Vitamin D Nutritional Status and Antenatal Depressive Symptoms in African American Women

Abstract

Background:

Vitamin D deficiency is associated with depression; however, no studies have examined the relationship of vitamin D and antenatal depression. Antenatal depression increases the risk of adverse birth outcomes and poorer postpartum maternal and infant health. African American women are at increased risk for vitamin D deficiency and antenatal depression. Thus, we examined if early pregnancy vitamin D nutrition (VDN) was associated with antenatal depressive symptoms among African American women in the second trimester of pregnancy.

Methods:

Women (n=178) were recruited from obstetrics clinics of a large health system. VDN was assessed by serum 25-hydroxyvitamin D (25-OHD). Depression symptoms were measured with the Center for Epidemiological Studies Depression (CES-D) scale; CES-D≥16 equates with criteria for clinical depression. Logistic regression was used to examine the association of log-transformed 25-OHD and elevated depression symptoms (CES-D≥16).

Results:

Mean 25-OHD was 13.4±8.4 ng/mL; most women (82.6%, n=147) were vitamin D inadequate or deficient (25-OHD<20 ng/mL). Mean CES-D was 15.2±10.7, and 74 (41.6%) women had a CES-D≥16, suggestive of clinical depression. A significant inverse relationship was found between log (25-OHD) and CES-D≥16 (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.29-0.99, p=0.046). For every 1-unit increase in log (25-OHD) (corresponding to ∼2.72 ng/mL increase in 25-OHD), the odds of CES-D≥16 decreased by 46%.

Conclusions:

African American women with lower VDN exhibit increased depressive symptoms. Research on vitamin D supplementation for reducing antenatal depressive symptoms is needed.

Introduction

There is growing interest in vitamin D nutrition (VDN) as a factor in many health concerns, including pregnancy complications.¹ This fat-soluble vitamin occurs naturally in very few foods and is primarily obtained by ingesting vitamin D-fortified foods or taking dietary supplements, or it is produced endogenously by the skin after exposure to sunlight.^2
–4 Vitamin D is needed for bone growth and modeling and is associated with modulation of cell growth, neuromuscular and immune function, and reduction of inflammation.^3,4

Although there is controversy about the classification of vitamin D deficiency,^5
–7 a 2011 report from the Institute of Medicine (IOM) indicates that people are at risk of vitamin D deficiency if serum 25-hydroxyvitamin D (25-OHD) concentrations are <12 ng/mL and at risk of vitamin D inadequacy if 25-OHD concentrations are between 12 ng/mL and <20 ng/mL.⁸ These values link serum 25-OHD levels with the recommended dietary allowance that meets 97.5% of the population's need.⁹ Vitamin D deficiency and inadequacy are common during pregnancy, especially among higher-risk groups.^2,10 Risk factors include vegetarianism, darker skin pigmentation, wearing protective clothing, decreased outdoor activities, living in northern latitudes, avoiding sun exposure (i.e., sunscreen), and underlying hyperparathyroidism.^2,4,11
–13 The role of VDN in adverse pregnancy outcomes is only beginning to be discovered. Studies have examined if VDN is associated with increased risk of preeclampsia, gestational diabetes mellitus (GDM), and small-for-gestational age (SGA) births, but the results are conflicting and current evidence is inconclusive.¹

The finding that vitamin D potentially has a causal role in the development of depression¹⁴ is of concern in pregnancy. Antenatal depression increases the risk of poor birth outcomes¹⁵ and, in the postpartum period, may adversely impact maternal and child health.^16,17 Antenatal depressive symptoms are more common among African American than Caucasian women,¹⁸ and pregnant African American women are at increased risk of vitamin D deficiency.¹ Findings from a recent pilot study raise concerns about the risk faced by African American women; in 97 postpartum women (30.9% African American), postpartum 25-OHD levels predicted the incidence of postpartum depressive symptoms.¹⁹

It has been hypothesized that vitamin D could help explain racial disparities in birth outcomes, but there is a recognized dearth of published obstetrics research on VDN in pregnancy, especially for African American women.²⁰ Further, to our knowledge, no study has examined the relationship of VDN with depressive symptoms during pregnancy. We address this gap in the literature by examining the association of VDN in early pregnancy with depressive symptoms among African American women in their second trimester of pregnancy.

