Search

In twin-to-twin transfusion syndrome (TTTS) communicating placental vessels on the chorionic plate between the donor and recipient twins are responsible for the chronic imbalance of blood flow. Evidence demonstrates that fetoscopic laser ablation is superior to serial amnioreductions in terms of survival and neurological outcome for stages II-IV TTTS. However, the optimal management of stage I TTTS remains poorly understood. It is well established that all chorionic plate anastomoses should be closed by laser ablation. Compared to the selective laser method, the Solomon technique yields a significant reduction of recurrent TTTS and post-laser twin anemia polycythemia sequence (TAPS). Over the past 25 years, survival rates after fetoscopic laser surgery have significantly increased. High volume centers report up to 70% double survival and at least one survivor in90% cases. In this review, we discuss the controversies in the diagnosis and management of TTTS, especially, the optimal management in stage I cases, very early or late diagnosis, and the optimal laser technique. Furthermore, we will discuss a stage-related outcome after laser surgery and examine whether it is necessary at all to distinguish between stages I and II. Finally, the optimal timing as well as mode of delivery after TTTS laser treatment will be discussed.

Fetal anemia secondary to incompatibility between maternal-fetal blood types can result in hydrops and demise. Intrauterine transfusions have improved survival in experience centers. Our objective was to determine the practice patterns amongst fetal centers.Thirteen fetal centers across the world were surveyed. Results from all participating centers were recorded, analyzed, and presented as ratios. Questions on the survey were related to experience of the physician, preferred methods of transfusion, fetal surveillance, and timing of delivery.Differences amongst centers were as follows: 54% of the centers performed transfusions in operating room, the remaining did them in a clinic room or close to the operating room; 31% did not use maternal anesthesia, 31% used oral or intravenous sedation and 38% used a combination of local with oral or intravenous sedation. The similarities include: 84% performed intravenous transfusions, while 2 centers reported intraperitoneal and intracardiac transfusions were performed for very early cases; 85% of centers performed the last transfusion at 34-35 weeks and 77% electively delivered their patients at 37 weeks.Method of transfusion and delivery timing was similar in most centers; however, differences were seen in location of procedure, anesthetic coverage, and surveillance. Further assessment is needed to determine if these differences in practice have any potential neonatal effects.

BACKGROUND: Pregnancy may be associated with adverse outcome in women with congenital heart disease (CHD). However, data regarding the outcome of pregnancy in women with CHD who receive care in cardiac-obstetric expert units are limited. METHODS: We retrospectively analyzed baseline characteristics and outcome of pregnancy in 67 females with CHD who received medical care in our tertiary center for 61 singleton and 6 twin pregnancies between 2009 and 2018. RESULTS: According to the modified World Health Organization (mWHO) risk scale for pregnancy, CHD lesions in 39 enrolled women (58%) were classified as mWHO class I or II, and in 28 females (42%) as mWHO class III or IV. Preterm births were more frequent in mWHO classes III or IV (P=0.003). Cardiac signs and complications occurred more often in mWHO classes III or IV than in women with cardiac lesions assigned to mWHO classes I or II (42.9% vs. 7.7%, P=0.002). N-terminal pro B-type natriuretic peptide (NT-proBNP) levels during pregnancy were higher in mWHO classes III or IV than in mWHO classes I or II (median 269.0 vs. 115.5 pg/mL, P=0.019). Presence of functional NYHA class III [odds ratio (OR) per standard deviation (SD) 8.8, 95% confidence interval (CI): 2.2–57.2, P=0.008] and mWHO classes III/IV (OR per SD 3.4, 95% CI: 1.2–9.9, P=0.018) prior to pregnancy were identified as independent predictors of adverse cardiac outcome of pregnancy. CONCLUSIONS: Adverse cardiac events and preterm deliveries should be anticipated in pregnant women with CHD, especially in those with mWHO classes III or IV. Therefore, these pregnancies should be under close surveillance and managed in specialized, multidisciplinary tertiary referral centers. Preconception counseling including individualized risk assessment is strongly recommended in women with CHD.

OBJECTIVE To compare the perinatal outcome of monochorionic twin pregnancies with twin-twin transfusion syndrome (TTTS), according to the disease severity, defined using Quintero staging, after treatment with fetoscopic laser surgery. METHODS This was a single-center study of 1020 consecutive cases with severe TTTS, which were treated with fetoscopic laser surgery. During the study period from January 1995 to March 2013, the participants were included at a mean ± SD gestational age of 20.8 ± 2.2 weeks. Perinatal survival analysis, including the rates of double survival and survival of at least one fetus, was undertaken according to the Quintero staging system. For blockwise comparisons of data, the whole population was divided into five chronologically consecutive study subgroups of 200 patients in each of the first four subgroups and 220 in the last one. RESULTS For the entire study population with known outcome (n = 1019), the rate of pregnancy with double fetal survival was 69.0% (127/184) in Stage-I, 71.4% (257/360) in Stage-II, 55.4% (236/426) in Stage-III and 51.0% (25/49) in Stage-IV TTTS cases. At least one twin survived in 91.3% (168/184) of pregnancies with Stage-I, 89.7% (323/360) of those with Stage-II, 83.1% (354/426) of those with Stage-III and 77.6% (38/49) of those with Stage-IV TTTS. The rates of double survival and survival of at least one fetus were both significantly higher in Stage-II TTTS compared with those in Stage-III TTTS cases (P

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 p 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.

