Right-sided congenital diaphragmatic hernia in a decade of fetal surgery.

OBJECTIVE: To report a recent update on fetuses with right-sided congenital diaphragmatic hernia (RCDH) in the era of fetal surgery. DESIGN: Retrospective review of prospectively collected data. SETTING: Fetal treatment centres in Leuven and Barcelona. POPULATION: Consecutive cases of RCDH between 2002 and 2012. METHODS: Data on prenatal imaging, genetic testing, pregnancy and neonatal outcomes were extracted from our databases, including structural and genetic anomalies, candidate outcome predictors such as lung size, liver herniation ratio, polyhydramnios, cervical length, preterm prelabour rupture of membranes and gestational age at birth. MAIN OUTCOME MEASURES: Survival and oxygen dependency at discharge. RESULTS: Ten out of 86 fetuses with RCDH had associated abnormalities. Of 76 isolated pregnancies, eight women opted for termination of pregnancy, most with severe hypoplasia and one was lost to follow up. Nineteen pregnancies were expectantly managed and delivered at a mean gestational age of 36.0 ± 3.0 weeks. Survival at discharge was 53% (10/19), one being oxygen dependent. In the fetal surgery group (n = 48), mean gestational age at delivery was 34.5 ± 3.0 weeks. In our recent experience not previously published (n = 23) survival rate was 52 and 39% were oxygen dependent at discharge. Pooling these data with earlier reported observations by our group we observed a 42% survival rate in 57 fetuses. Lung size on magnetic resonance imaging and an interval of >24 hours between reversal of tracheal occlusion and delivery were predictors of outcome. CONCLUSIONS: Right-sided CDH seems to have a poorer outcome than that reported for fetuses with left-sided CDH with similar lung size before birth. Survival rates after expectant management with observed/expected lung-to-head ratio values ≤45 and ≤30% were 17 and 0%, respectively. In those undergoing fetal surgery (observed/expected lung-to-head ratio ≤45%) there was an apparent increase (42%).

Correlation of observed-to-expected total fetal lung volume with intrathoracic organ herniation on magnetic resonance imaging in fetuses with isolated left-sided congenital diaphragmatic hernia.

OBJECTIVES: To assess using fetal magnetic resonance imaging (MRI) the relationship between the position of the stomach as well as the volume of herniation of organs into the thorax, and the observed-to-expected total fetal lung volume (o/e-TFLV), as a measure of pulmonary hypoplasia, in fetuses with isolated left-sided congenital diaphragmatic hernia (LCDH). METHODS: This was a single-center retrospective study using archived MR images from fetuses > 20 weeks' gestation evaluated for isolated LCDH over an 11-year period between July 2002 and September 2013. We retrieved data on the gestational age at MRI, o/e-TFLV and liver position. Images were also reviewed by a single operator to determine retrospectively the position of the stomach as well as the proportion of the total thorax volume occupied by the herniated fetal liver, stomach and other viscera. Following confirmation of reproducibility, we assessed the correlation of intrathoracic organ volumes and stomach position with o/e-TFLV. RESULTS: The study included 205 fetuses which underwent a total of 259 MR examinations. The reproducibility of organ volume measurements was excellent (intraclass correlation coefficient range, 0.928-0.997). The average time spent to obtain intrathoracic organ volumes ranged from 2.28 to 5.13 min. Of all herniated organ-to-thoracic volume ratios, the liver-to-thoracic volume ratio had the strongest correlation with o/e-TFLV (ρ = -0.429, P<0.0001). Stomach volume did not correlate, although, when categorized by the position and extent of stomach herniation, there was an inverse relationship to o/e-TFLV. No intrathoracic organ-to-thoracic volume ratio was related to gestational age. CONCLUSIONS: We observed in fetuses with isolated LCDH an inverse relationship between lung volume and the amount of liver herniated as well as the position of the stomach in the chest.

Comparison of matching by body volume or gestational age for calculation of observed to expected total lung volume in fetuses with isolated congenital diaphragmatic hernia.

OBJECTIVE: To determine the bias induced by matching fetuses according to gestational age (GA) or fetal body volume (FBV) when calculating the observed to expected total fetal lung volume (o/e TFLV) in cases of isolated congenital diaphragmatic hernia (CDH). METHODS: This was a single-center, retrospective study on archived magnetic resonance (MR) images of fetuses with isolated CDH over a 10-year period. We retrieved the TFLV, GA and o/e TFLVGA , and delineated FBV to obtain TFLVFBV in each case. We evaluated the relationship between o/e TFLVFBV and o/e TFLVGA by Bland-Altman analysis. All outliers were manually identified, and their specific clinical features were retrieved. RESULTS: Records of a total of 377 MR examinations of 225 fetuses were identified and included in the analysis. The mean ( ± SD) time spent on FBV measurement was 16.12 ± 4.95 min. On reproducibility analysis of FBV measurement (n = 10), the intraobserver intraclass correlation coefficient (ICC) was 0.998 and the interobserver ICC was 0.999. FBV was highly correlated with GA (R(2) = 0.899; P < 0.0001). There was good agreement between o/e TFLVGA and o/e TFLVFBV , with a mean difference of -1.10% and 95% limits of agreement of -8.58 to 6.39. There were no outliers in fetuses that had an o/e TFLV < 25%. Discrepancies induced by different methods were more likely in women with a body mass index ≥ 25 kg/m(2) (+16.5%), fetuses with an estimated fetal weight (EFW) ≤ 10(th) centile (+21.3%) or an EFW > 90(th) centile (+14.7%). CONCLUSIONS: Discrepancies in matching by FBV and GA when calculating o/e TFLV are more likely in fetuses with an abnormal EFW or in fetuses carried by overweight women. The clinical relevance of using FBV rather than GA for calculation of the o/e TFLV might be limited, as there was no discrepancy between the two methods in fetuses with small lungs ( < 25%), which is the group of most interest for lung volume assessment.

