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2.
Ann Surg ; 274(1): 186-194, 2021 07 01.
Article in English | MEDLINE | ID: mdl-31425289

ABSTRACT

OBJECTIVE: To determine the optimal timing of congenital diaphragmatic hernia (CDH) repair after extracorporeal membrane oxygenation (ECMO) cannulation. SUMMARY BACKGROUND DATA: The timing of CDH repair after ECMO cannulation remains a controversial topic due to studies with low power or strong selection bias. METHODS: This is a 2-aim retrospective cohort study based on the CDH Study Group registry for the period of 2007-2017. Aim 1-Compare On versus After ECMO repair. Aim 2-Compare Early versus Late repair on ECMO. In order to minimize selection bias and account for non-repairs, subjects in each aim were stratified into study groups based on their treatment center's characteristics. In each aim, the study groups were matched based on propensity score (PS). The main outcomes included mortality rate and incidence of non-repair. RESULTS: In aim 1, 136 patients remained in each group after PS matching. Compared to the After ECMO group, patients in the On ECMO group demonstrated a lower mortality rate, hazard ratio (HR) 0.54 (0.38, 0.77) (P < 0.001), and lower incidence of non-repair, 5.9% versus 33.8% (P < 0.001). In aim 2, 77 patients remained in each group after PS matching. Compared to the Late group, Early repair of CDH on ECMO was associated with a lower mortality rate, HR 0.51 (0.33, 0.77) (P = 0.002), and lower incidence of non-repair, 9.1% versus 44.2% (P < 0.001). CONCLUSIONS: The approach of early repair after ECMO cannulation is associated with improved survival compared to delayed surgical correction.


Subject(s)
Extracorporeal Membrane Oxygenation , Hernias, Diaphragmatic, Congenital/surgery , Herniorrhaphy , Time-to-Treatment , Female , Humans , Infant, Newborn , Male , Propensity Score , Proportional Hazards Models , Retrospective Studies , Survival Analysis
3.
J Pediatr ; 219: 160-166.e2, 2020 04.
Article in English | MEDLINE | ID: mdl-31704054

ABSTRACT

OBJECTIVE: To determine the natural history of pulmonary function for survivors of congenital diaphragmatic hernia (CDH). STUDY DESIGN: This was a retrospective cohort study of survivors of CDH born during 1991-2016 and followed at our institution. A generalized linear model was fitted to assess the longitudinal trends of ventilation (V), perfusion (Q), and V/Q mismatch. The association between V/Q ratio and body mass index percentile as well as functional status was also assessed with a generalized linear model. RESULTS: During the study period, 212 patients had at least one V/Q study. The average ipsilateral V/Q of the cohort increased over time (P < .01), an effect driven by progressive reduction in relative perfusion (P = .012). A higher V/Q ratio was correlated with lower body mass index percentile (P < .001) and higher probability of poor functional status (New York Heart Association class III or IV) (P = .045). CONCLUSIONS: In this cohort of survivors of CDH with more severe disease characteristics, V/Q mismatch worsens over time, primarily because of progressive perfusion deficit of the ipsilateral side. V/Q scans may be useful in identifying patients with CDH who are at risk for poor growth and functional status.


Subject(s)
Hernias, Diaphragmatic, Congenital/physiopathology , Lung/physiopathology , Ventilation-Perfusion Ratio , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Longitudinal Studies , Male , Retrospective Studies , Young Adult
4.
J Pediatr ; 216: 158-164.e2, 2020 01.
Article in English | MEDLINE | ID: mdl-31704056

