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Abstract

Newborn screening (NBS) program is an important tool for the early diagnosis and preventive treatment of life-long impairments. NBS is one of the strategies recommended by the World Health Organization to promote the primary prevention of congenital anomalies and the health of children with these conditions. However, NBS initiation and implementation in developing countries, especially South-East Asian and North African regions, are slow and challenging. Expanded NBS is not mandatory and has not yet been incorporated into the public healthcare system in our country. Limited funding, manpower shortages, inadequate support services, low public awareness, and uncertain commitment from healthcare practitioners are the main challenges in establishing this program at the national level. Involvement and support from policy makers are very important to the success of the program and the benefit of the entire population.

Keywords: newborn screening, inborn error of metabolism, congenital disorders, Malaysia

Introduction

Congenital anomalies affect approximately1 in 33 infants. These anomalies causeapproximately 3.2 million birth defect-relateddisabilities and an estimated 270,000 neonataldeaths annually (1). An increase in certifiedinfantdeathsfromcongenitalanomalieshasbeenobserved in Malaysia even though the rate hasdeclinedasaresultofimprovementsinnutritionandobstetricandneonatalservices(2).Congenitalabnormalities are the second leading cause ofneonataldeathinMalaysia(approximately50%)accordingtoNoraihanetal.(2).TheWorldHealthAssembly has recently called all member statestopromotetheprimarypreventionofcongenitalanomalies and thehealth of childrenwith theseconditions by (i) developing and strengtheningregistration and surveillance systems; (ii)developing expertise and building capacity; (iii)strengthening research and conducting studieson the etiology, diagnosis, and prevention ofanomalies; and (iv) promoting internationalcooperation (1). Newborn screening (NBS) isone of the recommended preventive measuresand involves clinical examination and screeningfor hematological, metabolic, and hormonaldisorders. This program facilitates life-savingtreatmentsandlimitstheprogressionofphysical,intellectual,visual,andauditorydisabilities.

SpecialCommunication

Present Status and Future Concerns of Expanded Newborn Screening in Malaysia: Sustainability, Challenges and PerspectivesYin Hui Leong, Chee Yuen gan, Mohd Adi Firdaus Tan, Mohamed Isa Abdul Majid

Centre for Advanced Analytical Toxicology Services, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia

Submitted: 18Sep2013Accepted:19Dec2013

NBS has been adopted worldwide as publichealth activity and has been well establishedin developed countries for over 40 years. NBSis recognized internationally as an essential,preventativehealthschemethatdetectsandtreatsinborn errors of metabolism (IEM) early priorto the onset of symptoms. Inherited metabolicdisorders or IEM are genetic enzyme defectsthatcausetheabnormalfunctionofbiochemicalpathways (3). Patients with these disorders areunable to use or synthesize certain compounds,such as fatty acids, amino acids, organic acids,or other macromolecules (4). Acute or chronicsymptoms of these conditions are frequentlyobserved in infants and young children. Thehealth of children with IEM often deterioratessuddenly,andtheconditionprogressesrapidlyasa result of severe, permanent braindamage (5).Individual IEM cases are rare but the collectiveprevalenceofthisconditionisestimatedtobe1in3,000to5,000births inthegeneralpopulation.According to Raghuveer et al. (6), IEM has anincidencerateofaminimumof1in1,500personsintheUnitedStates.AnumberofreportsonIEMin Malaysia have been published; however, theactualnumberofIEMpatientscannotbederivedfrompopulation-basedstudies(5). NBS involves a comprehensive system

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of education, screening, follow-up, diagnosis,treatment/management, and evaluation whichmust be institutionalised and sustained withinpublic health systems. This programoften faceseconomic, political, and cultural challenges. Forinstances, the initiation and implementation ofthis program in developing countries, especiallyin South-East Asian andNorth African regions,areslowandlimitedbypooreconomies,unstablegovernments, unique cultures, geographicextremes, and varying public health priorities(7,8). A consensus regarding the disorders toincludeinscreeningpanelshasnotbeenreached;therefore the coverage of congenital disordersis different among countries. However, mostscreening panels include various inborn errorsin the metabolism of amino acids, fatty acids,andorganic acids.We review thepresent statusofandfutureconcernsregardingexpandedNBSinMalaysia in thispaper.Wealsodiscuss someofthechallengesinimplementingandsustainingthisprogram.

