vitamin d ( 25-hydroxyvitamin d ( 25(oh)d ) ) is commonly known for its role in calcium metabolism and bone health , but more recently has gained attention for the significant role it plays in pregnancy and perinatal outcomes . thus , levels of neonates at birth depend entirely on that of the mother and , accordingly , several studies have consistently correlated cord blood 25(oh)d levels to those of their mothers . in addition , maternal vitamin d deficiency has been linked to decreased fetal growth and birth size in observational studies . maternal vitamin d deficiency is prevalent , the extent of which can be influenced by many variables including skin pigmentation , sun exposure , season , age , vitamin supplementation and obesity . several large observational studies and meta - analyses have described the association of maternal vitamin d deficiency with pregnancy complications such as pre - eclampsia , gestational diabetes and premature birth . racial disparities are also seen with pregnancy complications such as preterm birth , pre - eclampsia and gestational diabetes , as well as adverse neonatal outcomes including low birth weight and small - for - gestational - age ( sga ) status . however , the majority of studies examined maternal vitamin d levels during the first and second trimesters of pregnancy and correlated these levels to neonatal outcomes . far fewer studies have examined the relationship between cord blood vitamin d levels , which may more accurately reflect fetal levels of vitamin d , and neonatal outcomes . given the racial disparities seen in both vitamin d deficiency and perinatal outcomes , vitamin d has been proposed as part of the explanation for this disparity , particularly with regard to fetal growth and sga . increased awareness of the growing prevalence of maternal vitamin d deficiency has led to an urgent need for consideration of supplementation during pregnancy . although studies have shown that supplementation increases maternal and cord blood vitamin d levels , changes in clinical outcomes have not yet been well proven . thus , sufficient evidence is lacking at this time to recommend routine vitamin d supplementation during pregnancy . however , identification of specific risk factors for vitamin d deficiency and the additive effects of these risk factors may lead to opportunities for targeted supplementation with improved outcomes . thus , the primary purpose of this study was to examine the relationship between race , maternal characteristics , cord blood vitamin d levels and sga status among infants during one winter season in a midwestern us population . in particular , we wanted to evaluate the additive effects of race and maternal characteristics such as obesity on vitamin d deficiency and sga . our goal was to identify specific high - risk subsets of pregnant women who may benefit from vitamin d supplementation in order to mitigate adverse perinatal outcomes such as sga . this retrospective study was conducted at university of cincinnati medical center in cincinnati , oh , usa . this study was approved by the university of cincinnati and cincinnati children 's hospital medical center institutional review boards . previously collected cord blood samples from all singleton births from november 2010 to april 2011 ( one winter season ) served as the study population . maternal medical records were reviewed for the following information : race , prepregnancy body mass index ( bmi ) and bmi at delivery , insurance status , prenatal vitamin use and maternal complications including smoking , hypertension , diabetes , chorioamnionitis , preterm labor and premature rupture of membranes . neonatal medical records were reviewed for the following information : gestational age , gender , birth weight , birth length , birth head circumference and sga status . sga was defined as weight < 10% for gestational age according to the fenton growth chart and the who growth chart ( for infants of 37 weeks ) . cord blood 25(oh)d levels were analyzed using the liaison 25 oh vitamin d assay ( diasorin inc . , for categorical analysis of vitamin d levels , we used cutoff values of : sufficient ( 50  nmol  l ) and deficient ( < 50  nmol  l ) . distributions of continuous variables were evaluated for normality graphically using histogram and box plots and are described using means and s.d . or medians with interquartile ranges , if nonnormally distributed . to explore relationships between race , vitamin d levels and sga , we first evaluated race as a predictor of vitamin d levels ( sufficient or deficient ) in cord blood and assessed for potential confounders : medicaid status , bmi at delivery , hypertension , maternal age and prenatal vitamin use . these results informed the next stage of analyses that examined race and vitamin d levels with the outcome of sga by assessing potential confounders : race , smoking , pre - eclampsia , maternal age , medicaid status and bmi at delivery . the  tests or fisher 's exact tests were used to examine relationships between categorical variables . independent t - tests were used to examine the relationship between continuous variables and each outcome . potential predictors associated with each outcome at p<0.2 in bivariate analyses were entered into multiple regression models and evaluated using backward elimination . this retrospective study was conducted at university of cincinnati medical