Perinatal Outcome in Pregnant Women With Isolated Oligohydramnios Diagnosed With the Single Deepest Pocket Method.

AIM: The aim of this study was to investigate perinatal outcome in singleton pregnancies at term with isolated oligohydramnios, diagnosed by using the single deepest pocket method. PATIENTS AND METHODS: In this historic cohort study, the perinatal outcomes of 196 women with isolated oligohydramnios at term, diagnosed by using the single deepest pocket method, were compared to 8,676 women with normal amniotic fluid volume. The primary outcome measure was the Cesarean section rate. Further outcome parameters included the rate of induction of labor, abnormal cardiotocography, umbilical cord pH and base excess, Apgar, meconium-stained liquor and admission to neonatal intensive care unit. RESULTS: In the group with isolated oligohydramnios, there were significantly more Cesarean sections (p=0.0081) and more abnormal cardiotocographies (p=0.0005). Univariate and multivariate analyses showed that this difference was seen particularly in nulliparous women (p=0.0025 for Cesarean section and 0.0368 for abnormal cardiotocography). Peripartal and perinatal outcome parameters were not different between the two groups. CONCLUSION: In women with isolated oligohydramnios at term, there is no impact on fetal outcome. The influence of isolated oligohydramnios on the rate of cesarean section and abnormal cardiotocography is considered to be less than that of parity.

Toxoplasma gondii Infection in Pregnancy - Recommendations of the Working Group on Obstetrics and Prenatal Medicine (AGG - Section on Maternal Disorders).

Aim The AGG (Working Group for Obstetrics and Prenatal Diagnostics, Section Maternal Diseases) has issued these recommendations to improve the detection and management of Toxoplasma gondii infection in pregnancy. Methods Members of the Task Force developed the recommendations and statements presented here using recently published literature. The recommendations were adopted after a consensus process by members of the working group. Recommendations This article focuses on the epidemiology and pathophysiology of Toxoplasma gondii infection in pregnancy and includes recommendations for maternal and fetal diagnosis, transmission prophylaxis, therapy, prevention, screening, and peripartum management.

Cerebroplacental versus Umbilicocerebral Ratio-Analyzing the Predictive Value Regarding Adverse Perinatal Outcomes in Low- and High-Risk Fetuses at Term.

Background and Objectives: The aim of this study was to investigate the prediction of adverse perinatal outcomes using the cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in different cohorts of singleton pregnancies. Materials and Methods: In this retrospective cohort study, we established our own Multiple of Median (MoM) for CPR and UCR. The predictive value for both ratios was studied in the following outcome parameters: emergency cesarean delivery, operative intervention (OI), OI due to fetal distress, 5-min Apgar < 7, admission to neonatal intensive care unit, and composite adverse perinatal outcome. The performance of the ratios was assessed in the following cohorts: total cohort (delivery ≥ 37 + 0 weeks gestation, all birth weight centiles), low-risk cohort (delivery ≥ 37 + 0 weeks gestation, birth weight ≥ 10. centile), prolonged pregnancy cohort (delivery ≥ 41 + 0 weeks gestation, birth weight ≥ 10. centile) and small-for-gestational-age fetuses (delivery ≥ 37 + 0 weeks gestation, birth weight < 10. centile). The underlying reference values for MoM were estimated using quantile regression depending on gestational age. Prediction performance was evaluated using logistic regression models assessing the corresponding Brier score, combining discriminatory power and calibration. Results: Overall, 3326 cases were included. Across all cohorts, in the case of a significant association between a studied outcome parameter and CPR, there was an association with UCR, respectively. The Brier score showed only minimal differences for both ratios. Conclusions: Our study provides further evidence regarding predictive values of CPR and UCR. The results of our study suggest that reversal of CPR to UCR does not improve the prediction of adverse perinatal outcomes.

Feasibility and Acceptance of Self-Guided Mobile Ultrasound among Pregnant Women in Routine Prenatal Care.

