Seasonal Variation of Congenital Diaphragmatic Hernia: A Review of the Literature and Database Report from the United States and Canada.

INTRODUCTION: The etiology of congenital diaphragmatic hernia (CDH) remains unknown and only 10 to 30% of patients have a genetic cause. Seasonal variation is known to contribute to the development of some congenital anomalies. Our aim was to investigate whether CDH births have seasonal variation. MATERIALS AND METHODS: A literature review was conducted for CDH and seasonality. Moreover, data from the CDH International Patient Registry Database were collected for infants with due dates between 2008 and 2014. Due dates were used to determine seasonal distribution of births. Birth rates per month in the United States and Canada were extracted from publicly available databases. Data were analyzed using analysis of variance and contingency tables. RESULTS: First, the literature review revealed 11 articles, of which 3 were eligible for inclusion. These studies reported conflicting results on seasonality of CDH. Second, we extracted due dates from the CDH International Patient Registry Database (1,259 patients) and found that there were fewer due dates in winter months (12.1 ± 4 patients/month) than in summer (16.7 ± 6 patients/month; p = 0.011) and fall months (16.3 ± 5 patients/month; p = 0.022). Although this trend was similar to that of all births in the United States and Canada, a lower incidence was observed in winter for CDH infants (20.2%) than for the general population (24.1%, p = 0.0012). CDH survival rate did not vary by season. CONCLUSION: This study provides evidence for a seasonal variation of CDH births. No causative link was established between CDH development and seasonality. Population-based studies with a focus on exposome data are needed to explain seasonal variation in CDH.

Maternal cigarette smoking and alcohol consumption and congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) occurs when abnormal diaphragm development allows herniation of abdominal organs into the thoracic cavity. Its etiopathogenesis is not well understood, but cigarette smoking and alcohol exposure may impact diaphragm development. Using data from a large, population-based case-control study, we examined associations between maternal cigarette smoking and alcohol consumption and CDH in offspring. METHODS: We analyzed maternal interview reports of cigarette smoking and alcohol consumption during early pregnancy for 831 children with CDH and 11,416 children without birth defects with estimated dates of delivery during 1997-2011. Generalized linear mixed effects models with a random intercept for study site were used to estimate associations between measures of exposure to smoking (any, type, frequency, duration) and alcohol (any, quantity, frequency, variability, type) for all CDH combined and selected subtypes (Bochdalek and Morgagni). RESULTS: Mothers of 280 (34.0%) case and 3,451 (30.3%) control children reported early pregnancy exposure to cigarette smoking. Adjusted odds ratios for all CDH were increased for any (1.3; 95% confidence interval 1.1-1.5), active (1.3, 1.0-1.7), and passive (1.4, 1.1-1.7) smoking. Early pregnancy alcohol consumption was reported by mothers of 286 (34.9%) case and 4,200 (37.0%) control children; odds were near the null for any consumption (0.9, 0.8-1.1) and consumption with (0.9, 0.7, 1.1) or without (0.9, 0.8, 1.1) binging. Estimates for smoking and alcohol tended to be higher for Bochdalek CDH and Morgagni CDH than those for all CDH. CONCLUSIONS: Findings suggest that maternal early pregnancy exposure to cigarette smoking, but less so to alcohol consumption, contributes to CDH. These findings need to be replicated in additional large studies that use systematic case ascertainment and classification, detailed exposure assessment, and examine subtype-specific associations.

Parental risk factors for congenital diaphragmatic hernia - a large German case-control study.

