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Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia
Journal of Pediatric Surgery xxx (2016) xxx–xxx
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Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia Masaya Yamoto a,⁎, Noboru Inamura b, Keita Terui c, Kouji Nagata d, Yutaka Kanamori e, Masahiro Hayakawa f, Yuko Tazuke g, Akiko Yokoi h, Hajime Takayasu i, Hiroomi Okuyama g, Koji Fukumoto a, Naoto Urushihara a, Tomoaki Taguchi d, Noriaki Usui j a
Department of Pediatric Surgery, Shizuoka Children's Hospital, Shizuoka, Japan Department of Pediatric Cardiology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan c Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan d Department of Pediatric Surgery, Kyushu University, Fukuoka, Japan e Division of Surgery, National Center for Child Health and Development, Tokyo, Japan f Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan g Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan h Department of Pediatric Surgery, Hyogo Children's Hospital, Kobe, Japan i Department of Pediatric Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan j Department of Pediatric Surgery, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan b
a r t i c l e
i n f o
Article history: Received 6 August 2016 Accepted 12 September 2016 Available online xxxx Key words: Congenital diaphragmatic hernia Echocardiography Persistent pulmonary hypertension Left heart hypoplasia
a b s t r a c t Background/purpose: The purpose of this study was to investigate echocardiographic parameters in relation to the outcomes of isolated left-sided congenital diaphragmatic hernia (CDH). Methods: This multicenter, retrospective, observational study was conducted among patients with CDH born between 2006 and 2010. Patients in this study did not have severe cardiac malformations or chromosomal aberrations. Patients with incomplete echocardiographic examinations were excluded. In total, 84 patients with left-sided isolated CDH were included in this study. The prognostic parameters were obtained from postnatal echocardiographic images within 24 h after birth. Results: Eight patients died before 90 days of birth. Univariate analysis showed that the presence of continuous right to left shunt at the ductus, left pulmonary artery diameter of b 2.7 mm, right pulmonary artery diameter of b 3.3 mm, and left ventricular diastolic diameter of b 10.8 mm, were the predictors of poor prognosis. Multivariate logistic regression analysis showed that right pulmonary artery diameter of b3.3 mm (adjusted OR 10.28, 95% C.I.: 1.15–249.19) and left ventricular diastolic diameter of b 10.8 mm (adjusted OR 7.86, 95% C.I.: 1.01–82.82) were predictors of poor prognosis. Conclusions: This study revealed that the predictors of poor prognosis associated with CDH include smaller right pulmonary artery and left ventricular diastolic diameters. Retrospective Study-Level II. © 2016 Published by Elsevier Inc.
Morbidity and mortality remain significant problems in infants diagnosed with congenital diaphragmatic hernia (CDH). Prognostic factors that are known to adversely affect outcome include liver herniation [1], prematurity [2], low birth weight [3], presence of associated congenital anomalies [4], and prenatal lung-head ratio [5]. However, the main factor determining survival in CDH is the degree of pulmonary hypoplasia and its associated pulmonary hypertension [2]. Persistent pulmonary hypertension (PPHN) is intimately associated with the pathophysiology of cardiopulmonary distress in CDH. To predict PPHN
⁎ Corresponding author at: Department of Pediatric Surgery, Shizuoka Children's Hospital, 860 Urushiyama, Aoi-ku, Shizuoka, 420-8660, Japan. Tel.: +81 54 247 6251; fax: +81 54 247 6259. E-mail address: [email protected] (M. Yamoto).
severity and clinical outcome, several parameters such as fetal pulmonary artery (PA) size [6] and postnatal PA size and blood flow [7,8] have been reported to be reliable. In addition, the left ventricle is markedly underdeveloped, and the hypoplastic lung presents intractable pulmonary hypertension [9]. Therefore, severe cases of CDH frequently develop left ventricular failure secondary to an underdeveloped left ventricle and right heart failure owing to pulmonary hypertension after birth [10]. However, currently, there are no comprehensive reports that have examined various echocardiographic indices related to CDH. In the present study, we investigated parameters associated with of CDH prognosis and found factors associated with pulmonary circulation to be of interest. Therefore, we speculated that heart structure might have a significant impact on the outcomes of patients with CDH and undertook an analysis of echocardiographic parameters in the early stage after birth with respect to predicting the outcomes of isolated left-sided CDH.
http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014 0022-3468/© 2016 Published by Elsevier Inc.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014
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M. Yamoto et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
1. Material and methods
1.3. Echocardiography
1.1. Patient selection
Echocardiography was performed by skilled neonatologists or cardiologists to evaluate the pulmonary circulatory status. Diameters of the RPA and LPA were measured at the point of their bifurcation during systole. The LVDs and the LVDd were calculated with the M-mode images from the short axis view. The EF was derived from the end-diastolic diameters (EDD) and the end-systolic diameters (ESD) of the left ventricle. EDD and ESD were both obtained from M-mode images with the cursor perpendicular to the interventricular septum, just below the tip of the mitral valve leaflets. The FS was calculated as [(EDD − ESD)/ EDD] × 100%.
A multicenter, retrospective, observational study was conducted among patients with CDH born between 2006 and 2010. The data were obtained from nine consenting institutions. Results of a questionnaire survey targeted to the departments of pediatric surgery and/or tertiary perinatal care centers were retrospectively evaluated. In total, 228 neonates with CDH were born during the study period. Patients with severe cardiac malformations or chromosomal aberrations were excluded, as were patients with incomplete echocardiographic examinations. In total, 84 patients with left-sided isolated CDH were included in this study. Medical records during follow-up were retrospectively reviewed. The study was performed after being approved by the institutional ethics committee of Shizuoka children's hospital (approval number of 2016003) and the independent ethics committees of 9 other participating institutions: Chiba University, Hyogo College of Medicine, Kobe Children's Hospital, Kyushu University, Nagoya University, National Center for Child Health and Development, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka University, and Tsukuba University.
1.2. Data collection The outcome measure was survival to 90 days of age. The patient demographics, including sex, gestational age, birth weight, presence of prenatal diagnosis, intrathoracic liver herniation, contralateral stomach herniation, Apgar score at 1 and 5 min, highest PaO2, lowest PaCO2, and lowest oxygenation index (OI) within 24 h after birth, use of extracorporeal membrane oxygenation (ECMO), and use of inhaled nitric oxide (iNO), were reviewed. Intrathoracic liver herniation was liver occupying more than one-third of the thoracic space. Contralateral stomach herniation was more than one-half of the stomach herniating into the contralateral thoracic cavity. The postnatal echocardiographic parameters measured within 24 h of birth included the presence of continuous right to left shunt at the ductus (R-L shunt), right pulmonary artery (RPA) diameter, left pulmonary artery (LPA) diameter, left ventricular dimension at systole (LVDs), left ventricular dimension at diastole (LVDd), diameter of the descending aorta, tricuspid regurgitation (TR), ejection fraction (EF), and fractional shortening (FS).