BACKGROUND AND OBJECTIVES: Mobile and remote ultrasound devices are becoming increasingly available. The benefits and possible risks of self-guided ultrasound examinations conducted by pregnant women at home have not yet been well explored. This study investigated aspects of feasibility and acceptance, as well as the success rates of such examinations. METHODS: In this prospective, single-center, interventional study, forty-six women with singleton pregnancies between 17 + 0 and 29 + 6 weeks of gestation were included in two cohorts, using two different mobile ultrasound systems. The participants examined the fetal heartbeat, fetal profile and amniotic fluid. Aspects of feasibility and acceptance were evaluated using a questionnaire. Success rates in relation to image and video quality were evaluated by healthcare professionals. RESULTS: Two thirds of the women were able to imagine performing the self-guided examination at home, but 87.0% would prefer live support by a professional. Concerns about their own safety and that of the child were expressed by 23.9% of the women. Success rates for locating the target structure were 52.2% for videos of the fetal heartbeat, 52.2% for videos of the amniotic fluid in all four quadrants and 17.9% for videos of the fetal profile. CONCLUSION: These results show wide acceptance of self-examination using mobile systems for fetal ultrasonography during pregnancy. Image quality was adequate for assessing the amniotic fluid and fetal heartbeat in most participants. Further studies are needed to determine whether ultrasound self-examinations can be implemented in prenatal care and how this would affect the fetomaternal outcome.

A Causal Treatment for X-Linked Hypohidrotic Ectodermal Dysplasia: Long-Term Results of Short-Term Perinatal Ectodysplasin A1 Replacement.

X-linked hypohidrotic ectodermal dysplasia (XLHED), caused by a genetic deficiency of ectodysplasin A1 (EDA1), is a rare developmental disorder of ectodermal derivatives such as hair, sweat glands, and teeth. The absence of sweat glands and perspiration can evoke life-threatening hyperthermia. As molecular genetic findings are not always conclusive, the concentrations of circulating EDA1 may help to distinguish between total and partial EDA1 deficiencies. We previously treated nine male patients with obvious signs of XLHED with a recombinant EDA1 replacement protein, Fc-EDA, either shortly after birth (n = 3) or by prenatal administration in gestational week 26 and beyond (n = 6). Here, we present the long-term follow-up for up to six years. In patients who had received Fc-EDA after birth, neither sweat glands nor sweating ability were detected at the age of 12-60 months. In contrast, prenatal EDA1 replacement resulted in ample sweat gland development and pilocarpine-inducible sweating in all treated subjects, who also attained more permanent teeth than their untreated affected relatives. Normal perspiration has persisted for six years in the two oldest boys treated repeatedly with Fc-EDA in utero. When they had a sauna, adequate thermoregulation was evidenced. Lower sweat production after single prenatal dosing may indicate a dose-response relationship. The absence of circulating EDA1 in five prenatally treated subjects proved that these children would have been unable to perspire if they had been left untreated. The sixth infant was shown to produce an EDA1 molecule that, albeit interacting with its cognate receptor, cannot activate EDA1 signaling. In conclusion, a causal treatment of XLHED before birth is feasible.

Protocol for the Phase 2 EDELIFE Trial Investigating the Efficacy and Safety of Intra-Amniotic ER004 Administration to Male Subjects with X-Linked Hypohidrotic Ectodermal Dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and sweat glands, the teeth, and mucous glands of the airways, resulting in serious, sometimes life-threatening complications like hyperthermia or recurrent respiratory infections. It is caused by pathogenic variants of the ectodysplasin A gene (EDA). Most affected males are hemizygous for EDA null mutations that lead to the absence or inactivity of the signalling protein ectodysplasin A1 (EDA1) and, thus, to the full-blown phenotype with inability to perspire and few if any teeth. There are currently no long-term treatment options for XLHED. ER004 represents a first-in-class protein replacement molecule designed for specific, high-affinity binding to the endogenous EDA1 receptor (EDAR). Its proposed mechanism of action is the replacement of missing EDA1 in yet unborn patients with XLHED. Once bound to EDAR, ER004 activates the EDA/NFκB signalling pathway, which triggers the transcription of genes involved in the normal development of multiple tissues. Following preclinical studies, named-patient use cases demonstrated significant potential of ER004 in affected males treated in utero during the late second and third trimesters of pregnancy. In order to confirm these results, we started the EDELIFE trial, a prospective, open-label, genotype-match controlled, multicentre clinical study to investigate the efficacy and safety of intra-amniotic ER004 administration as a prenatal treatment for male subjects with XLHED. This article summarises the rationale, the study protocol, ethical issues of the trial, and potential pitfalls.