Current Status

NBS in Malaysia began with cord-bloodscreeningforglucose-6-phosphatedehydrogenasedeficiency (G6PD deficiency) in 1980. In 2003,theMinistry ofHealthMalaysia implemented anationwide,step-wise,congenitalhypothyroidism(CH) screeningprogram for all babies deliveredin government hospitals. With the developingof audiological and intervention services forhearing-impairedchildrensincetheearly1990s,a few hospitals have implemented hospital-

basednewbornhearingscreeninginearly2000s.However,expandedNBS(inclusiveofaminoacidmetabolism, fatty acid oxidation, and organicacidmetabolismdisorders)isnotmandatoryandhasnotyetbeen incorporated into thecountry’spublic healthcare system. At present, expandedNBS of IEM is being conducted mainly in twocenters, namely Institute for Medical Research(IMR) and Centre for Advanced AnalyticalToxicologyServices(CAATS)onrequestbysomeoftheprivatehospitals.IMRisundertheauspicesofMalaysianMinistryofHealth,whereasCAATS(formerly managed by the Doping ControlCentre)isaresearchandservicelaboratoryunderUniversiti Sains Malaysia. Table 1 shows someofthestatisticsonNBStestinginCAATS.Thesedata are obtained from routine samples sent byprivate hospitals with birthing and maternityfacilities.The resultsprovideanoverviewof thenumber of possible positive cases; however, theactual number of established IEM cases is notknown because patient profiles are confidentialandcannotberetrievedbytheservicecentre.

Newborn screening Implementation Challenges

ThepopulationoftheAsiaPacificconstitutesoverhalfofthetotalworldpopulationandbirthsin this region comprise 49% of annual birthsworldwide (9).However,NBS coverage in someof the developing countries in the Asia Pacificremains very low (< 1%) (10). Several factorscritical to a successful national NBS programhavebeenidentifiedinasurveyconductedamong

Table 1: StatisticsonnewbornscreeningtestingatCentreforAdvancedAnalyticalToxicologyServicesfrom2007–2013

Year Number of samples Number of positive samples*

Findings

2007 39 – –2008 745 3 Slightelevationoftyrosine&C162009 2081 3 Slightelevationofaminoacid&

acylcarnitineprofiles2010 966 1 Slightelevationofphenylalanine2011 1211 7 Slightelevationoftyrosine,alanine,

methionine,ornitine&C32012 801 – –2013** 501 – –Total 6284 14*Positivesampleisreferredtothesamplethatexceededthecutoffvalue.**Samplescountedupto31August2013.

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NBSmanagersinAsiancountries:(i)governmentprioritization; (ii) full or partial governmentfinancing; (iii)public educationandacceptance;(iv)healthpractitionercooperation/involvement;and(v)governmentparticipationinNBSsysteminstitutionalisation (7). The challenges faced byNBS in Malaysia are similar to those of otherdevelopingcountriesandthemainlimitationisthehighinfrastructurecostrequiredbythisprogram.Thecostoftheinstrumentsandmanpowertrainingusedinthescreeningprogramisasignificantissuein the establishment of this national program.The lackofmedicalor laboratorystaffgiventheincreased workload is another factor. Malaysiahasashortageofdoctorsandothersupportstaffsatpresent: thecurrentdoctor-to-patientratio inWestMalaysiais1:800,whereastheratioinEastMalaysia is approximately 1:1700. These ratiosare lower than the recommended ratio of 1:600set by the World Health Organization (11,12).Follow-uptreatmentsandconfirmationregardingpositive NBS diagnosis requires experiencedand knowledgeable personnel and medical ortechnical support is critical to sustainable NBS.However, very few specialists towhom referralscanbemadeonceapositivediseasediagnosishasbeenconfirmedinnewbornsarepracticinginthisregion (7). In the survey conducted by CAATSto investigate NBS awareness and acceptancelevels among parents, clinicians, and hospitaladministrators in Malaysia, only approximately20% of all registered private hospitals withbirthing and maternity facilities sent samplesfor freeexpandedNBS testing (13).Thisfindingreveals thatpublicawarenessofNBS is lowandthat clinicians and hospital administrators lackinterestinthisprogram.Perceivedexpensesandlong turn-aroundtimemayalsoaccount for lowIEM-screening rates. Insufficient knowledge,commitment, and the lack of ability to conductNBSfollow-uptreatments/servicesinhealthcareprovidershavealsocausedthediscontinuationorinitiationoftheprogram. Parental concern and perception play animportantroleinthechoicetoundergoscreening.Parents normally obtain information regardingNBS from either pediatricians, gynecologists, orprinted materials from clinics or hospitals. Themajority of parentswho consented to screeningunderstandtheprinciplebehindmetabolictestingaccordingtoBiswasetal.(14).Thereasonscitedby parentswho opted not to undergo screeningare either related to processes (IEM screeningis being unimportant because it is optional), orunderstanding (the previous child is unaffectedandwell;thepresentchildappearshealthy;NBS