Materials and Methods

Sample and Setting

The study population consisted of pregnant women who were patients in the Henry Ford Health System (HFHS),²¹ which provides medical care to 20%–30% of the metropolitan Detroit and surrounding population. Potential participants were identified by accessing upcoming patient appointment lists in the electronic medical record (EMR) of obstetrics and gynecology clinics at HFHS. Women aged 18–44 years and in the second trimester of pregnancy (approximately 13–28 weeks' gestation based on self-reported last menstrual period [LMP] or expected delivery date [EDD] defined by ultrasound) were identified. Patients unable to read or speak English or with evidence of illicit drug use or severe psychiatric illness were excluded.

Eligible women were sent recruitment letters approximately 2 weeks before an upcoming prenatal care appointment, and follow-up calls were attempted to all women to schedule a study appointment.²¹ The study was also advertised in clinics and on websites at HFHS and Wayne State University (WSU). Trained interviewers met women at an upcoming clinic appointment, with study visits occurring from February 23, 2009, to June 30, 2010. Written informed consent was obtained for all participants. The study protocols were approved by the Institutional Review Boards at HFHS and WSU.

A total of 203 women enrolled in the study (Fig. 1). Three women with very morbid obesity (body mass index [BMI] >60 kg/m²)²² were excluded a priori from the sample because of the difficulty in measuring basic clinical variables in the context of very morbid obesity (e.g., accurate assessment of maternal weight with a standard clinical scale or fetal growth using fundal height). Although most women completed the entire study protocol during one in-person visit, 11 women completed questionnaires by phone at a date after their inclusion into the study; 3 women completing the questionnaire after the second trimester were excluded. Women without any serum 25-OHD measurements (n=17) or who had measurements after the study visit (n=2) were excluded. The final analytic sample consisted of 178 women.

FIG. 1.

Study recruitment schematic. ^aNo phone contact made before recruitment goal reached. ^bMay have received intro letter, did not enter study via letter.

Vitamin D nutrition

As part of obstetrical care at HFHS, serum 25-OHD is measured during the first prenatal care visit (mean 9.5±3.6 weeks' gestation in this sample). Serum 25-OHD, considered the best measure of overall VDN status and the most useful clinically, was measured in the HFHS Bone & Mineral Research Laboratory using a competitive chemiluminescence immunoassay platform.³ The HFHS Bone & Mineral Research Laboratory participates in the Vitamin D External Quality Assessment Scheme (DEQAS); the methods used to measure 25-OHD are comparable to other reported methods.^23,24 All laboratory results were available electronically by searching on a patient's unique medical record number. By indexing on key dates (LMP and EDD), we obtained all 25-OHD values for study participants. For women without determination of 25-OHD levels, EMR abstraction was done to ensure that there were no available measures; none were found. Women were categorized by 25-OHD level using IOM criteria.⁸

Depression symptoms

The Center for Epidemiological Studies Depression Scale (CES-D), a 20-question instrument with responses in 4-point Likert format, was used to measure depressive symptoms in the past week.²⁵ CES-D scores were imputed for participants missing ≤4 individual CES-D items²⁶; no women were missing >4 CES-D items. CES-D scores ≥16 equate with symptoms of depression. The CES-D is a reliable and valid instrument and discriminates the general population from psychiatric populations,²⁵ with moderate to strong correlations with clinician ratings of depression and other depression scales. For CES-D, the current study Cronbach's α=0.90. The CES-D has been widely used in prenatal research,²⁷ has moderate to strong correlations (r=0.62–0.80) with other depression screening tools during pregnancy,^28,29 and is validated for use in pregnancy in African American women.³⁰

