Screening for Critical Congenital Heart Disease in Thai ... · PDF fileclassified to Critical Congenital Heart Disease ... metabolic acidosis, seizure and elevate creatinine. This

242 เสมอใจ เห็นประเสริฐแท้ และคณะ วารสารกุมารเวชศาสตร์ กรกฎาคม - กันยายน 2556

นิพนธ์ต้นฉบับ

Introduction Congenital cardiovascular malformation is one of the leading causes of infant death. The incidence is variable from 4/1000 to 50/1000 live births depend on the facilities to detect trivial lesions in each studies1. About ¼ of them had severe clinical presentation requiring surgical or catheter intervention during neonatal period2,3, classified to Critical Congenital Heart Disease (cCHD) group such as Hypoplastic left heart

Background : Pulse oximetry is widely used to early detect the Critical Congenital Heart Diseases (CCHD). Intervention prior end organs damage can improve survival rate and shorter duration in intensive care unit. Objectives : To initiate the screening program for critical congenital heart diseases in neonates who born at Ratchaburi hospital and study the incidence and efficacy of Pulse oximetry screening in this population.Patients and Methods : A prospective study was done between July 1, 2011 and April 30, 2013 in postpartum units and intermediate care nursery. Asymptomatic neonates were screened by pulse oximetry and physical examination. Echocardiography was a confirm test in positive screened or clinical suggestion cases.Results : 4,116 Asymptomatic neonates were enrolled and four cases were detected by this program. Standard pulse oximetry screening had the sensitivity, specificity, PPV and NPV of 60%, 95.21%, 1.74% and 99.94% respectively. This screening program was developed by rules of continuous quality improvement.Conclusion : Screening for Critical Congenital Heart Disease by Pulse oximetry had more benefit in delayed clinical presentation cases and in the hospital settings those unsuitable for cardiac intervention in neonatal period. Strategies to improve quality of the program and referral system should be developed. (Thai J Pediatr 2013 ; 52 : 242-249)Keywords : Critical congenital heart disease, Pulse oximetry screening, Outcomes.

Screening for Critical Congenital Heart Disease in Thai Neonates : Single center study

Samerjai Henprasertthae*, Paradee Chaonarin*** Department of Pediatrics, ** Nursing Department , Ratchaburi Hospital, Ratchaburi.

syndrome, Pulmonary atresia, Tetralogy of Fallot, Total anomalous pulmonary venous return, Transposition of the great arteries, Tricuspid atresia, Truncus arteriosus, Severe coarctation of aorta, Interrupted aortic arch and Severe aortic valve stenosis. In cCHD patients, Significant Physiologic Compromise (SPC) before intervention was related to mortality and prolong intensive care unit stay 4. Pulse Oximetry is widely used to detect the potentially preventable SPC group

การคัดกรองโรคหัวใจพิการแต่ก�าเนิดชนิดวิกฤตในทารกแรกเกิด : โรงพยาบาลราชบุรี 243

of the cCHD patients5. Asymptomatic newborn should be screened by pulse oximetry after 24 hours of life and confirmed with echocardiography in positive cases. In Thailand, pulse oximetry is not a routine newborn screening as Congenital hypothyroid and Phenylketonuria. This screening program was settled in Obstetrics and Pediatrics unit of Ratchaburi hospital since July 2011. The cCHD patients received proper initial resuscitation and transfer to the cardiac center that suitable for any intervention in this high risk patients before the cardiovascular collapse.

Methods We conducted a prospective study of asymptomatic neonates who born at Ratchaburi hospital between July 1, 2011 and April 30, 2013. Inclusion criteria were 1) no oxygen therapy; 2) no respiratory distress symptoms; 3) no visible cyanosis; 4) no signs of cardiovascular collapse. Exclusion criteria was any other life threatening congenital malformations. The screening with motion-tolerant pulse oximeter should be performed at right hand and any foot after 24 hours of life combined with physical examination by the physician. The criteria for positive screening were 1) Oxygen saturation < 95% in any sites; 2) different of pre-postductal part > 3%; 3) PPI <0.7; 4) Abnormal heart sounds. Abnormal pulse oximetry should be confirmed at 1 and 2 hour later. The echocardiography were performed in positive screened cases. The negative screened neonates were followed at least 2 months, by the hospital and national health insurance system database and direct information from the parents or local healthcare workers. Characteristics of study population, incidence of the disease, patients characteristic, quality of screening process and efficacy of the screening method were described and analysed. Significant physiologic compromise

was diagnosed in the patients with one of these signs and symptoms(6):cardiac arrest, severe metabolic acidosis, seizure and elevate creatinine. This study was approved by the Ethics Committee of Ratchaburi hospital. Epi Info version 7 was used for statistical analysis.

