Can Newborn Screening Miss Cystic Fibrosis?
Yes, a negative newborn metabolic screening does NOT rule out cystic fibrosis, and this 1-month-old infant with stridor, excessive sweating, and foul stools requires immediate sweat chloride testing regardless of the negative screening result. 1, 2, 3
Why Newborn Screening Can Be Falsely Negative
Newborn screening for CF has a sensitivity of only 93-98%, meaning 2-7% of infants with CF will have false-negative screening results 1. The screening uses immunoreactive trypsinogen (IRT) as the initial test, which can be falsely normal in some infants with CF 2. Additionally, screening algorithms may miss certain CFTR mutations, particularly in non-European ancestry populations whose mutations may not be included in standard mutation panels 1.
Providers must remain vigilant to detect CF among children with clinical symptoms even after negative screening 1. The American Academy of Pediatrics specifically urges healthcare providers not to rely solely on newborn screening results when clinical suspicion exists 1.
Clinical Presentation Strongly Suggests CF
This infant's symptoms are classic for cystic fibrosis:
- Foul-smelling stools (steatorrhea): This indicates pancreatic insufficiency with fat malabsorption, present in >80% of CF patients at diagnosis 1
- Excessive sweating: CF patients lose excessive salt in sweat, which is the basis for diagnostic sweat chloride testing 2, 4
- Stridor: While not the most common CF presentation, respiratory symptoms are frequent in CF, and acute viral infections commonly progress to lower respiratory tract infections in CF infants 1
The median age of clinical diagnosis based on symptoms (excluding meconium ileus) is 14.5 months, but symptoms often appear much earlier 1. Failure to thrive is particularly common in infants and young children with CF 1.
Immediate Diagnostic Steps Required
Sweat Chloride Testing (Priority)
Order bilateral sweat chloride testing immediately 2, 4. This infant meets criteria for testing:
Diagnostic interpretation 1, 2:
- ≥60 mmol/L = diagnostic for CF
- 30-59 mmol/L = intermediate/ambiguous - requires repeat testing and extended CFTR genetic analysis, as infants with CF often initially present with values in this range 1, 2
- Sweat testing should be performed bilaterally to increase likelihood of adequate collection 4
CFTR Genetic Testing
Order comprehensive CFTR genetic testing (blood or cheek swab) to identify disease-causing mutations 2. Identification of two CF-causing mutations confirms diagnosis regardless of sweat test results 2.
Additional Evaluation
- Stool pancreatic elastase: To document pancreatic insufficiency 3
- Respiratory cultures: For Pseudomonas aeruginosa and Staphylococcus aureus 4
- Nutritional assessment: Document growth parameters (weight, length, weight-for-age Z-score) 1
Critical Pitfall to Avoid
The most dangerous error is dismissing CF based on negative newborn screening 1, 3. A documented case from Minnesota showed a 1-month-old with failure to thrive, chronic diarrhea, and severe malnutrition who had negative NBS (IRT: 43 ng/mL) but positive sweat test (102 mmol/L) and homozygous F508del genotype 3. This represents exactly the scenario you're facing.
In states with universal CF screening, children with false-negative screens who are diagnosed clinically still receive diagnosis by age 12 months (median <4 months) when providers remain vigilant 1.
Immediate Management Pending Diagnosis
Refer urgently to a specialized CF center for comprehensive evaluation and management 1, 4. If CF is confirmed:
- Initiate pancreatic enzyme replacement and fat-soluble vitamin supplements immediately 1
- Begin high-fat diet (not low-fat) 1
- Establish aggressive monitoring for respiratory infections 1
Early diagnosis and treatment significantly reduce morbidity and mortality - diagnosis based on symptoms is associated with >2-fold greater risk of medical complications before diagnosis compared to early detection 1.