Prenatal assessment and prediction in CDH: for what purpose?

Congenital diaphragmatic hernia is most often diagnosed prenatally, and accurate assessment is crucial for prognosis parental counselling and therapeutic planning. The assessment of pulmonary hypoplasia is currently the most relevant prognostic indicator. Ultrasound and MRI parameters such as the observed-to-expected lung-to-head ratio and total fetal lung volume serve as the primary predictors of neonatal outcome.

The Vortex shunt: Short-term feasibility studies in the fetal lamb model of lower urinary tract obstruction and pleural effusion.

Background: The suboptimal shunt design of the currently available vesico-amniotic and thoraco-amniotic shunts is likely at tributed to the risk of shunt failure, either by displacement, kinking, or obstruction, resulting in treatment failure and the need for additional fetal intervention.

Objective: To evaluate the feasibility of ultrasound-guided insertion, drainage, and short-term dislodgement risks of the novel Vortex shunt in fetal lambs with surgically induced lower urinary tract obstruction (LUTO) and pleural effusion.

Study Design: LUTO was surgically created in eight fetal lambs at a median of 71 days (range 69-72; term = 145) gestation.

Experimental Induction of Complex Gastroschisis in the Fetal Lamb: Systematic Review.

We systematically reviewed experiments in the fetal lamb model of gastroschisis using PubMed, Embase, Web of Science, and Scopus, seeking for standardized surgical techniques to obtain complex gastroschisis. Eligible were studies where an abdominal wall defect was surgically induced and gross anatomical findings at birth were available. The primary outcome was complex gastroschisis, defined by the presence of bowel stenosis, atresia, volvulus, perforation, and/or necrosis.

Tracheomalacia and tracheomegaly in infants and children with congenital diaphragmatic hernia managed with and without fetoscopic endoluminal tracheal occlusion (FETO): a multicentre, retrospective cohort study.

Background: Temporary fetoscopic endoluminal tracheal occlusion (FETO) promotes lung growth and increases survival in selected fetuses with congenital diaphragmatic hernia (CDH). FETO is performed percutaneously by inserting into the trachea a balloon designed for vascular occlusion. However, reports on the potential postnatal side-effects of the balloon are scarce.

Self-reported respiratory and gastrointestinal outcomes in children with isolated congenital diaphragmatic hernia: A prospective multicentre study.

Objective: To evaluate medium-term self-reported respiratory and gastrointestinal (GI) outcomes in children with congenital diaphragmatic hernia (CDH).

Design: Self-reported respiratory and GI outcomes correlated with prenatal severity indicators.

Setting: Prospective study at three fetal medicine units.

Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids.

Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous.

Prenatal treprostinil improves pulmonary arteriolar hypermuscularization in the rabbit model of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a congenital malformation characterized by pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Pulmonary hypertension represents the major cause of neonatal mortality and morbidity. Prenatal diagnosis allows assessment of severity and selection of foetal surgery candidates.

Development and validation of a novel fetal vesico-amniotic shunt, the vortex shunt.

Fetal lower urinary tract obstruction (LUTO) is a severe malformation associated with an up to 80% mortality risk as well as significant renal and pulmonary morbidity in survivors. Fetal vesico-amniotic shunts (VAS) bypass the bladder obstruction, improve amniotic fluid volume and enhance in-utero pulmonary development. VAS has been shown to reduce respiratory morbidity and mortality in the neonatal period without proven benefit on long-term renal and bladder function.

Have the results of the TOTAL-trials changed the attitude and practice of maternal-fetal medicine specialists?

Objective: To explore the views and practices of maternal-fetal medicine specialists on offering fetoscopic endoluminal tracheal occlusion (FETO) for left- and right-sided congenital diaphragmatic hernia (LCDH, RCDH) in the post Tracheal Occlusion To Accelerate Lung growth (TOTAL)-trial era.

Method: Cross-sectional knowledge, attitude and practice survey was conducted among 105 attendees of the 19th World Congress of Fetal Medicine.

Results: On average, respondents were knowledgeable about CDH, involved in research, and provided antenatal treatment options.

Survival in very preterm infants with congenital diaphragmatic hernia and association with prenatal imaging markers: A retrospective cohort study.

Objectives: To describe the outcomes of preterm born infants with congenital diaphragmatic hernia (CDH; ≤32.0 weeks of gestation) and the associations between prenatal imaging markers and survival.

Design: Retrospective cohort study.

PBPK-based dose finding for sildenafil in pregnant women for antenatal treatment of congenital diaphragmatic hernia.

Sildenafil is a potent vasodilator and phosphodiesterase type five inhibitor, commercially known as Revatio and approved for the treatment of pulmonary arterial hypertension. Maternal administration of sildenafil during pregnancy is being evaluated for antenatal treatment of several conditions, including the prevention of pulmonary hypertension in fetuses with congenital diaphragmatic hernia. However, determination of a safe and effective maternal dose to achieve adequate fetal exposure to sildenafil remains challenging, as pregnancy almost always is an exclusion criterion in clinical studies.

