Newborn Screening for
Critical Congenital Heart Diseases
(CCHD)
Lazaros Kochilas, MD
Associate Professor of Pediatrics
University of Minnesota
Disclosures and Support
Pediatric Grand Rounds
Lazaros Kochilas, MD
I will not discuss off label use and/or
investigational use in my presentation
and
I have no conflicts of interest to disclose
…however, I have an interest in the
conflict of screening for CCHD!
Advocates:
Families with CHD
Ped. Cardiologists
Possible opponents:
Delivery Hospitals
Third party payers
Neutral:
Public Health analysts
Learning objectives
• Identify need for screening for CCHD in the nursery
• Discuss evidence-based recommendations for newborn screening for CCHD
• Describe efforts for screening implementation on state and national levels
• Discuss barriers for screening implementation
Criteria for using and appraising screening
• Population:
- sufficiently high incidence of screened condition
- likely to be compliant
• Condition:
- significant mortality / morbidity
- known natural history with detectable presymptomatic period
- treatment makes a difference when introduced early
• Test:
- suitable (simple, safe, reliable, validated)
- known distribution of values in diseased and non-diseased
- acceptable validation process for (+) screens
- widely available and acceptable
• Treatment:
- acceptable, available, effective, agreement on whom to treat
• Program:
- adequate staffing/facilities
- program is acceptable and effective
- acceptable cost
- quality management / ongoing re-evaluation
Selection Criteria for Newborn Screening
Conceptual Framework
Definition - Identifiable at birth - Condition characteristics
Test characteristics – Treatment - Cost effectiveness
Concepts in screening
• All screening programs do harm; some do good as well
• Criteria for appraising screening
• Screening is a program not a test
• Assess opportunity cost
Wilson, J and Jungner, J: Principles and practice of screening for disease: WHO, 1968
Gray, MJ: New concepts in screening; BJ Gen Practice, 2004, 54, 292-298
Particular challenges
• Limitations of randomized controlled studies
• Limited evidence to assess benefit/risk ratio
Disease
Screening
adverse
effects
+
-
-
A
B
+
C
D
• Need to calculate opportunity costs
“Would you spend $$$ for screening for CHD?” vs.
“If you had $$$ to spend for the field of CHD would you spend it for screening?”
• Public pressure for increasing sensitivity of the testing
• Challenge of definition
Process for addition of new conditions
to the uniform panel of newborn screening
Nomination
Form
• Not adding to the NBS
• Additional studies
• Pilot study
• Targeted screening
• Add to NBS
HRSA
Administrative
Review
Evidence
Review Group
SACHDNC*
Recommendations
to the HHS
Secretary
*Secretary’s Advisory Committee on Heritable
Disorders in Newborns and Children
Implementation
workgroup
Timeline of pulse oximetry screen for CCHD
Large European prospective studies
(Norway, Sweden, UK, Germany, Switzerland)
oximetry screen
1st clinical reports
Larger prospective study
In NY (Koppel)
Request to AHA
For recommendations
Several European countries
adopt pulse-ox screen
as standard of care
SACHDNC
recommended
adding pulse-ox screen
AHA comment
Evidence not sufficient
Proposed bill in TN
to mandate screening
2002
2005
AHA/AAP
statement comment
2008
2011
Definition of the primary target: Critical CHD (CCHD)
Requiring surgical, cath or pharmacologic intervention to
avoid death or end-organ damage
- Hypoplastic left heart syndrome (HLHS)
- Pulmonary atresia
-Tetralogy of Fallot (TOF)
-Total anomalous pulmonary venous return (TAPVR)
- Transposition of the great arteries (TGA)
- Tricuspid atresia
- Truncus arteriosus
Current Uniform Screening Panel
• 29 primary conditions
-20 metabolic detected by MS (AA, FAO, OA)
-3 Hg-pathies (S/S, S/β Thal, S/C)
- 6 Others (BIOT, CAH, CF, CH, GALT, HEAR*)
• 25 secondary targets
-22 metabolic detected by MS (AA, FAO, OA)
- 1 Hg-pathies variants
- 6 Others (GAL-epimerase, GAL-kinase)
* Only point-of-care type of screening
Congenital Heart Diseases: The magnitude of the problem
CHD:
5-10 / 1,000 live births
1.4 cyanotic CHD / 1,000 live births
2 critical CHD / 1,000 live births
25,000 cases of CHD/yr in US
25% of infantile deaths
31% of neonatal deaths
All together
1.55 /1,000 live births
Heron, M., et al. (2009). Deaths: Final data for 2006. National Vital Statistics Reports, 57(14). U.S. CDC and Prevention.