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.Mit Beginn der SARS-CoV-2 Pandemie haben die deutschen geburtshilflichen und pädiatrischen Fachgesellschaften im März 2020 Empfehlungen zur Versorgung infizierter Schwangerer und deren Neugeborener, wie auch notwendige Schutzmaßnahmen für das Personal veröffentlicht [1–3]. Eine Aktualisierung ist aufgrund des rasanten Wissenszuwachses notwendig. Die vorliegende Empfehlung versteht sich daher als Fortschreibung der bereits vorliegenden Publikationen [1–3].Von der Cochrane Pregnancy and Childbirth Group wurden weltweit nationale Empfehlungen verglichen und als Review veröffentlicht [4]. In methodischer Anlehnung hieran nehmen die vorliegenden aktualisierten Empfehlungen Stellung zu den Kernfragen der prä-, peri- und postnatalen Betreuung bei SARS-CoV-2 und COVID-19, auf der Grundlage der bis zum 30.05.2020 verfügbaren Publikationen. Die Stellungnahmen basieren auf einem sorgfältig abgestimmten ExpertInnenkonsens und können sich – insofern neue Erkenntnisse veröffentlicht werden – zeitnah ändern.Die Verantwortung für das konkrete Vorgehen bleibt bei dem vor Ort medizinisch betreuenden Team, dessen Entscheidungen durch diese Empfehlung unterstützt werden sollen.

Background There is evidence that pregnancy-related anxiety (PrA) has a negative impact on birth outcomes and infant development. However, little is known about worrisome levels and individual trajectories of PrA dimensions across pregnancy and their predictive factors, particularly the association of PrA with symptoms of social phobia (SP) and generalized anxiety disorder (GAD). Methods A sample of 180 pregnant women was assessed three times during pregnancy with the Pregnancy-Related Anxiety Questionnaire-Revised 2 (PRAQ-R2). Linear mixed model analyses were used to investigate the course of different PrA dimensions across pregnancy, and to relate PrA to symptoms of social and generalized anxiety. Additionally, distinct developmental patterns of PrA were explored by latent class growth analyses. Results While the PrA total score remained stable, the different dimensions of PrA varied significantly over time. After controlling for obstetric and sociodemographic factors as well as depression, perceived social support and self-efficacy, symptoms of SP significantly predicted higher levels of fear of childbirth, child-related worries and concerns about mother´s appearance. Symptoms of GAD predicted higher child-related worries. Moreover, two distinct groups of women with either consistently higher or lower PrA scores were identified. Limitations Our results are limited due to the use of self-report questionnaires and would benefit from a larger sample size and replication in high-risk samples. Conclusion Our study suggests that a longitudinal and differentiated investigation of specific forms of prenatal anxiety may improve our understanding of women at high risk for PrA and promote the development of individualized forms of interventions initiated during pregnancy.

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).Seit Beginn der SARS-CoV-2-Pandemie haben die Deutsche Gesellschaft für Gynäkologie und Geburtshilfe und die Gesellschaft für Peri-/Neonatalmedizin Empfehlungen zum Umgang mit SARS-CoV-2-positiven Schwangerschaften und Neugeborenen veröffentlicht und wiederholt aktualisiert. Als Weiterführung der bestehenden Empfehlungen werden in dem aktuellen Update Schlüsselfragen zur prä-, peri- und postnatalen Versorgung von Schwangeren, Gebärenden, Wöchnerinnen, Stillenden mit SARS-CoV-2 und COVID-19 sowie deren Un- oder Neugeborenen auf der Grundlage von Veröffentlichungen bis zum September 2021 behandelt. Die Empfehlungen und Stellungnahmen wurden sorgfältig aus den aktuell verfügbaren wissenschaftlichen Daten abgeleitet und anschließend im Expertenkonsens verabschiedet. Dieser Leitfaden – hier in der Kurzfassung vorliegend – soll eine Hilfe für die klinische Entscheidungsfindung darstellen. Die Auslegung und therapeutische Verantwortung obliegen weiterhin dem betreuenden medizinischen Team vor Ort, dessen Entscheidungen durch diese Empfehlungen unterstützt werden sollen. Aufgrund der raschen Dynamik neuer Erkenntnisse kann eine Anpassung erforderlich sein. Die Empfehlungen werden durch die Zustimmung der Fachgesellschaften getragen: Deutsche Gesellschaft für Perinatale Medizin (DGPM), Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), Deutsche Gesellschaft für Pränatal- und Geburtsmedizin (DGPGM), Deutsche Gesellschaft für Pädiatrische Infektiologie (DGPI), Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI).

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. ispartof: PRENATAL DIAGNOSIS vol:42 issue:1 pages:15-26 ispartof: location:England status: published

