Measurement of Lung Area at Chest Radiography to Define the Prognosis in Newborns With CDH

Congenital Diaphragmatic Hernia Clinical Trial

— NeoAPACHE  

Official title:

Assessment of the Pulmonary Area in Newborn With Congenital Diaphragmatic Hernia: a Retrospective Analysis of Respiratory Function, Risk of Recurrence and Mortality

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04396028
• Other study ID #: OSMAMI-04/05/2020-0015998-U
• Status: Recruiting
• Start date: July 9, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: August 2021
• Source: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Contact: Giacomo Cavallaro, MD, PhD
• Phone: +390255032234
• Email: giacomo.cavallaro[@]policlinico.mi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

CDH represents a malformative disorder characterized by an incomplete diaphragm formation. This results in poor lung development (pulmonary hypoplasia), associated with altered vascularization of the lung (pulmonary hypertension), determining respiratory and cardiovascular insufficiency at birth. CDH shows high mortality and significant morbidity so that its prognostic evaluation remains challenging.

The measurement of lung area at chest radiography is considered an alternative method to assess lung development in the newborn. A correlation between lung area and functional residual capacity (FRC) was demonstrated in newborns with CDH.

However, the relationship between lung area and other aspects of respiratory function has never been investigated. Since CDH compromises lung development as a whole, it is likely to assume that lung area at birth may have an impact on patient's performance at pulmonary function tests during follow-up. In particular, as lung area increased, a trend towards normalization in respiratory function would be expected.

Moreover, the role of the radiographic area at birth as a possible predictor of death should be further characterized, aiming to clarify the complex association between lung area and mortality, which is strongly influenced by both pulmonary hypoplasia and pulmonary hypertension.

The principal aim of this study is to determine if changes in the radiographic pulmonary area measured on the first day of life are related to patients' pulmonary function at one year of life, considering two main respiratory parameters: tidal volume (VT) and respiratory rate (RR).

Secondary objectives are the analysis of the association between radiographic pulmonary area and: 1) risk of death during the first year of life; 2) risk of hernia recurrence during the first year of life.

The investigators will retrospectively consider a cohort of newborns with CDH. For each patient, the investigators will measure lung area at chest radiography performed preoperatively within 24 hours after birth and will collect data regarding demographics, clinical course, and follow-up.

Through our study, the investigators aim to improve the current understanding of the role of radiographic lung area in characterizing lung development and prognosis in CDH patients. The investigators believe that this could become a low-cost and straightforward tool that will assist the clinician in making decisions regarding the patient's management and follow up.

Description:

The study period considered will be January 2012 - December 2018. From the medical record of each patient, the investigators will collect the following data: prenatal history, hernia severity, fetal endoscopic tracheal occlusion (FETO) procedure, demographics, respiratory insufficiency, and mechanical ventilation, cardiocirculatory insufficiency and pharmacological hemodynamic support, pulmonary hypertension and need for pulmonary vasodilators, need for extracorporeal life support (ECMO), comorbidities, timing of surgical repair, use of prosthetic patch, intra- and post-operative complications, clinical and instrumental follow-up, pulmonary function tests, recurrence, death. The confidentiality of all data will be maintained.

Regarding the assessment of the radiographic pulmonary area, two operators (a neonatologist and a pediatric radiologist) will independently review all preoperative digital radiograms performed within 24 hours of life. For each patient, the radiogram showing the best lung-recruitment will be selected. Lung area will be assessed by freehand tracing of the perimeter of the thoracic area, as outlined by the diaphragm and the rib cage, excluding the mediastinal structures and abdominal contents herniated in the thorax. The only aerated portion of the lungs will be considered. The corresponding area will be automatically calculated by the software. Three measures will be performed: 1) ipsilateral lung area (cm2); 2) contralateral lung area (cm2); 3) total lung area (cm2), derived from the sum of the preceding two. The agreement between lung measurements performed by the two operators will be evaluated to verify the reproducibility of the method.

