BACKGROUND:Open spinal dysraphism is a congenital malformation that causes major morbidity. Its consequences include sensory and motor impairment as well as bladder- and bowel dysfunction. It is often also associated with prenatal ventriculomegaly, which, in turn, necessitates postnatal treatment with a ventriculoperitoneal shunt in approximately 80% of cases. Prenatal therapy with coverage of neural tube defect can reduce the shunt rate and preserve motor function. In this review, we describe the different surgical procedures and their outcomes. METHODS:This review is based on publications that were retrieved by a selective literature search in the MEDLINE, Web of Science, EMBASE, Scopus, and Cochrane databases, employing pertinent keywords. Studies of all types (except case reports) that were published in English or German in the period 2010-2024 were included. RESULTS:The randomized, controlled MOMS trial showed that intrauterine surgery for defect closure resulted in less progressive neural tissue damage than postnatal surgery and reduced the need for shunting by approximately half (40% vs. 82%). Since the publication of these results, various prenatal surgical procedures have been established, including hysterotomy-assisted, percutaneous fetoscopic, and laparotomy-assisted fetoscopic closure. The individual surgical methods yield comparable results in terms of motor function and shunt rate. A problem with these procedures is that they increase the likelihood of preterm birth, to an extent that varies from one type of procedure to another. CONCLUSION:Prenatal surgery improves motor function and reduces the shunt rate but long-term outcomes beyond adolescence are still lacking. Transparent and interdisciplinary counseling is essential in prenatal communication to inform parents not only about the potential benefits of this treatment, but also about its limitations and risks.

INTRODUCTION:Breastfeeding to strengthen the immune system suggests allergy prevention as a possible option. The connection between breastfeeding and the development of atopic-allergic diseases is being discussed. The primary aim of this work was to investigate an association of the first early skin-to-skin contact following cesarean section with the development of atopic diseases within the 1st year of life. METHODS:The present study was conducted as a bicentric prospective cohort study in central Germany with a 15-month recruitment period. Data collection was by telephone interviews with a follow-up of 12 months. The statistical evaluation procedure was based on a hierarchical test of the association of early skin-to-skin contact between mother and child with the two main outcome measures. The primary outcome is the duration of breastfeeding. The second outcome is the onset of atopic-allergic disease within the 1st year of life. RESULTS:Mothers breastfed longer if they had skin-to-skin contact within the first 30 minutes postpartum [χ²(df=5) = 19.020, p=0.002], if they breastfed their newborns early immediately after birth (p<0.001), and if the first skin-to-skin contact lasted more than one hour [χ²(df=4) = 19.617, p<0.001]. Regarding atopic-allergic diseases, no significant effects of skin-to-skin contact were found in relation to disease development. Regarding breastfeeding, no significant effects of atopic-allergic diseases could be detected either. CONCLUSIONS:The results of this study reflect the benefits of skin-to-skin contact in the context of breastfeeding and atopic disease. The current scientific knowledge regarding skin contact and the development of atopic-allergic diseases should be extended and deepened.

ImportancePopulation-based analyses provided divergent data on the changes in preterm birth rates during the COVID-19 pandemic, and there is a gap of knowledge on the variations in birth characteristics.ObjectiveTo study changes in perinatal care, causes of preterm delivery, and very preterm (VPT; defined as <32 weeks’ gestation) birth rates before and during the COVID-19 pandemic.Design, Setting, and ParticipantsThis population-level cohort study used data from the quality assurance registry, which covers all births in Hesse, Germany. Deliveries during the COVID-19 pandemic (2020) were compared with the corresponding grouped prepandemic time intervals (2017 to 2019). Analyses were executed between August 2023 and July 2024.ExposuresAnalyses were directed to study differences in preterm births before and during 3 pandemic phases: first (March 14 to May 15, 2020) and second (October 19 to December 31, 2020) lockdowns and a period of less-vigorous restrictions between them (May 16 to October 18, 2020).Main Outcomes and MeasuresOutcomes of interest were variations in preterm birth rates in the context of baseline characteristics and causes of preterm births during vs before the first year of the COVID-19 pandemic.ResultsFrom the total cohort of 184 827 births from 2017 to 2020, 719 stillbirths occurred and 184 108 infants were liveborn. Compared with the prepandemic period, medical care characteristics did not differ during the COVID-19 period. The odds of VPT births were lower during the pandemic period (odds ratio [OR], 0.87; 95% CI, 0.79-0.95) compared with the prepandemic period, with the greatest reduction observed during the second lockdown period (OR, 0.69; 95% CI, 0.55-0.84). Reduction in VPT births was attributed to fewer births in pregnancies among individuals with a history of serious disease (OR, 0.64; 95% CI, 0.50-0.83), pathologic cardiotocography (OR, 0.66; 95% CI, 0.53-0.82), and intrauterine infection (OR, 0.82; 95% CI, 0.72-0.92) while incidences of history of preterm birth, multiple pregnancies, serious or severe psychological distress, and preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelet count syndrome as cause for preterm delivery remained unchanged.Conclusions and RelevanceIn this population-based cohort study on the COVID-19 pandemic and preterm birth rates, the duration of exposure to mitigation measures during pregnancy was associated with accelerated reductions in preterm births. The findings of lower rates of baseline risks and causes of preterm deliveries support efforts to intensify health care prevention programs during pregnancy to reduce the preterm birth burden. These findings of this study put particular focus on hygiene measures to reduce the rate of deliveries for intrauterine infection and highlight the potential of expanding strategies to the different risks and causes of preterm delivery.

