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Background: Newborns delivered by elective cesarean section (CS) are at higher respiratory risk than those delivered vaginally or by CS proceeded by labor (secondary CS). The oxytocin challenge test (OCT) induces uterine contractions that trigger the release of fetal hormones regulating lung fluid clearance during transition from the uterine to an air-breathing environment. Objectives: The aim is to summarize current evidence and outline the Lacarus trial protocol. Methods: Literature review informed the design of a randomized placebo-controlled multicenter trial of OCT preceding elective CS in 1,450 women with a singleton pregnancy due for CS at >35 weeks gestation, without preceding contractions, rupture of the membranes, or antenatal steroids. OCT comprises the infusion of oxytocin 5 IU/500 mL Ringer lactate at a rate of 12 mL/h, doubling every 10 min until inducing 5 uterine contractions per 15-min interval. The primary endpoint is the occurrence of neonatal respiratory morbidity within 24 h after birth. Secondary endpoints include biochemical and physiological parameters of fetal and maternal well-being, such as breastfeeding rate and fetal plasma copeptin concentrations. Conclusion: This is the first trial to test the hypothesis that oxytocin-induced contractions before elective CS is a promising application of physiologic principles gleaned from natural birth to improve neonatal and maternal outcomes.

BACKGROUND SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. METHODS This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. FINDINGS Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. INTERPRETATION The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. FUNDING Swiss Federal Office of Public Health, Fondation CHUV.

Zusammenfassung. Die Präeklampsie ist eine Multisystemerkrankung, die vorwiegend zu einer systemischen Beeinträchtigung der mütterlichen Endothelfunktion führt. Eine Dysbalance von proangiogenen und antiangiogenen Faktoren ist dabei massgeblich beteiligt. Die vaskuläre Erkrankung führt zur klinischen Manifestation der Symptome wie arterieller Hypertonie und zur Beteiligung der Endorgane, v.a. Niere, Leber und Gehirn. Das klassische Diagnosekriterium «Proteinurie» ist gemäss internationaler Empfehlungen nicht mehr obligat zur Diagnosestellung erforderlich, sondern nur noch ein mögliches Kriterium und kann durch die Kriterien mütterliche Organbeteiligung oder fetale Wachstumsretardierung ersetzt werden. Die Weisskittelhypertonie wird in die Klassifikation der hypertensiven Erkrankungen zusätzlich aufgenommen. Die Begrifflichkeit «leichte» Präeklampsie wird im klinischen Setting wegen der potenziell raschen Verschlechterung und damit einhergehenden mütterlichen und fetalen Gefährdung nicht empfohlen.

Resume Nous presentons un cas clinique d’une parturiente avec un deficit de facteur VII severe sans symptomes cliniques. Dans ce cas, un accouchement par cesarienne programme en anesthesie generale a ete effectue avec administration d’acide tranexamique (ATX) a titre prophylactique sans substitution de FVII apres ligature du cordon ombilical du nouveau-ne. Tout le processus s’est deroule sans hemorragie du post-partum et sans complication.

Background: Pregnant women represent a vulnerable population at higher risk of complications of infectious diseases. Data regarding the consequences of the emerging pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy are scarce. Recent evidence suggests that pregnant women might be at higher risk of severe disease, while exposed fetuses and newborns could suffer from preterm birth, growth restriction and neonatal infections. Methods: We developed an international web registry to allow structured data collection. Pregnant women at any stage during gestation tested for SARS-CoV-2 infection were enrolled. Maternal, obstetrical and neonatal outcomes were recorded. Findings: 1033 pregnant women tested for SARS-CoV-2 were included, among which 926 tested positive and 107 tested negative. Positive pregnant women were at higher risk of severe maternal outcomes compared to negative women [aRR 5.6, 95% CI 1.4-22.7]. Risk factors for severe maternal outcomes among positive women were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. No difference in term of obstetrical and neonatal outcomes were observed between positive and negative women. Positive pregnant women with severe maternal outcomes were at higher risk of cesarean sections [70.7% (n=53/75)], preterm deliveries [62.7% (n= 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n=31/75)]. A positive neonatal SARS-CoV-2 test was observed in 2.9% (n=11/384) of newborns with an available test at birth. Interpretation: Pregnant women, particularly those with associated comorbidities, seem to be at higher risk of severe complications of SARS-CoV-2 infection. Preliminary data regarding obstetrical and neonatal outcomes among women with a mild disease are reassuring. Funding Statement: None. Declaration of Interests: The authors declare that we have no conflicts of interest. Ethics Approval Statement: The study was approved by both the Swiss Ethical Board (CER-VD-2020-00548) and the local ethics boards at each participating center.

Background: Recent evidence suggests that pregnant women might be at higher risk of severe disease associated with the emerging pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while exposed fetuses/newborns could suffer from preterm birth, growth restriction and neonatal infections. The magnitude of this increased risk and specific risk factors for severity remains unclear. Methods: We performed a case control study comparing pregnant women with severe coronavirus disease 19 (case) to pregnant women with a milder form (controls) enrolled in COVI-Preg international registry cohort between from March 24 to July 26, 2020. Risk factors for severity, obstetrical, fetal and neonatal outcomes were assessed. Findings: A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented a severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of cesarean sections [70.7% (n=53/75)], preterm deliveries [62.7% (n= 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n=31/75)]. Interpretation: Pregnant women, particularly those with associated comorbidities, seem to be at higher risk of severe complications of SARS-CoV-2 infection. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease; complications include cesarean sections, prematurity and neonatal admission to the intensive care unit. Funding Statement: None. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The study was approved by both the Swiss Ethical Board (CER-VD- 2020-00548) and the local ethics boards at each participating center.

