[COVID-19 in Pregnancy - a Risk for the Unborn Child?] / COVID-19 in der Schwangerschaft: Ursache für eine intrakranielle Blutung bei einem Frühgeborenen?

Geburtskliniken werden zunehmend mit an Covid-19 erkrankten Schwangeren konfrontiert. Dies stellt Geburtshelfer vor große Herausforderungen, da einige Fragestellungen noch nicht ausreichend wissenschaftlich erforscht sind. Über Covid-19 während der Schwangerschaft und seine Auswirkungen auf das ungeborene und neugeborene Kind ist nicht viel bekannt.

Percent error of ultrasound examination to estimate fetal weight at term in different categories of birth weight with focus on maternal diabetes and obesity.

BACKGROUND: Sonography based estimate of fetal weight is a considerable issue for delivery planning. The study evaluated the influence of diabetes, obesity, excess weight gain, fetal and neonatal anthropometrics on accuracy of estimated fetal weight with respect to the extent of the percent error of estimated fetal weight to birth weight for different categories. METHODS: Multicenter retrospective analysis from 11,049 term deliveries and fetal ultrasound biometry performed within 14 days to delivery. Estimated fetal weight was calculated by Hadlock IV. Percent error from birth weight was determined for categories in 250 g increments between 2500 g and 4500 g. Estimated fetal weight accuracy was categorized as accurate ≤ 10% of birth weight, under- and overestimated by > ± 10% - ± 20% and > 20%. RESULTS: Diabetes was diagnosed in 12.5%, obesity in 12.6% and weight gain exceeding IOM recommendation in 49.1% of the women. The percentage of accurate estimated fetal weight was not significantly different in the presence of maternal diabetes (70.0% vs. 71.8%, p = 0.17), obesity (69.6% vs. 71.9%, p = 0.08) or excess weight gain (71.2% vs. 72%, p = 0.352) but of preexisting diabetes (61.1% vs. 71.7%; p = 0.007) that was associated with the highest macrosomia rate (26.9%). Mean percent error of estimated fetal weight from birth weight was 2.39% ± 9.13%. The extent of percent error varied with birth weight with the lowest numbers for 3000 g-3249 g and increasing with the extent of birth weight variation: 5% ± 11% overestimation in the lowest and 12% ± 8% underestimation in the highest ranges. CONCLUSION: Diabetes, obesity and excess weight gain are not necessarily confounders of estimated fetal weight accuracy. Percent error of estimated fetal weight is closely related to birth weight with clinically relevant over- and underestimation at both extremes. This work provides detailed data regarding the extent of percent error for different birth weight categories and may therefore improve delivery planning.

Induction of Labour. Guideline of the DGGG, OEGGG and SGGG (S2k, AWMF Registry No. 015-088, December 2020).

Aim The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society of Gynaecology and Obstetrics (OEGGG) and the Swiss Society of Gynaecology and Obstetrics (SGGG) is to provide a consensus-based overview of the indications, methods and general management of induction of labour by evaluating the relevant literature. Methods This S2k guideline was developed using a structured consensus process which included representative members from various professions; the guideline was commissioned by the guidelines commission of the DGGG, OEGGG and SGGG. Recommendations The guideline provides recommendations on the indications, management, methods, monitoring and special situations occurring in the context of inducing labour.

The cumulative impact of parity on the body mass index (BMI) in a non-selected Lower Saxony population.