2. Theory/calculation Statistical analyses were performed using the JMP software program (version 12.01; SAS Institute, Inc., Cary, NC, USA). Frequencies and percentages were used to describe categorical data. The chi-square test and Fisher's exact test were used to analyze categorical data. The median and interquartile ranges were used to describe continuous variables. The Mann–Whitney U test and an analysis of variance were used to compare continuous variables. Multiple logistic regression analyses were successively conducted on the factors that were significant at a p value of b0.05 in the univariate analysis and had low correlations with other factors (r b 0.7). Baseline variables included the presence of continuous R-L shunt, diameter of RPA, diameter of LPA, LVDs, LVDd, diameter of the descending aorta, TR, EF, and FS. The numerical data were divided into two groups based on a cut-off value that was calculated from a receiver operating characteristic (ROC) curve. Values of p b 0.05 were considered to indicate statistical significance. 3. Results 3.1. Patient demographics Pre- and postnatal characteristics with respect to survival to 90 days of age are shown in Table 1. Out of the total 228 CDH patients, 187 patients (82%) were alive at the time of discharge from the hospital. Out of the 84 CDH patients in this study, 76 patients (91%) were alive at the time of discharge from the hospital. There were significant differences between the surviving infants and those that died with respect to intrathoracic liver herniation (25% versus 63%, p = 0.02), contralateral
Table 1 Pre- and postnatal characteristics according to survival at 90 days of age. All CDH patients (n = 228)
Sex (male/female) Gestational age at birth (weeks), median (IQR) Birth weight (g), median (IQR) Presence of prenatal diagnosis Intrathoracic liver herniation Contralateral stomach herniation o/e-LHR, median (IQR) L/T ratio, median (IQR) Apgar score at 1 min, median (IQR) Apgar score at 5 min, median (IQR) Highest PaO2 (mmHg), median (IQR) Lowest PaCO2 (mmHg), median (IQR) Lowest OI, median (IQR) Use of ECMO Use of iNO
Included study (n = 84)
Survived (n = 187)
Did not survive (n = 41)
p value
Survived (n = 76)
Did not survive (n = 8)
p value
102 / 85 37 (37–38) 2744 (2446–2916) 160 (86%) 50 (27%) 20 (11%) 39.1 (23.5–51.4) 0.11 (0.09–0.15) 5 (3–7) 6 (4–8) 214 (120–332) 31.3 (26.6–39) 3.9 (2.9–6.3) 10 (5%) 126 (67%)
23 / 18 37 (36–38) 2634 (2159–2833) 39 (95%) 23 (56%) 15 (37%) 19.8 (15.5–26.2) 0.05 (0.04–0.07) 2 (1–4) 3 (2–5) 46 (29–80) 43 (31.6–62.5) 32 (14.7–48.1) 5 (12%) 32 (78%)
0.85 0.52 0.09 0.23 b0.01* b0.01* b0.01* b0.01* b0.01* b0.01* b0.01* 0.25 b0.01* 0.11 0.22
44 / 32 38 (37–39) 2753 (2465–2967) 68 (90%) 19 (25%) 10 (13%) 43.6 (24.6–50.2) 0.12 (0.09–0.14) 5 (3–7) 6 (3–8) 273 (157–357) 31.1 (26.3–41.6) 4.3 (3.2–5.9) 0 8 (100%)
3/5 37 (37–38.5) 2674 (2456–2787) 8 (100%) 5 (63%) 5 (63%) 20.5 (15.5–25.8) 0.05 (0.04–0.07) 3 (1–5) 3 (1–5) 55 (33.5–113.5) 38.5 (29.6–51.3) 37 (14.3–49.4) 1 (13%) 6 (82%)
0.29 0.76 0.72 0.63 0.02* b0.01* b0.01* b0.01* 0.02* b0.01* b0.01* 0.25 b0.01* 0.09 0.18
Intrathoracic liver herniation, liver occupying more than one-third of the thoracic space; Contralateral stomach herniation, more than one-half of the stomach herniating into the contralateral thoracic cavity; PaO2, partial pressure of oxygen; PCO2, partial pressure of carbon dioxide; OI, oxygenation index; ECMO, extracorporeal membrane oxygenation; iNO, inhaled nitric oxide; IQR, interquartile range.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014
M. Yamoto et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
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Table 2 Postnatal echocardiographic parameters within 24 h after birth according to survival at 90 days of age.
Continuous R-L shunt at the ductus Diameter of RPA (mm), median (IQR) Diameter of LPA (mm), median (IQR) LVDs (mm), median (IQR) LVDd (mm), median (IQR) Diameter of DA (mm), median (IQR) Tricuspid regurgitation EF (%), median (IQR) FS (%), median (IQR)
Survived (n = 76)
Did not survive (n = 8)
p value
48 (63%) 3.8 (3.5–4.3) 3.3 (2.7–3.7) 9.9 (8.2–10.9) 14.6 (12.5–16) 5.2 (4.7–5.7) 59 (78%) 62 (59–75) 47.5 (36.1–69.8)
7 (88%) 2.8 (2.5–3.1) 2.5 (2.2–2.7) 7.9 (6.1–9.3) 10.7 (9.8–12.1) 4.9 (4.5–5.8) 8 (100%) 67 (39–69) 45.9 (22.6–57.2)
b0.01* b0.01* b0.01* 0.06 b0.01* 0.59 0.86 0.53 0.29
R-L, right to left; LPA, Left pulmonary artery; RPA, right pulmonary artery; LVDs, left ventricular dimension at systole; LVDd, left ventricular dimension at diastole; DA, descending aorta; EF, ejection fraction; FS, fractional shortening; IQR, interquartile range.
