In this cohort of supplemented women, maternal prepregnancy obesity was associated with lower serum 25(OH)D concentrations and higher odds of vitamin D deficiency among mothers in mid-gestation and neonates at birth. Importantly, we found monotonic dose-dependent relations between prepregnancy BMI and maternal and newborn vitamin D status. The associations remained after controlling for race, supplement use, and other measured confounders. The relation was not as strong in mothers at term as it was at 4–22 wk, which may have been due to a longer period (37–42 wk) between BMI estimation and 25(OH)D measurement and/or the lower prevalence of vitamin D deficiency at term. Vitamin D deficiency was probably less common at term because more women were using multivitamins in the last 3 mo of pregnancy than in the periconceptional period.
We are unaware of any other published study to examine the effect of prepregnancy obesity on the vitamin D status of mothers or newborns. Our results are consistent with the numerous studies revealing low 25(OH)D concentrations in obese nonpregnant adults and children (13
), including several that reported a monotonic decline in 25(OH)D levels as BMI or body fat mass increased (13
). For instance, Parikh and colleagues (14
) reported a 24% decrease in 25(OH)D concentrations in obese adults (58.8 nmol/L) vs. nonobese adults (77.5 nmol/L) and a strong, negative correlation between 25(OH)D and BMI (r
= −0.4; P
< 0.0001) in a predominantly female cohort. In most other studies, correlations were more modest, ranging from −0.14 to −0.27 (15
), as we observed. Prior investigations were all cross-sectional (i.e. obesity and 25(OH)D were measured simultaneously). In contrast, our report of prepregnancy BMI in relation to gestational and cord 25(OH)D levels suggests that adiposity around conception may predict pregnancy and neonatal vitamin D status.
There is some evidence that the relation between obesity and 25(OH)D may vary by race/ethnicity. Recently, Looker (17
) showed that the negative association between fat mass and 25(OH)D was significantly stronger in white women than in black women. Smaller studies have reported either no association between 25(OH)D and obesity in blacks (16
) or a similar strong association in whites as in blacks (14
). In our study, the relation was similar in blacks and whites. However, our sample size may have limited our power to detect an interaction.
Previously, investigators demonstrated correlations between 25(OH)D and total body fat percentage by whole body dual energy X-ray absorptiometry that were as strong as or stronger than correlations between 25(OH)D and anthropometric measures such as BMI (13
). These findings highlight that it may be adiposity—not just body mass—that is related to vitamin D status. Indeed, the mechanism explaining the variability in 25(OH)D by obesity status is likely related to the ability of subcutaneous fat to sequester cutaneous synthesized D3, the precursor to 25(OH)D. In an elegant study, Wortsman et al. (12
) showed no difference between nonobese and obese individuals in the capacity of the skin to synthesize D3 but a striking 57% reduction in the increase of serum D3 after sun exposure in the obese subjects. Moreover, after providing obese subjects with a pharmacologic oral dose of D2, groups did not differ in peak serum D2 levels. These data suggest that the availability of excessive adipose tissue causes a decrease in endogenously synthesized D3
to be released into circulation. Their results also indicate that oral intake of D2 may be more bioavailable for obese individuals. Although some researchers thought that lower 25(OH)D concentrations may be due to a negative feedback at the hepatic level from elevated 1,25-dihydroxyvitamin D in the setting of obesity (19
), recent reports contradict this theory (14
). The lower 25(OH)D levels in obesity are thought to secondarily elevate intact parathyroid hormone concentrations (14
). High parathyroid hormone levels may enhance calcium uptake into adipocytes, thereby promoting lipogenesis and excess weight gain (38
). How this endocrine system is altered in pregnancy is not known.
Although a lowering of 25(OH)D concentrations with increasing BMI or fat mass is worrisome for all adults, it is particularly concerning for pregnant women and their fetuses. Not only is poor in-utero and early-life vitamin D status related to long-term negative health effects for the offspring (6
), but maternal vitamin D deficiency may also increase the risk of adverse pregnancy outcomes (8
). Importantly, vitamin D insufficiency is an independent risk factor for preeclampsia (8
), an outcome that is also more common in obese than normal weight women (40
). Our findings suggest that reduced 25(OH)D levels in pregravid obese women may partially mediate the obesity-preeclampsia association. Future studies are needed to explore this intriguing possibility.
We used prepregnancy BMI as a surrogate for prepregnancy fat mass because direct measures were not available. Our reliance on BMI may have led to an underestimation of the association between maternal obesity and 25(OH)D concentrations. We were also limited by our assay’s ability to detect 100% of 25(OH)D3 but only 75% of 25(OH)D2, which would underestimate concentrations of total 25(OH)D in women whose primary source of vitamin D was D2. If obese women were more likely to derive vitamin D from D2, this may have biased our results upwards and away from the null. We did not have detailed data on vitamin D intake to determine whether sources differed by obesity status. Additionally, we used self-reported physical activity and television watching as covariates in our regression models to represent surrogates of sun exposure. A direct measure of sun exposure would have allowed us to definitively rule out that lowered 25(OH)D levels were caused by a greater avoidance of sun by obese individuals, as some have proposed (19
). We did not have the resources to measure biomarkers of the vitamin D endocrine system or vitamin D-binding protein concentrations. We also lacked data on parathyroid hormone concentration or other functional indicators of vitamin D status in mothers and neonates.
Our results suggest that pregravid obese women and their newborns are at high risk of vitamin D deficiency, even when mothers regularly use prenatal vitamins. These data illustrate that prepregnancy obesity has a direct impact on the nutritional status of the neonate. Future research should investigate whether obese pregnant women may benefit from serum 25(OH)D screening and high-dose vitamin D supplementation during gestation to improve their own vitamin D stores and that of their infants. The dramatic rise in the prevalence of maternal prepregnancy obesity in the United States (41
) highlights that maternal and newborn vitamin D deficiency will continue to be a serious public health problem until steps are taken to identify and treat low 25(OH)D concentrations in clinical and public health settings.