Newborn Pulse Oximetry Utilization in CCHD Screening

Transcription

1 Newborn Pulse Oximetry Utilization in CCHD Screening Christopher L. Bosley BS, AAS, RRT-NPS, LRT, RCP Pediatric Respiratory Care Education Specialist Instructor in Anesthesiology Department of Anesthesia Respiratory Care Mayo Clinic-Eugenia Litta Children s Hospital 2014 MFMER slide-1

2 Conflict of Interest None 2014 MFMER slide-2

3 Objectives Understand how to use pulse oximetry equipment and the methods to obtain accurate readings Define CCHD & the associated cyanotic defects Identify the equipment needed for CCHD screening Explain what CCHD screening is and why it is important 2014 MFMER slide-3

4 48% of deaths from CHD Every 15 minutes occur in 1 st year 1 4.2% of infant deaths from CHD occur in the first 28 days of life 2 A baby is born with a congenital heart defect 1. Gilboa, SM., et al. Circulation 2010; 122: cdc.gov/ncbddd/heartdefects/data.html

5 Case #1 During nursery rounds you find that a DOL #2 infant failed his pulse oximetry screen overnight. Lower extremity S p O 2 of 91%, 88% and 86% on repeat screenings Thorough physical exam: Harsh murmur at the left upper sternal border Somewhat cyanotic appearing but is otherwise breathing comfortably on room air What are your next steps? 2014 MFMER slide-5

6 Infection, including sepsis Causes of Hypoxia Differential Lung disease (parenchymal or anatomic) Persistent pulmonary hypertension Transient tachypnea of the newborn Hemoglobinopathy Hypothermia Others... Non-critical CHD Critical CHD 2014 MFMER slide-6

7 Pulse Oximetry The History of Karl Matthes First oximeter to measure O 2 saturation Subsequent oximeters developed by Hewlett Packard were bulky and expensive ($10,000) Takuo Aoyagi Pulsatile changes in absorption of red and infra-red light to measure arterial oxygen saturation 1980 s - Beginnings of Pulse Oximetry Manufacturing BiOx, Novametrix Nellcor (started by anesthesiologist Bill New) Operating room as standard of care ASA recommends inclusion of pulse oximetry and capnography 2014 MFMER slide-7

8 Pulse Oximetry Oximeter Definition: Measures how much oxygen the blood is carrying (Hypoxemia) Noninvasive monitoring technique performed at bedside Differential absorption of light by oxyhemoglobin & deoxyhemoglobin A photodetector in the sensor measures unabsorbed light from the LEDs 2014 MFMER slide-8

9 Beer s Law 2014 MFMER slide-9

10 Beer-Lambert Law The combination of both Beer s Law and Lambert s Law Beer s Law Absorption of light is proportional to the concentration of a sample Lambert s Law Absorption is proportional to the thickness of a sample 2014 MFMER slide-10

11 Principles of Differential Absorption Pulse Oximetry Pulse oximetry is based on the differential absorption of light by oxyhemoglobin and deoxyhemoglobin The oxygenated hemoglobin allows red light to transmit through and absorbs more infrared light. Infrared Tracing Deoxygenated hemoglobin allows infrared to transmit through and absorbs more red light. Wavelengths: 660nm (red) 940nm (infrared) 2014 MFMER slide-11

12 Principles Pulse Oximetry A photodetector in the sensor measures unabsorbed light from the LEDs: Tissue, venous blood and non pulsatile arterial blood Surge in arterial blood with each heartbeat results in more light absorbed. Indirect measurement of blood volume under the sensor So the troughs of lower light absorption are subtracted from the peaks, leaving only arterial bloods light absorption being measured Hence Pulse Oximetry C HbO2 S p O 2 = C HbO2 +C Hb 2014 MFMER slide-12

