Critical Congenital Heart Disease screening in the newborn in Thailand Good morning Mr.chairman, our friends from all asean countries, Ladies and Gentlemen May I share my experience of critical CHD screening in the NB in Thailand Thanarat Layangool, MD. QSNICH

Issues Backgrounds of Critical CHD Statistic of Cyanotic CHD in the newborn Critical CHD screening program in neonate Results from our pilot study Results of the 3 years implemented this program in Thailand These are my topics today.

ทำไมต้องมีการคัดกรอง อุบัติการณ์ของ CHDพบประมาณ 6-8 ต่อ เด็กเกิดมีชีพ 1000 ราย Cyanotic CHD อาจจะมีความรุนแรงมากและมีอาการตั้งแต่แรกเกิด รายที่รุนแรงมักจะเสียชีวิตถ้าไม่ได้รับการวินิจฉัยและช่วยเหลือให้การรักษาที่รวดเร็วทันทีหลังเกิด การวินิจฉัยทางคลินิกทำได้ยาก มีรายงานเด็กที่เสียชีวิตจาก CHDเป็นการเสียชีวิตก่อนได้รับการวินิจฉัย 10-30% Undiagnosed death 4.4 /100,000 live birth ความหมายของ critical CHD

Background The prenatal screening (fetal echo) for CHD in Thailand is limited to the university hospitals and some tertiary care centers. Postnatal screening of critical CHD by using pulse oximeter is feasible with reasonable cost. Fetal echocardiogram or Prenatal screening for CHD in Thailand is limited….

Delayed Diagnosis complications complications Vicious cycle of the patients with critically ill in Thailand Not available ICU bed Delayed Diagnosis Prolong Length of stay Delayed Transfer complications complications This is our vicious cycle of the critical ill patients, especially neonate in Thailand We quite often face with the problem of not available of ICU bed, which causes delayed Tx and delayed Rx. So many complications may develop and cause increase LOS. Delayed diagnosis is the another factor of delayed treatment. If we can get early diagnosis, we may reduce LOS. MB and MT If asymptomatic baby with critical CHD can be diagnosed, we don’t need NICU, we need only normal or semi ICU bed. Delyed treatment - few CVT surgeon

Number of new cardiac patients at Queen Sirikit NICH (25,615 cases) The graph shows our new CHD cases in all age group. We have 12-14 hundred cases a year

Prevalence of Neonatal Heart Disease at Queen Sirikit NICH 1995-10 (2,259 cases) % total NB-CHD Neonatal CHD was about 25% in overall CHD. 2/3 of cases were noncyanotic group, about 1/3 of cases were cyanotic CHD

1. Cyanotic CHD presented during Neonate 795/2,259 cases(35%) % of NB-CCHD Look at diagnosis in cyanotic CHD group in neonate, we found that the most common diagnosis were…. The 5 most common include about 60 of cases

1. Cyanotic CHD presented during Neonate 795/2,259 cases(35%) % of NB-CCHD The disease that likely to be screened were shown by these cross mark. So most of the Cyanotic CHD can be screening by using pulse oximeter.

2. Cyanotic CHD presented during neonate 795/2,259 cases(35%) % of NB-CCHD These less common diagnosis of cyanic CHD in neonate were shown here.

2. Cyanotic CHD presented during neonate 795/2,259 cases(35%) % of NB-CCHD and 3 of these diagnostic groups could be screened after birth.

Fetal and neonatal circulation The diagram comparing hemodynamic of the fetus and the neonate. The fetus get the oxygen from the placenta in utero and change to receive oxygen from the lungs after birth. The new born baby after birth will become more pink than the fetus due to the separation the oxigenated and deoxygenated blood, especially in the lower exemities. The most important anatomically changes were closing of the …….

Background of O2 sat screening in CCHD Author Year Criteria Postnatal age Detection/ Total Result / comment Hoke TR, etal(8) 2002 >7% diff or< 92% 6-24 hr 4 / 2,908 Richmond S, et al(9). 2002 < 95% >2 hr 6 / 5,626 FN 3 (CoA) Reich JD, et al(10) 2003 < 95% *3 < 90%*1 >4% diff 2 / 2,114 FN 1 (TAPVR) Koppel RI.et al(11) 2003 < 96% >24 hr 3 / 11,281 FN 2 (CoA, hypo LPA) FP 1 Pulse oximeter had been studied for CCHD screening since 2002 In many reports, they used different diagnostic criteria and difference in postnatal age of the neonate. The true positive rate from many reports were about 1 in 1000 neonates. There were also either FN and FP cases.

