Management of Ebstein Anomaly in the Current Era: The Story of One Fetus and the Collaboration of Many-A Case Report.

Collaborative multicenter research has significantly increased our understanding of fetal Ebstein anomaly, delineating risk factors for adverse outcomes as well as predictors of postnatal management. These data are incorporated into prenatal care and therapeutic strategies and inform family counseling and delivery planning to optimize care. This report details the translation of findings from multicenter studies into multidisciplinary prenatal care for a fetus with Ebstein anomaly, supraventricular tachycardia, and a circular shunt, including transplacental therapy to control arrhythmias and achieve ductal constriction, informed and coordinated delivery room management, and planned univentricular surgical palliation.

Enhanced recovery after fetal spina bifida surgery: what is our global practice?

OBJECTIVE: Prenatal spina bifida closure results in improved outcomes for the child compared to postnatal surgery but is associated with significant maternal morbidity. Optimization of the perioperative care for women who underwent fetal spina bifida surgery could improve maternal and pregnancy outcomes. Enhanced Recovery After Surgery (ERAS) protocols are multimodal, evidence-based care plans that have been adopted for multiple surgical procedures to promote faster and better patient recovery and shorter hospitalization. This study aims to explore if fetal centers have implemented ERAS principles in this setting. Furthermore, we provide recommendations for the perioperative management of patients undergoing fetal spina bifida surgery. METHODS: Fifty-three fetal therapy centers offering prenatal surgery for open spina bifida were identified and invited to complete a digital questionnaire covering their pre-, intra- and postoperative management. An overall score was calculated per center based on the center's compliance with 20 key ERAS principles, extrapolated from ERAS guidelines for cesarean section, gynecologic oncology and colorectal surgery. Each item was scored 1 or 0 when the center did or did not comply with each principle, with a maximum score of 20. RESULTS: The questionnaire was completed by 46 centers in 17 countries (response rate 87%). Twenty-two centers (48%) exclusively perform open fetal surgery (laparotomy and hysterotomy), whereas 14 (30%) offer both open and fetoscopic procedures and 10 (22%) use fetoscopy only. The perioperative management of patients undergoing fetoscopic and open surgery was highly similar. The median ERAS score was 12 (mean 12.5, SD 2.4, range 8-17). Center compliance was the highest for the use of regional anesthesia (98%), avoidance of bowel preparation (96%), and thromboprophylaxis (96%), while the lowest compliance was achieved for preoperative carbohydrate loading (15%), postoperative nausea and vomiting prevention (33%), avoidance of overnight fasting (33%) and a 2-hour fasting period for clear fluids (20%). ERAS scores were similar in centers with a short (2-5 days), medium (6-10 days) and long (≥11 days) hospital stay (12.8 ± 2.4, 12.1 ± 2.0, and 10.3 ± 3.2, respectively, p=0.15). Furthermore, there was no significant association between ERAS score and surgical technique or center volume. CONCLUSION: The perioperative management of fetal spina bifida surgery is highly variable across fetal therapy centers worldwide. Standardizing protocols according to ERAS principles may improve patient recovery, reduce maternal morbidity, and shorten hospital stay after fetal spina bifida surgery. This article is protected by copyright. All rights reserved.

Neonates with a prenatal diagnosis of hydrops fetalis: A 10-year experience in a tertiary care center.

