SCREENING FOR

CONGENITAL AND
DEVELOPMENTAL
DISORDERS

Periodic Health Examination Task Force
2021

Philippine Guidelines on Periodic Health
Examination: Screening for Congenital and
Developmental Disorders






by Dr. Eric T. Cabayacruz
1. Pulse Oximetry Screening for Critical Congenital Heart
Disease
RECOMMENDATION CONSIDERATIONS REMARKS
Among asymptomatic, ▪ The use of pulse Pulse oximetry screening to
oximetry is cheap and detect critical CHD, which is a
apparently healthy
effective with moderate subset of CHDs that require
newborns, we early intervention within the
certainty of evidence.
recommend for the ▪ If detected early, there first 28 days of life, had an
screening of critical overall sensitivity of 76.3%
is a great benefit on the and a specificity of 99.9%.
congenital heart management of the Infants with CCHDs are
disease using pulse patients that screen usually asymptomatic during
oximetry. (Strong positive. the first few days of life. If
recommendation, moderate undiagnosed, babies with
certainty of evidence). CCHD rapidly deteriorate
without intervention due to
the closure of the ductus
arteriosus after birth.
2. Newborn Screening for Cystic Fibrosis
RECOMMENDATION CONSIDERATIONS REMARKS
Among asymptomatic, ▪ The very low burden of In the Philippines, there
apparently healthy disease among Filipinos remains a dearth of
coupled with the high information regarding CF.
newborns, we
cost of confirmatory In a study done in
recommend against testing and treatment of California, there were 5
the screening for the disease led the newborns of Filipino
cystic fibrosis. (Strong consensus panel to descent who were
recommendation, very low decide against the diagnosed with CF through
certainty of evidence). screening. a four-step screening
▪ The panel also agreed process. In the Philippines,
that there needs to be however, there is yet to be
stronger evidence to a detected case of CF.
recommend for the
screening of cystic
fibrosis among the study
3. Newborn Screening for Sickle Cell Disease
RECOMMENDATION
Among asymptomatic,
apparently healthy
newborns, we
recommend against
the screening for
sickle cell disease.
(Strong recommendation, very
low certainty of evidence).
CONSIDERATIONS REMARKS
▪ There is a lack of Sickle cell disease (SCD)
burden of this disease refers to a group of
among Filipinos. inherited disorders caused
▪ The very low certainty by structural variations in
of evidence did not the beta subunit of
provide enough basis for hemoglobin.
the panel to recommend In the Philippines, it has an
for the screening of estimated annual
sickle cell disease. incidence of 20 (Hb SS) to
40 (Hb SC) in every 2
million births.
There are only 8 registered
cases of sickle cell
disorders for the past 15
years (2006 to 2021) under
4. Newborn Screening for Thalassemia
RECOMMENDATION CONSIDERATIONS REMARKS
Among asymptomatic, ▪ There is a high Early recognition of the
apparently healthy burden of illness disease may play a pivotal
role in the outcome of the
newborns, we among Filipinos.
disease. Mean life
recommend for the ▪ Despite the very low expectancy is better in
screening of certainty of evidence, those afflicted that had
thalassemia using the panel agreed that early recognition and
BIORAD KIT. (Strong the benefit of early optimal care of
recommendation, very low recognition and thalassemia patients (41.5
certainty of evidence). years) versus those with no
treatment for those care (3 years), with noted
who test positive difference between mean
outweighs the risks. life expectancy of 38.5
years gained.
5. Newborn Screening for G6PD Deficiency
RECOMMENDATION
Among asymptomatic,
apparently healthy
newborns, we
recommend for the
screening of G6PD
deficiency using
fluorescence assay
(PE neonatal kit).
(Strong recommendation, very
low certainty of evidence).
CONSIDERATIONS REMARKS
▪ There is a high The AAP clinical practice
prevalence of this guideline on the management of
neonatal hyperbilirubinemia
disease.
