This retrospective study included a total of 25 children (12 boys and 13 girls) with epilepsy, at a mean age of 15.28 months (SD, 5.89 months). The average duration of VPA therapy was (7.92±2.86) months. Among the study participants, 10 patients had brain lesions on MRI, and 15 patients had normal brain MRI findings. Ten children were receiving monotherapy, and 15 children were receiving polytherapy. The demographic profiles of the boys and girls are presented in Table 1.
Variable Girl (n=13) Boy (n=12) P Age (months) 13.5 (6–27)* 17.2 (7–29)* 0.318 Brain MRI >0.999 Normal 8 7 Abnormal 5 5 AEDs >0.999 Monotherapy 5 5 Polytherapy 8 7 Seizure outcomes 0.688 Seizure free 7 8 No seizure free 6 4 VPA dose (mg/kg) 25.4±6.4# 29.8±8.4# 0.012 Duration of VPA therapy (months) 8.23±3.35# 7.58±2.31# 0.810 *These data are expressed as mean (range); #These data are expressed as mean±SD. MRI: magnetic resonance imaging; AEDs: antiepileptic drugs; VPA: valproic acid.
Table 1. Demographic profile of the patients
Table 2 shows the biochemical characteristics associated with longitudinal change of vitamin D status in the patients. There were no statistically significant differences in calcium, phosphorus and alkaline phosphatase levels between different groups.
Girl (n=13) Boy (n=12) Initial Middle Final P Initial Middle Final P Calcium (mmol/L) 2.45±0.08 2.44±0.08 2.45±0.07 0.957 2.44±0.09 2.43±0.07 2.37±0.08 0.147 Phosphorus (mmol/L) 1.76±0.23 1.82±0.11 1.78±0.12 0.670 1.70±0.27 1.84±0.23 1.80±0.18 0.282 ALP (U/L) 229.9±94.0 271.5±129.5 308.7±230.0 0.579 176.3±64.8 198.4±69.8 219.3±79.4 0.351 Serum VPA level (μg/mL) 75.9±31.7 69.0±25.0 73.2±21.4 0.797 52.7±18.7 63.0±10.8 70.0±19.8 0.053 All values in mean±SD. ALP: alkaline phosphatase; VPA: valproic acid.
Table 2. Biochemical characteristics associated with longitudinal change of vitamin D status
The 25(OH)D levels were (37.32±11.99) ng/mL and (35.56±11.61) ng/mL at the initial and middle measurements respectively. A decreasing trend was observed at the final measurement ([31.07±9.98] ng/mL) (Fig. 2A). The vitamin D deficiency or insufficiency status was 32%, 44%, and 48% at the initial, middle, and final measurements respectively (Fig. 2B).
Interestingly, the status of 25(OH)D levels showed a longitudinally significant decline in girls, but no significant changes in boys (Fig. 3A and B). The vitamin D deficiency or insufficiency status in these female patients was 23.1%, 53.8%, and 61.5% at the initial, middle, and final measurements respectively (Fig. 2B). The 25(OH)D status of two girls was decreased to deficiency (Fig. 3B, right).
Figure 3. The longitudinal change of the mean of 25(OH)D levels in boys and girls with epilepsy after taking VPA.
Potential risk factors that might reduce vitamin D levels from the onset of VPA treatment in girls were shown in Table 3. Polytherapy had a more negative impact on 25(OH)D levels than monotherapy. The remaining factors did not contribute significantly to the models (Table 3). In addition, there was a weak negative association between 25(OH)D levels and plasma trough concentration to dose ratio (C0/D) of VPA in the whole cohort (Fig. 4A, left). The correlation was stronger in girls, but no difference in boys (Fig. 4A, middle and right). The weak negative association was also found in 25(OH)D levels and duration of VPA therapy (Fig. 4B, left). The correlation was stronger in girls (Fig. 4B, middle) while no difference in boys as well (Fig. 4B, right).
Brain MRI Normal −2.31 −11.85 Abnormal −7.01 −13.24 P 0.482 0.787 AEDs Monotherapy 1.79 −2.95 Polytherapy −7.81 −18.88 P 0.133 0.003 Seizure outcomes Seizure free −3.03 −8.20 No seizure free −5.06 −15.97 P 0.757 0.196 Duration of VPA therapy (months) ≤6 −10.23 −17.72 >6 1.11 −7.81 P 0.062 0.091 *Δ25(OH)D1 was investigated as the value of middle measurement minus that of the initial measurement. #Δ25(OH)D2 was investigated as the value of final measurement minus that of the initial measurement. MRI: magnetic resonance imaging; AEDs: antiepileptic drugs; VPA: valproic acid. Bold font presents P<0.05
Table 3. Comparisons of the coupled variables in the longitudinal decrease 25(OH)D in girls
Valproic acid therapy decreases serum 25-hydroxyvitamin D level in female infants and toddlers with epilepsy— a pilot longitudinal study
- Received Date: 2020-04-23
- Accepted Date: 2020-09-24
- Rev Recd Date: 2020-09-22
- Available Online: 2020-11-20
- Publish Date: 2021-01-28
Abstract: To evaluate if valproic acid (VPA) therapy is associated with vitamin D deficiency among infants and toddlers with epilepsy, a cross-sectional clinical study was conducted in 25 children with epilepsy taking VPA. Blood levels of calcium, phosphorus, alkaline phosphatase, and 25-hydroxy vitamin D [25(OH)D] and plasma VPA level were measured at 1- to 3-month intervals. At the initial and final measurements, vitamin D deficiency or insufficiency was recognized in 8 (32%) and 12 (42%), respectively. In girls, a decreasing trend in serum 25(OH)D levels (P<0.05) was observed. Polytherapy had a significant negative effect on the longitudinal change of 25(OH)D (P<0.05) in girls. In conclusion, our study indicates that a high proportion of girls after VPA therapy had hypovitaminosis D.ΔThese authors contributed equally to this work.
|Citation:||Jinchun Qiu, Hongli Guo, Ling Li, Zeyue Xu, Zejun Xu, Xia Jing, Yahui Hu, Xiaoyi Wen, Feng Chen, Xiaopeng Lu. Valproic acid therapy decreases serum 25-hydroxyvitamin D level in female infants and toddlers with epilepsy— a pilot longitudinal study[J]. The Journal of Biomedical Research, 2021, 35(1): 61-67. doi: 10.7555/JBR.34.20200057|