Chapter 12.4 — Newborn Screening Interpretation

Newborn blood-spot screening detects rare but serious, treatable conditions before they cause irreversible harm — endocrine (congenital hypothyroidism, congenital adrenal hyperplasia), metabolic (phenylketonuria, MCAD deficiency and other inborn errors), hemoglobinopathies (sickle cell disease), cystic fibrosis, and increasingly others (e.g., SMA, SCID) depending on the program. The clinical priorities are correct sampling and timing, understanding that a positive is a screen (not a diagnosis) requiring urgent confirmation, recognizing time-critical positives, and applying the special rules for preterm/transfused/PN-fed infants.

• All newborns (screening) and NICU infants with special sampling considerations (preterm, sick, transfused, PN-fed, transferred).
• Teams responsible for taking, tracking, and acting on screening results.
• Cross-references: inborn errors of metabolism (12.1), genetic testing (12.2), thyroid disorders (4.2), adrenal insufficiency/CAH (4.1/4.3), and preterm discharge (2.5).

• Take the sample at the program-specified age (commonly around day 5; verify locally) — too early can miss some conditions (e.g., early thyroid/PKU) and too late delays diagnosis.
• Ensure good technique and adequate spot quality (avoid layering, contamination, or insufficient blood) to prevent repeats.
• Track the sample and its result for every baby — especially those transferred between units.

• The screen measures immunoreactive trypsinogen (IRT), an exocrine pancreatic protein raised in CF and in other GI disease. Critical illness alone can raise it, and multiple transfusions can produce a false negative.
• Elevated IRT on the initial 24–48 hour screen: repeat the newborn screen at 1–2 weeks. If the repeat is negative, nothing further is needed.
• IRT still elevated: the state automatically runs DNA analysis on the sample — a 60 + 4 variant panel identifying one or more variants in up to 90% of patients in Texas, depending on ethnicity, with results in up to 5 days. A very elevated IRT goes straight to DNA analysis without waiting.
• No pathogenic variants: no sweat test needed, but watch for respiratory symptoms. One or two pathogenic variants: refer for sweat testing.
• Sweat test eligibility: at least 2 kg, at least 36 weeks gestational age, and at least 2 weeks old. Testing is technically possible from 2 days of life, but the Cystic Fibrosis Foundation recommends waiting until 10 days; for preterm infants wait for 2 kg and beyond 36 weeks corrected where possible.
• A positive sweat test with two pathogenic variants needs a pulmonary medicine consultation. Clinical indications such as meconium ileus warrant a sweat test regardless of the screen result.

• Panel: more than 50 disorders — core and secondary conditions — including cystic fibrosis, congenital hypothyroidism, galactosaemia, haemoglobinopathies, CAH, biotinidase deficiency, SCID, SMA, and amino acid, organic acid and fatty acid oxidation disorders. Pompe disease, MPS I, MPS II and infantile Krabbe disease were due to be added in summer 2025 — check whether your programme has implemented them.
• Timing: first specimen at 24–48 hours on every newborn, regardless of feeding or prematurity. A routine second screen at 1–2 weeks is a feature of Texas and some other US states, not of every programme.
• Transfusion: collect the first screen before the first intervention — including emergency transfusion and ECMO. A transfused newborn must be retested 6–8 weeks after transfusion.
• Bilirubin as a screen: Baylor nurseries measure total and direct (conjugated) bilirubin at 24–48 hours, alongside the blood spot. An elevated direct bilirubin on this first sample is a marker for biliary atresia — see chapter 10.6.
• CCHD pulse oximetry is legally required for all Texas newborns after 24 hours of age and before discharge, and confirmed CCHD must be reported to the state. The algorithm and its limits are in chapter 3.3.