BACKGROUND: Evidence for periconceptional or prenatal environmental risk factors for the development of congenital diaphragmatic hernia (CDH) is still scarce. Here, in a case-control study we investigated potential environmental risk factors in 199 CDH patients compared to 597 healthy control newborns. METHODS: The following data was collected: time of conception and birth, maternal BMI, parental risk factors such as smoking, alcohol or drug intake, use of hairspray, contact to animals and parental chronic diseases. CDH patients were born between 2001 and 2019, all healthy control newborns were born in 2011. Patients and control newborns were matched in the ratio of three to one. RESULTS: Presence of CDH was significantly associated with maternal periconceptional alcohol intake (odds ratio = 1.639, 95% confidence interval 1.101-2.440, p = 0.015) and maternal periconceptional use of hairspray (odds ratio = 2.072, 95% confidence interval 1.330-3.229, p = 0.001). CONCLUSION: Our study suggests an association between CDH and periconceptional maternal alcohol intake and periconceptional maternal use of hairspray. Besides the identification of novel and confirmation of previously described parental risk factors, our study underlines the multifactorial background of isolated CDH.

Diaphragmatic Hernia Associated With Absent Ductus Venosus and Anomalous Connection of an Obliterated Umbilical Vein to the Coronary Sinus.

Umbilical vein anomalies are a rare congenital defect, which have been associated with absent ductus venosus, with few cases also involving a congenital diaphragmatic hernia. We describe a case of postnatal development of an anterior diaphragmatic hernia of Morgagni in a four-year-old patient diagnosed prenatally with mesocardia, absent ductus venosus with a large umbilical vein, a large secundum atrial septal defect, and patent ductus arteriosus.

Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside.

Congenital diaphragmatic hernia (CDH) is a devastating disease that still carries a high mortality and morbidity rate. Poor outcomes for fetuses and infants with CDH are mainly related to pulmonary hypoplasia (PH) and pulmonary vascular remodeling that leads to pulmonary hypertension (PHTN). Over the last five decades, research efforts have focused on modeling CDH not only to study the pathophysiology of the diaphragmatic defect, pulmonary hypoplasia, and pulmonary hypertension, but also to identify therapies that would promote lung growth and maturation, and correct vascular remodeling. As CDH is a multifactorial condition whose etiology remains unknown, there is not a single model of CDH, rather several ones that replicate different aspects of this disease. While small animals like the mouse and the rat have mainly been used to uncover biological pathways underlying the diaphragmatic defect and poor lung growth, larger animals like the lamb and the rabbit models have been instrumental for pursuing medical and surgical interventions. Overall, the use of animal models has indeed advanced our knowledge on CDH and helped us test innovative therapeutic options. For example, the lamb model of CDH has been the paradigm for testing fetal surgical procedures, including tracheal occlusion, which has been translated to clinical use. In this review, we outline the induction protocols of CDH in animals with the use of chemicals, dietary changes, genetic alterations, and surgical maneuvers, and we describe the studies that have translated experimental results to the bedside.

Maternal exposure to ambient cadmium levels, maternal smoking during pregnancy, and congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a rare musculoskeletal birth defect with a prevalence of 2.61 per 10,000 in the United States. There is limited evidence for ambient air pollutants in the etiology of CDH in humans. OBJECTIVES: We investigated the role of maternal exposure to ambient cadmium as a risk factor for CDH (overall and stratified by isolated and non-isolated subtypes) in Florida and whether maternal smoking during pregnancy was an effect modifier of this association. METHODS: We conducted a population-based, retrospective cohort study using data from the 1999-2012 Florida Birth Defects Registry linked to the National Air Toxic Assessment database. Analyses included chi-square tests; multilevel Poisson regression models to calculate measures of association between cadmium and CDH; and stratified analyses to examine effect modification by maternal smoking status. RESULTS: The study population consisted of 2,591,395 live births including 840 CDH cases. We did not find evidence for an association between maternal exposure to ambient cadmium concentration and CDH. We observed a 24% increased risk of CDH among isolated cases in the highest quartile of cadmium exposure (95% confidence interval [CI]: 1.00, 1.55). Although we were limited by small sample size for CDH cases, we found that among mothers who smoked during pregnancy, exposure to the highest quartile of cadmium was associated with more than two times higher risk for CDH among overall (95%CI: 1.04, 4.39) and isolated (95%CI: 1.07, 5.57) cases. CONCLUSIONS: Additional research is needed to elucidate the mechanism by which maternal ambient cadmium exposure may increase the risk of CDH in offspring, and the extent to which maternal smoking during pregnancy modifies this association.