ABSTRACT

OBJECTIVE: To analyze longitudinal trends of pulmonary function testing in patients with congenital diaphragmatic hernia (CDH) followed in our multidisciplinary clinic. STUDY DESIGN: This was a retrospective cohort study of CDH patients born between 1991 and 2013. A linear mixed effects model was fitted to estimate the trends of percent predicted forced expiratory volume in 1 second (FEV1pp), percent predicted forced vital capacity (FVCpp), and FEV1/FVC over time. RESULTS: Of 268 patients with CDH who survived to discharge, 119 had at least 1 pulmonary function test study. The FEV1pp (P < .001), FVCpp (P = .017), and FEV1/FVC (P = .001) decreased with age. Compared with defect size A/B, those with defect size C/D had lower FEV1pp by an average of 11.5% (95% CI, 2.9%-20.1%; P = .010). A history of oxygen use at initial hospital discharge also correlated with decreased FEV1pp by an average of 8.0% (95% CI, 1.2%-15.0%; P = .023). CONCLUSIONS: In a select cohort of CDH survivors, average pulmonary function declines with age relative to expected population normative values. Those with severe CDH represent a population at risk for worsening pulmonary function test measurements who may benefit from recognition and monitoring for complications.


Subject(s)
Forced Expiratory Volume , Hernias, Diaphragmatic, Congenital/physiopathology , Vital Capacity , Cohort Studies , Female , Humans , Infant, Newborn , Longitudinal Studies , Male , Respiratory Function Tests , Retrospective Studies
5.
Pediatr Surg Int ; 36(3): 325-331, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31707604

ABSTRACT

PURPOSE: This retrospective cohort study compares the natural history of patients with extralobar sequestrations (ELS) who do not undergo intervention with those who undergo resection to assess the safety of non-operative management. METHODS: 126 patients with pulmonary sequestrations or congenital pulmonary airway malformations born between 1999 and 2016 were identified. 49 patients had ELS on postnatal imaging, but two were excluded for associated congenital diaphragmatic hernia. Demographic and clinical data were retrospectively reviewed, with phone follow-up for non-operative patients with no records for > 1 year. Statistical analysis was by Fisher's exact test or Wilcoxon signed-rank test (two-tailed p < 0.05). RESULTS: 40% (19/47) were managed non-operatively and 60% (28/47) underwent resection. Non-operative patients were less likely to have an intrathoracic ELS: 47% (9/19) vs. 75% (21/28), p = 0.07. No symptoms were attributable directly to the ELS. Non-operative patients had median follow-up 3.2 years, during which time 88% (15/17) of ELS decreased in size on serial imaging. For patients who underwent resection, there was 100% concordance between imaging and intraoperative findings. There was no evidence of inflammation, infection or malignancy on final pathology, though 57% (16/28) of resected lesions had foci of non-aerated cysts. CONCLUSIONS: Although further longitudinal study is required, this study supports the safety of non-operative ELS management.


Subject(s)
Bronchopulmonary Sequestration/therapy , Conservative Treatment/methods , Bronchopulmonary Sequestration/diagnosis , Child , Child, Preschool , Female , Humans , Longitudinal Studies , Male , Pneumonectomy , Retrospective Studies , Treatment Outcome
6.
PLoS Genet ; 14(12): e1007822, 2018 12.
Article in English | MEDLINE | ID: mdl-30532227

ABSTRACT

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is often accompanied by other congenital anomalies. Previous exome sequencing studies for CDH have supported a role of de novo damaging variants but did not identify any recurrently mutated genes. To investigate further the genetics of CDH, we analyzed de novo coding variants in 362 proband-parent trios including 271 new trios reported in this study. We identified four unrelated individuals with damaging de novo variants in MYRF (P = 5.3x10(-8)), including one likely gene-disrupting (LGD) and three deleterious missense (D-mis) variants. Eight additional individuals with de novo LGD or missense variants were identified from our other genetic studies or from the literature. Common phenotypes of MYRF de novo variant carriers include CDH, congenital heart disease and genitourinary abnormalities, suggesting that it represents a novel syndrome. MYRF is a membrane associated transcriptional factor highly expressed in developing diaphragm and is depleted of LGD variants in the general population. All de novo missense variants aggregated in two functional protein domains. Analyzing the transcriptome of patient-derived diaphragm fibroblast cells suggest that disease associated variants abolish the transcription factor activity. Furthermore, we showed that the remaining genes with damaging variants in CDH significantly overlap with genes implicated in other developmental disorders. Gene expression patterns and patient phenotypes support pleiotropic effects of damaging variants in these genes on CDH and other developmental disorders. Finally, functional enrichment analysis implicates the disruption of regulation of gene expression, kinase activities, intra-cellular signaling, and cytoskeleton organization as pathogenic mechanisms in CDH.