is a research tool). Parents’ judgment on riskassessment (IEM is deemed uncommon) andtheiremotionalstatesalsoaffectdecision-makingregardingscreening(thetestistoopainfulorthebaby is too young to be tested) (14). However,Biswasetal.(14)foundthatcostisnotthemainbarrier to thechoice toundergoscreening,evenfor parents from low socio-economic strata.Unnecessaryworriesmaybeoneof theparentalconcerns because false-positive diagnoses areinevitable(15). NBS tests face challenges different fromthose of other biochemical analyses. The testis time-sensitive, and the screening must beconducted in the first week of birth. Specimen-collectiontimeframeisimportantbecausetimelytreatment before four weeks of age helps toprevent irreversiblemental retardation,physicaldisability,anddeathinmostcases(16).Innormalpractice, dried blood-spot NBS specimens arecollected from infantsbefore 72hoursof ageorpriortohospitaldischarge.However,thisprocessis logistically difficult for home deliveries or formothers who return to their rural hometownsfor a post-delivery confinement period of up to42days.Notalloftheseplaceshaveadedicatedpublic health facility to accommodate testing.Thus, following up and calling babies back tothe facility for blood sampling or re-samplingfor confirmation purposes or as a result ofunsatisfactoryandinvalidsamplesisdifficult.

Sustainability and Future Perspective

Integrating this program into the nationalhealthdeliverysystemisthemostcriticalelementto its success and sustainability. Innovativeand well-planned financial strategies (forexample inclusion in health insurance schemes)enhance program sustainability. The extent ofgovernment involvement and the successfulhandling of all limitations have a direct impacton the implementation of expanded NBS andits coverage. Although additional expenses anddifficulttechniquesarerequired,NBShasproventobecost-effectiveinreducingneonatalmortalityandmorbidityinbothdevelopedanddevelopingcountries. For instance, the implementation ofexpanded NBS in Texas is reported more cost-effective than unexpanded NBS because thescreened population benefited from greaterquality-adjusted life-years (QALYs) (17). Goodpartnershipamongallsectorsmustbeempoweredto participate in program implementation.This partnership involves all pediatricians,obstetricians, midwives, neonatologists,

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geneticists, endocrinologists,nurses, communityhealth workers, hospital administrators, andpolicymakers.

Conclusion

NBS isan important tool inearlydiagnosisand treatment. Even though the prevalence ofIEMmaybelow,thisproblemmustbeaddressedearly to avoid life-long impairments. Numerouspublished studies on expanded NBS havedemonstrated that the program is feasible andbeneficial.However, limited funding,manpowershortage, inadequate support services, lowpublic awareness, and uncertain commitmentby healthcare practitioners to NBS initiationand implementation are the typical obstaclesencountered by several developing countries,including Malaysia. To ensure a better lifeespeciallyforthenextgeneration,theinvolvementand support from the policy makers are veryimportant for the implementation of expandedNBSinthecountry.

Acknowledgement

AspecialthankstoProfDato’MohamedIsaAbdulMajidforhisguidance.

Conflict of Interest

None.

Funds

None.

Author Contribution

Draftingofthearticle:YHLCritical revision of the article for the importantintellectualcontent:CYG,MAFT,MIAM

Correspondence

DrLeongYin-HuiPhD(UniversitiSainsMalaysia)CentreforAdvancedAnalyticalToxicologyServicesUniversitiSainsMalaysia11800USMPenang,MalaysiaTel:+6046536176Fax:+6046534688Email:yinhui_leong@yahoo.com

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