INTRODUCTION: Hydrops fetalis (HF) is a rare condition with a high mortality. This study analysed the obstetric and perinatal outcomes of antenatally diagnosed HF according to its aetiology and the possibility of intrauterine treatment (IUT). PATIENTS AND METHODS: We carried out a retrospective review of the health records of 164 pregnant women with a prenatal diagnosis of HF in a tertiary care centre between 2011-2021. We analysed prenatal interventions, clinical findings, aetiologies and obstetric and live-born infant outcomes. RESULTS: An invasive prenatal study had been performed in 79.3% cases. The most common aetiologies were genetic disorders (31%), TORCH and parvovirus B19 infections (9.7%) and structural heart diseases (9.1%). Intrauterine treatment was performed in 25.6%, and 74.4% of pregnancies were terminated. Pregnancies with a prenatal diagnosis of genetic or chromosomal disorders had higher rates of elective termination compared to other aetiologies (P < .01). Among all pregnancies, only 25.6% resulted in live births (LBs), most of them preterm. Perinatal and 1-year survival rates were higher in the group that received IUT (P < .001). Among the LBs, structural heart diseases had the worst survival rates, while the aetiology with the best outcomes was tachyarrhythmia. Survival at 1 year of life among those born alive was 70%, but 58.6% of these infants had significant morbidity at discharge. CONCLUSIONS: Despite advances in the management of FH, the poor obstetric prognosis, perinatal mortality and morbidity of survivors is still significant. These data are important for the purpose of counselling families when HF is diagnosed antenatally.

Neonatos con diagnóstico prenatal de hidrops fetal: experiencia durante 10 años en un centro de tercer nivel / Neonates with a prenatal diagnosis of hydrops fetalis: A 10-year experience in a tertiary care center

Introducción: El hidrops fetal (HF) es una condición rara con una alta mortalidad. Este estudio analiza la evolución obstétrica y perinatal de los diagnósticos prenatales de HF, relacionándola con la etiología y el tratamiento intrauterino (TIU) recibido. Pacientes y métodos: Se revisaron 164 gestantes con diagnóstico prenatal de HF entre 2011 y 2021. Se registraron intervenciones prenatales, hallazgos clínicos, etiologías y resultados de los recién nacidos vivos. Resultados: Se realizó un estudio invasivo prenatal en el 79,3% de los pacientes. Las etiologías mayoritarias fueron alteraciones genéticas (31%), infecciones TORCH y por parvovirus B19 (9,7%), y cardiopatías estructurales (9,1%). En el 25,6% se realizó TIU, y entre todas las gestaciones, el 74,4% fueron interrumpidas. Las alteraciones genéticas tuvieron tasas más altas de interrupción legal del embarazo respecto a otras etiologías (p<0,01). Del total, solo nacieron el 25,6% de los fetos, la mayoría pretérmino. Los que recibieron TIU gozaron de mayores tasas de supervivencia perinatal y al año de vida (p<0,001). De entre aquellos nacimientos, las cardiopatías estructurales presentaron las peores tasas de supervivencia, mientras que las causas con mejor pronóstico fueron las taquiarritmias. La supervivencia al año de vida entre aquellos recién nacidos vivos fue del 70%, pero el 58,6% asociaron morbilidad significativa al alta. Conclusiones: A pesar de los avances en el manejo del HF, el mal pronóstico obstétrico, la mortalidad perinatal y la morbilidad de los supervivientes siguen siendo significativos. Estos datos son importantes para asesorar a las familias que reciben un diagnóstico prenatal de HF.(AU)

Introduction: Hydrops fetalis (HF) is a rare condition with a high mortality. This study analysed the obstetric and perinatal outcomes of antenatally diagnosed HF according to its aetiology and the possibility of intrauterine treatment (IUT). Patients and methods: We carried out a retrospective review of the health records of 164 pregnant women with a prenatal diagnosis of HF in a tertiary care centre between 2011 and 2021. We analysed prenatal interventions, clinical findings, aetiologies and obstetric and live-born infant outcomes. Results: An invasive prenatal study had been performed in 79.3% cases. The most common aetiologies were genetic disorders (31%), TORCH and parvovirus B19 infections (9.7%) and structural heart diseases (9.1%). Intrauterine treatment was performed in 25.6%, and 74.4% of pregnancies were terminated. Pregnancies with a prenatal diagnosis of genetic or chromosomal disorders had higher rates of elective termination compared to other aetiologies (P<.01). Among all pregnancies, only 25.6% resulted in live births (LBs), most of them preterm. Perinatal and 1-year survival rates were higher in the group that received IUT (P<.001). Among the LBs, structural heart diseases had the worst survival rates, while the aetiology with the best outcomes was tachyarrhythmia. Survival at 1year of life among those born alive was 70%, but 58.6% of these infants had significant morbidity at discharge. Conclusions: Despite advances in the management of FH, the poor obstetric prognosis, perinatal mortality and morbidity of survivors is still significant. These data are important for the purpose of counselling families when HF is diagnosed antenatally.(AU)