13 Clinical Application & Practice Oximetry Hemoximetry (Co-oximetry): Blood Gas Analyzer Pulse oximetry: Noninvasive monitoring technique performed at bedside. Accurate to within ±3% to 5% of hemoximetry. Combines principles of pectrophotometry with photoplethysmography. Not as accurate as hemoximetry Venous oximetry: Invasive monitoring through fiberoptic catheter placed in vena cava or pulmonary artery. Assesses balance between oxygen delivery & utilization as indirect index of global tissue oxygenation & perfusion. Normal values for mixed venous (pulmonary artery oxygen saturation monitoring (S v O 2 ) range between 60 to 80% Tissue oximetry: Noninvasive method of measuring saturation of hemoglobin at tissue level. Oxygen saturation at tissue level (S t O 2 ) assesses adequacy of circulation & oxygen delivery. Early detection of low S t O 2 can be used as an early detection method of tissue hypoperfusion in patients with traumatic injuries MFMER slide-13

14 Fetal Hemoglobin HbF 80-90% of total hemoglobin in fetus is feral hemoglobin (HbF) Birth: Majority of Hb is HbF, within first year changes to HbA 2,3-DPG Giving HbF increased affinity for O 2 Large content of O 2 in spite of relatively low PO 2 Left shift on the Oxygen dissociation curve Adult: 2,3-DPG will reduce oxygen s affinity Off loads oxygen to the tissue more easily 2014 MFMER slide-14

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17 Pulse Oximetry Signal Quality Confidence Indicator: Signal IQ 1. Tools and Technology to Start Your CCHD Screening Program. Masimo International MFMER slide-17

18 Keys to Accurate Readings Pulse Oximetry 1. Pulse oximeter device & probes are approved for use in newborns & neonates 2. Make sure that the sensor is flush on the infant s skin 3. Ensure that the infant s skin is clean and dry 4. Ensure that the infant is calm and warm 5. Reduce environmental factors High intensity lighting (Phototherapy lights or Fluorescent lights) Blood Pressure Cuff 6. Confirm confidence indicator (PI) & pulse oximeter reading is accurate 7. Pulse oximetry readings are not instantaneous MFMER slide-18

19 What is the prevalence of babies born with a Congenital Heart Defect? CHD in the United States A. 3.3% B. 1% C. 0.1% D. 0.03% 1. Data & Statistics. (2014, October 20) cdc.gov/ncbddd/birthdefects/datahtml 2014 MFMER slide-19

20 ~3,977,000 Births Per Year United States 45,000 40,000 35,000 30,000 25,000 20,000 15,000 10,000 5, ,000 10, ,200 [7200] CHD (1%) CCHD (25%) CHD CCHD Deaths Lives Saved 1,2 3,6 [ ] 4 Unrecognized Deaths (0.5%) CCHD Screening - Lives Saved 5 1. Hoffman JL, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39(12): Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in Atlanta, J Pediatr. 2008;153: Oster, ME, et al. Temporal trends in survival among infants with critical congenital heart defects. Pediatrics May;131(5):e cdc.gov/ncbddd/heartdefects/documents/ncbddd_birth-defects_cchd-newborn-screening.pdf 5. Broussard CS, Gilboa SM, Lee KA, Oster M, Petrini JR, Honein MA. Racial/Ethnic Differences in Infant Mortality Attributable to Birth Defects by Gestational Age. Pediatrics. 2012; 130:e518-27

21 Critical Congenital Cardiac Defects Definition Critical CHD refers to lesions requiring surgery or catheter-based intervention in the first year of life. This category includes ductal-dependent and cyanotic lesions as well as less severe forms of CHD that are not dependent on the PDA. 1,2 Clinical Presentation: Normal, respiratory distress, weak pulse, poor feeding, very sleepy, heart murmur, tachypnea, hypotension, cyanosis & hypoxemia. Newborn screening using pulse oximetry can detect hypoxemia, a clinical sign of CCHD. 3,4 1. Talner CN. Report of the New England Regional Infant Cardiac Program, by Donald C. Fyler, MD, Pediatrics, 1980;65(suppl): Pediatrics 1998; 102: Olney RS, Ailes EC, Sontag MK. Detection of critical congenital heart defects: Review of contributions from prenatal and newborn screening. Seminars in perinatology. 2015;39(3): Mahle WT, Newburger JW, Matherne GP, et al.; Role of pulse oximetry in examining newborns for congenital heart disease: a scientific statement from the AHA and AAP. Pediatrics 2009;124: cdc.gov/ncbddd/heartdefects/documents/ncbddd_birth-defects_cchd-newborn-screening.pdf 2014 MFMER slide-21