Results Among 5,662 live births in this cohort, we found 5,079 asymptomatic newborns who met the criteria for screening test. 81.04% of them (4,116 newborns) were screened. We could make conclusion for status of cCHD in 87% of the newborns who were screened (3,581 newborns). We found 4 cCHD cases among them and we had 1 questionable conclusion because of non-definite cause of death. And we found the other 5 cCHD cases among 583 symptomatic newborns who were not screened. (Figure 1)

Figure 1: Schematic of the study population.


Figure 2: Trend of screening coverage by month


Totally 10 cCHD cases were detected from this cohort. The incidence was 1.77 per 1000 live births. Five cases developed cardiovascular compromise within 12 hour of life. Two of them died within first week. Four patients were diagnosed by this screening program. Two patients had abnormal oxygen saturation, one patient had both of abnormal oxygen saturation and heart murmur and another had heart murmur with left ventricular hypertrophy detected by electrocardiography. The diagnosis were tran-sposition of the great arteries, severe coarctation of aorta, truncus arteriosus and severe aortic valve stenosis. Three patients were transfered before significant physiologic compromise occurred and another developed oliguria during the right in processed but alive all. (Table 1) One of negative result infants had sudden death at 35 days old.

Characteristic of study population for efficacy measurement was shown in table 2. We compared the efficacy of screening test between

Table 1 : Information of all definite cCHD patients.

SexGA

(week)

Birth weight(gm.)

Age at diag.

Clinical or

Screen

Details of symptom

Diagnosis Treatment Status

F 39 3340 2 d. S - Truncus arteriosus Follow up Alive

M 39 2880 3 d. S oliguria (d 22)

Aortic valve stenosis PBAV* Alive

M 39 2990 2 d. C cyanosis PA/VSD RMBT Alive

M 38 2950 3 hr. C cyanosis TGA BAS Alive

M 38. 3440 5 hr. C cyanosis TOF/AVSD Follow up Alive

F 38 2160 3 hr. C cyanosis PA/IVS Central shunt Dead

F 40+6 3040 2 d. S cyanosis (1+m) TGA BAS ** Alive

M 39 2,370 6 hr. C CHB, shock HLHS - Dead

M 41+ 2,820 2 d. S - Severe CoA Surgical correction Alive

S=detected by screening program, C=detected by clinical PA/VSD=Pulmonary atresia/Ventricular septal defect, TGA=Transposition of the great arteriesTOF/AVSD=Tetralogy of fallot/atrioventricular septal defect, IVS=intact ventricular septumHLHS=Hypoplastic left heart syndrome, CoA=Coarctation of aorta*foreign patient, transfer after the rights confirmed*against operation at first time, accept after clinical worsen

Table 2: Characteristic of study population (n = 4,116)

Variables Result

Gestational age (Mean + SD) 38.2 + 1.4 wk

Birth weight (Mean + SD) 3047 + 419 gm.

Male (Percentage (95% CI)) 51.4 (49.8 – 52.9)

5 categories in table 3. Standard and postductal oximetry could detect 3 of 5 cCHD cases (60% sensitivity). Cardiac murmur from physical examination only could detect 2 of 5 cCHD cases (40% sensitivity). When we combined standard oximetry and cardiac murmur together could detect 4 in all 5 cCHD cases whereas peripheral perfusion index could not detect any case. Specificity of all categories had range


between 93.23 to 99.04. Highest PPV found in cardiac murmur then postductal oximetry, combination of standard oximetry with cardiac murmur, only standard oximetry and the lowest found in peripheral perfusion index category (4.44, 4.23, 1.85, 1.74 and 0 percent respectively) Coverage of screening in target popu-lation was pretty low at the beginning phase of program implementation (26% in 1st trimester) and then we improved by participated quality process leading to 94-98% coverage in last year.(Figure 2) The other aspects of quality, we focus on technique and timing. Among asymptomatic newborns who had positive screening, 49 in 60 ones (81.7%) of the group which met the criteria “Saturation lower than 95%” were not repeated the standard procedure and the group which met

the criteria “3 percentage different” were not repeated all. Proper time is very important for accuracy of the screening test because the 1st 24 hours after birth is transitional adaptation of fetal circulation. We found that only 91.36% of study population were screened after 24 hours after birth. (Table 4) Coverage of echocardiography in positive result was only 10%. Cardiac murmur was the most concerned. Coverage of the follow-up data was 87%. Most of missing data were foreigners causing language problems and wrong telephone numbers. Five infants were death during the follow-up periods. Their causes of death were inborn error of metabolism, severe pneumonia, malignant tumor of eyes, drowning and sudden infant death syndrome.