▪ The panel agreed that
recognizes G6PD deficiency as a
major etiologic risk factor for the
the management is cost- development of severe
effective and hyperbilirubinemia, with
preventative against the kernicterus being one of the
development of most severe and life-threatening
clinical consequences. Once an
kernicterus, which would
infant is diagnosed with G6PD
greatly benefit those deficiency, the RR for severe
patients that screen hyperbilirubinemia is said to be
positive. 3.5 fold higher than those who
are not deficient and is strongly
associated with mortality and
long term neurodevelopmental
6. Newborn Screening for Homocystinuria and MAT
Deficiency
RECOMMENDATION
Among asymptomatic,
apparently healthy
newborns, we
recommend against
the screening of
homocystinuria and
methionine adenosyl
transferase deficiency.
(Strong recommendation, very
low certainty of evidence).
CONSIDERATIONS REMARKS
▪ The very low burden of There are only two detected
disease among Filipinos cases of homocystinuria
since 1996. Patients may
coupled with the high
present with
cost of confirmatory
testing and treatment of
neurodevelopmental and
ocular symptoms, connective
the disease led the tissue involvement, or
consensus panel to thromboembolism.
decide against the There has been difficulty in
screening. ascertaining the true
incidence of MAT deficiency
since most patients are
asymptomatic, although some
cases may develop
neurological symptoms later
in life.
7. Newborn Screening for Tyrosinemia
RECOMMENDATION CONSIDERATIONS REMARKS
Among asymptomatic, ▪ The very low burden of Inborn errors of tyrosine
disease among Filipinos metabolism may manifest as
apparently healthy hypertyrosinemia and include
coupled with the high
newborns, we Tyrosinemia type I, II, and III.
cost of confirmatory They differ in incidence with type
recommend against testing and treatment of 1 being the most severe. In the
the screening of the disease led the Philippines, 10 have been
tyrosinemia I/II. (Strong consensus panel to diagnosed with Tyr I and no
recommendation, very low decide against the cases of Tyr II and Tyr III have
certainty of evidence). been detected since the
screening.
introduction of ENBS in 2014.
Tyr I can either be early onset or
late onset. The disease can be
fatal before 10 years of age in
untreated children as they can
present with severe liver disease,
renal disease, rickets, and
8. Newborn Screening for Fatty Acid Oxidation Disorders
RECOMMENDATION CONSIDERATIONS REMARKS
1. Among asymptomatic, ▪ The very low burden of Fatty acid oxidation
apparently healthy disease among Filipinos disorders (FAODs) are
newborns, we coupled with the high metabolic disorders of
recommend against the cost of confirmatory clinical significance due to
screening of LCHADD and testing and treatment of its effect on pediatric
MTPD. (Strong the disease led the morbidity and mortality.
recommendation, very low consensus panel to However, as of June 2021,
certainty of evidence). decide against the no cases of LCHADD,
2. Among asymptomatic, screening of LCHADD, MTPD, CPT1D, CPT2D, and
apparently healthy MTPD, CPT1D, CPT2D GA2 were identified by the
newborns, we and GA2. ENBS since its
recommend against the implementation.
screening of CPT1D,
CPT2D and GA2. (Strong
recommendation, very low
9. Newborn Screening for Biotidinase Deficiency
RECOMMENDATION
Among asymptomatic,
apparently healthy
newborns, we
recommend against
the screening of
biotidinase deficiency.
(Strong recommendation, very
low certainty of evidence).
CONSIDERATIONS REMARKS
▪ The very low burden of According to the Metabolic Registry
of the Institute of Human Genetics,
disease among Filipinos there was only 1 case of biotinidase
coupled with the high deficiency reported in the Philippines
cost of confirmatory since screening was started in 2014
testing of the disease and
resulting to an estimated prevalence
of 1 in 1,748,857.
the very low certainty of Clinical manifestations of biotinidase
evidence led the deficiency usually appear in
untreated patients between ages
consensus panel to one week and ten years (median age
decide against the of 3 months) with profound
screening of biotidinase biotinidase deficiency presenting as
neurologic abnormalities and skin
deficiency. manifestations while those with
partial biotinidase deficiency exhibits
hypotonia, skin rash, and hair loss,
particularly during times of stress or
infection.
