Newborn screening (NBS) is a cornerstone of modern pediatric healthcare, designed to detect conditions early—before symptoms appear—to prevent severe complications, disability, or even death. Several laboratory tests are routinely included in newborn screenings, each targeting specific metabolic, endocrine, hematologic, or lipid-related abnormalities. Among the most common tests are phenylketonuria (PKU), blood glucose assessment, white blood cell (WBC) evaluation, and cholesterol measurement. Understanding the purpose, methodology, and clinical implications of these tests is crucial for healthcare providers, parents, and policymakers.
Phenylketonuria (PKU) Screening
PKU is an inherited metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase, leading to accumulation of the amino acid phenylalanine in the blood. Without treatment, elevated phenylalanine levels can result in intellectual disability, developmental delays, and neurological damage. Screening is typically conducted 24–48 hours after birth using a heel-prick blood sample collected on filter paper (Guthrie card). Analysis is usually performed via tandem mass spectrometry (MS/MS) to detect elevated phenylalanine levels. If PKU is detected, infants are placed on a phenylalanine-restricted diet under the guidance of a metabolic specialist, often supplemented with specially formulated medical foods.
Glucose Screening
Blood glucose monitoring in newborns identifies hypoglycemia, which can be particularly dangerous in infants due to their small glycogen stores and immature gluconeogenesis. Low glucose levels can cause seizures, brain injury, and developmental delays if unrecognized. Risk factors include preterm birth, low birth weight (<2500 g), infants of diabetic mothers, and perinatal stress or asphyxia. A heel-prick blood sample is taken to measure glucose levels, with normal newborn glucose ranging 45–90 mg/dL in the first 24 hours. Persistent hypoglycemia (<40 mg/dL) requires intervention, which may include early feeding, intravenous glucose, and serial monitoring until stable.
White Blood Cell (WBC) Count Screening
A WBC count assesses the immune and hematologic status of a newborn. Abnormal WBC levels can indicate infection, inflammation, or hematologic disorders. Leukocytosis (high WBC count) may signal bacterial sepsis, stress response, or inflammation, while leukopenia (low WBC count) may indicate congenital infections, bone marrow suppression, or immunodeficiency. Blood is collected via heel-prick or venous sampling, and automated analyzers provide total and differential counts, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Abnormal WBC counts prompt further evaluation such as blood cultures, CRP testing, and clinical monitoring, with early intervention being critical for neonates at risk of sepsis.
Cholesterol Screening
Cholesterol measurement, while not part of every standard newborn panel, is increasingly used to detect congenital lipid metabolism disorders like familial hypercholesterolemia. Blood is obtained via heel-prick or venous sampling, and the lipid panel includes total cholesterol, LDL, HDL, and triglycerides. Elevated cholesterol may indicate genetic lipid disorders requiring dietary or pharmacologic intervention, while low cholesterol is rare but may suggest liver dysfunction or malabsorption. Infants with abnormal levels are referred to a pediatric lipid specialist, and family screening may be indicated in inherited cases.
Table 1: Summary of Common Newborn Screening Tests
| Test | Purpose | Sample Method | Normal Range / Outcome | Intervention if Abnormal |
|---|---|---|---|---|
| PKU | Detect metabolic disorder (phenylalanine) | Heel-prick blood | Phenylalanine <2 mg/dL | Low-phenylalanine diet |
| Glucose | Identify hypoglycemia | Heel-prick blood | 45–90 mg/dL (first 24 hours) | Feeding support, IV glucose if needed |
| WBC Count | Assess immune status, detect infection | Heel-prick / venous | 9,000–30,000/mm³ total WBC (neonate) | Infection workup, antibiotics if needed |
| Cholesterol | Detect lipid metabolism disorders | Heel-prick / venous | Total cholesterol 120–200 mg/dL | Specialist referral, dietary/pharmacologic management |
Performing these tests together provides a comprehensive assessment of metabolic, endocrine, immune, and lipid status. Benefits include early detection, prevention of complications, and guidance for family counseling, particularly in genetic or metabolic disorders. Parents should be educated on the purpose, procedure, and possible outcomes, and confirmatory testing is essential if initial results are abnormal. Advances in technology, such as tandem mass spectrometry, genomic screening, and point-of-care testing, are expanding the scope and efficiency of newborn screening programs. Comprehensive newborn screening, including PKU, glucose, WBC, and cholesterol, ensures that infants receive timely interventions and supports optimal growth, development, and long-term health outcomes.