Irma Capolupo

Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.

Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe

Congenital diaphragmatic hernia (CDH) is associated with high mortality and morbidity. To date, there are no standardized protocols for the treatment of infants with this anomaly. However, protocols based on the literature and expert opinion might improve outcome. This paper is a consensus statement from the CDH EURO Consortium prepared with the aim of achieving standardized postnatal treatment in European countries. During a consensus meeting between high-volume centers with expertise in the treatment of CDH in Europe (CDH EURO Consortium), the most recent literature on CDH was discussed. Thereafter, 5 experts graded the studies according to the Scottish Intercollegiate Guidelines Network (SIGN) Criteria. Differences in opinion were discussed until full consensus was reached. The final consensus statement, therefore, represents the opinion of all consortium members. Multicenter randomized controlled trials on CDH are lacking. Use of a standardized protocol, however, may contribute to more valid comparisons of patient data in multicenter studies and identification of areas for further research.

Conventional Mechanical Ventilation Versus High-frequency Oscillatory Ventilation for Congenital Diaphragmatic Hernia: A Randomized Clinical Trial (The VICI-trial).

Objectives:To determine the optimal initial ventilation mode in congenital diaphragmatic hernia. Background:Congenital diaphragmatic hernia is a life-threatening anomaly with significant mortality and morbidity. The maldeveloped lungs have a high susceptibility for oxygen and ventilation damage resulting in a high incidence of bronchopulmonary dysplasia (BPD) and chronic respiratory morbidity. Methods:An international, multicenter study (NTR 1310), the VICI-trial was performed in prenatally diagnosed congenital diaphragmatic hernia infants (n = 171) born between November 2008 and December 2013, who were randomized for initial ventilation strategy. Results:Ninety-one (53.2%) patients initially received conventional mechanical ventilation and 80 (46.8%) high-frequency oscillation. Forty-one patients (45.1%) randomized to conventional mechanical ventilation died/ had BPD compared with 43 patients (53.8%) in the high-frequency oscillation group. An odds ratio of 0.62 [95% confidence interval (95% CI) 0.25–1.55] (P = 0.31) for death/BPD for conventional mechanical ventilation vs high-frequency oscillation was demonstrated, after adjustment for center, head-lung ratio, side of the defect, and liver position. Patients initially ventilated by conventional mechanical ventilation were ventilated for fewer days (P = 0.03), less often needed extracorporeal membrane oxygenation support (P = 0.007), inhaled nitric oxide (P = 0.045), sildenafil (P = 0.004), had a shorter duration of vasoactive drugs (P = 0.02), and less often failed treatment (P = 0.01) as compared with infants initially ventilated by high-frequency oscillation. Conclusions:Our results show no statistically significant difference in the combined outcome of mortality or BPD between the 2 ventilation groups in prenatally diagnosed congenital diaphragmatic hernia infants. Other outcomes, including shorter ventilation time and lesser need of extracorporeal membrane oxygenation, favored conventional ventilation.

Hearing impairment in congenital diaphragmatic hernia: the inaudible and noiseless foot of time

AIM OF THE STUDY Infants with congenital diaphragmatic hernia (CDH) are at high risk of sensorineural hearing loss (SNHL). Extracorporeal membrane oxygenation is known to increase this risk, but little is known about other potential causes. We evaluated the impact of several risk factors on SNHL development in CDH survivors not treated with extracorporeal membrane oxygenation. METHODS All high-risk CDH survivors consecutively treated between 1999 and 2005 were included. SNHL was diagnosed based on formal assessment with standard audiologic tests. Patients with and without SNHL were compared for patient-related and treatment-related risk factors. Subsequently, a logistic regression analysis was performed to identify independent risk factors associated with SNHL development. MAIN RESULTS Out of 87 CDH survivors, 82 had a formal audiologic evaluation and 40 (49%) had SNHL. Patients with SNHL had significantly lower gestational age (P = .045); higher prevalence of sepsis (P < .001); older age at audiologic examination (P < .001); more episodes of hypocapnia (P = .045); higher prevalence of inhaled nitric oxide use (P = .005); longer mechanical ventilation (P = .009); and longer aminoglycosides (P = .006), furosemide (P = .004), and pancuronium bromide (P = .001) treatments. On logistic regression analysis, the only variable independently associated with the development of SNHL was patients age at audiologic follow-up (P = .012). CONCLUSIONS Several risk factors were associated with SNHL development at univariate analysis. After logistic regression, only age at evaluation remained independently associated with SNHL. Routine audiologic follow-up is advocated in all CDH patients. Further studies are needed to define if other (genetic) factors may be involved in the pathogenesis of SNHL in patients with CDH.

