High-Sensitivity Cardiac Troponin I Enhances Preeclampsia Prediction Beyond Maternal Factors and the sFlt-1/PlGF Ratio.

BACKGROUND: Preeclampsia shares numerous risk factors with cardiovascular diseases. Here, we aimed to assess the potential utility of high-sensitivity cardiac troponin I (hs-cTnI) values during pregnancy in predicting preeclampsia occurrence. METHODS: This study measured hs-cTnI levels in 3721 blood samples of 2245 pregnant women from 4 international, prospective cohorts. Three analytical approaches were used: (1) a cross-sectional analysis of all women using a single blood sample, (2) a longitudinal analysis of hs-cTnI trajectories in women with multiple samples, and (3) analyses of prediction models incorporating hs-cTnI, maternal factors, and the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio. RESULTS: Women with hs-cTnI levels in the upper quarter had higher odds ratios for preeclampsia occurrence compared with women with levels in the lower quarter. Associations were driven by preterm preeclampsia (odds ratio, 5.78 [95% CI, 2.73-12.26]) and remained significant when using hs-cTnI as a continuous variable adjusted for confounders. Between-trimester hs-cTnI trajectories were independent of subsequent preeclampsia occurrence. A prediction model incorporating a practical hs-cTnI level of detection cutoff (≥1.9 pg/mL) alongside maternal factors provided comparable performance with the sFlt-1/PlGF ratio. A comprehensive model including sFlt-1/PlGF, maternal factors, and hs-cTnI provided added value (cross-validated area under the receiver operator characteristic, 0.78 [95% CI, 0.73-0.82]) above the sFlt-1/PlGF ratio alone (cross-validated area under the receiver operator characteristic, 0.70 [95% CI, 0.65-0.76]; P=0.027). As assessed by likelihood ratio tests, the addition of hs-cTnI to each prediction model significantly improved the respective prediction model not incorporating hs-cTnI, particularly for preterm preeclampsia. Net reclassification improvement analyses indicated that incorporating hs-cTnI improved risk prediction predominantly by correctly reclassifying women with subsequent preeclampsia occurrence. CONCLUSIONS: These exploratory findings uncover a potential role for hs-cTnI as a complementary biomarker in the prediction of preeclampsia. After validation in prospective studies, hs-cTnI, alongside maternal factors, may either be considered as a substitute for angiogenic biomarkers in health care systems where they are sparce or unavailable, or as an enhancement to established prediction models using angiogenic markers.

Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

The Arabin cervical pessary for the prevention of preterm birth in twin-to-twin transfusion syndrome treated by fetoscopic laser coagulation: a multicenter randomized controlled trial.

BACKGROUND: Miscarriage and preterm birth are leading causes of loss and disability in monochorionic twins after laser treatment of twin-twin transfusion syndrome. OBJECTIVE: This study aimed to investigate the use of cervical pessary to reduce preterm birth before 32 weeks of gestation in monochorionic diamniotic twin pregnancies after fetal surgery for twin-twin transfusion syndrome. STUDY DESIGN: In this open-label multicenter randomized trial, pregnant women carrying monochorionic diamniotic twins requiring fetoscopic laser coagulation for twin-twin transfusion syndrome were randomly assigned in a 1:1 ratio to pessary placement or conservative management. The primary outcome was birth before 32 weeks of gestation. The secondary outcomes were birth before 28, 30, 34, or 37 weeks of gestation; preterm premature rupture of membranes; fetal and neonatal survival; and a composite of maternal and neonatal complications. The estimated sample size was 364 patients, with 182 cases in each arm of the study. The analysis was performed according to the intention-to-treat principle. Moreover, 2 interim analyses were planned. RESULTS: The trial was stopped prematurely after the first planned interim analysis for futility. Overall, 137 women were included in the analysis, 67 in the pessary group and 70 in the conservative management group. Preterm birth before 32 weeks of gestation occurred in 27 of 67 women (40.3%) in the pessary group and in 25 of 70 women (35.7%) in the conservative management group (adjusted odds ratio, 1.19; 95% confidence interval, 0.58-2.47; P=.63). No differences between groups was observed in the rate of deliveries before 28, 30, 34, and 37 weeks of gestation. Overall survival to delivery was 91.2% (125/137) for at least 1 twin, and 70.8% (97/137) for both twins, with no difference between groups. Neonatal survival at 30 days was 76.5% (208/272). There was no difference between the groups in maternal or neonatal morbidity. CONCLUSION: In monochorionic diamniotic twin pregnancies requiring fetal therapy for twin-twin transfusion syndrome, routine use of cervical pessary did not reduce the rate of preterm birth before 32 weeks of gestation.

Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach.

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction.

Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology.

OBJECTIVE: Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. METHOD: Existing severity grading for pregnant AEs and definitions/indicators of 'severe' and 'life-threatening' conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. RESULTS: Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n = 12) and fetal (n = 19) AE definitions and severity grading criteria were developed and ratified by consensus. CONCLUSIONS: This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety.

[Recommendations for SARS-CoV-2/COVID-19 during Pregnancy, Birth and Childbed - Update November 2021 (Long Version)]. / Empfehlungen zu SARS-CoV-2/COVID-19 in Schwangerschaft, Geburt und Wochenbett ­ Update November 2021 (Langfassung).

Since the onset of the SARS-CoV-2 pandemic, the German Society of Gynecology and Obstetrics and the Society for Peri-/Neonatal Medicine have published and repeatedly updated recommendations for the management of SARS-CoV-2 positive pregnancies and neonates. As a continuation of existing recommendations, the current update addresses key issues related to the prenatal, perinatal, and postnatal care of pregnant women, women who have given birth, women who have recently given birth, women who are breastfeeding with SARS-CoV-2 and COVID-19, and their unborn or newborn infants, based on publications through September 2021. Recommendations and opinions were carefully derived from currently available scientific data and subsequently adopted by expert consensus. This guideline - here available in the long version - is intended to be an aid to clinical decision making. Interpretation and therapeutic responsibility remain with the supervising local medical team, whose decisions should be supported by these recommendations. Adjustments may be necessary due to the rapid dynamics of new evidence. The recommendations are supported by the endorsement of the professional societies: German Society for Perinatal Medicine (DGPM), German Society of Gynecology and Obstetrics (DGGG), German Society for Prenatal and Obstetric Medicine (DGPGM), German Society for Pediatric Infectiology (DGPI), Society for Neonatology and Pediatric Intensive Care Medicine (GNPI).

[Recommendations for SARS-CoV-2/COVID-19 during Pregnancy, Birth and Childbed - Update November 2021 (Short Version)]. / Empfehlungen zu SARS-CoV-2/COVID-19 in Schwangerschaft, Geburt und Wochenbett ­ Update November 2021 (Kurzfassung).

Since the onset of the SARS-CoV-2 pandemic, the German Society of Gynecology and Obstetrics and the Society for Peri-/Neonatal Medicine have published and repeatedly updated recommendations for the management of SARS-CoV-2 positive pregnancies and neonates. As a continuation of existing recommendations, the current update addresses key issues related to the prenatal, perinatal, and postnatal care of pregnant women, women who have recently given birth, women who are breastfeeding with SARS-CoV-2 and COVID-19, and their unborn or newborn infants, based on publications through September 2021. Recommendations and opinions were carefully derived from currently available scientific data and subsequently adopted by expert consensus. This guideline - here available in the short version - is intended to be an aid to clinical decision making. Interpretation and therapeutic responsibility remain with the supervising local medical team, whose decisions should be supported by these recommendations. Adjustments may be necessary due to the rapid dynamics of new evidence. The recommendations are supported by the endorsement of the professional societies: German Society for Perinatal Medicine (DGPM), German Society of Gynecology and Obstetrics (DGGG), German Society for Prenatal and Obstetric Medicine (DGPGM), German Society for Pediatric Infectiology (DGPI), Society for Neonatology and Pediatric Intensive Care Medicine (GNPI).

Correction: The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

[This corrects the article DOI: 10.1371/journal.pmed.1002220.].

Intrauterine fetoscopic laser surgery versus expectant management in stage 1 twin-to-twin transfusion syndrome: an international randomized trial.