Outcome of fetuses with congenital diaphragmatic hernia and associated intrafetal fluid effusions managed in the era of fetal surgery.

OBJECTIVE: Fetuses with congenital diaphragmatic hernia (CDH) and for whom additional ultrasound findings are abnormal typically are considered to have a dismal prognosis. Our aim was to assess the outcome of fetuses with CDH and associated intrafetal fluid effusions. METHODS: This was a retrospective bicentric cohort study on the perinatal management of fetuses with CDH and intrafetal fluid effusions. RESULTS: The incidence of effusions was 5.2% (n = 14) in 269 consecutive cases of left-sided CDH and 29.2% (n = 14) in 48 cases of right-sided CDH. Hydrothorax (n = 19 (68%)) and ascites (n = 16 (57%)) were the most common effusions. A combination of both was present in 11 (39%) fetuses. Of 20 ongoing pregnancies with CDH and fluid effusions, without other anomalies, five with moderate or mild pulmonary hypoplasia were managed without fetoscopic endoluminal tracheal occlusion (FETO). The 15 other cases underwent FETO because of severe pulmonary hypoplasia. Neonatal survival rate was similar in both groups (n = 2/5 and n = 6/15, respectively (P = 1.0)). Survival among those who underwent FETO was similar to previously published results concerning isolated cases undergoing FETO. CONCLUSIONS: Our observations do not support the view that intrafetal effusions are an adverse prognostic factor in fetuses with CDH. In CDH fetuses with effusions and severe pulmonary hypoplasia treated with FETO, neonatal survival is similar to that in isolated cases undergoing the intervention. Whether pleural effusions should be addressed by thoracic drainage procedures remains unproven.

[Amniopatch to treat iatrogenic rupture of the fetal membranes]. / Traitement de la rupture iatrogène des membranes fœtales par "patch" amniotique.

OBJECTIVE: With the increased use of invasive fetal procedures, the number of patients facing postprocedure membrane rupture is increasing. We aimed to describe the use of platelets and fresh frozen plasma for sealing iatrogenic fetal membrane defects. PATIENTS AND METHODS: We describe the mechanisms of action of the amniopatch procedure as well as published experience. RESULTS: Amniopatch effectively sealed the fetal membranes in over two thirds of published cases (n=44). There is a risk of 17% of in utero fetal death, which may occur remotely from the procedure and is often unexplained. DISCUSSION AND CONCLUSION: In case of early onset but persistent amniotic fluid leakage following an invasive fetal procedure, amniopatch may be offered.

The fetal respiratory system as target for antenatal therapy.

The widespread use of prenatal ultrasound has made the fetus a patient. A number of conditions diagnosed as such may require therapy prior to birth. Herein we describe past, current and potential future procedures designed to treat pulmonary conditions in the antenatal period. When congenital cystic adenomatoid malformation (CCAM) is -associated with fetal hydrops, treatment is required. Prior to viability this may be in utero resection of the pathologic lung lobe or shunting of cystic lesions. More recently, fetuses with isolated congenital diaphragmatic hernia (CDH) with lethal lung hypoplasia have been offered percutaneous fetal tracheal occlusion to provoke lung growth. A very rare condition is laryngeal atresia, which requires peripartum re-establishment of the airways. As we get more -experience with access to the fetal airways, this may open the doors for novel therapies. One of these is gene delivery to treat fetuses with serious monogenic disorders or to induce transient overexpression of certain proteins. We review the individual hurdles that are being met by researchers when designing fetal gene therapeutic strategies, in particular for the fetal lung. Also the use of stem cells for pulmonary disorders is currently explored.

Fetal cerebral blood flow velocities in congenital diaphragmatic hernia.

OBJECTIVES: Left ventricular cardiac output is decreased in fetuses with congenital diaphragmatic hernia (CDH). Our aim was to assess whether this alters cerebral perfusion or growth in utero. METHODS: Fetal head circumference, biparietal diameter, lung-to-head ratio and middle cerebral artery (MCA) Doppler flow patterns were assessed by ultrasonography in 103 fetuses with prenatally diagnosed CDH. Total fetal lung volume and cerebral volume were measured using magnetic resonance imaging. Values were transformed to gestational age-independent scores (multiples of the median (MoM)) and compared with controls. Subanalyses were made according to whether the CDH was left- (n = 86) or right-sided (n = 17) and to whether it was isolated (n = 86) or associated with other anomalies (n = 17). RESULTS: MCA flow velocity was significantly lower in fetuses with CDH than in healthy fetuses (0.79 ± 0.19 MoM; P < 0.0001) but MCA pulsatility index was unchanged (0.99 ± 0.25 MoM; P = 0.79). Cranial biometry and cerebral volume in CDH fetuses fell in the normal range. Gestational age-adjusted lung area was correlated with MCA peak systolic velocity, which was in turn correlated with brain volume. CONCLUSIONS: Fetal cerebral blood flow velocities are decreased in CDH yet cranial and cerebral growth are conserved. Further work will be needed to address whether part of the neurologic impairment observed in long-term survivors of CDH finds its origin in the prenatal period.