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).Seit Beginn der SARS-CoV-2-Pandemie haben die Deutsche Gesellschaft für Gynäkologie und Geburtshilfe und die Gesellschaft für Peri-/Neonatalmedizin Empfehlungen zum Umgang mit SARS-CoV-2-positiven Schwangerschaften und Neugeborenen veröffentlicht und wiederholt aktualisiert. Als Weiterführung der bestehenden Empfehlungen werden in dem aktuellen Update Schlüsselfragen zur prä-, peri- und postnatalen Versorgung von Schwangeren, Gebärenden, Wöchnerinnen, Stillenden mit SARS-CoV-2 und COVID-19 sowie deren Un- oder Neugeborenen auf der Grundlage von Veröffentlichungen bis zum September 2021 behandelt. Die Empfehlungen und Stellungnahmen wurden sorgfältig aus den aktuell verfügbaren wissenschaftlichen Daten abgeleitet und anschließend im Expertenkonsens verabschiedet. Dieser Leitfaden – hier in der Langfassung vorliegend – soll eine Hilfe für die klinische Entscheidungsfindung darstellen. Die Auslegung und therapeutische Verantwortung obliegen weiterhin dem betreuenden medizinischen Team vor Ort, dessen Entscheidungen durch diese Empfehlungen unterstützt werden sollen. Aufgrund der raschen Dynamik neuer Erkenntnisse kann eine Anpassung erforderlich sein. Die Empfehlungen werden durch die Zustimmung der Fachgesellschaften getragen: Deutsche Gesellschaft für Perinatale Medizin (DGPM), Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), Deutsche Gesellschaft für Pränatal- und Geburtsmedizin (DGPGM), Deutsche Gesellschaft für Pädiatrische Infektiologie (DGPI), Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI).

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.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with 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 caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

ZusammenfassungPlazentare Chorangiome sind als benigne Tumore des Choriongewebes seltene Ursache fetaler und maternaler Morbidität. Wir beschreiben den Fall eines großen plazentaren Chorangioms, das zu einem Polyhydramnion, konsekutiver Frühgeburt und kindlicher High-Output-Herzinsuffizienz führte. Aus einer Literaturrecherche leiten wir zudem Hinweise zur Diagnostik und Empfehlungen zur optimalen Schwangerschaftsbetreuung bei Verdacht auf Chorioangiom ab.

Obstetrical complications such as spontaneous abortion/miscarriage, fetal growth restriction, preeclampsia or preterm birth occur in approx. 15% of human pregnancies. Clinical experts often state that a previous uncomplicated pregnancy reduces the risk for complications in subsequent pregnancies. Vice versa, a prior pregnancy affected by obstetrical complications increases the risk for reoccurrence. However, published evidence directly underpinning these clinical statements is sparse. Considering that the maternal immune adaptation may be causally involved in determining the outcome of subsequent pregnancies, a comprehensive analysis of clinical data was long overdue. We here present a systematic analysis of clinical data using a PubMed-based approach to identify human studies with relevant information on birth weight and incidences of pregnancy complications in first and second pregnancies. From initially 18,592 publications, 37 studies were included in the quantitative data analysis. Women with a previous pregnancy affected by complications where a derailed immune response can be inferred have a 2.2-3.2-fold increased risk to be affected again in a subsequent pregnancy. Conversely, a normally progressing primary pregnancy reduced the risk for complications in a subsequent pregnancy by 35-65%. Moreover, an uncomplicated primary pregnancy was associated with a 4.2% increased birth weight in a following pregnancy without a difference in gestational age at delivery. In conclusion, the increased birth weight after previously uncomplicated pregnancies suggests that an immune memory is mounted during primary pregnancies. This immune memory may promote the successful outcome of subsequent pregnancies or - if missing or compromised - account for a risk perpetuation of pregnancy complications.

To compare the intertwin umbilical cord coiling in twin-twin transfusion syndrome (TTTS) before fetoscopic laser treatment and to correlate these with Doppler findings in both twins.We performed a prospective study using three-dimensional (3D) ultrasound with color Doppler imaging of the umbilical cord in TTTS. Coiling index was measured as a reciprocal value of one complete vascular coil. Ultrasound hypocoiling was thus defined as0.2 coils/cm and hypercoiling as0.6 coils/cm, respectively. Umbilical artery pulsatility index (PI) and peak systolic velocity, middle cerebral artery peak systolic velocity and ductus venosus PI of flow-velocity waveformes of both twins were measured.We included 65 women in the study. The average gestational age was 21.1 ± 2.7 weeks. In 65 recipients and 56 donors coiling index could be quantified. The median (interquartile range) coiling index of recipient twins was significantly higher than of donors, 0.55 (0.41-0.68) vs. 0.26 (0.2-0.5); P 0.0001. The proportions of abnormal intertwin coiling were significantly (P = 0.0015) different. Out of 65 recipient with coiling indices evaluation, 1 (1.5%) showed hypocoiled and 27 (41.5%) hypercoiled cords. In contrast, 27 donor twins (48.2%) showed hypocoiled and 5 (8.9%) hypercoiled umbilical cords. There were no significant correlations between the fetal Doppler values and coiling indices.Evaluation of umbilical cord coiling index using 3D color Doppler in both twins complicated by TTTS is feasible in both, donors and recipients. Coiling indices differ significantly between recipient and donor twins and do not correlate with Doppler findings.

Pregnant women have been carefully observed during the COVID-19 pandemic, as the pregnancy-specific immune adaptation is known to increase the risk for infections. Recent evidence indicates that even though most pregnant have a mild or asymptomatic course, a severe course of COVID-19 and a higher risk of progression to diseases have also been described, along with a heightened risk for pregnancy complications. Yet, vertical transmission of the virus is rare and the possibility of placental SARS-CoV-2 infection as a prerequisite for vertical transmission requires further studies. We here assessed the severity of COVID-19 and onset of neonatal infections in an observational study of women infected with SARS-CoV-2 during pregnancy. Our placental analyses showed a paucity of SARS-CoV-2 viral expression ex vivo in term placentae under acute infection. No viral placental expression was detectable in convalescent pregnant women. Inoculation of placental explants generated from placentas of non-infected women at birth with SARS-CoV-2 in vitro revealed inefficient SARS-CoV-2 replication in different types of placental tissues, which provides a rationale for the low ex vivo viral expression. We further detected specific SARS-CoV-2 T cell responses in pregnant women within a few days upon infection, which was undetectable in cord blood. Our present findings confirm that vertical transmission of SARS-CoV-2 is rare, likely due to the inefficient virus replication in placental tissues. Despite the predominantly benign course of infection in most mothers and negligible risk of vertical transmission, continuous vigilance on the consequences of COVID-19 during pregnancy is required, since the maternal immune activation in response to the SARS-CoV2 infection may have long-term consequences for children’s health.