BACKGROUND: Selective fetoscopic laser coagulation of the intertwin anastomotic chorionic vessels is the first-line treatment for twin-twin transfusion syndrome. However, in stage 1 twin-twin transfusion syndrome, the risks of intrauterine surgery may be higher than those of the natural progression of the condition. OBJECTIVE: This study aimed to compare immediate surgery and expectant follow-up in stage 1 twin-twin transfusion syndrome. STUDY DESIGN: We conducted a multicentric randomized trial, which recruited from 2011 to 2018 with a 6-month postnatal follow-up. The study was conducted in 9 fetal medicine centers in Europe and the Unites States. Asymptomatic women with stage 1 twin-twin transfusion syndrome between 16 and 26 weeks' gestation, a cervix of >15 mm, and access to a surgical center within 48 hours of diagnosis were randomized between expectant management and immediate surgery. In patients allocated to immediate laser treatment, percutaneous laser coagulation of anastomotic vessels was performed within 72 hours. In patients allocated to expectant management, a weekly ultrasound follow-up was planned. Rescue fetoscopic coagulation of anastomoses was offered if the syndrome worsened as seen during a follow-up, either because of progression to a higher Quintero stage or because of the maternal complications of polyhydramnios. The primary outcome was survival at 6 months without severe neurologic morbidity. Severe complications of prematurity and maternal morbidity were secondary outcomes. RESULTS: The trial was stopped at 117 of 200 planned inclusions for slow accrual rate over 7 years: 58 women were allocated to expectant management and 59 to immediate laser treatment. Intact survival was seen in 84 of 109 (77%) expectant cases and in 89 of 114 (78%) (P=.88) immediate surgery cases, and severe neurologic morbidity occurred in 5 of 109 (4.6%) and 3 of 114 (2.6%) (P=.49) cases in the expectant and immediate surgery groups, respectively. In patients followed expectantly, 24 of 58 (41%) cases remained stable with dual intact survival in 36 of 44 (86%) cases at 6 months. Intact survival was lower following surgery than for the nonprogressive cases, although nonsignificantly (78% and 71% following immediate and rescue surgery, respectively). CONCLUSION: It is unlikely that early fetal surgery is of benefit for stage 1 twin-twin transfusion syndrome in asymptomatic pregnant women with a long cervix. Although expectant management is reasonable for these cases, 60% of the cases will progress and require rapid transfer to a surgical center.

Fetoscopic techniques for prenatal covering of gastroschisis in an ovine model are technically demanding and do not lead to permanent anchoring on the fetus until the end of gestation.

INTRODUCTION: This is the cumulative technical report on the operative procedures and limitations of fetoscopic bag insertion, intestinal bag placement, and bag fixation to the fetus in a series of pilot studies in an ovine model for prenatal treatment of gastroschisis. MATERIAL AND METHODS: In 24 German blackhead sheep, a surgically created gastroschisis was managed by fetoscopic placement of the extruded intestines into a bag. The bag was then fastened onto the fetal abdominal wall. Different materials (sterile gloves, latex condoms, laparosopic retrieval bags) and different fixation techniques (laparoscopic staplers, interrupted and continuous sutures) have been examined. The fetuses were retrieved and evaluated at the end of gestation. RESULTS: Uterine bag insertion was successful in 15 of 24 (62.5%) and intestinal bag placement in 10 of 15 available fetuses (66.6%). The main factor limiting fetoscopic procedures was chorioamniotic separation (CAS). Sterilized condoms provided the most appropriate type of bags and the V-Loc™ running suture, the most expedient type of fixation, which was achieved in 9 of the 10 fetuses (complete = 2, partially = 7) by using a three port access (5 mm and 2 × 3 mm). All bags were encountered completely or partially dislocated from the fetus at the end of gestation. CONCLUSIONS: Fetoscopic intestinal bag placement and fixation in gastroschisis technically demanding. None of the evaluated techniques led to permanent anchorage of the bag to the fetus. The development of specially designed instruments, bags and fixation methods is required to optimize this approach.

Fetal dynamic magnetic resonance imaging using Doppler ultrasound gating for the assessment of the aortic isthmus: A feasibility study.