Developmental outcomes for survivors of placental laser photocoagulation for the management of twin-to-twin transfusion syndrome.

BACKGROUND: Fetoscopic laser coagulation of placental anastomoses reverses the pathological process in twin-to-twin transfusion syndrome, thereby increasing survival, but there are a paucity of studies addressing long-term neurodevelopmental outcome of survivors. This study aimed to ascertain the presence of neurodevelopmental disabilities in child survivors of monochorionic pregnancies managed by placental laser photocoagulation in the Australian state of Victoria. METHODS: All pregnancies undergoing placental laser photocoagulation with the Victorian Fetal Therapy Service between 2006-2017 were included. Information on each surviving child, including demographics, perinatal course, and developmental progress was collected from parents, and consent was sought to complete the Child Behaviour Checklist. Interviewers evaluated whether this information was consistent with a diagnosis of any of 14 neurodevelopmental conditions. A three-tiered outcome measure was allocated for each child: (1) unimpaired or developmentally normal, (2) mild or moderate neurological impairment, or (3) severe neurological impairment. Clinical predictors for adverse outcome were identified. RESULTS: Of 116 pregnancies (113 twin, 3 triplet), 96 (83%) resulted in 1 + surviving fetuses. 57/113 (50%) twin pregnancies resulted in 2 survivors, 36 (32%) in 1 survivor, and 20 (18%) in no survivors. Of the 235 fetuses, 154 (65.5%) survived to follow-up. Survival increased from 59% in 2006-2008 to 73% in 2015-2017. 90/154 (58%) survivors were followed up at a mean age of 7.5 [SD 3.0] years. Based on parental interview and Child Behaviour Checklist data, 28/90 (31%) participants were assessed as having neurodevelopmental impairment, 27 of mild-moderate severity and 1 severe. Speech/language disorders, attention deficit (hyperactivity) disorders, and fine motor impairment were most common. Neonatal length of stay conferred the highest risk of impairment. CONCLUSION: Substantial variation exists between fetal therapy services in the type and length of neonatal follow-up following fetoscopic laser coagulation, contributing to a lack of data on long-term outcomes. The findings from this study support increasingly urgent calls to undertake systematic and sustained follow-up of fetoscopic laser coagulation survivors until school age. Information from this study may assist parents in their decision-making when offered fetal surgery. Importantly, it highlights a group for targeted surveillance and early intervention.

Successful Prenatal Treatment of Cardiac Rhabdomyoma in a Fetus with Tuberous Sclerosis.

Cardiac rhabdomyomas are a possible early manifestation of the Tuberous Sclerosis Complex (TSC). They often regress spontaneously but may grow and cause cardiac dysfunction, threatening the child's life. Treatment with rapalogs can stop the growth of these cardiac tumors and even make them shrink. Here, we present the case of a successful treatment of a cardiac rhabdomyoma in a fetus with TSC by administering sirolimus to the mother. The child's father carries a TSC2 mutation and the family already had a child with TSC. After we confirmed the TSC diagnosis and growth of the tumor with impending heart failure, we started treatment at 27 weeks of gestation. Subsequently, the rhabdomyoma shrank and the ventricular function improved. The mother tolerated the treatment very well. Delivery was induced at 39 weeks and 1 day of gestation and proceeded without complications. The length, weight, and head circumference of the newborn were normal for the gestational age. Rapalog treatment was continued with everolimus. Metoprolol and vigabatrin were added because of ventricular preexcitation and epileptic discharges in the EEG, respectively. We provide the follow-up data on the child's development in her first two years of life and discuss the efficacy and safety of this treatment.