stomach herniation (13% versus 63%, p b 0.01), median o/e-LHR (43.6 versus 20.5, p b 0.01), median L/T ratio (0.12 versus 0.05, p b 0.01), median Apgar score at 1 min (5 versus 3, p = 0.02), median Apgar score at 5 min (6 versus 3, p b 0.01), highest median PaO2 within 24 h (273 mmHg versus 55 mmHg, p b 0.01), and lowest median OI within 24 h (4.3 versus 37, p b 0.01). There were no significant differences in sex, gestational age, birth weight, presence of prenatal diagnosis, lowest PaCO2, use of ECMO, and use of iNO between infants who survived to 90 days and those who did not. 3.2. Postnatal echocardiographic parameters Postnatal echocardiographic parameters obtained within 24 h after birth are shown in Table 2. There were significant differences between the surviving infants and those that died at 90 days of age with respect to the presence of continuous R-L shunt (63% versus 88%, p b 0.01), diameter of RPA (3.8 mm versus 2.8 mm, p b 0.01), diameter of LPA (3.3 mm versus 2.5 mm, p b 0.01), and LVDd (14.6 mm versus 10.7 mm, p b 0.01). There were no differences in LVDs, diameter of the descending aorta, TR, EF, and FS between the two groups. 3.3. Analysis of risk factors and predictors of poor prognosis in echocardiographic parameters According to the ROC curve analysis, the recommended cutoff values for the diameter of RPA, diameter of LPA, LVDs, LVDd, diameter of the
descending aorta, EF, and FS for the prediction of death at 90 days of age were 3.3 mm [area under the curve (AUC), 0.92; p b 0.01], 2.7 mm (AUC, 0.79; p = 0.01), 9.3 mm (AUC, 0.69; p = 0.06), 10.8 mm (AUC, 0.87; p b 0.01), 4.5 mm (AUC, 0.58; p = 0.75), 45% (AUC, 0.56; p = 0.22), and 23% (AUC, 0.62; p = 0.13), respectively (Fig. 1). Univariate analysis showed that continuous R-L shunt [crude odds ratio (OR), 10.66; 95% confidence interval (CI), 1.22–93.32], RPA diameter of b 3.3 mm (crude OR, 28.47; 95% CI, 3.24–249.34), LPA diameter of b 2.7 mm (crude OR, 24.29; 95% CI, 2.79–221.42), and LVDd of b10.8 mm (crude OR, 9.86; 95% CI, 2.01–48.29) were significant risk factors for death at 90 days of age (Table 3). Multiple logistic regression analysis showed that an RPA diameter of b3.3 mm (adjusted OR, 10.28; 95% CI, 1.15–249.19) and LVDd of b10.8 mm (adjusted OR, 7.86; 95% CI, 1.01–82.82) were significant risk factors for death at 90 days of age (Table 4). Continuous R-L shunt (adjusted OR, 4.31; 95% CI, 0.41–114.23) and LPA diameter of b2.7 mm (adjusted OR, 6.89; 95% CI, 0.74–160.86) were no longer significant. 4. Discussion Survival rates for patients with CDH have increased during the past decades because of strategies such as iNO, ECMO, gentle ventilation, and delayed surgery [2,11,12]. However, CDH continues to be a vexing congenital malformation with a broadly variable cardiopulmonary disease severity at birth, and the survival rates of patients with severe
Fig. 1. Receiver operating characteristic(ROC) analysis for predicting non-survival with congenital diaphragmatic hernia according to the diameter of RPA, diameter of LPA, LVDs, LVDd, diameter of the descending aorta, EF, and FS cut-off values. LPA, left pulmonary artery; RPA, right pulmonary artery; LVDs, left ventricular dimension at systole; LVDd, left ventricular dimension at diastole; DA, descending aorta; EF, ejection fraction; FS, fractional shortening; AUC, area under the curve.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014
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M. Yamoto et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
Table 3 Univariate analysis for death before 90 days of age. Variables
Crude odds ratio
95% CI
p value
Continuous R-L shunt at the ductus Diameter of RPA of b3.3 mm Diameter of LPA of b2.7 mm LVDs of b9.3 mm LVDd of b10.8 mm Diameter of DA of b4.5 mm Tricuspid regurgitation EF of b45% FS of b23%
10.66 28.47 24.29 2.01 9.86 1.71 2.02 4.66 3
1.22–93.32 3.24–249.34 2.79–221.42 0.44–9.02 2.01–48.29 0.15–18.97 0.23–17.55 0.74–29.37 0.28–31.28
b0.01* b0.01* b0.01* 0.48 b0.01* 0.53 0.46 0.08 0.36
R-L, right to left; LPA, left pulmonary artery; RPA, right pulmonary artery; LVDs, left ventricular dimension at systole; LVDd, left ventricular dimension at diastole; DA, descending aorta; EF, ejection fraction; FS, fractional Shortening; CI, confidence interval.
CDH remain far from satisfactory. CDH presents with a spectrum of disease severity that makes it difficult to accurately predict outcome. Several publications have attempted to describe an accurate outcome predictor for neonates with CDH [13–15]. ++Furthermore, advances in diagnostic imaging in the assessment of CDH have facilitated the planning of appropriate management and therapeutic strategies [16,17]. Although these parameters are excellent predictors of lung volume, they share the limitation of being structural measurements that do not offer information regarding lung vasculature and function. Until functional predictors are identified, the prognostic information concerning fetal CDH will remain incomplete [18]. We evaluated the association of pulmonary circulation parameters with the prognosis of CDH. In this study, baseline variables and univariate analysis revealed significant differences in the presence of the continuous R-L shunt, diameter of RPA, diameter of LPA, and LVDd between patients who survived to 90 days of age and those who did not. Cardiac output within 24 h after birth was not strongly correlated with a poor prognosis. These four factors were confounding factors, although they certainly represent the severity of the disease among CDH patients. Finally, multiple logistic regression analysis revealed that an RPA diameter of b3.3 mm and LVDd of b 10.8 mm were significant prognostic factors among the related clinical and anatomic features evaluated by echocardiography. In general, the diameter of the PA depends on the physical size of the infant. However, fetal/postnatal PA diameters of babies with CDH are not correlated with physical size but instead depend on the severity of pulmonary hypoplasia [6]. Additionally, this study demonstrated that RPA diameter was more significantly correlated with severity than LPA diameter, which suggests that the analysis of the RPA enables the clinician to assess disease severity more precisely than LPA analysis. We suggest that RPA diameter correlates with capacity and function of the side of the lung that is unaffected, and thus, prognosis. Furthermore, this study suggests that diastolic dysfunction and hypoplasia of the left ventricle occurs with compression by the visceral organs shortly after birth in severe cases of CDH. In the literature, there are descriptions of three possible pathogenic mechanisms leading to a small left ventricle in patients with severe CDH. First, abdominal viscera displacement and high pressure of right ventricle induces a persistent mechanical compression of the left heart and creates a hemodynamic situation similar to that in chronic cardiac tamponade, with the result that cardiac diastolic dysfunction prevents sufficient left ventricle Table 4 Multiple logistic regression analysis for death before 90 days of age. Variables
Adjusted odds ratio
95% CI
p value
Continuous R-L shunt at the ductus Diameter of RPA of b3.3 mm Diameter of LPA of b2.7 mm LVDd of b10.8 mm
4.31 10.28 6.89 7.86
0.41–114.23 1.15–249.19 0.74–160.86 1.01–82.82
0.23 0.03* 0.09 0.04*
R-L, right to left; LPA, left pulmonary artery; RPA, right pulmonary artery; LVDd, left ventricular dimension at diastole; CI, confidence interval.