OBJECTIVES: During the last decade obesity has been continuously rising in adults in industrial countries. The increased occurrence of perinatal complications caused by maternal obesity poses a major challenge for obstetricians during pregnancy and childbirth. This study aims to examine the association between parity, pregnancy, birth risks, and body mass index (BMI) of women from Lower Saxony, Germany. METHODS: This retrospective cohort study examined pseudonymized data of a non-selected singleton cohort from Lower Saxony's statewide quality assurance initiative. Mothers were categorized according to BMI as normal weight (18.5 to <25 kg/m2) or obese (≥30 kg/m2). RESULTS: Most of the mothers in this study population were either in their first (33.9%) or second pregnancy (43.4%). The mean age of women giving birth for the first time was 28.3 years. Maternal age increased with increasing parity. The proportion of pregnant women with a BMI over 30 was 11% in primiparous women, 14.3% in second para, 17.3% in third para and 24.1% in fourth para or more women. Increasing parity was positively correlated with the incidence of classical diseases related to obesity, namely diabetes mellitus, gestational diabetes, hypertension, pregnancy-related hypertension and urinary protein excretion. An increased risk of primary or secondary cesarean section was observed in the obese women, particularly during the first deliveries. CONCLUSIONS: There is a positive and significant correlation between parity and increased maternal BMI. The highest weight gain happens during the first pregnancy. The rate of operative deliveries and complications during delivery is increased in obese pregnant women.

Fetal Weight Estimation Using Automated Fractional Limb Volume With 2-Dimensional Size Parameters: A Multicenter Study.

OBJECTIVES: To develop new fetal weight prediction models using automated fractional limb volume (FLV). METHODS: A prospective multicenter study measured fetal biometry within 4 to 7 days of delivery. Three-dimensional data acquisition included the automated FLV that was based on 50% of the humerus diaphysis (fractional arm volume [AVol]) or 50% of the femur diaphysis (fractional thigh volume [TVol]) length. A regression analysis provided population sample-specific coefficients to develop 4 weight estimation models. Estimated and actual birth weights (BWs) were compared for the mean percent difference ± standard deviation of the percent differences. Systematic errors were analyzed by the Student t test, and random errors were compared by the Pitman test. RESULTS: A total of 328 pregnancies were scanned before delivery (BW range, 825-5470 g). Only 71.3% to 72.6% of weight estimations were within 10% of actual BW using original published models by Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337) and INTERGROWTH-21st (Ultrasound Obstet Gynecol 2017; 49:478-486). All predictions were accurate by using sample-specific model coefficients to minimize bias in making these comparisons (Hadlock, 0.4% ± 8.7%; INTERGROWTH-21st, 0.5% ± 10.0%; AVol, 0.3% ± 7.4%; and TVol, 0.3% ± 8.0%). Both AVol- and TVol-based models improved the percentage of correctly classified BW ±10% in 83.2% and 83.9% of cases, respectively, compared to the INTERGROWTH-21st model (73.8%; P < .01). For BW of less than 2500 g, all models slightly overestimated BW (+2.0% to +3.1%). For BW of greater than 4000 g, AVol (-2.4% ± 6.5%) and TVol (-2.3% ± 6.9%) models) had weight predictions with small systematic errors that were not different from zero (P > .05). For these larger fetuses, both AVol and TVol models correctly classified BW (±10%) in 83.3% and 87.5% of cases compared to the others (Hadlock, 79.2%; INTERGROWTH-21st, 70.8%) although these differences did not reach statistical significance. CONCLUSIONS: In this cohort, the inclusion of automated FLV measurements with conventional 2-dimensional biometry was generally associated with improved weight predictions.

Ultrasound Fetal Weight Estimation in Diabetic Pregnancies.

OBJECTIVES: To evaluate different formulas for estimating fetal weight in diabetic pregnancies. METHODS: This retrospective study evaluated the precision of ultrasound fetal weight estimation in 756 pregnancies complicated by gestational diabetes between 2002 and 2016. The estimated fetal weights (EFWs) were obtained within 7 days of delivery from 10 weight estimation formulas and were compared with pair-wise matched controls from 15,701 patients. The precision of the evaluated formulas for EFW was analyzed by median absolute percentage errors (MAPEs), mean percentage errors (MPEs), and proportions of estimates within 10% of actual birth weight. RESULTS: Among the tested formulas, the lowest MAPE was detected with formula I of Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337), and the formula of Schild et al (Ultrasound Obstet Gynecol 2004; 23:30-35) had the highest proportion of estimates within the 10% range. The EFW in diabetic patients showed a slight trend toward overestimation in comparison with the matched controls (MPE estimates showed a trend toward more positive values). In most of the EFW formulas that were evaluated, no significant differences were detected in MAPEs and estimates within the 10% range. The MPE estimates with most formulas in both groups were close to zero. Overall, the differences between most of the evaluated formulas were small. CONCLUSIONS: Little evidence was found for differences in the accuracy of the EFW in diabetic pregnancies and controls. The Hadlock I formula showed the lowest MAPE, and the Schild formula had the highest proportion of estimates within the 10% range.