Antenatal diagnosis of congenital anomaly: a really traumatic experience?

Objective:With increasing use of routine prenatal ultrasound, prenatal counseling after diagnosis of congenital malformations is frequently offered to prospective parents. We aimed to assess if the communication of diagnosis of a congenital anomaly in the fetus meets American Psychiatric Association (APA) criteria for trauma in parents.Study Design:In the period ranging from 2003 to 2009 a preliminary investigation was conducted with 165 prospective mothers and 91 prospective fathers being interviewed after communication of diagnosis. Analysis of statements was made independently by two psychologists considering the APA definition of trauma.Result:A total of 145 mothers and 76 fathers experienced the communication of diagnosis in their fetus as a traumatic event. There was no correlation between type of malformation and trauma nor was there statistical difference between mother and father regarding the stressor.Conclusion:Communication of diagnosis of a fetal anomaly can be a traumatic event and should be dealt with consequently. Given the therapeutic value of sharing traumatic experience such practice should be encouraged as part of the consultation process.

Congenital diaphragmatic hernia: defect size correlates with developmental defect.

PURPOSE The aim of our study was to elucidate if the defect size reflects the magnitude of the developmental defect in patients with CDH. METHODS All patients recorded in the CDH Study Group registry between January 1, 2007, and December 31, 2010, and with defect classification were included in the study. They were divided according to defect size (A-D) and compared for: gestational age (GA), birth weight (BW), number of abnormal organ systems, prevalence of associated anomalies, cardiovascular malformations (CVM), chromosomal anomalies, liver in the chest, and hernia sac. RESULTS A total of 1350 of 1778 patients had defect classification: 173 A, 557 B, 438 C, and 182 D. Mortality rate was 0.6%, 5.3%, 22.6%, and 45.6% in group A, B, C, and D, respectively, (p<0.0001; p for trend <0.0001). GA, BW, prevalence of associated anomalies, particularly CVM, number of abnormal organ systems, and prevalence of sac were significantly different between the groups, with a significant reduction of GA, BW, and prevalence of sac. There was an increase in prevalence of associated anomalies, liver in the chest, and number of abnormal systems as the defect size increased. CONCLUSION Defect size is directly correlated with mortality rate, prevalence of other anomalies (particularly CVM), and number of abnormal systems, and inversely with GA, BW, and prevalence of hernia sac. The defect size may be a marker for the magnitude of developmental abnormality, thereby explaining its relationship with the outcome.

When uncertainty generates more anxiety than severity: the prenatal experience with cystic adenomatoid malformation of the lung

Abstract Aim: To assess reasons for higher levels of anxiety generated by prenatal counselling of a condition with good outcome such as cystic adenomatoid malformation (CCAM) of the lung compared to a life-threatening malformation such as congenital diaphragmatic hernia (CDH). Materials and methods: The Spielberger State-Trait Anxiety Inventory (STAI-S) was used to measure anxiety in two groups of mothers carrying a fetus with the respective malformation. Results: Forty-four mothers completed the questionnaire (CCAM, n=21 and CDH, n=23). Before consultation, the mean STAI-S scores in the CCAM group (44.80±5.92) and in CDH group (44.05±4.96) were not significantly different but was significantly reduced in both groups after consultation (CCAM 44.80 vs. 41.60, P=0.014 and CDH 44.05 vs. 34.35, P=0.0001). The groups were not significantly different regarding gestational age at diagnosis. Conclusions: After initial prenatal counselling, uncertainty about prenatal outcome and lack of defined management plans in CCAM seems to be more important than higher mortality rate occurring in CDH.

Neurodevelopmental outcome in congenital diaphragmatic hernia survivors: role of ventilatory time.