INTRODUCTION: Cardiovascular magnetic resonance imaging (MRI) is established in cardiac evaluation in postnatal life, but its application to the fetus has been hampered by technical limitations. We aimed to investigate the feasibility of dynamic MRI of the fetal aortic isthmus using a magnetic resonance-compatible Doppler ultrasound device for cardiac gating. MATERIAL AND METHODS: This prospective study included 19 fetuses at a median gestational age of 32.3 weeks (range 26-38 weeks). Imaging of the fetal aortic isthmus was assessed by (a) dynamic steady-state free precession MRI using a magnetic resonance-compatible Doppler ultrasound device for cardiac gating and (b) echocardiography. Diameters of the aortic isthmus were compared by two blinded observers. Magnetic resonance image quality was assessed independently by two observers using a four-point scale (1 = low quality, 4 = high quality). Furthermore, we performed four-dimensional flow MRI of the fetal aorta in three of these fetuses. RESULTS: The Doppler ultrasound device for cardiac gating allowed successful dynamic MRI examinations of the aortic isthmus in 18/19 (95%) fetuses. Evaluation of the fetal aortic isthmus was possible by both MRI (15/18, 83%) and echocardiography (16/18, 89%) (P < .05). Diameters of the aortic isthmus were concordant for MRI (3.8 ± 0.9 mm) and echocardiography (4.0 ± 1.1 mm), with a variability of 10.8% (bias -2.3%, 95% limits of agreement -23.9% to 19.3%). Overall magnetic resonance image quality was good (score 4 in 67% and score 3 in 23%) with good inter-observer agreement (κ = 0.75; 95% CI 0.5-1). Fetal four-dimensional flow MRI allowed visualization of aortic flow dynamics. CONCLUSIONS: Doppler ultrasound-gating allows dynamic MRI of the fetal aorta with the potential to serve as a complementary imaging tool in cases where echocardiography is inconclusive.

Third Trimester Umbilical Artery Doppler in Low-Risk Pregnancies and its Correlation to Estimated Fetal Weight and Birthweight.

PURPOSE: This study investigated the correlation between the umbilical artery (UA) pulsatility index (PI) and the estimated fetal weight percentile and birthweight (BW) percentile, respectively. MATERIALS AND METHODS: We included low-risk pregnancies, in which UA Doppler investigations after 28 weeks were performed. Cases were allocated according to BW percentiles: small for gestational age (SGA) with BW < 10th percentile; appropriate for gestational age (AGA) and large for gestational age (LGA) with BW > 90th percentile. We analyzed differences in the mean UA-PI and UA-PI z-score for gestational age according to the three groups. Linear regression was performed to evaluate any relationship between Doppler indices and BW percentiles. Multiple logistic regression analysis was performed to determine the independent association of UA-PI with LGA babies. In a second step, we considered data on estimated fetal weight (EFW) percentiles and performed the same analysis. RESULTS: We analyzed 14 554 pregnancies from 2004 to 2015. The mean UA-PI and mean UA-PI z-scores in the LGA group were lower than in the AGA and SGA groups (p < 0.001). UA-PI and UA-PI z-scores were linearly related to birthweight percentiles (p < 0.001) and to EFW percentiles (p < 0.001). Logistic regression analysis showed that low UA-PI was independently associated with neonatal LGA (p < 0.001). CONCLUSION: The higher the EFW and BW percentiles, the lower the UA-PI. However, reference ranges for UA Doppler are only based on gestation weeks. Further studies are needed to clarify whether customized reference ranges based on EFW percentiles are more appropriate for the evaluation of fetal wellbeing in the third trimester.

Screening, Management and Delivery in Twin Pregnancy. / Überwachung und Betreuung von Zwillingsschwangerschaften (AWMF 015-087 S2e-Leitlinie).

The following AWMF guideline (DGGG/AGG & DEGUM responsible) deals with the diagnosis, screening and management of twins as well as the timing and mode of birth.Twin pregnancies can be classified as dichorionic diamniotic (DC DA), monochorionic diamniotic (MC DA) and monochorionic monoamniotic (MC MA) which are always monochorionic.Twin pregnancies can be concordant (both twins are affected) or discordant (only one twin is affected) for chromosomal defects, malformations, growth restriction and hemodynamic disorders.Chorionicity is the prognostically most significant parameter. Monochorial twins have significantly higher risks of intrauterine morbidity and mortality compared to dichorial twins.In particular, general aspects of twin pregnancies such as dating, determination of chorionicity and amnionicity, the labeling of twin fetuses and the perinatal switch phenomenon are discussed.Routine monitoring of MC and DC twin pregnancies with ultrasound at 11-13+ 6 weeks of gestation for chromosomal defects, invasive prenatal diagnosis, first-trimester NT or CRL discrepancies, early diagnosis of fetal anatomical defects, and management of twins with abnormalities, including selective fetocide, is described.Second trimester screening and management for preterm birth, intrauterine selective growth restriction (sFGR), classification of monochorial twins with sFGR, and management of the surviving twin after the death of the co-twin are described.Complications exclusively affecting MC twins include Twin to Twin Transfusion Syndrome (TTTS) with the important topics screening, prognosis, complications of laser therapy, timing of delivery, risks for brain abnormalities and delayed neurological development, Twin Anemia-Polycythemia Sequence (TAPS) and Twin Reversed Arterial Perfusion (TRAP) Sequence. This also includes MC MA twins as well as conjoined twins.Finally, the birth mode and time for DC and MC twin pregnancies are described.The information is summarized in 62 recommendations for action, 4 tables and 8 illustrations with comprehensive background texts.The guideline is an international guideline adaptation (ISUOG, NICE) as well as a systematic literature search and is up-to-date.

