Efficacy of fat-soluble vitamin supplementation in infants with biliary atresia

Abstract

Objective: Cholestasis predisposes to fat-soluble vitamin (FSV) deficiencies. A liquid multiple FSV preparation made with tocopheryl polyethylene glycol-1000 succinate (TPGS) is frequently used in infants with biliary atresia (BA) because of ease of administration and presumed efficacy. In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation.

Methods: Infants received FSV/TPGS coadministered with additional vitamin K as routine clinical care in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after hepatoportoenterostomy (HPE) for BA (identifier NCT 00294684). Levels of FSV, retinol binding protein, total serum lipids, and total bilirubin (TB) were measured 1, 3, and 6 months after HPE.

Results: Ninety-two infants with BA were enrolled in this study. Biochemical evidence of FSV insufficiency was common at all time points for vitamin A (29%-36% of patients), vitamin D (21%-37%), vitamin K (10%-22%), and vitamin E (16%-18%). Vitamin levels were inversely correlated with serum TB levels. Biochemical FSV insufficiency was much more common (15%-100% for the different vitamins) in infants whose TB was ≥2 mg/dL. At 3 and 6 months post HPE, only 3 of 24 and 0 of 23 infants, respectively, with TB >2 mg/dL were sufficient in all FSV.

Conclusions: Biochemical FSV insufficiency is commonly observed in infants with BA and persistent cholestasis despite administration of a TPGS containing liquid multiple FSV preparation. Individual vitamin supplementation and careful monitoring are warranted in infants with BA, especially those with TB >2 mg/dL.

Trial registration: ClinicalTrials.gov NCT00294684.

FIGURE 1

Scatterplot of serum vitamin levels 6 months after HPE. Individual values measured from each subject are shown. The rectangle represents the target range for a specific measurement. The horizontal line represents the mean for each measurement. An additional thick horizontal line indicates the revised level for vitamin D of 20 ng/mL. Levels for vitamins A, D, and E are indicated on the left vertical axis in μg/dL, ng/mL, and μg/mL, respectively. Ratios for A/RBP (molar) and E/lipid (mg/g) are indicated on the right vertical axis.

FIGURE 2

Scatterplot of serum 25-hydroxyvitamin D levels plotted against TB. All measured 25-hydroxyvitamin D levels from all time points after HPE are plotted relative to total serum bilirubin. Spline correlation is depicted by the solid line. The darker shaded box reflects measurements that would be categorized as insufficient with a cutoff of 15 ng/mL, whereas the lighter shaded box reflects the revised cutoff of 20 ng/mL.

FIGURE 3

Prevalence of fat-soluble vitamin sufficiency relative to TB level ≥ or <2 mg/dL. The presence (unfilled bar) or absence (shaded bar) of any FSV insufficiency (A, D, E, or K as defined in Table 1) at a given time point post HPE is depicted in the bar graph. The prevalence is reported for those infants with a TB <2 mg/dL relative to those with a TB ≥2 mg/dL. The y axis represents absolute numbers of subjects reported.