Major depression during pregnancy affects up to 12.7% of pregnant women1 and is associated with severe maternal and perinatal morbidity, including maternal self-harm or suicide,2 impaired fetal growth, preterm delivery or low-birth-weight neonates,3 impaired maternal functioning,4 inadequate mother–child bonding,5 and adverse effects on later childhood development.6,7 To address these issues, the Council on Patient Safety in Women's Health Care has published recommendations to improve the screening and management of women with perinatal mood disorders, including depression.8 Furthermore, the U.S. Preventive Services Task Force recommends depression screening for pregnant and postpartum women.9
Given that 54% of women with depression before pregnancy have depression during pregnancy10,11 and that 50% of U.S. pregnancies are unplanned,12 better diagnosis and treatment of nonpregnant women with depression may reduce the burden of perinatal mental illness. Epidemiologic studies are needed to plan management strategies for women with major depression before pregnancy. However, few studies have examined the prevalence of major depression among women of childbearing age.10,13,14 Furthermore, postpartum women were not clearly differentiated from nonpregnant women remote from pregnancy in these studies. Therefore, our primary aim was to describe the prevalence of major depression among nonpregnant women of childbearing age using National Health and Nutrition Examination Survey data. Secondary aims were to describe the prevalence of minor depression, examine rates of antidepressant use among women with major and minor depression, and perform an exploratory analysis to identify potential predictors for major and minor depression.
MATERIALS AND METHODS
The National Health and Nutrition Examination Survey is a nationally representative cross-sectional survey to assess the health and nutritional status of a representative sample of noninstitutionalized U.S. civilians selected using a complex, multistage probability design. Data are collected continuously and released in 2-year cycles.15 We received a waiver from the Stanford University institutional review board because the analysis relied on publicly available data without participant identifiers.
We combined data from the 2007–2014 data collection cycles. Because pregnancy status was not available for women aged younger than 20 years and older than 44 years, these women were excluded. To limit the likelihood of misclassifying women with perinatal or postpartum depression,1,11,16 we excluded pregnant women and postpartum women (up to 12 months after delivery). Pregnancy status was self-reported or determined with a urine pregnancy test.
The Patient Health Questionnaire 9 was administered as part of the National Health and Nutrition Examination Survey to detect major and minor depression. We used the Patient Health Questionnaire 9 scores to identify women with major and minor depression. The Patient Health Questionnaire 9 is a nine-item depression questionnaire17 used to assess depressive symptomatology. It is a well-established screening instrument to identify patients at risk for depression in a number of clinical settings with good evidence of reliability and validity.17 For each question, participants select a response based on a Likert-type scale with responses including not at all (0); several days (1); more than half the days (2); and nearly every day (3). The Patient Health Questionnaire 9 diagnosis of major depression is based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition18 criteria and requires that patients have five or more of the nine depressive symptoms for at least “more than half the days” in the past 2 weeks with at least one of the symptoms being depressed mood or anhedonia. One symptom, “thoughts that you would be better off dead or hurting yourself in some way,” counts if present at all. Potential risk factors for major depression were abstracted from the data set. These included age, race; marital status, education, monthly income-to-poverty ratio (categorized as low, medium, or high based on tertiles of their distribution), body mass index (BMI, calculated as weight (kg)/[height (m)]2), health insurance, physical activity, alcohol use over the past year, smoking history, and a history of asthma, hypertension, or diabetes.
The Patient Health Questionnaire 9 diagnosis of minor depression was based on Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria,18 which was classified by the presence of two, three, or four depressive symptoms for at least “more than half the days” in the past 2 weeks with one of the symptoms being depressed mood or anhedonia.
Use of antidepressant medication was ascertained from the Prescription Medication questionnaire. The questionnaire inquired about the intake of prescribed medication in the past 30 days. The complete list of antidepressants is presented in Table 1. Patients were classified as taking antidepressants if any of the medications were taken at least once in the past month.
All statistical analyses were performed using STATA 14.0 accounting for the complex survey design and population weights.15 Means and standard errors were calculated for continuous variables and proportions were calculated for categorical variables. Statistical differences between continuous variables were tested with an adjusted Wald test for survey data analogous to the parametric t test. Statistical differences between categorical variables were tested with χ2 tests.
The prevalences of major and minor depression and antidepressant use by type of depression were calculated. Univariate and multivariate associations between major depression and minor depression with potential risk factors were estimated using multinomial logistic regression. The results are presented as unadjusted and adjusted relative risk (RR) ratios with 95% CIs. We identified variables independently associated with major and minor depression where the P value was <.05. To account for multiple comparisons, a false discovery rate criteria of less than 5% was applied.
A cohort flow diagram is presented in Figure 1. Between 2007 and 2014, we identified 4,567 nonpregnant childbearing-aged women. After excluding 862 women with missing Patient Health Questionnaire 9 data, our final study cohort comprised 3,705 women. Characteristics of women with reported Patient Health Questionnaire 9 scores compared with those missing Patient Health Questionnaire 9 scores are presented in Table 2. Compared with those missing data, women reporting Patient Health Questionnaire 9 scores were more likely to be non-Hispanic white, college educated or higher, have a high income-to-poverty ratio, BMI greater than 18.5, report alcohol consumption, have a smoking history, asthma, be insured, do moderate exercise, and report good general health status. The overall prevalences of major and minor depression were 4.8% (95% CI 4.0–5.7%) and 4.3% (95% CI 3.5–5.2%), respectively.