Vascular and ventilatory mechanical responses in three different stages of pulmonary development in the rabbit model of congenital diaphragmatic hernia 1.

PURPOSE: To evaluate the vascular ventilatory response in different stages of lung development and to compare them to the neonates with congenital diaphragmatic hernia (CDH) in a rabbit model. METHODS: New Zealand rabbits were divided into 8 groups (n=5): E25, E27, E30, and CDH. All groups were ventilated on a FlexiVent (Scireq, Montreal, QC, Canada), compounding the other 4 groups. The CDH surgery was performed at E25 and the harvest at E30. Dynamic compliance (CRS), dynamic elastance (ERS) and dynamic resistance (RRS) were measured every 4 min/24 min. Median wall thickness (MWT) and airspace were measured. ANOVA Bonferroni tests were used to perform statistical analysis. Significance was considered when p<0.05. RESULTS: CRS was higher in E30 compared to all other groups (p<0.05). CRS and RRS of CDH and E27 were similar and were higher in E25 (p<0.05). MWT was decreased according to the gestational age, was increased in E27V and E30V (p<0.05) and decreased in CDHV (p<0.05), airspace was decreased in E25 and increased in all ventilated groups (p<0.05). CONCLUSIONS: The ventilation response of congenital diaphragmatic hernia is like the pseudoglandular stage of the lung development. These findings add information about the physiology of pulmonary ventilation in CDH.

Prenatal treatment with rosiglitazone attenuates vascular remodeling and pulmonary monocyte influx in experimental congenital diaphragmatic hernia.

INTRODUCTION: Extensive vascular remodeling causing pulmonary hypertension (PH) represents a major cause of mortality in patients with congenital diaphragmatic hernia (CDH). The chemokine monocyte chemoattractant protein-1 (MCP-1) is a biomarker for the severity of PH and its activation is accompanied by pulmonary influx of monocytes and extensive vascular remodeling. MCP-1 activation can be reversed by application of rosiglitazone (thiazolidinedione). We performed this study to evaluate the role of MCP-1 for the pathogenesis of PH in experimental CDH. We hypothesized that vascular remodeling and MCP-1 activation is accompanied by pulmonary influx of fetal monocytes and can be attenuated by prenatal treatment with rosiglitazone. METHODS: In a first set of experiments pregnant rats were treated with either nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were harvested on D21 and divided into CDH and control. Quantitative real-time polymerase chain reaction, Western blot (WB), and immunohistochemistry (IHC) were used to evaluate MCP-1 expression, activation, and localization. Quantification and localization of pulmonary monocytes/macrophages were carried out by IHC. In a second set of experiments nitrofen-exposed dams were randomly assigned to prenatal treatment with rosiglitazone or placebo on D18+D19. Fetal lungs were harvested on D21, divided into control, CDH+rosiglitazone, and CDH+placebo and evaluated by WB as well as IHC. RESULTS: Increased thickness of pulmonary arteries of CDH fetuses was accompanied by increased systemic and perivascular MCP-1 protein expression and significantly higher amounts of pulmonary monocytes/macrophages compared to controls (p<0.01). These effects were reversed by prenatal treatment with rosiglitazone (p<0.01 vs. CDH+P; control). CONCLUSION: Prenatal treatment with rosiglitazone has the potential to attenuate activation of pulmonary MCP-1, pulmonary monocyte influx, and vascular remodeling in experimental CDH. These results provide a basis for future research on prenatal immunomodulation as a novel treatment strategy to decrease secondary effects of PH in CDH.