Correlation of short-term variation and Doppler parameters with adverse perinatal outcome in small-for-gestational age fetuses at term.

OBJECTIVE: To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in small-for-gestational-age (SGA) fetuses at term. METHODS: In this retrospective single-center study 97 patients with singleton SGA fetuses at term (≥ 37 + 0 weeks' gestation) were examined. Inclusion criteria were a birth weight < 10th centile, cephalic presentation and planned vaginal birth. Only cases with available Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) with calculated cerebroplacental ratio (CPR) in combination with a computerized CTG (cCTG) and STV 72 h prior to delivery were eligible for analysis. Pulsatility indices (PI) were converted into multiples of median (MoM), adjusted for gestational age. The association between Doppler indices and STV values with mode of delivery [secondary cesarean delivery (CD), operative vaginal delivery (OVD), as well as secondary CD and OVD due to fetal distress] and neonatal outcome [UA blood pH ≤ 7.15 and the need of admission to the neonatal intensive care unit (NICU)] was analyzed using logistic regression analysis. RESULTS: There was a significant association between UA PI MoM and the rate of CD. CD due to fetal distress, OVD and OVD due to fetal distress did not show a correlation with the evaluated Doppler parameters. Furthermore, we did not find an association between low UA birth pH and Doppler parameters while neonates with the need of admission to NICU had significant higher UA PI MoM and significant lower MCA PI MoM and CPR MoM. Regarding STV, a significant effect of low STV on NICU admission was found while none of the other assessed outcome parameters were significantly associated with STV. CONCLUSION: STV and Doppler parameters in SGA fetuses at term are significantly associated to the rate of NICU admission.

Correlation of short-term variation and Doppler parameters with adverse perinatal outcome in low-risk fetuses at term.

OBJECTIVE: To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in low-risk fetuses at term. METHODS: This was a retrospective study of 1008 appropriate-for-gestational age (AGA) term fetuses. Doppler measurements [umbilical artery (UA), middle cerebral artery (MCA), and cerebroplacental ratio (CPR)] and computerized CTG (cCTG) with STV analysis were performed prior to active labor (≤ 4 cm cervical dilatation) within 72 h of delivery. The association between Doppler indices and STV values with adverse perinatal outcome was analyzed using univariate regression analysis. RESULTS: No significant association between Doppler parameters and the need for secondary cesarean delivery (CD) or operative vaginal delivery (OVD) was shown. Regarding fetuses delivered by CD due to fetal distress, regression analyzes revealed significantly higher UA PI MoM. However, the differences in MCA PI MoM and CPR MoM were not statistically significant. Fetuses with the need for emergency CD showed significantly higher UA PI MoM, lower MCA PI MoM and lower CPR MoM. Neonates with a 5-min Apgar score < 7 had significantly lower MCA PI MoM and neonatal acidosis (UA pH ≤ 7.10) showed a significant association with UA PI MoM. None of the assessed outcome parameters were significantly associated to STV. CONCLUSION: Doppler indices assessed close to delivery in low-risk fetuses at term show a moderate association with adverse outcome parameters, whereas STV does not appear to predict poor perinatal outcome in this group of fetuses.

Piepkorn type of osteochondrodysplasia: Defining the severe end of FLNB-related skeletal disorders in three fetuses and a 106-year-old exhibit.