Long-term neurological cognitive, behavioral, functional, and quality of life outcomes after fetal myelomeningocele closure: a systematic review.

BACKGROUND: Myelomeningocele is a lifelong condition that features several comorbidities, such as hydrocephalus, scoliosis, club foot, and lower limb sensory and motor disabilities. Its management has progressed over time, ranging from supportive care to early postnatal closure to prenatal closure of the defect. Recent research discovered that fetal myelomeningocele closure (fMMC) provided superior neurological outcomes to those of postnatal closure. When performed at 12 months of age, fMMC can avert or delay the need for a ventriculoperitoneal shunt and reversed the hindbrain herniation. Moreover, fMMC reportedly enhanced motor function and mental development at 30 months of age. However, its long-term outcomes remain dubious. PURPOSE: This systematic review aimed to determine the long-term neurological cognitive, behavioral, functional, and quality of life (QoL) outcomes after fMMC. METHODS: The PubMed, Directory of Open Access Journals, EBSCO, and Cochrane databases were extensively searched for articles published in 2007-2022. Meta-analyses, clinical trials, and randomized controlled trials with at least 5 years of follow-up were given priority. RESULTS: A total of 11 studies were included. Most studies revealed enhanced long-term cognitive, behavioral, functional, and QoL outcomes after fMMC. CONCLUSION: Our results suggest that fMMC substantially enhanced patients' long-term neurological cognitive, behavioral, functional, and QoL outcomes.

Prenatal repair of gastroschisis using partial carbon dioxide insufflation fetoscopy: lessons learned

ABSTRACT We report the long-term outcomes of a case of prenatal gastroschisis repair using a fully percutaneous fetoscopic approach with partial carbon dioxide insufflation. Surgery was performed as an experimental procedure before the scheduled elective birth. The fetal intestines were successfully returned to the abdominal cavity without any fetal or maternal complications. Ultrasonography performed 24 hours later revealed bowel peristalsis and no signs of fetal distress. After 48 hours, partial extrusion of the small bowel was observed, and the fetus was delivered. Gastroschisis repair was immediately performed upon delivery using the EXIT-like procedure as per our institutional protocol. The newborn did not require assisted mechanical ventilation, was discharged at 14 days of age and was then exclusively breastfed. At 3-year follow-up, the patient had no associated gastroschisis-related complications. This is the first case of prenatal repair of gastroschisis, which provides baseline knowledge for future researchers on the potential hurdles and management of prenatal repair.

Prenatal diagnosis and intrauterine treatment of a giant fetal hepatic hemangioma:a case report / 中华围产医学杂志

This article reported a case of fetal giant hepatic hemangioma with cardiomegaly managed with intrauterine treatment. At 23 weeks of gestation, the patient was referred to Guangdong Women and Children Hospital due to abnormal abdominal echogenicity of the fetus, which was suspected to be a hepatic hemangioma or a hepatic arteriovenous fistula. The prenatal ultrasound at 26 weeks of gestation revealed an enlarged fetal hepatic hemangioma of 45 mm×35 mm×42 mm and an enlarged heart (cardiothoracic area ratio of 0.50). So, with the patient's informed consent, the fetus was treated with intrauterine administration of propranolol and dexamethasone and closely monitored by ultrasound. The volume of the lump still increased at the beginning of the medication, but started to shrink in the 7th week. Besides, the fetal cardiac load was reduced and the condition was controlled. The patient delivered at 37 weeks of gestation. The baby received a CT examination on the fourth day after birth which revealed an abdominal mass of 40 mm×30 mm×44 mm requiring no treatment, and no abnormalities were reported during a one-year follow-up.