Table 3: Attributable of the screening program, Percentage

(95% confident interval)

Categories of Screening test

Sensitivity SpecificityPositive

Predictive Value

Negative Predictive

Value

1.Standard Oximetry*60

(14.66-94.73)95.21

(94.44-95.88)1.74

(0.36-5.01)99.94

(99.76-99.99)

2.Postductal Oximetry60

(14.66-94.73)98.08

(97.99-98.49)4.23

(0.88-11.86)99.94

(99.77-99.99)

3.Peripheral Perfusion Index

0(0-52.18)

98.49(98.01-98.85)

0(0-6.72)

99.86(99.64-99.95)

4.Cardiac Murmur40

(5.27-85.34)98.69

(98.22-99.04)4.44

(0.54-15.15)99.91

(99.7-99.98)

5. Standard Oximetry or Cardiac Murmur

80(28.36-99.49)

94.07(93.23-94.81)

1.85(0.51-4.67)

99.97(99.81-100)

*Pre and Post ductal oximetry measurement

Table 4: Quality of Standard Oximetry Measurement 4,060

from 4,116 newborns were screened by this test

Topics Result

Technique Among Positive results Followed lower than 95% criteria repeated not repeated Followed 3 percentage different criteria not repeated Negative results

199 (4.9)60 (30.2)11 (18.3)49 (81.7)

139 (69.85)139 (100%)3,861 (95.1)

Time to conduct screening test 24 hours after birth or later Within 24 hours after birth

% (95%CI)91.36

(90.44-92.20)8.64 (7.8-9.56)

Discussion Critical congenital heart diseases were the important causes of infant death. At the present, the survival rate is increasing from advance surgical techniques and early detection6. New trend in diagnosis are prenatal diagnosis and pulse oximetry screening7. Fetal ultrasound in the indicated patients should done by well trained physicians and need time to careful evaluation 8. Screening in asymptomatic neonates with pulse oximeter has been recommended by the American Academy of Pediatrics, the American Heart Association and the American


College of cardiology Foundation9. This method is rapid, easy, painless and inexpensive. The author start this screening program in Ratchaburi hospital before standard guideline was announced by the Centers for Disease Control and Preven- tion10. At that time many studies were reported, but inconclusively in site (pre & post ductal or postductal only), cut-off values (uncommon conditions eg.prematurity, high altitude popula-tion) and the timing of screening. Screening after 24 hours of life may be reasonable to allowed transitional circulation to resolved11,12. Pre- and post-ductal oximetry were performed. Criteria for further investigation were similar to previous Granelle and colleagues study as same as peripheral perfusion index (PPI) to cover the left-side obstruction disease13. All neonates who bed-in with mother were included to our study. Asymptomatic neonates in intermediate care nursery were also included and used the same cut-off point14. The common abnormal finding leading to cardiologist consultation was cardiac murmur. But most of them were normal physiologic adaptation or trivial lesion. We con- sidered echocardiography in normal pulse oximetry neonates with cardiac murmur when it persisted more than 48 hours. Data showed pulse oximetry screening had more detection rate than physical examination and better when combined both. Sensitivity of postductal oximetry was similar to standard pulse oximetry method. Meta-analysis data in Shakira study showed the sensitivity was moderate and the specificity was high15. The author used pulse oximetry add-on routine physical examination because human eye was inability to detect mild cyanosis but the detection rate was improved when combining physical examination and pulse oximetry11,13,16,17,18. Sensitivity and specificity calculated by this program were similar to prior studies although low study population but 88% were followed.