The Piepkorn type of lethal osteochondrodysplasia (POCD) is a rare and lethal dwarfing condition. Four cases have been reported to date. The characteristic features are distinctly shortened "flipper-like" limbs, polysyndactyly, excessive underossification, especially of the limb bones and vertebrae, and large (giant) chondrocytes in the cartilaginous bone primordia. These characteristics allowed the diagnosis of Piepkorn type of osteochondrodysplasia in four new cases, three fetuses of 15 to 22 weeks and one 106-year-old museum exhibit. Piepkorn type of osteochondrodysplasia has been assigned to the giant cell chondrodysplasias such as atelosteogenesis type 1 (AO1) and boomerang dysplasia (BD). Analysis of the Filamin B gene in 3p14.3, which is associated with these disorders, allowed the identification of the first FLNB mutations in Piepkorn type of osteochondrodysplasia. The heterozygous missense mutations, found in the three fetuses, were located in exons 28 and 29, encoding the immunoglobulin-like repeat region R15, one of three mutational hot spots in dominant FLNB-related skeletal disorders. Direct preparations and alcian blue staining revealed single upper and lower arm and leg bone primordia, preaxial oligodactyly, and polysyndactyly with complete fusion and doubling of the middle and end phalanges II-V to produce eight distal finger rays. Considering the unique clinical features and the extent of underossification, Piepkorn type of osteochondrodysplasia can be regarded as a distinct entity within the AO1-BD-POCD continuum.

Longitudinal z Score Distribution in Sonographic Fetal Biometry: Influence of Examiner and Experience.

OBJECTIVES: To analyze the influence of examiners and their experience on the quality of biometric measurements via the evolution of z scores in a longitudinal multicenter study. METHODS: This retrospective study included 4607 sonographic fetal biometric examinations performed by 18 examiners at the beginning of their sonography training. To analyze the quality of biometric measurements, z scores comparing the individual measurements with the expected values from a standard population were computed. To investigate the effect of examiners and their experience, we applied a multivariable regression analysis via generalized additive mixed models. RESULTS: Mean z scores for biparietal diameter, abdominal circumference, and femur length were statistically different from the expected value of 0 (P < .001); no significant differences were found for head circumference measurements. Regression analyses showed a significant effect of the number of examinations on the distribution of z scores for each type of measurement. This effect yielded z score values close to the expected value of 0 at 100 to 200 examinations for all biometric measurements, indicating good consistency with the distribution of values in the reference population. Near the end of the study period, an increasing tendency toward either overestimation (head circumference) or underestimation (biparietal diameter, abdominal circumference, and femur length) was observed. CONCLUSIONS: A longitudinal analysis of the z score distribution for quality control of biometry is feasible. A prospective and automatized use of this technique could help identify potential systematic errors and therefore improve the detection rate for high-risk pregnancies.

Longitudinal Assessment of Examiner Experience and the Accuracy of Sonographic Fetal Weight Estimation at Term.

OBJECTIVES: To evaluate the influence of examiner experience on the accuracy of sonographic weight estimation and to further analyze examiners' individual learning curves. METHODS: In this multicenter study, 4613 sonographic weight estimations performed by 18 examiners at the beginning of their ultrasound training were included. To assess the effect of experience on the accuracy of weight estimation, a multivariable mixed regression model analysis was performed, with percentage error and absolute percentage error as outcome variables and the examiner, the examiner's experience (number of examinations), birth weight, gestational age, scan-to-delivery interval, and maternal body mass index as fixed effects and the perinatal center as random intercepts. To further analyze the individual learning curves of the examiners, the cumulative summation technique was used. RESULTS: Regression analyses showed a significant influence of the number of examinations on the accuracy of sonographic weight estimation after adjustment for the above-mentioned parameters (P < .001). A typical learning curve with improving accuracy was found until approximately 200 examinations. Between 200 and 300 examinations, the diagnostic performance started to deteriorate again, with a continuous decrease until the end of the study period. Cumulative summation charts representing individual learning curves varied greatly between different examiners. CONCLUSIONS: These findings indicate the great importance of continuous quality control systems in sonographic weight estimation.