Subject(s)
Genetic Variation , Hernias, Diaphragmatic, Congenital/genetics , Membrane Proteins/genetics , Mutation , Transcription Factors/genetics , Child, Preschool , DNA Copy Number Variations , Developmental Disabilities/genetics , Female , Heart Defects, Congenital/genetics , Hernias, Diaphragmatic, Congenital/metabolism , Humans , Infant, Newborn , Longitudinal Studies , Male , Membrane Proteins/metabolism , Mutation, Missense , Phenotype , Sequence Analysis, RNA , Syndrome , Transcription Factors/metabolism , Exome Sequencing , Whole Genome Sequencing
7.
Patient Educ Couns ; 101(9): 1624-1629, 2018 09.
Article in English | MEDLINE | ID: mdl-29729857

ABSTRACT

BACKGROUND: Inadequate patient knowledge about transplantation can result in low patient satisfaction and contribute to poor clinical outcomes. The purpose of this patient-oriented research project was to develop an educational intervention for patients awaiting kidney transplantation. METHODS: An educational intervention was developed by patients and health care providers, experts in medication adherence, video education, motivational psychology, and cultural education. Project objectives were defined and content was guided by a series of studies conducted with stakeholders. A review process was undertaken with additional patients, external health care providers and ninth grade high school students and edits were applied accordingly. RESULTS: A set of six educational videos, ranging in length from 3 to 24 min, was created to describe the transplant process. The videos are patient friendly in design, and incorporate animations to explain complex information to accommodate low health literacy, and patient testimonials align the content with principles of adult learning theory. Feedback from external patient reviews [n = 8], external care providers [n = 13] and students [n = 26], indicate that the mini-series is informative and useful. CONCLUSION: Patient involvement significantly influenced the development of a video series about kidney transplantation. PRACTICE IMPLICATIONS: Patient engagement is integral for developing high quality and relevant educational interventions.


Subject(s)
Kidney Transplantation/education , Patient Education as Topic/methods , Patient Participation , Videotape Recording , Health Personnel , Humans
8.
Proc Natl Acad Sci U S A ; 115(20): 5247-5252, 2018 05 15.
Article in English | MEDLINE | ID: mdl-29712845

ABSTRACT

Congenital diaphragmatic hernia (CDH), characterized by malformation of the diaphragm and hypoplasia of the lungs, is one of the most common and severe birth defects, and is associated with high morbidity and mortality rates. There is growing evidence demonstrating that genetic factors contribute to CDH, although the pathogenesis remains largely elusive. Single-nucleotide polymorphisms have been studied in recent whole-exome sequencing efforts, but larger copy number variants (CNVs) have not yet been studied on a large scale in a case control study. To capture CNVs within CDH candidate regions, we developed and tested a targeted array comparative genomic hybridization platform to identify CNVs within 140 regions in 196 patients and 987 healthy controls, and identified six significant CNVs that were either unique to patients or enriched in patients compared with controls. These CDH-associated CNVs reveal high-priority candidate genes including HLX, LHX1, and HNF1B We also discuss CNVs that are present in only one patient in the cohort but have additional evidence of pathogenicity, including extremely rare large and/or de novo CNVs. The candidate genes within these predicted disease-causing CNVs form functional networks with other known CDH genes and play putative roles in DNA binding/transcription regulation and embryonic development. These data substantiate the importance of CNVs in the etiology of CDH, identify CDH candidate genes and pathways, and highlight the importance of ongoing analysis of CNVs in the study of CDH and other structural birth defects.


