Objective
We evaluated vitamin D insufficiency in a nationally representative sample of women and assessed the role of vitamin supplementation.
Study Design
We conducted secondary analysis of 928 pregnant and 5173 nonpregnant women aged 13-44 years from the National Health and Nutrition Examination Survey 2001-2006.
Results
The mean 25-hydroxyvitamin D (25[OH]D) level was 65 nmol/L for pregnant women and 59 nmol/L for nonpregnant women. The prevalence of 25(OH)D <75 nmol/L was 69% and 78%, respectively. Pregnant women in the first trimester had similar 25(OH)D levels as nonpregnant women (55 vs 59 nmol/L), despite a higher proportion taking vitamin D supplementation (61% vs 32%). However, first-trimester women had lower 25(OH)D levels than third-trimester women (80 nmol/L), likely from shorter duration of supplement use.
Conclusion
Adolescent and adult women of childbearing age have a high prevalence of vitamin D insufficiency. Current prenatal multivitamins (400 IU vitamin D) helped to raise serum 25(OH)D levels, but higher doses and longer duration may be required.
Over the past few decades, vitamin D has reemerged as an important nutritional factor in maternal and infant health. The resurgence of childhood rickets and other problems of bone mineralization associated with severe vitamin D deficiency appears to represent only part of the story for vitamin D and health. Indeed, vitamin D regulates >1000 human genes, and vitamin D receptors are found in most tissues and cells throughout the body. Accordingly, in utero or early life vitamin D insufficiency has been linked to increased risk of childhood wheezing, respiratory infection, type 1 diabetes, multiple sclerosis, schizophrenia, and even placental development and function. Vitamin D insufficiency in adults has also been linked to cardiovascular disease, infection, cancer, and even mortality. While relatively small amounts of vitamin D prevent nutritional rickets, larger doses and higher serum 25-hydroxyvitamin D (25[OH]D) levels appear necessary for optimal general health outcomes.
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Individuals with darker skin pigment, those who cover their skin with clothing for religious or cultural reasons, and those living further away from the equator during the winter season are at particular risk for vitamin D insufficiency. Additionally, successful campaigns to control sun exposure through avoidance and sun protection, coupled with decreased outdoor physical activity, have likely led to rising prevalence of vitamin D insufficiency in the general population. Until recently, serum 25(OH)D levels ≥50 nmol/L (to convert to ng/mL divide by 2.496) appeared adequate based on improved skeletal outcomes, but increasing evidence suggests that 75 nmol/L or even 100 nmol/L may be required for optimum health. Indeed, current recommended doses of vitamin D supplementation, 200-600 IU daily, may be inadequate to achieve these higher serum 25(OH)D levels on a population level.
Since 25(OH)D readily crosses the placenta, fetal and newborn vitamin D status is almost entirely dependent on vitamin D from the mother. Not surprisingly, cord blood 25(OH)D levels are strongly correlated with maternal vitamin D status. Additionally, because vitamin D secretion in breast milk is limited, lactating women require robust serum 25(OH)D levels to support vitamin D status in nursing infants. A high prevalence of vitamin D insufficiency has been documented in pregnant and lactating women, particularly in high-risk cohorts. These studies have raised awareness of higher doses of vitamin D supplementation that may be required to improve maternal and infant skeletal and general health outcomes. For instance, the Canadian Pediatric Society recently recommended 2000 IU daily of vitamin D supplementation, and higher target serum 25(OH)D levels for pregnant and lactating women.
In this study, we sought to measure vitamin D insufficiency in a nationally representative sample of adolescent and adult women of childbearing age in the United States and to evaluate the role of vitamin D supplementation and outdoor activity in prevention of vitamin D insufficiency.
Materials and Methods
Study design and participants
Annually, the National Center for Health Statistics conducts the National Health and Nutrition Examination Survey (NHANES), a nationally representative probability sample of the noninstitutionalized US civilian population. Because the data are publicly available and deidentified, we received a waiver from our institutional review board to analyze the 3 most recent cycles of NHANES data (ie, January 2001 through December 2006).
