Early Pregnancy Maternal Vitamin D Concentrations in Relation to Gestational Diabetes Mellitus, Mood or Anxiety Disorders, and Preeclampsia
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Background: Previous studies examining associations of maternal vitamin D (Vit-D) with gestational diabetes mellitus (GDM), mood or anxiety disorders (MAD), and preeclampsia (PE) risk reported inconsistent findings. Whether pre- or mid-pregnancy body mass index (pp-BMI or mp-BMI) or maternal cigarette smoking modify or mediate these associations is unknown. Methods: In a case-cohort study nested within a prospective cohort, we examined these associations. Analytic samples included: 135 GDM cases and a randomly selected sub-cohort of 517; 148 MAD cases diagnosed before or during pregnancy and a sub-cohort of 554 (and additional cross-sectional analyses using 46 MAD cases diagnosed during pregnancy only)); and 73 PE cases and 600 sub-cohort members. GDM was diagnosed according to the American Diabetes Association guidelines. MAD cases were identified based on physician-diagnosis and/or self-report using medical records. PE diagnosis was made based on the American College of Obstetricians and Gynecologists guidelines. Liquid chromatography-tandem mass spectroscopy was used to measure maternal serum Vit-D (total 25[OH]D and 25[OH]D3) in early pregnancy (16 weeks on average). Logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CI). Gestational Diabetes Mellitus Results: GDM cases had lower mean total 25[OH]D (27.3 vs. 29.3ng/ml) and 25[OH]D3 (23.9 vs. 26.7ng/ml) concentrations compared with women who did not develop GDM (both p-values<0.05). Overall, 25[OH]D3, but not total 25[OH]D, was significantly associated with GDM risk. A 5ng/ml increase in 25[OH]D3 was associated with a 14% decrease in GDM risk (p-value=0.02). Women in the lowest quartile for 25[OH]D3 had a 2-fold (95%CI 1.15-3.58) higher risk of GDM compared with women in the highest quartile (p-value for trend<0.05). We did not observe interactions between pp-BMI and Vit-D on GDM risk (interaction p-value>0.05). Mp-BMI accounted for 18% of the effect of 25[OH]D3 on GDM risk. Conclusion: Early pregnancy Vit-D, particularly 25[OH]D3, is inversely associated with GDM risk. These associations are mediated, at least in part, by mp-BMI. Larger prospective studies are needed to further elucidate these relationships. Mood or Anxiety Disorders Results: Mean serum total 25[OH]D and 25[OH]D3 concentrations were higher among women with MAD compared with women without MAD (31.4 vs.29.2 ng/ml for total 25[OH]D, and, 29.2 vs.26.4 ng/ml for 25[OH]D3, respectively) (both P-values<0.05). Increases of 5 ng/ml in 25[OH]D or 25[OH]D3 were associated with 1.14 and 1.16-fold higher in risk of MAD, respectively (both P-values<0.05). Similarly, linear decreases in risk of MAD were observed across decreasing quartiles of total 25[OH]D (trend P-value=0.044) and 25[OH]D3 (trend P-value=0.067). We observed significant interactions of vitamin D with maternal ppOS or maternal smoking history on risk of MAD (interaction P-values<0.05). Decreased risk in MAD related to vitamin D insufficiency/deficiency was observed only among participants who were over-weight/obese or were current/former smokers. Results of analyses on data that excluded cases that were diagnosed at or before blood draw were similar to results reported above, although associations did not reach statistical significance. Conclusion: Contrary to previous reports and expectations, serum total 25[OH]D and 25[OH]D3 concentrations were directly associated with diagnosed MAD. We also observed potential interactions between maternal pre-pregnancy obesity/overweight status or smoking status and maternal vitamin D on MAD. Future prospective studies that employ standardized and validated measures of mood or anxiety symptoms are needed. Preeclampsia Results: Early pregnancy mean serum total 25[OH]D and 25[OH]D3 concentrations were lower among women who subsequently developed PE (28.6 and 25.7 ng/ml, respectively) compared with women who did not (29.2 and 26.6 ng/ml, respectively), although the differences were not statistically significant (both p-values>0.05). Risk estimates indicated consistently higher risk of PE (10-40% higher) among women with vitamin D deficiency or women in the lowest quartile for vitamin D concentrations compared with women who were vitamin D sufficient or were in the upper three quartiles for vitamin D concentrations, respectively. However, none of the risk estimates were statistically significant. Associations between vitamin D and PE risk did not vary depending upon women's pre-pregnancy overweight/obesity status (interaction p-value>0.05). Conclusions: In the current study, we did not observe significant associations between early pregnancy vitamin D and risk of PE. Given the inconsistency of findings to date and strong mechanistic evidence for this association, future larger prospective studies are warranted.
- Epidemiology