Die Versorgungsstrukturen der Perinatalmedizin stehen unter zunehmendem Druck. Umfassende Reformpläne zur Vergütung und Versorgung sowie eine regulatorische Digitalisierungsoffensive sollen Entlastung bringen und die medizinische Qualität verbessern. Mit der Opt-out-Regelung zur „elektronischen Patientenakte für alle“ (ePA) bietet das Digital-Gesetz (DigiG) eine zweite Chance für den elektronischen Mutterpass. Die Erforschung, Entwicklung und Etablierung von hybriden, digital gestützten Versorgungsmodellen und -programmen hat sich in anderen Fachdisziplinen bereits etabliert und zeigt Potenzial in der Betreuung von Risikoschwangerschaften. Dies beinhaltet die Verbesserung der Behandlung von Mutter und Kind durch kontinuierliches Telemonitoring und strukturelle wie finanzielle Entlastung der Behandelnden und Kostenträger. Die Erhebung umfassender Real-World-Daten kann die Versorgung direkt verbessern und perspektivisch die Entwicklung robuster KI(Künstliche Intelligenz)-Modelle für Schwangerschaften fördern.

Fryns syndrome (FS) is a multiple congenital anomaly syndrome with different multisystemic malformations. These include congenital diaphragmatic hernia, pulmonary hypoplasia, and craniofacial dysmorphic features in combination with malformations of the central nervous system such as agenesis of the corpus callosum, cerebellar hypoplasia, and enlarged ventricles. We present a non-consanguineous northern European family with two recurrent cases of FS: a boy with multiple congenital malformations who died at the age of 2.5 months and a female fetus with a complex developmental disorder with similar features in a following pregnancy. Quad whole exome analysis revealed two likely splicing-affecting disease-causing mutations in the PIGN gene: a synonymous mutation c.2619G>A, p.(Leu873=) in the last nucleotide of exon 29 and a 30 bp-deletion c.996_1023+2del (NM_176787.5) protruding into intron 12, with both mutations in trans configuration in the affected patients. Exon skipping resulting from these two variants was confirmed via RNA sequencing. Our molecular and clinical findings identified compound heterozygosity for two novel splice-affecting variants as the underlying pathomechanism for the development of FS in two patients.

Einleitung und Fragestellung Die antenatale Therapie der Spina bifida aperta (SBA) kann die Morbidität dieser angeborenen Fehlbildung reduzieren. Im Rahmen des Zentrums für fetale Diagnostik und Therapie am Uniklinikum Giessen und Marburg wurde seit 2021 die fetale MRT für die prä- und postoperative Diagnostik i.R. der antenatalen Therapie bei SBA implementiert.

Open spina bifida (OSB) is a congenital, non-lethal malformation with multifactorial etiology. Fetal therapy can be offered under certain conditions to parents after accurate prenatal diagnostic and interdisciplinary counseling. Since the advent of prenatal OSB surgery, various modifications of the original surgical techniques have evolved, including laparotomy-assisted fetoscopic repair. After a two-year preparation time, the team at the University of Giessen and Marburg (UKGM) became the first center to provide a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach in the German-speaking area. We point out that under the guidance of experienced centers and by intensive multidisciplinary preparation and training, a previously described and applied technique could be transferred to a different setting.