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. ispartof: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY vol:224 issue:5 ispartof: location:United States status: published

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.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.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.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.Dreiviertel aller Gebärenden erhalten während der Geburt eine Analgesie. Es stehen regionale und systemische Analgesieverfahren zur Verfügung. Diese Übersichtsarbeit analysiert die Datenlage zu den Auswirkungen einer geburtshilflichen Analgesie mit systemischen Opioiden auf das Neugeborene.Die Datenbanken PubMed und Cochrane Library wurden nach den folgenden Begriffen durchsucht: „Meptazinol“, „Meptid“, „analgesia“, „painkiller“, „pain reliever“, „obstetrics“, „labor“, „labour“, „delivery“, „neonate“, „newborn“, „child“, „baby“, „infant“, „fetus“, „fetal“, „opioid“ und „opiate“ sowie zusätzlich eine MeSH Terms Suche in PubMed durchgeführt.Von 355 potenziell relevanten Studien wurden 23 Studien in diese Arbeit eingeschlossen. Die Studien variierten stark in Qualität, Stichprobengröße und Outcome-Kriterien. Das neonatale Outcome war häufig nur ein sekundärer Endpunkt. Selten wurden signifikante Unterschiede bezogen auf das Outcome der Neugeborenen zwischen den verschiedenen systemischen Opioiden oder im Vergleich zu Kontrollgruppen berichtet. In 12 Studien wurden die APGAR-Werte der Neugeborenen zwischen Behandlungsgruppen verglichen, wobei sich bei 10 (83%) dieser Studien keine Unterschiede zeigten.Die Evidenzlage zu Auswirkungen geburtshilflicher Analgesie mit systemischen Opioiden ist insgesamt gering und Studien zum Langzeit-Outcome von Neugeborenen fehlen. Auch die Frage, ob eine postnatale Überwachung der Neugeborenen notwendig ist, kann nicht klar beantwortet werden. Studien mit prospektivem Studiendesign sollten durchgeführt werden.

N/A

Background: During the last decades, fathers have increasingly participated in prenatal care, birth preparation classes, and childbirth. However, comparably little is known about the prenatal emotional well-being of fathers, particularly content and extent of broader paternal concerns that may arise during pregnancy beyond those focusing on childbirth. Thus, the aims of this study were to investigate the manifestation of paternal pregnancy-related worries in a population-based sample and to identify relevant associated factors.Materials and Methods: As part of a longitudinal pregnancy cohort at the University Medical Center Hamburg-Eppendorf, Germany, N = 129 expectant fathers were assessed once during pregnancy. Pregnancy-related worries centering around medical procedures, childbirth, health of the baby, as well as socioeconomic aspects were assessed with the Cambridge Worry Scale (CWS). Additionally, paternal socioeconomic background and maternal obstetrical history, symptoms of generalized anxiety and depression, and level of hostility were investigated, as well as perceived social support. The cross-sectional data were analyzed based on multiple regression analyses.Results: The level of reported worries was overall low. Some fathers reported major worries for individual aspects like the health of a significant other (10.9%) and the baby (10.1%), as well as the current financial (6.2%) and employment situation (8.5%). Pregnancy-related worries were negatively associated with household income and positively associated with anxious and depressive symptoms and low perceived social support. Associations varied for specific pregnancy-related worries.Limitations: Due to the cross-sectional data examined in this study, a causal interpretation of the results is not possible. The sample was rather homogeneous regarding its socioeconomic background. More research needs to be done in larger, more heterogeneous samples.Conclusion: Though overall worries were rather low in this sample, specific major worries could be identified. Hence, addressing those fathers reporting major worries regarding specific aspects already in prenatal care might support their psychosocial adjustment. Fathers with little income, those with elevated levels of general anxious and depressive symptoms, and those with less social support reported higher pregnancy-related worries. Our results indicate the relevance of concerns beyond health- and birth-related aspects that could be relevant for fathers. Measurements developed specifically for expectant fathers are needed to properly capture their perspective already during pregnancy.