growth [19]. Second, reduced pulmonary vasculature causes a reduction in pulmonary blood flow, leading to a decreased preloading of the left ventricle, which, in fetuses, is defined as the sum of pulmonary blood flow and blood flow passing through the foramen ovale from the right atrium to the left atrium. In patients with severe CDH and pulmonary hypoplasia owing to persistent mechanical compression from herniated viscera, pulmonary blood flow cannot increase in late pregnancy, and a marked reduction is observed in the blood flow returning from pulmonary circulation compared with that in normal fetuses [20,21]. Finally, intrathoracic herniation of the liver, which presumably results from the rerouting of the majority of the ductus venous and inferior vena cava flow toward the right side of the heart, is observed in the majority of fetuses with severe CDH and predominant left heart hypoplasia [22]. If the compression by the visceral organs cause small left ventricle, early surgery may eliminate the left ventricle diastolic disorder and improve the left ventricle performance for patients with small LVDd. This study was limited by the restrictions inherent in a retrospective, multicenter, cohort study design. It was conducted in a retrospective manner using a questionnaire. In this study, the nine participating institutions do not have a standardized protocol, and thus, there was a lack of consensus for indications for treatment. Nonetheless, an excellent positive correlation was observed between the diameter of RPA and LVDd in the present study. This statistical analysis would be practical and helpful for the parental counseling and prognostic prediction, and contains potentially important data on which to base further prospective studies. More accurate prospective studies and an analysis of the correlation based on the methods of the measurement and treatment are, therefore, needed to confirm the present findings. 5. Conclusions Echocardiography provides useful information for predicting the outcomes of patients with isolated left-sided CDH. In particular, smaller diameter of the RPA and smaller LVDd were good predictors of mortality in infants with CDH. Further advances that can improve patient outcomes are still needed, and elucidation of more accurate cardiac function parameters for predicting prognosis is also essential to make progress in the treatment of patients with severe, isolated left-sided CDH. Conflict of interest The authors declare that they have no conflicts of interest. Acknowledgments This work was supported by a grant from the Ministry of Health, Labor and Welfare of Japan (Health and Labor Sciences Research Grants for Research on Intractable Diseases). The authors gratefully acknowledge the contributions of all the pediatric surgery and/or tertiary perinatal care centers for the collection of the data that were used in this study. References [1] Albanese CT, Lopoo J, Goldstein RB, et al. Fetal liver position and perinatal outcome for congenital diaphragmatic hernia. Prenat Diagn 1998;18:1138–42. [2] Boloker J, Bateman DA, Wung JT, et al. Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/ elective repair. J Pediatr Surg 2002;37:357–66. [3] Casaccia G, Crescenzi F, Dotta A, et al. Birth weight and McGoon index predict mortality in newborn infants with congenital diaphragmatic hernia. J Pediatr Surg 2006; 41:25–8. [4] Fauza DO, Wilson JM. Congenital diaphragmatic hernia and associated anomalies: their incidence, identification, and impact on prognosis. J Pediatr Surg 1994;29: 1113–7. [5] Waag KL, Loff S, Zahn K, et al. Congenital diaphragmatic hernia: a modern day approach. Semin Pediatr Surg 2008;17:244–54.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014
M. Yamoto et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx [6] Sokol J, Bohn D, Lacro RV, et al. Fetal pulmonary artery diameters and their association with lung hypoplasia and postnatal outcome in congenital diaphragmatic hernia. Am J Obstet Gynecol 2002;186:1085–90. [7] Hasegawa S, Kohno S, Sugiyama T, et al. Usefulness of echocardiographic measurement of bilateral pulmonary artery dimensions in congenital diaphragmatic hernia. J Pediatr Surg 1994;29:622–4. [8] Okazaki T, Kohno S, Hasegawa S, et al. Congenital diaphragmatic hernia: efficacy of ultrasound examination in its management. Pediatr Surg Int 2003;19:176–9. [9] Vogel M, McElhinney DB, Marcus E, et al. Significance and outcome of left heart hypoplasia in fetal congenital diaphragmatic hernia. Ultrasound Obstet Gynecol 2010; 35:310–7. [10] Mohseni-Bod H, Bohn D. Pulmonary hypertension in congenital diaphragmatic hernia. Semin Pediatr Surg 2007;16:126–33. [11] Bagolan P, Casaccia G, Crescenzi F, et al. Impact of a current treatment protocol on outcome of high-risk congenital diaphragmatic hernia. J Pediatr Surg 2004;39:313–8. [12] Wung JT, Sahni R, Moffitt ST, et al. Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube. J Pediatr Surg 1995;30:406–9. [13] Congenital Diaphragmatic Hernia Study Group. Estimating disease severity of congenital diaphragmatic hernia in the first 5 minutes of life. J Pediatr Surg 2001;36: 141–5. [14] Schultz CM, DiGeronimo RJ, Yoder BA. Congenital diaphragmatic hernia: a simplified postnatal predictor of outcome. J Pediatr Surg 2007;42:510–6.
