT) interventions, speech therapy, orthodontic treatment as well as other surgical interventions are part of the interdisciplinary treatment concept.

Turner syndrome-omphalocele association: Incidence, karyotype, phenotype and fetal outcome.

OBJECTIVE: Omphalocele is known to be associated with genetic anomalies like trisomy 13, 18 and Beckwith-Wiedemann syndrome, but not with Turner syndrome (TS). Our aim was to assess the incidence of omphalocele in fetuses with TS, the phenotype of this association with other anomalies, their karyotype, and the fetal outcomes. METHOD: Retrospective multicenter study of fetuses with confirmed diagnosis of TS. Data were extracted from a detailed questionnaire sent to specialists in prenatal ultrasound. RESULTS: 680 fetuses with TS were included in this analysis. Incidence of small omphalocele in fetuses diagnosed ≥12 weeks was 3.1%. Including fetuses diagnosed before 12 weeks, it was 5.1%. 97.1% (34/35) of the affected fetuses had one or more associated anomalies including increased nuchal translucency (≥3 mm) and/or cystic hygroma (94.3%), hydrops/skin edema (71.1%), and cardiac anomalies (40%). The karyotype was 45,X in all fetuses. Fetal outcomes were poor with only 1 fetus born alive. CONCLUSION: TS with 45,X karyotype but not with X chromosome variants is associated with small omphalocele. Most of these fetuses have associated anomalies and a poor prognosis. Our data suggest an association of TS with omphalocele, which is evident from the first trimester.

[Telemedical support of feto-neonatal care in one region - Part II: Structural requirements and areas of application in neonatology]. / Telemedizinische Unterstützung der feto-neonatalen Versorgung in einer Region ­ Teil II: Strukturelle Voraussetzungen und Anwendungsbereiche in der Neonatologie.

Telemedical infrastructure for patient assessment, care and follow-up as well as interdisciplinary exchange can contribute to ensuring patient care that is close to home and meets the highest quality standards, even outside specialised centres. In neonatology, synchronous audio-visual communication across institutions has been used for many years, especially in the Anglo-American countries. Areas of application include extended neonatal primary care and resuscitation, specific diagnostic applications, e.g. ROP screening and echocardiography, as well as parental care, regular telemedical ward rounds and further training of medical staff, especially using simulation training. For the implementation of such telemedical infrastructures, certain organisational, medical-legal and technical requirements for hardware, software and structural and process organisation must be met. The concrete realisation of a telemedical infrastructure currently being implemented for the region of Eastern Saxony is demonstrated here using the example of the Saxony Center for feto/neonatal Health (SCFNH). Within the framework of feto-neonatal competence networks such as the SCFNH, the quality of medical care, patient safety and satisfaction in a region can be increased by means of a comprehensive, well-structured and established telemedical infrastructure.

[Telemedical Support of Feto-Neonatal Care in One Region - Part I: Demand Analysis Using the Example of East Saxony]. / Telemedizinische Unterstützung der feto-neonatalen Versorgung in einer Region ­ Teil I: Bedarfsanalyse am Beispiel Ost-Sachsen.

Excellence in feto-neonatal care forms the basis for health in adulthood and requires a collaboration of stakeholders in the health care system. As in other regions, demographic changes such as rural depopulation pose a risk to feto-neonatal care in Eastern Saxony. Areas in need of regional, perinatal collaboration have been identified: (I) multi-professional counselling of families with a suspected fetal disease, (II) immediately available expertise of a neonatologist during neonatal resuscitation, (III) evidence-based neonatal antibiotic therapy, (IV) backtransfer of extremely preterm infants or sick neonates, and (V) adequate psychosocial support of families with extremely preterm infants or sick neonates. Telemedicine enables regional partners to communicate efficiently and gives an audiovisual impression of the patient. The Saxony Center for feto/neonatal Health (SCFNH) collaborates with regional partners to establish a feto-neonatal telemedicine network "Sichere Geburt". The network will be scientifically evaluated and might be of help as a model for other regions with structural challenges.

Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening.