Pulmonary function test performed during spontaneous sleeping at the age of 1 year will be reviewed. The measurements of VT and RR will be recorded. The predicted value of VT and RR will be obtained, and their Z-Score will be calculated using reference equations of a population of healthy children. Z-Score is a numerical measure used to express how much an observed value deviates from the mean expected normal value in terms of standard deviation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 85
• Est. completion date: December 31, 2021
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

Inclusion Criteria:

• Inborn and outborn patients admitted to the NICU within 24 hours after birth.

• Prenatal or postnatal (within 24 hours after birth) diagnosis of CDH.

• Preoperative chest radiograph performed for clinical purposes within 24 hours after birth in our NICU.

Exclusion Criteria:

• Diagnosis of CDH made beyond 24 hours after birth

• Admission to the NICU beyond 24 hours after birth

• Preoperative chest radiograph performed beyond 24 hours after birth, rotated/asymmetric, with air leak (pneumothorax, pneumoperitoneum), not performed in our NICU or not accessible

• Early death (within 1 hour after birth)

Related Conditions & MeSH terms

• Congenital Diaphragmatic Hernia
• Hernia
• Hernia, Diaphragmatic
• Hernias, Diaphragmatic, Congenital

Intervention

Other:
• data collection
retrospective data collection

Locations

Country	Name	City	State
Italy	Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico	Milan	MI

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Country where clinical trial is conducted

Italy, 

References & Publications (19)

Al-Iede MM, Karpelowsky J, Fitzgerald DA. Recurrent diaphragmatic hernia: Modifiable and non-modifiable risk factors. Pediatr Pulmonol. 2016 Apr;51(4):394-401. doi: 10.1002/ppul.23305. Epub 2015 Sep 7. — View Citation

American Academy of Pediatrics Section on Surgery; American Academy of Pediatrics Committee on Fetus and Newborn, Lally KP, Engle W. Postdischarge follow-up of infants with congenital diaphragmatic hernia. Pediatrics. 2008 Mar;121(3):627-32. doi: 10.1542/peds.2007-3282. Review. — View Citation

Bagolan P, Morini F. Long-term follow up of infants with congenital diaphragmatic hernia. Semin Pediatr Surg. 2007 May;16(2):134-44. Review. — View Citation

Chen C, Jeruss S, Chapman JS, Terrin N, Tighiouart H, Glassman E, Wilson JM, Parsons SK. Long-term functional impact of congenital diaphragmatic hernia repair on children. J Pediatr Surg. 2007 Apr;42(4):657-65. — View Citation

Coughlin MA, Werner NL, Gajarski R, Gadepalli S, Hirschl R, Barks J, Treadwell MC, Ladino-Torres M, Kreutzman J, Mychaliska GB. Prenatally diagnosed severe CDH: mortality and morbidity remain high. J Pediatr Surg. 2016 Jul;51(7):1091-5. doi: 10.1016/j.jpedsurg.2015.10.082. Epub 2015 Nov 10. — View Citation

Dassios T, Ali K, Makin E, Bhat R, Krokidis M, Greenough A. Prediction of Mortality in Newborn Infants With Severe Congenital Diaphragmatic Hernia Using the Chest Radiographic Thoracic Area. Pediatr Crit Care Med. 2019 Jun;20(6):534-539. doi: 10.1097/PCC.0000000000001912. — View Citation

Dassios T, Curley A, Krokidis M, Morley C, Ross-Russell R. Correlation of radiographic thoracic area and oxygenation impairment in bronchopulmonary dysplasia. Respir Physiol Neurobiol. 2016 Jan;220:40-5. doi: 10.1016/j.resp.2015.09.009. Epub 2015 Sep 26. — View Citation

Deprest J, Brady P, Nicolaides K, Benachi A, Berg C, Vermeesch J, Gardener G, Gratacos E. Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial. Semin Fetal Neonatal Med. 2014 Dec;19(6):338-48. doi: 10.1016/j.siny.2014.09.006. Epub 2014 Nov 11. Review. — View Citation

Dimitriou G, Greenough A, Davenport M, Nicolaides K. Prediction of outcome by computer-assisted analysis of lung area on the chest radiograph of infants with congenital diaphragmatic hernia. J Pediatr Surg. 2000 Mar;35(3):489-93. — View Citation