Boosting distributional copula regression.

Capturing complex dependence structures between outcome variables (e.g., study endpoints) is of high relevance in contemporary biomedical data problems and medical research. Distributional copula regression provides a flexible tool to model the joint distribution of multiple outcome variables by disentangling the marginal response distributions and their dependence structure. In a regression setup, each parameter of the copula model, that is, the marginal distribution parameters and the copula dependence parameters, can be related to covariates via structured additive predictors. We propose a framework to fit distributional copula regression via model-based boosting, which is a modern estimation technique that incorporates useful features like an intrinsic variable selection mechanism, parameter shrinkage and the capability to fit regression models in high-dimensional data setting, that is, situations with more covariates than observations. Thus, model-based boosting does not only complement existing Bayesian and maximum-likelihood based estimation frameworks for this model class but rather enables unique intrinsic mechanisms that can be helpful in many applied problems. The performance of our boosting algorithm for copula regression models with continuous margins is evaluated in simulation studies that cover low- and high-dimensional data settings and situations with and without dependence between the responses. Moreover, distributional copula boosting is used to jointly analyze and predict the length and the weight of newborns conditional on sonographic measurements of the fetus before delivery together with other clinical variables.

Limited Effects of SARS-CoV-2 Pandemic-related Lockdowns and Reduced Population Mobility on Preterm Birth Rates: A Secondary Analysis of Bavarian Obstetric Quality Parameters from 2010 to 2020.

Introduction International studies on preterm birth rates during COVID-19 lockdowns report different results. This study examines preterm birth rates during lockdown periods and the impact of the mobility changes of the population in Bavaria, Germany. Material and Methods This is a secondary analysis of centrally collected data on preterm births in Bavaria from 2010 to 2020. Preterm births (< 37 weeks) in singleton and twin pregnancies during two lockdowns were compared with corresponding periods in 2010 - 2019. Fisher's exact test was used to compare raw prevalence between groups. Potential effects of two fixed lockdown periods and of variable changes in population mobility on preterm birth rates in 2020 were examined using additive logistic regression models, adjusting for long-term and seasonal trends. Results Unadjusted preterm birth rates in 2020 were significantly lower for singleton pregnancies during the two lockdown periods (Lockdown 1: 5.71% vs. 6.41%; OR 0.88; p < 0.001; Lockdown 2: 5.71% vs. 6.60%; OR = 0.86; p < 0.001). However, these effects could not be confirmed after adjusting for long-term trends (Lockdown 1: adj. OR = 0.99; p = 0.73; Lockdown 2: adj. OR = 0.96; p = 0.24). For twin pregnancies, differences during lockdown were less marked (Lockdown 1: 52.99% vs. 56.26%; OR = 0.88; p = 0.15; Lockdown 2: 58.06% vs. 58.91%; OR = 0.97; p = 0.70). Reduced population mobility had no significant impact on preterm birth rates in singleton pregnancies (p = 0.14) but did have an impact on twin pregnancies (p = 0.02). Conclusions Reduced preterm birth rates during both lockdown periods in 2020 were observed for singleton and twin pregnancies. However, these effects are reduced when adjusting for long-term and seasonal trends. Reduced population mobility was associated with lower preterm birth rates in twin pregnancies.

Influence of Timing of Antenatal Corticosteroid Administration on Morbidity of Preterm Neonates.