Neonatal passive immunity, derived from transplacental transfer of IgG antibodies from mother to fetus during pregnancy, can mitigate the risk for severe infections in the early postnatal period. Understanding the placenta as the gateway organ in this process, we aimed to evaluate the influence of specific factors modulating the transplacental IgG transfer rate (TPTR) in 141 mother/neonate pairs. We further evaluated the potential health advantage elicited by maternal IgG with regard to respiratory tract infections during infancy and early childhood. Data and biological samples collected within the prospective longitudinal pregnancy cohort study PRINCE (Prenatal Identification of Children's Health) were used for these analyses. We tested IgG antibody levels against seven pathogens (measles, mumps, rubella, tetanus, diphtheria, pertussis and influenza A) by ELISA and detected seropositivity in 72.6-100% of pregnant women and in 76.3-100% of their neonates, respectively. Cord blood IgG levels reached 137-160% of levels detected in maternal blood. Strikingly, assessment of TPTR for all seven antigens highlighted that TPTR strongly depends on individual placental function. Subsequent in-depth analysis of anti-influenza A IgG revealed a link between cord blood levels and uterine perfusion, measured by uterine artery pulsatility index. Moreover, higher cord blood anti-influenza A IgG levels were associated with a significantly reduced risk for respiratory tract infections during the first six months of life, indicating a high degree of cross-reactivity and possible pathogen-agnostic effects of anti-influenza A antibodies. Taken together, our data suggest that early life immunity is modulated by maternal IgG levels and individual placental features such as perfusion. Vaccination of pregnant women, i.e. against influenza, can increase neonatal antibody levels and hereby protect against early life respiratory infections. Consequently, specific guidelines should evolve in order to safeguard neonates born from pregnancies with poorer placental capacity for vertical transfer of protective antibodies.

Fetal growth restriction (FGR) is the most common pregnancy complication in developed countries. Pregnancies affected by FGR, frequently concur with complications and high risk of neonatal morbidity and mortality. To date, no approved treatment is available for pregnant women affected with FGR. The objective of this study was to investigate the contribution of galectin-3 (gal-3), a β-galactoside binding protein involved in pregnancy, placental function and fetal growth. We demonstrated that lack of gal-3 during mouse pregnancy leads to placental dysfunction and drives FGR in the absence of a maternal preeclampsia syndrome. Analysis of gal-3 deficient dams revealed placental inflammation and malperfusion, as well as uterine natural killer cell infiltration with aberrant activation. Our results also show that FGR is associated with a failure to increase maternal circulating gal-3 levels during the second and third trimester in human pregnancies. Placentas from human pregnancies affected by FGR displayed lower gal-3 expression, which correlated with placental dysfunction. These data highlight the importance of gal-3 in the promotion of proper placental function, as its absence leads to placental disease and subsequent FGR.

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7&ndash, 28, range: 1&ndash, 119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6&ndash, 33.7, range: 19.0&ndash, 41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients (p &lt, 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%, 51/118) and recipients (37%, 54/145), p = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, p = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1&ndash, 8.3, p &lt, 0.001), and GA at birth (OR = 0.8, 95%CI 0.7&ndash, 0.9, p = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3&ndash, 1.7, p &lt, 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.

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

Pregnancy poses a threat to women with aortopathy. Conclusive data on the obstetric and aortic outcome in this risk collective, especially when it comes to aortic complications in the long term, are still missing. This study offers a comparative analysis of pregnancy-associated outcome in 113 consecutive women with Marfan syndrome or bicuspid aortic valve disease, including 46 ever-pregnant and 37 never-pregnant women with Marfan syndrome, and 23 ever-pregnant and 7 never-pregnant females with bicuspid aortic valve disease. The overall obstetric outcome was comparable between ever-pregnant women with Marfan syndrome and with bicuspid aortic valve disease (p = 0.112). Pregnancy-associated aortic dissection occurred in two women with Marfan syndrome (3%) during a total of 62 completed pregnancies, whereas no single case of aortic event occurred in women with bicuspid aortic valve disease during a total of 36 completed pregnancies (p = 0.530). In the long-term follow-up, aortic dissection occurred in 21% of ever-pregnant women with Marfan syndrome, but in none of the women with bicuspid aortic valve disease (p = 0.022). Proximal aortic surgery was performed with similar frequency in ever-pregnant women with Marfan syndrome and with bicuspid aortic valve disease in the long term (p = 0.252). However, ever-pregnant women with Marfan syndrome were younger when surgery was performed (44 ± 9 vs. 59 ± 7 years, p = 0.041). In Marfan syndrome, long-term growth of the aorta was comparable between ever-pregnant and never-pregnant women. Pregnancy thus exhibited an increased immediate aortic risk only in women with Marfan syndrome, but not in women with bicuspid aortic valve disease. Previous pregnancy did not relate to an increased long-term risk of adverse aortic events in women with Marfan syndrome or with bicuspid aortic valve disease.

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.

International audience; Pregnancy represents an immunological challenge for the maternal immune system. Pregnancy augments innate immune responses, and particularly monocytes contribute to maintaining the balance between pro- and anti-inflammatory immune responses required for the successful sequence of distinct immunological phases throughout pregnancy. Nonetheless, studies that focus on the heterogeneity of monocytes and analyze the alteration of monocyte subsets in a longitudinal approach throughout healthy pregnancies have remained scarce. In this study, we characterized the gradual phenotypic changes of monocyte subsets and the secretory potential of bulk monocytes in peripheral blood mononuclear cells of healthy pregnant women from a population-based prospective birth cohort study. Blood samples at predefined time points were analyzed using flow cytometry for in-depth characterization of monocyte subsets, which confirmed a shift from classical towards intermediate monocytes throughout pregnancy. Principal component analysis revealed characteristic phenotypic changes on monocyte subsets, especially on the intermediate monocyte subset, throughout pregnancy. Pregnancy-related hormones were measured in serum and β-human chorionic gonadotropin levels were significantly associated with expression of CD11b, CD116 and CCR2 on monocyte subsets. TLR4 and TLR7/8 stimulation of monocytes furthermore showed reduced polycytokine production towards the end of pregnancy. These data provide a comprehensive overview of phenotypic changes and secretory potential of monocytes in healthy pregnant women and establish a selective contribution of different monocyte subsets to healthy pregnancy. The results from this study therefore build a basis for future comparisons and evaluation of women with adverse pregnancy outcomes.