Background Oxytocin receptor (OXTR) gene variants have been shown to affect the prevalence of preterm birth, mode of delivery and oxytocin (OXT) requirements for labor induction and augmentation. We hypothesized that this might be associated with different myometrium responses to oxytocin. Our aim was to investigate the influence of a selection of eight OXTR gene single nucleotide variants on oxytocin-induced stimulation of human myometrium contractility in vitro. Methods Human myometrium biopsies were collected during elective cesarean sections at term, if patients had given informed consent. Myometrial strips were submerged under tension in an organ bath and allowed to contract; the remaining material was stored at − 80 °C for further determination of relevant genetics and mRNA level. The area under the curve (AUC) of all contractions taking place in the absence of OXT and of those occurring upon OXT addition (for 30 min each) was measured. OXT stimulation, defined as the ratio between AUC measurements after OXT addition and those in the absence of OXT was calculated for each strip. TaqMan™ Assays were used to detect the allele distribution of the eight OXTR variants and to determine the relative amounts of OXTR-mRNA in the samples. For each variant, oxytocin stimulation of contractility was compared between samples homozygous for the reference allele (reference group) and samples with at least one variant allele (variant group) by linear regression. Results Sixty samples were included in the present study. For rs1042778, rs11706648, rs4686301, rs53576, rs237895, and rs237902, OXT stimulation was similar in the reference and in the variant groups. However, the values of OXT stimulation differed significantly between the reference and the variant groups for rs4686302 (3.1 vs. 4.1 times; p = 0.022) and rs237888 (3.2 vs. 5.5 times; p = 0.001). No significant differences between the levels of OXTR-mRNA in the various reference and corresponding variant groups were detected. Conclusions Patients with variant alleles of rs237888 and/or rs4686302 may be more sensitive to oxytocin stimulation, explaining why these sequence variants have been associated with lower cesarean section prevalence and premature birth, respectively., BMC Medical Genetics, 20 (1), ISSN:1471-2350

Background To analyze blood loss after delivery in women with induction of labor compared to women with spontaneous onset of labor. Methods In this secondary analysis of a prospective cohort study investigating postpartum hemorrhage, 965 deliveries were analyzed including 380 women with induction of labor (39%) between 2015 and 2016. Primary outcome parameters were rate of postpartum hemorrhage, estimated blood loss and post-partum decrease in hemoglobin. Results Rates of postpartum hemorrhage and estimated blood loss were not significantly different in women with induction of labor. Women with induction of labor had a significantly reduced decrease in hemoglobin after delivery. In the multivariate linear regression analysis, induction of labor remained associated with reduced decrease in hemoglobin. Secondary maternal and neonatal outcomes were unaffected. Conclusions Induction of labor is not associated with increased blood loss after delivery and should not be regarded as a risk factor for postpartum hemorrhage.

Objective: This work aimed to analyze the association between maternal position at birth in spontaneous deliveries and the occurrence of anal sphincter tears (AST) given the lack of evidence related to the least traumatic birth position. Study design: A total of 7832 vaginal deliveries were included. Vaginal-operative deliveries and deliveries with fundal pressure were excluded. Birth positions on bed, in water, kneeling, and in a squatting position on a low stool were compared. Birth position on bed was considered as the reference group, and a logistic regression analysis adjusting for important fetomaternal parameters was performed. Results: The overall incidence of AST was 1.1%. AST rate was significantly increased in squatting (2.9%) and kneeling (2.1%) positions compared with birth position on bed (1.0%) or in water (0.9%). Logistic regression analysis revealed a significantly higher risk for ASTs in squatting (OR 2.92, CI 95% 1.04–8.18) and in kneeling positions (OR 2.14, CI 95% 1.05–4.37) compared with the reference group on bed. When adjusting for risk factors, birth in a kneeling position remained significantly associated with ASTs (adj. OR 2.21, CI 95% 1.07–4.54). Conclusions: Birth in squatting or in kneeling position is associated with an elevated risk for ASTs. Birth in water is not associated with an increased risk for AST. Based on the results, women should be informed about the association of certain birth positions with the occurrence of AST.