Fetoscopic laser coagulation for placental chorioangioma: a report of three cases and literature review / 中华围产医学杂志

Objective:To evaluate the outcome of laser coagulation under fetoscope for placental chorioangioma (CA).Methods:The clinical data of three pregnant women with giant CA treated by laser coagulation under fetoscope in Peking University Third Hospital from January 2018 to December 2020 were analyzed retrospectively. Relevant articles up to September 2022 were retrieved from Wanfang Database, China National Knowledge Infrastructure and PubMed, and the clinical data of all patients were retrospectively summarized. Indications and intervention effects of fetoscopic laser therapy were analyzed. Descriptive statistics was used to describe the data.Results:Thirteen patients were involved in this study including 10 cases retrieved from the databases. The average age of the pregnant women was (30.3±6.2) years old. There were 12 cases of single pregnancy and one case of twin pregnancy (monochorionic diamnionic twin pregnancy). Except for cases for which data were not available in the literatures, at the diagnosis of CA, the average gestational age was (19.9±4.5) weeks ( n=7) and the average maximum diameter of the mass was (6.1±4.1) cm ( n=6). The patients underwent fetoscopic laser therapy at an average gestational age of (25.0±2.0) weeks ( n=13) with the average maximum tumor diameter of (7.6±2.8) cm ( n=9). After treatment, the amniotic fluid volume of three cases decreased to normal. In one case, the amniotic fluid volume decreased but was still above the upper limit of the normal range. Moreover, the maximum tumor diameter decreased in four cases; the peak systolic velocity of the fetal middle cerebral artery decreased to normal in one case; fetal heart function became normal in two cases and fetal edema was relieved in one case. Among the three patients treated in our hospital, the blood supply of CA disappeared after treatment. Intrauterine fetal death occurred in two cases. The other 11 patients gave birth to live babies at the gestational age of (36.6±3.8) weeks with five through cesarean section (5/11), five through vaginal delivery (4/11) and two not reported. The birth weight of the neonates was (2 712±1 023) g and all of them survived. The gender of five neonates were reported and all were females, two of them were monochorionic diamnionic twins. No abnormality was found in the three neonates delivered in our hospital during a six-month follow-up. No abnormality was reported in the other neonates during ten days to six months of follow-up. Conclusions:Fetoscopic laser coagulation may help reduce the size of CA, decrease complications and improve pregnancy outcomes.

Progress in antenatal magnesium sulfate exposure for neuroprotection in preterm infants / 中华围产医学杂志

Magnesium sulfate has been administered to pregnant women at imminent risk of preterm delivery for fetal neuroprotection, but its adverse effects and target population have not been fully studied. This paper summarizes the current protocols according to the existing guidelines and the latest research progress, including the gestational age at intervention, dose, duration of therapy and the need for re-administration, hoping to provide a reference for the clinical use of magnesium sulfate for fetal neuroprotection in China.

Terapia laser intrafetal para la secuencia perfusión arterial inversa en gemelos (TRAP). Comunicación de un caso y revisión de la literatura

Una primigesta de 41 años con gestación doble monocoriónica biamniótica, con diagnóstico de secuencia perfusión gemelar arterial reversa (TRAP, por sus siglas en inglés) y mal pronóstico perinatal fue intervenida mediante terapia laser intrafetal a las 18 semanas de gestación. Se complicó con rotura prematura de membranas que fue manejada en forma expectante hasta las 33 semanas 3 días, cuando se realizó cesárea electiva sin complicaciones. Se obtuvo un recién nacido vivo sano de 2,255 g que fue dado de alta hospitalaria el día 15 de nacido, sin complicaciones. Comunicamos el primer caso de terapia laser intrafetal realizado en nuestro país y resaltamos su eficacia, sencillez, bajo costo y abordaje ambulatorio en casos de secuencia TRAP.

