Vitamin D levels and perinatal anxiety in an anxiety-focused behavioral intervention program in Pakistan

Purpose: This study investigates Vitamin D levels across the perinatal period and relationships with perinatal anxiety and immune markers in women in Pakistan. Methods: We analyzed plasma levels of 25-hydroxyvitamin D and cytokines and chemokines from 117 participants from the “Happy Mother-Healthy Baby” trial, which evaluated a non-specialist delivered cognitive behavioral therapy intervention for perinatal anxiety. Blood samples were collected at four timepoints: T1 (10–22 weeks), T2 (22–26 weeks), T3 (34–38 weeks), and T4 (six weeks postpartum). Participants were categorized into anxiety groups using K-means clustering. Mixed-effect models were used to examine Vitamin D trajectories, and moderation analysis explored the impact of immune markers on the Vitamin D-anxiety relationship. Results: Vitamin D levels were severely deficient across all timepoints (< 5 ng/ml) and declined significantly from T1 to T2 (β = -0.549, p =.006) before rebounding postpartum (β = 1.492, p <.0001). Despite this widespread Vitamin D deficiency, no significant differences in Vitamin D trajectories were observed across anxiety groups. Higher innate immune activity correlated with higher Vitamin D levels at T1. IL-6 and CXCL-8 levels moderated the Vitamin D and anxiety relationship at T2 (IL-6: β = 2.98, p =.015; CXCL-8: β = 0.72, p =.030); among those with higher levels of IL-6 and CXCL-8, higher Vitamin D levels were associated with higher levels of anxiety. Conclusions: These findings indicate the need for further research on maternal Vitamin D deficiency and its relationship with immune function in low- and middle-income countries.