Vitamin D Status and Response to Calcifediol Supplementation in Term and Preterm Infants with Cholestasis

Infants with cholestasis are at risk of vitamin D status impairment; the role of prematurity remains unclear. The primary aim of this study was to characterize vitamin D status in term and preterm infants with cholestasis and to determine whether serum 25OHD concentrations were associated with gestational age, etiology of cholestasis, and biochemical markers of cholestatic activity. The secondary aim was to assess changes in serum 25OHD concentrations during calcifediol supplementation and to identify factors associated with follow-up 25OHD concentrations.

In this prospective observational study with a concurrent control group, infants with cholestasis and controls underwent assessment, including serum 25-hydroxyvitamin D (25OHD), at baseline and after calcifediol supplementation in cholestatic infants. Predictors of 25OHD were evaluated using multivariable models.

We included 127 infants: 70 with cholestasis (39 term, 31 preterm) and 57 controls (30 term, 27 preterm). Biliary atresia was diagnosed in 21 (30%) infants. Calcifediol was administered to 38 (54%) cholestatic infants: 18 (46%) term and 20 (64%) preterm at baseline. The remaining 32 infants with cholestasis were receiving vitamin D3 supplementation. Following enrollment and review of the baseline 25OHD results, calcifediol treatment was continued or initiated in 66 of the 70 infants. Treatment was discontinued in four infants based on their high serum 25OHD concentrations. Baseline 25OHD was similar in cholestasis and controls (34.81 ± 21.33 vs. 31.55 ± 10.14 ng/mL; p = 0.261). However, vitamin D deficiency (<20 ng/mL) was more frequent in cholestatic infants than controls (22.8% vs. 5%; p < 0.05), and 25OHD concentrations > 50 ng/mL were also more frequent (18.6% vs. 3.5%; p < 0.05). Among 13 infants with 25OHD concentrations > 50 ng/mL, 11 (84.6%) infants had received calcifediol; only three exceeded 100 ng/mL. Each 1 µg/kg increase in calcifediol dose was associated with 15.7% higher expected baseline 25OHD. At follow-up, preterm and term infants had comparable 25OHD (44.15 ± 20.36 vs. 45.73 ± 18.77 ng/mL; p = 0.737); nevertheless, <30 ng/mL persisted in 23%, while >50 ng/mL occurred in 40% of cholestatic infants. Baseline 25OHD concentration and cumulative calcifediol exposure were associated with follow-up 25OHD concentration.

Vitamin D status in cholestatic infants is highly variable. Cumulative exposure of calcifediol is associated with higher 25OHD concentrations, but heterogeneous responses require monitoring and individualized dose adjustment.