22 Oxygen transport starts from the time of conception

23 Primary Targets for CCHD Screening Critical Congenital Heart Defect 1,2,3 Right-Sided Obstruction: 1. Pulmonary atresia (intact septum)** 2. Tetralogy of Fallot** 3. Tricuspid atresia** 4. Ebstein anomaly Mixing Lesions: 8. Truncus arteriosus** 9. Total anomalus pulmonary venous connection** 10. Double-outlet right ventricle 11. Single ventricle Left-Sided Obstruction: 5. Aortic interruption atresia/hypoplasia 6. Coarctation of the aorta 7. Hypoplastic left heart syndrome** Parallel Circulation: 12. D-transposition of the great arteries** 1. aap.org/en-us/advocacy-and-policy/aap-healthinitiatives/pehdic/pages/newborn-screening-for-cchd.aspx 2. cdc.gov/ncbddd/heartdefects/facts.html 3. cdc.gov/ncbddd/heartdefects/documents/ncbddd_birthdefects_cchd-newborn-screening.pdf 2014 MFMER slide-23

24 CCHD Identification Physical Exam & Screening Historically newborns with CCHD are diagnosed in the newborn nursery. Mid-trimester ultrasound Postnatal physical examination: Heat murmurs Assess pulses Tachypnea Cyanosis 4-limb BP cuff measurements Low detection rate, poor sensitivity and specificity 1. aap.org/en-us/advocacy-and-policy/aap-healthinitiatives/pehdic/pages/newborn-screening-for-cchd.aspx 2. Institute for Advanced Medical Education Ewer, AK., et al. The Lancet MFMER slide-24

25 CCHD Identification Screening Technique Limitations Limitations of the Physical exam: Usually occurs with in the first 24 hours of life Performed by pediatricians, licensed health care providers prior to discharge May have only one exam prior to discharge Are we missing those asymptomatic patient s prior to ductal dependant closure...? Early hospital dismissal or late ductal closure 1. aap.org/en-us/advocacy-and-policy/aap-healthinitiatives/pehdic/pages/newborn-screening-for-cchd.aspx 2014 MFMER slide-25

26 CCHD Identification Traditional Screening Techniques Using pulse oximetry in conjunction with the routine practices, CCHD can be detected over in over 90% of newborns 1,2 1. Pulse Oximetry Screening for Critical Congenital Heart Disease. 2. de-wahl Granelli A, Wennergren M, Sandberg K, et al. Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study in newborns. BMJ. 2009;338(jan08 2):a3037 a MFMER slide-26

27 CCHD Screening Before Leaving the Hospital 2011, CCHD was added to the US Recommended Uniform Screening Panel for newborn screening. 1,2 CCHD Pulse Oximetry Screening allows the detection of CCHD during the asymptomatic period prior to closure of the ductus arteriosus. 3 Some children with critical congenital heart disease will have no symptoms and have an entirely normal physical examination at the time they are sent home from the hospital after birth. 1. cdc.gov/ncbddd/heartdefects/documents/ncbddd_birth-defects_cchdnewborn-screening.pdf 2. hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/recomm endedpanel/index.html 3. aap.org/en-us/advocacy-and-policy/aap-healthinitiatives/pehdic/pages/newborn-screening-for-cchd.aspx 2014 MFMER slide-27

