Measurement of vitamin D status

We measured 25(OH)D levels, a combination of 25(OH)D ₂ and 25(OH)D ₃ , in previously frozen maternal blood samples that were obtained during a routine nonfasting clinical blood draw at 26-28 weeks gestation. We refrigerated blood samples, centrifuged the samples, and stored plasma aliquots at –80°C. We measured 25(OH)D levels for each specimen twice, first with an automated chemiluminescence immunoassay and then with a manual radioimmunoassay. For quality control, the laboratory used US National Institute of Standards and Technology level 1. Because the singlicate 25(OH)D results from the 2 assays were not identical (r = 0.81), we averaged the 2 values for each specimen to obtain a more stable estimate of 25(OH)D level. In general, analyses that use either the chemiluminescence immunoassay data only or radioimmunoassay data only yielded similar results.

Ascertainment of GDM

We obtained data on GDM from the clinical record. Women underwent routine screening for GDM at 26-28 weeks’ gestation with a nonfasting oral glucose challenge test. If, 1 hour after a nonfasting 50-g oral glucose load, the glucose level was ≥140 mg/dL, the participant was referred for a 100-g fasting glucose 3-hour tolerance tests. Normal results were a fasting blood glucose level of <95 mg/dL at baseline, <180 mg/dL at 1 hours, <155 mg/dL at 2 hours, and <140 mg/dL at 3 hours. We categorized participants with a normal glucose screening as having normal glucose tolerance and participants who did not have a normal result after the screening as having IGT ( Figure 1 ). We classified women with at least 2 abnormal results on the fasting glucose tolerance test as having GDM.

Project Viva

Categorization of glucose tolerance based on 50-g, 1-hour, nonfasting glucose challenge test and subsequent fasting 100-g, 3-hour glucose tolerance test.

GDM , gestational diabetes mellitus; GTT , glucose tolerance test; IGT , impaired glucose tolerance.

Burris. Vitamin D and GDM. Am J Obstet Gynecol 2012.

Assessment of covariates

Through the interviews, study questionnaires, and medical record reviews, we collected information on self-designated maternal age, race/ethnicity, parity, smoking habits, education, marital status, and household income. We calculated gestational age in weeks at the time of the blood sample by subtracting the date of the last menstrual period from the date of the blood draw. Eighty-six percent of the participants had ultrasound data available at 16-20 weeks’ gestation. For approximately 12% of the ultrasound scans, gestational age estimates differed by >10 days from the last menstrual period pregnancy dating; for these, we used the dating that was obtained from the ultrasound scan. We calculated prepregnancy body mass index on the basis of self-reported prepregnancy height and weight. We calculated gestational weight gain at 20 weeks’ gestation by subtracting the self-reported prepregnancy weight from the weight measured at 20 weeks’ gestation. We defined physical activity as hours spent walking or time spent performing light-to-moderate or vigorous activities in the 3 months before the 26- to 28-week blood draw. We obtained dietary intake data (fish and micronutrient intake that included calcium and vitamin D) with a previously validated, semiquantitative food frequency questionnaire that was administered in the first and second trimesters of pregnancy. We adjusted micronutrient intake for energy intake using a residuals model.

Statistical analysis

We first performed bivariate analyses to determine maternal and infant characteristics that were associated with previously described clinical categories of vitamin D status : severe deficiency (<25 nmol/L), deficiency (25 to <50 nmol/L), insufficiency (50 to <75 nmol/L), and sufficiency (≥75 nmol/L). We further dichotomized 25(OH)D levels at 25 nmol/L because preliminary analyses of the odds of GDM demonstrated a threshold; compared with women with 25(OH)D levels <25 nmol/L, women with levels of 25 to <50, 50 to <75 and ≥75 had unadjusted odds ratios (ORs) for GDM of 0.25, 0.32, and 0.20, respectively. We used multivariable-adjusted multinomial logistic regression models to examine associations between severe vitamin D deficiency and the odds of the development of GDM or IGT compared with women with normal glucose tolerance. We excluded covariates that did not confound the relationship between 25(OH)D level and the odds of GDM.

To analyze the relationship between vitamin D status and blood glucose measurement after the 1-hour glucose challenge screening test, we conducted analyses that predicted glucose as a continuous variable using multivariate linear regression models. In these models, we used 25(OH)D status as a continuous independent variable and adjusted for the same covariates as the GDM analyses.

As is common in large epidemiologic studies, many covariates were missing on some subjects. We used chained equations to multiply impute values for these covariates. We generated 10 imputed datasets; all model results are generated by appropriately combining these results. To avoid incorrect imputations, all 2128 Project Viva subjects were used in the imputation process ; however, only those with observed 25(OH)D were included in the analysis. All analyses were performed in SAS software (version 9.3; SAS Institute Inc, Cary, NC).

Second-trimester 25(OH)D levels

The mean (SE) 25(OH)D level was 59 ± 0.6 nmol/L. The levels were lower among women with higher body mass index, lower pregnancy weight gain, lower vitamin D intake, and lower calcium intake ( Table 1 ). Women with lower levels were more likely to have less than a college education, to be single, to be from households with <$70,000 annual income, and to be nonwhite. Counter to our expectations, physical activity appeared to be associated inversely with 25(OH)D level; women in the lowest category (<25 nmol/) reported 9.3 hours/week of physical activity vs 7.2 hours/week among women with 25(OH)D levels of ≥75 nmol/L. Younger women in our cohort reported more physical activity (Pearson correlation coefficient, –0.15; P < .001) and had lower 25(OH)D levels than older women (Pearson correlation coefficient, 0.15; P < .001). We do not have data on whether physical activity was indoor or outdoor.

GDM and IGT

Sixty-eight women(5.2%) met criteria for GDM. Unadjusted analysis revealed that women with 25(OH)D levels of <25 vs >25 nmol/L had significantly increased odds of GDM (OR, 3.6; 95% confidence interval [CI], 1.7–7.8; Table 2 ). Adjustment for race/ethnicity, age, education, marital status, smoking, parity, and season of blood draw made little difference to this estimate (OR, 3.1; 95% CI, 1.3–7.4). Additional adjustment for maternal body mass index attenuated the association; the confidence interval included the null value (OR, 2.2; 95% CI, 0.9–5.6). Further adjustment for pregnancy weight gain made little difference (OR, 2.3; 95% CI, 0.9–5.7). Addition of physical activity and dietary intakes of fish and calcium also made little difference (OR, 2.2; 95% CI, 0.8–5.5).

TABLE 2

Odds of gestational diabetes mellitus in subjects with severe vitamin D deficiency ^{a , b}

25-hydroxyvitamin D exposure	Odds ratio (95% CI)
	Model 1 c	Model 2 d	Model 3 e	Model 4 f
Gestational diabetes mellitus vs normal glucose tolerance	3.6 (1.7, 7.8)	3.1 (1.3, 7.4)	2.3 (0.9, 5.7)	2.2 (0.8, 5.5)
Impaired glucose tolerance vs normal glucose tolerance	1.4 (0.7, 3.0)	1.6 (0.7, 3.5)	1.4 (0.6, 3.2)	1.4 (0.6, 3.3)

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Strenuous exercise during pregnancy: is there a limit?
2. Laparoscopic versus open radical hysterectomy for elderly patients with early-stage cervical cancer
3. Preoperative intravascular balloon catheters and surgical outcomes in pregnancies complicated by placenta accreta: a management paradox
4. Successful conservative management of a large iatrogenic vesicovaginal fistula after loop electrosurgical excision procedure

Stay updated, free articles. Join our Telegram channel

Join