Abstract
Introduction:
The purpose of this study was to examine the clinical features/outcomes associated with tracheostomy in infants with congenital diaphragmatic hernia (CDH).
Methods:
The study population consisted of liveborn infants reported to the CDH Study Group registry between 2007 and 2017. Subjects were identified as having a tracheostomy if they were discharged or transferred to another hospital with tracheostomy and/or on mechanical ventilation. Multivariate mixed models were used for analyses.
Results:
The registry population consisted of 5434 subjects, of whom 230 (4.2%) underwent tracheostomy placement. Only 3830 (70.5%) infants survived until discharge/transfer. The median age of tracheostomy placement was 3.3 months (range, 1.3–13.4 when known; n = 58 out of 154 survivors). The mortality rate among subjects with tracheostomy was 32.8% with a median of 37 days (range, 8–189 when known; n = 32 out of 75 deceased) ensuing between tracheostomy placement and death. The clinical features found to be associated with increased odds ratio of tracheostomy placement included male sex, birth weight, 5-minute APGAR score, defect size, liver in chest, ECMO use, cardiac abnormality, other congenital abnormalities, pulmonary hypertension, and the presence of a feeding tube. There was center variation in the rate of tracheostomy placement, which may be partially accounted for by disease severity, but not center size.
Conclusion:
There are several clinical features that are associated with increased likelihood of tracheostomy placement. Most deaths in subjects with tracheostomies occurred outside the immediate postoperative period. The utility of a standardized protocol for tracheostomy in infants with CDH should be considered.
Keywords: congenital diaphragmatic hernia, mechanical ventilators, tracheostomy
1 |. INTRODUCTION
Congenital diaphragmatic hernia (CDH) is a developmental discontinuity of the diaphragm that allows migration of abdominal viscera into thorax. Between 1986 and 2013 the overall incidence of CDH was 2.7 to 4.9 per 10 000 live births.1–3 CDH causes decreased bronchiolar branching, loss of pulmonary mass, and pulmonary vasculopathy, leading to pulmonary hypoplasia and pulmonary hypertension.4–6 These pulmonary sequelae are major contributors to the mortality and respiratory morbidities seen with this disorder.7
Despite medical advances, the overall mortality rate for CDH has remained unchanged over the last 20 years.8,9 The mortality rate for live births in the United State ranges from 31% to 33%,10,11 and in Europe ranges from 36% to 62%.1–3 However, these estimates may underestimate mortality as they do not necessarily capture elective abortion, spontaneous abortion, or still birth.2,3,12 Several risk factors are known to be associated with mortality. These include the size of the CDH defect, the presence of liver within the thorax, prenatal diagnosis, lower birth weight, and lower APGAR scores.1,2,5,7,8,13–15
Respiratory morbidities may include chronic respiratory failure with tracheostomy and home ventilator dependence. In contrast to mortality, the data are more limited regarding risk factors and clinical course associated with the significant morbidity of tracheostomy placement, which ranges from 2.4% to 4% of CDH patients.16,17 One center found that right-sided CDH was associated with tracheostomy.4 In another small study, liver herniation, was not associated with tracheostomy among the 17 patients who survived.18
In this study, we sought to examine risk factors associated with tracheostomy placement and long-term mechanical ventilation in patients with CDH using a large, international, multicenter registry. Based on published literature and our experience, we hypothesized that certain clinical features were associated with a higher incidence of tracheostomy and long-term mechanical ventilation in patients with CDH. These features included demographic factors, prenatal factors, birth history, CDH defect characteristics, CDH surgical approaches, respiratory features, and other comorbidities. We also examined timing of tracheostomy placement, center variation in the incidence of tracheostomy, and outcomes after tracheostomy.
2 |. METHODS
Data were queried from the Congenital Diaphragmatic Hernia Study Group (CDHSG), which maintains a voluntary international registry of infants and children with CDH. Participants in this registry include 82 centers in 15 countries across six continents (Table A1). Predefined data are collected by each center using a standardized data collection form. This study used data form versions 3 and 4, which were instituted in 2007 and 2015, respectively. Inclusion criteria included liveborn infants with CDH born from 2007 through 2017. Local institutional review board approval was obtained for analysis of deidentified registry data (Johns Hopkins University, IRB#: 00127299). International data collection and collaborative investigation using the CDHSG registry was approved by the University of Texas McGovern Medical School in Houston, Center for the Protection of Human Subjects/Institutional Review Board (HSC-MS-03-223).
All clinical data utilized in this study were obtained from the CDHSG registry. Individuals with tracheostomy were defined as discharged or transferred to another hospital with tracheostomy and/or on mechanical ventilation. Standardized defect sizes are described in the CDHSG Staging System.7 “A” represents the smallest defects, while “D” represents the largest defects. Small for gestational age was defined as weighing less than 10th percentile at birth corrected for gestational age.19 The presence of pulmonary hypertension was defined as evidence of its presence on the last echocardiogram obtained before discharge or death. Severe reflux was defined as requirement of fundoplication and/or gastro-jejunal feeding tube. Lung-to-head ratio was not included in analyses as it was only collected on participants born after 1 January 2015.
Baseline characteristic for subjects with and without tracheostomies and for subjects with tracheostomies who survived until initial discharge and those who did not were compared using χ2 tests and t tests (Tables 1 and 3). Stepwise multivariate logistic mixed models were used to examine the clinical features associated with tracheostomy placement by dropping nonsignificant variables sequentially (Table 2). Models were nested by center to account for individual center variation regarding decision to proceed with tracheostomy placement. The final multivariate model included only those factors associated with tracheostomy placement. The majority of reported analyses were limited to subjects surviving until discharge owing to data missingness for deceased subjects and the likelihood that tracheostomy placement would not necessarily be a considered as an option for these subjects.
