Isolated Congenital Diaphragmatic Hernia Cases Research Articles

Influence of Gestational Age and Mode of Delivery on Neonatal Outcomes in Prenatally Diagnosed Isolated Congenital Diaphragmatic Hernia

Aim: The optimal gestational age (GA) at delivery and mode of delivery (MoD) for pregnancies with fetal congenital diaphragmatic hernia (CDH) is undetermined. The impact of early term (37–38 weeks 6 days) versus full term (39–40 weeks 6 days) and MoD on immediate neonatal outcomes in prenatally diagnosed isolated CDH cases was evaluated. Material and Methods: A retrospective chart review of pregnancies evaluated and delivered with the prenatal diagnosis of CDH between July 1, 2008, and December 31, 2018. The primary outcome was survival to hospital discharge. Secondary outcomes included neonatal intensive care unit (NICU) length of stay (LOS), extracorporeal membrane oxygenation (ECMO) requirement and need for supplemental oxygen at day 30 of life. Results: A total of 296 patients were prenatally evaluated for CDH and delivered in a single center during the study period. After applying exclusion criteria, data were available on 113 women who delivered early term and 72 women who delivered full term. Survival to hospital discharge was comparable between the 2 groups – 83.2% in the early term versus 93.1% in the full term (p = 0.07; 95% CI of 0.13–1.04). No difference was observed in any other secondary outcomes. MoD was stratified into spontaneous vaginal, induced vaginal, unplanned cesarean and scheduled cesarean delivery with associated neonatal survival rates of 74.2, 90.6, 89.7 and 88.2%, respectively, p = 0.13. The 5-min Apgar score was higher in the elective cesarean group (7.94) followed by the induced vaginal delivery group (7.8) compared to 7.17 and 7.18 in the spontaneous vaginal and unplanned cesarean groups, respectively (p = 0.03). The GA and MoD did not influence survival to hospital discharge nor NICU LOS in multivariate analysis. Conclusions: Though there were no significant differences in neonatal outcomes for early term compared to full term deliveries of CDH neonates, a trend toward improved survival rates and lower ECMO requirements in the full term group may suggest an underlying importance GA at delivery. Further studies are warranted to validate these findings.

Neurodevelopmental outcomes in children with isolated congenital diaphragmatic hernia: A systematic review and meta-analysis.

Congenital diaphragmatic hernia (CDH) reportedly has neurologic consequences in childhood however little is known about the impact in isolated CDH. Herein we aimed to describe the risk of neurodevelopmental complications in children born with isolated CDH. We systematically reviewed literature for reports on the neurological outcome of infants born with isolated CDH. The primary outcome was neurodevelopmental delay. Secondary outcomes included, motor skills, intelligence, vision, hearing, language and behavior abnormalities. Thirteen out of 87 (15%) studies reported on isolated CDH, including 2624 out of 24,146 children. Neurodevelopmental delay was investigated in four studies and found to be present in 16% (3-34%) of children. This was mainly attributed to motor problems in 13% (2-30%), whereas cognitive dysfunction only in 5% (0-20%) and hearing in 3% (1-7%). One study assessed the effect of fetal surgery. When both isolated and non-isolated children were included, these numbers were higher. This systematic review demonstrates that only a minority of studies focused on isolated CDH, with neurodevelopmental delay present in 16% of children born with CDH. To accurately counsel patients, more research should focus on isolated CDH cases and examine children that underwent fetal surgery.

A proteome signature of umbilical cord serum associated with congenital diaphragmatic hernia.

ABSTRACTCongenital diaphragmatic hernia (CDH) is a congenital anomaly characterized by a defect in the diaphragm. Despite the recent improvements in its treatment, CDH is associated with a high rate of neonatal mortality, which is often related to pulmonary hypoplasia (PH) as well as pulmonary hypertension. A better understanding of the underlying pathological mechanisms of PH in CDH could help establish a new treatment to improve its prognosis. In this study, we investigated serum biological profiles in neonates with CDH. For comprehensive investigation, umbilical cord serum samples were collected from isolated CDH cases (n = 4) and matched healthy controls (n = 4). Samples were analyzed using liquid chromatography–tandem mass spectrometry. A total of 697 proteins were detected; of them, 98 were identified as differentially expressed proteins. Among these differentially expressed proteins, complement C1q subcomponent showed the largest fold change, followed by complement C5. In the pathway enrichment analysis, the complement and coagulation cascades expressed the most significant enrichment (p = 2.4 × 10−26). Thus, the complement pathway might play some role in the pathophysiology of CDH.

Genome-wide enrichment of damaging de novo variants in patients with isolated and complex congenital diaphragmatic hernia.