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[15] Skarsgard ED, MacNab YC, Qiu Z, et al. SNAP-II predicts mortality among infants with congenital diaphragmatic hernia. J Perinatol 2005;25:315–9. [16] Kitano Y, Nakagawa S, Kuroda T, et al. Liver position in fetal congenital diaphragmatic hernia retains a prognostic value in the era of lung-protective strategy. J Pediatr Surg 2005;40:1827–32. [17] Usui N, Okuyama H, Sawai T, et al. Relationship between L/T ratio and LHR in the prenatal assessment of pulmonary hypoplasia in congenital diaphragmatic hernia. Pediatr Surg Int 2007;23:971–6. [18] Badillo A, Gingalewski C. Congenital diaphragmatic hernia: treatment and outcomes. Semin Perinatol 2014;38:92–6. [19] Inamura N, Kubota A, Nakajima T, et al. A proposal of new therapeutic strategy for antenatally diagnosed congenital diaphragmatic hernia. J Pediatr Surg 2005;40: 1315–9. [20] Baumgart S, Paul JJ, Huhta JC, et al. Cardiac malposition, redistribution of fetal cardiac output, and left heart hypoplasia reduce survival in neonates with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation. J Pediatr 1998;133:57–62. [21] Yamoto M, Tanaka Y, Fukumoto K, et al. Cardiac fetal ultrasonographic parameters for predicting outcomes of isolated left-sided congenital diaphragmatic hernia. J Pediatr Surg 2015;50:2019–24. [22] Stressig R, Fimmers R, Eising K, et al. Intrathoracic herniation of the liver (‘liver-up’) is associated with predominant left heart hypoplasia in human fetuses with left diaphragmatic hernia. Ultrasound Obstet Gynecol 2011;37:272–6.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014
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Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia Masaya Yamoto a,⁎, Noboru Inamura b, Keita Terui c, Kouji Nagata d, Yutaka Kanamori e, Masahiro Hayakawa f, Yuko Tazuke g, Akiko Yokoi h, Hajime Takayasu i, Hiroomi Okuyama g, Koji Fukumoto a, Naoto Urushihara a, Tomoaki Taguchi d, Noriaki Usui j a
Department of Pediatric Surgery, Shizuoka Children's Hospital, Shizuoka, Japan Department of Pediatric Cardiology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan c Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan d Department of Pediatric Surgery, Kyushu University, Fukuoka, Japan e Division of Surgery, National Center for Child Health and Development, Tokyo, Japan f Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan g Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan h Department of Pediatric Surgery, Hyogo Children's Hospital, Kobe, Japan i Department of Pediatric Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan j Department of Pediatric Surgery, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan b
a r t i c l e
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Article history: Received 6 August 2016 Accepted 12 September 2016 Available online xxxx Key words: Congenital diaphragmatic hernia Echocardiography Persistent pulmonary hypertension Left heart hypoplasia
a b s t r a c t Background/purpose: The purpose of this study was to investigate echocardiographic parameters in relation to the outcomes of isolated left-sided congenital diaphragmatic hernia (CDH). Methods: This multicenter, retrospective, observational study was conducted among patients with CDH born between 2006 and 2010. Patients in this study did not have severe cardiac malformations or chromosomal aberrations. Patients with incomplete echocardiographic examinations were excluded. In total, 84 patients with left-sided isolated CDH were included in this study. The prognostic parameters were obtained from postnatal echocardiographic images within 24 h after birth. Results: Eight patients died before 90 days of birth. Univariate analysis showed that the presence of continuous right to left shunt at the ductus, left pulmonary artery diameter of b 2.7 mm, right pulmonary artery diameter of b 3.3 mm, and left ventricular diastolic diameter of b 10.8 mm, were the predictors of poor prognosis. Multivariate logistic regression analysis showed that right pulmonary artery diameter of b3.3 mm (adjusted OR 10.28, 95% C.I.: 1.15–249.19) and left ventricular diastolic diameter of b 10.8 mm (adjusted OR 7.86, 95% C.I.: 1.01–82.82) were predictors of poor prognosis. Conclusions: This study revealed that the predictors of poor prognosis associated with CDH include smaller right pulmonary artery and left ventricular diastolic diameters. Retrospective Study-Level II. © 2016 Published by Elsevier Inc.
Morbidity and mortality remain significant problems in infants diagnosed with congenital diaphragmatic hernia (CDH). Prognostic factors that are known to adversely affect outcome include liver herniation [1], prematurity [2], low birth weight [3], presence of associated congenital anomalies [4], and prenatal lung-head ratio [5]. However, the main factor determining survival in CDH is the degree of pulmonary hypoplasia and its associated pulmonary hypertension [2]. Persistent pulmonary hypertension (PPHN) is intimately associated with the pathophysiology of cardiopulmonary distress in CDH. To predict PPHN
⁎ Corresponding author at: Department of Pediatric Surgery, Shizuoka Children's Hospital, 860 Urushiyama, Aoi-ku, Shizuoka, 420-8660, Japan. Tel.: +81 54 247 6251; fax: +81 54 247 6259. E-mail address: [email protected] (M. Yamoto).
severity and clinical outcome, several parameters such as fetal pulmonary artery (PA) size [6] and postnatal PA size and blood flow [7,8] have been reported to be reliable. In addition, the left ventricle is markedly underdeveloped, and the hypoplastic lung presents intractable pulmonary hypertension [9]. Therefore, severe cases of CDH frequently develop left ventricular failure secondary to an underdeveloped left ventricle and right heart failure owing to pulmonary hypertension after birth [10]. However, currently, there are no comprehensive reports that have examined various echocardiographic indices related to CDH. In the present study, we investigated parameters associated with of CDH prognosis and found factors associated with pulmonary circulation to be of interest. Therefore, we speculated that heart structure might have a significant impact on the outcomes of patients with CDH and undertook an analysis of echocardiographic parameters in the early stage after birth with respect to predicting the outcomes of isolated left-sided CDH.
http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014 0022-3468/© 2016 Published by Elsevier Inc.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014
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M. Yamoto et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
1. Material and methods
1.3. Echocardiography
1.1. Patient selection
Echocardiography was performed by skilled neonatologists or cardiologists to evaluate the pulmonary circulatory status. Diameters of the RPA and LPA were measured at the point of their bifurcation during systole. The LVDs and the LVDd were calculated with the M-mode images from the short axis view. The EF was derived from the end-diastolic diameters (EDD) and the end-systolic diameters (ESD) of the left ventricle. EDD and ESD were both obtained from M-mode images with the cursor perpendicular to the interventricular septum, just below the tip of the mitral valve leaflets. The FS was calculated as [(EDD − ESD)/ EDD] × 100%.
A multicenter, retrospective, observational study was conducted among patients with CDH born between 2006 and 2010. The data were obtained from nine consenting institutions. Results of a questionnaire survey targeted to the departments of pediatric surgery and/or tertiary perinatal care centers were retrospectively evaluated. In total, 228 neonates with CDH were born during the study period. Patients with severe cardiac malformations or chromosomal aberrations were excluded, as were patients with incomplete echocardiographic examinations. In total, 84 patients with left-sided isolated CDH were included in this study. Medical records during follow-up were retrospectively reviewed. The study was performed after being approved by the institutional ethics committee of Shizuoka children's hospital (approval number of 2016003) and the independent ethics committees of 9 other participating institutions: Chiba University, Hyogo College of Medicine, Kobe Children's Hospital, Kyushu University, Nagoya University, National Center for Child Health and Development, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka University, and Tsukuba University.
1.2. Data collection The outcome measure was survival to 90 days of age. The patient demographics, including sex, gestational age, birth weight, presence of prenatal diagnosis, intrathoracic liver herniation, contralateral stomach herniation, Apgar score at 1 and 5 min, highest PaO2, lowest PaCO2, and lowest oxygenation index (OI) within 24 h after birth, use of extracorporeal membrane oxygenation (ECMO), and use of inhaled nitric oxide (iNO), were reviewed. Intrathoracic liver herniation was liver occupying more than one-third of the thoracic space. Contralateral stomach herniation was more than one-half of the stomach herniating into the contralateral thoracic cavity. The postnatal echocardiographic parameters measured within 24 h of birth included the presence of continuous right to left shunt at the ductus (R-L shunt), right pulmonary artery (RPA) diameter, left pulmonary artery (LPA) diameter, left ventricular dimension at systole (LVDs), left ventricular dimension at diastole (LVDd), diameter of the descending aorta, tricuspid regurgitation (TR), ejection fraction (EF), and fractional shortening (FS).