Effects of Antenatal Betamethasone on Fetal Doppler Indices and Short Term Fetal Heart Rate Variation in Early Growth Restricted Fetuses.

PURPOSE: To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses. MATERIALS AND METHODS: Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (baseline value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV. RESULTS: We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p < 0.001). CONCLUSION: Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.

[Effects of Obstetric Analgesia with Systemic Opioids on the Newborn - A Review]. / Auswirkungen geburtshilflicher Analgesie mit systemischen Opioiden auf das Neugeborene ­ eine Übersichtsarbeit.

INTRODUCTION: Three-quarters of all women receive analgesia during labor. There are regional and systemic analgesia procedures available. In this review, we investigate the impact of obstetric analgesia using systemic opioids on neonatal outcomes. METHODS: We searched the PubMed and Cochrane Library databases using the following search terms: "meptazinol", "meptide", "analgesia", "painkiller", "pain reliever", "obstetrics", "labor", "labour", "delivery", "neonate", "newborn", "child", "baby", "infant", "fetus", "fetal", "opioid" and "opiate" as well as performed an additional MeSH Terms search in PubMed. RESULTS: Of 355 potentially relevant studies, we included 23 studies in this review. The studies varied widely in quality, sample size, and outcome criteria. Neonatal outcome was often only a secondary endpoint. Rarely were significant differences related to neonatal outcome reported between the different systemic opioids or compared with control groups. Twelve studies compared neonatal APGAR scores between treatment groups, with ten (83%) of these studies showing no differences. DISCUSSION/OUTLOOK: In summary, we assess the evidence as limited and ambiguous as to whether systemic obstetric opioid therapy negatively affects the newborn. Studies regarding the long-term outcome of the newborns are lacking. A statement regarding the necessity of postnatal monitoring of newborns after maternal obstetric opioid therapy cannot be concluded. Further studies, ideally with a prospective study design and control group, should be considered.

Longitudinal adrenal gland measurements and growth trajectories as risk markers for late preterm delivery.

BACKGROUND: The fetal adrenal gland receives rising awareness as a predictor of spontaneous preterm birth. We hereby provide longitudinal growth assessments of the fetal adrenal gland in a low risk population with an additional focus on trajectories in fetuses born preterm. METHODS: Fetal adrenal gland was assessed via transabdominal ultrasound at gestational weeks (gw) 24-26, 28-30, and 34-36 in a low-risk pregnancy cohort. Longitudinal trajectories of the total gland and the mark (so called fetal zone) as well as ratio of fetal zone width/ total widths (w/W) were analyzed using repeated ANOVA analyses. To compare trajectories of the ratio w/W for preterm and term fetuses respectively, as well as women with and without clinical signs of preterm labor, the propensity score method was applied. RESULTS: Fetal zone width increased over the course of pregnancy (p < 0.0001), while the ratio w/W decreased (p < 0.0001) (n = 327). Comparing the trajectories of the ratio w/W in fetuses born preterm (n = 11) with propensity-score matched term born fetuses (n = 22), a decrease between gw 24-26 and 28-30 was observed in both groups, which continued to decrease for the term born fetuses. However, in preterm born fetuses, the ratio increased above the term born values at gw 34-36. CONCLUSION: Our study provides for the first time longitudinal growth data on the fetal adrenal gland and supports the hypothesis that fetal zone enlargement is associated with preterm birth which could play an important role in risk-prediction.

Psychometric properties of 13-item versions of the maternal and paternal antenatal attachment scales in German.