TABLE 1.
Discharged population demographics
| Characteristic, mean ± SD [range] | Surviving until discharge (n = 3830) | Without tracheostomy (n = 3676) | With tracheostomy (n = 154) | P value |
|---|---|---|---|---|
| Sex (% males) | 60.3 (n = 3822) | 59.9 (n = 3668) | 69.5 | .017 |
| Prenatal history | ||||
| Prenatal diagnosis (% yes) | 63.7 (n = 3819) | 63.3 (n = 3665) | 74.0 | .007 |
| Prenatal steroids (% yes) | 24.7 (n = 2883) | 24.4 (n = 2771) | 31.3 (n = 112) | .10 |
| Birth history | ||||
| Birth weight, kg | 3.05 ± 0.58 [0.70–5.15] (n = 3816) | 3.06 ± 0.58 [0.70–5.15] (n = 3663) | 2.80 ± 0.68 [0.91–4.11] (n = 153) | <.001 |
| Gestational age, wk | 37.8 ± 2.1 [26–42] (n = 3789) | 37.8 ± 2.0 [26–42] (n = 3636) | 37.0 ± 2.9 [27–41] (n = 153) | <.001 |
| Small for gestational age (% < 10th percentile) | 17.4 (n = 3780) | 17.1 (n = 3627) | 22.9 (n = 153) | .07 |
| Method of delivery, % | ||||
| Spontaneous vaginal | 38.5 | 38.8 | 30.9 | .009 |
| Induced vaginal | 16.8 | 16.7 | 19.1 | |
| Elective C-section | 26.5 | 26.7 | 22.4 | |
| Nonelective C-section | 18.2 (n = 3804) | 17.8 (n = 3652) | 27.6 (n = 152) | |
| APGAR score, 1 min | 5.3 ± 2.5 [0–10] (n = 3592) | 5.4 ± 2.5 [0–10] (n = 3450) | 3.8 ± 2.2 [0–9] (n = 142) | <.001 |
| APGAR score, 5 min | 7.2 ± 1.9 [0–10] (n = 3564) | 7.2 ± 1.8 [0–10] (n = 3423) | 5.7 ± 2.0 [1–10] (n = 141) | <.001 |
| CPR in delivery room (% yes) | 11.7 (n = 3611) | 11.3 (n = 3467) | 22.2 (n = 144) | <.001 |
| CDH history | ||||
| Side of CDH, % | ||||
| Left | 84.1 | 84.5 | 73.4 | <.001 |
| Right | 15.7 | 15.3 | 24.0 | |
| Bilateral | 0.3 (n = 3826) | 0.2 (n = 3672) | 2.6 | |
| Defect size, % | ||||
| A | 15.9 | 16.4 | 3.6 | <.001 |
| B | 44.2 | 45.4 | 14.3 | |
| C | 30.7 | 30.0 | 50.7 | |
| D | 9.1 (n = 3772) | 8.3 (n = 3632) | 31.4 (n = 140) | |
| Hernia sac (% yes) | 21.2 (n = 3703) | 21.7 (n = 3565) | 10.1 (n = 138) | .001 |
| Liver in chest, % | 40.6 (n = 3734) | 39.2 (n = 3590) | 75.0 (n = 144) | <.001 |
| CDH surgery | ||||
| Type of CDH repair, % | ||||
| Primary | 53.1 | 54.6 | 14.3 | <.001 |
| Patch | 47.0 (n = 3815) | 45.4 (n = 3668) | 85.7 (n = 147) | |
| Thoracic approach, % | 3.6 (n = 3658) | 3.6 (n = 3523) | 4.4 (n = 135) | .60 |
| Thoracoscopic approach, % | 16.4 (n = 3658) | 16.9 (n = 3523) | 3.0 (n = 135) | <.001 |
| Pulmonary history | ||||
| Surfactant (% yes) | 9.4 (n = 3696) | 8.8 (n = 3552) | 23.6 (n = 144) | <.001 |
| ECMO (% yes) | 20.3 | 18.6 | 60.4 | <.001 |
| Pulmonary status at 30 d of age (% on supplemental oxygen) | 41.6 (n = 3747) | 39.4 (n = 3608) | 99.3 (n = 139) | <.001 |
| Other history | ||||
| Cardiac abnormality, % | ||||
| Major | 4.3 | 3.8 | 16.2 | <.001 |
| Minor | 12.8 | 12.3 | 24.7 | |
| None | 82.9 | 83.9 | 59.1 | |
| Pulmonary hypertension on last echocardiogram (% yes) | 46.6 (n = 3629) | 45.5 (n = 3482) | 71.4 (n = 147) | <.001 |
| Feeding tube (% with GJT or GT) | 13.1 | 11.5 | 51.3 | <.001 |
| Severe reflux (% with fundoplication or GJT) | 9.3 | 8.5 | 28.0 | <.001 |
| Chromosomal abnormality (% yes) | 4.5 | 4.2 | 11.7 | <.001 |
| Other abnormalities (% yes) | 10.8 | 10.3 | 21.4 | <.001 |
Abbreviations: CDH, congenital diaphragmatic hernia; CPR, cardiopulmonary resuscitation; ECMO, extracorporeal membrane oxygenation.
TABLE 3.