http://www.cdc.gov/ncbddd/features/heartdefects-keyfindings2010.html
Incidence of CHD
Timing of death from CHD
50% of deaths from CHD occur in 1st year
and
50% of infantile deaths occur in 1st month of life
Boneva, R: Circulation. 2001;103:2376
Deaths from undiagnosed CHD in Wisconsin
• 345,573 births (2002-2006)
• 14 deaths during first 2 wks of life (1: 24,684)
Benton, N and Hokanson,J: Missed Congenital Heart Disease in Neonates
Congenital Heart Disease 2010; 5(3):292-296
Significant physiologic compromise from
undiagnosed CHD
• 490 patients with undiagnosed critical CHD (2000-2003)
• 76 (15.5%) with significant physiologic compromise
• 33 (6.7%) preventable
• Incidence of potentially preventable 1:15,000-1:26,000
Schultz, A: Epidemiologic features of the presentation of critical CHD: implications for screening
Pediatrics 2008; 121(4):751-757
Missed Critical Congenital Heart Diseases (CCHD)
Hoffman, J. It is time for routine neonatal screening by pulse oximetry.
Neonatology 2011;99:1-9
Types of frequently unrecognized CCHD
Hoffman, J. It is time for routine neonatal screening by pulse oximetry. Neonatology 2011;99:1-9
Screening for CCHD
- Fetal ultrasonography
- Physical examination
- Pulse oximetry
Pulse oximetry as screening method
- pulse oximetry measures the amount of O2Hgb in the arterial blood
- based on differential absorption of O2Hgb and RHgb
- coupled with ability to separate pulsatile from non-pulsatile components
- non-invasive and painless
- accurate with newer generation oximeters
- “motion resistant” (SET) technology
- fast (<2 min) and reliable
- inexpensive
- peripheral perfusion index (PPI)
Distribution of O2 saturations in 24h newborns with
newer generation pulse oximeters
Newborns
Critical CHD
de-Wahl Grannelli, A: Acta Paediatrica 2005;94:1590
O2 saturation values in patients with CCHD
de-Wahl Grannelli, A: Acta Paediatrica 2005;94:1590
Reliability in wide range of O2 saturations
de-Wahl Grannelli, A: Acta Paediatrica 2005;94:1590
Peripheral perfusion index (PPI) for screening for
critical left heart obstructive disease (LVOD)
PPI < 0.7 in at least one limb
suggesting of LVOD
OR 23.8 [95% CI (6.4-88.7)]
de-Wahl Grannelli, A:
Acta Paediatrica 2007;96:1455
Studies examining pulse oximetry screening for CCHD
- 13 large studies ( > 200,000 newborns )
- Overall test performance >24h:
- Sensitivity 70%
Specificity 99.9%
- False Positive Rate 0.035%
False Negative Rate 0.01%
- Positive Predictive Value 47%
Negative Predictive Value 99.9%
- overall improved detection rate vs physical exam alone
- improved outcomes?