Hintergrund Eine Spina bifida aperta (SBA) ist oftmals mit multiplen lebenslangen Problemen assoziiert. Dazu zählen – neben der durch die lokale Schädigung der Nervenbahnen des Rückenmarks entstehenden Bewegungsstörung – der Hydrocephalus, die neurogene Blasenentleerungsstörung mit sekundären Nierenerkrankungen und orthopädische Komplikationen wie die Hüftluxation oder die Skoliose, mit oftmals lebenslangen Folgen.

Hintergrund Nierenersatzverfahren werden auf der NICU selten angewendet. Nur wenige deutsche Perinatalzentren verfügen über die notwendigen Voraussetzungen, um diese durchführen zu können. In Hessen ist dies nur in Marburg und in Frankfurt möglich.

Einleitung und Fragestellung Seit 7/2021 bietet das Klinikum Giessen und Marburg (UKGM) nach den Vorgaben des „International Fetoscopic Myelomeningocele Repair Consortium“ Diagnostik und Therapie der Spina bifida aperta in der Hybridtechnik an.

Einleitung und Fragestellung: Die Spina bifida aperta (SBA) ist eine angeborene, nicht letale Fehlbildung, welche mit einer erheblichen Morbidität einhergeht. Hierzu gehören u.a. senso-motorische Einschränkungen, Blasen- und Mastdarmstörungen, außerdem kann die Anlage eines VP-Shunts notwendig werden [1].

Aim of the Study The aim of the study is to examine the detection rates of malformations before and after the introduction of extended basic screening in Hesse by the Federal Joint Committee (Gemeinsamer Bundesausschuss, GQH) on July 1, 2013. Method This is a retrospective, mainly exploratory data analysis of quality assurance data from the Office for Quality Assurance in Hesse (GQH). The data was collected in the period from January 1, 2010 to December 31, 2016 in the obstetric departments of the Hessian hospitals using documentation forms. The classification and evaluation of the diagnoses is based on ICD-10-GM-2019. Results At least one malformation is present in 0.7% of the cases. With a share of 30.0%, most of the congenital malformations are from the musculoskeletal system. 12.2% of the malformations come from the facial cleft, closely followed by malformations of the circulatory system with 11.3%. The highest prenatal detection rate (PDR) is found in congenital malformations of the nervous system at 56.8%. The lowest PDR is found in those of the genital organs with 2.1%. The PDR of cardiovascular malformations is 32.9%. Overall, a PDR of 25.2% is achieved. There was no change in the number of prenatal malformation diagnoses after the introduction of extended basic ultrasound. The distribution of malformation diagnoses not detected prenatally to the organ systems also has not changed after the introduction. Conclusion The introduction of extended basic ultrasound did not bring the desired improvement with regard to the PDR in Hesse. Alternative approaches should be considered.