A 41-year-old primigravida with double monochorionic biamniotic gestation, with a diagnosis of twin reverse arterial perfusion sequence (TRAP) and poor perinatal prognosis underwent intrafetal laser surgery at 18 weeks of gestation. It was complicated with premature rupture of membranes that was managed expectantly until 33 weeks 3 days, when elective caesarean section was performed without complications. A healthy live newborn of 2,255 g was obtained and was discharged from the hospital on the 15th day of birth without complications. We report the first case of intrafetal laser surgery performed in our country and highlight its efficacy, simplicity, low cost and ambulatory approach in cases of TRAP sequence.

Percutaneous transuterine fetal cerebral embolisation to treat vein of Galen malformations at risk of urgent neonatal decompensation: study protocol for a clinical trial of safety and feasibility.

INTRODUCTION: Although endovascular techniques have improved outcomes in vein of Galen malformations (VOGM), there is still a high rate of morbidity and mortality, particularly among cases with decompensation in the neonatal period. The dimension of the draining venous sinus on fetal imaging correlates with the risk of neonatal decompensation. In fetuses within this high-risk group who do not have end-organ injury, there is a theoretical therapeutic opportunity to reduce the arteriovenous shunt before the normal physiological changes of birth precipitate decompensation. This study investigates the safety and potential benefit of treating a VOGM in utero, which has not been previously studied. METHODS AND ANALYSIS: This study aims to enroll 20 subjects: pregnant women with a fetus harbouring a high-risk VOGM (defined on MRI by a narrowest medial-lateral width greater than 8 mm in the draining venous sinus). Unfortunately, the subset of fetuses with in utero end-organ injury is ineligible, because the late stage of pathology is not amenable to recovery from a cerebrovascular intervention, likely not even in utero. This study aims to alter the physiology before such developments accrue.At or after 23 weeks of gestation, a transuterine transposterior fontanelle needle puncture to the torcular allows ultrasound-guided deployment of coils to embolise the draining venous malformation.This study has 97.5% power to detect major safety events at 30% or greater, and 80% power to detect a reduction in the rate of neonatal intervention from 80% to 30%. In the staged study design, an interval evaluation after 11 patients invokes study termination if safety events occur above the allowed threshold. ETHICS AND DISSEMINATION: The institutional review boards at Mass General Brigham and Boston Children's Hospital (BCH) reviewed and approved this protocol. The BCH Department of Radiology and a patient family philanthropic donation fund this study. The trial results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04434729.

¿Cuál es el rol actual de la toracocentesis en el hidrotórax fetal severo? Presentación de caso

Se llama hidrotórax a una efusión pleural primaria que ocurre durante la vida prenatal (denominado 'quilotórax primario' después del nacimiento). En ciertos casos, esta efusión es severa y produce compresión pulmonar y cardiaca, por lo cual, la mortalidad perinatal sigue siendo alta. Los recién nacidos con hidrotórax requieren, muchas veces, de drenaje, nutrición parenteral total y medicación específica para su recuperación. Sin embargo, las intervenciones prenatales, principalmente con derivaciones toraco-amnióticas, pueden mejorar estos resultados. Reportamos el caso de un feto con hidrotórax severo a quien se le realizó una toracocentesis y revisamos la literatura acerca de su rol en el tratamiento prenatal actual.

Hydrothorax is a primary pleural effusion that occurs during prenatal life (called "primary chylothorax" after birth). In certain cases, this effusion is severe and produces pulmonary and cardiac compression, and perinatal mortality remains high. Newborns with hydrothorax often require drainage, total parenteral nutrition and specific medication for their recovery. However, prenatal interventions, mainly with thoraco-amniotic shunts, can improve these results. We report the case of a fetus with severe hydrothorax who underwent thoracentesis and review the literature on its role in current prenatal management.

Is fetal middle cerebral artery peak systolic velocity correlated with hemoglobin levels in cases of nonimmune fetal anemia?