center in cincinnati , oh , usa . this study was approved by the university of cincinnati and cincinnati children 's hospital medical center institutional review boards . previously collected cord blood samples from all singleton births from november 2010 to april 2011 ( one winter season ) served as the study population . maternal medical records were reviewed for the following information : race , prepregnancy body mass index ( bmi ) and bmi at delivery , insurance status , prenatal vitamin use and maternal complications including smoking , hypertension , diabetes , chorioamnionitis , preterm labor and premature rupture of membranes . neonatal medical records were reviewed for the following information : gestational age , gender , birth weight , birth length , birth head circumference and sga status . sga was defined as weight < 10% for gestational age according to the fenton growth chart and the who growth chart ( for infants of 37 weeks ) . cord blood samples were spun and the serum was frozen at 80  c . cord blood 25(oh)d levels were analyzed using the liaison 25 oh vitamin d assay ( diasorin inc . , stillwater , mn , usa ) . this is a direct competitive chemiluminescence immunoassay used to quantitatively determine total 25(oh)d concentrations . for categorical analysis of vitamin d levels , we used cutoff values of : sufficient ( 50  nmol  l ) and deficient ( < 50  nmol  l ) . distributions of continuous variables were evaluated for normality graphically using histogram and box plots and are described using means and s.d . or medians with interquartile ranges , if nonnormally distributed . to explore relationships between race , vitamin d levels and sga , we first evaluated race as a predictor of vitamin d levels ( sufficient or deficient ) in cord blood and assessed for potential confounders : medicaid status , bmi at delivery , hypertension , maternal age and prenatal vitamin use . these results informed the next stage of analyses that examined race and vitamin d levels with the outcome of sga by assessing potential confounders : race , smoking , pre - eclampsia , maternal age , medicaid status and bmi at delivery . the  tests or fisher 's exact tests were used to examine relationships between categorical variables . independent t - tests were used to examine the relationship between continuous variables and each outcome . potential predictors associated with each outcome at p<0.2 in bivariate analyses were entered into multiple regression models and evaluated using backward elimination . of the 506 non - hispanic white and black infants , 438 with available data on vitamin d status , bmi at delivery , prenatal vitamin use and pre - eclampsia / pregnancy - induced hypertension ( pih ) history were included in final analyses . the mean cord blood 25(oh)d level for our study population ( n=438 ) was 46.9  nmol  l , with a range of 5.0 to 135.8  nmol  l. differences in the distributions of cord blood 25(oh)d concentrations by race were evident ( figure 1 ) , with a higher proportion of vitamin d - deficient samples found in the black population . the mean birth weight of our study cohort was 3119  g and 12.8% of our study population was sga . the mean bmi at delivery was 32.3  kg  m. maternal and neonatal characteristics of our study population , stratified by race , are shown in table 1 . compared with whites , blacks had a lower mean cord blood 25(oh)d level and higher incidence of sga ( p0.01 ) . race , medicaid status , higher bmi at delivery and lack of prenatal vitamin use were all associated with vitamin d deficiency ( 25(oh)d < 50  nmol l ; p<0.01 ) . after adjusting for medicaid status , bmi at delivery and prenatal vitamin use , black infants had a 3.6 greater odds ( 95% confidence interval ( ci ) : 2.4 , 5.6 ) of having vitamin d deficiency compared with white infants ( table 2 ) . similarly , infants on medicaid , a marker of socioeconomic status , had higher odds of vitamin d deficiency ( odds ratio ( or ) 2.3 , 95% ci : 1.4 , 3.8 ) , whereas prenatal vitamin use showed a protective effect ( or 0.24 , 95% ci : 0.09 , 0.62 ) . for every 5-unit increase in maternal bmi , infants had a 1.2 greater odds ( 95% ci : 1.1 , 1.4 ) of vitamin d deficiency ( table 2 ) . the predicted probabilities of vitamin d deficiency , based on significant predictors in the multivariable regression model , are shown in figure 2 . for instance , at a mean maternal bmi of 32.3  kg  m , an infant who is black , on medicaid and no prenatal vitamin use has an 86% ( 95% ci : 82 , 97 ) probability of vitamin d deficiency , whereas a black infant who is not on medicaid and with prenatal vitamin use has a 66% ( 95% ci : 44 , 67 ) probability of vitamin d deficiency . blacks had a significantly greater proportion of sga when compared with whites ( p=0.01 ; table 1 ) . as vitamin d levels also differed by race , we stratified the models predicting sga by race and examined vitamin d deficiency , smoking , pre - eclampsia , maternal age , medicaid status and bmi at delivery as covariates ( table 3 ) . black infants with vitamin d deficiency had 2.4 greater odds of sga ( 95% ci : 1.0 , 5.8 ) after adjusting for maternal history of pih and maternal bmi , two significant confounding variables in our model ( table 3 ) . similarly , infants of black mothers with history of pih were associated with 2.3 greater odds of sga after adjustment for confounding variables . vitamin d deficiency was not significantly associated with sga for white infants in our study population ( table 3 ) . we examined several additional models with various cutpoints for 25(oh)d based on clinical guidelines and previous literature , while adjusting for maternal pih and maternal bmi at delivery . < 25  nmol  l had an even greater odds of being sga ( or 3.8 , 95% ci : 1.4 , 10.6 ) compared with those with levels 50  nmol  l. the or was 2.2 ( 95% ci : 0.88 , 5.4 ) for black neonates with 25(oh)d levels 25 to 50  nmol  l compared with 50  nmol  l. the small proportion of neonates who were sga with 25(oh)d levels > 75  nmol  l precluded evaluation at higher cutpoints . although sga status was the main outcome of our study , we also evaluated models of 25(oh)d and birth weight percentile after adjusting for maternal pih and maternal bmi at delivery . birth weight percentiles for neonates with 25(oh)d levels < 25  mol  l were significantly lower compared with those with 25(oh)d levels 50  nmol  l ( adjusted mean weight percentile 0.35 ( 95% ci : 0.27 , 0.43 ) vs 0.46 ( 95% ci : 0.39 , 0.53 ) , p=0.02 ) . mean birth weight percentile for neonates with 25(oh)d levels 25 and < 50  nmol  l was 0.39 ( 95% ci : 0.34 , 0.45 ) . in our study population , we found that compared with white infants , black infants had significantly lower cord blood vitamin d levels and a greater proportion of vitamin d deficiency . although the prevalence of vitamin d deficiency in black mothers and neonates is well known , debate exists as to the relationship between race , vitamin d deficiency and sga . we examined this relationship in conjunction with additional maternal characteristics in order to identify groups of pregnant women who could benefit most from vitamin d supplementation . we found that black race was associated with a significantly greater incidence of sga , and that black race and vitamin d deficiency together were associated with even greater odds of sga . based on our analysis , a minimum threshold cord blood 25(oh)d level of 50  nmol  l was protective against sga status among black infants . interestingly however , white race with vitamin d deficiency was not significantly associated with increased odds of sga . only a small proportion of white infants were sga , and this may have limited our ability to detect significant associations between vitamin d and sga among white infants . vitamin d may affect fetal growth through its effect on calcium metabolism , bone growth and placental development . although initial studies showed conflicting results , more recent studies suggest that vitamin d deficiency may adversely affect growth and lead to low birth weight or sga infants . because of a known relationship between race and vitamin d status , attention then turned to investigation of the relationship between race , vitamin d deficiency and sga . review of published literature regarding this relationship revealed several relevant studies to ours . conducted a case  control study to examine the association between vitamin d levels , race and sga . for white mothers , measurement of maternal serum 25(oh)d at < 22 weeks ' gestation showed a u - shaped relationship between vitamin d status and risk of sga , where the highest risk for sga was seen with both low and high vitamin d levels . however , no relationship was seen between vitamin d status and sga among black mothers . in a larger study , burris et al . examined the relationship between second - trimester serum 25(oh)d levels and sga in blacks and whites and found a higher risk of sga in both vitamin d - deficient black and white infants . also examined second - trimester vitamin d levels and risk of sga in a population at risk of pre - eclampsia . they found that vitamin d status was associated with risk of sga in white and nonobese women , but that there was no association between vitamin d and sga in black or obese mothers . in contrast to the above - mentioned studies , our results show that the combination of black race and vitamin d deficiency was associated with increased odds of sga , but this relationship was not preserved for white infants . burris et al . were white , whereas the majority of our study population was black . furthermore , this study was conducted in hamilton county , ohio , an area with worse perinatal outcomes than national averages , including higher infant mortality , preterm birth and low birth weight rates , as well as considerable racial disparities in infant mortality and perinatal outcomes . all of cord blood samples were collected over one winter season , thus negating seasonal variations in vitamin d levels that may have been seen in other studies . finally , we analyzed cord blood vitamin d levels at the time of delivery , rather than maternal serum vitamin d levels during pregnancy . although cord blood 25(oh)d levels do correlate to maternal levels , factors that affect fetal growth may not be uniform throughout pregnancy and this difference in timing could affect study findings . in addition , maternal characteristics such as obesity or pre - eclampsia could also affect results that may not have been seen if vitamin d samples were obtained during early pregnancy . concurrently , we also examined maternal variables known to potentially affect vitamin d levels and sga in an effort to better understand the role of these risk factors in vitamin d levels and