What newborn screening panel should be performed before hospital discharge (including timing of heel‑stick collection) and how should abnormal results be confirmed and treated?

Newborn Screening Panel and Timing

All newborns should undergo comprehensive screening for 29 core panel conditions plus 25 secondary target conditions, with heel-stick blood collection performed at 24-48 hours after birth to optimize test accuracy while allowing sufficient time for metabolic abnormalities to manifest. 1, 2

Screening Panel Components

Mandatory Core Panel

• Screen for all 29 core panel conditions that meet three critical criteria: identifiable at 24-48 hours before clinical detection, validated test with appropriate sensitivity/specificity, and demonstrated benefits of early intervention on mortality and morbidity 1, 2
• Report all 25 secondary target conditions identified through differential diagnosis or incidentally detected by screening technology, even when efficacious treatment may be limited 1, 2
• Communicate all clinically significant findings including carrier status identification to healthcare providers and families 1, 2

Additional Required Screenings Before Discharge

• Blood glucose testing in at-risk infants (maternal diabetes, prematurity, low birth weight) to prevent neurological damage from hypoglycemia 3
• Blood typing and direct antiglobulin test (DAT) to identify maternal-fetal blood group incompatibilities that could cause hemolytic disease 3
• Transcutaneous or serum bilirubin screening to detect hyperbilirubinemia and prevent kernicterus 3
• Hearing screening to identify congenital hearing loss and prevent speech/language delays 3
• Critical congenital heart disease (CHD) screening via pulse oximetry to detect life-threatening cardiac defects 3, 4

Optimal Timing of Heel-Stick Collection

Standard Timing Protocol

• Collect blood spot at 24-48 hours after birth as the optimal window that balances early detection with test accuracy 1, 2
• Wait at least 24 hours after milk feeding for metabolic screening to minimize false positives from the physiological neonatal TSH surge and allow metabolic abnormalities to accumulate 3, 5
• Minimum 12 hours of age before initial screening to reduce false positive rates, particularly for phenylketonuria screening 6

Special Circumstances Requiring Modified Timing

• NICU infants require different protocols: Screen on day of birth prior to interventions (aminoglycosides, blood transfusions, NPO status, heparinized solutions), then repeat at 1-2 weeks of life as these factors can cause false results 7
• Early discharge (<48 hours) mandates repeat screening at 1-2 weeks to capture conditions that may be missed with early collection 7, 5
• Premature and low birth weight infants have higher false positive rates with early screening and require careful interpretation and repeat testing 5

Confirmation and Treatment of Abnormal Results

Follow-Up System Requirements

• Establish close communication between the medical home and public/private screening program components to ensure test result confirmation 1, 2
• Standardize result reporting procedures with documented confirmatory results obtained for all screen-positive cases 1
• Schedule newborn follow-up within 3-5 days (72-120 hours) after discharge, with earlier visits (48-72 hours) required for infants discharged before 48 hours 4
• Implement enhanced oversight of hospital-based screening activities to improve tracking of screen-positive cases 1

Confirmation Protocol

• Review all screening results before discharge including metabolic screening, hearing screening, and CHD screening 3, 4
• Arrange appropriate follow-up for abnormal findings with specialists experienced in diagnosis, treatment, and management of specific conditions 1
• Obtain confirmatory diagnostic testing promptly for screen-positive results to minimize delays in treatment initiation 1

Treatment Initiation

• Begin treatment immediately for confirmed cases to minimize neonatal CNS exposure to metabolic derangements and prevent irreversible neurological damage 7, 5
• Treat all suspected cases as true positives during the first 3 years of life, even if transient hypothyroidism is suspected, given the risk of mental retardation 5
• Implement dietary, hormonal, and other interventions as indicated by specific condition to prevent metabolic acidosis, seizures, coma, and death 7

Critical Pitfalls to Avoid

• Do not screen before 24 hours unless NICU protocols require it, as physiological TSH surge causes false positives 5
• Do not assume single screening is sufficient for early discharge or NICU infants—repeat testing is mandatory 7, 5
• Do not delay treatment while awaiting confirmatory results if clinical suspicion is high, as conditions can be life-threatening within the first 2 weeks 7
• Do not fail to communicate carrier status or secondary findings to families, as this information has clinical significance 1, 2

System-Level Quality Assurance

• Implement centralized health information data collection for longitudinal assessment of disease-specific screening programs 1, 2
• Apply total quality management principles with uniform performance standards and enhanced quality assurance programs 1
• Maximize multiplex technologies to identify the broadest range of clinically significant conditions 1