Details of survey methodology are described elsewhere. During 2001-2006, NHANES collected household interview data for 7932 (83%) of 9521 invited adolescent and adult women aged 12-49 years. Subsequently, 7642 (96%) received physical and laboratory examination in a mobile examination center, of which 7026 had serum 25(OH)D testing (616 missing). Pregnancy status was determined by self-report, supplemented by urine human chorionic gonadotropin testing for most women. The NHANES data included an adjudicated pregnancy status variable that was used for analysis in this study, as recommended by the NHANES instructions for data analysis. Since the age range for pregnant women in NHANES was 13-44 years, our analysis included 928 pregnant and 5173 nonpregnant women aged 13-44 with serum 25(OH)D levels recorded. This represents approximately 62 million US women.
Data collection
Throughout the NHANES years, strategies for sampling and methodologies for data collection were very similar to maintain consistency and facilitate comparisons. To avoid weather issues and improve response, the NHANES mobile examination centers preferentially scheduled data collection in the lower latitudes (further south) during winter months, and higher latitudes (further north) during the summer months. Since month of data collection was not reported in the NHANES 2001-2006 data set (to protect participant confidentiality), we were unable to record or control for season.
Demographic data (age, sex, race/ethnicity) and current breast-feeding were recorded based on self-report. The poverty-income ratio is provided in the NHANES data set and was used to control for socioeconomic status; values <1 were considered low socioeconomic status. Physical activity was measured by a query of 48 common leisure-time activities over the past month. We categorized activities as outdoor (eg, walking, gardening), indoor (eg, aerobics, weightlifting), or indeterminate (eg, basketball, swimming), as previously described. We then classified leisure-time activities during the past month for each study participant as: none; at least 1 outdoor activity; or indoor/indeterminate activities only. For pregnant women, month of pregnancy was recorded based on last menstrual period (if known), and we stratified the estimated gestational ages into trimesters or unknown gestational age. For the vitamin supplement data, the interviewer identified all of the vitamin/mineral supplements being used and duration of use.
Blood samples for serum 25(OH)D testing collected during the examination were centrifuged, aliquoted, and frozen to –70°C until analysis. Serum 25(OH)D levels were measured by a radioimmunoassay kit after extraction with acetonitrile (DiaSorin, Stillwater, MN) by the National Center for Environmental Health (Atlanta, GA).
Data analysis
We performed statistical analyses using software (Stata 9.0; StataCorp, College Station, TX). We applied the recommended subsample weights for the interview plus examination data to account for unequal probabilities of selection and to provide population estimates of 25(OH)D levels. Although all results are presented as weighted values, we also provide the raw numbers to allow for insight about the sample size. We calculated variance based on NHANES-provided masked variance units, using Taylor Series linearization method. We reported mean serum 25(OH)D levels and further stratified results by 2 common definitions of vitamin D insufficiency, <50 nmol/L, and <75 nmol/L. Primary analysis is descriptive with 95% confidence intervals (CIs).
We made univariate statistical comparisons using χ 2 test or analysis of variance, as appropriate. All P values are 2-tailed with P < .05 considered statistically significant. To evaluate the independent association between covariates and serum 25(OH)D levels, we created multivariable linear and logistic regression models for mean 25(OH)D levels and dichotomous outcomes of vitamin D insufficiency, respectively. We included vitamin D supplementation dose, but not duration of vitamin D supplements, due to colinearity. We reported β coefficients and odds ratios with 95% CI for variables in the multivariable models.
Results
In NHANES 2001-2006, there were 928 pregnant women and 5173 nonpregnant women of childbearing age who were eligible for inclusion, which represents 4 million (7%) and 58 million (93%) women, respectively. Demographic and clinical characteristics of the study population are presented in Table 1 .