The prevalence of any antidepressant use among women with major depression and minor depression was 32.4% (95% CI 25.3–40.4%) and 20.0% (95% CI 12.9–29.7%), respectively (Table 1). Among women with major depression, the most commonly used antidepressants were selective serotonin reuptake inhibitors (21.3%), phenylpiperazines (8.4%), and serotonin–norepinephrine reuptake inhibitors (7.2%). Selective serotonin reuptake inhibitors were the most common antidepressant used among women with minor depression (9.5%). No women were taking trimipramine, amoxapine, maprotiline, isocarboxazid, or tranylcypromine.
Table 3 shows the demographic and medical characteristics among childbearing-aged women with major depression, minor depression, and no depression. Table 4 shows the associations between correlates with major and minor depression in the multinomial models. In the multivariable analysis, being a current smoker, having hypertension, and government insurance were independently associated with major depression. In contrast, factors independently associated with minor depression were black race, other race, all education categories below college graduate level, current smoker, and asthma. Factors most strongly associated with major depression were government insurance (adjusted RR 2.49, 95% CI 1.56–3.96) and hypertension (adjusted RR 2.09, 95% CI 1.25–3.5), whereas, for minor depression, these were education less than high school (adjusted RR 4.34, 95% CI 2.09–9.01) and high school education (adjusted RR 2.92, 95% CI 1.35–6.31). To account for possible overfitting in our models, we performed sensitivity analyses using backward selection for variable inclusion in each multivariable model (Table 5). Risk factors identified in these sensitivity analyses were consistent with those identified in our full models.
Our findings indicate that 1 in 20 nonpregnant women of childbearing age experience major depression with approximately one in three women with major depression reporting antidepressant use. Given these findings and the limited guidance for managing severely depressed women before pregnancy,16 there is unmet need for stakeholders in obstetrics, primary care, and psychiatry to coordinate approaches to optimize care and prepregnancy counseling for women with major depression.
Our prevalence estimate for major depression falls within the range reported for depression during pregnancy (3.1–4.9%).1 In contrast, in two national surveys, the prevalence of a major depressive episode among nonpregnant women of childbearing age ranged from 11.1% to 12.2%.13,14 However, neither survey differentiated postpartum women from nonpregnant women remote from pregnancy; therefore, these estimates may be inflated. We observed similar prevalences for minor and major depression (4.3% vs 4.8%, respectively). This has public health relevance because high rates of comorbid psychiatric disorders have been reported among adolescents with subclinical depression.19,20 Of additional concern, up to 27% of adults with minor depression develop more severe forms, including major depression or dysthymia.21 Longitudinal studies are needed to examine perinatal outcomes among women with minor depression.
Rates of antidepressant use varied according to depression severity with a higher rate among women with major depression (32.4%) compared with those with minor depression (20%). In contrast to our findings, Ko et al13 reported that 47% of women with a past year history of major depression received treatment with prescription medication. Rate discrepancies may be explained by the different time windows for assessing antidepressant use and different definitions for depression. Despite these rate discrepancies, findings from these national studies are consistent with other population-wide studies that report undertreatment of major depression in the general population.22,23 For women with minor depression, the efficacy of antidepressant use is unclear,24 which may explain the lower utilization rate in this group.
In our multivariable analysis, several modifiable states—hypertension and smoking—were independently associated with major depression. Links between hypertension and smoking with depression have been reported in other studies.25–28 Although we cannot ascertain causation, the prevalence of each comorbid state among women with major depression was high (hypertension 33.5%, smoking 47.7%). Compared with women with private insurance, women with public insurance had a 2.5-fold increased risk of major depression. Prior research indicated that patients with mental health problems are more likely to be uninsured compared with those without these problems.29 Our data showed a similar trend, but these associations were not statistically significant.
Our study has several limitations. The cross-sectional nature of National Health and Nutrition Examination Survey data limited our ability to assess the effect of treatment on recently diagnosed women or to estimate the rate of a partial response to treatment. It is unclear whether antidepressants were exclusively prescribed for depression treatment. Medications in the classes under study can be used for anxiety, obsessive–compulsive disorder, binge eating, mood stabilization for bipolar disorders, insomnia, different pain conditions, and urinary incontinence.30 Furthermore, nonpharmacologic treatments for depression such as cognitive–behavioral therapy were not described in the data set. Because National Health and Nutrition Examination Surveys only provide information on pregnancy history for women aged 20–44 years, we could not account for women aged younger than 20 years or older than 44 years in our analysis. Our examination of predictors for major and minor depression was exploratory and the reported associations may be altered in the presence of unmeasured confounders. The statistically significant associations may also represent chance findings, especially as multiple comparisons were performed. We could not account for parity or number of prior live births in our analysis because of a high rate of missing data for each variable in our study cohort (44% and 50%, respectively). Lastly, 862 women had missing Patient Health Questionnaire 9 data, and these women differed from our study population along variables that were important for determining depression risk; therefore, our findings are potentially prone to selection bias.
Our results provide a cross-sectional estimate of the prevalence of major and minor depression affecting nonpregnant women of childbearing age in the United States. These data also suggest that a substantial proportion of women with severe depression are untreated or undertreated. Further studies are needed to determine whether improved screening and treatment of severe depression in nonpregnant women of childbearing age can secondarily reduce the prevalence of perinatal and postpartum depression.
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