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.

Characterization of human placental fetal vessels in gestational diabetes mellitus.

Gestational diabetes mellitus is one of the most common complications during pregnancy. Its prevalence is rapidly increasing worldwide. Gestational diabetes mellitus is leading to an elevated risk for the development of endothelial dysfunction and cardiovascular diseases both in the mother and the child in later life. The underlying pathophysiological mechanisms are not well-understood. Therefore, we aimed to characterize the endothelial function in fetal placental vessels from mothers with gestational diabetes mellitus. In this study, we distinguished between insulin-treated and diet-controlled gestational diabetes mothers and compared them to a normoglycemic control group. The clinical data confirmed pre-conceptional overweight as a risk factor in women with insulin-treated gestational diabetes mellitus. The insulin-treated gestational diabetes group was also characterized by a recent family history of diabetes compared to mothers of the control or diet-controlled gestational diabetes group. Analyses of blood serum from umbilical cords suggested a reduced fetal insulin metabolism in the insulin-treated gestational diabetes group. Vascular function analysis in fetal placental vessels revealed an altered substance P-induced vasorelaxation in vessels from patients with insulin-dependent gestational diabetes. Inhibition of nitric oxide synthase affected only fetal vessel segments from the control group or diet-controlled gestational diabetes group, but not from insulin-dependent gestational diabetes. Finally, we found a significantly decreased substance P receptor (TACR1) mRNA expression in fetal vessel segments from patients with insulin-treated gestational diabetes. In conclusion, we provide evidence that different pathophysiological mechanisms might be responsible for the development of insulin-treated versus diet-controlled gestational diabetes. Only in fetal vessels from patients with insulin-treated gestational diabetes were we able to detect an endothelial dysfunction and a reduced fetal insulin conversion. This provides novel insights into the pathophysiology of the subtypes of gestational diabetes.

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.

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.

[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.

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.

[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.

[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.

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.

[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.

Idiopathic polyhydramnios and fetal gender.

OBJECTIVES: To determine the relationship between idiopathic polyhydramnios and fetal gender in the absence of fetal or maternal abnormalities. METHODS: This was a retrospective population-based register study. 295 women with singleton pregnancies complicated by idiopathic polyhydramnios (amniotic fluid index (AFI) higher than 24 cm) who were delivered at our institution from January 2002 till December 2012 were included. Only pregnancies with an uncomplicated outcome were accepted in this study. The incidence of the male to female fetuses was compared with the one in the general population. RESULTS: Among pregnancies complicated by idiopathic polyhydramnios, the following gender distribution was found: 72.9% male and 37.1% female. The distribution in the general population was 51.5% female and 48.5% male. The mean AFI was significantly increased in male fetuses (p < 0.001). The increased AFI did not correlate with gestation age, fetal head circumference or estimated fetal weight. CONCLUSIONS: Idiopathic polyhydramnios is more frequent in male normal fetuses than in female ones.

Maternal serum copeptin, MR-proANP and procalcitonin levels at 11-13 weeks gestation in the prediction of preeclampsia.

PURPOSE: We investigated the potential value of maternal serum copeptin, midregional proatrial natriuretic peptide (MR-proANP) and Procalcitonin (PCT) levels at 11-13 weeks' gestation in the prediction of preeclampsia (PE) in a case-control study. MATERIALS AND METHODS: Maternal serum concentration of copeptin, MR-proANP and PCT were measured at 11-13 weeks' gestation in cases of PE (n = 35) and controls (n = 100). The PE group was divided into early-onset PE (EO-PE) and late-onset PE (LO-PE). From the regression model, the value in each case and control was expressed as a multiple of the expected median (MoM). The Mann-Whitney test was used to determine the significance of differences in the median MoM in each outcome group from that in the controls. RESULTS: In the PE group, compared to controls, maternal serum concentrations of copeptin, MR-proANP and PCT were not significantly different. CONCLUSION: The maternal serum copeptin, MR-proANP and PCT levels are higher in EO-PE and LO-PE patients, but the difference is not significant. Thus, their levels in first trimester are not proven to be effective markers to screen for PE.

Embryo reduction in dichorionic triplets to dichorionic twins by intrafetal laser.

OBJECTIVE: To describe a new technique for embryo reduction (ER) in dichorionic triplet (DCT) pregnancies. METHODS: In 22 DCT pregnancies, ER to dichorionic twins was carried out at 11.3-13.9 weeks' gestation by ultrasound-guided laser ablation of the pelvic vessels of one of the monochorionic twins. RESULTS: Intrafetal laser was successfully carried out in all cases, but ultrasound examination within 2 weeks of the procedure demonstrated that the co-twin had died in 11 cases and was alive in the other 11. In the dichorionic group there was one miscarriage at 23 weeks due to cervical incompetence and in the other 10 cases there were two live births at a median gestational age of 35.0 (range 32.2-37.1) weeks. In the 11 cases where both monochorionic fetuses died the separate triplet was live born at a median gestation of 38.0 (range 32.2-40.5) weeks. CONCLUSIONS: In the management of DCT pregnancies, ER to dichorionic twins by intrafetal laser is an additional option to the traditional ones of expectant management, ER by intrafetal injection of potassium chloride (KCl) to monochorionic twins or ER by KCl to singleton.