10. Newborn Screening for Beta-Ketothiolase Deficiency
RECOMMENDATION CONSIDERATIONS REMARKS
Among asymptomatic, The very low burden of In the Philippines, no case
apparently healthy disease among Filipinos of BKTD has been reported
coupled with the high since the introduction of
newborns, we
cost of confirmatory expanded newborn
recommend against testing of the disease led screening in 2014.
the screening of beta- the consensus panel to
ketothiolase decide against the
deficiency. (Strong screening of beta-
recommendation, very low ketothiolase deficiency.
certainty of evidence).
11. Newborn Screening for Holocarboxylase Synthetase
Deficiency
RECOMMENDATION CONSIDERATIONS REMARKS
Among asymptomatic, The very low burden of Considered as one of the rarest
disease among Filipinos inborn error of metabolism;
apparently healthy exact prevalence worldwide is
coupled with the high
newborns, we currently unknown.
cost of confirmatory According to the 2020
recommend against testing of the disease led Philippine Newborn Screening
the screening of the consensus panel to Report, the prevalence of HCLS
holocarboxylase decide against the is 1/1,069,667 since inception
of routine testing in the country.
synthetase deficiency. screening of In the absence of early
(Strong recommendation, very holocarboxylase
recognition and treatment,
low certainty of evidence). synthetase deficiency. patients with HCLS deficiency
often have a severe natural
course resulting to long-term
neurological sequelae and
significant intellectual disability.
12. Newborn Screening for Isovaleric Acidemia
RECOMMENDATION
Among asymptomatic,
apparently healthy
newborns, we
recommend against
the screening of
isovaleric acidemia.
(Strong recommendation, very
low certainty of evidence).
CONSIDERATIONS REMARKS
The very low burden of In the Philippines, there are
disease among Filipinos 3 confirmed cases of IVA
coupled with the high from the 3,209,001 babies
cost of confirmatory screened since 2014,
testing of the disease led giving a prevalence of 1.1
the consensus panel to in 1,000,000.
decide against the
screening of isovaleric
acidemia.
13. Screening for Developmental Delay
RECOMMENDATION
1. Among
asymptomatic,
apparently healthy
children born preterm,
we recommend
screening for
developmental delay
at 3-5 months, 12
months, 24 months
corrected age and at
36-48 months of age.
(Strong recommendation, low
certainty of evidence). delay.
CONSIDERATIONS
The consensus panel agreed
that along with the high
prevalence of premature
births, the screening for
developmental delay will lead
to early intervention and
therefore, improved outcome.
These benefits outweigh the
risks of screening. The ages at
which these children should
be screened was an issue
discussed by the panel. In the
end, the frequency for
screening was based on the
2017 NICE Guidelines on
Developmental Follow-up of
Children and Young People
REMARKS
Early identification of children
at risk of having
developmental disabilities
facilitates parental counseling
and early intervention services
to prevent delays, stimulate
emerging skills, and create a
more supportive and
protective environment. It
also prevents over servicing
children who are typically
developing, and facilitates
targeted interventions for
those with a higher risk of
developmental delay.
13. Screening for Developmental Delay
RECOMMENDATION CONSIDERATIONS REMARKS
2. Among asymptomatic, The ages at which these
apparently healthy children children should be
who have any of the screened was discussed
following risk factors: and the final
maternal alcohol use recommendation is
during pregnancy, based on the AAP
gestational diabetes, Guidelines.
gestational hypertension
or maternal obesity, we
recommend screening for
developmental delay at 9-,
18- and 24-30 months.
(Strong recommendation, low
certainty of evidence).