Background of O2 sat screening in CCHD Author Year Criteria Postnatal age Detection/ Total Result / comment Bakr AF, et al(12) 2005 < 93 % Before D/C 5,211 Sens. 77% Spec 100% PPV 66.7% (PE + O2sat) Knowles R, et al(13) SR (HTA) Life threatening CHD 121/100,000 C-CHD 39% by PE 68% by PO FP 0.5% by PE 1.3% by PO Rosati E, et al(14) < 96 >24 hr 3 / 5,292 Sens 66.7% PPV 50% NPV 100% Reich JD, et al(15) 2008 12 / 7,962 Human factors (placement time, training, nursing degree) The results from later studies showed the sensitivity, or true positive rate screening was about 70%, specificity was nearly 100% with PPV about 60%

Background of O2 sat screening in CCHD Author Year Criteria Postnatal age Detection/ Total Result / comment De-Wahl Granelli, et al(16). 2009 < 95% *3 < 90%*1 >4% diff > 24 hr 29/39,821 Sens 82.8%* Spec 97.8%* Riede FT, et al(17).2010 < 96% (post fetal diagnosis) >24 hr 14 / 41,445 Sens 77.8% Spec 99.9% PPV 25.9% NPV 99.9% Walsh W.(18) 2011 < 94 % (only foot) 1/ 14,983 No echo confirm positive screening test Comparison with late detection cases, MR decrease in early diagnosed gr. from 18% to 0.9% In 2009, Dr. Granelli from Sweden used pulse oximeter measurement at RH and one foot, the criteria were if < 95%*3 times of measurement, or < 90% in any measurements or more than 4% difference between RH and foot at more than 24 hrs postnatal. The results showed sensitivity was 82% and specificity was 97.8%. She also compare the the result of screening and treatment in two area, using pulse oximeter screening area to another non screening area and showed that the early diagnosed cases had decrease MR from 18 % to 0.9% compare to the late detection cases, So if we can diagnosis earlier, we can have 20 times decrease in MR.

Anne De-Wahl Granelli

Background of O2 sat screening in CCHD Author Year Criteria Postnatal age Detection/ Total Result / comment Ewer AK, et al.(19) 2011 24/ 20,055 (2.6/1000) Sens 75% Spec 99.2% Thangaratinum S, et al.(20) 2012 Meta-analysis 13 studies 229,421 Sens 76.5% Spec 99.9% FP 0.14% FN 0.05% after, 0.5% before 24 hr. In 2012, Dr. Thangaratinum showed meta-analysis of 13 studies, in more than two hundred thousand cases, the sens………..

It is a non invasive measure pulse Ox at RH and either one of foot

แนวทางการคัดกรองภาวะหัวใจพิการแต่กำเนิดในทารกแรกเกิด ทารกแรกเกิดตรวจร่างกายปกติทุกราย ให้จับSat.O2มือขวาและเท้า ที่อายุ >24 ชั่วโมง SatO2<90%ที่มือขวาหรือเท้า Sat.O2<95%ทั้งมือขวาและเท้า หรือ มีความต่างของSatO2ระหว่างมือขวาและเท้า>3% Sat.O2>95%ที่มือขวาหรือที่เท้า และ มีความต่างของSatO2ระหว่างมือขวาและเท้า<3% ใช่ ไม่ผ่าน จับSat.O2ซ้ำ ทั้งมือขวาและเท้า อีก1ชั่วโมงต่อมา ผ่าน ใช่ ใช่ ผ่าน ไม่ผ่าน จับSat.O2ซ้ำ ทั้งมือขวาและเท้า อีก1ชั่วโมงต่อมา ผ่าน ใช่ ผลผิดปกติ ให้ประเมินอาการทารก พิจารณาตรวจเพิ่มเติม ผลปกติ  Normal newborn care

Positive screening criteria Any O2 saturation < 90% or O2 saturation < 95% in both RH and F or > 3% difference on 3 measurement , each separate by 1 hr.