28 Importance of Critical CHD Diagnosis Unrecognized CCHD ~300 newborns per year are discharged with unrecognized CCHD [Median diagnosis 6 weeks] CCHD diagnosed after dismissal from hospital Risk of circulatory collapse, shock and acidosis More frequent hospitalizations & length of stay Poor clinical status at time of surgery surgical morbidity and mortality hospital costs compared with babies that had a critical CHD diagnosed in the hospital S p O 2 screening can reduce missed diagnoses by ~30% 1. Franklin O. et al. Heart Peterson. et al. Pediatrics Tworetsky W. et al. Circulation Brown JW, et al. Ann Thoracic Surg Aamir, T., Kruse, L., Ezeakudo, O. Acta Paediatr. 2007;96: aap.org/en-us/advocacy-and-policy/aap-health-initiatives/pehdic/pages/newborn-screening-for-cchd.aspx 2014 MFMER slide-28

29 How Does Pulse Oximetry Screening Help? Synopsis EARLY detection = EARLY treatment: Reduces prehospital and in-hospital morbidity and mortality Reduces length of stay and hospital costs 1. Surgical death rates. CNN.com Pulse Oximetry Screen for CCHD. CDC.org 2014 MFMER slide-29

30 What is the estimated CCHD Patient Screening Cost? United States A. $14 B. $20 C. $36 D. $ MFMER slide-30

31 CCHD Screening Costs In the United States Hospital CHD costs were about $1.4 Billion. [2011 $1.9 Billion] Severe CHDs accounted for about $511 million 37%, of the hospital costs associated with CHDs The costs of critical CHD screening is about $5 to $14 (USD) for each newborn baby screened 2,3 The cost of CCHD screening depends on many factors: 2 Number of births in a hospital Type of equipment used Capital costs Screening time (Staff Labor) 1. cdc.gov/ncbddd/heartdefects/data.html 2. cdc.gov/ncbddd/heartdefects/screening.html 3. heart.org/idc/groups/heartpublic/@wcm/@adv/documents/downloadabl e/ucm_ pdf 2014 MFMER slide-31

32 How to Perform the CCHD Screening Equipment What pulse-oximetry equipment should I use? 1 Hospital-grade pulse oximeter & probes that are designed for newborns Using reusable probes can decrease the overall cost of CCHD screening. 1. aap.org/en-us/advocacy-andpolicy/aap-healthinitiatives/pehdic/pages/newborn- Screening-for-CCHD.aspx 2. Masimo International. # B- 0512

33 How to Perform the CCHD Screening Who Gets Screened? Which babies should be screened? All newborns at risk for undetected CCHD should be screened. Infants must be on room air Should I screen my patient that is receiving supplemental oxygen? NO: If they have had an echocardiogram evaluation Echocardiogram can be used to screen for CCHD 1. aap.org/en-us/advocacy-and-policy/aap-healthinitiatives/pehdic/pages/newborn-screeningfor-cchd.aspx 2014 MFMER slide-33

34 How to Perform the CCHD Screening Premature infant? CCHD screening guidelines focused on newborn nursery. Given the ICU population, the screening protocol may need to be modified based on timing or use of supplemental oxygen It is reasonable to: 1. Wait until the infant is weaned from O 2 before screening 2. Obtain an echocardiogram for those unable to be weaned before discharge 3. No screening required if previous echocardiography evaluation 1. Oster, ME., et al. Pediatrics aap.org/en-us/advocacy-and-policy/aap-healthinitiatives/pehdic/pages/newborn-screening-for-cchd.aspx 2014 MFMER slide-34

35 How to Perform the CCHD Screening Personnel Screening should be performed by qualified personnel: 1 Individuals who are trained in the use of pulse oximetry Knowledgeable CCHD algorithm Who have pulse-oximetry testing within their scope of practice Who regularly use pulse oximetry for other purposes 1. aap.org/en-us/advocacy-and-policy/aap-health- initiatives/pehdic/pages/newborn-screening-for- CCHD.aspx MFMER slide-35