13. Screening for Developmental Delay
RECOMMENDATION
3. Among
asymptomatic,
apparently healthy
children who were
exposed to maternal
cigarette smoking
during pregnancy,
there is insufficient
evidence to
recommend for the
screening of
developmental delay.
(Low certainty of evidence).
CONSIDERATIONS REMARKS
Although the panel agrees Maternal smoking Low
that maternal cigarette quality evidence from 2
smoking during pregnancy studies showed conflicting
has been associated with results. One prospective
poor outcomes for both cohort showed non-
mothers and their babies, significant increased risk of
the studies revealed gross motor delay.
insignificant results for
screening for
developmental delay, in
particular.
13. Screening for Developmental Delay
RECOMMENDATION CONSIDERATIONS REMARKS
4. Among The panel decided that Low quality evidence from
asymptomatic, the lone study was not a prospective study
enough basis to make a showed non-significant
apparently healthy
recommendation. increased risk of
children whose suspected developmental
mothers were anemic, delay.
there is insufficient
evidence to
recommend for the
screening of
developmental delay.
14. Screening for Autism Spectrum Disorder
RECOMMENDATION CONSIDERATIONS REMARKS
Among asymptomatic, Although the M-CHAT ASD is a
apparently healthy R/F has not been neurodevelopmental
validated in Filipino as of disorder marked by
children, we
press time, the very high impairments in social
recommend for the burden of disease along interaction and
screening of autism with the benefit of early communication, and/or
spectrum disorder intervention for those restricted, repetitive
between the ages of who screen positive for patterns of behavior. While
18 to 24 months old ASD led the panel to vote the mean age at diagnosis
for this recommendation. of ASD is 5 years old,
using the M-CHAT R/F. symptoms can be
(Strong recommendation,
moderate certainty of observed as early as
evidence). infancy.
15. Screening for Learning Disorders
RECOMMENDATION
Among asymptomatic,
apparently healthy
children, there is
insufficient evidence
to recommend for or
against the screening
of specific learning
disorders (reading
disability) in the
primary health care
setting. (Very low certainty
of evidence).
CONSIDERATIONS
▪ There is no unified
standard tool identified to
screen for learning
disorders, specifically
reading disabilities.
▪ The panel also
considered whether it is
more appropriate for the
primary educators of
these children rather than
physicians to screen them
for the reading disabilities.
REMARKS
Among all learning
disorders, the most
common is reading
disorder also named as
dyslexia.
Epidemiological studies
report prevalence rates of
4.9% to 7.5% for reading
disability.
In the Philippines, 6.4% of
our 10-14 years old and
2.8% of 15-19 years old
cannot read and write.
Periodic Health Examination Task Force Summary of Recommendation
Recommend For Recommend Against Insufficient Evidence for
1. Screening of Critical 1. Screening for cystic fibrosis; 1. screening of
Congenital Heart Disease 2. Screening for sickle cell disease; developmental delay among
using Pulse Oximetry; 3. Screening of homocystinuria and methionine adenosyl asymptomatic, apparently
2. Screening of thalassemia transferase deficiency; healthy children who were
using BIORAD KIT; 4. Screening of tyrosinemia I/II; exposed to maternal
3. screening of G6PD 5. screening of LCHADD, MTPD, CPT1D, CPT2D and GA2; cigarette smoking during
deficiency using 6. screening of biotidinase deficiency; pregnancy;
fluorescence assay (PE 7. screening of beta-ketothiolase deficiency; and among asymptomatic,
neonatal kit); 8. screening of holocarboxylase synthetase deficiency; apparently healthy children
4. developmental delay 9. screening of holocarboxylase synthetase deficiency; whose mothers were anemic;
born pre-term; 10. screening of isovaleric acidemia; 2. screening of specific
5. Developmental delay learning disorders
with following risk
factors: maternal alcohol
use during pregnancy,
gestational diabetes,
gestational hypertension
or maternal obesity
6. screening of autism
spectrum disorder