To evaluate the outcome of a cesarean myomectomy (CM) versus a cesarean delivery (CD) alone in women with uterine myomas and the risk factors for adverse outcomes.A retrospective cohort study of all women undergoing CDs with uterine leiomyomatas and singleton pregnancies was performed. Patients with known risk factors for hemorrhage were excluded. Measured adverse outcome parameters included estimated blood loss, drop in hemoglobin levels (pre/postoperatively), operation time, and the use of additional uterotonics. Outcome parameters of women with CM were compared to women with CD alone. Possible risk factors for adverse outcomes were analyzed in a multivariate regression analysis. Evaluated risk factors for CM were according to localization and type of myomatas, the myoma size, BMI ≥30 kg/mOf the 162 women with uterine myomatas during CD, 48 underwent CM and were analyzed. Overall, CM was not associated with adverse outcomes. Independent of a concomitant myomectomy, a large myoma size of ≥5 cm was associated with an increased blood loss of ≥500 ml (adj. OR 2.7 CI 95 % 1.2-6.2, p = 0.02), and women ≥40 years of age had a significant postoperative drop in hemoglobin (adj. OR 2.4 CI 95 % 1.0-5.4, p = 0.04). In the univariate subgroup analysis, CM of multiple myomatas was associated with an increased blood loss and an increased operation time compared to women with multiple myomatas and CD alone. Prolonged operation times were also observed in women with pedunculated and subserosal myomatas with concomitant myomectomy. There were no cases of hysterectomy or blood transfusions.CM performed by an experienced obstetrician can be safe in selected patients who are without additional preexisting risk factors. Risk factors that are associated with increased blood loss in women with uterine leiomyomatas include a larger size of the leiomyoma (≥5 cm) and a maternal age of ≥40 years.

Objectives To measure the tocolytic effect of the combination of the oxytocin receptor antagonist atosiban with the β-mimetic agent fenoterol on human myometrium of pregnant women. Methods An in vitro study of contractility in human myometrium at the Laboratory of the Department of Obstetrics, University Hospital of Zürich, Switzerland, was performed. Thirty-six human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Tissue samples were exposed to atosiban, fenoterol and the combination of atosiban with fenoterol. Contractility was measured as area under the curve during 30 min of spontaneous contractions. The effect of treatment was expressed as the percentage of change from basal activity during 30 min of exposure. Differences were calculated using a paired Wilcoxon signed-rank test. An additive effect of dual tocolysis was assumed when no significant difference was detected between the observed and expected inhibition of dual tocolysis. When inhibition was greater or lower than expected, the dual combination was characterised as “synergistic” or “antagonistic”, respectively. Results Atosiban and fenoterol alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The combination of atosiban plus fenoterol was measured at a level of 67.3% inhibition. There was no significant difference in the expected (63.2%) and observed inhibition effect of dual tocolysis (P=0.945). Conclusion This study demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on human myometrium in vitro, but no synergistic or antagonistic effect.

Preeclampsia: New Classifications Abstract. Preeclampsia is a multisystem disease leading to systemic impairment of the maternal endothelial function. A dysbalance of pro- and antiangiogenic factors appears to be significantly involved. The vascular disease leads to the manifestation of symptoms such as arterial hypertension and involvement of end organs such as kidney, liver and brain. The classical diagnostic criterion for arterial hypertension, 'proteinuria' has been downgraded and is no longer obligatory for diagnosis, if other criteria, as maternal organ dysfunction or intrauterine growth retardation, are present. In addition, white-coat hypertension has been included in the classification of hypertension in pregnancy. To classify preeclampsia as 'mild' is being discouraged in the clinical setting to account for the possibility of rapid worsening with significant danger for mother and foetus.Zusammenfassung. Die Präeklampsie ist eine Multisystemerkrankung, die vorwiegend zu einer systemischen Beeinträchtigung der mütterlichen Endothelfunktion führt. Eine Dysbalance von proangiogenen und antiangiogenen Faktoren ist dabei massgeblich beteiligt. Die vaskuläre Erkrankung führt zur klinischen Manifestation der Symptome wie arterieller Hypertonie und zur Beteiligung der Endorgane, v.a. Niere, Leber und Gehirn. Das klassische Diagnosekriterium «Proteinurie» ist gemäss internationaler Empfehlungen nicht mehr obligat zur Diagnosestellung erforderlich, sondern nur noch ein mögliches Kriterium und kann durch die Kriterien mütterliche Organbeteiligung oder fetale Wachstumsretardierung ersetzt werden. Die Weisskittelhypertonie wird in die Klassifikation der hypertensiven Erkrankungen zusätzlich aufgenommen. Die Begrifflichkeit «leichte» Präeklampsie wird im klinischen Setting wegen der potenziell raschen Verschlechterung und damit einhergehenden mütterlichen und fetalen Gefährdung nicht empfohlen.

Purpose The Hadlock et al. formula tends to underestimate fetal weight, in particular > 3500 g. At the high end of the range, the Merz et al. formula is more accurate, but becomes less so in smaller fetuses. This study was designed to improve fetal weight estimation in fetuses > 3500 g by identifying the fetal biometric parameter providing the most reliable guidance to optimal formula selection. Materials and Methods Regression analysis of 12 032 pregnancies showed that multiplication of abdominal circumference by femur length (AC × FL) gave the best choice of appropriate formula: Hadlock for AC × FL Results The PE using the Zurich method was lower in both > 3500 g groups than with the Hadlock formula alone (3500 – 3999 g: 0.9 % vs. – 5.3 %, > 4000 g: – 3.2 % vs. – 8.6 %), similar to that with the Merz formula alone, and lower than with the Kehl formulas (3500 – 3999 g: – 9.0 % vs. – 3.2 %, > 4000g: – 5.1 % vs. 0.9 %). The Zurich method and Hadlock formula also shared the lowest PE in the 4000 g group, while sharing the lowest value with the Hadlock formula in the Conclusion The Zurich method uses a pivotal value of the biometry parameter AC × FL to switch between formulas and corrects for the errors of the Hadlock formula in fetuses ≥ 3500 g and those of the Merz formula in fetuses