INTRODUCTION: Extreme levels of either PAPP-A or free ß-hCG may be a serious clinical concern. A multicentre study was carried out to determine the frequency and clinical consequences of high (minimum 2,0 MoM) maternal (PAPP)-A and free beta hCG. METHODS: A total number of 8591 patients with singleton pregnancies between 11 + 0-13 + 6 weeks of gestation were enrolled. A total number of 612 cases with first trimester serum level of PAPP-A corresponding to ≥ 2,0 MoM and/or free ß-hCG to ≥ 2,0 MoM were included in the statistical analysis. All serum samples were analysed with Roche (Cobas) or Kryptor (Brahms) devices. A retrospective analysis of perinatal outcomes was conducted. RESULTS: Values of PAPP-A ≥ 2,0 MoM and free ß-hCG < 2.0 MoM were detected in 48,5% of patients (n = 297), free ß-hCG ≥ 2,0 MoM and PAPP-A concentration < 2,0 MoM in 38,1% of patients (n = 233) and both PAPP-A and free ß-hCG ≥ 2,0 multiple of median in 13,4% of patients (n = 82). The highest PAPP-A and free ß-hCG concentrations were 19,2 MoM and 16,3 MoM respectively. Patients with both PAPP-A and free ß-hCG above 2,0 MoM had a slightly higher (but statistically not significant) prevalence of history of low birthweight (8,3%). DISCUSSION: Pregnancy outcomes in women with normal ultrasound findings and high PAPP-A /free ß-hCG concentration are good. Higher prevalence of pregnancy complications was not detected in either extremely high PAPP-A and free ß-hCG concentration groups. In cases of normal ultrasound and isolated high (even extreme) biochemical markers levels the counselling should be comforting.

Is Fetal Hydrops in Turner Syndrome a Risk Factor for the Development of Maternal Mirror Syndrome?

Mirror syndrome is a rare and serious maternal condition associated with immune and non-immune fetal hydrops after 16 weeks of gestational age. Subjacent conditions associated with fetal hydrops may carry different risks for Mirror syndrome. Fetuses with Turner syndrome are frequently found to be hydropic on ultrasound. We designed a retrospective multicenter study to evaluate the risk for Mirror syndrome among pregnancies complicated with Turner syndrome and fetal hydrops. Data were extracted from a questionnaire sent to specialists in maternal fetal medicine in Germany. Out of 758 cases, 138 fulfilled our inclusion criteria and were included in the analysis. Of the included 138, 66 presented with persisting hydrops at or after 16 weeks. The frequency of placental hydrops/placentomegaly was rather low (8.1%). Of note, no Mirror syndrome was observed in our study cohort. We propose that the risk of this pregnancy complication varies according to the subjacent cause of fetal hydrops. In Turner syndrome, the risk for Mirror syndrome is lower than that reported in the literature. Our observations are relevant for clinical management and parental counseling.

A review of image processing methods for fetal head and brain analysis in ultrasound images.

BACKGROUND AND OBJECTIVE: Examination of head shape and brain during the fetal period is paramount to evaluate head growth, predict neurodevelopment, and to diagnose fetal abnormalities. Prenatal ultrasound is the most used imaging modality to perform this evaluation. However, manual interpretation of these images is challenging and thus, image processing methods to aid this task have been proposed in the literature. This article aims to present a review of these state-of-the-art methods. METHODS: In this work, it is intended to analyze and categorize the different image processing methods to evaluate fetal head and brain in ultrasound imaging. For that, a total of 109 articles published since 2010 were analyzed. Different applications are covered in this review, namely analysis of head shape and inner structures of the brain, standard clinical planes identification, fetal development analysis, and methods for image processing enhancement. RESULTS: For each application, the reviewed techniques are categorized according to their theoretical approach, and the more suitable image processing methods to accurately analyze the head and brain are identified. Furthermore, future research needs are discussed. Finally, topics whose research is lacking in the literature are outlined, along with new fields of applications. CONCLUSIONS: A multitude of image processing methods has been proposed for fetal head and brain analysis. Summarily, techniques from different categories showed their potential to improve clinical practice. Nevertheless, further research must be conducted to potentiate the current methods, especially for 3D imaging analysis and acquisition and for abnormality detection.