Tracheostomy population demographics
| Characteristic, mean ± SD [range] | With tracheostomy (n = 229) | Alive at initial discharge (n = 154) | Died before discharge (n = 75) | P value |
|---|---|---|---|---|
| Sex (% males) | 65.1 | 69.5 | 56.0 | .045 |
| Prenatal history | ||||
| Prenatal diagnosis (% yes) | 76.3 (n = 228) | 74.0 | 81.1 (n = 74) | .24 |
| Prenatal steroids (% yes) | 28.1 (n = 171) | 31.3 (n = 112) | 22.0 (n = 59) | .20 |
| Birth history | ||||
| Birth weight, kg | 2.80 ± 0.67 [0.68–4.15] (n = 228) | 2.80 ± 0.68 [0.91–4.11] (n = 153) | 2.78 ± 0.65 [0.68–4.15] | .79 |
| Gestational age, wk | 37.0 ± 2.8 [25–41] (n = 227) | 37.0 ± 2.9 [27–41] (n = 153) | 37.0 ± 2.5 [25–41] (n = 74) | .85 |
| Small for gestational age (% < 10th percentile) | 25.1 (n = 227) | 22.9 (n = 153) | 29.7 (n = 74) | .26 |
| Method of delivery, % | ||||
| Spontaneous vaginal | 28.3 | 30.9 | 23.0 | .16 |
| Induced vaginal | 18.1 | 19.1 | 16.2 | |
| Elective C-section | 27.0 | 22.4 | 36.5 | |
| Nonelective C-section | 26.6 (n = 226) | 27.6 (n = 152) | 24.3 (n = 74) | |
| APGAR score , 1 min | 3.8 ± 2.2 [0–9] (n = 213) | 3.8 ± 2.2 [0–9] (n = 142) | 3.9 ± 2.3 [1–9] (n = 71) | .63 |
| APGAR score, 5 min | 5.9 ± 2.1 [1–10] (n = 212) | 5.7 ± 2.0 [1–10] (n = 141) | 6.3 ± 2.1 [1–10] (n = 71) | .05 |
| CPR in delivery room (% yes) | 19.8 (n = 212) | 22.2 (n = 144) | 14.7 (n = 68) | .20 |
| CDH history | ||||
| Side of CDH, % | ||||
| Left | 75.1 | 73.4 | 78.7 | .32 |
| Right | 23.1 | 24.0 | 21.3 | |
| Bilateral | 1.8 | 2.6 | 0.0 | |
| Defect size, % | ||||
| A | 2.4 | 3.6 | 0.0 | .11 |
| B | 16.1 | 14.3 | 20.0 | |
| C | 46.8 | 50.7 | 38.5 | |
| D | 34.6 (n = 205) | 31.4 (n = 140) | 41.5 (n = 65) | |
| Hernia sac (% yes) | 11.3 (n = 203) | 10.1 (n = 138) | 13.9 (n = 65) | .44 |
| Liver in chest, % | 75.7 (n = 210) | 75.0 (n = 144) | 77.3 (n = 66) | .72 |
| CDH surgery | ||||
| Type of CDH repair, % | ||||
| Primary | 13.6 | 14.3 | 12.1 | .67 |
| Patch | 86.4 (n = 213) | 85.7 (n = 147) | 87.9 (n = 66) | |
| Thoracic approach, % | 4.5 (n = 199) | 4.4 (n = 135) | 4.7 (n = 64) | .94 |
| Thoracoscopic approach, % | 2.0 (n = 199) | 3.0 (n = 135) | 0.0 (n = 64) | .16 |
| Pulmonary history | ||||
| Surfactant (% yes) | 22.2 (n = 216) | 23.6 (n = 144) | 19.4 (n = 72) | .49 |
| ECMO (% yes) | 63.8 | 60.4 | 70.7 | .13 |
| Pulmonary status at 30 d of age (% on supplemental oxygen) | 99.5 (n = 200) | 99.3 (n = 139) | 100.0 (n = 61) | .51 |
| Other history | ||||
| Cardiac abnormality, % | ||||
| Major | 19.2 | 16.2 | 25.3 | .22 |
| Minor | 22.7 | 24.7 | 18.7 | |
| None | 58.1 | 59.1 | 56.0 | |
| Pulmonary hypertension on last echocardiogram (% yes) | 78.7 (n = 221) | 71.4 (n = 147) | 93.2 (n = 74) | <.001 |
| Feeding tube (% with GJT or GT) | 41.1 | 51.3 | 20.0 | <.001 |
| Severe reflux (% with fundoplication or GJT) | 25.8 | 27.9 | 21.3 | .29 |
| Chromosomal abnormality (% yes) | 13.1 | 11.7 | 16.0 | .36 |
| Other abnormalities (% yes) | 23.1 | 21.4 | 26.7 | .38 |
Abbreviations: CDH, congenital diaphragmatic hernia; CPR, cardiopulmonary resuscitation; ECMO, extracorporeal membrane oxygenation.
TABLE 2.
