Newborn screening examinations

Screening Examinations of Newborns

• Screening in pediatrics occurs at preschool and school age.

Basic Requirements of Screening Tests

• The disease is not apparent on physical examination.
• Untreated diseases exhibit mortality or severe morbidity.
• Diseases must be treatable, with early treatment yielding better results than late treatment.
• Tests should be sensitive, detecting a high proportion of affected infants.
• Screening should be cost-effective, including cost savings from early intervention.

General Screening

• Obligatory screenings are performed on the 3rd-4th day of life.
• Laboratory screening involves examination of a blood sample (dry blood spot).
• Laboratory screening includes screening for metabolic and endocrine diseases, as well as cystic fibrosis (PKU, SKH, CAH, CF)

Congenital Metabolic Disorders

• Conditions screened for include phenylketonuria, amino acid disorders, and disorders of fatty acid oxidation.
• Phenylketonuria is the most common and important metabolic disorder screened for.
• Appropriate diet can decrease the risk of brain impairment in phenylketonuria cases.
• The positive impact of screening for amino and fatty acid oxidation disorders is questionable due to the low incidence.

Congenital Adrenal Hyperplasia

• Assessed by evaluating 17-hydroxy-progesterone levels.

• This involves an enzymatic defect in the synthesis of suprarenal gland hormones.

• It is dangerous for newborns due to missing glucocorticoids and mineralocorticoids.

• Aldosterone deficiency may lead to a salt crisis, causing hyponatremia, hyperkalemia, brain edema, and heart disturbances.

• Virilization may develop in girls, while boys may be asymptomatic.

Congenital Hypothyroidism

• Assessed by evaluating TSH levels.
• Early treatment with thyroid hormones (L-thyroxin) can prevent mental retardation.

Cystic Fibrosis

• Screened by immunoreactive trypsin.
• Elevated immunoreactive trypsin indicates an increased risk of cystic fibrosis.
• Abnormal screenings necessitate genetic testing for the most common genetic abnormality, delta F508.
• Some countries also include screening for severe congenital immunodeficiency, with plans to include it in other regions.

Dry Blood Spot Sampling

• Capillary blood sample from the heel is used.
• The first sample is taken at 72-96 hours of age, repeated 10-14 days later if the baby is ill or the mother received antenatal steroids, totaling 2x-3 samples.

Hearing Screening

• Should be done at 3 days - 1 month using transient otoacoustic emission testing of both ears.

• Early diagnosis of hearing disturbance is important to do, as hearing defects affect further neurological development of hearing.

• If a baby cannot hear, they cannot speak, leading to delayed speech, cognitive, and psychomotor development.

• Sensitivity is very high in these tests.

• Positive screening results in further ENT examination via otoscopy and tympanometry.

• Repeated screening is done 1 month after the first testing.

• Still positive results warrant special examination via acoustic evoked potentials.

• A suspected hearing disorder requires special equipment to increase hearing for the baby.

Congenital Cataract Screening

• This is done during first 2 weeks of life.
• Congenital cataract is the 4th most common cause of blindness in the world.
• Screening is based on visualization of the red reflex of the eye using a handheld ophthalmoscope.
• Babies with high pigmentation of retina may show positive screening, requiring specialized ophthalmologic examination.
• Positive screening indicates the presence of congenital cataracts, mandating surgical treatment.
• Untreated congenital cataract may otherwise lead to complete blindness.

Screening of Hip Dysplasia

• This condition involves an abnormal relationship between the femoral head and acetabulum and is the most common congenital abnormality of the skeleton.

• This includes frank dislocation/luxation, partial dislocation/subluxation, and instability.

• Clinical observations include resting posture, movement, unequal leg length (Galeazzi sign), and decreased range of motion in abduction.

• Abnormal clinical observation warrants ultrasound at orthopedics.

• Examiner maneuvers include:

  • Barlow: Adducting the hip to promote dislocation.
  • Ortolani: Abducting the hip to reduce dislocation.
  • Graf classification is used according to ultrasound findings to assess the severity.

General Optional Scans

• Risk factors include breech position, oligohydramnios, anatomic deformities, and genetic factors.

Ultrasound Examination

• Involves the brain and kidneys.
• For the brain, check through the big fontanelle in coronal and sagittal planes.
• Exclude bleedings into ventricles, cysts, tumors, subdural, or epidural bleedings, and congenital anomalies, such as agenesis of corpus callosum.
• Hydrocephalus (dilatation of ventricles) can also be identified.
• For the kidneys (done at 3 days of age), size is assessed in a full urinary bladder (kidney size in mm = gestational week).
• Agenesis of kidney, compensatory hypertrophy, and obstructive uropathies (hydronephrosis) are detected.
• Bleeding into adrenal glands also warrants exclusion.

Pulse Oximetry

• Performed during the first day to screen for congenital heart defects.

• Extremely useful screening, helping identify critical congenital heart defects dependent on patent ductus arteriosus.

• The ductus arteriosus remains open during the first 3 days of life, and its closure is when heart failure symptoms are likely to appear.

• Based on detection of right-to-left shunt through the ductus arteriosus.

• If there are pulmonary problems or cardiac defects, right-to-left shunting is sustained.

• Preductal pulse oximetry is placed on the right arm (should be >95%).

• Postductal pulse oximetry is placed on either foot (should be >95%).

• Difference between saturation should not be higher than 3%.

• Testing results include saturations over 95% with less than 3% difference, saturations between 90-94% with more than 3% variance etc.

• Lower limb saturation higher than 3% than upper limb triggers suspect for coarctation of aorta.

Screening tests added in January 2024

• Spinal muscular atrophy (SMA).
• Primary immunodeficiencies, by checking levels of TRECs (T-cell receptor excision circles) and KRECs (Kappa-deleting recombination excision circles).

TRECS

• Small circles of DNA created in maturing T cells.
• Reduced amounts suggest immunodeficiency, as is present in severe combined immunodeficiency disease.

SCID

• The transplant is conducted to treat the condition earlier.
• If surgery is required, Thymuses from healthy donors during heart surgery is used.
• The Thymus is then transplanted into the recipient's thigh.

Immune System Basics

• Non-Specific Immunity (Innate Immunity):
  • Includes rapid, non-antigen-specific defense mechanisms, phagocytes, complement proteins, NK cells, and cytokines.
  • Acts before the adaptive immune system is activated.
• Humoral Immunity (Adaptive Immunity):
  • Involves B cells and Antibodies
  • Targeted to specific antigens, long-lasting immune memory
  • Disorders affecting antibody production fall

Primary Disorders of Specific Cellular Immunity

• Severe combined immunodeficiencies, syndromic immunodeficiencies.

Severe Combined Immunodeficiency (SCID)

• A real immunological emergency, often called "bubble boy disease".
• Babies are born with low T cells and sometimes also low B cells.