Subject(s)
Comparative Genomic Hybridization/methods , DNA Copy Number Variations , Genetic Markers , Hernias, Diaphragmatic, Congenital/genetics , Polymorphism, Single Nucleotide , Case-Control Studies , Humans , Prognosis
9.
Ann Surg ; 267(5): 977-982, 2018 05.
Article in English | MEDLINE | ID: mdl-28134682

ABSTRACT

OBJECTIVE: The objectives of this study were (i) to evaluate infants with congenital diaphragmatic hernia (CDH) that do not undergo repair, (ii) to identify nonrepair rate by institution, and (iii) to compare institutional outcomes based on nonrepair rate. BACKGROUND: Approximately 20% of infants with CDH go unrepaired and the threshold to offer surgical repair is variable. METHODS: Data were abstracted from a multicenter, prospectively collected database. Standard clinical variables, including repair (or nonrepair), and outcome were analyzed. Institutions were grouped based on volume and rate of nonrepair. Preoperative mortality predictors were identified using logistic regression, expected mortality for each center was calculated, and observed /expected (O/E) ratios were computed for center groups and compared by Kruskal-Wallis ANOVA. RESULTS: A total of 3965 infants with CDH were identified and 691 infants (17.5%) were not repaired. Nonrepaired patients had lower Apgar scores (P < 0.05) and increased incidence of anomalies (P < 0.0001). Low-volume centers ("Lo", n=44 total, < 10 CDH pts/yr) and high-volume centers ("Hi", n = 21) had median nonrepair rates of 19.8% (range 0%-66.7%) and 16.7% (5.1%-38.5%), respectively. High-volume centers were further dichotomized by rate of nonrepair (HiLo = 5.1-16.7% and HiHi = 17.6-38.5%), leaving 3 groups: HiLo, HiHi, and Lo. Predictors of mortality were lower birth weight, lower Apgar scores, prenatal diagnosis, and presence of congenital anomalies. O/E ratios for mortality in the HiLo, HiHi, and Lo groups were 0.81, 0.94, and 1.21, respectively (P < 0.0001). For every 100 CDH patients, HiLo centers have 2.73 (2.4-3.1, 95% confidence interval) survivors beyond expectation. CONCLUSIONS: There are significant differences between repaired and nonrepaired CDH infants and significant center variation in rate of nonrepair exists. Aggressive surgical management, leading to a low rate of nonrepair, is associated with improved risk-adjusted mortality.


Subject(s)
Forecasting , Hernias, Diaphragmatic, Congenital/surgery , Herniorrhaphy/methods , Registries , Female , Follow-Up Studies , Hernias, Diaphragmatic, Congenital/mortality , Humans , Infant , Infant, Newborn , Male , Prospective Studies , Survival Rate/trends , Treatment Outcome , United States/epidemiology
10.
Prog Transplant ; 27(1): 58-64, 2017 03.
Article in English | MEDLINE | ID: mdl-28555528

ABSTRACT

CONTEXT: Poor knowledge about immunosuppressive (IS) medications remains a major problem for patients in the posttransplant setting. Therefore, more effective educational strategies in the pretransplant setting are being considered as a possible method to improve knowledge and readiness for the challenges of posttransplant care. However, the most effective/relevant content of a pretransplant educational program is yet to be determined. OBJECTIVE: To identify pretransplant education topics from the posttransplant patient perspective. DESIGN: A focus group meeting was conducted among 7 high-functioning, stable adult kidney transplant recipients recruited from the Saskatchewan Transplant Program. Demographic information including age, gender, occupation, background/ethnicity, and time since transplant were recorded. A moderator, assistant moderator, and research assistant facilitated the 90-minute focus group meeting using a predetermined semistructured interview guide. The session was audio recorded and transcribed verbatim. Nvivo software was used to code the data and identify emerging themes exploring views of participants relating to the educational information required for pretransplant patients. RESULTS: Patients were satisfied with the education they had received. Ideas were classified into the following major themes-patient satisfaction, transplant waitlist, surgery, medications, posttransplant complications, lifestyle and monitoring, knowledge acquisition, illusion of control, and life changes posttransplant. Knowledge gaps were identified in all areas of the transplantation process and were not exclusive to IS medications. CONCLUSION: Misconceptions regarding transplantation were identified by a group of high-functioning, stable adult recipients who were satisfied with their clinical care. Future educational strategies should aim to address the entire transplantation process and not be limited to medications.