Clinical Standards Committee: The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high-quality teaching and research related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care, because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

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. 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. 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. 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.

Objectives Stress during pregnancy is known to have negative effects on fetal outcome. The purpose of this exploratory study was to examine placental perfusion alterations after stress challenge during pregnancy in a mouse model. Material and Methods Seven Tesla MRI was performed on pregnant mice at embrionic day (ED) 14.5 and 16.5. Twenty dams were exposed to an established acoustic stress challenge model while twenty non-exposed dams served as controls. Placental perfusion was analyzed in dynamic contrast-enhanced (DCE) MRI using the steepest slope model. The two functional placental compartments, the highly vascularized labyrinth and the endocrine junctional zone, were assessed separately. Results Statistical analysis revealed decreased perfusion levels in the stress group at ED 14.5 compared to controls in both placenta compartments. On ED 16.5, the perfusion level increased significantly in the stress group while placenta perfusion in controls remained similar or even slightly decreased leading to an overall increased perfusion in the stress group on ED 16.5 compared to controls. Conclusion MR imaging allows noninvasive placenta perfusion assessment in this fetal stress mimicking animal model. In this exploratory study, we demonstrated that stress challenge during pregnancy leads to an initial reduction followed by an increase of placenta perfusion.

Objective To investigate the growing experience and learning curve of fetoscopic laser coagulation of the placental vascular anastomoses in severe mid-trimester twin–twin transfusion syndrome (TTTS) and its influence on perinatal outcome in a single-center setting. Methods Between January 1995 and March 2013 we performed laser therapy in 1020 consecutive pregnancies with TTTS between 15.1 and 27.4 weeks' gestation. We compared perinatal outcome in blocks of five sequential groups of 200 cases, taking into account several covariates in order to adjust for case mix and to demonstrate learning curves and success rates. Results The percentage of pregnancies with survival of both fetuses increased from 50.0% (n = 100) in the first 200 cases to 69.5% (n = 153) in the last 220 cases (P = 0.018 for trend) and the overall survival rate for both fetuses in the complete series of 1019 cases with known outcome was 63.3% (n = 645). The survival rate of at least one fetus increased from 80.5% (161/200) in the first group to 91.8% (202/220) in the last group (P = 0.072 for trend) and the overall survival rate of at least one fetus in the complete series was 86.7% (883/1019). In the total population, the mean gestational age at delivery of pregnancies with at least one liveborn neonate was 33.7 ± 3.2 weeks, with a mean interval of 12.9 ± 4.0 weeks between intervention and delivery. Among the first two groups, 124 pregnancies had anterior placentae and were treated with a 0° fetoscope. These cases had the poorest overall outcome, with a double-twin survival rate of 44.4% (55/124), which increased to 65.1% (207/318; P = 0.001) after the introduction of a 30° fetoscope for cases with anterior placenta. The success rate for double-twin survival reached a plateau of 69% at 600 procedures, a rate equalled by a new operator who was trained hands-on and performed 174 of the last 400 procedures. Conclusions We report the largest single-center experience of laser coagulation in TTTS. We observed a continuous increase in double-twin survival rate owing to the growing experience based on the learning curve and refinements in fetoscopic instruments and techniques. These data provide strong arguments for the centralization of minimally invasive intrauterine surgery in specialized high-volume centers. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Background Paracetamol is the first choice for antipyretic or analgesic treatment throughout pregnancy. Products with Paracetamol are readily available over the counter and therefore easily accessible for self-medication. Epidemiological data on Paracetamol intake pattern during pregnancy and its potential immunological effects are sparse. We aimed to analyze a possible association between Paracetamol medication and numbers of hematopoietic stem cells (HSC) in cord blood. Methods The objective was addressed in the PRINCE (PRENATAL DETERMINANTS OF CHILDREN'S HEALTH) study, a population-based prospective pregnancy cohort study initiated in 2011 at the University Medical Center in Hamburg, Germany. 518 healthy pregnant women with singleton pregnancies were recruited during the first trimester. Three examinations were scheduled at the end of the 1st (gestational week 12–14), the 2nd (gestational week 22–24) and the 3rd trimester (gestational week 34–36). For 146 of these women, cord blood flow cytometry data were available. Paracetamol intake was assessed for each trimester of pregnancy. Findings Among the 518 enrolled women, 40% took Paracetamol as main analgesic treatment during pregnancy. The intake frequency and dosage of Paracetamol varied between the women and was overall low with a tendency towards higher frequencies and higher dosages in the third trimester. Paracetamol intake, particularly during the third trimester, resulted in decreased relative numbers of HSCs in cord blood, independent of maternal age, first-trimester BMI, parity, gestational age and birth weight (− 0.286 (95% CI − 0.592, 0.021), p = 0.068). Interpretation Prenatal Paracetamol intake, especially during the third trimester, may be causally involved in decreasing HSCs in cord blood., Graphical Abstract Image 1, Highlights • Paracetamol is the main analgesic agent used during pregnancy. • Maternal Paracetamol intake was negatively associated with hematopoietic stem cell frequencies in cord blood. • The third trimester seems to be most susceptible for Paracetamol induced reduction of the immune cell progenitors. Our study focuses on the impact of Paracetamol intake during pregnancy on the offspring's immune development. We were able to show that maternal Paracetamol intake, particularly in the third trimester of pregnancy, was negatively associated with hematopoietic stem cell frequencies in cord blood. These results provide a potential missing link for an association between prenatal Paracetamol medication and childhood disease, particularly asthma, by adding a possible immunological pathway. While we fully acknowledge the medical need of analgesics in pregnancy to prevent or treat more harmful events, our data are valuable for clinical recommendations on self-medication with the OTC drug Paracetamol.