Demographic and clinical features associated with tracheostomy placement
| Characteristics, odds ratio [95% CI](n = 2910) | Univariate regressions | ORP value | Final multivariate model | Adjusted ORP value |
|---|---|---|---|---|
| Sex (male = 0; female = 1) | 0.65 [0.42, 1.01] | .054 | 0.54 [0.33, 0.90] | .018 |
| Prenatal diagnosis (no = 0; yes = 1) | 1.66 [1.05, 2.62] | .030 | … | NS |
| Birth history | ||||
| Birth weight, kg | 0.47 [0.34, 0.64] | <.001 | 0.43 [0.29, 0.64] | <.001 |
| Gestational age, wk | 0.86 [0.80, 0.93] | <.001 | … | NS |
| Method of delivery (vaginal or elective C-section = 0; nonelective C-section = 1) | 1.64 [1.03, 2.62] | .037 | … | NS |
| APGAR score, 1 min | 0.76 [0.70, 0.83] | <.001 | … | NS |
| APGAR score, 5 min | 0.71 [0.65, 0.77] | <.001 | 0.84 [0.75, 0.95] | .004 |
| CPR in delivery room (no = 0; yes = 1) | 2.20 [1.30, 3.71] | .003 | … | NS |
| CDH history | ||||
| Side of CDH (compared to left) | ||||
| Right | 1.85 [1.15, 2.96] | .011 | … | NS |
| Bilateral | 9.81 [1.26, 76.32] | .029 | … | NS |
| Defect size (compared to A) | ||||
| B | 1.22 [0.39, 3.80] | .73 | … | NS |
| C | 7.33 [2.56, 20.99] | <.001 | … | NS |
| D | 24.30 [8.19, 72.17] | <.001 | 2.43 [1.39, 4.25] | .002 |
| Hernia sac (no = 0; yes = 1) | 0.50 [0.27, 0.92] | .027 | … | NS |
| Liver in chest (no = 0; yes = 1) | 5.32 [3.33, 8.50] | <.001 | 2.02 [1.16, 3.52] | .013 |
| CDH surgery | ||||
| Type of CDH repair (no = primary; yes = patch) | 8.96 [4.91, 16.35] | <.001 | … | NS |
| Thoracoscopic approach (no = 0; yes = 1) | 0.09 [0.02, 0.37] | .001 | … | NS |
| Pulmonary history | ||||
| Surfactant (no = 0; yes = 1) | 3.26 [1.98, 5.35] | <.001 | … | NS |
| ECMO (no = 0; yes = 1) | 7.94 [5.09, 12.39] | <.001 | 4.30 [2.47, 7.50] | <.001 |
| Other history | ||||
| Cardiac abnormality (compared to none) | ||||
| Major | 5.47 [3.12, 9.58] | <.001 | 4.04 [2.06, 7.93] | <.001 |
| Minor | 1.68 [1.01, 2.79] | .046 | … | NS |
| Pulmonary hypertension on last echocardiogram (no = 0; yes = 1) | 3.20 [2.02, 5.06] | <.001 | 3.01 [1.78, 5.12] | <.001 |
| Feeding tube (no = 0; GJT or GT = 1) | 13.09 [8.13, 21.06] | <.001 | 5.92 [3.42, 10.25] | <.001 |
| Severe reflux (no = 1; fundoplication and/or GJT = 1) | 4.79 [2.80, 8.19] | <.001 | … | NS |
| Chromosomal abnormality (no = 0; yes = 1) | 4.67 [2.55, 8.54] | <.001 | … | NS |
| Other abnormalities (no = 0; yes = 1) | 2.37 [1.44, 3.90] | .001 | 2.48 [1.37, 4.51] | .003 |
Note: Multilevel mixed effects logistic regression was used to generate the mixed models in this table with tracheostomy placement (no = 0; yes = 1) as the independent variable, the various listed characteristics as independent variables (all significant factors from Table 1), and nesting by clinical center. Stepwise regression was used to generate the final model with nonsignificant characteristics being dropped sequentially. The final model compares having a type D defect vs A, B, or C. Only 2910 subjects out of the 3830 subjects surviving until discharge had complete ascertainment of all variables for the model. Abbreviations: CDH, congenital diaphragmatic hernia; CI, confidence interval; CPR, cardiopulmonary resuscitation; ECMO, extracorporeal membrane oxygenation; OR, odds ratio.
Survival analysis was used to study the ages at tracheostomy placement, hospital discharge, and death (Figures 1–3). A Kruskal-Wallis equality-of-populations rank test and the mixed model above was used to study center variation in tracheostomy placement. Logistic regression was used to study the odds ratio (OR) of tracheostomy placement by center size. Statistical significance was defined as P < .05. All analyses were performed using Stata/IC 15 (StataCorp, College Station, TX).
FIGURE 1.
Age at tracheostomy placement
FIGURE 3.
Age of death for patients with tracheostomies
3 |. RESULTS
3.1 |. Study demographics
Between 2007 and 2017, a total of 5434 infants were entered into the registry, of whom 3830 (70.5%) survived until discharge/transfer, 1573 (28.9%) died before initial discharge/transfer, and 31 (0.6%) whose mortality status was unknown. Of the entire population of 5434, a total of 230 had documentation of receiving a tracheostomy (4.2%) and of the 3830 who survived until initial discharge, 154 received a tracheostomy (4.0%). The population for this study are infants who survived until discharge (n = 3830) unless otherwise stated.