Subject(s)
Kidney Transplantation/education , Patient Education as Topic , Postoperative Care/education , Transplant Recipients/education , Adult , Aged , Female , Focus Groups , Humans , Immunosuppression Therapy , Male , Middle Aged , Patient Satisfaction , Saskatchewan
11.
J Pediatr Surg ; 52(6): 933-937, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28385427

ABSTRACT

PURPOSE: Percent predicted lung volume (PPLV)<15% on fetal MRI predicts high-risk CDH. Potential changes in PPLV throughout gestation and impact on risk stratification are unknown. We reviewed CDH patients with serial fetal MRIs to follow PPLV and determine correlation with postnatal outcomes. METHODS: CDH patients with serial fetal MRIs from 2005 to 2015 were included. We recorded prenatal MRI gestational age (GA) and PPLV, postnatal ECMO use, and survival. Data were analyzed by logistic regression and Fisher's exact test. RESULTS: 57 patients had 127 fetal MRI studies. PPLV decreased from mean 25.4% to 19.6% between GA 22.1 and 32.6weeks. A steeper decline in PPLV, regardless of final PPLV, was independently predictive of higher ECMO use (p=0.046) and death (p=0.045). All patients with first PPLV<15% remained high-risk with poor outcomes. Of those with first PPLV>15%, 31% dropped below 15%, having similar ECMO use as the high-risk cohort, but trending toward greater survival (p=0.09). Those with first and final PPLV>15% had significantly less ECMO use (p=0.015) and greater survival (p<0.001) than the high-risk cohort. CONCLUSIONS: On average, PPLV decreases throughout gestation in fetuses with CDH. Serial MRI is recommended for those with initial PPLV>15%, as clinical outcomes tend to mirror the lowest PPLV. TYPE OF STUDY: Treatment study LEVEL OF EVIDENCE: III.


Subject(s)
Hernias, Diaphragmatic, Congenital/diagnostic imaging , Lung/diagnostic imaging , Magnetic Resonance Imaging , Prenatal Diagnosis , Extracorporeal Membrane Oxygenation , Female , Follow-Up Studies , Gestational Age , Hernias, Diaphragmatic, Congenital/embryology , Hernias, Diaphragmatic, Congenital/mortality , Hernias, Diaphragmatic, Congenital/therapy , Humans , Infant, Newborn , Logistic Models , Lung/embryology , Lung/physiopathology , Lung Volume Measurements , Male , Pregnancy , Prognosis , Retrospective Studies
12.
Hum Genet ; 136(6): 679-691, 2017 06.
Article in English | MEDLINE | ID: mdl-28303347

ABSTRACT

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.


Subject(s)
Genome-Wide Association Study , Hernias, Diaphragmatic, Congenital/genetics , Gene Expression Regulation, Developmental , Humans , Protein Binding
13.
J Pediatr Surg ; 52(1): 22-25, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27836357

ABSTRACT

PURPOSE: In high-risk congenital diaphragmatic hernia (CDH), significant barotrauma or death can occur before extracorporeal membrane oxygenation (ECMO) can be initiated. We previously examined ex utero intrapartum treatment (EXIT)-to-ECMO in our most severe CDH patients, but demonstrated no survival advantage. We now report morbidity outcomes in survivors of this high-risk cohort to determine whether EXIT-to-ECMO conferred any benefit. METHODS: All CDH survivors with <15% predicted lung volume (PPLV) from September 1999 to December 2010 were included. We recorded prenatal imaging, defect size, and pulmonary, nutritional, cardiac, and neurodevelopmental outcomes. RESULTS: Seventeen survivors (8 EXIT-to-ECMO, 9 non-EXIT) had an average PPLV of 11.7%. Eight of 9 non-EXIT received ECMO within 2days. There were no significant defect size differences between groups, mostly left-sided (13/17) and type D (12/17). Average follow-up was 6.7years (0-13years). There were no statistically significant differences in outcomes, including supplemental oxygen, diuretics, gastrostomy, weight-for-age Z scores, fundoplication, pulmonary hypertension, stroke or intracranial hemorrhage rate, CDH recurrence, and reoperation. No survivor in our cohort was neurologically devastated. All had mild motor and/or speech delay, which improved in most. CONCLUSIONS: In this pilot series of severe CDH survivors, EXIT-to-ECMO confers neither significant survival nor long-term morbidity benefit. LEVEL OF EVIDENCE: Level III treatment study.


