Prospective, long-term study of fat-soluble vitamin status in children with cystic fibrosis identified by newborn screen.

OBJECTIVE: To prospectively evaluate the biochemical status of vitamins A, D, and E in children with cystic fibrosis (CF). SUBJECTS: A total of 127 infants identified by the Colorado CF newborn screening program. DESIGN: Vitamin status (serum retinol, 25-hydroxy vitamin D, ratio of alpha-tocopherol/total lipids) and serum albumin were assessed at diagnosis (4 to 8 weeks), ages 6 months, 12 months, and yearly thereafter, to age 10 years. RESULTS: Deficiency of 1 or more vitamins was present in 44 (45.8%) of 96 patients at age 4 to 8 weeks as follows: vitamin A 29.0%, vitamin D 22.5%, and vitamin E 22.8%. Of these patients with initial deficiency, the percent that was deficient at 1 or more subsequent time points, despite supplementation, was vitamin A 11.1%, vitamin D 12.5%, and vitamin E 57.1%. Of the initial patients with vitamin sufficiency, the percent who became deficient at any time during the 10-year period was as follows: vitamin A 4.5%, vitamin D 14.4%, and vitamin E 11.8%. The percent of patients deficient for 1 or more vitamins ranged from 4% to 45% for any given year. CONCLUSIONS: Despite supplementation with standard multivitamins and pancreatic enzymes, the sporadic occurrence of fat-soluble vitamin deficiency and persistent deficiency is relatively common. Frequent and serial monitoring of the serum concentrations of these vitamins is therefore essential in children with CF.

Clinical evaluation of the macroduct sweat collection system and conductivity analyzer in the diagnosis of cystic fibrosis.

The purposes of this study were to compare sweat tests used in diagnosing cystic fibrosis (CF), as performed with the Macroduct collection system, with those utilizing the more laborious quantitative pilocarpine iontophoresis test (QPIT), and to ascertain the efficacy of the Sweat-Chek conductivity analyzer in eliminating some possibly unnecessary chloride analyses. A Macroduct sweat test was performed on one arm and a QPIT on the other on 1090 patients, 93 of whom had CF. Of these, 514 patients (43 with CF) also had a conductivity determination on the Macroduct sweat sample. All subjects were referred to the laboratory of one of us (K.B.H.) for sweat testing. Of the QPIT samples, 0.7% were inadequate, as were 6.1% of those from the Macroduct system. When sodium and chloride concentrations from the two tests were compared, the standard errors of the estimate were 3.90 and 3.85, respectively. Agreement within 8 mEq/L could then be expected with 95% confidence limits. With use of the Sweat-Chek analyzer, no patient with CF was found to have a conductivity of less than 90 mmol/L, whereas 430 (91%) of the non-CF subjects had a conductivity of less than 50 mmol/L. None of those 430 subjects had a sweat chloride value > 32 mmol/L. We conclude that the Macroduct collection system provides results equally as satisfactory as those provided by the QPIT and that the Sweat-Chek analyzer frequently eliminates the necessity of measuring chloride concentrations.

Pancreatic insufficiency, growth, and nutrition in infants identified by newborn screening as having cystic fibrosis.

To evaluate the impact of early pancreatic insufficiency on growth and nutritional status in cystic fibrosis, we studied 49 infants identified by a newborn screening program. Pancreatic insufficiency, determined by increased 72-hour fecal fat excretion, was present in 59% (23/39) of infants at diagnosis (7.0 +/- 0.8 weeks; mean +/- SEM). Before initiation of pancreatic enzyme replacement, growth and nutritional status of pancreatic-insufficient (n = 16) and pancreatic-sufficient (n = 13) infants were compared. Pancreatic-insufficient infants gained less weight from birth to diagnosis (13.4 +/- 3.4 vs 22.3 +/- 4.0 gm/day; p = 0.05), had decreased triceps skin-fold thicknesses (4.5 +/- 0.3 vs 6.1 +/- 0.4 mm; p less than 0.005), and had lower blood urea nitrogen (3.07 +/- 0.42 vs 4.62 +/- 0.65 mg/dl; p = 0.02) and albumin (2.99 +/- 0.14 vs 3.54 +/- 0.14 gm/dl; p less than 0.01) levels despite higher gross calorie (154 +/- 8 vs 116 +/- 13 kcal/kg per day; p less than 0.01) and protein intakes (2.81 +/- 0.21 vs 2.14 +/- 0.33 gm/kg per day; p = 0.03). Fecal nitrogen loss was correlated with fat loss (r = 0.79; p less than 0.001). Fat malabsorption was present in 79% (30/38) and 92% (33/36) of infants tested at 6 months and 12 months of age, respectively, indicating that pancreatic insufficiency persists and increases in frequency throughout infancy. We conclude that pancreatic insufficiency is prevalent in young infants with cystic fibrosis and has a significant impact on growth and nutrition.

Early bacteriologic, immunologic, and clinical courses of young infants with cystic fibrosis identified by neonatal screening.

To understand better the events associated with the initiation of lung disease in young children with cystic fibrosis (CF), we prospectively performed a longitudinal study examining the early bacteriologic, immunologic, and clinical courses of 42 children with CF diagnosed after identification by neonatal screening. Serial evaluations included history and physical examination, chest radiographs, throat cultures for bacteria, and determinations of serum immunoglobulin levels and circulating immune complexes. At a mean follow-up age of 27 months, 19% of the children had serial throat cultures positive for Pseudomonas aeruginosa; the first positive culture was found at a mean age of 21 months. In three infants the initial P. aeruginosa isolates were mucoid. As determined by typing with a DNA probe, serial P. aeruginosa isolates from each patient were identical over time but were genetically distinct from isolates recovered from other patients. Of 11 infants with P. aeruginosa, nine (82%) had previous isolates of Staphylococcus aureus or Haemophilus influenzae; all had received prior antibiotic therapy. In comparison with other infants with CF, children with P. aeruginosa grown on serial throat cultures more frequently had daily cough (p less than 0.01), lower chest radiograph scores (p less than 0.05), and elevated levels of circulating immune complexes (p less than 0.01). None of the study infants had persistent hypogammaglobulinemia or hypergammaglobulinemia. We conclude that (1) S. aureus and H. influenzae remain the isolates most frequently recovered from infants with CF; (2) initial recovery of P. aeruginosa by throat culture is often preceded by the onset of chronic respiratory signs; (3) elevations of circulating immune complexes can occur early, often after the initial recovery of P. aeruginosa; and (4) early P. aeruginosa isolates are genetically distinct, demonstrating the lack of cross-colonization in this newborn population.