OBJECTIVE: To assess the impact of maternal smoking during pregnancy (MSDP) on the neonatal hypothalamic-pituitary-adrenal axis. STUDY DESIGN: In a prospective observational study, salivary cortisol and cortisone levels were measured at the fourth day of life during resting conditions and in response to a pain-induced stress event in healthy neonates whose mothers smoked cigarettes during each stage of pregnancy and compared with controls. RESULTS: Neonates in the control group (n=70) exhibited a physiologic stress response with a significant increase in cortisol (1.3 to 2.1 ng ml-1; P

Erythropoietin (EPO) is mainly synthesized within renal peritubular fibroblasts, and also other tissues such as the liver possess the ability. However, to what extent non-kidney produced EPO contributes to the hypoxia-induced increase in circulating EPO in adult humans remains unclear. We aimed to quantify this by assessing the distribution of EPO glycoforms which are characterized by posttranslational glycosylation patterns specific to the synthesizing cell. The analysis was performed on samples obtained in seven healthy volunteers before, during and after 1 month of sojourn at 3,454 m altitude. Umbilical cord (UC) plasma served as control. As expected a peak (p

Objective To evaluate the quality of anthropometric measures to improve the prediction of shoulder dystocia by combining different sonographic biometric parameters. Methods This was a retrospective cohort study of 12 794 vaginal deliveries with complete sonographic biometry data obtained within 7 days before delivery. Receiver–operating characteristics (ROC) curves of various combinations of the biometric parameters, namely, biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference, abdominal diameter (AD), abdominal circumference (AC) and femur length were analyzed. The influences of independent risk factors were calculated and their combination used in a predictive model. Results The incidence of shoulder dystocia was 1.14%. Different combinations of sonographic parameters showed comparable ROC curves without advantage for a particular combination. The difference between AD and BPD (AD – BPD) (area under the curve (AUC) = 0.704) revealed a significant increase in risk (odds ratio (OR) 7.6 (95% CI 4.2–13.9), sensitivity 8.2%, specificity 98.8%) at a suggested cut-off ≥ 2.6 cm. However, the positive predictive value (PPV) was low (7.5%). The AC as a single parameter (AUC = 0.732) with a cut-off ≥ 35 cm performed worse (OR 4.6 (95% CI 3.3–6.5), PPV 2.6%). BPD/OFD (a surrogate for fetal cranial shape) was not significantly different between those with and those without shoulder dystocia. The combination of estimated fetal weight, maternal diabetes, gender and AD – BPD provided a reasonable estimate of the individual risk. Conclusion Sonographic fetal anthropometric measures appear not to be a useful tool to screen for the risk of shoulder dystocia due to a low PPV. However, AD – BPD appears to be a relevant risk factor. While risk

OBJECTIVE To evaluate postpartum blood loss in women with treated intrahepatic cholestasis of pregnancy. METHODS In a retrospective case-control study, 15,083 deliveries including 348 women with intrahepatic cholestasis of pregnancy (2.3%) were analyzed from 2004 to 2014. To adjust for differences in baseline characteristics, a propensity analysis was performed and women in the control group were matched to the women in the intrahepatic cholestasis of pregnancy group in a 5:1 ratio. Blood loss was analyzed by estimated blood loss and Δ hemoglobin (Hb, difference between prepartum and postpartum Hb). A subgroup analysis regarding severity of intrahepatic cholestasis of pregnancy based on maximum bile acid level (mild [less than 40 micromoles/L], moderate [40-99 micromoles/L], and severe intrahepatic cholestasis of pregnancy [100 micromoles/L or greater]) was performed. Differences in estimated blood loss, ΔHb, and meconium staining between subgroups were analyzed. A Spearman rank correlation was performed to evaluate the association of bile acid levels and blood loss within subgroups. RESULTS Estimated blood loss (median 400 [300-600] mL compared with 400 [300-600] mL, P=.22), ΔHb (14.0 [5.0-22.0] compared with 12.0 [4.0-21.0] g/L, P=.09), meconium staining (14.5% compared with 11.4%, P=.12), and number of stillbirths after 26 weeks of gestation (0.6% compared with 1.8%, P=.10) were not significantly different in the study compared with the control group. In moderate and severe intrahepatic cholestasis of pregnancy, meconium staining was observed significantly more often compared with that in a control group (23.0% and 32.3% compared with 11.4%, P

