Preconception Partner-Specific Vitamin D Biomarkers and Risk of Preeclampsia Among Couples Undergoing Fertility Treatment: A Secondary Cohort Analysis of FAZST

Background/Objectives: Maternal vitamin D deficiency has been associated with preeclampsia, but evidence regarding preconception partner-specific vitamin D biomarkers is limited. We evaluated associations between preconception maternal and paternal vitamin D biomarkers and the odds of preeclampsia. Methods: This secondary prospective cohort analysis used data from the Folic Acid and Zinc Supplementation Trial (FAZST), a multicenter study conducted in the United States between 2013 and 2017. Of the 2370 enrolled couples who were seeking infertility treatment, 1054 couples achieved a documented pregnancy. Because preeclampsia can only be ascertained among pregnancies progressing beyond 20 weeks of gestation, the primary analytic population was restricted to 826 pregnancies that reached ≥20 weeks, including 98 with preeclampsia and 728 without preeclampsia. Preconception serum total 25-hydroxyvitamin D (25(OH)D), vitamin D-binding globulin (VDBG), albumin, free 25(OH)D, and bioavailable 25(OH)D were assessed in both partners. Multivariable logistic regression models estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: In categorical analyses, maternal total 25(OH)D findings were consistent with a possible U-shaped pattern. Compared with concentrations of 30–< 50 ng/mL, concentrations ≤20 ng/mL were associated with higher odds of preeclampsia (aOR = 2.58, 95% CI: 1.13–5.88), as were concentrations ≥50 ng/mL (aOR = 5.45, 95% CI: 1.71–17.41). Similar categorical patterns were observed for maternal free 25(OH)D, with higher odds at concentrations ≤8.25 pg/mL (aOR = 2.23, 95% CI: 1.13–4.43) and ≥12.5 pg/mL (aOR = 4.71, 95% CI: 1.97–11.29), and for maternal bioavailable 25(OH)D concentrations ≤3.5 ng/mL (aOR = 2.61, 95% CI: 1.19–5.72) and ≥5.0 ng/mL (aOR = 5.38, 95% CI: 2.15–13.46). Lower paternal bioavailable 25(OH)D was associated with lower odds of preeclampsia in the fully adjusted model (aOR = 0.50, 95% CI: 0.28–0.89); however, this finding should be considered exploratory. Conclusions: Among pregnancies progressing to ≥20 weeks, lower and higher categories of maternal total, free, and bioavailable 25(OH)D were associated with the odds of preeclampsia relative to intermediate categories. These categorical findings are consistent with a possible U-shaped pattern but do not establish a nonlinear dose–response relationship. Paternal findings were limited and should be considered exploratory.