Mahle, W et al.: Role of Pulse Oximetry in Examining Newborns for Congenital Heart Disease
A Scientific Statement From the AHA and AAP, Circulation 2009; 120:447-458
The Swedish prospective study (2004-2007)
de-Wahl Grannelli, A: BMJ 2009; 338
W. Göteland
Contemporary cohort
Total
46,693
108,604
Screened
39,821
-
62
2
41 / 5
19
5
0
109
9
72
28
0
62%
N/A
69 (0.17%)
N/A
99.8%
N/A
11 (0.03%)
N/A
CCHD
Prenatal Dx
Clinically / PE (only)
Pulse Ox
Undiagnosed
Deaths
Sensitivity
False positives / FPR
Specificity
False negatives / FNR
p-value
0.0025*
0.16*
Screening in Minnesota:
Region’s Hospital, Saint Paul
•
•
•
•
Location: Urban (Twin Cities metropolitan area)
Number of deliveries:  2,500/year
Majority of pregnancies receive prenatal care
No high risk pregnancies
Newborn screen by pulse oximetry
(Data provided by Larry Condon, MD)
• Start of implementation: 2005
• Implemented as new standard of care – No consent
• Timing: date of discharge (most cases≥ 24h)
• Cut off for normal ≥ 95%
• Location of probe: foot
• Type of probe: reusable
• No consent
• No formal f/u procedure
Screening Results
Total patients
12,462
Total ECHOs
34 (0.27 %)
Indications
Murmur
22
Syndromes
7
IDM
2
Abnormal screens
3 (0.024%)
CCHD
2 (0.016 %)
False positives
1
False negatives
0
Practical considerations
• asymptomatic newborns in well baby nursery ≥ 24h of age
• newer generation pulse oximeters
• motion resistant technology measuring functional O2 saturation
• accuracy (±2% root mean square error)
• both single use and reusable probes acceptable
• two sites: right arm and a foot
• cut-off for positive screen: < 95% and │O2Sats RA- F│> 3 points (3 times)
• any value <90% is abnormal
• cut-off values for areas in high altitude not defined
• screening incorporated with nursery’s practice and other screening activities
Screening Protocol in well baby nursery for asymptomatic newborns >24h or shortly before discharge
check pulse ox in right arm and foot in room air
90-94% in both sites or
arm-foot difference > 3 points
Re-screen in 1h
< 90% in either site
Irrespective or difference
POSITIVE SCREEN
90-94 % in both sites or
arm-foot difference > 3 points
≥ 95% or higher in either site and
arm – foot difference ≤ 3 points
Re-screen in 1h
PASSED TEST
PCP notified
(FURTHER ACTION)
90-94% in both sites or
arm - foot difference >3 points
POSITIVE SCREEN
DISCHARGE
Response suggestions for primary caretaker to failed pulse oximetry screening
for Critical Congenital Heart Diseases (CCHD)
Failed Pulse ox screening: one value equal or less than 90%
OR
three times <95% in both sites or absolute difference of >3 points
1. Confirm accuracy of reading
2. If <24h consider deferring discharge and repeat test at 24h or later;
otherwise, follow same algorithm as in older infants
3. Perform additional clinical evaluation to assess for non-cardiac causes
4. Echocardiogram (in-center, transfer, telemedicine)
Comparative cost of screening
• CCHD: 8,000 cases per year in the US
• Screen will cause additional 8,000 ECHOs per year
• Cost: $9,000 (5.5-29K) per asymptomatic case diagnosed
• Metabolic disorders: 6,400 cases per year in the US
Cost of metabolic screen $110 / infant X 4 million/year = $440M / yr
or $68,750 per patient diagnosed
Expected annual activity for Minnesota
• Minnesota birth rate:
70,000
• Distribution: 60% access to pediatric cardiology services
(50% metro and 10% non-metro cities)
• Expected positive screens:
46
• Expected false positive screens: 25
• Need for transfer:
18
Estimated financial cost
• Nursing time: 5-10 min / screen
$200K-$400K
• Pulse oximeter equipment:
$100K
• Pulse oximeter supplies:
$200K (reusable)
$700K (single use)
• Echocardiography cost:
$70K-200K
• Transport costs:
$50K
• Estimated total cost:
$620K-$950K
• Additional hospital time / hidden costs:
?
* Annual Budget - Minnesota Department of Health (MDH)
$500M / year ($7.5 M/ year on Newborn Screening)
Barriers in implementation
• Regulatory (informed consent, reusable probes)
• Cost (equipment, supplies, personnel, transfers, days in hospital)
• Health care personnel: nursing staff
community practitioners
echo technicians
pediatric cardiologists
• Equipment:
pulse oximeters / ECHO machines & probes
• Infrastructure & Accessibility
• Medico-legal concern
• Skepticism
Summary
• CCHD causes significant morbidity and mortality
• Newborn screening for CCHD with pulse oximetry is promising
• Physical examination still useful
• Early diagnosis of CCHD may improve outcomes
• Guidelines for implementation of screening have been defined
• Future refinements likely
Pulse Ox screening for CCHD is coming soon to
a nursery close to you!