Vascular and ventilatory mechanical responses in three different stages of pulmonary development in the rabbit model of congenital diaphragmatic hernia

Abstract Purpose: To evaluate the vascular ventilatory response in different stages of lung development and to compare them to the neonates with congenital diaphragmatic hernia (CDH) in a rabbit model. Methods: New Zealand rabbits were divided into 8 groups (n=5): E25, E27, E30, and CDH. All groups were ventilated on a FlexiVent (Scireq, Montreal, QC, Canada), compounding the other 4 groups. The CDH surgery was performed at E25 and the harvest at E30. Dynamic compliance (CRS), dynamic elastance (ERS) and dynamic resistance (RRS) were measured every 4 min/24 min. Median wall thickness (MWT) and airspace were measured. ANOVA Bonferroni tests were used to perform statistical analysis. Significance was considered when p<0.05. Results: CRS was higher in E30 compared to all other groups (p<0.05). CRS and RRS of CDH and E27 were similar and were higher in E25 (p<0.05). MWT was decreased according to the gestational age, was increased in E27V and E30V (p<0.05) and decreased in CDHV (p<0.05), airspace was decreased in E25 and increased in all ventilated groups (p<0.05). Conclusions: The ventilation response of congenital diaphragmatic hernia is like the pseudoglandular stage of the lung development. These findings add information about the physiology of pulmonary ventilation in CDH.

PBX transcription factors drive pulmonary vascular adaptation to birth.

A critical event in the adaptation to extrauterine life is relaxation of the pulmonary vasculature at birth, allowing for a rapid increase in pulmonary blood flow that is essential for efficient gas exchange. Failure of this transition leads to pulmonary hypertension (PH), a major cause of newborn mortality associated with preterm birth, infection, hypoxia, and malformations including congenital diaphragmatic hernia (CDH). While individual vasoconstrictor and dilator genes have been identified, the coordination of their expression is not well understood. Here, we found that lung mesenchyme-specific deletion of CDH-implicated genes encoding pre-B cell leukemia transcription factors (Pbx) led to lethal PH in mice shortly after birth. Loss of Pbx genes resulted in the misexpression of both vasoconstrictors and vasodilators in multiple pathways that converge to increase phosphorylation of myosin in vascular smooth muscle (VSM) cells, causing persistent constriction. While targeting endothelin and angiotensin, which are upstream regulators that promote VSM contraction, was not effective, treatment with the Rho-kinase inhibitor Y-27632 reduced vessel constriction and PH in Pbx-mutant mice. These results demonstrate a lung-intrinsic, herniation-independent cause of PH in CDH. More broadly, our findings indicate that neonatal PH can result from perturbation of multiple pathways and suggest that targeting the downstream common effectors may be a more effective treatment for neonatal PH.

Incarcerated right-sided diaphragmatic hernia in a patient undergoing Roux-en-Y gastric bypass

Bochdalek hernia is the most common congenital diaphragmatic hernia. Its symptoms are normally diagnosed and treated during the neonatal period. Conversely, in adults it is usually asymptomatic and, as a consequence, this group is misdiagnosed. A case of a 64-year-old female patient with an uncommon incarcerated right-sided diaphragmatic hernia formed three years after a Roux-en-Y gastric bypass and a significant weight loss is reported. The importance of this abnormality as a complication of the bariatric surgery should be considered(AU)

Síndrome PAGOD y anomalías vasculares: ¿es un defecto de la angiogénesis embrionaria? Un nuevo caso y revisión / PAGOD syndrome and vascular anomalies: is a defect embryonic angiogenesis? A case report and review