OBJECTIVES: To establish whether a correlation exists between the fetal middle cerebral artery peak systolic velocity (MCA PSV) and fetal hemoglobin levels before intrauterine transfusion (IUT) in cases of severe fetal anemia. METHODS: This was a single-center, retrospective study of data from 49 fetuses treated with IUT for fetal anemia between 2003 and 2018. Severe fetal anemia was suspected when MCA PSV was or exceeded 1.55 multiples of the median. RESULTS: The causes of anemia were largely idiopathic, and the overall survival rate was 57%. MCA PSV and hemoglobin were correlated in all 34 fetuses with alloimmune fetal anemia, whereas the 15 fetuses with nonimmune causes showed no correlation. Of the 15 noncorrelated cases, twin pregnancy was most common, followed by idiopathic causes. All the twin pregnancies involved monochorionic twins. Fetal hydrops, especially ascites, was significantly associated with severe anemia. CONCLUSIONS: Fetal MCA PSV may not be a reliable independent factor for the diagnosis of severe fetal anemia in nonimmune cases, and the presence of associated hydrops implies that the fetus is more likely to have severe fetal anemia than in a fetus without hydrops.

A New Ethical Framework for Assessing the Unique Challenges of Fetal Therapy Trials.

New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk-benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of fetal therapies. Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research (e.g., only for life-threatening conditions). Instead, we propose that the individual risks for the pregnant woman and the fetus should be justified by the benefits for them and the study's social value. Studies that meet this overall proportionality criterion but have mildly unfavorable risk-benefit ratios for pregnant women and/or fetuses may be acceptable.

Development course of indications of intrauterine management for fetal hydrocephalus / 中华围产医学杂志

Surgical treatment of intrauterine hydrocephalus can prevent irreversible fetal brain damage through early decompression of the lateral ventricle. In 1980s, the prognosis of fetuses with hydrocephalus who received intrauterine treatment were poor due to non-specific surgical indications, lacking skilled operators, and underdeveloped imaging technology. We review the development of the surgical indications for fetal hydrocephalus in the following four stages: the introduction of surgical indications, the exclusion of extracranial malformations, the clear definition of isolated hydrocephalus, and the popularization of micro-array and gene sequencing techniques. The outcomes of fetuses with hydrocephalus who received intrauterine treatment with different selection criteria are summarized to explore the inclusion and exclusion criteria.

Effect of materal anti-Sj?gren's syndrome type A/Sj?gren's syndrome type B antibodies on fetal heart development and the management / 中华围产医学杂志

Anti-Sj?gren's syndrome type A（SSA) and anti-Sj?gren's syndrome type B（SSB) antibodies both belong to the antinuclear antibody spectrum and are common in patients with systemic lupus erythematosus, Sj?gren's syndrome and undifferentiated connective tissue disease as well as asymptomatic patients. Approximately 1% of pregnant women are positive for anti-SSA and anti-SSB antibodies and only 1%-3% of the fetuses carried by primiparae with anti-SSA and anti-SSB antibodies show immune-mediated cardiac conduction and structural abnormalities. Due to its low incidence and insidious onset, some pregnant women were diagnosed positive for antibodies against SSA and SSB for the first time only due to fetal heart block or structural abnormalities during pregnancy. Domestic and international research on the effects of anti-SSA and anti-SSB antibodies on fetal heart and the prenatal monitoring, diagnosis, intrauterine treatment and prognosis of fetal cardiac abnormalities related to anti-SSA and anti-SSB exposure are reviewed to guide the clinical work of obstetrics.

Pharmacokinetics and pharmacodynamics of sildenafil in fetal lambs on extracorporeal support.