Die Spina bifida aperta (SBA) ist eine angeborene, nicht letal verlaufende Fehlbildung des Zentralnervensystems, welche mit einer erheblichen Morbidität einhergeht [1]. Hierzu gehören senso-motorische Einschränkungen der unteren Extremität, orthopädische Probleme (Klumpfuß, Skoliose etc.) und Blasen- und Mastdarmstörungen, außerdem kann die Anlage eines ventriculo-peritonealen Shuntsystems bei Hydrocephalus notwendig werden [2]. Die Überlegungen zur vorgeburtlichen Therapie fußen auf der Idee durch eine intrauterine Defektdeckung die progrediente Schädigung des neuronalen Gewebes zu minimieren. Den wissenschaftlichen Beleg erbrachte das „MOMS-Trial“, in dem eine Verbesserung der motorischen Funktion mit Möglichkeit des selbstständigen Laufens, sowie ein Rückgang der Mortalität und Shuntpflichtigkeit nach antenataler OP gezeigt werden konnte. Bei diesem Ansatz ist jedoch ein Kaiserschnitt obligatorisch, desweiteren ist die Frühgeburtsrate erhöht [3]. Die Modifikation der operativen Technik führte zur Etablierung der fetoskopischen Defektdeckung [4]. Eine davon ist die sog. „Hybridmethode“. Hierbei wird eine Unterbauchquerlaparotomie angelegt und der Uterus im Anschluss externalisiert, dann folgt das Einbringen von drei Arbeitstrokaren. Der fetoskopische Verschluss der SBA ist dreischichtig, hierbei wird zunächst ein boviner Durapatch eingebracht und darüber Muskulatur und Haut verschlossen. Vorteile dieser Methode sind die geringere Rate an vorzeitigen Blasensprüngen, sowie Möglichkeit der vaginalen Geburt [5]. 2019 begannen am UKGM die Vorbereitungen für die Implementierung dieser „Hybridmethode“. Es folgte der Beitritt zum “International Fetoscopic Myelomeningocele Repair Consortium“. Hierbei handelt es sich um einen internationalen, multizentrischen Zusammenschluss mit Expertise in der fetoskopischen SBA-Versorgung [6]. Die Operation kann zwischen der 19+0–28+0 SSW nach Prüfung der Ein- und Ausschlusskriterien und sorgfältiger interdisziplinärer Beratung der Eltern erfolgen. Im Juli 2021 wurde die erste Patientin am UKGM operiert. Eine Supervision der beteiligten Abteilungen während der ersten sieben Operationen erfolgte durch Vertreter des Konsortiums (Baylor College of Medicine, USA) [7]. Seitdem wurden insgesamt 13 Patientinnen am UKGM (Stand 01/23) operiert. Kindliches und maternales Outcome werden systematisch über insgesamt fünf Jahre nachuntersucht. Derzeit sind insgesamt 12 Fachabteilungen an beiden Standorten in die Behandlung eingebunden. Die langfristige Betreuung von Kindern mit Spina bifida aperta ist komplex und profitiert von einer guten interdisziplinären Zusammenarbeit. Durch den Aufbau des interdisziplinären Zentrums wird eine umfassende Patientenversorgung möglich, welche die unterschiedlichen Abschnitte der fetalen, kindlichen und familiären Entwicklung beinhaltet. Die intensive Vorbereitung und hohe Bereitschaft der beteiligten Fachabteilungen zur engen Kooperation bilden eine tragende Säule für die optimale Behandlung der Pat.

Biallelic pathogenic variants in the neuroblastoma amplified sequence (NBAS) gene affecting the Sec39 domain are associated with a predominant hepatic phenotype named infantile liver failure syndrome type 2 (ILFS2). Individuals are at risk of developing life-threatening acute liver failure episodes, most likely triggered by febrile infections. Pregnancy, delivery, and the postpartum period are well known triggers of decompensation in different inherited metabolic diseases and therefore entail a potential risk also for individuals with ILFS2. We studied pregnancy, birth, and postpartum period in a woman with ILFS2 (homozygous for the NBAS variant c.2708 T > G, p.(Leu903Arg)). During two pregnancies there were no complications associated with the underlying genetic condition. Two healthy boys were born by cesarean section. To reduce the risk of fever and febrile infections, we avoided prolonged labor, epidural analgesia, and breastfeeding. Maternal body temperature and liver function were closely monitored. In case of elevated body temperature, antipyretic treatment (acetaminophen, metamizole) was given without delay. Alanine and aspartate aminotransferases as well as liver function remained normal throughout the observation period. Hence, pregnancy and childbirth are feasible in women with ILFS2 under careful monitoring.

ZusammenfassungSeit Beginn der Pandemie dominiert die SARS-CoV-2-Infektion den klinischen Alltag. In der Behandlung von Hochrisikopopulationen bestand lange Unklarheit über das Ausmaß und die Konsequenzen der Infektion. Zu diesem Risikokollektiv gehört auch die schwangere Patientin. Die Etablierung von klinischen Registerstudien konnte innerhalb kürzester Zeit und unter enormer Anstrengung zu einer Einschätzung der pandemischen Lage für dieses Kollektiv beitragen. Anhand eines klinischen Falls wird im folgenden Bericht die Assoziation zwischen SARS-CoV-2-Infektion einer schwangeren Patientin mit klinischen Zeichen der Präeklampsie bis hin zur Ausbildung eines posterioren reversiblen Enzephalopathiesyndroms (PRES) beschrieben. Anhand des Falles wird die differentialdiagnostische Abklärung zwischen fulminanten Verlauf der Infektion und Präeklampsie dargelegt. Der Artikel stellt die aktuelle Datenlage zum Auftreten eines PRES in der Schwangerschaft im Zusammenhang mit einer SARS-CoV-2-Infektion dar und setzt sich mit möglichen Differentialdiagnosen auseinander. Durch die interdisziplinäre Betreuung der Patientin kann eine Übersicht zu den Aspekten des jeweiligen Fachgebietes dargelegt werden.