Are two children at once better than one? Risk analysis of twin pregnancies and births after assisted reproduction.

OBJECTIVES: Pregnancies and births following assisted reproductive treatment (ART) are related to an increased risk for adverse perinatal outcomes. The aim of this retrospective cohort study at a University Hospital with a tertiary perinatal center was the combined risk analysis of singleton and twin pregnancies after ART in comparison to spontaneously conceived pregnancies. STUDY DESIGN: Maternal and fetal risks were analyzed in subgroups after spontaneous conception (N = 14,233) and ART (N = 785) during the 6-year study period from 2014 to 2019. Odds ratios for perinatal risks between the groups were calculated and adjusted for maternal age and gestational week at birth using a matched control analysis. Subgroups of preterm delivery were compared. RESULTS: The overall maternofetal risks after ART are higher than after spontaneous conception. Maternal risks after ART are mainly related to higher maternal age (p < 0.001). Preterm delivery and neonatal complications are more frequent in twins than in singletons (p < 0.001), but no statistically significant differences were seen in comparison in the subgroup of twins due to conception. Higher maternal age and body mass index did not increase the risk of preterm birth in twin pregnancies. CONCLUSIONS: Maternal risks in pregnancies after ART are mainly influenced by maternal age. The strongest risk factor in ART pregnancies is a multiple pregnancy. Every 5th pregnancy after ART was a twin pregnancy with higher risks for preterm delivery, maternal hospitalization and adverse neonatal outcome (p < 0.001). Advanced maternal age in ART cannot be altered, but twin pregnancies can be actively avoided using the single embryo transfer strategy.

Evaluation of carcinoembryonic antigen-related cell adhesion molecule 1 blood serum levels in women at high risk for preeclampsia.

PROBLEM: The aim of this study was to evaluate the sCEACAM1 concentrations in serum from patients in the first trimester who have a high risk for developing PE during pregnancy. METHOD OF THE STUDY: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) levels were determined with ELISA. The patients (n = 109) were divided into two groups: patients who have a high risk of developing PE early-onset and a control group. Patients who have a high risk of developing PE were then divided into two subgroups depending on PE development in third trimester of pregnancy: PE in third trimester versus no PE in third trimester. RESULTS: sCEACAM1 concentrations in patients who were screened as having a high risk for developing PE were significantly higher than in healthy pregnant women in the first trimester (p = .03). The highest sCEACAM1 concentration was found in the high-risk group with PE development compared to the control group (p = .004). CONCLUSION: Elevated sCEACAM1 blood serum levels in women with PE suggest that there is immune dysregulation in early pregnancy, which may be helpful in PE prediction and therapy.

Placenta accreta spectrum disorders-experience of management in a German tertiary perinatal centre.

PURPOSE: Placenta accreta spectrum (PAS) disorders can cause major intrapartum haemorrhage. The optimal management approach is not yet defined. We analysed available cases from a tertiary perinatal centre to compare the outcome of different individual management strategies. METHODS: A monocentric retrospective analysis was performed in patients with clinically confirmed diagnosis of PAS between 07/2012 and 12/2019. Electronic patient and ultrasound databases were examined for perinatal findings, peripartum morbidity including blood loss and management approaches such as (1) vaginal delivery and curettage, (2) caesarean section with placental removal versus left in situ and (3) planned, immediate or delayed hysterectomy. RESULTS: 46 cases were identified with an incidence of 2.49 per 1000 births. Median diagnosis of placenta accreta (56%), increta (39%) or percreta (4%) was made in 35 weeks of gestation. Prenatal detection rate was 33% for all cases and 78% for placenta increta. 33% showed an association with placenta praevia, 41% with previous caesarean section and 52% with previous curettage. Caesarean section rate was 65% and hysterectomy rate 39%. In 9% of the cases, the placenta primarily remained in situ. 54% of patients required blood transfusion. Blood loss did not differ between cases with versus without prenatal diagnosis (p = 0.327). In known cases, an attempt to remove the placenta did not show impact on blood loss (p = 0.417). CONCLUSION: PAS should be managed in an optimal setting and with a well-coordinated team. Experience with different approaches should be proven in prospective multicentre studies to prepare recommendations for expected and unexpected need for management.