Fetoscopic endoluminal tracheal occlusion with Smart-TO balloon: Study protocol to evaluate effectiveness and safety of non-invasive removal.

Introduction: One of the drawbacks of fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia is the need for a second invasive intervention to reestablish airway patency. The "Smart-TO" (Strasbourg University-BSMTI, France) is a new balloon for FETO, which spontaneously deflates when positioned near a strong magnetic field, e.g.

Brain development is altered in rabbit fetuses with congenital diaphragmatic hernia.

Introduction: Children with congenital diaphragmatic hernia (CDH) are at risk for neurodevelopmental delay. Some changes are already present prenatally. Herein, we further examined how the brain develops in fetal rabbits with surgically created DH.

Patient-reported outcomes for congenital diaphragmatic hernia: A qualitative study.

Objective: To identify Patient-reported outcomes (PROs) for parents with a lived experience of a prenatal diagnosis of isolated congenital diaphragmatic hernia (CDH).

Method: Thematic analysis of in-depth interview transcripts.

Results: Interviews (n = 26) identified 11 PROs for given time points throughout the CDH trajectory.

Sildenafil during the 2nd and 3rd Trimester of Pregnancy: Trials and Tribulations.

Sildenafil, a phosphodiesterase 5 inhibitor with a vasodilatory and anti-remodeling effect, has been investigated concerning various conditions during pregnancy. Per indication, we herein review the rationale and the most relevant experimental and clinical studies, including systematic reviews and meta-analyses, when available. Indications for using sildenafil during the second and third trimester of pregnancy include maternal pulmonary hypertension, preeclampsia, preterm labor, fetal growth restriction, oligohydramnios, fetal distress, and congenital diaphragmatic hernia.

Outcomes of Monoamniotic Twin Pregnancies from the First Trimester Onward.

Introduction: Monochorionic monoamniotic (MCMA) twins are rare, and information is lacking on pregnancy outcomes from the first trimester onward. This study compares the pregnancy and neonatal outcomes between MCMA and monochorionic diamniotic (MCDA) twin pregnancies from the first trimester onward. We also report on the outcomes of MCMA twin pregnancies continuing after 28 weeks and on the neurodevelopmental outcomes of MCMA twins.

Are there differences between monochorionic twin placentas after spontaneous and assisted conception?

Introduction: No data are available on the placental characteristics of monochorionic twin pregnancies conceived by in vitro fertilization (IVF). This study investigates the differences between placentas from monochorionic diamniotic (MCDA) twin pregnancies conceived spontaneously and those conceived after IVF.

Methods: This is a retrospective analysis of placental data from a consecutive series of MCDA twin pregnancies followed from the first trimester.

Pulmonary hypertension in congenital diaphragmatic hernia: Antenatal prediction and impact on neonatal mortality.

Objective: To determine the prevalence of pulmonary hypertension (PAH) in left-sided congenital diaphragmatic hernia (CDH); how we could predict it; and how PAH contributed to the model for mortality prediction.

Study Design: Retrospective analysis in three European centers. The primary outcome was the presence of PAH on postnatal day (d) 1, 7, and at discharge.

Prenatal treprostinil reduces the pulmonary hypertension phenotype in the rat model of congenital diaphragmatic hernia.

Background: Persistent pulmonary hypertension (PH) causes significant mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Since pulmonary vascular abnormalities in CDH develop early during foetal development, we hypothesized that prenatal maternal administration of treprostinil, through its anti-remodelling effect, would improve the PH-phenotype in the nitrofen rat model of CDH.

Methods: In a dose-finding study in normal, healthy pregnant rats, we demonstrated target-range foetal plasma treprostinil concentrations without signs of toxicity.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

Objective: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies.

Data Sources: A search of MEDLINE, EMBASE, ClinicalTrials.

Neonatal and fetal therapy of congenital diaphragmatic hernia-related pulmonary hypertension.

Congenital diaphragmatic hernia (CDH) is a complex malformation characterised by a triad of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. Much of the mortality and morbidity in CDH is largely accounted for by PH, especially when persistent beyond the neonatal period and refractory to available treatment. Gentle ventilation, haemodynamic optimisation and pulmonary vasodilation constitute the foundations of neonatal treatment of CDH-related PH (CDH-PH).

The randomized Tracheal Occlusion To Accelerate Lung growth (TOTAL)-trials on fetal surgery for congenital diaphragmatic hernia: reanalysis using pooled data.

Background: Two randomized controlled trials compared the neonatal and infant outcomes after fetoscopic endoluminal tracheal occlusion with expectant prenatal management in fetuses with severe and moderate isolated congenital diaphragmatic hernia, respectively. Fetoscopic endoluminal tracheal occlusion was carried out at 27 to 29 weeks' gestation (referred to as "early") for severe and at 30 to 31 weeks ("late") for moderate hypoplasia. The reported absolute increase in the survival to discharge was 13% (95% confidence interval, -1 to 28; P=.

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.