To evaluate pregnancy outcome in pregnant women aged ≥45 years, termed very advanced maternal age (VAMA).We retrospectively compared the outcome of pregnancies in VAMA patients with controls aged 30 years at time of delivery. Subgroups of singleton and multiple pregnancies were also analysed. Incidences of maternal and fetal adverse outcomes were measured. Statistical significance was set at p0.05. Odds ratios (ORs) were adjusted where necessary.One hundred and twenty-seven VAMA pregnancies and 2066 control pregnancies of women aged 30 years were analysed. VAMA pregnancies had a higher rate of maternal complications such as gestational hypertension (3.9% vs 0.6%; OR 6.5), preeclampsia (14.2% vs 3.0%; OR 5.4, adjusted OR 4.4) and gestational diabetes (12.6% vs 3.6%; OR 3.8). Likewise, increased need for blood transfusion (3.2% vs 0.7%; OR 4.8, adjusted OR 4.4) and prolonged hospitalisation7 days (37.8% vs 15.1%; OR 3.42) was found. Infant complications such as prematurity (44.9% vs 16.2%; OR 4.2) and low birthweight5th percentile (11.0% vs 5.6%; OR 2.1) were also increased.Pregnant women of very advanced maternal age (≥45 years) have significantly increased maternal and fetal risks. Women postponing pregnancy or planning a pregnancy in very advanced age should be informed about these risks, in particular before artificial reproductive technologies are applied or "social freezing".

To evaluate the predictive value of a combination of sonographic, clinical and demographic data for detecting fetal macrosomia compared to ultrasound fetal weight estimation alone.Retrospective cohort data were obtained from 1062 pregnancies in an unselected population. Estimated fetal sonographic weight was obtained within the last week prior to delivery. Two different combination models-published by Mazouni et al. and Nahum and Stanislaw-were employed to predict the presence of macrosomia at birth in these infants. Receiver-operating characteristics (ROC) curves were generated to compare the prediction of macrosomia when using different observation methods and sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy were calculated.Macrosomia (birth weightor= 4000 g) was present in 135/1062 (12.7%) newborns. ROC curve analysis revealed the prediction of macrosomia using ultrasound alone to be significantly superior to the combined method of Mazouni et al. (area under the curve (AUC) 0.922, 95% CI 0.902-0.943 vs. 0.747, 95% CI 0.700-0.794, respectively; P0.0005), whereas the performance of the Nahum and Stanislaw equation was similar but not superior to ultrasound alone (AUC 0.895, 95% CI 0.839-0.950 vs. 0.912, 95% CI 0.867-0.958, respectively; P0.05). The accuracy of macrosomia prediction was similar for ultrasound alone and the Nahum and Stanislaw equation (approximately 90%), whereas the nomogram of Mazouni et al. reached only 51.7% accuracy (using a probability cut-off level of 50%). The NPV was found to be over 90% for all methods.Combination of sonographic estimates with clinical and demographic variables does not improve the prediction of macrosomia at delivery in comparison with a routine ultrasound scan within a week before delivery, at least in unselected populations.

The cardiac sympathetic nervous system is one putative key factor involved in the intrauterine programming of adult cardiovascular disease. We therefore analyzed cardiac autonomic system activity in small for gestational age (SGA) neonates. Heart rate variability (HRV) from 24-h ECG recordings were analyzed for time-domain and frequency-domain parameters in 27 SGA neonates [median 261 (240–283) days of gestation] compared with 27 appropriate for gestational age (AGA) neonates [median 270 (239–293) days of gestation]. In addition, salivary α-amylase levels were analyzed during resting conditions and in response to a pain-induced stress event in 18 SGA [median 266 (240–292) days of gestation] and 34 AGA [median 271 (240–294) days of gestation] neonates. Overall HRV was not significantly different in SGA neonates compared with AGA neonates (SD of all valid NN intervals: P = 0.14; triangular index: P = 0.29), and the sympathovagal balance [low frequency (LF)/high frequency (HF)] was similar ( P = 0.62). Parameters mostly influenced by sympathetic activity did not reveal significant differences: (SD of the average of valid NN intervals: P = 0.27; average of the hourly means of SDs of all NN intervals: P = 0.66, LF: P = 0.83) as well as vagal tone-influenced parameters were unaltered (average of the hourly square root of the mean of the sum of the squares of differences between adjacent NN intervals: P = 0.59; proportion of pairs of adjacent NN intervals differing by >50 ms: P = 0.93; HF: P = 0.82). Median resting levels for α-amylase were not significantly different in SGA neonates ( P = 0.13), and a neonatal stress stimulus revealed similar stress response patterns ( P = 0.29). HRV and salivary α-amylase levels as indicators of cardiac autonomic activity were not altered in SGA neonates compared with AGA neonates. Thus, it appears that the intrauterine activation of the sympathetic system in SGA fetuses does not directly persist into postnatal life, and neonatal sympathovagal balance appears to be preserved.

Purpose:Uterine rupture is a rare but serious event with a median incidence of 0.09%. Previous uterine surgery is the most common risk factor. The aim of our study was to analyze retrospectively women with uterine rupture during labor and to evaluate postulated risk factors such as uterine fundal pressure (UFP).Methods:Twenty thousand one hundred and fifty-two deliveries were analyzed retrospectively. Inclusion criteria were 22 weeks and 0 days–42 weeks and 0 days of gestation, singleton pregnancy and cephalic presentation. Women with primary cesarean section were excluded. A logistic regression analysis adjusting for possible risk factors was conducted and a subgroup analysis of women with unscarred uterus was performed.Results:Twenty-eight cases of uterine rupture were identified (incidence: 0.14%). Uterine rupture was noticed in multipara patients only. In the multivariate analysis among all study patients, only previous cesarean section remained a statistically significant risk factor [adjusted odds ration (adj. OR) 12.52 confidence interval (CI) 95% 5.21–30.09]. In the subgroup analysis among women with unscarred uterus (n=19,415) three risk factors were associated with uterine rupture: UFP (adj. OR 5.22 CI 95% 1.07–25.55), abnormal placentation (adj. OR 20.82 CI 95% 2.48–175.16) and age at delivery >40 years (adj. OR 4.77 CI 95% 1.44–15.85).Conclusions:The main risk factor for uterine rupture in the whole study population is previous uterine surgery. Risk factors in women with unscarred uterus were UFP, abnormal placentation, and age at delivery >40 years. The only factor which can be modified is UFP. We suggest that UFP should be used with caution at least in presence of other supposed risk factors.