Prenatal Prediction of Outcome by Fetal Gastroschisis in a Tertiary Referral Center.

: The aim of this study was to find a prenatal parameter to be able to predict possible prenatal complications or postnatal surgical options, thus allowing the fetal medicine specialist, together with pediatric surgeons and neonatologists, to improve the counseling of the parents and to determine the timing of delivery and therapy. This was a retrospective analysis of prenatal diagnosis and outcome of fetuses with 34 cases of gastroschisis between the years 2007 and 2017. A total of 34 fetuses with gastroschisis were examined and 33 outcomes registered: 22 cases of simple gastroschisis (66.7%) and 11 cases of complex gastroschisis (33.3%). A cut-off value of 18 mm for intraabdominal bowel dilatation (IABD) showed a positive predictive value (PPV) of 100% for predicting simple gastroschisis. IABD gives the best prediction for simple versus complex gastroschisis (cut-off of 18 mm). Extra-abdominal bowel dilatation (EABD) cut-off values of 10 mm and 18 mm showed low sensitivity and specificity to predict complex gastroschisis.

[Intrauterine Growth Restriction: Transsectoral, Interdisciplinary and Multiprofessional Care for Pregnant Women and Newborns in a Feto-neonatal Pathway: A Project of the Innovationsfonds]. / Intrauterine Wachstumsrestriktion: Transsektorale, interdisziplinäre und multiprofessionelle Betreuung von Schwangeren und Neugeborenen im Feto-Neonat-Pfad: Ein Projekt des Innovationsfonds.

Intrauterine growth restriction (IUGR) is present in fetuses that do not achieve their full in-utero growth potential. IUGR needs to be discriminated from small for gestational age (SGA) because IUGR newborns in particular experience long-term side effects from their small growth. IUGR fetuses have a significantly increased risk of prematurity and a distinct risk profile compared to adequate-for-gestational-age preterm newborns. Complications of prematurity are more frequent, including bronchopulmonary dysplasia, intraventricular hemorrhage, and meconium ileus. IUGR newborns are at risk of long-term health issues like cerebral palsy, impaired lung function, and delayed speech development. Interdisciplinary and interprofessional care of IUGR pregnancies in the context of a standardized health care research project is feasible: Pregnant women at risk are identified, early therapy with acetylsalicylic acid is started as indicated, risk-adapted care at level III centers is organized including psychosocial interventions and neonatal consultations. Postnatally, integrated neonatal care focusing on parent-child interaction and optimized nutrition is a hallmark. Afterwards, in-depth pediatric follow-up visits with local pediatricians help to identify growth and neurodevelopment problems early. The effects, acceptance. and cost efficiency of this approach are evaluated prospectively as part of an Innovationsfonds project.

["Crystal" and Pregnancy - The Preliminary Results of a Retrospective Study on the Course of Pregnancy and Delivery of Women Consuming Methamphetamine]. / "Crystal" und Schwangerschaft ­ erste Ergebnisse einer retrospektiven Studie zum Schwangerschafts- und Geburtsverlauf Methamphetamin-konsumierender Frauen in Sachsen.

INTRODUCTION: It can be observed that there is an increase in the methamphetamine (MA) consumption in Saxony (Federal Republic of Germany). There is so far no data available in German speaking countries about the risk of MA consumption in pregnancy or delivery. METHODS: The data from all pregnant women who were examined or delivered at the Clinic for Obstetrics and Gynaecology between 2010-2015 were retrospectively searched for MA consumption. 119 pregnancies with 113 deliveries of 115 women consuming MA could be evaluated. 88 women admitted the consumption according to the history, 28 women denied it and there was no information available in the records of 3 cases. 113 women agreed to test MA in blood and 93 cases were positive (28 cases of them with low-dose consumption). The statistical analysis was performed by the Institute for Medical Informatics and Biometry. The data driven from the quality control report of the department of Gynaecology in 2015 was used as a control group. RESULTS: MA-consumers are significantly younger, without a permanent relationship, without a job and have a low education level. The first detection of the pregnancy was late and the number of performed routine examinations including ultrasound assessment was lower compared to the controls. 7 women had no routine examination. The number of premature contractions, cervical insufficiency and gestational diabetes were significantly higher. The number of patients needing tocolysis, antenatal glucocorticoid treatment for prevention of neonatal respiratory distress syndrome or in-patient care was significantly higher in patients consuming MA. The number of amniotic infection syndrome and premature rupture of membranes were higher. The rate of intrauterine fetal death was 3,5% which was much higher than the rate of control group (0,2%). DISCUSSION: The MA-consumption increases the risk for mother and child significantly during the pregnancy and delivery (pregnancy complications, premature delivery, increased rate of abortion, intrauterine death). A special attention must be taken for the young pregnant, non-working women without a partner who do not take the routine examinations in account or start having them late.