Subject(s)
Extracorporeal Membrane Oxygenation , Fetal Therapies/methods , Hernias, Diaphragmatic, Congenital/surgery , Barotrauma/etiology , Extracorporeal Membrane Oxygenation/adverse effects , Female , Fetal Therapies/adverse effects , Hernias, Diaphragmatic, Congenital/complications , Humans , Infant, Newborn , Male , Pilot Projects , Postoperative Complications , Retrospective Studies , Risk Factors , Survivors , Treatment Outcome
14.
Am J Med Genet A ; 170(9): 2457-61, 2016 09.
Article in English | MEDLINE | ID: mdl-27363585

ABSTRACT

COUP-TFII (NR2F2) is mapped to the 15q26 deletion hotspot associated with the common and highly morbid congenital diaphragmatic hernia (CDH). Conditional homozygous deletions of COUP-TFII in mice result in diaphragmatic defects analogous to the human Bochdalek-type hernia phenotype. Despite evidence from animal models however, mutations in the coding sequence of COUP-TFII have not been reported in patients, prompting the speculation that additional coding or non-coding sequences in the 15q26 locus are necessary for diaphragmatic hernias to develop. In this report, we describe a case of a patient with a heterozygous de novo COUP-TFII frameshift mutation, presenting with CDH and an atrial septal defect. The p.Pro33AlafsTer77 mutation specifically disrupts protein isoform 1 which contains the DNA binding domain. In addition, we review other COUP-TFII sequence variations and deletions that have been described in cases of CDH. We conclude that COUP-TFII mutations can cause diaphragmatic hernias, and should be included in the differential diagnosis of CDH patients, particularly those with comorbid congenital heart defects. © 2016 Wiley Periodicals, Inc.


Subject(s)
COUP Transcription Factor II/genetics , Frameshift Mutation , Genetic Association Studies , Hernias, Diaphragmatic, Congenital/diagnosis , Hernias, Diaphragmatic, Congenital/genetics , Phenotype , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Alleles , DNA Mutational Analysis , Female , Genotype , Humans , Infant, Newborn , Male , Pedigree , Polymorphism, Single Nucleotide
15.
Cureus ; 7(4): e263, 2015 Apr.
Article in English | MEDLINE | ID: mdl-26180687

ABSTRACT

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is utilized for cardiopulmonary failure. We aimed to qualify and quantify the predictors of morbidity and mortality in infants requiring VA-ECMO. METHODS: Data was collected from 170 centers participating in the extracorporeal life support organization (ELSO) registry. Relationships between in-hospital mortality and risk factors were assessed using logistic regression. Survival was defined as being discharged from the hospital. RESULTS: Six hundred and sixty-two eligible records were reviewed. Mortality occurred in 303 (46%) infants. Congenital diaphragmatic hernia patients (OR=3.83, 95% CI 1.96-7.49, p<0.001), cardiac failure with associated shock (OR= 2.90, 95% CI 1.46-5.77, p=0.002), and pulmonary failure including respiratory distress syndrome (OR=4.06, 95% CI 1.72-9.58, p=0.001) had the highest odds of mortality in this cohort. Birth weight (BW) < 3 kg (OR=1.83, 95% CI 1.21-2.78, p=0.004), E-CPR (OR=3.35, 95% CI 1.57-7.15, p=0.002), hemofiltration (OR=2.04, 95% CI 1.32-3.16, p=0.001), and dialysis (OR=6.13, 95% CI 1.70-22.1, p<0.001) were all independent predictors of mortality. CONCLUSION: Infants requiring VA-ECMO experience diverse sequelae and their mortality are high.