Successful pregnancy outcome is the result of a tailored adaptation of the maternal endocrine and immune system throughout gestation. We aimed to investigate if maternal endocrine, anthropometric and life style factors assessed longitudinally throughout pregnancy allow prediction of birth weight.Data on maternal factors and obstetrical characteristics from 220 pregnancies from a German prospective pregnancy cohort were analyzed using univariate and multivariate regression models. The association between maternal progesterone levels at the end of the 1st (gw 12-14), the 2nd (gw 22-24) and the 3rd trimester (gw 34-36) and birth weight of children born at term was examined. Interaction terms were included to identify possible sex-specific associations. Furthermore, associations between maternal and obstetric characteristics and progesterone levels were tested.After controlling for possible confounders, progesterone in the 2nd trimester emerged as an independent predictor for birth weight in pregnancies with female (p=0.01), but not male fetuses (p=0.6). In female fetuses each increase of progesterone by 1ng/ml in the 2nd trimester was associated with an increase of birth weight by 6.8g (95%-CI=1.44-12.24). Maternal 1st trimester BMI showed a significant inverse correlation to progesterone levels throughout gestation (p0.0001 in the 1st and 2nd, p=0.01 in the 3rd trimester). This inverse association between maternal BMI and progesterone levels was confined to overweight women.Our data support that maternal progesterone levels have the potential to serve as early biomarker for reduced birth weight and underpins the importance of normal weight when entering the reproductive phase.

OBJECTIVES: In the recent TRUFFLE study it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks, monitoring of the ductus venosus (DV) combined with computerised cardiotocography (cCTG) as a trigger for delivery, increased the chance of infant survival without neurological impairment. However, concerns in interpretation were raised as DV monitoring appeared associated with a non-significant increase in fetal death, and part of the infants were delivered after 32 weeks, after which the study protocol was no longer applied. This secondary sensitivity analysis focuses on women who delivered before 32 completed weeks, and analyses fetal death cases in detail. METHODS: We analysed the monitoring data of 317 women who delivered before 32 weeks, excluding women with absent infant outcome data or inevitable perinatal death. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. RESULTS: The primary outcome (two year survival without neurological impairment) occurred more often in the two DV groups (both 83%) than in the CTG-STV group (77%), however the difference was not statistically significant (p = 0.21). Nevertheless, in surviving infants 93% was free of neurological impairment in the DV groups versus 85% in the CTG-STV group (p = 0.049). All fetal deaths (n = 7) occurred in women allocated to DV monitoring, which explains this difference. Assessment of the monitoring parameters that were obtained shortly before fetal death in these 7 cases showed an abnormal CTG in only one. Multivariable regression analysis of factors at study entry demonstrated that higher gestational age, larger estimated fetal weight 50th percentile ratio and lower U/C ratio were significantly associated with the (normal) primary outcome. Allocation to the DV groups had a smaller effect, but remained in the model (p

Objective To investigate the antenatal management and outcome in a large international cohort of monochorionic twin pregnancies with spontaneous or post‐laser twin anemia–polycythemia sequence (TAPS). Methods This study analyzed data of monochorionic twin pregnancies diagnosed antenatally with spontaneous or post‐laser TAPS in 17 fetal therapy centers, recorded in the TAPS Registry between 2014 and 2019. Antenatal diagnosis of TAPS was based on fetal middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) in the TAPS donor and, This article's abstract has been translated into Spanish and Chinese. Follow the links from the abstract to view the translations. A video abstract of this article is available online here.

This study investigated the correlation between the umbilical artery (UA) pulsatility index (PI) and the estimated fetal weight percentile and birthweight (BW) percentile, respectively. 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 10 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). 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.ZIEL: Diese Studie untersuchte den Zusammenhang zwischen dem Pulsatilitätsindex (PI) der Nabelarterie (UA) und den geschätzten Perzentilen des Fetalgewichts sowie des Geburtsgewichts (BW). Aufgenommen wurden Low-Risk-Schwangerschaften nach der 28. Schwangerschaftswoche, bei denen UA-Doppleruntersuchungen durchgeführt wurden. Die Fälle wurden nach den BW-Perzentilen wie folgt eingeteilt: zu klein („small for gestational age“, SGA) mit BW 10. Perzentile; entsprechend („appropriate“, AGA) und zu groß für das Gestationsalter („large“, LGA) mit BW 90. Perzentile. Wir analysierten die Unterschiede im mittleren UA-PI und UA-PI-Z-Score nach dem Schwangerschaftsalter entsprechend den 3 Gruppen. Eine lineare Regression wurde durchgeführt, um jegliche Relation zwischen Doppler-Indizes und BW-Perzentilen zu bewerten. Multiple logistische Regressionsanalysen wurden durchgeführt, um den unabhängigen Zusammenhang des UA-PI mit LGA-Kindern zu bestimmen. In einem zweiten Schritt führten wir die gleiche Analyse im Hinblick auf die geschätzten Fetalgewicht (EFW)-Perzentilen durch. Von 2004 bis 2015 analysierten wir 14 554 Schwangerschaften. Der mittlere UA-PI und der mittlere UA-PI-Z-Score in der LGA-Gruppe waren niedriger als in der AGA- und SGA-Gruppe (p 0,001). Der UA-PI und die UA-PI-Z-Scores standen in linearem Zusammenhang mit den BW-Perzentilen (p 0,001) und den EFW-Perzentilen (p 0,001). Die logistische Regressionsanalyse zeigte, dass ein niedriger UA-PI unabhängig mit LGA des Neugeborenen assoziiert war (p 0,001). Je höher die EFW- und BW-Perzentilen, desto niedriger der UA-PI. Die Referenzbereiche für den UA-Doppler basieren jedoch nur auf Schwangerschaftswochen. Weitere Studien sind erforderlich um zu klären, ob angepasste Referenzbereiche auf Basis von EFW-Perzentilen für die Beurteilung des fetalen Wohlbefindens im dritten Trimenon besser geeignet sind.