BACKGROUND Neurodevelopmental impairment is one of the most significant morbidities among CDH survivors. PURPOSE Assess correlation between ventilatory time (VT) and short-term neurodevelopmental outcome in congenital diaphragmatic hernia (CDH) survivors. METHODS A prospective longitudinal study was conducted between 2008 and 2012. Assessment of mental and motor development was performed at 6 and 12months by Bayley Scales of Infant and Toddler Development - 3rd Edition (BSID-III). ROC curve analysis was used. RESULTS Forty-two subjects were included in the study. There was a significant inverse correlation between neurodevelopment at 6 and 12months and VT during first admission (p<0.0001). VT predicting the risk of moderate (BSID-III <85) and severe (BSID-III <70) delay was 13 and 28days, respectively (area under the curve - delay <85: 6months mental 0.943 and motor 0.992; 12months mental 0.877 and motor 0.925; delay <70: 6months mental 0.934 and motor 0.943; 12months mental 0.906 and motor 0.975; p<0.0001). CONCLUSIONS VT should be considered an important marker to identify subjects at risk for short-term neurodevelopmental delay in CDH survivors. Early follow-up intervention therapy should be activated in every baby with a history exceeding 13days of VT.

Prenatal diagnosis of esophageal duplication cyst: the value of prenatal MRI

Esophageal duplication cysts are rare malformations of the gut, thought to derive from the failure of coalescence of vacuoles early in development of the foregut (Cohen et al., 1982). The exact incidence in the general population is not well defined mainly because of the absence of population-based studies. In this regard, Winslow and colleagues estimated an incidence of 1 : 8.200 live births with considerable male preponderance (Winslow et al., 1984). Esophageal duplication cysts are commonly asymptomatic at birth and they may become evident when complicated, even during adulthood (Cioffi et al., 1998). According to Wootton-Gorges et al., some newborn may experience respiratory distress or feeding difficulties at birth due to the size of the lesions or due to the rapid growth of the mass secondary to infection, or secretions within the cyst (Wootton-Gorges et al., 2002). Moreover, one third of esophageal duplication cysts contain gastric ectopic mucosa that may lead to ulceration and bleeding within the cyst (Holcomb et al., 1989) or produce peptic esophageal stricture (Stringer et al., 1995). A 29-year-old woman para 0, gravida 1, with no relevant medical or surgical history, was referred to our prenatal diagnosis centre for the incidental finding of a lesion in the fetal chest. The woman did not take any medication since expecting and the pregnancy progressed normal. As illustrated in Figure 1(A) and (B), we performed a first prenatal ultrasound (US) evaluation at 29 weeks of gestational age. During this examination, a mediastinal oval anechoic lesion in the fetal thorax was observed. Its diameters were 22 mm × 16.9 mm × 9 mm. The tumour was localized at the right side of the thoracic vertebras, below the carina. The main diagnostic hypotheses were an esophageal duplication, a congenital cystic adenomatoid malformation of the lung, and a bronchogenic cyst. A second US evaluation was performed at 33 weeks of gestation. The lesion was enlarged, with anechoic appearance, and diameters were 29 mm × 20 × mm 20 mm, bulging towards the diaphragm. As illustrated in Figure 1(C), a fetal magnetic resonance imaging (MRI) was performed

Isolated Fetal Ascites Secondary to Persistent Urogenital Sinus

Objective. To present a case of isolated ascites secondary due to urogenital abnormalities (urogenital sinus) without any other prenatal ultrasound marker. Method. A 36-year-old woman with prenatal isolated ascites delivered a female baby, weighing 2.285 g; ascites was drained at birth and the baby underwent several episodes of urinary retention prior to undergoing X-ray investigations. Results. A voiding cystourethrogram revealed a short urogenital sinus: a vesicostomy was performed. A vaginoscopy revealed double vagina with a large posterior vagina. A posterior sagittal anorectal pull-through with genitoplasty was performed at 2 years old with 1-year follow-up. Conclusions. Though rare, a urogenital abnormality is to be suspected in fetal ascites cases with negative viral tests and no cardiac anomalies. The most common ultrasound marker of such abnormalities (fluid filled cavity) may be missing because of complete drainage of urine through the tubes into peritoneum.