El Síndrome PAGOD es un acrónimo de hipoplasia de pulmón y arterias pulmonares, agonadismo, onfalocele / defecto diafragmático y dextrocardia. Se describe una serie de 21 pacientes, en la cual, 90,5 % presentó un cariotipo 46,XY y solo dos casos 46,XX; el 66,6 % exhibió un fenotipo femenino y 28,6 % genitales ambiguos. La ocurrencia de dos paciente 46,XX excluye al cromosoma Y como portador del defecto genético y plantea la posibilidad de una herencia recesiva ligada al cromosoma X, sin descartar que los casos observados en hermanos puedan deberse a mutaciones en otros genes como STRA6, VEGFA, VEGFB, VEGFC, transcritos de empalmes alternativos de VEGFA, HIF1, HIF2, entre otros. Las malformaciones congénitas observadas en los pacientes fueron: genitales y gónadas 85,7 %, diafragma y pared 66,6 %, cardíaco 80,9 %, pulmonar 71,4 %, vascular 80,9 % y abdomen 42,8 %. La revisión de los pacientes ha demostrado un alto grado de variabilidad en la expresividad de malformaciones de órganos, aparatos o sistemas. Las malformaciones vasculares representan un componente importante y característico del síndrome PAGOD y cuya base morfogenética del síndrome pueda deberse a un defecto de la angiogénesis embrionaria temprana con repercusión en la organogénesis de aparatos y sistemas. Dentro de los genes relacionados con el remodelamiento vascular durante la embriogénesis, regeneración tisular y carcinogénesis está el Factor de Crecimiento del Endotelio Vascular D (VEGFD), localizado en Xp22.31, con expresión en pulmón, corazón, intestino delgado, pulmón fetal, útero, mamas, tejido neural y neuroblastoma, el cual representa un fuerte candidato para su análisis molecular como una de las posibles causa del síndrome.

PAGOD Syndrome is an acronym for lung and pulmonary arteries hypoplasia, agonadism, omphalocele / diaphragmatic defect and dextrocardia. A series of 21 patients is described, where 90.5% had a 46,XY karyotype and only two cases 46,XX; 66.6% exhibited a female phenotype and 28.6% ambiguous genitalia. The occurrence of two patients 46,XX excludes the Y chromosome as a carrier of the genetic defect and raises the possibility of a recessive X-linked inheritance, without ruling out that the observed cases in siblings may be due to mutations in other genes as Stra6, VEGFA, VEGFB, VEGFC, and alternative splicing of transcripts VEGFA, HIF1, HIF2, among others. Congenital malformations were observed in patients’ genitals and gonads 85.7%, 66.6% in diaphragm and abdominal wall , heart 80.9%, 71.4% lungs, blood vessels 80.9% and 42.8% in abdomen. The review of patients has demonstrated a high degree of variability in the expression of malformations of organs and organ systems. Vascular malformations represent an important and characteristic component of PAGOD syndrome and whose base morphogenetic syndrome may be due to a defect in early embryonic angiogenesis with impact on organogenesis and system development. Among genes related to vascular remodeling during embryogenesis, tissue regeneration and carcinogenesis, the Endothelial Growth Factor D Vascular (VEGFD), located in the Xp22.31 region, with expression in lung, heart, small intestine, uterus, breast, neuroblastoma and neural tissue, represents a strong candidate for molecular analysis as a cause of the syndrome.

PAGOD syndrome and vascular anomalies: is a defect embryonic angiogenesis? A case report and review.

PAGOD Syndrome is an acronym for lung and pulmonary arteries hypoplasia, agonadism, omphalocele / diaphragmatic defect and dextrocardia. A series of 21 patients is described, where 90.5% had a 46,XY karyotype and only two cases 46,XX; 66.6% exhibited a female phenotype and 28.6% ambiguous genitalia. The occurrence of two patients 46,XX excludes the Y chromosome as a carrier of the genetic defect and raises the possibility of a recessive X-linked inheritance, without ruling out that the observed cases in siblings may be due to mutations in other genes as Stra6, VEGFA, VEGFB, VEGFC, and alternative splicing of transcripts VEGFA, HIF1, HIF2, among others. Congenital malformations were observed in patients' genitals and gonads 85.7%, 66.6% in diaphragm and abdominal wall , heart 80.9%, 71.4% lungs, blood vessels 80.9% and 42.8% in abdomen. The review of patients has demonstrated a high degree of variability in the expression of malformations of organs and organ systems. Vascular malformations represent an important and characteristic component of PAGOD syndrome and whose base morphogenetic syndrome may be due to a defect in early embryonic angiogenesis with impact on organogenesis and system development. Among genes related to vascular remodeling during embryogenesis, tissue regeneration and carcinogenesis, the Endothelial Growth Factor D Vascular (VEGFD), located in the Xp22.31 region, with expression in lung, heart, small intestine, uterus, breast, neuroblastoma and neural tissue, represents a strong candidate for molecular analysis as a cause of the syndrome.