Subjects with tracheostomies were more likely to be male (69.5% vs 59.9%; P = .017) and be prenatally diagnosed with CDH (74.0% vs 63.3%; P = .007), compared to those without tracheostomies. Subjects with tracheostomies had a lower mean birth weight (2.80 vs 3.06 kg; P < .001) and earlier gestational age (37.0 vs 37.8 weeks; P < .001) compared with subjects without tracheostomies, but were similar in terms of frequency of infants born small for gestational age (P = .07). Advanced stage CDH defects (C and D) were more prevalent in subjects with tracheostomies, as were right-sided and bilateral CDH defects and “liver-up” defects (all P < .001). This was consistent with increased patch repairs among subjects with tracheostomies (85.7%) vs those without tracheostomies (45.4%; P < .001). Subjects with tracheostomies were more likely to have congenital and cardiac abnormalities, pulmonary hypertension, extracorporeal membrane oxygenation (ECMO) use, severe gastro-esophageal reflux, and feeding via enteral tube (all P < .001). The percentage of subjects who required supplemental oxygen at 30 days of life was higher among subjects with tracheostomies (99.3% vs 39.4%; P < .001) (Table 1).
3.2 |. Predictors of tracheostomy placement
Prolonged intubation was not necessarily a predictor of tracheostomy placement. Examining the entire population of 5434 subjects, 671 remained intubated at 30 days with 34 (5.1%) eventually receiving a tracheostomy, 167 remained intubated at 60 days with 17 (10.2%) eventually receiving a tracheostomy, and 58 remained intubated at 90 days with 7 (12.1%) eventually receiving a tracheostomy. Of the 154 subjects surviving until discharge/transfer who did receive tracheostomies, the age of tracheostomy placement was known for 58 of them, yielding a median age of tracheostomy placement of 3.3 months (Figure 1). Stepwise regression analysis was used to determine which demographic and clinical features were associated with tracheostomy placement. The initial model included all factors from Table 1 that were statistically different between subjects with tracheostomies and those without. In the final multivariate model, factors that remained associated with tracheostomy placement included the presence of a feeding tube (5.92; P < .001), prior ECMO use (4.30; P < .001), major cardiac abnormalities (4.04; P < .001), pulmonary hypertension (3.01; P < .001), other congenital abnormalities (2.48; P = .003), CDH defect size “D” (2.43; P = .002), low birth weight (2.33 per kg decrease; P < .001), liver in the chest (2.02; P = .013), male sex (1.85; P = .018), and lower APGAR score at 5 minutes (1.19 per 1 point decrease in score; P = .004) (Table 2). Of note, neither type “C” defect size, nor laterality of CDH defect, were associated with increased OR of tracheostomy placement.
3.3 |. Outcomes and tracheostomies
The age at discharge or transfer from the initial hospitalization was reported for 3802 subjects. Out of these, the median time of discharge or transfer was 1.1 months for 3655 subjects who did not have tracheostomies vs 5.7 months for subjects with tracheostomies (P < .001) (Figure 2).
FIGURE 2.
Hospital length of stay
Among the 230 subjects who underwent tracheostomy placement, 154 remained alive at their initial discharge or transfer to another hospital and 75 died (1 had an unknown status), yielding a mortality rate of 32.8%. This mortality rate was similar to the 5174 subjects who did not undergo tracheostomy placement (29.0%; P = .22). The median age of death for all subjects with tracheostomies was 3.4 months (n = 74; age at death not known for 1 subject) (Figure 3). Where data were available (n = 32), there was median of 37 days ensuing between tracheostomy placement and death (range, 8–189 days).
The median age of tracheostomy placement was reported for 90 subjects, which was similar at 3.3 months for the subjects who survived (n = 58) vs those who were deceased (n = 32) (P = .53; Figure 1). Subjects with tracheostomies who died were more likely to be female (44.0% vs 31.5%; P = .045), have evidence of pulmonary hypertension (93.2% vs 71.4%; P < .001), and less likely to undergo feeding tube placement (20.0% vs 51.3%; P < .001) compared to those with tracheostomies who survived to initial discharge or transfer (Table 3).
3.4 |. Tracheostomy placement and center variation
A total of 82 centers reported data from 5434 subjects of which 230 had tracheostomies. Centers reported on a median of 57.5 subjects each (range, 1–195) with a median tracheostomy rate of 2.7% (range, 0%-28.6%). Using a Kruskal-Wallis rank test, we confirmed that tracheostomy placement rates varied by center (P = .0001). To adjust for factors that were associated with tracheostomy placement, we compared the regression model in Table 2 to a multivariate one-level regression model using a likelihood ratio test (P < .0001), which also suggested that there was center variation in terms of tracheostomy placement. To determine if demographic or clinical factors were associated with rates of tracheostomy placement, these factors were compared between centers where less than 5% of subjects received tracheostomies vs those with greater rates of tracheostomy placement (Table 4). Factors associated with higher center rates of tracheostomy placement include prenatal diagnosis, reduced use of prenatal steroids, delivery methods, lower APGAR scores, larger defect sizes, the presence of liver in the chest, patch repairs, use of surfactant, ECMO, cardiac anomalies, pulmonary hypertension, feeding tubes, severe reflux, and other abnormalities. Again to adjust for factors that were associated with higher rates of tracheostomy placement, we compared the regression model using the pertinent factors from Table 4 to a multivariate one-level regression model using a likelihood ratio test (P < .0001), which continued to suggest that there was center variation in terms of tracheostomy placement even after adjustment. Lastly, it should be noted that the rate of tracheostomy placement by center was not associated with the total number of subjects each center reported on (P = .86) using unadjusted linear regression.
TABLE 4.
