newborn screening

1. Dr Sarath M B
DNB Resident
Pediatrics

2. WHAT?
 Public health program
 Now an integral part of neonatal care
 Screening babies for potentially
treatable conditions, not clinically
evident in newborn period
 “Catch them early”
◦ Aim to identify early before significant morbidities set in
 List of disorders vary from country to country
◦

3. Seven components :-
1. Education :- Parents / public and the professionals
2. Screening :- Collection, submission, testing & storage
3. Diagnosis :- Interpretation of results & reporting
4. Conveying :-To doctor & parents, Counselling

4. 5) Follow up :- Repeat test if positive & confirm
6) Management :- Treatment & Monitor long term outcome
7) Evaluation:- Program quality assurance, outcome&cost
effectiveness

5. Criteria:-
 Health problem resulting significant morbidity or death
 Effective treatment should be readily accessible
 Early treatment should lead to better outcomes
 Availability of a reliable screening test
 Simple & inexpensive
 Timely availability of results
 Definitive confirmatory test available

6.  When ?
◦ Term babies :- Between 2nd & 7th day of life
◦ Sick & premature babies :- 7th day with repeat test at 1 month
 How ?
◦ A health professional pricks baby’s heel & collects a small amount of
blood onto a special filter paper
◦ Card is then sent to the laboratory & analysed

7. How did it all start ?
 Father of newborn screening
 Screening test for phenylketonuria
(PKU) using bacterial inhibition assay
 Filter paper (Guthrie card) system for the
collection & transportation of small
blood samples
Robert Guthrie

8.  1960s :-
◦ Bacterial inhibition assay for phenylketonuria (PKU) by Guthrie
 Gradual evolution over the years
◦ Over the next two decades:-
 Congenital hypothyroidism (CH)
 Sickle cell disease
 Congenital adrenal hyperplasia (CAH)
 Cystic Fibrosis
 Metabolic disorder
◦ Today:-
 Screening as many as 40-50 conditions mandatory in the
West
 Indian scenario ??

9.  Phenylalanine(PKU) facilitate bacterial growth in a culture
medium with an inhibitor
 Bacterial colony growth used as a semi quantitative indicator to
measure the concentration of phenylalanine in a sample
 Others :- MSUD, homocystinuria, tyrosinemia & histidinemia

10. Current methods :-
 Radioimmunoassay (T4) :- congenital hypothyroidism
 Isoelectric focusing & liquid chromatography :- hemoglobinopathies
 Polymerase chain reaction (PCR) :- mutations in hemoglobin genes
 Biochemical and genetic tests :- cystic fibrosis & SCID

11. Tandem Mass Spectrometry
 Introduced in the 90’s
 Multiple disorders using single assay
 Increased efficiency with low cost per sample
 Detects molecules by measuring their weight
 Best used for inborn errors of metabolism

12.  All newborns before one month of age
 Otoacoustic emissions(OAE) or auditory brainstem response
(ABR)
 Single-stage or two-stage
◦ Two staged :- OAE first & ABR if OAE fails
◦ Decreases referral rate
 NICU admissions:-
◦ Increased risk for auditory neuropathy
◦ ABR initial choice
Ref:- United States Preventive Services Task Force recommendations
HEARING LOSS

13.  Otoacoustic emissions (OAE):-
◦ detect sound produced by movements of outer hair cells of the cochlea
 Auditory brain-stem response (ABR) :-
◦ measures average neural response to sound stimuli-auditory neuropathy
 In USA, the average age at which hearing loss is confirmed
has dropped from 24 to 30 months to 2 to 3 months
 Audiologic assessment of all infants who fail their screening
test by three months of age

14. Critical Congenital Heart Disease
 Timing:- after 24 hours of life
 SaO2 measured in right hand (preductal) & either foot (postductal)
 Positive screen if any :-
1) SaO2 < 90 % in either extremity
2) SpO2 90 - 94 % in both upper & lower extremities on three measurements,
each separated by one hour
3) SpO2 difference >3 % between upper & lower extremities on three
measurements, each separated by one hour
* Sensitivity around 75% & specificity > 99 %
* Positive screen should be followed by echocardiogram
Ref:- AAP guidelines

15. USA during 2006
Disorder Estimated Number of cases
Hearing loss 5,073
Congenital hypothyroidism 2,156
Cystic fibrosis 1,248
Hemoglobin SS 1,128
Galactosemia 224
Phenylketonuria
Congenital adrenal hyperplasia
215
202
* 4 million newborns screened
* 12,500 infants with various disorders diagnosed & treated

16.  WHO :-
 Genetic services should be introduced in countries with IMR < 50
 Indian Scenario:- IMR-41
◦ Goa (10)
◦ Kerala (12)
◦ Daman & Diu and Puducherry (18)
◦ Chandigarh (20)
◦ Lakshadweep (21)

17.  Limited programmes at govt level
 Paediatric age group :-
◦ Rashtriya Bal Swasthya Karyakram introduced for early detection &
treament
• Hypothyroidism * Mental retardation * Speech & hearing disabilities
But....!!!
 No nationwide newborn screening programme YET which can
detect these disorders early & prevention of morbidities
 What do we have?
◦ Increased reliance on private labs

18. Disorders Which Should be Screened:-
 NNF recommendation:-
◦ Universal screening for
 Congenital hypothyroidism
 Congenital adrenal hyperplasia
 G6PD deficiency
 Expanded newborn screening (TMS) offered to affordable
group especially in urban settings

19. The Goa Experience (2008-2011)
 First Indian state to introduce newborn screening program
 Total newborns screened :- 27,578
 But.....wound up in 2013 !!
Fatty Acid Oxidation Disorders 57
Amino Acid Disorders 8
Organic Acid Disorders 12
CH 8
G6PD Deficiency 33
CAH 2

20. Failed programme :-
 No in place infrastructure for management of diagnosed cases
 Purpose lost as benefits of screening couldn’t be highlighted

21.  KERALA model (2012)
 All babies born in government hospitals undergo
mandatory screening for four congenital metabolic
disorders:-
◦ Congenital hypothyroidism
◦ Phenylketonuria
◦ Congenital adrenal hyperplasia
◦ Glucose 6 phosphate dehydrogenase deficiency

22.  Our challenges :-
◦ Costs involved
◦ Non-availability of demographic data about diseases in question
◦ Massive annual birth cohort
◦ Limitations of treatment modalities
◦ Logistics :- Lack of trained staff & physicians, reliable labs

23.  A nationwide program for screening for CH should be initiated
without delay
 All hospitals in urban areas should initiate NBS for CH, CAH
and G6PD deficiency
 Facilities for confirmation of diagnosis, follow up & treatment
should be established
 A need to increase the number of physicians trained in
metabolic disorders
Newborn screening: need of the hour in India
Verma IC, Bijarnia-Mahay S, Jhingan G, Verma J