OBJECTIVE: To assess scale reliability and factorial validity of the Maternal and Paternal Antenatal Attachment Scale in a German sample. BACKGROUND: Prenatal bonding to the child is an important aspect for parents and has been associated with the early parent-child relationship. The maternal and paternal versions of the Antenatal Attachment Scale (MAAS/PAAS) with the dimensions bonding quality and intensity are among the best-established questionnaires for parental-fetal bonding. However, a German translation of the PAAS and investigations of the factor structure of both MAAS and PAAS are still lacking. METHOD: 263 women and 128 men from Hamburg, Germany, were assessed during pregnancy (total sample N = 391). RESULTS: Factor analyses did not support the original factor structures of both scales. Still, two factors equivalent to the original quality and intensity dimensions were identified. Scale reliability for the extracted factors was satisfying to good for both instruments. CONCLUSION: The revised 13-item versions for MAAS and PAAS are proposed as reliable and valuable measurements of parental-foetal bonding. The scales contribute to the cross-cultural comparison of research on maternal and paternal-foetal bonding. Identifying parents with bonding difficulties already prenatally can enable specific forms of support addressing the parent-child-relationship in the peripartum period. ABBREVIATIONS: Maternal Antenatal Attachment Scale (MAAS). Paternal Antenatal Attachment Scale (PAAS). confirmatory factor analysis (CFA). Root Mean Squared Error of Approximation (RMSEA). Standardized Root Mean Square Residual (SRMR). Comparative Fit Index (CFI). Tucker Lewis Index (TLI). principal axis factoring (PAF). mean (M). standard deviation (SD). standard error (SE). item difficulty (Pi). Kaiser-Meyer-Olkin value (KMO).

[Chorangioma of the Placenta - A Rare Placental Cause of Fetal High Output Cardiac Failure]. / Chorioangiom der Plazenta ­ eine seltene Ursache fetaler High-Output-Herzinsuffizienz.

Chorangiomas of the placenta, benign tumors of chorionic tissue, are a rare placental cause of adverse fetal and maternal outcomes. We describe the case of a large placental chorangioma leading to polyhydramnios as well as consecutive preterm birth and high output cardiac failure of the newborn. Derived from a literature review, we suggest instructions for diagnosis and optimal prenatal care in case of a a suspected placental chorangioma.

[Update on Recommendations for SARS-CoV-2/COVID-19 During Pregnancy, Birth and Childbed]. / Aktualisierte Empfehlungen zu SARS-CoV-2/COVID-19 und Schwangerschaft, Geburt und Wochenbett.

With begin of the SARS-CoV-2 pandemic the german obstetric, peri-/neonatological and pediatric professional societies published recommendations for care of pregnant and newborn, as well as for necessary staff protection in March 2020 [1-3]. Because of the rapid emerging increase of knowledge an update is required. This work therefore perceives as prosecution of the existing recommendations [1-3].Worldwide national recommendations were recently compared and published in a consensual review [4]. In methodological dependence this update of recommendations comments on key questions of pre-, peri- and postnatal care at SARS-CoV-2 and COVID-19, based on publications up to 30.05.2020. Statements represent a carefully concerned expert consensus and can change contemporary as new knowledge appears.The responsibility for concrete management remains at the local medical team, decisions should be supported by these recommendations.

Comparative analysis of high field MRI and histology for ex vivo whole organ imaging: assessment of placental functional morphology in a murine model.

OBJECTIVES: The purpose of our study was to evaluate MRI as a tool to examine placental morphology in a murine model in comparison to classical histology techniques. METHODS: Assessment of placental samples (n = 24) from C57Bl/6 J mice was performed using MR imaging and histomorphological analyses. To optimize image contrast for MRI, a protocol for gadolinium-mediated enhancement of placental tissue was established. To test method sensitivity, placental zone assessment with MRI and histology was applied to a model of prenatal stress exposure known to affect placental morphology (n = 10). Mean data acquisition time for both methods was estimated. Difference between groups was calculated using the Mann-Whitney U test. RESULTS: Tissue fixation with formaldehyde and staining with gadolinium resulted in the best image quality. Placental functional zones were identified and measured with both MRI and histology. MRI and histology were able to detect changes in the L/Jz ratio upon a prenatal stress challenge (p = 0.001; p = 0.003). Data acquisition time was shorter using MRI assessment. CONCLUSIONS: Ex vivo MRI analyses of murine placental functional morphology with MRI are feasible and results are comparable to time-consuming histology. Both MRI and histology allow the detection of experimentally induced morphological tissue alterations.