BACKGROUND/AIM: We investigated the impact of the timing of antenatal corticosteroid (ACS) administration on the clinical outcome of preterm infants. PATIENTS AND METHODS: Two hundred and fifty-five preterm infants between 28+0 and 34+0 weeks of gestation were retrospectively assigned to one of two groups: In the first group, ACS was given within 7 days before birth; the second group, did not receive ACS during that period. The primary outcome parameter was respiratory failure (defined by need for continuous positive airway pressure or mechanical ventilation) due to grade 1-4 respiratory distress syndrome (RDS). Secondary outcomes included the rates of intraventricular hemorrhage (IVH), periventricular leukomalacia, and necrotizing enterocolitis. RESULTS: The rate of RDS was significantly higher in the no ACS group (40% vs. 62%, p=0.0009), especially of the more severe grades 24 (n=37 vs. n=48, p=0.0121). In addition, IVH (1% vs. 9%, p=0.0041) and neonatal infections (72% vs. 89%, p=0.0025) were significantly increased. Univariable and multivariable regression analyses showed a lower likelihood of RDS in the ACS group [odds ratio (OR)=0.295] in infants born closer to term (OR=0.907) and following preterm onset of labor (OR=0.495). Similarly, we observed a lower probability of IVH in the ACS group (OR=0.098), with a higher probability of occurrence of IVH in pre-eclampsia/HELLP syndrome (hemolysis, elevated liver enzyme levels, low platelet count) (OR=7.914). CONCLUSION: ACS treatment within the last 7 days before birth significantly reduced the risk of RDS and IVH in preterm. These data emphasize that the timing of ACS administration determines its success.

Prevalence of SARS-CoV-2 in Pregnant Women Assessed by RT-PCR in Franconia, Germany: First Results of the SCENARIO Study (SARS-CoV-2 prEvalence in pregNAncy and at biRth In FrancOnia).

Purpose Detection of SARS-CoV-2-infected pregnant women admitted to maternity units during a pandemic is crucial. In addition to the fact that pregnancy is a risk factor for severe COVID-19 and that medical surveillance has to be adjusted in infected women and their offspring, knowledge about infection status can provide the opportunity to protect other patients and healthcare workers against virus transmission. The aim of this prospective observational study was to determine the prevalence of SARS-CoV-2 infection among pregnant women in the hospital setting. Material and Methods All eligible pregnant women admitted to the nine participating hospitals in Franconia, Germany, from 2 June 2020 to 24 January 2021 were included. COVID-19-related symptoms, secondary diseases and pregnancy abnormalities were documented. SARS-CoV-2 RNA was detected by RT-PCR from nasopharyngeal swabs. The prevalence of acute SARS-CoV-2 infection was estimated by correcting the positive rate using the Rogan-Gladen method. The risk of infection for healthcare workers during delivery was estimated using a risk calculator. Results Of 2414 recruited pregnant women, six were newly diagnosed RT-PCR positive for SARS-CoV-2, which yielded a prevalence of SARS-CoV-2 infection of 0.26% (95% CI, 0.10 - 0.57%). Combining active room ventilation and wearing FFP2 masks showed an estimated reduction of risk of infection for healthcare workers in the delivery room to < 1%. Conclusions The prevalence of newly diagnosed SARS-CoV-2 infection during pregnancy in this study is low. Nevertheless, a systematic screening in maternity units during pandemic situations is important to adjust hygienic and medical management. An adequate hygienic setting can minimise the calculated infection risk for medical healthcare workers during patients' labour.

Amniotic-Umbilical-to-Cerebral Ratio - A Novel Ratio Combining Doppler Parameters and Amniotic Fluid Volume to Predict Adverse Perinatal Outcome in SGA Fetuses At Term.