Participant characteristics

Participants self-reported date of birth, marital status, education, employment status, income, cigarette smoking, and alcohol use. Self-reported prepregnancy height and weight were used to calculate prepregnancy BMI (weight in kg/height in m²). Administrative databases were used to identify women with a history of essential hypertension (ICD-9 code 401.*) or type II diabetes mellitus (ICD-9 code 250.*). LMP (or EDD, if LMP unknown), parity, history of preterm birth, history of prior depressive illness (including postpartum depression), and prenatal vitamin (PNV) and vitamin D supplementation prescriptions were obtained from the EMR.

Statistical analysis

Statistical significance was defined as p<0.05. All analysis was performed using SAS 9.2. To reduce nonnormality, 25-OHD was natural log transformed and is referred to as log (25-OHD). For descriptive purposes, women with and without elevated depressive symptoms (CES-D≥16) were compared using t test for continuous variables and Pearson's chi-square test for discrete variables.

Logistic regression was used to examine the association of log (25-OHD) with elevated depression symptoms (CES-D≥16). Models were fit unadjusted, adjusted for demographic factors (i.e., maternal age, education, and marital status), and additionally adjusted for season of 25-OHD measurement and time between 25-OHD measurement and CES-D measurement. Because of the controversy surrounding the classification of vitamin D, particularly within pregnancy, our primary analysis focused on continuous rather than categorical 25-OHD.^5
–7,31 However, we additionally conducted a secondary analysis using IOM categories of 25-OHD⁸ as the explanatory variable.

As a sensitivity analysis, we refit the final model examining continuous 25-OHD with CES-D≥16: (1) examining BMI or income as potential additional confounding variables and (2) excluding women with a prior history of depression.

Results

Data on age, 25-OHD, and discharge diagnoses of depression were available electronically (through automated data) on most women (n=399) identified as eligible for the study but who did not participate (Fig. 1). There was no difference between these 399 nonparticipators and the 203 women participating in the study with respect to age (p=0.21), 25-OHD level (p=0.72), or history of depressive illness (p=0.87). The enrolled study population is representative of the underlying eligible population for these selected characteristics.

Table 1 presents participant characteristics by CES-D≥16. Mean 25-OHD was 13.4±8.4 ng/mL. Based on IOM criteria, most women were vitamin D inadequate (n=56, 31.5%) or vitamin D deficient (n=91, 51.1%). The mean CES-D score was 15.2±10.7, and 74 (41.6%) women had elevated depressive symptoms. Although women with a prior history of depression had nonstatistically significantly higher CES-D scores than those without such history (19.8±11.7 compared to 14.9±10.6, p=0.08), there was no difference in 25-OHD by prior depression history (12.3±3.5 ng/mL compared to 13.5±8.7 ng/mL, p=0.79). Women with currently elevated depressive symptoms (CESD≥16), however, had significantly lower 25-OHD levels (p=0.003) and were significantly more likely to be in the 25-OHD-deficient category (p=0.016). Depressive symptoms were not significantly associated with any other participant descriptive characteristic.

Table 1.

Descriptive Characteristics of Study Population (n=178), Stratified by Elevated Depressive Symptoms