16.
J Pediatr Surg ; 50(5): 849-55, 2015 May.
Article in English | MEDLINE | ID: mdl-25783313

ABSTRACT

PURPOSE: Pulmonary support (PS) on day-of-life-30 (DOL-30) has been shown to be the strongest predictor of subsequent morbidity and in-patient mortality in congenital diaphragmatic hernia (CDH). We hypothesized that PS on DOL-30 can also predict long-term outcomes in CDH survivors. METHODS: We analyzed records of 201 CDH survivors followed by a single multidisciplinary clinic (1995-2010). Follow-up was 83 and 70% at 1 and 5years respectively. PS was defined as: (1) invasive support (n=44), (2) noninvasive support (n=54), or (3) room air (n=103). Logistic regression was used to estimate the adjusted association of PS on DOL-30 with outcomes at 1 and 5-years. RESULTS: Use of PS on DOL-30 was significantly associated with pulmonary and developmental morbidities at 1 and 5-years. Even after adjusting for defect-size and presence of ventilation/perfusion mismatch, greater PS on DOL-30 was associated with a significantly increased odds of requiring supplemental oxygen and developmental referral at 1-year, and asthma and developmental referral at 5-years. CONCLUSION: CDH survivors continue to have significant long-term pulmonary and developmental morbidities. PS on DOL-30 is a strong independent predictor of morbidity at 1 and 5-years and may be used as a simple prognostic tool to identify high-risk infants.


Subject(s)
Hernias, Diaphragmatic, Congenital/therapy , Respiration, Artificial/methods , Survivors , Child, Preschool , Female , Follow-Up Studies , Hernias, Diaphragmatic, Congenital/epidemiology , Humans , Infant , Infant, Newborn , Male , Massachusetts/epidemiology , Morbidity/trends , Prognosis , Survival Rate/trends , Time Factors
17.
J Pediatr Surg ; 50(1): 74-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25598097

ABSTRACT

BACKGROUND: Malnutrition is prevalent among congenital diaphragmatic hernia (CDH) survivors. We aimed to describe the nutritional status and factors that impact growth over the 12-months following discharge from the pediatric intensive care unit (PICU) in this cohort. METHODS: CDH survivors, who were discharged from the PICU from 2000 to 2010 with follow-up of at least 12months, were included. Nutritional intake, anthropometric, and clinical variables were recorded. Multivariable linear regression was used to determine factors associated with weight-for-age Z-scores (WAZ) at 12months. RESULTS: Data from 110 infants, 67% male, 50% patch repair, were analyzed. Median (IQR) WAZ for the cohort was -1.4 (-2.4 to -0.3) at PICU discharge and -0.4 (-1.3 to 0.2) at 12-months. The percentage of infants with significant malnutrition (WAZ<-2) decreased from 26% to 8.5% (p<0.001). Patch repair (p=0.009), protein intake<2.3g/kg/day (p=0.014), and birth weight (BW)<2.5kg (p<0.001) were associated with lower WAZ at 12-months. CONCLUSIONS: CDH survivors had a significantly improved nutritional status in the 12-months after PICU discharge. Patch repair, lower BW, and inadequate protein intake were significant predictors of lower WAZ at 12-months. A minimum protein intake in the PICU of 2.3g/kg/day was essential to ensure optimal growth in this cohort.


Subject(s)
Hernias, Diaphragmatic, Congenital/surgery , Nutritional Status , Adult , Body Weight , Child , Dietary Proteins/administration & dosage , Female , Humans , Infant , Intensive Care Units, Pediatric , Linear Models , Male , Retrospective Studies , Survivors
18.
Proc Natl Acad Sci U S A ; 111(34): 12450-5, 2014 Aug 26.
Article in English | MEDLINE | ID: mdl-25107291