Deep-DM: Deep-driven deformable model for 3D image segmentation using limited data.

Objective - Medical image segmentation is essential for several clinical tasks, including diagnosis, surgical and treatment planning, and image-guided interventions. Deep Learning (DL) methods have become the state-of-the-art for several image segmentation scenarios. However, a large and well-annotated dataset is required to effectively train a DL model, which is usually difficult to obtain in clinical practice, especially for 3D images. Methods - In this paper, we proposed Deep-DM, a learning-guided deformable model framework for 3D medical imaging segmentation using limited training data. In the proposed method, an energy function is learned by a Convolutional Neural Network (CNN) and integrated into an explicit deformable model to drive the evolution of an initial surface towards the object to segment. Specifically, the learning-based energy function is iteratively retrieved from localized anatomical representations of the image containing the image information around the evolving surface at each iteration. By focusing on localized regions of interest, this representation excludes irrelevant image information, facilitating the learning process. Results and conclusion - The performance of the proposed method is demonstrated for the tasks of left ventricle and fetal head segmentation in ultrasound, left atrium segmentation in Magnetic Resonance, and bladder segmentation in Computed Tomography, using different numbers of training volumes in each study. The results obtained showed the feasibility of the proposed method to segment different anatomical structures in different imaging modalities. Moreover, the results also showed that the proposed approach is less dependent on the size of the training dataset in comparison with state-of-the-art DL-based segmentation methods, outperforming them for all tasks when a low number of samples is available. Significance - Overall, by offering a more robust and less data-intensive approach to accurately segmenting anatomical structures, the proposed method has the potential to enhance clinical tasks that require image segmentation strategies.

Anti-Mullerian-hormone levels during pregnancy and postpartum.

BACKGROUND: The number of unintentionally childless couples is increasing as more couples seek to conceive for the first time in the third or fourth decade of the woman's life. Determination of ovarian reserve is an essential component of infertility assessment. The Anti-Müllerian-Hormone (AMH) seems to be the most reliable predictor of ovarian reserve. In this study we analyzed AMH in a cohort of pregnant women without fertility impairment to determine age-dependent decline and possible AMH fluctuations during pregnancy and postpartum. METHODS: A total of 554 healthy women aged 16 to 47 years without history of infertility or previous surgery on the ovaries were enrolled in the study between 1995 and 2012. In 450 women, a single measurement of AMH was taken during pregnancy, allowing for cross sectional analysis of trimester- and age-related differences in AMH levels. For another 15 women longitudinal data on AMH levels for all trimesters was recorded. In addition, for 69 women AMH was measured at the time just before and after delivery, and for another 20 AMH was measured just before delivery and once on each of the first four days after delivery. We used AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, USA) for the assessment of AMH levels. Non-parametric statistical tests were used to compare AMH levels between age groups, trimesters and postpartum. RESULTS: Comparison between the trimesters revealed a significant difference in AMH values at each trimester (first trimester: 1.69 ng/ml (IQR 0.71-3.10), second trimester: 0.8 ng/ml (IQR 0.48-1.41), third trimester: 0.5 ng/ml (IQR 0.18-1.00)). AMH significantly dropped during the course of pregnancy and immediately after delivery, whereas an increase was observed over the first four days postpartum. Women, greater than or equal to 35 years, showed significant lower AMH levels than those <35 years across all trimesters. CONCLUSIONS: AMH levels decrease during pregnancy. The decline in AMH levels during pregnancy indicates ovarian suppression. AMH levels recover quickly after delivery. AMH levels assessed in pregnant women are not an accurate indicator of ovarian reserve, since AMH levels during pregnancy seem not to be independent of gestational age.

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.

Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population.

OBJECTIVE: We sought to assess performance of noninvasive prenatal testing for fetal trisomy in a routinely screened first-trimester pregnancy population. STUDY DESIGN: This was a cohort study of 2049 pregnant women undergoing routine screening for aneuploidies at 11-13 weeks' gestation. Plasma cell-free DNA analysis using chromosome-selective sequencing was used. Laboratory testing on a single plasma sample of 2 mL was carried out blindly and results were provided as risk score (%) for trisomies 21 and 18. RESULTS: Trisomy risk scores were given for 95.1% (1949 of 2049) of cases including all 8 with trisomy 21 and 2 of the 3 with trisomy 18. The trisomy risk score was >99% in the 8 cases of trisomy 21 and 2 of trisomy 18 and <1% in 99.9% (1937 of 1939) of euploid cases. CONCLUSION: Noninvasive prenatal testing using chromosome-selective sequencing in a routinely screened population identified trisomies 21 and 18 with a false-positive rate of 0.1%.