2. Theory/calculation Statistical analyses were performed using the JMP software program (version 12.01; SAS Institute, Inc., Cary, NC, USA). Frequencies and percentages were used to describe categorical data. The chi-square test and Fisher's exact test were used to analyze categorical data. The median and interquartile ranges were used to describe continuous variables. The Mann–Whitney U test and an analysis of variance were used to compare continuous variables. Multiple logistic regression analyses were successively conducted on the factors that were significant at a p value of b0.05 in the univariate analysis and had low correlations with other factors (r b 0.7). Baseline variables included the presence of continuous R-L shunt, diameter of RPA, diameter of LPA, LVDs, LVDd, diameter of the descending aorta, TR, EF, and FS. The numerical data were divided into two groups based on a cut-off value that was calculated from a receiver operating characteristic (ROC) curve. Values of p b 0.05 were considered to indicate statistical significance. 3. Results 3.1. Patient demographics Pre- and postnatal characteristics with respect to survival to 90 days of age are shown in Table 1. Out of the total 228 CDH patients, 187 patients (82%) were alive at the time of discharge from the hospital. Out of the 84 CDH patients in this study, 76 patients (91%) were alive at the time of discharge from the hospital. There were significant differences between the surviving infants and those that died with respect to intrathoracic liver herniation (25% versus 63%, p = 0.02), contralateral
Table 1 Pre- and postnatal characteristics according to survival at 90 days of age. All CDH patients (n = 228)
Sex (male/female) Gestational age at birth (weeks), median (IQR) Birth weight (g), median (IQR) Presence of prenatal diagnosis Intrathoracic liver herniation Contralateral stomach herniation o/e-LHR, median (IQR) L/T ratio, median (IQR) Apgar score at 1 min, median (IQR) Apgar score at 5 min, median (IQR) Highest PaO2 (mmHg), median (IQR) Lowest PaCO2 (mmHg), median (IQR) Lowest OI, median (IQR) Use of ECMO Use of iNO
Included study (n = 84)
Survived (n = 187)
Did not survive (n = 41)
p value
Survived (n = 76)
Did not survive (n = 8)
p value
102 / 85 37 (37–38) 2744 (2446–2916) 160 (86%) 50 (27%) 20 (11%) 39.1 (23.5–51.4) 0.11 (0.09–0.15) 5 (3–7) 6 (4–8) 214 (120–332) 31.3 (26.6–39) 3.9 (2.9–6.3) 10 (5%) 126 (67%)
23 / 18 37 (36–38) 2634 (2159–2833) 39 (95%) 23 (56%) 15 (37%) 19.8 (15.5–26.2) 0.05 (0.04–0.07) 2 (1–4) 3 (2–5) 46 (29–80) 43 (31.6–62.5) 32 (14.7–48.1) 5 (12%) 32 (78%)
0.85 0.52 0.09 0.23 b0.01* b0.01* b0.01* b0.01* b0.01* b0.01* b0.01* 0.25 b0.01* 0.11 0.22
44 / 32 38 (37–39) 2753 (2465–2967) 68 (90%) 19 (25%) 10 (13%) 43.6 (24.6–50.2) 0.12 (0.09–0.14) 5 (3–7) 6 (3–8) 273 (157–357) 31.1 (26.3–41.6) 4.3 (3.2–5.9) 0 8 (100%)
3/5 37 (37–38.5) 2674 (2456–2787) 8 (100%) 5 (63%) 5 (63%) 20.5 (15.5–25.8) 0.05 (0.04–0.07) 3 (1–5) 3 (1–5) 55 (33.5–113.5) 38.5 (29.6–51.3) 37 (14.3–49.4) 1 (13%) 6 (82%)
0.29 0.76 0.72 0.63 0.02* b0.01* b0.01* b0.01* 0.02* b0.01* b0.01* 0.25 b0.01* 0.09 0.18
Intrathoracic liver herniation, liver occupying more than one-third of the thoracic space; Contralateral stomach herniation, more than one-half of the stomach herniating into the contralateral thoracic cavity; PaO2, partial pressure of oxygen; PCO2, partial pressure of carbon dioxide; OI, oxygenation index; ECMO, extracorporeal membrane oxygenation; iNO, inhaled nitric oxide; IQR, interquartile range.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014
M. Yamoto et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
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Table 2 Postnatal echocardiographic parameters within 24 h after birth according to survival at 90 days of age.
Continuous R-L shunt at the ductus Diameter of RPA (mm), median (IQR) Diameter of LPA (mm), median (IQR) LVDs (mm), median (IQR) LVDd (mm), median (IQR) Diameter of DA (mm), median (IQR) Tricuspid regurgitation EF (%), median (IQR) FS (%), median (IQR)
Survived (n = 76)
Did not survive (n = 8)
p value
48 (63%) 3.8 (3.5–4.3) 3.3 (2.7–3.7) 9.9 (8.2–10.9) 14.6 (12.5–16) 5.2 (4.7–5.7) 59 (78%) 62 (59–75) 47.5 (36.1–69.8)
7 (88%) 2.8 (2.5–3.1) 2.5 (2.2–2.7) 7.9 (6.1–9.3) 10.7 (9.8–12.1) 4.9 (4.5–5.8) 8 (100%) 67 (39–69) 45.9 (22.6–57.2)
b0.01* b0.01* b0.01* 0.06 b0.01* 0.59 0.86 0.53 0.29
R-L, right to left; LPA, Left pulmonary artery; RPA, right pulmonary artery; LVDs, left ventricular dimension at systole; LVDd, left ventricular dimension at diastole; DA, descending aorta; EF, ejection fraction; FS, fractional shortening; IQR, interquartile range.