Wt1 and ß-catenin cooperatively regulate diaphragm development in the mouse.

The developing diaphragm consists of various differentiating cell types, many of which are not well characterized during organogenesis. One important but incompletely understood tissue, the diaphragmatic mesothelium, is distinctively present from early stages of development. Congenital Diaphragmatic Hernia (CDH) occurs in humans when diaphragm tissue is lost during development, resulting in high morbidity and mortality postnatally. We utilized a Wilms Tumor 1 (Wt1) mutant mouse model to investigate the involvement of the mesothelium in normal diaphragm signaling and development. Additionally, we developed and characterized a Wt1(CreERT2)-driven ß-catenin loss-of-function model of CDH after finding that canonical Wnt signaling and ß-catenin are reduced in Wt1 mutant mesothelium. Mice with ß-catenin loss or constitutive activation induced in the Wt1 lineage are only affected when tamoxifen injection occurs between E10.5 and E11.5, revealing a critical time-frame for Wt1/ ß-catenin activity. Conditional ß-catenin loss phenocopies the Wt1 mutant diaphragm defect, while constitutive activation of ß-catenin on the Wt1 mutant background is sufficient to close the diaphragm defect. Proliferation and apoptosis are affected, but primarily these genetic manipulations appear to lead to a change in normal diaphragm differentiation. Our data suggest a fundamental role for mesothelial signaling in proper formation of the diaphragm.

Iatrogenic diaphragmatic hernia in paediatric patients.

BACKGROUND AND METHODS: Iatrogenic diaphragmatic hernia in childhood is rare, with only scanty case reports available in the literature. It is a potentially life-threatening condition resulting in intestinal obstruction and bowel strangulation. In this study, we retrospectively reviewed four patients with iatrogenic diaphragmatic hernia following right hepatic trisectionectomy with caudate lobectomy and liver transplantation in a tertiary referral centre. The patient characteristics, clinical presentation and risk factors were assessed. CONCLUSIONS: Iatrogenic diaphragmatic hernia should be considered in differential diagnosis in paediatric patients presenting with intestinal obstruction or respiratory distress after hepatic resection or liver transplantation for early diagnosis and management.

Risk factors for the recurrence of the congenital diaphragmatic hernia-report from the long-term follow-up study of Japanese CDH study group.

AIM OF THE STUDY: Few follow-up studies focused on the recurrence regarding the postoperative course of congenital diaphragmatic hernia (CDH) survivors. The aim of this study was to report on risk factor for CDH patients who had the recurrence during the follow-up. MATERIALS AND METHODS: A multicenter retrospective survey was conducted on neonates diagnosed to have CDH between January 2006 and December 2010. Follow-up survey was conducted between September 2013 and October 2013 (ethical approval: No. 25-222). Nine institutions agreed to participate in this survey. Out of 228, 182 (79.8%) patients were alive and 180 patients were included in this study. Two patients were excluded because the defect had not repaired at the primary operation. The patients were divided into the recurrence group (n=21) and the nonrecurrence group (n=159). Postnatal and postoperative variables were compared between these two groups. Baseline variables which showed significance in univariate analysis were entered into multiple logistic regression analysis for analyzing the recurrence. A value of p<0.05 was considered to be statistically significant by using the JMP software program (version 9; SAS Institute, Inc, Cary, North Carolina, United States). MAIN RESULTS: Out of 180, 21 (11.7%) CDH neonates had the recurrence during the course of the follow-up. Five (2.8%) patients had the recurrence before primary discharge and 16 (8.9%) patients had the recurrence after discharge. Univariate analysis showed that liver herniation (crude odds ratio [OR], 7.4; 95% confidence interval [CI], 2.73-23.68), defect size C and D, proposed by the CDH Study Group (crude OR, 7.09; 95% CI, 2.73-19.99) and patch repair (crude OR, 5.00; 95% CI, 1.91-14.70) were risk factors. Multivariate logistic regression analysis showed liver herniation (adjusted OR, 3.96; 95% CI, 1.01-16.92) was the risk factor for the recurrence. CONCLUSION: A wide spectrum of the disease severity and the rarity of the disease mask the risk of the recurrence for CDH patients. This study showed the only factor to predict the recurrence was the liver herniation. These data will be helpful for providing information for the long-term follow-up of the CDH patients.