INTRODUCTION The study aims were to analyze the experience of women and their physicians of nakedness when moving between changing room and examination chair and during pelvic examination itself, and to assess the protective benefit of a wrap skirt in alleviating the associated discomfort and vulnerability. MATERIAL AND METHODS We offered 1000 women a wrap skirt for pelvic examination and asked them to complete a post-procedure questionnaire. Physicians were invited to complete a similar but separate questionnaire. Data were analyzed using chi-squared contingency tables. RESULTS A total of 425 women (43%, age 15-78 years) completed the questionnaire; 51% felt uncomfortable and embarrassed during the examination, Muslim women significantly more so (p < 0.001). Most women (n = 255; 58%) rated the wrap skirt a significant improvement; 69% requested it for future examinations, significantly more so if the physician was male rather than female (66% vs. 54%, p = 0.003). Even the one-third of women experiencing no discomfort reported improvement. Most examiners (n = 45; 56%) found the wrap skirt beneficial; 31 (38%) were unconvinced. CONCLUSIONS Pelvic examination as practiced in many countries, on women naked from the waist down throughout, causes unnecessary embarrassment. A simple protective measure, such as a wrap skirt, significantly alleviates the discomfort and sense of vulnerability associated with nakedness.

Aim:This study aimed to evaluate maternal and fetal outcomes after uterine fundal pressure (UFP) in spontaneous and assisted vaginal deliveries.Methods:In a retrospective cohort study, 9743 singleton term deliveries with cephalic presentation were analyzed from 2004 to 2013. Spontaneous and assisted vaginal deliveries were analyzed separately with and without the application of UFP. Odds ratios were adjusted in a multivariate logistic regression analysis.Results:Prevalence of UFP was 8.9% in spontaneous and 12.1% in assisted vaginal deliveries. UFP was associated with a higher incidence of shoulder dystocia in both spontaneous (adjusted odds ratio [adj. OR] 2.44, confidence interval [CI] 95% 1.23–4.84) and assisted vaginal deliveries (adj. OR 6.88 CI 95% 3.50–13.53). Fetal acidosis (arterial umbilical pHConclusions:UFP is associated with increased occurrence of shoulder dystocia and fetal acidosis. In spontaneous deliveries, the risk for lower Apgar scores after 5 and 10 min is increased, as well as the risk for AST.

There is evidence for a correlation between placental weight and future chronic disease, notably hypertension and diabetes. However, there are no reference scales for placentas that are readily weighed in the delivery room.This cross-sectional study generated reference values for the weight of freshly delivered untrimmed placentas, and placental weight-birth weight (pw/bw) ratios from a database of 11,141 uncomplicated singleton term pregnancies (37-42 weeks). The data analysis followed stringent validated and state of the art methodological recommendations. A regression model was fitted to estimate the mean and standard deviation for placental weight and pw/bw ratios at each week of gestational age.Reference scales, percentile tables and regression equations are presented for placental weights according to the mode of delivery and for pw/bw ratios. Mean placental weight from vaginal deliveries was 76 g lighter than from Caesarean sections (545+/-107 g versus 621+/-139 g, respectively, P0.05). Mean placental weight increased by 60 g from 37 to 42 weeks irrespective of the mode of delivery. The pw/bw ratio decreased from 17.6 to 15.6 between 37 and 42 weeks.For the first time, reference values for freshly delivered term placental weights depending on the mode of delivery were generated. In the light of growing evidence for a correlation of placental weight with chronic diseases in later life, these values provide the possibility to judge placentas at site for abnormalities in weight and to estimate the potential risks for chronic diseases in later life.

Local tissue oxygenation profoundly influences placental development. To elucidate the impact of hypoxia on cellular and molecular adaptation in vivo, pregnant mice at embryonic days 7.5–11.5 were exposed to reduced environmental oxygen (6–7% O2) for various periods of time. Hypoxia-inducible factor (HIF)-1α mRNA was highly expressed in the placenta, whereas HIF-2α was predominantly found in the decidua, indicating that HIF-1 is a relevant oxygen-dependent factor involved in placental development. During severe hypoxia, HIF-1α protein was strongly induced in the periphery but, however, not in the labyrinth layer of the placenta. Accordingly, no indication for tissue hypoxia in this central area was detected with 2-(2-nitro-1 H-imidazol-1-yl)- N-(2,2,3,3,3-pentafluoropropyl)acetamide staining and VEGF expression as hypoxic markers. The absence of significant tissue hypoxia was reflected by preserved placental architecture and trophoblast differentiation. In the search for mechanisms preventing local hypoxia, we found upregulation of endothelial nitric oxide synthase (NOS) expression in the labyrinth layer. Inhibition of NOS activity by Nω-nitro-l-arginine methyl ester application resulted in ubiquitous placental tissue hypoxia. Our results show that placental oxygenation is preserved even during severe systemic hypoxia and imply that NOS-mediated mechanisms are involved to protect the placenta from maternal hypoxia.