Dimitriou G, Greenough A, Kavvadia V, Shute M, Karani J. A radiographic method for assessing lung area in neonates. Br J Radiol. 1999 Apr;72(856):335-8. — View Citation

Hollinger LE, Buchmiller TL. Long term follow-up in congenital diaphragmatic hernia. Semin Perinatol. 2020 Feb;44(1):151171. doi: 10.1053/j.semperi.2019.07.010. Epub 2019 Jul 31. Review. — View Citation

Jancelewicz T, Chiang M, Oliveira C, Chiu PP. Late surgical outcomes among congenital diaphragmatic hernia (CDH) patients: why long-term follow-up with surgeons is recommended. J Pediatr Surg. 2013 May;48(5):935-41. doi: 10.1016/j.jpedsurg.2013.02.005. — View Citation

May C, Prendergast M, Salman S, Rafferty GF, Greenough A. Chest radiograph thoracic areas and lung volumes in infants developing bronchopulmonary dysplasia. Pediatr Pulmonol. 2009 Jan;44(1):80-5. doi: 10.1002/ppul.20952. — View Citation

Nguyen TT, Hoo AF, Lum S, Wade A, Thia LP, Stocks J. New reference equations to improve interpretation of infant lung function. Pediatr Pulmonol. 2013 Apr;48(4):370-80. doi: 10.1002/ppul.22656. Epub 2012 Sep 4. — View Citation

Putnam LR, Gupta V, Tsao K, Davis CF, Lally PA, Lally KP, Harting MT; Congenital Diaphragmatic Hernia Study Group. Factors associated with early recurrence after congenital diaphragmatic hernia repair. J Pediatr Surg. 2017 Jun;52(6):928-932. doi: 10.1016/j.jpedsurg.2017.03.011. Epub 2017 Mar 16. — View Citation

Rocha G, Azevedo I, Pinto JC, Guimarães H. Follow-up of the survivors of congenital diaphragmatic hernia. Early Hum Dev. 2012 Apr;88(4):255-8. doi: 10.1016/j.earlhumdev.2011.08.025. Epub 2011 Sep 23. — View Citation

Snoek KG, Greenough A, van Rosmalen J, Capolupo I, Schaible T, Ali K, Wijnen RM, Tibboel D. Congenital Diaphragmatic Hernia: 10-Year Evaluation of Survival, Extracorporeal Membrane Oxygenation, and Foetoscopic Endotracheal Occlusion in Four High-Volume Centres. Neonatology. 2018;113(1):63-68. doi: 10.1159/000480451. Epub 2017 Oct 28. — View Citation

Snoek KG, Reiss IK, Greenough A, Capolupo I, Urlesberger B, Wessel L, Storme L, Deprest J, Schaible T, van Heijst A, Tibboel D; CDH EURO Consortium. Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update. Neonatology. 2016;110(1):66-74. doi: 10.1159/000444210. Epub 2016 Apr 15. — View Citation

Van der Veeken L, Russo FM, De Catte L, Gratacos E, Benachi A, Ville Y, Nicolaides K, Berg C, Gardener G, Persico N, Bagolan P, Ryan G, Belfort MA, Deprest J. Fetoscopic endoluminal tracheal occlusion and reestablishment of fetal airways for congenital diaphragmatic hernia. Gynecol Surg. 2018;15(1):9. doi: 10.1186/s10397-018-1041-9. Epub 2018 May 8. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association between radiographic pulmonary area and respiratory function	To evaluate the association between changes in radiographic pulmonary area at birth and trend in VT and RR measured at pulmonary function tests performed during follow-up at the age of 1 year. The association will be studied through linear regression models.	12 months
Secondary	Association between radiographic pulmonary area and mortality	To evaluate the association between changes in radiographic pulmonary area and the risk of death during the first year of life, following logistic regression models.	12 months
Secondary	Association between radiographic pulmonary area and hernia recurrence	To evaluate the association between changes in radiographic pulmonary area and the risk of hernia recurrence during the first year of life, following logistic regression models.	12 months