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.Plazentare Chorangiome sind als benigne Tumore des Choriongewebes seltene Ursache fetaler und maternaler Morbidität. Wir beschreiben den Fall eines großen plazentaren Chorangioms, das zu einem Polyhydramnion, konsekutiver Frühgeburt und kindlicher High-Output-Herzinsuffizienz führte. Aus einer Literaturrecherche leiten wir zudem Hinweise zur Diagnostik und Empfehlungen zur optimalen Schwangerschaftsbetreuung bei Verdacht auf Chorioangiom ab.

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. 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. 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. 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.

To assess scale reliability and factorial validity of the Maternal and Paternal Antenatal Attachment Scale in a German sample.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.263 women and 128 men from Hamburg, Germany, were assessed during pregnancy (total sampleFactor 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.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.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).

Objective: To determine whether a novel therapy for placental insufficiency could achieve orphan drug status by estimating the annual incidence of placental insufficiency, defined as an estimated fetal weight below the 10th centile in the presence of abnormal umbilical artery Doppler velocimetry, per 10 000 European Union (EU) population as part of an application for European Medicines Agency (EMA) orphan designation. Design: Incidence estimation based on literature review and published national and EU statistics. Setting and population: European Union. Methods: Data were drawn from published literature, including national and international guidelines, international consensus statements, cohort studies and randomised controlled trials, and published national and EU statistics, including birth rates and stillbirth rates. Rare disease databases were also searched. Results: The proportion of affected pregnancies was estimated as 3.17% (95% CI 2.93–3.43%), using a weighted average of the results from two cohort studies. Using birth rates from 2012 and adjusting for a pregnancy loss rate of 1/100 gave an estimated annual incidence of 3.33 per 10 000 EU population (95% CI 3.07–3.60 per 10 000 EU population). This fell below the EMA threshold of 5 per 10 000 EU population. Conclusions: Maternal vascular endothelial growth factor gene therapy for placental insufficiency was granted EMA orphan status in 2015 after we demonstrated that it is a rare, life-threatening or chronically debilitating and currently untreatable disease. Developers of other potential obstetric therapies should consider applying for orphan designation, which provides financial and regulatory benefits. Tweetable abstract: Placental insufficiency meets the European Medicines Agency requirements for orphan disease designation. (Less)

OBJECTIVE This study aimed to identify peripartum and neonatal factors associated with elevated Interleukin-6 levels in the cord blood of neonates without clinical signs of an infection. STUDY DESIGN We conducted a prospective single-center study with healthy term and preterm neonates between March and November 2017. We investigated correlations between 21 peripartum factors and neonatal IL-6 concentrations. RESULTS Four hundred and seventy-one infants (GA: 32.9-42.3 weeks) were included. The risk for elevated neonatal IL-6 levels was 3.1 to 4.5-fold increased in the presence of either peripartum maternal temperature >37.5 °C (p = 0.012), duration of labor >12 h (p 8 × 109 cells/L (p

Objective To report the outcome of monochorionic twins with twin reversed arterial perfusion (TRAP) sequence following interstitial laser therapy in the first trimester. Methods This was a retrospective cohort study of all consecutive cases of TRAP that underwent interstitial laser therapy at ≤ 14 + 3 weeks' gestation between January 2014 and April 2016. Interstitial laser treatment was performed under ultrasound guidance using a 400-nm Nd:YAG laser fiber. Hospital records were reviewed to ascertain perinatal survival and morbidity. Results Twelve monochorionic twin pregnancies underwent interstitial laser treatment of the umbilical artery of the acardiac fetus, at a median gestational age of 13 + 5 (interquartile range (IQR), 13 + 4 to 14 + 0) weeks. In all cases, one treatment was sufficient to achieve complete interruption of the perfusion of the acardiac twin. There were no procedure-related complications during or within 48 h after the procedure. In one (8.3%) case, intrauterine death of the pump twin occurred 2 weeks after the intervention. All other cases (91.7%) resulted in a live birth at a median gestational age of 39 + 6 (IQR, 37 + 1 to 41 + 2) weeks and with a median birth weight of 3370 (IQR, 2980-3480) g. No neonatal mortality or serious morbidity occurred. Conclusions Our results support the use of interstitial laser therapy in the first trimester of pregnancy complicated by TRAP sequence, showing a live birth rate of 92%. The results of a randomized controlled trial, evaluating early vs late intervention in pregnancy with TRAP sequence, are awaited. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.