Maternal characteristic	CESD<16 n=104, 58.4%	CESD≥16 n=74, 41.6%	p
Age (years)	26.9±6.2	25.8±5.2	0.200
Married/living as married	28 (26.9%)	14 (18.9%)	0.215
≥High school education	93 (89.4%)	60 (81.1%)	0.114
Income ($)^a	37266.3±37374.5	28451.8±20945.8	0.088
Currently employed	53 (51.0%)	37 (50.0%)	0.763
Prepregnancy BMI (kg/m²)	29.2±7.4	29.6±7.9	0.699
BMI category			0.856
Underweight/normal weight (<24.9 kg/m²)	35 (33.7%)	22 (29.7%)
Overweight (25.0–29.9 kg/m²)	27 (26.0%)	20 (27.0%)
Obese (≥30 kg/m²)	42 (40.4%)	32 (43.2%)
Nulliparous^b	44 (42.3%)	33 (44.6%)	0.762
History of preterm birth	16 (15.4%)	9 (12.2%)	0.542
Smoked during pregnancy	6 (5.8%)	6 (8.1%)	0.540
Alcohol consumption in last month	1 (1.0%)	4 (5.4%)	0.077
History of hypertension	15 (14.4%)	11 (14.9%)	0.934
History of diabetes	4 (3.8%)	6 (8.1%)	0.224
History of depression	6 (5.8%)	7 (9.5%)	0.351
25-OHD (ng/mL)	15.0±9.9	11.2±4.9	0.003
25-OHD category^c			0.016
Deficient (<12 ng/mL)	45 (43.3%)	46 (62.2%)
Inadequate (12–20 ng/mL)	33 (31.7%)	23 (31.1%)
Sufficient (20–30 ng/mL)	19 (18.3%)	5 (6.8%)
No additional value (30–50 ng/mL)	6 (5.8%)
Potentially toxic (≥50 ng/mL)	1 (1.0%)
Season of 25-OHD measurement			0.144
January–March	42 (40.4%)	28 (37.8%)
April–June	17 (16.3%)	22 (29.7%)
July–September	21 (20.2%)	9 (12.2%)
October–December	24 (23.1%)	15 (20.3%)
Gestational age (weeks) 25-OHD measured	9.7±3.8	9.2±3.4	0.333
Gestational age (weeks) CES-D measured	21.0±3.8	20.4±3.6	0.326
Time between 25-OHD and CES-D measurement (weeks)	11.4±4.3	11.2±4.7	0.855

Data are n (%) or mean±standard deviation.

n=156 reported income.

Defined as no previous pregnancy lasting at least 6 months.

Based on Institute of Medicine (2011) categorization.⁸

BMI, body mass index; CES-D, Center for Epidemiological Studies Depression Scale; 25-OHD, 25-hydroxyvitamin D.

All but 3 women had PNV prescriptions (98.3%). All PNV prescribed contained 400 IU of vitamin D. In addition, vitamin D supplements were prescribed as part of routine prenatal care to 155 (87.1%) women, with nearly all prescriptions (n=152; 98.1%) occurring after VDN assessment (mean 4.3±6.3 weeks after VDN assessment). Most vitamin D supplements prescribed were 50,000 IU of vitamin D₂ taken once weekly (150 women, 96.8%).

In univariable analyses, maternal age (p=0.02), marital status (p=0.04), having a high school education or greater (p<0.01), and income (p=0.01) were each statistically significantly associated with increasing log (25-OHD). As expected, season of measure was significantly associated with log (25-OHD); women with 25-OHD measured in April–June, July–September, or October–December had significantly higher 25-OHD (all p≤0.05) compared to women measured in January–March.

Association of 25-OHD with elevated depression symptoms

Table 2 presents the association of 25-OHD with elevated depression symptoms (CES-D≥16). In the fully adjusted model, a significant inverse relationship was found between log (25-OHD) and CES-D≥16 (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.29-0.99, p=0.046). For every 1-unit increase in log (25-OHD) (corresponding to ∼2.72 ng/mL increase in 25-OHD), the odds of women having an elevated depression score (CES-D≥16) decreased by 46%.

Table 2.

Association of Log-Transformed 25-Hydroxyvitamin D (Log (25-OHD)) with Elevated Depression Symptoms (CES-D≥16)

Log (25-OHD) (per 1 unit increase)	Odds ratio (95% CI)	p
Unadjusted	0.49 (0.28-0.87)	0.014
Adjusted for maternal age, ≥high-school education, and marital status	0.55 (0.30-0.98)	0.041
Adjusted for maternal age, ≥high-school education, marital status, season of 25-OHD measure, and number of days between 25-OHD and CES-D measure	0.54 (0.29-0.99)	0.046

CES-D, center for epidemiological studies depression scale; CI, confidence interval.