Congenital Diaphragmatic Hernia (CDH) is a common and often lethal birth defect characterized by diaphragmatic structural defects and pulmonary hypoplasia. CDH is isolated in 60% of newborns, but may also be part of a complex phenotype with additional anomalies. We performed whole exome sequencing (WES) on 87 individuals with isolated or complex CDH and on their unaffected parents, to assess the contribution of de novo mutations in the etiology of diaphragmatic and pulmonary defects and to identify new candidate genes. A combined analysis with 39 additional trios with complex CDH, previously published, revealed a significant genome-wide burden of de novo variants compared to background mutation rate and 900 control trios. We identified an increased burden of likely gene-disrupting (LGD, i.e. nonsense, frameshift, and canonical splice site) and predicted deleterious missense (D-mis) variants in complex and isolated CDH patients. Overall, an excess of predicted damaging de novo LGD and D-mis variants relative to the expected frequency contributed to 21% of complex cases and 12% of isolated CDH cases. The burden of de novo variants was higher in genes expressed in the developing mouse diaphragm and heart. Some overlap with genes responsible for congenital heart defects and neurodevelopmental disorders was observed in CDH patients within our cohorts. We propose that de novo variants contribute significantly to the development of CDH.

Epidemiology of congenital diaphragmatic hernia in Europe: a register-based study

IntroductionPublished prevalence rates of congenital diaphragmatic hernia (CDH) vary. This study aims to describe the epidemiology of CDH using data from high-quality, population-based registers belonging to the European Surveillance of...

Effect of hospital volume on the mortality of congenital diaphragmatic hernia in Japan

During the last decade, new supportive modalities and new therapeutic strategies to treat congenital diaphragmatic hernia (CDH) have been introduced. In Japan, the large number of hospitals prevents centralizing infants with CDH in tertiary centers. The aim of this study was to evaluate the correlations between the number of CDH patients, survival rates, and the current strategies employed to treat CDH at the individual hospitals. Eighty-three hospitals with 674 CDH cases were analyzed using questionnaires. We classified the hospitals into three groups according to the number of CDH patients treated: Group 1 (G1; more than 21 patients), Group 2 (G2; 11-20 patients), and Group 3 (G3; fewer than 10 patients). The median number of CDH patients in G1, G2, and G3 were 28, 14, and 4, respectively. The overall survival rate was 74.5%. When only the isolated CDH cases with a prenatal diagnosis were included, the overall survival rate was 79.3%. The survival rate of isolated CDH cases with a prenatal diagnosis was significantly higher in G1 than that in G2 or G3 (87.2% vs 75.2% vs 74.3%; P < 0.001). There were no differences in perinatal therapeutic strategies among the three groups. We concluded that it might therefore be important to centralize infants with CDH, especially those with isolated CDH with a prenatal diagnosis, to tertiary centers in Japan in order to improve the survival rates.

Epidemiology and outcome of congenital diaphragmatic hernia: a 9‐year experience

The aim of this study was to report the birth prevalence and short-term outcome of congenital diaphragmatic hernia (CDH) in a large geographically defined population, and to assess the feasibility of performing a randomised control trial (RCT) in this population. Data were collected on all cases of CDH reported to the East Midlands and South Yorkshire Congenital Anomalies Register between 1997 and 2005. A total of 194 cases of CDH were identified from 547,025 births; a birth prevalence of 3.5/10,000. Overall 1-year survival was 42%. In total, 69% of cases resulted in a live birth, of these 61% survived to 1 year; 73% were diagnosed antenatally and 22% postnatally, with 1-year survivals 30% and 71%, respectively. A total of 54% were isolated cases and 46% associated with another anomaly, with more live births (80% vs. 56%) and better 1-year survival (62% vs. 19%) with isolated CDH. Overall, only 83 babies were born alive with an isolated CDH: the only group suitable for inclusion in a RCT. In conclusion, given the small numbers of live isolated CDH cases it is impossible that any network alone would be able to perform a valid RCT of treatments, highlighting the need for collaborative international trials to address this complex condition.

