The CDH Registry and Study GroupPast, Present and Future

CDH Registry

Background of the Registry Current Status Major Publications Future Plans

5 Neonatologists

7 Pediatric Surgeons

3 Intensivists

CDH Registry

Existing data forms collated and modified Voluntary collection A priori plan to limit total amount of data Data collection begun 1995 Data in secure, anonymized database Some PHI – DOB, DOS

The Congenital Diaphragmatic Study Group

Versions of the CDH Registry• Version 1 1995-2000

oDefining the problem - medications, ventilator strategies, ECLS use

Version 1

Version 1

Versions of the CDH Registry• Version 1 1995-2000

oDefining the problem - medications, ventilator strategies, ECLS use

• Version 2 2001-2006oUnderstanding the details - delivery, oxygen/carbon dioxide, discharge

status, cardiac anomalies

CDH Registry – Why it has worked Management (2000 – 2019)

Version 2

Versions of the CDH Registry• Version 1 1995-2000

oDefining the problem - medications, ventilator strategies, ECLS use

• Version 2 2001-2006oUnderstanding the details - delivery, oxygen/carbon dioxide, discharge

status, cardiac anomalies

• Version 3 2007-2014oStaging - classifying defect size, pulmonary hypertension

Version 3

Version 3

Versions of the CDH Registry• Version 1 1995-2000

oDefining the problem - medications, ventilator strategies, ECLS use

• Version 2 2001-2006oUnderstanding the details - delivery, oxygen/carbon dioxide, discharge

status, cardiac anomalies

• Version 3 2007-2014oStaging - classifying defect size

• Version 4 2015-presentoThe role of the heart and PH, prenatal dx

Issues addressed by version 4• Timing of surgical repair when receiving ECLS• Cardiac dysfunction in CDH• CDH-associated pulmonary hypertension• Prenatal diagnosis / prediction in CDH

85 Centers/17 countries/12,000 Patients

Hernia Side

Left Right

Bilateral

79% 20%

Operative Approach

SubcostalThoracic

Other

90%6%

4%

1995-1996

Subcostal ThoracicOther

82%14%

1%

2017-2018

2%

1%ThoracoscopicLaparoscopic

Patch Used In Repair

Yes No

49%51%

1995-1996

Yes

58% 42%

2017-2018

No

Repair On ECMO (Of all ECMO)

Yes No

23% 77%

1995-1996

Yes No

52% 48%

2017-2018

1200-1800

Time of Day For Repair

0600-12002400-0600

1800-2400

1995-1996

2%

10%40%

48%

1200-18001800-2400

0600-1200

2017-2018

45%

51%

4%

05

101520253035404550

0-24 24-48 48-72 72-96 96-120 >120Hours of Age

Timing of Operation (No ECMO)

(38)

(14)(11)(10)

(8)

(19)

1995-1996

0

50

100

150

200

250

0-24 24-48 48-72 72-96 96-120 >120Hours of Age

Timing of Operation (No ECMO)

(7)

(12)

(18)(18)

(13)

(32)

2017-2018

Publications• Data available only to CDHSG members• Authored by writing committee on behalf of CDHSG• 55 publications • Multiple studies in progress

0102030405060708090

100

Primaryrepair

Patch - noagenesis

Patch -Agenesis

Defect Size

Size Does Matter!

It became apparent that not all CDH were created equal and that size of defect was important

Version III designed to quantitate size of defect

Defect Size

Standardized Reporting for Congenital Diaphragmatic Hernia

An International Consensus

MethodsFactors Evaluated

Defect class Cardiac anomalies Chromosomal anomalies Birthweight /Gestational age Apgar Scores

CDHSG Staging

A B C D

Lally, et al, J Pediatr Surg, 2013

44% 30% 13%13%96% 78% 58%99%Survival

Frequency

V. 3 of Registry Grouped by defect size Compared for associated anomalies

Methods

0

5

10

15

20

25

30

35

40

45

A B C D

All Major Anomalies Major Cardiac

PEDIATRICS Volume 138: 2016:e2016204

V. 3 of Registry Evaluated recorded morbidity at d/c Correlated degree of morbidity to defect Analysis between groups and time

Methods

Defect correlated with morbidity as well as mortality Overall improving morbidity No major changes in large defect patients

Conclusions

Is aggressive surgical management worth it?

Harting et al, Ann Surg, 2018

Is aggressive surgical management worth it?

Harting et al, Ann Surg, 2018

Aggressive approach leads to highest survival It is costly Morbidity is high

Conclusions

What about Nitric Oxide ?

Putnam et al, JAMA Pediatrics, 2017

What about Nitric Oxide ?

Putnam et al, JAMA Pediatrics, 2017

What about Nitric Oxide ?

Putnam et al, JAMA Pediatrics, 2017

Putnam et al, JAMA Pediatrics, 2017

What about Nitric Oxide ?

Treatment with iNO was associated with a 15% higher absolute mortality

iNO use highly variable between centers > 1/3 patients w/o CDH-PHTN received iNO Little data to support iNO benefit in CDH iNO use is associated with worse outcome iNO use in patients with CDH needs re-evaluation

Conclusions

Centers with at least 22 years of continual participation Grouped by 5 year intervals Evaluated Overall Survival Looked at O:E survival

25 Years – Any Progress?

Significant increase in survival over years Current overall survival is 73% for all comers Surgical survival is 85% Remains a large variation amongst centers

25 Years – Any Progress?

The CDH Study Registry

• Ability to study infrequent problems• Data on very large number of patients• Individual centers can compare themselves with others• Demonstrate changes over time of management and outcome

PROs

The CDH Study Registry

• Observational data• Inability to evaluate long-term sequelae• Difficult to collect complicated information• Wide spectrum of patients and treatment philosophies

CONs

The “Gold Standard”Randomized Clinical Trial

• Expensive ($500k-$3 million+)• Labor intensive• Takes a long time (5-10 years)• Requires consent / challenges of recruitment• Requires multi-institutional cooperation• Answers a single question• Nearly impossible to achieve appropriate sample size in CDH

The future of the CDHSG• Ongoing evolution of versions to address current questions

• Version 5 – Breakout session this meeting• Management standardization• Long term data collection• Novel statistical analysis

John Roesler – DOB 11/26/2019