PURPOSE: Introduction of a novel ratio - the amniotic-umbilical-to-cerebral ratio (AUCR) - to predict adverse perinatal outcome in SGA fetuses at term and comparison of its predictive accuracy with established parameters. MATERIALS AND METHODS: This retrospective cohort study included 165 singleton pregnancies with SGA fetuses (birth weight < 10th percentile) at term. Cases with planned vaginal delivery and documented pulsatility indices (PI) of the umbilical artery (UA), middle cerebral artery (MCA), and single deepest pocket (SDP) were included. CPR was calculated as the ratio between MCA PI and UA PI, UCR as the ratio between UA PI and MCA PI. AUCR was defined as follows: SDP/(UA PI/MCA PI). Adverse perinatal outcomes were defined as operative intervention (OI), OI due to fetal distress, admission to the neonatal intensive care unit (NICU), and composite adverse perinatal outcome (CAPO). Associations between Doppler parameters and these outcomes were estimated using regression analyses. RESULTS: OI was statistically significantly associated with UCR, SDP, and AUCR, whereas no association was observed for UA PI, MCA PI, and CPR. Fetuses requiring OI due to fetal distress revealed a significantly higher UA PI and UCR as well as a lower MCA PI, CPR, and AUCR. With regard to NICU admission and CAPO, a significantly higher UA PI and lower CPR were found. Furthermore, a significant association was shown for SDP, UCR, and AUCR. AUCR achieved the best area under the curve for all outcome parameters. CONCLUSION: AUCR leads to an improvement in the prediction of unfavorable outcome in SGA fetuses at term. Furthermore, results of our study show that UCR might be superior to CPR.

Influence of Sonographic Fetal Weight Estimation Inaccuracies in Macrosomia on Perinatal Outcome.

OBJECTIVE: To evaluate the influence of inaccurate sonographic fetal weight estimation in macrosomia on the mode of delivery and neonatal outcome (NO). METHODS: In 14 633 pregnancies between 2002 and 2016, this retrospective study evaluated the association between sonographic fetal weight estimation, true birth weight (BW), mode of delivery (primary cesarean section [pCS], secondary cesarean section, vaginal delivery, and operative vaginal delivery rates) and NO parameters (5-min Apgar < 7, pH < 7.1, neonatal intensive care unit [NICU] admission, shoulder dystocia). Singleton pregnancies > 37 + 0 weeks with ultrasound-estimated fetal weight (EFW) within 7 days before delivery were included. The study population was divided into four groups: Group 1 (false-negative): EFW < 4000 g/BW ≥ 4000 g; Group 2 (true-positive): EFW ≥ 4000 g/BW ≥ 4000 g; Group 3 (false-positive): EFW ≥ 4000 g/BW < 4000 g; and Group 4 (true-negative): EFW < 4000 g/BW < 4000 g. RESULTS: As expected, the highest secondary cesarean section (sCS) rate was found in Group 2 (true-positive) (30.62 %), compared with only 17.68 % in Group 4 (true-negative). The sCS rate in the false-positive Group 3 was significantly higher (28.48 %) in comparison with the false-negative Group 1 (21.22 %; OR 1.48; 95 % CI, 1.16 to 1.89; P = 0.002). In comparison with the true-negative Group 4, univariate analyses showed significantly higher rates for sCS in all other groups: odds ratio (OR) 2.06 for Group 2 (95 % CI, 1.74 to 2.42; P < 0.001), 1.85 for Group 3 (95 % CI, 1.54 to 2.22, P < 0.001), and 1.25 for Group 1 (95 % CI, 1.05 to 1.49; P < 0.01). No significant differences were found for NO between Groups 1 and 3 for the parameters 5-min Apgar < 7 (P = 0.75), pH < 7.1 (P = 0.28), or NICU admission (P = 0.54). However, there was a significantly higher chance for shoulder dystocia in Group 1 compared with Group 3 (OR 4.58; 95 % CI, 1.34 to 24.30; P = 0.008). CONCLUSION: Sonographic EFW inaccuracies in fetal macrosomia appear to have a greater impact on the mode of delivery than birth weight itself. Underestimation of fetal weight may be associated with a higher probability of shoulder dystocia.

Labour Induction with Misoprostol in German Obstetric Clinics: What Are the Facts on Such Use?