As a secondary analysis, we also examined the association of IOM 25-OHD category with depression; categorical 25-OHD was associated with CES-D≥16. Women with 25-OHD levels that were sufficient or higher were 80% less likely to have CES-D≥16 than women who were vitamin D deficient (aOR 0.20, 95% CI 0.07-0.59, p=0.004).

Sensitivity analysis

Refitting the final continuous model in the subgroup of women (n=156) with income data, using income rather than education as the socioeconomic status variable, model inferences were the same (aOR for 25-OHD level 0.52, 95% CI 0.27-1.00, p=0.050). Refitting the final model additionally adjusting for BMI resulted in similar inferences (aOR for 25-OHD level 0.51, 95% CI 0.27-0.97, p=0.041). The relationship between 25-OHD level and elevated depressive symptoms remained the same when the model was run restricting the sample to women without a history of depression. Therefore, our results are not unduly influenced by women with prior diagnosed depressive illness.

Discussion

We provide, for the first time, evidence suggesting that lower VDN, as assessed by serum 25-OHD, in early pregnancy is associated with antenatal depressive symptoms among African American women.

The potential pathophysiologic role of vitamin D in depression has been described in detail elsewhere.³² Vitamin D is a potential neurosteroid³³; the vitamin D receptor and the vitamin D activating enzyme are both present in the human brain.³⁴ In addition to other impairments, mice lacking the vitamin D receptor gene exhibit increased anxiety-like behavior.³⁵ Dysregulation of glucocorticoid signaling, which is involved in development of depression, can be remediated with vitamin D₃ exposure in cell lines.³⁶ Thus, there is evidence supporting the plausibility of a link between VDN and depression.

Prenatal depressive symptoms are associated with poorer birth outcomes and postpartum depression.^15,16 Treatment of antenatal depression, particularly the use of antidepressants, requires careful consideration of the risks and benefits to both the mother and the fetus,³⁷ with long-term negative effects just being discovered. For instance, prenatal exposure to antidepressants is associated with child internalizing behavior at age 3 years and also with increased risk of autism spectrum disorders.^38,39 Vitamin D supplementation, considered a cost-effective and safe intervention during pregnancy,⁴⁰ may reduce prepartum and postpartum depression and also may benefit the developing fetus. In a recent partially randomized clinical trial, vitamin D₃ supplementation during pregnancy was associated with improved newborn anthropometric characteristics (e.g., increased birth weight and length).⁴¹ Future studies on the use of vitamin D supplementation for reducing antenatal depression are needed.

Based on IOM criteria, a high percentage of women in this study are vitamin D inadequate or deficient. This is consistent with a previous systematic review of VDN in pregnancy.¹ Regardless of the classification used, African American women are at especially high risk for vitamin D deficiency because of their darker skin, which limits the amount of vitamin D that can by synthesized in the skin, and a lower intake of supplemental vitamin D.²⁰

Vitamin D is necessary for optimal maternal and fetal health during pregnancy.⁴² VDN is associated with poorer obstetric outcomes, although results have been inconsistent.¹ Maternal vitamin D deficiency places newborns at risk for a similar deficiency.⁴³ In addition to potential bone problems (e.g., osteomalacia, compromised skeletal growth, congenital rickets), one recent study found an inverse association between maternal serum 25-OHD levels and childhood asthma.⁴⁴ As a result of concern for child health, the American Academy of Pediatrics recommended that all pregnant women be screened for vitamin D deficiency.⁴⁵ The Committee Opinion of the American College of Obstetricians and Gynecologists, however, recommends screening only women at increased risk of deficiency.² Screening African American women would be consistent with both guidelines.

