Vitamins A, D, E status as related to supplementation and lung disease markers in young children with cystic fibrosis

Abstract

Background: The variable response to fat-soluble vitamin supplementation in young children with cystic fibrosis (CF), and factors contributing to this variability, remain under-investigated.

Objective: To determine if recommended supplement doses normalize serum vitamins A (retinol), D (25-hydroxy-vitamin D, 25OHD), and E (α-tocopherol), and identify factors predictive of achieving sufficiency, in children with CF in the first 3 years of life.

Design: We studied 144 infants born during 2012-2017 and diagnosed with CF through newborn screening. Serum retinol, 25OHD, α-tocopherol and plasma cytokines interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α were measured in early infancy and yearly thereafter. Vitamin supplement intakes and respiratory microbiology were assessed every 1-2 months in infancy and quarterly thereafter.

Results: The prevalence of vitamin D insufficiency (<30 ng/ml) at all ages combined was significantly higher (22%) compared to vitamin A (<200 ng/ml, 3%) and vitamin E (<5 µg/ml, 5%). All children were vitamin A sufficient by age 2 years. Vitamin E insufficiency was rare. Only 42% were early responders of vitamin D and 17% remain insufficient despite high supplement intakes. IL-6 was positively correlated, while IL-8, IL-10, and TNF-α were negatively correlated, with retinol and 25OHD. Multiple regression analysis revealed that supplement dose, season, α-tocopherol, pancreatic insufficiency, respiratory infections and IL-10 were significant predictors of 25OHD.

Conclusion: Diagnosis through newborn screening coupled with supplementation normalized serum retinol and α-tocopherol in almost all infants with CF by age 3 years. However, response to vitamin D supplements in young children with CF occurred later and variably despite early and sustained supplementation.

Keywords: 25-hydroxyvitamin D; children; cystic fibrosis; fat-soluble vitamins; infection; inflammation; vitamin A; vitamin D; vitamin D supplementation; vitamin E.

FIGURE 1.

Boxplots of serum concentrations and supplement intakes of vitamins A, D and E at ages 4 mo, 1 y, 2 y and 3 y of age. The percentage under each bar indicates the prevalence of vitamin insufficiency (retinol <200 ng/mL; 25OHD <30 ng/mL; α-tocopherol <5 μg/mL) or supplement intake meeting the lower limit recommended in the CFF guidelines (vitamin A: ≥1500 IU for age ≤ 1 y and ≥5000 IU for age ≥2 y; vitamin D: ≥400 IU for age ≤ 1 y and ≥800 IU for age ≥2 y; vitamin E: ≥40 IU for age ≤ 1 y and ≥80 IU for age ≥2 y). P values indicate differences across age groups.

FIGURE 2.

Distribution of vitamins A, D and E responder groups in the first 3 y of life by pancreatic phenotype, meconium ileus (MI), pancreatic insufficiency (PI) and pancreatic sufficiency (PS). R4m, R1y, R2y and R3y denote responders who achieved vitamin sufficiency (retinol ≥200 ng/mL; 25OHD ≥30 ng/mL; α-tocopherol ≥5 μg/mL) at age 4 mo, 1 y, 2 y and 3 y, respectively. TR&NR denotes transient responders and non-responders who temporarily or never achieved sufficiency in the first 3 y of life.

FIGURE 3.

Top panel shows the prevalence of vitamin A insufficiency (serum retinol <200 ng/mL) by respiratory cultures classified into 5 categories: normal flora, positive for Staphylococcus aureus (SA), positive for Pseudomonas aeruginosa (PA), positive for both SA and PA, and positive for organisms other than SA and PA (non-SAPA). Bottom 4 panels show the correlations between serum retinol and 4 plasma cytokines with corresponding Pearson’s correlation coefficients (r) and p values. The percentages of samples with not-detectable (ND) values are shown on the left of the x-axis. Elevated cytokine levels (pg/mL) are defined as IL-6 >2.5, IL-8 >9.4, IL-10 >5.3 and TNF- α >14.5 and shown by the vertical dashed lines.

FIGURE 4.

Top panel shows the prevalence of vitamin D insufficiency (serum 25OHD <30 ng/mL) by respiratory cultures classified into 5 categories: normal flora, positive for Staphylococcus aureus (SA), positive for Pseudomonas aeruginosa (PA), positive for both SA and PA, and positive for organisms other than SA and PA (non-SAPA). Bottom 4 panels show the correlations between serum 25OHD and 4 plasma cytokines with corresponding Pearson’s correlation coefficients (r) and p values. The percentages of samples with not-detectable (ND) values are shown on the left of the x-axis. Elevated cytokine levels (pg/mL) are defined as IL-6 >2.5, IL-8 >9.4, IL-10 >5.3 and TNF- α >14.5 and shown by the vertical dashed lines.