Targeted array comparative genomic hybridisation (array CGH) identifies genomic imbalances associated with isolated congenital diaphragmatic hernia (CDH)

Congenital diaphragmatic hernia (CDH) is a congenital birth defect affecting around 1/3000 births. We propose that a significant number of isolated CDH cases have an underlying genetic cause, and that a subset of these result from copy number variations (CNVs) identifiable by array CGH. We have designed a custom array targeted at genes and genomic loci associated with CDH. A total of 79 isolated CDH patients were screened using this targeted array. In three patients, we detected genomic imbalances associated with the observed diaphragmatic hernia; a deletion of 8p22-p23.3, 14.2 Mb in size, a 340 kb duplication of Xq13.1 including the ephrin-B1 gene (EFNB1), and mosaicism for trisomy 2. Using this approach, we detected genomic imbalances associated with CDH in 3/79 (4%) isolated CDH patients. Our findings further implicate 8p deletions as being associated with CDH. The duplication of EFNB1 further highlights this gene as a potential candidate involved in diaphragm development. Mosaicism for trisomy 2 is a rare event and unlikely to be a common cause of CDH. Further investigations of isolated CDH patients by array CGH will continue to identify novel submicroscopic loci and refine genomic regions associated with CDH.

Concomitant malformations and chromosomal abnormalities in prenatally diagnosed congenital diaphragmatic hernia

Objective To analyze the concomitant malforrnations,chromosomal abnormalities and outcomes in prenatally diagnosed congenital diaphragmatic hernia (CDH) cases. Methods Cases of fetal CDH,prenatally identified in the First Affiliated Hospital of Sun Yat-sen University from January 2002 to November 2008,were recruited.The concomitant realformations,chromosomal abnormalities and outcomes of fetal CDlH were analyzed.Fisher's exact test was applied. Results During the study period,71 CDH cases were identified including 62(87.3%) left-sided CDH and 9 (12.7%) right-sided ones.Among the 71 CDH fetuses,38(53.5%)were isolated CDH.33 (46.5%)were complicated with other realformations(complex CDH),including 18(54.5 0A) cardiovascular defects,10 (30.3%)central nervous system abnormalities,9(27.2 0A)genitourinary abnormalities and others.Fetal karyotying was performed in 19 out of the 71 CDH fetuses.among which 12 were isolated CDH cases with normal karyotype,and 4 of the rest 7(4/7)complex CDH cases with chromosomal abnormalities showing a significant differenee compared to the isolated CDH (P.0.009).Sixty-five pregnancies were terminated including all complex CDH(n=33)and 32 isolated CDH.The rest 6 isolated CDH fetuses were term delivered and 5 of them survived after repair of diaphragmatic hernia and one died after birth. Conclusions Left-sided CDH are more common than right-sided ones. Approximately half of the CDH cases are complicated with other malformations,especially cardiovascular abnormalities.The risk of chromosomal abnormalities increases in complex CDH and is relatively low in isolated CDH.The influence of surgical procedure on the prognosis of CDH has not yet determined. Key words: Hernia,diaphragmatic; Ultrasonography,prenatal; Chromosome aberrations

Antenatal detection and impact on outcome of congenital diaphragmatic hernia: A 12-year experience in Auvergne (France)

Objective To evaluate the detection rate of prenatal diagnosis and its impact on outcome in congenital diaphragmatic hernia (CDH). Study design We retrospectively studied 51 cases of CDH registered in the Auvergne area from January 1992 to December 2003 (Birth Defect Registry of Auvergne, Institut Européen des Génomutations). Our main outcome measurements were the detection rate of prenatal diagnosis, the incidence and types of associated anomalies and outcome (termination of pregnancy, in utero fetal demise, neonatal death, survival at the time of registration). Results Twenty-nine cases of isolated CDH were identified of which 13 were detected prenatally (45%) at a mean gestational age of 26.1 weeks and 22 cases of CDH with associated anomalies with prenatal diagnosis of CDH or any associated anomaly in 16 (73%; p = 0.03) at a mean gestational age of 23.9 weeks. In the prenatally detected group (29 cases), there was 1 (3%) in utero fetal death (IUFD), 17 (59%) terminations of pregnancy (TOP) and 11 (38%) live births with early neonatal death in 7 (24%) cases despite delivery in a tertiary care centre in 10/11 cases (four survivors = 14%). Most of the undetected cases were isolated CDH (16/22 = 73%) of which 1 (5%) was a stillborn and 21 (95%) live births with 17 survivors (77%) although 15/21 (71%) were not born at the tertiary care centre ( p = 0.001). The overall survival rate was 41% with a large variability depending on associated anomalies and prenatal diagnosis ( p < 0.0001) (prenatally detected cases: 3/13 (23%) isolated CDH and 1/16 (6%) CDH with associated anomalies; undetected cases: 13/16 (81%) isolated CDH and 4/6 (67%) CDH with associated anomalies). Conclusion Prenatal diagnosis of CDH leads to the delivery of affected babies in tertiary care centres but it remains a challenge in particular for isolated CDH cases and it is associated with a lower survival rate. Associated anomalies contribute to prenatal detection, are related to a higher TOP rate but do not facilitate the detection of diaphragmatic defect per se.