Discharged population demographics by center tracheostomy rate
| Characteristic, mean ± SD [range] | Surviving until discharge (n = 3830) | <5% of subjects at center with tracheostomy(n = 2493) | ≥5% of subjects at center with tracheostomy(n = 1337) | P value |
|---|---|---|---|---|
| Sex (% males) | 60.3 (n = 3822) | 60.0 (n = 2487) | 60.8 (n = 1335) | .62 |
| Prenatal history | ||||
| Prenatal diagnosis (% yes) | 63.7 (n = 3819) | 62.1 (n = 2483) | 66.7 (n = 1336) | .005 |
| Prenatal steroids (% yes) | 24.7 (n = 2883) | 27.1 (n = 1831) | 20.5 (n = 1052) | <.001 |
| Birth history | ||||
| Birth weight, kg | 3.05 ± 0.58 [0.70–5.15] (n = 3816) | 3.04 ± 0.57 [0.73–5.15] (n = 2482) | 3.06 ± 0.61 [0.70–5.08] (n = 1334) | .40 |
| Gestational age, wk | 37.8 ± 2.1 [26–42] (n = 3789) | 37.8 ± 2.0 [26–42] (n = 2462) | 37.8 ± 2.2 [27–42] (n = 1327) | .78 |
| Small for gestational age (% < 10th percentile) | 17.4 (n = 3780) | 17.4 (n = 2456) | 17.3 (n = 1324) | .94 |
| Method of delivery, % | ||||
| Spontaneous vaginal | 38.5 | 37.4 | 40.5 | .029 |
| Induced vaginal | 16.8 | 17.2 | 16.1 | |
| Elective C-section | 26.5 | 27.8 | 24.0 | |
| Nonelective C-section | 18.2 (n = 3804) | 17.6 (n = 2471) | 19.4 (n = 1333) | |
| APGAR score, 1 min | 5.3 ± 2.5 [0–10] (n = 3592) | 5.4 ± 2.5 [0–10] (n = 2298) | 5.1 ± 2.5 [0–9] (n = 1294) | <.001 |
| APGAR score, 5 min | 7.2 ± 1.9 [0–10] (n = 3564) | 7.3 ± 1.8 [0–10] (n = 2278) | 6.9 ± 1.9 [0–10] (n = 1286) | <.001 |
| CPR in delivery room (% yes) | 11.7 (n = 3611) | 12.3 (n = 2349) | 10.8 (n = 1262) | .19 |
| CDH history | ||||
| Side of CDH, % | ||||
| Left | 84.1 | 84.8 | 82.8 | .08 |
| Right | 15.7 | 15.1 | 16.8 | |
| Bilateral | 0.3 (n = 3826) | 0.2 (n = 2492) | 0.5 (n = 1334) | |
| Defect size, % | ||||
| A | 15.9 | 15.8 | 16.2 | .014 |
| B | 44.2 | 46.0 | 40.9 | |
| C | 30.7 | 29.2 | 33.6 | |
| D | 9.1 (n = 3772) | 9.0 (n = 2450) | 9.3 (n = 1322) | |
| Hernia sac (% yes) | 21.2 (n = 3703) | 22.2 (n = 2410) | 19.5 (n = 1293) | .06 |
| Liver in chest, % | 40.6 (n = 3734) | 39.0 (n = 2435) | 43.5 (n = 1299) | .007 |
| CDH surgery | ||||
| Type of CDH repair, % | ||||
| Primary | 53.1 | 55.3 | 48.8 | <.001 |
| Patch | 47.0 (n = 3815) | 44.7 (n = 2485) | 51.2 (n = 1330) | |
| Thoracic approach, % | 3.6 (n = 3658) | 3.7 (n = 2417) | 3.4 (n = 1241) | .60 |
| Thoracoscopic approach, % | 16.4 (n = 3658) | 16.9 (n = 2417) | 15.3 (n = 1241) | .21 |
| Pulmonary history | ||||
| Surfactant (% yes) | 9.4 (n = 3696) | 8.3 (n = 2395) | 11.5 (n = 1301) | .001 |
| ECMO (% yes) | 20.3 | 17.6 | 25.4 | <.001 |
| Pulmonary status at 30 d of age (% on supplemental oxygen) | 41.6 (n = 3747) | 40.6 (n = 2442) | 43.5 (n = 1305) | .09 |
| Other history | ||||
| Cardiac abnormality, % | ||||
| Major | 4.3 | 3.9 | 5.2 | <.001 |
| Minor | 12.8 | 10.9 | 16.5 | |
| None | 82.9 | 85.3 | 78.4 | |
| Pulmonary hypertension on last echocardiogram (% yes) | 46.6 (n = 3629) | 42.5 (n = 2358) | 54.2 (n = 1271) | <.001 |
| Feeding tube (% with GJT or GT) | 13.1 | 11.2 | 16.5 | <.001 |
| Severe reflux (% with fundoplication or GJT) | 9.3 | 10.6 | 7.0 | <.001 |
| Chromosomal abnormality (% yes) | 4.5 | 4.2 | 4.9 | .38 |
| Other abnormalities (% yes) | 10.8 | 9.5 | 13.2 | <.001 |
Abbreviations: CDH, congenital diaphragmatic hernia; CPR, cardiopulmonary resuscitation; ECMO, extracorporeal membrane oxygenation.
4 |. DISCUSSION
We conducted a retrospective study examining risk factors associated with tracheostomy placement and long-term mechanical ventilation in subjects with CDH using an international multicenter registry. In our study, we identified predictors of tracheostomy placement, assessed the morbidity and mortality associated with tracheostomy placement, and examined the role of center variation. Many of the factors we observed to be associated with tracheostomy placement are likely a function of chronic respiratory failure secondary to interrupted alveolar and pulmonary vascular growth.