A New Sonographic Weight Estimation Formula for Small-for-Gestational-Age Fetuses.

OBJECTIVES: The purpose of this study was to develop a new specific weight estimation formula for small-for-gestational-age (SGA) fetuses that differentiated between symmetric and asymmetric growth patterns. METHODS: A statistical estimation technique known as component-wise gradient boosting was applied to a group of 898 SGA fetuses (symmetric, n = 750; asymmetric, n = 148). A new formula was derived from the data obtained and was then compared to other commonly used equations. RESULTS: The new formula derived is as follows: estimated fetal weight = e^[1.3734627 + 0.0057133 × biparietal diameter + 0.0011282 × head circumference + 0.0201147 × abdominal circumference + 0.0183081 × femur length - 0.0000177 × biparietal diameter(2) - 0.0000018 × head circumference(2) - 0.0000297 × abdominal circumference(2) -0.0001007 × femur length(2) + 0.0397563 × I(sex = male) + 0.0064505 × gestational age (days) + 0.0096528 × I(SGA = asymmetric)], where the function I denotes an indicator function, which is 1 if the expression is fulfilled (sex = male; SGA type = asymmetric) and otherwise 0. In the whole study group and the 2 subgroups, the new formula showed the lowest median absolute percentage error, mean percentage error, and random error and the best distribution of absolute percentage errors within prespecified error bounds. CONCLUSIONS: The new formula substantially improves weight estimation in SGA fetuses.

Cytokines in noninvasively obtained amniotic fluid as predictors of fetal inflammatory response syndrome.

BACKGROUND: In patients with preterm premature rupture of membranes, intrauterine inflammation and/or infection is frequently present, can lead to fetal inflammatory response syndrome, and is associated with adverse neonatal outcome. Clinical decision making requires balancing the potential benefits of pregnancy prolongation against the risk of intrauterine infection. Diagnostic tests in maternal serum are of moderate prediction value and amniocentesis is an invasive procedure. Therefore, markers obtained noninvasively would be helpful in patients with expectant management. OBJECTIVES: To determine the predictive values of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions for fetal inflammatory response syndrome and/or histologic funisitis and for adverse neonatal outcome in patients with preterm premature rupture of membranes. STUDY DESIGN: In this prospective multicenter case-control study, vaginal secretions were sampled daily with a noninvasive method from 99 women with preterm premature rupture of membranes and expectant management. Amniotic fluid interleukin-6 and tumor necrosis factor-α were measured by 2 different immunoassays (an automated chemiluminescent enzyme immunoassay and a lateral flow immunoassay). After delivery, patients were divided into a control or a fetal inflammatory response syndrome group according to neonatal interleukin-6 in cord plasma and/or the presence of funisitis. Univariate and multivariate regression analyses were performed and prediction models were developed by calculating receiver operating characteristic curves. RESULTS: Gestational age at delivery was lower and latency period was longer in the fetal inflammatory response syndrome group compared to the control group. The strongest risk factor for composite adverse neonatal outcome was fetal inflammatory response syndrome (odds ratio, 2.48; confidence interval, 1.40-4.38). The median concentrations of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions were significantly higher in the fetal inflammatory response group compared to the control group in both immunoassays (P < .001). The area under the curve of the clinical reference model (including common clinical parameters) was 0.66. Adding interleukin-6 and tumor necrosis factor-α into the model improved the area under the curve to 0.92 (in both assays, interleukin-6 IMMULITE and QuickLine); 0.87 (tumor necrosis factor-α IMMULITE) and 0.94 (tumor necrosis factor-α QuickLine), respectively. CONCLUSION: The strongest risk factor for worse neonatal outcome (composite neonatal outcome) was fetal inflammatory response syndrome. Amniotic fluid interleukin-6 and tumor necrosis factor-α seem to be good predictors for fetal inflammatory response syndrome and for histologic funisitis and may improve the clinical management of patients with preterm premature rupture of membranes. The noninvasive technique of sampling amniotic fluid from vaginal secretions facilitates daily measurements and bedside assessment of cytokines and is in this respect preferable to invasive amniocentesis.