Congenital diaphragmatic hernia: where and what is the evidence?

Congenital diaphragmatic hernia (CDH) retains high mortality and morbidity due to lung hypoplasia, pulmonary hypertension and severe co-existent anomalies. This article offers a comprehensive state-of-the-art review for the paediatric surgeon whilst also describing key contributions from the basic sciences in the search to uncover the cause of the birth defect together with efforts to develop new and better therapies for CDH.

Morgagni hernia with respiratory failure aggravated by noninvasive positive pressure ventilation: a case report and overview of the literature.

An elderly woman diagnosed with multiple myeloma (MM) in 2007 had improved with chemotherapy. She had severe kyphosis and a diaphragmatic hernia (DH), but no respiratory symptoms. In 2011, because of thoracic deformity and emaciation, we advised her to continue the previously prescribed domiciliary noninvasive positive pressure ventilation (NPPV) therapy for chronic type II respiratory failure. However, she refused to continue NPPV. She was later admitted for deterioration in respiratory status and carbon dioxide (CO2) narcosis. We believed her low adherence to domiciliary NPPV caused CO2 narcosis; hence, we advised her to continue domiciliary NPPV and she complied. In May 2012, the now 79-year-old patient was admitted for acute exacerbation of chronic respiratory failure and CO2 narcosis. Chest imaging suggested that DH had caused a deterioration of her status. She underwent laparoscopic diaphragmatic hernia repair. Operative findings revealed a retrosternal hernia sac, and she was diagnosed as having a Morgagni hernia (MH). Her respiratory status subsequently improved. We hypothesize that NPPV increased intra-abdominal pressure, thereby worsening the MH and exacerbating respiratory failure. We believe that clinicians should be cautious when prescribing NPPV for MH patients.

Incidence, predictors and outcomes of congenital diaphragmatic hernia: a population-based study of 32 million births in the United States.

OBJECTIVES: To evaluate the incidence, risk factors and neonatal outcomes associated with a congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a population-based cohort study using the CDC's Linked Birth-Infant Death and Fetal Death data files on all births and foetal deaths in USA between 1995 and 2002. We estimated the yearly incidence of CDH and measured its adjusted effect on various outcomes using unconditional logistic regression analysis. RESULTS: About 32,145,448 births during the 8-year study period met the study's inclusion criteria. The incidence of CDH was 1.93/10,000 births. Risk factors for the development of CDH included foetal male gender [OR 1.12, 95% CI: 1.06, 1.17], maternal age beyond 40 [OR 1.51, 95% CI: 1.26, 1.80], Caucasian ethnicity [OR 1.15, 95% CI: 1.10, 1.21], smoking [OR 1.34, 95% CI: 1.22, 1.46] and alcohol use during pregnancy [OR 1.37, 95% CI: 1.05, 1.79]. As compared to foetuses with no CDH, foetuses with CDH were at an increased risk of preterm birth [OR 2.90, 95% CI: 2.72, 3.11], intrauterine growth restriction [OR 3.84, 95% CI: 3.51, 4.18], stillbirth [OR 9.65, 95% CI: 8.20, 11.37] and overall infant death [OR: 94.80, 95% CI: 88.78, 101.23]. The 1-year mortality was 45.89%. CONCLUSION: Congenital diaphragmatic hernia is strongly associated with an increased risk of adverse pregnancy, foetal and neonatal outcomes. These findings may be helpful in counselling pregnancies affected by CDH, and may aid in the understanding of the burden of this condition at the public health level.