Not surprisingly, many of the risk factors we found to be associated with tracheostomy placement have been associated with respiratory morbidity and mortality in previous studies. These included low birth weight, major cardiac abnormalities, larger defect size “D,” intrathoracic liver, and prior ECMO use. These are known predictors of pulmonary morbidity and mortality in CDH.7,10,20–22 The presence of chronic lung disease could be a confounder. The percentage of subjects who required supplemental oxygen at 30 days of life was higher among subjects with tracheostomies (99.3% vs 39.4%; P < .001), suggesting that chronic lung disease plays a role in tracheostomy requirement. In a study using the same CDHSG registry, chronic lung disease was found in 41% of the subjects at 30 days of life.10
In our study, pulmonary hypertension was associated with increased tracheostomy placement (adjusted OR = 3.01). Although postnatal vascular remodeling occurs in patients with CDH, and thus, pulmonary hypertension may improve with growth23; pulmonary hypertension continues to be associated with mortality in CDH despite advances in treatment.24,25 This is consistent with a single-center study by Panitch et al,26 where patients who required ECMO, pulmonary vasodilators, intrathoracic liver position, or patch repair were found to have abnormal lung function.
Patients rely on feeding via an enteral tube for a prolonged period of time while intubated, and following tracheostomy surgery.27,28 Thus, it was not surprising for subjects with feeding tubes to have a high likelihood of tracheostomy. In our study, this was the highest OR in the multivariate analysis.
There were novel factors identified to be associated with tracheostomy placement. These include male sex and other anomalies. The presence of congenital abnormalities, such as upper airway, skeletal, gastrointestinal, and genitourinary defects, increased the risk of tracheostomy placement by 2.5-fold. This suggests that the presence of an underlying genetic syndrome (particularly if it may be associated with an inability to protect one’s airway) may be associated with a worse respiratory outcome. CDH can be found in a number of syndromes such as myelin regulatory factor, Pallister-Killian, Donnai-Barrow, Fryns, Simpson-Golabi-Behmel, Cornelia de Lange, and Matthew-Wood syndromes.29–32 The literature is limited on association of these syndromes with tracheostomy and long-term mechanical ventilation. A few case reports discuss the utility of tracheostomy in patients with Pallister-Killian syndrome and Cornelia de Lange syndrome. These were due to various reasons including hypotonia, apnea, or upper airway obstruction due to secretions.33–35
The overall mortality among subjects who had tracheostomy placed was similar to those who did not. The tracheostomy placement procedure itself appeared to be safe in the CDH population. Subjects that did not survive after tracheostomy typically did not die in the immediate perioperative period with a median of 37 days (range, 8–189 days) ensuing between tracheostomy placement and death. The current timing of tracheostomy placement in the CDHSG did not show a difference in survival. Additionally, the median age of tracheostomy placement was 3.3 months regardless of survival.
Even though male sex was associated with increased tracheostomy placement (adjusted OR = 1.85), the females who had tracheostomies placed had higher mortality. This is likely a reflection of an overall higher mortality in females with CDH (32.1% in females vs 26.8% in males, overall). Subjects with tracheostomies who died were more likely to have evidence of pulmonary hypertension (93.2% vs 71.4%; P < .001), and less likely to undergo feeding tube placement (20.0% vs 51.3%; P < .001) compared to those with tracheostomies who survived to initial discharge or transfer. This may be a marker of multiorgan disease severity, and suggests that continued aggressive therapy may be warranted in CDH subjects with tracheostomy and pulmonary hypertension.
We found that there was center variation in terms of tracheostomy placement even after adjusting for some demographic and clinical factors associated with tracheostomy placement and/or higher center tracheostomy rates. This center variation may be secondary to other unmeasured clinical factors or provider decision-making, but it was not associated with the total number of subjects reported by each center, a proxy for center volume. More studies need to be done on possible standardization of care of infants with CDH. While a study based on this registry may be adequately powered to detect differences in tracheostomy placement, the registry does not capture decision-making variables related to tracheostomy (assuming that a hypothetical given decision-making factor is present in 50% of the “high usage” centers, and 30% in a “low usage” centers, one would need 93 subjects in each group [high vs low usage] to have 80% power to detect this difference).
There were several limitations in this study. Data entry into the registry could be variable despite published guidelines. The incidence of tracheostomy may also be underestimated due to an incomplete reports of respiratory status. Though 90% of subjects were extubated by 39 days of life, we were unable to study whether the duration of intubation predicted tracheostomy due to the small numbers of subjects with tracheostomies. Likewise, the variation in age of tracheostomy placement among the different centers could not be studied due to missing age data. Long-term morbidities beyond the initial hospitalization are not captured by the registry.
In conclusion, there are several clinical features that are associated with increased OR of tracheostomy placement. The majority of deaths in the population with tracheostomy do not tend to occur in the immediate postoperative period. More extensive studies need to be done in treatment of pulmonary hypertension and major cardiac comorbidities, as these had the highest OR of tracheostomy placement. The utility of a standardized protocol for tracheostomy and long-term mechanical ventilation in infants with CDH should be studied further. Increasing the number of participating centers in the study group would increase the study sample size, and allow to study tracheostomy practices in more details. We believe that the best way to study center effect on tracheostomy placement and outcomes, is through multicenter studies. Utilizing multicenter registries would facilitate that. Since the difference among centers persisted despite correcting for patients’ demographic and clinical features, future studies should focus on center factors (such as size, level of care, access to otolaryngology service, support for technology-dependent children, and long-term outcomes of patients). The individual physician beliefs, practices, and experience should also be studied. This can influence heavily the decision of discharging the patient with tracheostomy and mechanical ventilation vs other types of respiratory support such as noninvasive positive pressure ventilation. Ultimately, tracheostomies may be highly beneficial to selected patients as the observed comorbidities are more likely a function of disease severity than a consequence of tracheostomy.