Differential effects of low birthweight and intrauterine growth restriction on umbilical cord blood insulin-like growth factor concentrations.

OBJECTIVE: Alterations in the growth hormone-insulin-like growth factor (IGF) axis have been considered as a causal factor for intrauterine growth restriction (IUGR) and for the increased risk of metabolic disease in later life. We compared members of the IGF axis in umbilical cord blood between IUGR neonates, small for gestational age without foetal restriction (SGA) and appropriate for gestational age (AGA) neonates. DESIGN: Prospective controlled multicenter study. PATIENTS: Sixteen ultrasound-proven IUGR, 8 SGA and 40 AGA neonates. MEASUREMENTS: Concentrations of total IGF-I and total IGF-II by immunoassays, bioactive IGF by cell-based bioassay and IGFBP-I in mixed venous and arterial umbilical cord blood samples at birth. Auxological parameters at birth. RESULTS: IGF-I concentrations in IUGR [17·7 µg/l (CI 13·8;21·6)] were clearly below those in AGA [48·3 µg/l (CI 43·7;52·9)] and SGA neonates [36·0 µg/l (CI 26·6;45·4)]. IGF-II levels were significantly reduced in IUGR [201·4 µg/l (CI 190·2;212·6)] compared to AGA neonates [231·2 µg/l (CI 220·6;241·9)]. A trend for lower IGF-II concentrations was observed in IUGR when compared to SGA neonates [232·0 µg/l (CI 207·2;256·8)]. These differences could not be explained by confounding. For IGFBP-1, a trend towards higher values in IUGR was observed. CONCLUSIONS: Low IGF-I cord blood concentrations in hypotrophic neonates after IUGR might not only result from low birthweight per se, but also reflect prenatal placental environment. Alterations of the IGF axis could be in the causal pathway of IUGR and thus constitute a potential surrogate marker for IUGR in the assessment of foetal programming.

Interinstitutional variations in mode of birth after a previous caesarean section: a cross-sectional study in six German hospitals.

AIMS: Regional and interinstitutional variations have been recognized in the increasing incidence of caesarean section. Modes of birth after previous caesarean section vary widely, ranging from elective repeat caesarean section (ERCS) and unplanned repeat caesarean section (URCS) after trial of labour to vaginal birth after caesarean section (VBAC). This study describes interinstitutional variations in mode of birth after previous caesarean section in relation to regional indicators in Germany. MATERIAL AND METHODS: A cross-sectional study using the birth registers of six maternity units (n=12,060) in five different German states (n=370,209). Indicators were tested by χ2 and relative deviations from regional values were expressed as relative risks and 95% confidence intervals. RESULTS: The percentages of women in the six units with previous caesarean section ranged from 11.9% to 15.9% (P=0.002). VBAC was planned for 36.0% to 49.8% (P=0.003) of these women, but actually completed in only 26.2% to 32.8% (P=0.66). Depending on the indicator, the units studied deviated from the regional data by up to 32% [relative risk 0.68 (0.47-0.97)] in respect of completed VBAC among all initiated VBAC. CONCLUSIONS: There is substantial interinstitutional variation in mode of birth following previous caesarean section. This variation is in addition to regional patterns.

17α-hydroxylase deficiency diagnosed in early infancy caused by a novel mutation of the CYP17A1 gene.