No correlation between PPI and left side obstruction case in our study. Further large studies in Thai neonates should be performed. Because of low percentage in abnormal oximetry confirmation, PPV and NPV should be reassess in the future. Strategies to improve this process should be discussed in healthcare team. Some patients developed decompensated cardiovascular symptoms within 24 hours of life. Their life threatening cardiac malformations were detected by routine standard of patient care. Our screening program was target to the patients with slow progression of symptoms. The median age at death of missed patient in previous study was 13.5 days 3, accordingly the negative result neonates were followed at least 2 months. Five infant deaths were discovered. None of them reported heart disease as the causes of death. But sudden infant death syndrome in a 35 days non-autopsy infant is questionable. In our country, the experienced interven-tionist and surgeons for complicated structural heart practicing mostly in the large cardiac centers. Limitation in number of cardiac intensive care unit and timing to transfer before clinical worsen. Significant Physiologic Compromise before intervention was related to mortality and prolong intensive care unit stay. Early detection in critical congenital heart patients will improve number of access to care patients and short term outcome. We settled this screening program to improve the quality of patient care. Parent counseling and suitable management were per-formed during transfer contact. Shorter period of ICU care resulting more cases to reach to the expert. Management planning in minority group is an important problem. One foreign case was transfered after purchased the health insurance card, the first procedure was successful but the patient loss follow up finally. Another Thai- Karen race case with Thai national health


insurance right rejected the procedure prior returned after the patients worsen. Difficulties in transportation and difference of languages and cultures should be the causes. Key performance index of program at initial phase was number of enrolled neonates. Although total coverage was 81.04% of target neonates, but increasing from 26% in first trimester to 94-98% in the last year. After accomplish the first goal, the next process should be target to proper time to screening, healthcare team awareness for positive screened criteria, confirm the positive result then consult the cardiologist before discharge. Adjustment of the case record form and revised the saturation measurement techniques were performed.

Conclusion Efficacy of pulse oximetry screening and incident of cCHD in the authors’ study is similarly to previous reports. Early detection improved short term outcome of individual cases and increased number of access to care patients in overall. But the survival time depend on natural history of each defect and the consistency in follow up period. Minority group management should be concerned. Comfort care with kindness is one of the choices. Quality in screening process should be continuously improved by team. Proper initial stabilization of the cases and effective referral system were developing.

Acknowledgement The authors wish to thank our healthcare team, our epidemiologist and all staff of hospital in our network. This study was supported by Chief of Pediatric department, Chief of Excel- lent Cardiac center and Head of Nursing depart-ment of Ratchaburi hospital.

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congenital heart disease. J. Am. Coll. Cardiol. 2002; 39: 1890–900.

2. Carolyn A. Congenital heart disease in the newborn: Presentation and screening for critical CHD. Uptodate. Internet [cited 2013 Apr 3]. Available from :http://www.uptodate.com/contents/congenital-heart-disease-chd-in-the-newborn-presentatio…

3. Chang R-KR, Gurvitz M, Rodriguez S. Missed diagnosis of critical congenital heart disease. Arch Pediatr Adolesc Med. 2008; 162: 969–74.

4. Brown KL, Ridout DA, Hoskote A, Verhulst L, Ricci M, Bull C. Delayed diagnosis of congenital heart disease worsens preoperative condition and outcome of surgery in neonates. Heart. 2006; 92: 1298–302.

5. Schultz AH, Localio AR, Clark BJ, Ravis-hankar C, Videon N, Kimmel SE. Epidemio-logic Features of the Presentation of Critical Congenital Heart Disease: Implications for Screening. PEDIATRICS. 2008; 121: 751–7.

6. The Lancet. A new milestone in the history of congenital heart disease. The Lancet. 2012; 379(9835): 2401.

7. Wren C, Reinhardt Z, Khawaja K. Twenty-year trends in diagnosis of life-threatening neonatal cardiovascular malformations. Arch. Dis. Child. Fetal Neonatal Ed. 2008; 93: F33–35.

8. Rychik J, Ayres N, Cuneo B, et al. American society of echocardiography guidelines and standards for performance of the fetal echo- cardiogram. Journal of the American Society of Echocardiography. 2004; 17: 803–10.

9. Mahle WT, Martin GR, Beekman RH, et al. Endorsement of Health and Human Services Recommendation for Pulse Ox-imetry Screening for Critical Congenital Heart Disease. Pediatrics. 2012; 129: 190–2.