Subject While the synthetic prostaglandin E1 analogue misoprostol is the most effect labour induction agent, its use is off-label for the most part. For this reason, and in view of its potential adverse effects and varying approaches to its administration, the drug has recently once again become a focus of critical attention. The objective of this survey was thus to establish a record of labour induction with misoprostol in German clinics and determine the impact of the negative reporting on everyday obstetric practice. Material and Methods In this cross-sectional study, 635 obstetrics and gynaecology departments in Germany were requested by email to participate in our survey in February/March 2020. Online responses to 19 questions were requested regarding the clinic, use of misoprostol before and after the critical reporting, use of misoprostol (sourcing, method of administration, dosage, monitoring) and other labour induction methods. Results A total of 262 (41.3%) of the clinics solicited for the survey completed the questionnaire. There were no differences regarding the care level (Perinatal Centre Level I, Perinatal Centre Level II, Clinic with Perinatal Focus or Obstetric/Private Clinic; p = 0.2104) or birth counts (p = 0.1845). In most cases, misoprostol was prepared in the clinic's own pharmacy (54%) or imported from another country (46%) and administered orally in tablet form (95%). Misoprostol dosage levels varied (25 µg [48%], 50 µg [83%], 75 µg [6%], 100 µg [47%] and > 100 µg [5%]). Most of the clinics used premanufactured tablets/capsules (59%), although Cytotec tablets were also divided (35%) or dissolved in water (5%). Misoprostol administration intervals were mainly every 4 hours (64%) or every 6 hours (30%). CTG checks were run in most cases before and after administration of a dose of misoprostol (78% and 76%) and before and after administration of a dose of prostaglandin E2 (both 88%). Presence of contractions led to no misoprostol (59%) or no prostaglandin E2 (64%) being administered in most cases. The critical reporting resulted in discontinuation of use of misoprostol in 17% of the clinics - mainly smaller obstetric/private clinics with fewer than 1000 births. Labour cocktails were used mainly in obstetric and private clinics (61%). Conclusion Misoprostol is an established agent for labour induction in German clinics. The dosing schemes used vary. Improvements of currently common management practices are required, especially in the area of labour induction (CTG checks before and after administration of labour-inducing medication, no administration of prostaglandin if contractions are ongoing). The discussion of use of misoprostol in the media resulted in stoppage of its use mainly in smaller clinics.

The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration.

OBJECTIVES: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination. METHODS: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU). RESULTS: In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272). CONCLUSIONS: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length.

Influence of Preeclampsia on Induction of Labor at Term: A Cohort Study.

BACKGROUND/AIM: Even though vaginal delivery is a feasible option in patients with preeclampsia, the cesarean section rate in those patients is high. The aim of this study was to evaluate the influence of preeclampsia on induction of labor at term. PATIENTS AND METHODS: This historical cohort study analyzed inductions of labor in women at term having preeclampsia versus women who were induced due to other reasons. The primary outcome measure was the cesarean section rate. RESULTS: The cesarean section rate was higher in the preeclampsia group for both nulliparous and multiparous women after induction of labor but failed to reach statistical significane. The induction-to-delivery interval was longer in nulliparous women and the rate of vaginal birth within 48 h was lower in the nulliparous patiens with preeclampsia. However, the impact of preeclampsia on the cesarean section rate was not significant in the multivariable analysis following adjustment for BMI and parity. CONCLUSION: Preeclampsia at term did not influence the cesarean section rate in nulliparous and parous women when labor was induced.

Safety and immunogenicity of Fc-EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects.

In X-linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X-linked hypohidrotic ectodermal dysplasia patients may lead to life-threatening hyperthermia, especially during hot weather or febrile illness. Fc-EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc-EDA and efficacy if applied prenatally. Anti-drug antibodies were detected after intravenous administration in adult males and nonpregnant females, but not in pregnant women when Fc-EDA was delivered intra-amniotically. Most importantly, there was no detectable immune response to the investigational drug in neonates treated by intravenous infusions and in infants who had received Fc-EDA in utero. In conclusion, the safety profile of this drug encourages further development of prenatal EDA1 replacement therapy.

[Does Induction of Labor for Preterm Premature Rupture of Membranes at 34 Weeks of Gestation Increase the Risk for Cesarean Section?] / Erhöht die Geburtseinleitung wegen eines frühen vorzeitigen Blasensprungs ab 34+0 SSW das Risiko für einen Kaiserschnitt?