BACKGROUND: Mutations of the CYP17A1 gene cause 17α-hydroxylase deficiency (17OHD) resulting in 46,XY disorder of sex development, hypertension, hypokalemia and absent pubertal development. It is a rare, autosomal recessive form of congenital adrenal hyperplasia (CAH). PATIENT: We report on a neonate with prenatally determined 46,XY karyotype. At 20 weeks of gestation, lack of development of male external genitalia was noticed. A phenotypically female child was born at 41 weeks of gestation. RESULTS: Postnatal ultrasound revealed testes in both labia majora, an absence of uterus and normal adrenal glands. Steroid hormone analysis in serum revealed low basal levels of cortisol, testosterone and androstenedione in the presence of massively elevated corticosterone at the age of 2 weeks. The urinary steroid profile from spot urine showed excessive excretion of 17-desoxysteroids, decreased glucocorticoid metabolites and absent C19 steroids, thus proving 17OHD. Molecular analysis identified a novel mutation of the CYP17A1 gene: c.896T>A (p.I299N) in exon 5. Substitution with hydrocortisone was started. The child is raised as a girl and is developing well so far. CONCLUSION: Herein, we report the unusually early diagnosis of a newborn with the rare CAH form of 17OHD allowing an early start of treatment.

Regulation of the human endogenous retroviral Syncytin-1 and cell-cell fusion by the nuclear hormone receptors PPARγ/RXRα in placentogenesis.

Cytotrophoblast (CT) cell fusion into a syncytiotrophoblast is obligatory for placentation and mediated by the human endogenous retrovirus (HERV)-W envelope gene Syncytin-1. Abnormal placentation is associated with preeclampsia (PE), HELLP and intrauterine growth restriction (IUGR). In placentogenesis, the MAP-kinase p38α regulates PPARγ/RXRα signaling and target genes, like leptin, resistin, ABCG2, and hCG. The aim of this study was to analyze PPARγ/RXRα signaling and target gene regulation using primary CT cultures, the trophoblastic cell line BeWo and placental tissues from patients with normal and abnormal placentation. CT from four different human control placentae and BeWo cells demonstrated that Syncytin-1, other signaling members and CT cell fusions were regulated with PPARγ/RXRα activators troglitazone and 9-cis retinoic acid, via protein kinase A and p38α inhibition. Significant discordant regulations between CTs and BeWo were found. Two PPARγ/RXRα-response-elements from upstream regulatory elements and the 5'LTR of HERV-W were confirmed with DNA-protein binding assays using nuclear extracts and recombinant PPARγ/RXRα proteins. These promoter elements were validated with luciferase assays in the presence of PPARγ/RXRα modulators. Furthermore, troglitazone or 9-cis retinoic acid treatment of siRNA-PPARγ and siRNA-RXRα transfected BeWo cells proved the requirement of these proteins for Syncytin-1 regulation. Thirty primary abnormal placentae from PE, HELLP and IUGR patients compared to 10 controls showed significant deregulation of leptin RNA and protein, p38α, phospho-p38α, PPARγ, ABCG2, INSL4 and Syncytin-1. Our study characterized PPARγ/RXRα signaling in human CT and cell fusions identifying Syncytin-1 as a new target gene. Based on these results, a disturbed PPARγ/RXRα pathway could contribute to pathological human pregnancies.

Sex-specific differences in the concentration of tubular parameters in the amniotic fluid of second trimester fetuses.

OBJECTIVE: Renal dysplasia and obstructive uropathy are more common in males and are associated with an increased tubular loss of electrolytes. We aimed to compare the midtrimester concentration of tubular parameters in the prenatal period between healthy male and female fetuses. METHODS: Amniotic fluid was collected at 16 weeks of gestation at the time of genetic amniocentesis. The concentration of sodium, chloride, potassium, calcium, phosphate, magnesium, α1-microglobulin, creatinine and urea was determined in the amniotic fluid of 92 male and 108 female fetuses. RESULTS: The concentration of sodium, chloride and calcium was not significantly higher in male than in female fetuses. In contrast, the concentration of potassium (p=0.01), phosphate (p=0.04), magnesium (p=0.04) and α1-microglobulin (p=0.04) was significantly increased in the amniotic fluid of male fetuses. The concentration of electrolytes correlated to the concentration of creatinine, urea and α1-microglobulin. CONCLUSION: The concentration of specific tubular parameters in the amniotic fluid was higher in male compared with female fetuses. Whether this might point to sex-specific differences in tubular function in second trimester fetuses or reflect glomerular filtration or other interfering factors remains speculative.