Afamin: an early predictor of preeclampsia.

PURPOSE: Oxidative stress is involved in the pathogenesis of hypertensive disorders such as preeclampsia (PE) and associated with the human vitamin E-binding protein afamin. The aim of this study was, therefore, to analyse afamin in the first trimester of patients developing PE later in pregnancy and in control subjects without pregnancy complications. METHODS: In this retrospective study, 137 serum samples from the first trimester of pregnancy were analysed in a case-control study design. 39 patients developed PE (10 patients with early-onset and 29 patients with late onset disease) and 98 women had an uncomplicated pregnancy. Mann-Whitney U test, t test, logistic regression and ROC analyses were performed for statistical evaluation. RESULTS: Pregnant women developing PE presented with higher afamin concentrations in the first trimester [median 101.81 mg/L; interquartile range (IQR) 88.94-113.26] compared to subjects with uncomplicated pregnancy (median 86.40; IQR 75.26-96.92; p < 0.001). After adjusting for confounders, the odds ratio per afamin standard deviation was 1.60 (95% CI: 1.04-2.58; p = 0.04). An afamin threshold concentration of 87.8 mg/L exhibited the best sensitivity (79.5%) and specificity (57.1%) in predicting PE. Subgroup analysis of early- and late-onset disease resulted in substantially higher afamin concentrations in women with developing late-onset PE compared to controls (p < 0.001) with an odds ratio per afamin standard deviation of 1.62 (95% CI: 0.98-2.70; p = 0.06). CONCLUSIONS: Serum afamin concentrations are elevated in the first trimester among patients developing PE compared to controls. Substantial differences were observed mainly among patients with late-onset PE.

Soluble B7-H4 blood serum levels are elevated in women at high risk for preeclampsia in the first trimester, as well as in patients with confirmed preeclampsia.

PROBLEM: B7-H4 negatively regulates T-cell-mediated immunity and might play an important role in preeclampsia (PE). Here, we have investigated the association between PE and maternal soluble B7-H4 (sB7-H4) serum levels and B7-H4 mRNA expression in the placenta. METHOD OF STUDY: Maternal serum levels of sB7-H4 were determined by enzyme-linked immunosorbent assay in women between 11 and 13 weeks' gestation with elevated risk for PE (n = 48) and women without elevated risk for PE (n = 47). In the third trimester, sB7-H4 serum levels (n = 166) and B7-H4 mRNA expression in the placenta (n = 54) were determined in women with early-onset PE, late-onset PE, fetal growth restriction (FGR), and in healthy controls. RESULTS: In the first trimester, significant higher levels of sB7-H4 were detected in women at elevated risk for PE compared to women without risk for PE (P < .0001). sB7-H4 has some predictive ability to identify cases with an elevated risk of developing PE with area under the curve (AUC) value of 0.88 (95% CI 0.8-0.94). Using a specificity of 90.0% led to a sensitivity of 47.9% and a threshold of 3.63 ng/mL. In the third trimester, the highest serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in early-onset PE. Significant higher serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in women with early-onset PE (P = .01 and P = .006, respectively) and late-onset PE (P = .03 and P = .004, respectively) compared to healthy controls, but not compared to FGR. CONCLUSION: sB7-H4 is involved in the regulation of immune tolerance in women with PE in the third trimester. In the first trimester of pregnancy, sB7-H4 might serve as a predictive immunological biomarker for women who are at elevated risk of developing PE.