risk of sga . our results showed several factors to be significant , including bmi at delivery , pre - eclampsia , medicaid status ( as a measure of socioeconomic status ) and prenatal vitamin use . obesity is well known to be a risk factor for vitamin d deficiency because of a sequestering of vitamin d in adipose tissue . maternal obesity during pregnancy has also been associated with lower vitamin d levels in neonates at delivery . our data are consistent and illustrate the inverse relationship between maternal bmi at delivery and vitamin d status after adjusting for confounding variables . the increased odds of vitamin d deficiency in neonates relative to maternal bmi level were seen in both blacks and whites in our study population and supports similar findings seen in a study done by bodnar et al . although prenatal vitamin use was not significantly different between blacks and whites in our study , prenatal vitamin use was significant among those with and without vitamin d deficiency . furthermore , the protective effect against vitamin d deficiency was seen in both blacks and whites in our study , in contrast to a recently published study by burris et al . , who found that lack of prenatal vitamin use was associated with vitamin d deficiency in white but not black women . importantly , our study illustrates the additive effect of maternal risk factors and their predictive probabilities for vitamin d deficiency and sga . black mothers on medicaid who were obese and did not take prenatal vitamins had the highest probability of having an infant with vitamin d deficiency . pre - eclampsia , coupled with black race and vitamin d deficiency , resulted in significant increases in the predicted probability of delivering an sga infant . interestingly , our results show that increasing maternal bmi had a mild protective effect on risk of sga . this corresponds to the well - known association that women with higher bmi tend to deliver infants with higher birth weights . furthermore , identification and recognition of women and infants at high risk of vitamin d deficiency and sga can lead to opportunities for risk modification and reduction in adverse outcomes . specifically , this study supports a need to target supplementation strategies to mitigate the impact of adverse perinatal outcomes such as sga . vitamin d supplementation during pregnancy has been shown to positively affect cord blood vitamin d levels at birth . studies of vitamin d supplementation during pregnancy thus far have shown conflicting results with respect to birth weight and reduction of sga . adequately powered and randomized controlled trials of vitamin d supplementation during pregnancy are needed to assess the impact of supplementation on sga as well as the appropriate dose and timing of supplementation . in addition , individuals with the risk factors that we have identified may benefit even more from supplementation or higher dose supplementation . if vitamin d supplementation does not occur during pregnancy , it may be imperative to identify and offer additional supplementation beyond the routinely recommended 400  iu per day for all infants . first , we did not have information regarding exact amounts of dietary maternal vitamin d intake and sun exposure that may affect maternal and cord blood vitamin d levels . we collected samples over one winter season to mitigate the effect of varying sun exposure . this would have allowed for a more expansive definition of the relationship between maternal vitamin d status and perinatal outcomes . finally , as a retrospective study , we were limited by available data and the amount of cord blood available for further testing . black obese mothers on medicaid without prenatal vitamin use were at the highest risk of delivering neonates with vitamin d deficiency . furthermore , black race and vitamin d deficiency were associated with an increased risk of sga . we identified additive and modifiable maternal risk factors that would benefit most from risk reduction and targeted vitamin d supplementation . a greater understanding of the variables that influence vitamin d status during pregnancy can have an immense public health impact in the reduction of adverse perinatal outcomes such as sga .
objective : to examine the relationship of race and maternal characteristics and their association with cord blood vitamin d levels and small - for - gestational - age ( sga ) status.study design : cord blood vitamin d levels were measured in 438 infants ( 276 black and 162 white ) . 
 multivariable logistic regression models were used to evaluate associations between maternal characteristics , vitamin d status and sga.results:black race , medicaid status , mean body mass index at delivery and lack of prenatal vitamin use were associated with vitamin d deficiency . 
 black infants had 3.6 greater adjusted odds ( 95% confidence interval ( ci ) : 2.4 , 5.6 ) of vitamin d deficiency when compared with white infants . 
 black infants with vitamin d deficiency had 2.4 greater adjusted odds ( 95% ci : 1.0 , 5.8 ) of sga . 
 vitamin d deficiency was not significantly associated with sga in white infants.conclusion:identification of risk factors ( black race , medicaid status , obesity and lack of prenatal vitamin use ) can lead to opportunities for targeted prenatal vitamin supplementation to reduce the risk of neonatal vitamin d deficiency and sga status .