As with all studies, there are limitations to consider when interpreting results and planning future studies. We a priori selected African American women because of their high risk of poorer obstetric outcomes relative to other racial/ethnic groups. Thus, our results may not be generalizeable to other racial/ethnic groups, and similar studies in broader populations are needed.

As part of routine prenatal care, nearly all women in the current study were prescribed a PNV containing 400 IU of vitamin D, largely considered insufficient to increase serum 25-OHD to normal levels.^3,46 After 25-OHD assessment, many women were prescribed additional vitamin D supplements (most commonly 50,000 IU/week of vitamin D₂). However, in an evaluation study of vitamin D repletion regimens, in a small group (n=14) of male and female vitamin D-deficient patients prescribed 50,000 IU/week of vitamin D₂ supplementation over an 8-week period, only 13% (n=1) of study subjects achieved vitamin D sufficiency.⁴⁷ In a recent study, 50,000 IU/week of vitamin D₂ for an average of 17 weeks resulted in a little over half (58%) of subjects attaining vitamin D sufficiency within 6 months.⁴⁸ Vieth et al.⁴⁹ have suggested that optimal serum 25-OHD and other biochemical responses (e.g., parathyroid hormone levels) occur after 6 months of supplementation. If there is a short-term benefit of vitamin D supplementation on depressive symptoms, this may have attenuated the association detected in the current study. Alternatively, our results may actually reflect an unmeasured confounder that is associated with both early VDN and second trimester depressive symptoms. Although time between 25-OHD and CES-D measurements did not influence our final model inferences, longitudinal studies examining changes in 25-OHD with changes in depression symptoms across pregnancy are needed.

In addition to sunlight and supplement use, serum 25-OHD is associated with consumption of fatty fish (e.g., salmon, tuna) and fortified food products (e.g., milk, breakfast cereal, orange juice).^31,50 Dietary assessments were not part of the current study; thus, we are unable to examine if particular food sources of vitamin D are the strongest determinants of 25-OHD level in our population. Future studies should consider including dietary and outdoor activity questions to address this issue.

The prevalence of elevated depressive symptoms in our study population was slightly lower compared to other studies of pregnant African American women (prior estimates ranging from 49% to 56%).^18,51 This suggests that women with depression were not overrepresented in the current study and minimizes the risk that the findings reported are a result of selection bias.

Vitamin D has been implicated as a potential causal factor in depression.¹⁴ However, Bertone-Johnson⁵² has cautioned against assuming a causal relationship because of methodologic limitations and potential unmeasured confounding in previous studies. In the current study, in addition to unmeasured confounding factors, reverse causality may explain the association we detected.⁵³ For instance, women may have lower VDN because of poorer health (e.g., a woman experiencing depression may be less likely to go outdoors and, thus, would have lower 25-OHD). Additional work is needed to parse out potential causality of VDN in depression among pregnant women.

Conclusions

Although there is growing evidence that the levels of vitamin D needed in pregnancy are greater than those needed in the nonpregnant state,⁴⁶ the limited knowledge about the effect of 25-OHD levels in early pregnancy poses a challenge in obstetrical care.¹ We demonstrate that low levels of 25-OHD in early pregnancy are associated with antenatal depression symptoms. Future studies examining the potential direct effect of vitamin D, as well as possible mediating or moderating effects between prenatal 25-OHD levels and depressive symptoms, on obstetrical outcomes are needed. There is a clear need for more research on the role of VDN in pregnancy, particularly given that most studies on VDN in pregnancy report a significant number of women to be vitamin D deficient.¹

Footnotes

Acknowledgments

We thank Ms. Cathy Collins-Fulea, M.S.N., C.N.M., Division Head Midwifery, HFHS, for her critical review of the manuscript. This study was funded by the Institute for Population Sciences, Health Assessment, Administration, Services, and Economics (INPHAASE).

Disclosure Statement

No competing financial interests exist.

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