stomach herniation (13% versus 63%, p b 0.01), median o/e-LHR (43.6 versus 20.5, p b 0.01), median L/T ratio (0.12 versus 0.05, p b 0.01), median Apgar score at 1 min (5 versus 3, p = 0.02), median Apgar score at 5 min (6 versus 3, p b 0.01), highest median PaO2 within 24 h (273 mmHg versus 55 mmHg, p b 0.01), and lowest median OI within 24 h (4.3 versus 37, p b 0.01). There were no significant differences in sex, gestational age, birth weight, presence of prenatal diagnosis, lowest PaCO2, use of ECMO, and use of iNO between infants who survived to 90 days and those who did not. 3.2. Postnatal echocardiographic parameters Postnatal echocardiographic parameters obtained within 24 h after birth are shown in Table 2. There were significant differences between the surviving infants and those that died at 90 days of age with respect to the presence of continuous R-L shunt (63% versus 88%, p b 0.01), diameter of RPA (3.8 mm versus 2.8 mm, p b 0.01), diameter of LPA (3.3 mm versus 2.5 mm, p b 0.01), and LVDd (14.6 mm versus 10.7 mm, p b 0.01). There were no differences in LVDs, diameter of the descending aorta, TR, EF, and FS between the two groups. 3.3. Analysis of risk factors and predictors of poor prognosis in echocardiographic parameters According to the ROC curve analysis, the recommended cutoff values for the diameter of RPA, diameter of LPA, LVDs, LVDd, diameter of the
descending aorta, EF, and FS for the prediction of death at 90 days of age were 3.3 mm [area under the curve (AUC), 0.92; p b 0.01], 2.7 mm (AUC, 0.79; p = 0.01), 9.3 mm (AUC, 0.69; p = 0.06), 10.8 mm (AUC, 0.87; p b 0.01), 4.5 mm (AUC, 0.58; p = 0.75), 45% (AUC, 0.56; p = 0.22), and 23% (AUC, 0.62; p = 0.13), respectively (Fig. 1). Univariate analysis showed that continuous R-L shunt [crude odds ratio (OR), 10.66; 95% confidence interval (CI), 1.22–93.32], RPA diameter of b 3.3 mm (crude OR, 28.47; 95% CI, 3.24–249.34), LPA diameter of b 2.7 mm (crude OR, 24.29; 95% CI, 2.79–221.42), and LVDd of b10.8 mm (crude OR, 9.86; 95% CI, 2.01–48.29) were significant risk factors for death at 90 days of age (Table 3). Multiple logistic regression analysis showed that an RPA diameter of b3.3 mm (adjusted OR, 10.28; 95% CI, 1.15–249.19) and LVDd of b10.8 mm (adjusted OR, 7.86; 95% CI, 1.01–82.82) were significant risk factors for death at 90 days of age (Table 4). Continuous R-L shunt (adjusted OR, 4.31; 95% CI, 0.41–114.23) and LPA diameter of b2.7 mm (adjusted OR, 6.89; 95% CI, 0.74–160.86) were no longer significant. 4. Discussion Survival rates for patients with CDH have increased during the past decades because of strategies such as iNO, ECMO, gentle ventilation, and delayed surgery [2,11,12]. However, CDH continues to be a vexing congenital malformation with a broadly variable cardiopulmonary disease severity at birth, and the survival rates of patients with severe
Fig. 1. Receiver operating characteristic(ROC) analysis for predicting non-survival with congenital diaphragmatic hernia according to the diameter of RPA, diameter of LPA, LVDs, LVDd, diameter of the descending aorta, EF, and FS cut-off values. LPA, left pulmonary artery; RPA, right pulmonary artery; LVDs, left ventricular dimension at systole; LVDd, left ventricular dimension at diastole; DA, descending aorta; EF, ejection fraction; FS, fractional shortening; AUC, area under the curve.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014
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M. Yamoto et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
Table 3 Univariate analysis for death before 90 days of age. Variables
Crude odds ratio
95% CI
p value
Continuous R-L shunt at the ductus Diameter of RPA of b3.3 mm Diameter of LPA of b2.7 mm LVDs of b9.3 mm LVDd of b10.8 mm Diameter of DA of b4.5 mm Tricuspid regurgitation EF of b45% FS of b23%
10.66 28.47 24.29 2.01 9.86 1.71 2.02 4.66 3
1.22–93.32 3.24–249.34 2.79–221.42 0.44–9.02 2.01–48.29 0.15–18.97 0.23–17.55 0.74–29.37 0.28–31.28
b0.01* b0.01* b0.01* 0.48 b0.01* 0.53 0.46 0.08 0.36
R-L, right to left; LPA, left pulmonary artery; RPA, right pulmonary artery; LVDs, left ventricular dimension at systole; LVDd, left ventricular dimension at diastole; DA, descending aorta; EF, ejection fraction; FS, fractional Shortening; CI, confidence interval.
CDH remain far from satisfactory. CDH presents with a spectrum of disease severity that makes it difficult to accurately predict outcome. Several publications have attempted to describe an accurate outcome predictor for neonates with CDH [13–15]. ++Furthermore, advances in diagnostic imaging in the assessment of CDH have facilitated the planning of appropriate management and therapeutic strategies [16,17]. Although these parameters are excellent predictors of lung volume, they share the limitation of being structural measurements that do not offer information regarding lung vasculature and function. Until functional predictors are identified, the prognostic information concerning fetal CDH will remain incomplete [18]. We evaluated the association of pulmonary circulation parameters with the prognosis of CDH. In this study, baseline variables and univariate analysis revealed significant differences in the presence of the continuous R-L shunt, diameter of RPA, diameter of LPA, and LVDd between patients who survived to 90 days of age and those who did not. Cardiac output within 24 h after birth was not strongly correlated with a poor prognosis. These four factors were confounding factors, although they certainly represent the severity of the disease among CDH patients. Finally, multiple logistic regression analysis revealed that an RPA diameter of b3.3 mm and LVDd of b 10.8 mm were significant prognostic factors among the related clinical and anatomic features evaluated by echocardiography. In general, the diameter of the PA depends on the physical size of the infant. However, fetal/postnatal PA diameters of babies with CDH are not correlated with physical size but instead depend on the severity of pulmonary hypoplasia [6]. Additionally, this study demonstrated that RPA diameter was more significantly correlated with severity than LPA diameter, which suggests that the analysis of the RPA enables the clinician to assess disease severity more precisely than LPA analysis. We suggest that RPA diameter correlates with capacity and function of the side of the lung that is unaffected, and thus, prognosis. Furthermore, this study suggests that diastolic dysfunction and hypoplasia of the left ventricle occurs with compression by the visceral organs shortly after birth in severe cases of CDH. In the literature, there are descriptions of three possible pathogenic mechanisms leading to a small left ventricle in patients with severe CDH. First, abdominal viscera displacement and high pressure of right ventricle induces a persistent mechanical compression of the left heart and creates a hemodynamic situation similar to that in chronic cardiac tamponade, with the result that cardiac diastolic dysfunction prevents sufficient left ventricle Table 4 Multiple logistic regression analysis for death before 90 days of age. Variables
Adjusted odds ratio
95% CI
p value
Continuous R-L shunt at the ductus Diameter of RPA of b3.3 mm Diameter of LPA of b2.7 mm LVDd of b10.8 mm
4.31 10.28 6.89 7.86
0.41–114.23 1.15–249.19 0.74–160.86 1.01–82.82
0.23 0.03* 0.09 0.04*
R-L, right to left; LPA, left pulmonary artery; RPA, right pulmonary artery; LVDd, left ventricular dimension at diastole; CI, confidence interval.