10. CDC-Pulse Oximetry Screening for Critical Congenital Heart Disease, Pediatric Genetics – NCBDDD. Internet.[cited 2013 Mar 21]. Available from : http://www.cdc.gov/ncbddd/Pediatricgenetics/pulse.html

11. John SH. Pulse Oximetry Screening for Unrecognized Congenital Heart Disease in Neonates. Congenital cardiology Today. Internet[cited 2011 Jan]. Available from: http://www.Congenital Cardiology Today.com

12. O’Brien L, Stebbens V, Poets C, Heycock E, Southall D. Oxygen saturation during the first 24 hours of life. Arch Dis Child Fetal Neonatal Ed. 2000; 83: F35–F38.

13. 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 screen-ing study in 39 821 newborns. BMJ. 2009; 338(jan08 2): a3037–a3037.

14. Røsvik A, Øymar K, Kvaløy JT, Berget M. Oxygen saturation in healthy newborns; influence of birth weight and mode of deliv-ery. Journal of Perinatal Medicine. 2009; 37.

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16. Wren C, Richmond S, Donaldson L. Presen-tation of congenital heart disease in infancy: implications for routine examination. Arch Dis Child Fetal Neonatal Ed. 1999; 80: F49–F53.

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การคัดกรองโรคหัวใจพิการแต่กำาเนิดชนิดวิกฤตในทารกแรกเกิด : โรงพยาบาลราชบุรี

เสมอใจ เห็นประเสริฐแท้ *, ภารดี ชาวนรินทร์ **

* กลุ่มงานกุมารเวชกรรม โรงพยาบาลราชบุรี** กลุ่มการพยาบาล โรงพยาบาลราชบุรี

วัตถุประสงค์ : เพื่อวางแนวทางในการคัดกรองโรคหัวใจพิการแต่ก�าเนิดชนิดวิกฤตในทารกแรกเกิด

ที่มารดามาคลอดที่โรงพยาบาลราชบุรี ร่วมกับศึกษาอุบัติการณ์ของโรคและประสิทธิภาพของการ

คัดกรองด้วยเครื่องวัดค่าความอิ่มตัวของออกซิเจนในเลือดผ่านทางผิวหนัง

วิธีการศึกษา : เป็นการศึกษาแบบไปข้างหน้าในทารกแรกเกิดที่มารดามาคลอดที่โรงพยาบาลราชบุรี

ตั้งแต่ 1 กรกฎาคม พ.ศ.2554 ถึง 30 เมษายน พ.ศ.2556 ที่หอผู้ป่วยหลังคลอดและหอผู้ป่วยทารก

แรกเกิด ใช้การคัดกรองด้วยเครื่องวัดค่าความอิ่มตัวของออกซิเจนในเลือดผ่านทางผิวหนังร่วมกับ

การตรวจร่างกายโดยแพทย์ในรายทีย่งัไม่มอีาการ ตรวจยนืยนัด้วยเครือ่งตรวจคลืน่เสยีงสะท้อนความ

ถี่สูงของหัวใจในรายที่ผลการคัดกรองเป็นบวกหรือมีข้อบ่งชี้ทางคลินิก

ผลการศึกษา : ทารกกลุ่มที่ยังไม่มีอาการและเข้าในการศึกษาทั้งหมด 4,116 ราย พบเป็นโรค 4 ราย

ค่า sensitivity, specificity, PPV และ NPV ของการคัดกรองโดยการวัดค่าความอิ่มตัวของออกซิเจน

ในเลือดเท่ากับ 60%, 95.21%, 1.74% และ 99.94% ตามล�าดับ แนวทางการพัฒนาระบบการคัดกรอง

ใช้หลัก Plan-Do-Check-Act ระหว่างกุมารแพทย์และทีมพยาบาล

สรุปผล : การคัดกรองด้วยเครื่องวัดค่าความอิ่มตัวของออกซิเจนในเลือดผ่านทางผิวหนังจะให้

ประโยชน์อย่างมากในผู้ป่วยที่มีอาการแสดงเกิดขึ้นช้า และในโรงพยาบาลท่ีไม่สามารถผ่าตัดหรือ

สวนหัวใจในช่วงแรกเกิดได้ ควรมีการประเมินและพัฒนากลยุทธ์เพื่อเพิ่มประสิทธิภาพของ

กระบวนการคัดกรอง การดูแลรักษาเบื้องต้นและระบบการส่งต่อ (วารสาร กุมารเวชศาสตร์ 2556 ;

52 : 242-249)

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Screening for Critical Congenital Heart Disease in Thai ... · PDF fileclassified to Critical Congenital Heart Disease ... metabolic acidosis, seizure and elevate creatinine. This