36 How to Perform the CCHD Screening When Should I Screen? Initial pulse oximetry screening is best performed: Between 24 and 48 hours Close as possible to the time of discharge Earlier screening may produce false positive results Newborn's transition from fetal to neonatal circulation Stabilization of systemic oxygen saturation levels 2014 MFMER slide-36

37 How to Perform the CCHD Screening Improving Accuracy Reduce false positives: Screen the newborn while he or she is alert Screen the newborn when he or she is at least 24 hours old Reduce false negatives: Perform thorough physical examination 1. Pulse Oximetry Screen for CCHD CDC.org 2014 MFMER slide-37

38 Improving CCHD Accuracy Pulse Oximetry & Auscultation Pulse oximetry + auscultation Grade II murmur considered abnormal Screened over 160,000 asymptomatic newborns S p O 2 : 77.3% sensitivity (34/44) S p O 2 + auscultation: 95.5% sensitivity 42/44) However, the false positive rate increased from 0.2% to 1.2%. Detecting other CHDs: PDA, VSD, ASD 2014 MFMER slide-38

39 Pulse Oximetry Screening Effectiveness Sensitivity 76.5% Specificity 99.9% Not meant to replace family history, pregnancy history, clinical exam and/or echocardiogram 1. Thangaratinam, S., et al. Lancet. 2012;379: Infant pulse oximetry. Archive.jsonline.com MFMER slide-39

40 How to Perform the CCHD Screening Pulse Oximeter Probe Placement Preductal (Right hand) Place sensor on the outer lateral aspect of the RIGHT hand under the 4 th or 5 th finger. Verify that the emitter and detector are aligned. Post-Ductal (Either Foot) Place sensor on the outer lateral aspect of EITHER foot under 4 th or 5 th toe. Verify that the emitter and detector are aligned. 1. Masimo International. # B MFMER slide-40

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42 CCHD Screening Algorithm Screening Results Negative Screen [PASS] S p O 2 95% in Right hand OR either foot, AND hand-foot difference 3% Positive Screen [Repeat 3 Times to Confirm] S p O % in the Right hand AND foot, OR Right hand-foot difference is > 3% Repeat measurement in one hour Positive CCHD [FAILED] S p O 2 < 90% in Right hand OR foot, OR 3 repeated positive screens Refer infant for echocardiogram & further medical evaluation 1. Alex R. Kemper et al. Pediatrics 2011;128:e1259-e Masimo International. # B cdc.gov/ncbddd/heartdefects/hcp.html#kemper

43 Case #2 Continuing morning nursery rounds You are asked by the parents of the infant in the first case if his twin brother also needs an echocardiogram. Pulse oximetry screening overnight was normal with saturations in upper 90 s and no differential. You perform a thorough physical examination and note a murmur at the left sternal border but otherwise normal work of breathing, pulses and perfusion. Should you be concerned? What next? 2014 MFMER slide-43

44 Failed Asymptomatic Screening Positive Predictive Value for CCHD Two large European studies: 21-26% of babies with a failed screen had CCHD 47% had another disease process such as pulmonary pathology or sepsis 28% were well. (False Positive) New Jersey study, asymptomatic babies with a failed CCHD screen: 10% had CCHD 67% had non-critical congenital heart defect or were well. 23% had another disease process causing hypoxemia German data suggests a false negative rate of < 1:10, aap.org/en-us/advocacy-and-policy/aap-health- initiatives/pehdic/pages/newborn-screening-for- CCHD.aspx 2014 MFMER slide-44

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46 Pulse Oximetry Screening What Does it Miss? 29 infants with ductal dependent circulation: 24/29 cases physical exam + pulse oximetry Sensitivity 82.8% 5 missed cases - All aortic arch obstruction 1. de-wahl Granelli Anne, Wennergren Margareta, Sandberg Kenneth, Mellander Mats, Bejlum Carina, Inganäs Leif et al. Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study in newborns. BMJ 2009;338:a Radiology teaching files. Eurorad.org MFMER slide-46