growth [19]. Second, reduced pulmonary vasculature causes a reduction in pulmonary blood flow, leading to a decreased preloading of the left ventricle, which, in fetuses, is defined as the sum of pulmonary blood flow and blood flow passing through the foramen ovale from the right atrium to the left atrium. In patients with severe CDH and pulmonary hypoplasia owing to persistent mechanical compression from herniated viscera, pulmonary blood flow cannot increase in late pregnancy, and a marked reduction is observed in the blood flow returning from pulmonary circulation compared with that in normal fetuses [20,21]. Finally, intrathoracic herniation of the liver, which presumably results from the rerouting of the majority of the ductus venous and inferior vena cava flow toward the right side of the heart, is observed in the majority of fetuses with severe CDH and predominant left heart hypoplasia [22]. If the compression by the visceral organs cause small left ventricle, early surgery may eliminate the left ventricle diastolic disorder and improve the left ventricle performance for patients with small LVDd. This study was limited by the restrictions inherent in a retrospective, multicenter, cohort study design. It was conducted in a retrospective manner using a questionnaire. In this study, the nine participating institutions do not have a standardized protocol, and thus, there was a lack of consensus for indications for treatment. Nonetheless, an excellent positive correlation was observed between the diameter of RPA and LVDd in the present study. This statistical analysis would be practical and helpful for the parental counseling and prognostic prediction, and contains potentially important data on which to base further prospective studies. More accurate prospective studies and an analysis of the correlation based on the methods of the measurement and treatment are, therefore, needed to confirm the present findings. 5. Conclusions Echocardiography provides useful information for predicting the outcomes of patients with isolated left-sided CDH. In particular, smaller diameter of the RPA and smaller LVDd were good predictors of mortality in infants with CDH. Further advances that can improve patient outcomes are still needed, and elucidation of more accurate cardiac function parameters for predicting prognosis is also essential to make progress in the treatment of patients with severe, isolated left-sided CDH. Conflict of interest The authors declare that they have no conflicts of interest. Acknowledgments This work was supported by a grant from the Ministry of Health, Labor and Welfare of Japan (Health and Labor Sciences Research Grants for Research on Intractable Diseases). The authors gratefully acknowledge the contributions of all the pediatric surgery and/or tertiary perinatal care centers for the collection of the data that were used in this study. References [1] Albanese CT, Lopoo J, Goldstein RB, et al. Fetal liver position and perinatal outcome for congenital diaphragmatic hernia. Prenat Diagn 1998;18:1138–42. [2] Boloker J, Bateman DA, Wung JT, et al. Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/ elective repair. J Pediatr Surg 2002;37:357–66. [3] Casaccia G, Crescenzi F, Dotta A, et al. Birth weight and McGoon index predict mortality in newborn infants with congenital diaphragmatic hernia. J Pediatr Surg 2006; 41:25–8. [4] Fauza DO, Wilson JM. Congenital diaphragmatic hernia and associated anomalies: their incidence, identification, and impact on prognosis. J Pediatr Surg 1994;29: 1113–7. [5] Waag KL, Loff S, Zahn K, et al. Congenital diaphragmatic hernia: a modern day approach. Semin Pediatr Surg 2008;17:244–54.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014
M. Yamoto et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx [6] Sokol J, Bohn D, Lacro RV, et al. Fetal pulmonary artery diameters and their association with lung hypoplasia and postnatal outcome in congenital diaphragmatic hernia. Am J Obstet Gynecol 2002;186:1085–90. [7] Hasegawa S, Kohno S, Sugiyama T, et al. Usefulness of echocardiographic measurement of bilateral pulmonary artery dimensions in congenital diaphragmatic hernia. J Pediatr Surg 1994;29:622–4. [8] Okazaki T, Kohno S, Hasegawa S, et al. Congenital diaphragmatic hernia: efficacy of ultrasound examination in its management. Pediatr Surg Int 2003;19:176–9. [9] Vogel M, McElhinney DB, Marcus E, et al. Significance and outcome of left heart hypoplasia in fetal congenital diaphragmatic hernia. Ultrasound Obstet Gynecol 2010; 35:310–7. [10] Mohseni-Bod H, Bohn D. Pulmonary hypertension in congenital diaphragmatic hernia. Semin Pediatr Surg 2007;16:126–33. [11] Bagolan P, Casaccia G, Crescenzi F, et al. Impact of a current treatment protocol on outcome of high-risk congenital diaphragmatic hernia. J Pediatr Surg 2004;39:313–8. [12] Wung JT, Sahni R, Moffitt ST, et al. Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube. J Pediatr Surg 1995;30:406–9. [13] Congenital Diaphragmatic Hernia Study Group. Estimating disease severity of congenital diaphragmatic hernia in the first 5 minutes of life. J Pediatr Surg 2001;36: 141–5. [14] Schultz CM, DiGeronimo RJ, Yoder BA. Congenital diaphragmatic hernia: a simplified postnatal predictor of outcome. J Pediatr Surg 2007;42:510–6.
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[15] Skarsgard ED, MacNab YC, Qiu Z, et al. SNAP-II predicts mortality among infants with congenital diaphragmatic hernia. J Perinatol 2005;25:315–9. [16] Kitano Y, Nakagawa S, Kuroda T, et al. Liver position in fetal congenital diaphragmatic hernia retains a prognostic value in the era of lung-protective strategy. J Pediatr Surg 2005;40:1827–32. [17] Usui N, Okuyama H, Sawai T, et al. Relationship between L/T ratio and LHR in the prenatal assessment of pulmonary hypoplasia in congenital diaphragmatic hernia. Pediatr Surg Int 2007;23:971–6. [18] Badillo A, Gingalewski C. Congenital diaphragmatic hernia: treatment and outcomes. Semin Perinatol 2014;38:92–6. [19] Inamura N, Kubota A, Nakajima T, et al. A proposal of new therapeutic strategy for antenatally diagnosed congenital diaphragmatic hernia. J Pediatr Surg 2005;40: 1315–9. [20] Baumgart S, Paul JJ, Huhta JC, et al. Cardiac malposition, redistribution of fetal cardiac output, and left heart hypoplasia reduce survival in neonates with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation. J Pediatr 1998;133:57–62. [21] Yamoto M, Tanaka Y, Fukumoto K, et al. Cardiac fetal ultrasonographic parameters for predicting outcomes of isolated left-sided congenital diaphragmatic hernia. J Pediatr Surg 2015;50:2019–24. [22] Stressig R, Fimmers R, Eising K, et al. Intrathoracic herniation of the liver (‘liver-up’) is associated with predominant left heart hypoplasia in human fetuses with left diaphragmatic hernia. Ultrasound Obstet Gynecol 2011;37:272–6.
Please cite this article as: Yamoto M, et al, Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia, J Pediatr Surg (2016), http://dx.doi.org/10.1016/j.jpedsurg.2016.09.014