Einleitung und Fragestellung Seit 2021 wird die vorgeburtliche Therapie der SBA angeboten. Die angewendete OP-Technik beinhaltet die Unterbauchquerlaparotomie mit Externalisierung des Uterus und fetoskopischen Verschluss der SBA, die sog. „Hybridmethode“ [1].

Hintergrund LUTO ist eine angeborene Fehlbildung der Urethra (Klappen oder Atresie), die mit ca. 2-3/10.000 Fällen insb. männliche Neugeborene (NG) betrifft und in 50% d. F. bereits pränatal identifiziert wird. Die resultierende Obstruktion in Kombination mit einer primären Anlagestörung der Nieren schädigen die fetalen Nieren teils bis zum Oligo-/Anhydramnion und kann zur schweren Lungenhypoplasie führen. Die Anlage vesico-amnialer Shunts (VAS), Fruchtwasserauffüllungen und fetale Zystoskopie stellen pränatale Behandlungsoptionen dar, die ein Überleben der NG bei unbehandelt sehr schlechter Prognose sichern sollen.

Purpose Fetal megacystis (MC) can be severe and is mainly caused by fetal lower urinary tract obstruction (LUTO). Mortality of fetal LUTO can be high as a result of pulmonary hypoplasia and/or (chronic) renal insufficiency. Several technical procedures for vesicoamniotic shunting (VAS) were developed to improve fetal MC outcomes. Material and methods We present the outcome of nine fetuses with MC who received VAS in the prenatal period (14 + 6 to 27 + 6 weeks GA) using the Somatex(R) intrauterine shunt system. MC was defined as an increased longitudinal measurement of the bladder >15 mm. The median follow-up time after birth was 18 months. Results Eight Fetuses had uncomplicated VAS intervention. One case developed PPROM 24 h after VAS leading to abortion. Pregnancy was later terminated in further two cases. All six live-born infants received intensive care treatment. Invasive-mechanical ventilation was necessary in one case who died 24 h post-partum of severe cardiac depression. Five infants who survived the follow-up time developed chronic renal insufficiency (CRI), with one infant developing end-stage renal failure requiring peritoneal dialysis. Conclusion Overall, 5 of 9 LUTO fetuses (55%) undergoing VAS with the Somatex(R) intrauterine shunt system showed long-term survival beyond the neonatal period of 28 d (5/9; 55%) with varying morbidity.

Since the beginning of the pandemic, SARS-CoV-2 infection has dominated clinical practice. In the treatment of high-risk populations, there has long been uncertainty about the extent and consequences of infection. This high-risk population includes pregnant patients. The establishment of clinical registry studies was able to contribute an assessment of the pandemic situation for this collective within a very short time and with enormous effort. Based on a clinical case, the following report describes the association between SARS-CoV-2 infection of a pregnant patient with clinical signs of preeclampsia to the development of posterior reversible encephalopathy syndrome (PRES). Based on the case, the differential diagnostic workup between fulminant course of infection and preeclampsia is presented. The article presents the current data on the occurrence of PRES in pregnancy in the context of SARS-CoV-2 infection and addresses possible differential diagnoses. Interdisciplinary care of the patient allows an overview of aspects of each specialty to be presented.

Introduction: Twin anemia-polycythemia sequence (TAPS) is a complication in monochorionic-diamniotic (MCDA) twin pregnancies. This study analyzes whether the prenatal diagnosis using delta middle cerebral artery-peak systolic velocity (MCA-PSV) > 0.5 multiples of the median (MoM) (delta group) detects more TAPS cases than the guideline-based diagnosis using the MCA-PSV cut off levels of >1.5 and <1.0 MoM (cut-off group), in a heterogenous group of MCDA twins. Methods: A retrospective analysis of 348 live-born MCDA twin pregnancies from 2010 to 2021 with available information on MCA-PSV within one week before delivery and hemoglobin-values within 24 h postnatally were considered eligible. Results: Among postnatal confirmed twin pairs with TAPS, the cut-off group showed lower sensitivity than the delta group (33% vs. 82%). Specificity proved higher in the cut-off group with 97% than in the delta group at 86%. The risk that a TAPS is mistakenly not recognized prenatally is higher in the cut-off group than in the delta group (52% vs. 18%). Conclusions: Our data shows that delta MCA-PSV > 0.5 MoM detects more cases of TAPS, which would not have been diagnosed prenatally according to the current guidelines. In the collective examined in the present study, TAPS diagnostics using delta MCA-PSV proved to be a more robust method.