PURPOSE: Induction of labor at 34 weeks of gestation is often linked to increased risk for cesarean section. Recently, the PPROMT trial demonstrated a higher cesarean section rate when labor was induced for preterm premature rupture of membranes (PPROM). The purpose of this study was therefore to evaluate the success rate of induction of labor for PPROM at 34 and 35 weeks of gestation in comparison with a higher gestational age. MATERIAL AND METHODS: In this historic cohort study, cases with labor inductions for PPROM ≥ 34 weeks of gestation were included. Induction of labor at 34 and 35 weeks of gestation (group 1) were compared with those performed at 36 weeks (group 2) and 37 weeks (group 3). Induction of labor was started 12 to 24 hours after (preterm) premature rupture of membranes. Antibiotics were given routinely. The primary outcome was the rate of cesarean section. RESULTS: There were significantly more cesarean sections in group 3 in comparison with group 2 (7 vs. 25%, p=0.0136). However, univariable and multiple logistic regression analysis of the primary outcome measure showed that there was no impact of the group affiliation on cesarean section rate. Significant parameters influencing the risk of cesarean section were body mass index and Bishop score. CONCLUSION: Induction of labor for PPROM at 34 weeks of gestation is not associated with an increased rate of cesarean section.

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.

Longitudinal Course of Short-Term Variation and Doppler Parameters in Early Onset Growth Restricted Fetuses.

PURPOSE: To evaluate the longitudinal pattern of fetal heart rate short term variation (STV) and Doppler indices and their correlation to each other in severe growth restricted (IUGR) fetuses. MATERIALS AND METHODS: In this retrospective study, pregnancies with a birth weight below the 10th percentile, born between 24 and 34 gestational weeks with serial Doppler measurements in combination with a computerized CTG (cCTG) with calculated STV were included. Longitudinal changes of both Doppler indices and STV values were evaluated with generalized additive models, adjusted for gestational age and the individual. For all measurements the frequency of abnormal values with regard to the time interval before delivery and Pearson correlations between Doppler indices and STV values were calculated. RESULTS: 41 fetuses with a total of 1413 observations were included. Over the course of the whole study period, regression analyses showed no significant change of STV values (p = 0.38). Only on the day of delivery, a prominent decrease was observed (mean STV d28-22: 7.97 vs. mean STV on day 0: 6.8). Doppler indices of UA and MCA showed a continuous, significant deterioration starting about three weeks prior to delivery (p = 0.007; UA and p < 0.001, MCA). Correlation between any Doppler index and STV values was poor. CONCLUSION: Fetal heart rate STV does not deteriorate continuously. Therefore, cCTG monitoring should be performed at least daily in these high-risk fetuses. Doppler indices of umbilical artery (UA) and middle cerebral artery (MCA), however, showed continuous deterioration starting about 3 weeks prior to delivery.

Comparison of Current Swiss Fetal Biometry Reference Charts with Reference Charts from 1999. Are Fetuses Getting Bigger?

PURPOSE: To create current fetal biometry reference ranges and to compare them with references published in 1999, from the same local area in order to generate data for secular trend in fetal size. MATERIALS AND METHODS: Applying the same methodology as previously published, we calculated reference ranges for biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference (HC), abdominal circumference (AC) and femur length (FL) in 7863 patients examined at the obstetric clinics in a cross-sectional, prospective study in a university setting from January 2008 to December 2014. In order to compare the new reference ranges with our previously published data, we used Z-Scores and displayed the pick-up of fetal biometry data below the 5th and above the 95th percentile using the previously published reference charts. RESULTS: The comparison of the charts showed a minimal but clinically relevant increase in mean fetal body measures (BPD, HC, AC). Applying the 1999 charts to the new dataset, we would classify only 162 of 339 fetuses (47.8 %) to be correctly below the 5th percentile for AC and only 134 of 349 (38.4 %) fetuses were correctly below the 5th percentile for HC. On the other hand, the 1999 charts classified 426 instead of 332 fetuses to be above the 95th percentile for AC, which means an overestimation of 28.3 %. CONCLUSION: Applying a similar methodology, study collective and clinical setting, our new charts showed clinically relevant differences compared to the 1999 charts. The data suggest that within one generation fetuses are getting bigger and regular updates of fetal reference charts are needed.