The transforming growth factor-beta 3 (TGF-beta 3) is involved in oxygen-dependent differentiation processes during placental development and pregnancy disorders. However, the importance of oxygen partial pressure for the regulation of TGF-beta 3 expression is presently unclear. We and others presented preliminary evidence that the hypoxia-inducible factor-1 (HIF-1) confers TGF-beta 3 transcription but it was unknown whether this occurred directly or indirectly. To analyze how HIF-1 regulates TGF-beta 3 gene transcription, we cloned and sequenced the mouse TGF-beta 3 promoter region. Multiple putative HIF-1 binding sites (HBSs) were identified, many of which co-localized with two G+C rich CpG islands 5' to the TGF-beta 3 transcription start site. A 6.8 kb fragment of the TGF-beta 3 promoter induced reporter gene expression under hypoxic conditions or when treated with an iron chelator known to stabilize and activate the HIF-1 alpha subunit. Deletion of a 2.4 kb fragment upstream of the distal CpG island abolished inducibility of reporter gene expression. Two HBSs (HBS1 and HBS6) that bound the HIF-1 protein could be identified within this 2.4 kb fragment. These results suggest that TGF-beta 3 gene expression is directly regulated by HIF-1.

The heterodimeric hypoxia-inducible factor (HIF)-1 is a transcriptional master regulator of several genes involved in mammalian oxygen homeostasis, including erythropoietin, vascular endothelial growth factor, and factors involved in glucose transport and metabolism. The mouse Hif1a gene is expressed from two distinct promoter/first exon combinations resulting in tissue-specific (mHIF-1alphaI.1) and ubiquitous (mHIF-1alphaI.2) mRNA isoforms. By in situ hybridization, we detected mHIF-1alphaI.1 mRNA exclusively in the elongated spermatids of the testis. In vitro studies indicated that the switch from mHIF-1alphaI.2 to mHIF-1alphaI.1 mRNA expression does not occur at the premeiotic stages of mouse spermatogenesis. Exposure of mice to hypoxic conditions induced mHIF-1alphaI.2 protein in spermatocytes and probably in Sertoli cells but not in spermatogonia. In contrast, expression of the putative mHIF-1alphaI.1 protein in spermatozoa of the testis and epididymis was oxygen independent and located to the midpiece of the spermatozoal flagellum. Both the switch in transcript expression during spermiogenesis and the unexpected protein localization in mature sperm cells suggest a so far unrecognized function of HIF-1alpha.

Results: 9743 vaginal deliveries were analyzed. FUP was applied in 8.9% of spontaneous deliveries (n = 7995) and 12.1% of assisted vaginal deliveries (n = 1748). FUP was associated with a higher incidence of shoulder dystocia in both spontaneous – (1.6% vs. 0.9%, p = 0.14, n. s.; adj. OR 2.44 (CI 95% 1.23 – 4.84)) and assisted vaginal deliveries (9.0% vs. 1.4%, p < 0.01; adj. OR 6.88 (CI 95% 3.50 – 13.53)). In spontaneous vaginal deliveries, FUP was associated with fetal acidosis (arterial pH < 7.2) (31.5% vs. 15.1%, p < 0.01; adj. OR 3.18 (CI 95% 2.64 – 3.82)) and 10’-Apgar < 7 (0.8% vs. 0.3%, p = 0.02; adj. OR 3.04 (CI 95% 1.17 – 7.88)). In assisted vaginal deliveries, FUP was associated with fetal acidosis as well (36.0% vs. 26.8%, p < 0.01; adj. OR 1.59 (CI 95% 1.17 – 2.16)). FUP was notsignificantly associated with adverse maternal outcome such as anal sphincter tears, uterine rupture or increased blood loss. Conclusions: FUP is associated with increased occurrence of shoulder dystocia and fetal acidosis. Fetal acidosis may be increased due to selection bias in a retrospective study. Possible advantages of FUP (prevention of caesarean section) cannot be evaluated.

In the first-trimester mammalian fetus, skin wounds heal with perfect reconstitution of the dermal architecture without scar formation. Understanding environmental molecular regulation in fetal wound healing may reveal scar-limiting therapeutical strategies for the prevention of postnatal scarring wound repair. Therefore, we performed studies on fetal skin oxygenation and skin and wound expression of hypoxia-inducible factor 1alpha (HIF-1alpha) in the sheep model in vivo and performed studies on the potential relevance of HIF-1alpha during wound healing in vitro. Skin oxygen partial pressure levels were hypoxic throughout normal development. In nonscarring fetal skin at gestation day (GD)60, HIF-1alpha could be detected neither in healthy nor in wounded tissue. At GD100, in wounds with minimal scar formation, HIF-1alpha was expressed in fibroblasts and was markedly up-regulated at the wound edge. In scarring fetal wounds at GD120, HIF-1alpha was predominantly expressed in inflammatory cells. Expression of transforming growth factor beta3 (TGF-beta3), a potent antiscarring cytokine, overlapped with HIF-1a expression at GD100. HIF-1alpha-deficient mouse embryonic fibroblasts showed impaired migratory capabilities and demonstrated that TGF-beta3, but not proscarring TGF-beta1, manifests hypoxia- and HIF-1alpha-dependent regulation. In conclusion, HIF-1alpha-dependent regulation of a potent antiscarring cytokine may provide new strategies for antiscarring manipulation of wound healing.