ABSTRACT

Congenital diaphragmatic hernia (CDH) is a common and severe birth defect. Despite its clinical significance, the genetic and developmental pathways underlying this disorder are incompletely understood. In this study, we report a catalog of variants detected by a whole exome sequencing study on 275 individuals with CDH. Predicted pathogenic variants in genes previously identified in either humans or mice with diaphragm defects are enriched in our CDH cohort compared with 120 size-matched random gene sets. This enrichment was absent in control populations. Variants in these critical genes can be found in up to 30.9% of individuals with CDH. In addition, we filtered variants by using genes derived from regions of recurrent copy number variations in CDH, expression profiles of the developing diaphragm, protein interaction networks expanded from the known CDH-causing genes, and prioritized genes with ultrarare and highly disruptive variants, in 11.3% of CDH patients. These strategies have identified several high priority genes and developmental pathways that likely contribute to the CDH phenotype. These data are valuable for comparison of candidate genes generated from whole exome sequencing of other CDH cohorts or multiplex kindreds and provide ideal candidates for further functional studies. Furthermore, we propose that these genes and pathways will enhance our understanding of the heterogeneous molecular etiology of CDH.


Subject(s)
Hernias, Diaphragmatic, Congenital/etiology , Hernias, Diaphragmatic, Congenital/genetics , Animals , Cohort Studies , Computational Biology , DNA Copy Number Variations , Diaphragm/embryology , Exome , Genetic Variation , Hernias, Diaphragmatic, Congenital/embryology , Humans , Mice , Protein Interaction Maps
19.
J Pediatr Surg ; 49(6): 895-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24888830

ABSTRACT

BACKGROUND/PURPOSE: We determined the incidence of sensorineural hearing loss (SNHL; >20dB at any frequency) in a contemporary cohort of congenital diaphragmatic hernia (CDH) survivors at a single tertiary care center and identified potential risk factors for SNHL. METHODS: From 2000 through 2011, clinical and audiologic data were collected on 122 surgically-repaired Bochdalek CDH patients. CDH defect size, duration of ventilation, and cumulative aminoglycoside treatment were used for multivariate logistic regression. RESULTS: Incidence of SNHL was 7.4% (9/122). We identified one significant independent predictor of SNHL: cumulative length of aminoglycoside treatment (P<.001; OR 1.44, 95% CI: 1.13-1.83). CONCLUSIONS: Over the last decade, the incidence of SNHL in our CDH patients is low compared to previous reports in the literature (7.4%) and is not associated with CDH defect size or the need for extracorporeal membrane oxygenation. Prolonged duration of aminoglycoside treatment increases the risk of SNHL independent of defect size and duration of ventilation.


Subject(s)
Hearing Loss, Sensorineural/epidemiology , Hernias, Diaphragmatic, Congenital/complications , Herniorrhaphy/adverse effects , Audiometry , Female , Follow-Up Studies , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/etiology , Hernias, Diaphragmatic, Congenital/mortality , Hernias, Diaphragmatic, Congenital/surgery , Humans , Incidence , Infant, Newborn , Male , Massachusetts/epidemiology , Retrospective Studies , Risk Factors , Survival Rate/trends
20.
J Environ Health ; 76(7): 8-16; quiz 60, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24683934

ABSTRACT

Green building systems have proliferated recently, but studies are limited of associated health and housing outcomes. The authors measured self-reported resident physical and mental health, allergens, and building conditions at baseline and one-year follow-up in a low-income housing development being renovated in accordance with green healthy housing improvements (Enterprise Green Communities standards and Leadership in Energy & Environmental Design [LEED] gold certification). Self-reported general health in adults significantly improved from 59% to 67% (p = .026), with large statistically significant improvements in water/ dampness problems, cockroaches and rodents, and reduced pesticide use. Median cockroach (Bla g1) and mouse (Mus m1) allergen dust loadings showed large and statistically significant reductions from baseline to three months postintervention and were sustained at one year (both p < .05). Energy and water cost savings were 16% and 54%, respectively. Incorporating Enterprise Green Communities and LEED standards in low-income housing renovation improves health and housing conditions and can help to reduce disparities. All green housing standards should include health-related requirements.


Subject(s)
Allergens/analysis , Conservation of Natural Resources/methods , Housing , Public Housing/standards , Urban Health , Adult , Age Factors , Child , District of Columbia , Female , Follow-Up Studies , Health Status , Housing/economics , Humans , Male , Mental Health , Self Report , Time Factors
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