47 Pulse Oximetry Screening What Does it Miss? 1. Lancet 2011;378: MFMER slide-47

48 Pulse Oximetry Screening Where are We Now? 47 states have mandatory screening policies for critical CHDs 1. Pulse Oximetry Screen for CCHD CDC.org 2014 MFMER slide-48

49 Pulse Oximetry Screening Impact of CCHD Screening In the 8 states with mandatory policies for newborn CCHD screening: Early infant death from CCHD DECREASED by 33.4% (95%CI 10.6%-50.3%) with an absolute decline of 3.9 deaths per 100,000 births. In addition, early infant deaths from other/unspecified cardiac causes DECLINED by 21.4% (95%CI, 6.9%- 33.7%). 1. Abouk, R. JAMA MFMER slide-49

50 Special Considerations

51 The Oxygen Non Responders Alternate Screening Tools 1. CCHD *Common [Truncus Arteriosus / Transposition of the Great Arteries / Tricuspid Atresia / Tetralogy of Fallot / TAPVR] 2. Large Intrapulmonary Shunt **Uncommon 3. Methemoglobinemia ***Rare Hyperoxia Oxygen Test [F i O x min] ΔP a O 2? ΔS p O 2? Normal >500torr P a O 2 100% CCHD* <150torr P a O 2 Δ NO/ Pulmonary** >150torr P a O 2 Δ YES/ Hemoglobinemias*** >200torr P a O 2 Δ NO/

52 Perfusion Index & Pulse Oximetry Alternate Screening Tools Can detection of left-sided obstructive lesions be improved by assessing peripheral perfusion index (PI<0.9)? Over 42,000 newborns screened with POX-PI 194 screened positive 191 false positive [23 with ASD, VSD, PDA] 3 true positive: 2 - low S p O low PI = aortic coarctation 4 false negatives [2 CoA, 1 truncus with IAA] Requires further evaluation! 1. Schena, F., et al. J Pediatr MFMER slide-52

53 Screening at Altitude The pulse oximetry screen positive rate increases as altitude increases. 600 meters: positive screen rate = 0.2% meters: 1.2% >1800 meters: 6% Stopped enrollment at the site located at 2500 meters as 35% screened positive Consider correcting for altitude with oxygen challenge test O 2 hood to achieve PO 2 equivalent to room air at sea level 1. Paranka, MS. J Perinatol MFMER slide-53

54 Back To Our Cases Twin A: TOF and severe pulmonary valve stenosis Twin B: Type B interrupted aortic arch Both found to have DiGeorge Syndrome 22q11.2 deletion syndrome 1. Digilio, MC., Marino, B., Capolino, R., Dallapiccola, B. Clinical manifestations of Deletion 22q11.2 syndrome (DiGeorge/Velo-Cardio- Facial syndrome). Images Paediatr Cardiol Apr-Jun;7(2): MFMER slide-54

55 DiGeorge Syndrome DiGeorge/Velo-Cardio-Facial syndrome Deletion 22q11.2 syndrome (Del22) is characterized by: Congenital heart defect (CHD) Palatal anomalies Facial dysmorphisms Neonatal hypocalcemia Immune deficit Speech and learning disabilities 1. Digilio, MC., Marino, B., Capolino, R., Dallapiccola, B. Clinical manifestations of Deletion 22q11.2 syndrome (DiGeorge/Velo-Cardio- Facial syndrome). Images Paediatr Cardiol Apr-Jun;7(2): MFMER slide-55

56 In Summary Pulse-ox screening is a non-invasive, safe and cost effective CCHD screening tool The CCHD screening algorithm is an effective tool to identify critical congenital heart disease and other causes of hypoxemia in the newborn population The CCHD screening algorithm is an effective way to identify asymptomatic infants prior to hospital dismissal Pulse oximetry screening is an adjunct to and does NOT replace a thorough history and physical examination Although not perfect, it has a moderate sensitivity and high specificity with low false positive and false negative rates Timely screening can reduce delayed diagnoses and associated morbidity, mortality and high resource utilization 2014 MFMER slide-56