| Characteristic | Pregnant (n = 928) (95% CI) | Nonpregnant (n = 5173) (95% CI) | P value |
|---|---|---|---|
| Age, y | < .001 | ||
| 13–19 (n = 2710) | 9% (7–12) | 21% (20–23) | |
| 20–34 (n = 2203) | 78% (73–82) | 44% (41–46) | |
| 35–44 (n = 1188) | 13% (10–18) | 35% (32–37) | |
| Race | < .001 | ||
| NH white (n = 2296) | 56% (50–62) | 65% (62–69) | |
| NH black (n = 1572) | 16% (12–22) | 13% (11–16) | |
| Hispanic (n = 1969) | 20% (16–26) | 16% (13–18) | |
| Other (n = 264) | 8% (6–10) | 6% (4–7) | |
| Poverty-income ratio | .03 | ||
| ≤1 (n = 1650) | 25% (20–30) | 18% (17–20) | |
| >1 (n = 4182) | 71% (65–76) | 78% (76–79) | |
| Unknown (n = 269) | 4% (2–8) | 4% (3–5) | |
| Gestational age | – | ||
| First trimester (n = 198) | 29% (24–34) | – | |
| Second trimester (n = 331) | 31% (26–36) | – | |
| Third trimester (n = 312) | 30% (25–36) | – | |
| Unknown (n = 87) | 10% (7–15) | – | |
| Vitamin D supplement dose (IU) | < .001 | ||
| 0 (n = 4268) | 28% (22–34) | 68% (66–70) | |
| 1–399 (n = 157) | 7% (5–10) | 3% (2–4) | |
| ≥400 (n = 1676) | 66% (59–71) | 29% (27–31) | |
| Duration of vitamin D supplement use (d) a | < .001 | ||
| 0 (n = 4269) | 28% (22–34) | 68% (66–70) | |
| 1–30 (n = 251) | 12% (8–17) | 4% (3–5) | |
| 31–180 (n = 423) | 21% (16–26) | 4% (4–5) | |
| ≥181 (n = 1152) | 29% (33–45) | 24% (22–26) | |
| Physical activity in past 30 d | < .001 | ||
| None (n = 1784) | 39% (32–46) | 26% (24–28) | |
| Outdoor (n = 3516) | 53% (45–60) | 62% (59–64) | |
| Indoor/indeterminate only (n = 801) | 8% (5–12) | 12% (11–14) |
a Based on longest duration of use for any current vitamin D-containing supplement; 6 missing/unknown.
Overall, the mean serum 25(OH)D level among all US women aged 13-44 years was 59 nmol/L (95% CI, 57-61). Table 2 displays the mean 25(OH)D levels of participants, stratified by characteristics. Serum 25(OH)D levels were higher among pregnant compared to nonpregnant women (65 vs 59 nmol/L; P < .001). Currently breast-feeding women (n = 139) had similar 25(OH)D levels as other nonpregnant women (60 vs 59 nmol/L; P = .40); thus these groups were combined in the analysis.
| Variable | Pregnant (n = 928) nmol/L (95% CI) | Nonpregnant (n = 5173) nmol/L (95% CI) |
|---|---|---|
| Total (n = 6101) | 65 (61–68) | 59 (57–61) |
| Age, y | ||
| 13–19 (n = 2710) | 57 (50–64) | 59 (56–61) |
| 20–34 (n = 2203) | 64 (61–68) | 60 (57–63) |
| 35–44 (n = 1188) | 71 (64–79) | 57 (54–60) |
| Race | ||
| NH white (n = 2296) | 77 (73–80) | 67 (65–70) |
| NH black (n = 1572) | 39 (35–42) | 33 (32–35) |
| Hispanic (n = 1969) | 56 (51–62) | 48 (46–49) |
| Other (n = 264) | 54 (46–62) | 46 (42–50) |
| Poverty-income ratio | ||
| ≤1 (n = 1650) | 56 (50–63) | 53 (49–56) |
| >1 (n = 4182) | 68 (64–72) | 60 (58–62) |
| Unknown (n = 269) | 53 (48–59) | 60 (53–66) |
| Gestational age | ||
| First trimester (n = 198) | 55 (50–60) | – |
| Second trimester (n = 331) | 62 (62–57) | – |
| Third trimester (n = 312) | 80 (73–87) | – |
| Unknown (n = 87) | 53 (45–61) | – |
| Vitamin D supplement dose (IU) | ||
| 0 (n = 4268) | 46 (41–50) | 55 (53–57) |
| 1–399 (n = 157) | 68 (59–77) | 65 (59–71) |
| ≥400 (n = 1676) | 72 (69–76) | 67 (65–69) |
| Duration of vitamin D supplement use, d a | ||
| 0 (n = 4269) | 46 (41–50) | 55 (53–57) |
| 1–30 (n = 251) | 62 (55–68) | 62 (55–68) |
| 31–180 (n = 423) | 68 (62–73) | 62 (57–66) |
| ≥181 (n = 1152) | 77 (72–82) | 68 (66–70) |
| Physical activity in past 30 d | ||
| None (n = 1784) | 56 (51–61) | 50 (47–52) |
| Outdoor (n = 3516) | 72 (67–76) | 63 (61–65) |
| Indoor/indeterminate only (n = 801) | 62 (54–71) | 56 (53–59) |
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