Purpose The cumulative summation technique (CUSUM) is an innovative method for the quality control of nuchal translucency (NT) measurements. CUSUM allows immediate corrective intervention as soon as an unacceptable tendency is noted. The aim of this study was to implement an objective and dynamic quality control method based on the CUSUM technique for prompt analysis of fetal NT measurement which would be compatible with different standards in routine clinical practice. The findings were compared to the standard NT quality control methods currently in use. Materials and methods Three sets of fetal NT measurements performed by three experienced examiners (I, II and III) were selected for retrospective evaluation. One additional set of NT measurements performed by examiner IV was prospectively assessed to approve the practicability of the method. NT measurements were conducted according to the recommendations of Fetal Medical Foundation (FMF) Germany and London. NT values were converted to Z-scores. For quality and accuracy evaluation, data were fed into the Digisono CUSUM software to create double CUSUM charts of Z-scores. In addition, histograms were composed from the Z-scores of each set of measurements and plotted against a normal Gaussian distribution. Results Three different patterns of retrospective performance and one set of NT measurements that was evaluated prospectively are presented. The full alignment of Z-scores using CUSUM curves reflected exact periods of under- and overestimation of NT measurements. The CUSUM chart of the prospective data set reveals that prompt corrective intervention of poor performance resulted in reconstitution of optimal results and provided sufficient control. In contrast, histograms of NT Z-scores only showed a minor positive or negative shift as compared to the expected values on the basis of Gaussian distribution, but could not identify poor performance. Conclusion Use of the CUSUM technique analysing the quality of sonographic NT measurements provides the possibility to prospectively observe the development of the examiner's skills, to maintain competence and to promptly define the time when inaccurate measurements start to occur.

Beneficial effects of antenatal glucocorticoid treatment in pregnancies at risk for preterm delivery may entail long-term consequences for the establishment of sympathoadrenergic system balance. We analyzed the cardiac autonomic system activity in neonates with a single course of antenatal betamethasone (2 × 12 mg) treatment by calculating heart rate variability (HRV) time-domain parameters from 24 h ECG recordings and short-term frequency-domain parameters during infant active and resting states. In addition, resting and challenged salivary α-amylase levels were measured in 23 betamethasone-exposed neonates and compared with controls. Indicators for overall HRV (SDNN: p = 0.258; triangular index: p = 0.179) and sympathovagal balance [low- to high-frequency power (LF/HF): p = 0.82 (resting state)] were not significantly different in neonates of the betamethasone treatment group. Parameters mostly influenced by sympathetic activity [SD of the average of valid NN intervals (SDANN): p = 0.184 and SDs of all NN intervals (SDNNi): p = 0.784] and vagal tone [RMSSD: p = 1.0; NN50: p = 0.852; HF: p = 0.785 (resting state)] were unaltered. Resting α-amylase levels were not significantly different in the betamethasone treatment group (p = 0.304); however, α-amylase release after a neonatal challenge was slightly reduced (p = 0.045). Thus, cardiac autonomic balance seems to be preserved in neonates exposed to a single course of antenatal betamethasone treatment.

Objective To apply the cumulative summation (CUSUM) technique for an evaluation of the learning process of sonographic fetal weight estimation at term in combination with the z-scores of biometry determinants and to assess the time of appearance and sources of errors. Methods Learning curve (LC-CUSUM) and double CUSUM charts for systematic error detection based on absolute and signed mean percentage error were generated to retrospectively estimate the longitudinal accuracy of sonographic fetal weight estimation conducted by three trainees and one experienced examiner. For LC-CUSUM analysis an examination was considered to be a failure when there was an absolute error in birth weight estimation ≥ 15%. Fetal biometry measurements (head circumference, abdominal circumference (AC) and femur length (FL)) from 227 routine ultrasound scans of one examiner were separately transformed into z-scores and double CUSUM charts were generated to assess the systematic errors for each determinant. Results The LC-CUSUM charts revealed that different numbers of scans are required for different examiners to achieve competence in estimating birth weight. AC and FL deviated most significantly from expected values (P < 0.05). The double CUSUM charts revealed exact periods of systematic errors in the measurement of biometry determinants, clearly reflecting errors of fetal weight estimation. Conclusions The use of CUSUM techniques in the analysis of sonographic data allows observation of the development of an examiner's skill and maintenance of competence. The CUSUM technique not only allows the reasons for impaired fetal weight estimation to be revealed but also allows determination of the exact time when inaccurate measurements start to occur. We suggest that CUSUM charts should be implemented in routine clinical practice as a measure of objective quality evaluation of sonographic fetal biometry. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.