BACKGROUND: Maternal transplacental administration of sildenafil is being considered for a variety of fetal conditions. Clinical translation also requires evaluation of fetal safety in a higher species, such as the fetal lamb. Experiments with the pregnant ewe are curtailed by minimal transplacental transfer as well as limited access to the fetus. The EXTra-uterine Environment for Neonatal Development (EXTEND) model renders the isolated fetal lamb readily accessible and allows for direct fetal administration of sildenafil. METHODS: Five fetal lambs were placed on extracorporeal support in the EXTEND device and received continuous intravenous (IV) sildenafil (0.3-0.5-0.7 mg/kg/24hr) for a duration of one to seven days. Plasma sildenafil concentrations were sampled at regular intervals to establish the pharmacokinetic profile using population pharmacokinetic modeling. Serial Doppler ultrasound examination, continuous non-invasive hemodynamic monitoring and blood gas analysis were done to evaluate the pharmacodynamic effects and fetal response. FINDINGS: The target concentration range (47-500 ng/mL) was attained with all doses. Sildenafil induced an immediate and temporary reduction of pulmonary vascular resistance, mean arterial pressure and circuit flow, without change in fetal lactate levels and acid-base status. The duration of the systemic effects increased with the dose. INTERPRETATION: Immediate temporary pulmonary vascular and systemic hemodynamic changes induced by sildenafil were biochemically well tolerated by fetal lambs on extracorporeal support, with the 0.5 mg/kg/24 h dose balancing rapid attainment of target concentrations with short-lived systemic effects. RESEARCH IN CONTEXT: None. SEARCH STRATEGY BEFORE UNDERTAKING THE STUDY: A literature review was conducted searching online databases (Medline, Embase and Cochrane), using search terms: fetal OR prenatal OR antenatal AND sildenafil, without time-limit and excluding human studies. Where relevant, investigators were contacted in order to avoid duplication of work. EVIDENCE BEFORE THIS STUDY: Prenatal therapy with sildenafil, a phosphodiesterase-5 inhibitor with vasodilatory and anti-remodeling effects on vascular smooth muscle cells, has been considered for a variety of fetal conditions. One multicenter clinical trial investigating the benefit of sildenafil in severe intrauterine growth restriction (the STRIDER-trial) was halted early due to excess mortality in the sildenafil-exposed arm at one treatment site. Such findings demonstrate the importance of extensive preclinical safety assessment in relevant animal models. Transplacentally administered sildenafil leads to decreased pulmonary arterial muscularization, preventing or reducing the occurrence of pulmonary hypertension in rat and rabbit fetuses with diaphragmatic hernia (DH). Validation of these results in a higher and relevant animal model, e.g. fetal lambs, is the next step to advance clinical translation. We recently demonstrated that, in contrast to humans, transplacental transfer of sildenafil in sheep is minimal, precluding the in vivo study of fetal effects at target concentrations using the conventional pregnant ewe model. ADDED VALUE OF THIS STUDY: We therefore used the extracorporeal support model for fetal lambs, referred to as the EXTra-uterine Environment for Neonatal Development (EXTEND) system, bypassing placental and maternal metabolism, to investigate at what dose the target concentrations are reached, and what the fetal hemodynamic impact and response are. Fetal hemodynamic and metabolic tolerance to sildenafil are a crucial missing element on the road to clinical translation. This is therefore the first study investigating the pharmacokinetics, hemodynamic and biochemical effects of clinical-range concentrations of sildenafil in fetal lambs, free from placental and maternal interference. IMPLICATIONS OF ALL THE AVAILABLE EVIDENCE: We demonstrated self-limiting pulmonary vasodilation, a decrease of both systemic arterial pressures and circuit flows, induced by clinical range concentrations of sildenafil, without the development of fetal acidosis. This paves the way for further investigation of prenatal sildenafil in fetal lambs on extracorporeal support. A dose of 0.5 mg/kg/24 h offered the best trade-off between rapid achievement of target concentrations and shortest duration of systemic effects. This is also the first study using the EXTEND as a model for pharmacotherapy during pregnancy.