Negative screening criteria 1. O2 saturation at RH or F more than or equal to 95 % and 2. The difference of O2 saturation between RH and F less than or equal to 3 %

Primary target diseases(critical CHD) Hypoplastic left heart syndrome. (2.2%) Pulmonary atresia.(8%) Transposition of the great arteries.(4%) Tetralogy of Fallot.(4%) Total anomalous pulmonary venous return. (1.2%) Tricuspid atresia.(0.7%) Truncus arteriosus.(1.2%) Others. Coarctation of the aorta (2%) Interrupted aortic arch (1%) Critical AS (0.4%) These are the primary target diseases that could be screened. Mostly are the severe Cyanotic CHD, either duct dependent pulmonary circulation and duct dependent systemic circulation group.

Hypoplastic left heart syndrome RA

In Pulmonary atresia, there is no forward flow across the PV, ductus arteriosus is necessary for pulmonary blood flow, So we call this condition is ductus dependent pulmonary circulation.

Pulmonary atresia with VSD, this is also ductus arteriosus pulmonary circulation.

Transposition of the great arteries In TGA, there is a problem of mixing blood between Rt and Lt heart cause deoxygenated blood supply the brain and body, while the oxygenated blood supply the lungs. So, patent ductus arteriosus and atrial septal defect are important for cardiac mixing blood.

Coarctation of aorta In neonate with severe CoA Ductus arteriosus is necessary for blood supply to the lower extremities. We can see that in many critical CHD, ductus arteriosus is necessary either to pulmonary blood flow or systemic blood flow. If the PDA is closed with usually occur at few days after birth, the patients will develop symptoms of cyanosis or low tissue perfusion of the body.

We started the pilot study in April 2012 12 general hospitals (6 provinces and Bangkok) Using AAP guideline plus peripheral perfusion index > 0.7 Age > 24 hrs Pulse Oximeter: Masimo (Rad 6) Positive screening-> echo Negative screening-> advice Phone call at 1-2 m of age We started program in Apr 2012 in 12 hospitals, 6 hospitals in BKK and 6 hospitals nearby BKK.

NHSO Funding Supported from the National Health Security Office of Thailand With the supported from ...

Results From Apr 2012- Oct 2014 50,000 NB babies received screening True positive 21 cases False negative 11 cases For two and a half years, Fifty thousand neonates received screening. We got True positive in twenty one cases and false negative in 11 cases.

True Positive Cases 13. Critical PS รพ.เจริญกรุง 14. PA and MA รพ.พระนครศรีอยุธยา 15. TOF รพ. พระนครศรีอยุธยา 16. TA, VSD, PS รพ.สุพรรณ 17. Critical PS รพ. พระนั่งเกล้า TGA,VSD,hypo arch รพ.ตำรวจ PA, VSD รพ.อยุธยา SV, PA, PDA รพ.เจริญกรุง PA, VSD รพ.เจริญกรุง TA, VSD,PS, ASD : FU รพ.พระนั่งเกล้า DS, AVSD,PDA,PH : Med Rx รพ.นพรัตน์ TGA, small VSD, PDA : BAS รพ.ราชบุรี CoA, PDA : repair รพ.ราชบุรี TGA,IVS : ASO รพ.พระนั่งเกล้า Dextro, complex heart disease รพ.พระนั่งเกล้า TOF : FU รพ.ภูมิพล Rt isomerism complex รพ.ราชบุรี PA,IVS รพ. อยุธยา TGA, IVS รพ.ภูมิพล TA รพ.ภูมิพล TAPVR รพ.นพรัตน์ All these are asymptomatic newborn patients had initial and rescue therapy and all survive before the definite treatment.

This was our first positive case, By clinically we can’t detect cyanosis in this child which her O2 sat was 91%

This is another case of asymptomatic severe CoA, we can see the difference in O2 sat at upper and lower extremities, 97% at Rt hand and 91% at Rt foot.

ICU stay > 2 m

False Negative Cases Dextroposition,TA,PA, hypo LPA, small PDA รพ.นพรัตน์ PA, hypo RV (22 d) : BT shunt รพ.สุพรรณ TOF (8m) : FU รพ.สุพรรณ TAPVR : FU รพ.ภูมิพล Severe PS : loss FU รพ.พยลฯ Single ventricle, PS : waiting for BT shunt รพ.พยล DORV : FU รพ.พยล TOF รพ.อยุธยา Hypo AA, VSD: arch repaired , PAB* รพ.สุพรรณ Truncus Arteriosus รพ.ภูมิพล TOF (11 m) รพ.นพรัตน์ We had 11 FN cases. TOF were the most common, they may not severe enough to detect initially and had late presentation.