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58 Resources Aamir, T., Kruse, L., Ezeakudo, O. Delayed diagnosis of critical congenital cardiovascular malformations (CCVM) and pulse oximetry screening of newborns. Acta Paediatr 2007;96: Abouk, R., Grosse, SD., Ailes, EC., Oster, ME. Association of US State Implementation of Newborn Screening Policies for Critical Congenital Heart Disease With Early Infant Cardiac Deaths. JAMA 2017 Dec 5;318(21): American Academy of Pediatrics initiatives/pehdic/pages/newborn-screening-for- CCHD.aspx American Heart Association. Pulse Oximetry Screening for Critical Congenital Heart Disease. uments/downloadable/ucm_ pdf Broussard, CS., Gilboa, SM., Lee, KA., Oster, M., Petrini, JR., Honein, MA. Racial/Ethnic Differences in Infant Mortality Attributable to Birth Defects by Gestational Age. Pediatrics 2012; 130:e Brown, JW., et al. Surgical results in patients with double outlet right ventricle: a 20-year experience. Ann Thorac Surg 2001 Nov;72(5): Centers for Disease Control and Prevention birth-defects_cchd-newborn-screening.pdf de-wahl Granelli, Anne., Wennergren, Margareta., Sandberg, Kenneth., Mellander, Mats., Bejlum, Carina., Inganäs, Leif., et al. Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study in newborns. BMJ 2009;338:a3037 Digilio, MC., Marino, B., Capolino, R., Dallapiccola, B. Clinical manifestations of Deletion 22q11.2 syndrome (DiGeorge/Velo- Cardio-Facial syndrome). Images Paediatr Cardiol 2005 Apr- Jun;7(2):23 34 Ewer, AK., Middleton, LJ., Furmston, AT., Bhoyar, A., Daniels, JP., Thangaratinam, S., Deeks, JJ., Khalid S Khan, KS. on behalf of the PulseOx Study Group. Pulse oximetry screening for congenital heart defects in newborn infants (PulseOx): a test accuracy study. Lancet 2011;378: Franklin, O., et al. Prenatal diagnosis of coarctation of the aorta improves survival and reduces morbidity. Heart 2002 Jan;87(1): MFMER slide-58

59 Resources Gilboa, SM., et al. Mortality resulting from congenital heart disease among children and adults in the United States, 1999 to Circulation 2010 Nov 30;122(22): Health Resources & Services Administration bledisorders/recommendedpanel/index.html Hoffman, JL., Kaplan, S. The incidence of congenital heart disease. J Am Coll Cardiol 2002;39(12): Masimo International Tools and Technology to Start Your CCHD Screening Program. Newborn CCHD Screening: Step-by-Step Instructional Guide. (# B-0512) Reller, MD., Strickland, MJ., Riehle-Colarusso, T., Mahle, WT., Correa, A. Prevalence of congenital heart defects in Atlanta, J Pediatr 2008;153: Schena, F., et al. Perfusion Index and Pulse Oximetry Screening for Congenital Heart Defects. J Pediatr 2017;183:74-9.e1 Thangaratinam S., et al. Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis. Lancet 2012;379: Tworetsky W., et al. Improved surgical outcome after fetal diagnosis of hypoplastic left heart syndrome. Circulation 2001 Mar 6;103(9): Oster, ME, et al. Temporal trends in survival among infants with critical congenital heart defects. Pediatrics 2013 May;131(5):e Paranka, MS., et al. The impact of altitude on screening for critical congenital heart disease. Journal of Perinatology: volume 38, pages (2018) Peterson, C., et al. Cost-effectiveness of routine screening for critical congenital heart disease in US newborns. Pediatrics 2013 Sep;132(3):e MFMER slide-59

60 Questions & Discussion MFMER slide-60