ACKNOWLEDGEMENTS
Gratitude is expressed to the families and centers who participated in the Congenital Diaphragmatic Hernia Study Group. Grant number: 2 T32 HL 72748-16 A1—NIH Pediatric Pulmonary Fellow Salary (Al Baroudi S). This grant covered the fellow’s salary, and was not aimed specifically toward this study project.
APPENDIX A
TABLE A1.
Centers that participated in the Congenital Diaphragmatic Hernia Study Group from 2007 to 2017
| Center | Country |
|---|---|
| Alberta Children’s Hospital | Canada |
| Arkansas Children’s Hospital | USA |
| Astrid Lindgren Children’s Hospital | Sweden |
| Azienda Ospedaliera Papa Giovanni XXIII | Italy |
| BC Children’s & Women’s Health Centre | Canada |
| Cairo University Pediatric Hospital (Aboul Reesh) | Egypt |
| Carolinas Medical Center, Levine Children’s Hospital | USA |
| Children’s Hospital & Research Center Oakland | USA |
| Childrens Hospital at Skanes University Hospital | Sweden |
| Children’s Hospital Boston | USA |
| Children’s Hospital of Akron | USA |
| Children’s Hospital of Georgia, AU Health | USA |
| Children’s Hospital of Illinois at OSF St. Francis Med Center | USA |
| Children’s Hospital of Los Angeles | USA |
| Children’s Hospital of Orange County | USA |
| Children’s Hospital of San Antonio | USA |
| Children’s Hospital of Wisconsin | USA |
| Children’s Hospital Omaha | USA |
| Childrens Hospital, University Bonn | Germany |
| Children’s Hospitals and Clinics (Minneapolis) | USA |
| Children’s Memorial Hermann Hospital | USA |
| Children’s of Alabama | USA |
| Cincinnati Children’s Hospital Medical Center | USA |
| Cleveland Clinic Foundation, Children’s Hospital | USA |
| Connecticut Children’s Medical Center | USA |
| Dell Children’s Medical Center of Central Texas | USA |
| Duke University Medical Center | USA |
| Emory University | USA |
| Golisano Children’s Hospital at Strong | USA |
| Hospital Clinico Universidad Católica de Chile | Chile |
| IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico | Italy |
| James Whitcomb Riley Children’s Hospital | USA |
| Johns Hopkins All Children’s Hospital | USA |
| Johns Hopkins Hospital | USA |
| Juan P. Garrahan Children Hospital | Argentina |
| Le Bonheur Children’s Medical Center | USA |
| Legacy Emanuel Children’s Hospital | USA |
| Loma Linda University Children’s Hospital | USA |
| Lucile Salter Packard Children’s Hospital | USA |
| Mattel Children’s Hospital at UCLA | USA |
| Miami Valley Hospital | USA |
| National Center for Child Health and Development | Japan |
| NICU Health Sciences Centre | Canada |
| Norton Children’s Hospital | USA |
| Osaka University Graduate School of Medicine | Japan |
| Ospedale Pediatrico Bambino Gesù | Italy |
| Palmetto Health Richland | USA |
| Phoenix Children’s Hospital | USA |
| Polish Mother’s Memorial Hospital Research Institute | Poland |
| Primary Children’s Hospital | USA |
| Radboud University Nijmegen Medical Centre | The Netherlands |
| Rady Children’s Hospital | USA |
| Research Center for Obstetrics, Gynecology and Perinatology | Russia |
| Research Institute at Nationwide Children’s Hospital | USA |
| Royal Children’s Hospital | Australia |
| Royal Hospital for Sick Children | Scotland |
| Shands Children’s Hospital/University of Florida | USA |
| Sophia Children’s Hospital | The Netherlands |
| St. Francis Children’s Hospital | USA |
| St. Joseph’s Hospital and Medical Center | USA |
| St. Louis Children’s Hospital | USA |
| St. Louis University School of Medicine at SSM Health Cardinal Glennon Children’s Hospital | USA |
| Stollery Children’s Hospital | Canada |
| Sydney Children’s Hospital | Australia |
| Texas Children’s Hospital | USA |
| The Children’s Hospital at Oklahoma University Medical Center | USA |
| The Children’s Hospital of Pittsburgh of UPMC | USA |
| The Hospital for Sick Children | Canada |
| The Queen Silvia Children’s Hospital SU/Östra | Sweden |
| Tufts Medical Center | USA |
| University of North Carolina School of Medicine | USA |
| University Childrens Hospital | Sweden |
| University Malaya Medical Centre | Malaysia |
| University of Michigan, C.S. Mott Children’s Hospital | USA |
| University of Nebraska Medical Center | USA |
| University of Padua | Italy |
| University of Texas Medical Branch at Galveston | USA |
| University of Virginia Medical School | USA |
| Vanderbilt Children’s Hospital | USA |
| Vladivostok State Medical University | Russia |
| Winnie Palmer Hospital for Women & Babies | USA |
| Yale New Haven Children’s Hospital | USA |
Footnotes
The abstract was presented at: American Thoracic Society International Conference May 2019; Rapid Poster Presentation Session; Johns Hopkins University Resident/Fellow Achievement Day; and Johns Hopkins University Excellence in Diversity Symposium.
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