False Positive Pulmonary Hypertension BMP hosp.(4) Normal AYT hosp.(5) Pneumonia KJB hosp. There were not many False Positive cases, but this may be some under-recorded.

Diagnosis before 24 hrs (26 cases) PA, IVS 3 cases PA, VSD 2 cases TOF 7 cases TGA 5 cases CoA 2 cases Truncus 1 case TAPVR 1 case IAA 1 case AS 1 case TA 1 case Ebstein’s TV 1 case HLHS 1 case 26 cases of cCHD had been diagnosed before the screening or before 24 hours of age.

Conclusions from our study Pulse Oximeter can be used as a screening CHD in NB Sensitivity 65.5 % Specificity 99.9% True Positive rate 0.4: 1,000 (with comparable to the previous reports) Higher false negative rate Asymptomatic critical CHD babies can be detected, received early management and may improve survival.

Comparison the results of screening > 24 hr number TP FP FN TN Bakr 5211 3 2 5206 Reich 2114 4 2110 Koppel 11281 1 11275 Rosati 5292 5288 de Wahl 39821 19 68 10 39724 Reide 41442 14 40 41384 Kawalec 27200 7 13 27179 132361 48 129 18 132166 average 1000 0.362645 0.974607 0.135992 Thailand 27290 11 5 27264 0.40307 0.1832 0.3664 In 2014, we compared our results with the other 7 papers. There are not difference in TP and FP cases from our paper, but we have 3 times higher in FN. This means that we can’t detect more patients, we have to improve our performance. It may be from human error.

แนวทางการคัดกรองภาวะหัวใจพิการแต่กำเนิดในทารกแรกเกิด ทารกแรกเกิดตรวจร่างกายปกติทุกราย ให้จับSat.O2มือขวาและเท้า ที่อายุ >24 ชั่วโมง SatO2<90%ที่มือขวาหรือเท้า Sat.O2<95%ทั้งมือขวาและเท้า หรือ มีความต่างของSatO2ระหว่างมือขวาและเท้า>3% Sat.O2>95%ที่มือขวาหรือที่เท้า และ มีความต่างของSatO2ระหว่างมือขวาและเท้า<3% ใช่ ไม่ผ่าน จับSat.O2ซ้ำ ทั้งมือขวาและเท้า อีก1ชั่วโมงต่อมา ผ่าน ใช่ ใช่ ผ่าน ไม่ผ่าน จับSat.O2ซ้ำ ทั้งมือขวาและเท้า อีก1ชั่วโมงต่อมา ผ่าน ใช่ ผลผิดปกติ ให้ประเมินอาการทารก พิจารณาตรวจเพิ่มเติม ผลปกติ  Normal newborn care

For yellow color means has to repeat, and the red color means abnormal.

In Thailand, We have 77 provinces or 12 Health services area, BBK is number 13. Each area will have about 4-8 provinces.

2014 : Implementation of Critical CHD screening in the newborn program at secondary and tertiary care hospitals in 4 of 13 health service regions in Thailand. In the year 2014, we implement the screening program into the provincial hospitals which may be the secondary and tertiary care hospital in 4 of 12 health service area, not include BKK.

+ Community base hospitals 2014 : (1, 8, 4, 7) 2015 : (2, 5, 9, 11) + Community base hospitals in 30/77 provinces 2016: (3, 6, 10, 12) In 2015, we implement this program into the provincial hospital in another 4 area, and in this year, 30 provincial hospitals teach their community hospital to do pulse oximeter screening. This year we will finish the implementation to all provincial hospital of 12 area outside BKK.

http://pacs.lph.go.th:8181/ScreeningHeart/ The data of screening were sent via web-base program

Data until 6-12-15 88 hospitals: 104,000 cases Until Dec last year, 88 hospitals and some community hospitals register, we have more than one hundred thousand cases were screened,

Data until 17-6-16 107 hospitals: 159,323 cases Positive screening 159 cases Up to now, the number of hospital are increasing to 107. and more than one hundred fifty nine thousand cases were screening, which means more than 50 thousand cases were screening in the last 6 m, or more than 100, 000 cases /year receive pulse ox screening. So far, we have 159 cases of positive screening

http://pacs.lph.go.th:8181/cchd/ 89 93 89

Thank you for your attention Thank you our team. Esp. Khun Somphan Khun Prawdoa, our colleagues, Dr. Siraporn our director to support this program And thank you for your attention