Lit Review (Results Section)

Perinatal Depressive Symptoms in HIV-Infected Versus HIV-Uninfected Women:

A Prospective Study from Preconception to Postpartum

Leah H. Rubin, Ph.D.,1 Judith A. Cook, Ph.D.,2 Dennis D. Grey, B.A.,2 Kathleen Weber, R.N., B.S.N.,3

Christina Wells, M.D.,4 Elizabeth T. Golub, Ph.D., M.P.H.,5 Rodney L. Wright, M.D., M.S.,6

Rebecca M. Schwartz, Ph.D.,7 Lakshmi Goparaju, Ph.D.,8 Deborah Cohan, M.D., M.P.H.,9

Melissa L. Wilson, Ph.D., M.P.H.,10 and Pauline M. Maki, Ph.D.1

Abstract

Objective: Depression is common among HIV-infected women, predicts treatment nonadherence, and conse- quently may impact vertical transmission of HIV. We report findings from a study evaluating preconception, pregnancy, and postpartum depressive symptoms in HIV-infected vs. at-risk, HIV-uninfected women. Methods: We examined the prevalence and predictors of elevated perinatal (i.e., pregnancy and/or postpartum) depressive symptoms using a Center for Epidemiological Studies-Depression (CES-D) scale score of ‡ 16 in 139 HIV-infected and 105 HIV-uninfected women (62% African American) from the Women’s Interagency HIV Study (WIHS). Results: The prevalence of elevated perinatal depressive symptoms did not differ by HIV serostatus (HIV-infected 44%, HIV-uninfected 50%, p = 0.44). Among HIV-infected women, the strongest predictor of elevated symptoms was preconception depression (odds ratio [OR] 5.71, 95% confidence interval [CI] 2.67-12.19, p < 0.001); crack, cocaine, and/or heroin use during preconception was marginally significant (OR 3.10, 95% CI 0.96-10.01, p = 0.06). In the overall sample, additional significant predictors of perinatal depression included having multiple sex partners preconception (OR 2.20, 95% CI 1.12-4.32, p = 0.02), use of preconception mental health services (OR 2.51, 95% CI 1.03-6.13, p = 0.04), and not graduating from high school (OR 1.92, 95% CI 1.06-3.46, p = 0.03). Conclusions: Elevated perinatal depressive symptoms are common among HIV-infected and at-risk HIV- uninfected women. Depressive symptoms before pregnancy were the strongest predictor of perinatal symptoms. Findings underscore the importance of early and ongoing assessment and treatment to ensure low vertical transmission rates and improving postpregnancy outcomes for mothers and children.

Introduction

Psychiatric illnesses, in particular mood disorders,commonly co-occur with the human immunodeficiency virus (HIV).1–4 Numerous studies report high rates of de-

pression and depressive symptoms in HIV-infected individ- uals compared to uninfected individuals in the general population, and the rates have been reported to be signifi- cantly higher in women than in men.5 The relationship be- tween depression and HIV infection is clinically important

1Department of Psychiatry and 2Center on Mental Health Services Research and Policy, Department of Psychiatry, University of Illinois at Chicago, Illinois.

3The Core Center of the John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois. 4University of Illinois School of Medicine, Chicago, Illinois. 5Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 6Department of Obstetrics and Gynecology and Women’s Health Division of Maternal Fetal Medicine, Albert Einstein College of Med-

icine, Bronx, New York. 7Department of Community Health Sciences in the School of Public Health at SUNY Downstate Medical Center, Brooklyn, New York. 8Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia. 9San Francisco General Hospital, University of California San Francisco Department of Obstetrics, Gynecology and Reproductive Sciences,

San Francisco, California. 10University of Southern California, Department of Obstetrics and Gynecology and Department of Preventive Medicine, Los Angeles,

California.

JOURNAL OF WOMEN’S HEALTH Volume 20, Number 9, 2011 ª Mary Ann Liebert, Inc. DOI: 10.1089/jwh.2010.2485

1287

because the co-occurrence of the two conditions provides an additional health burden and can contribute to poor treatment adherence in women6,7 and thereby affect disease progres- sion, viral suppression, and survival.8–11 For example, the Women’s Interagency HIV Study (WIHS), a large multicenter investigation of 3766 women, found that in analyses adjusting for possible confounding factors, HIV-infected women with high levels of depressive symptoms were significantly less likely to be on highly active antiretroviral therapy (HAART) regimens.6 Depressive symptoms in HIV-infected women are associated with substance use, including the use of crack, cocaine, heroin, and amphetamines,7 and injected drugs.12

Depression in HIV-infected women has also been shown to be related to AIDS-related mortality,13 social and economic ad- verse events, and risk-taking behaviors, such as an increased number of sexual partners.12 Other predictors of depressive symptoms in HIV-infected women include low income, less than a high school education, and Hispanic ethnicity.12 Taken together, these findings suggest that reducing depressive symptoms in HIV-infected women may contribute to in- creased medication adherence, improved health, and a re- duction in drug use and other maladaptive behaviors.

Despite a wealth of knowledge about factors related to depression and depressive symptoms in HIV-infected wo- men, little is known about the prevalence of and risk factors for perinatal depression symptoms in this high-risk popula- tion. Perinatal depression encompasses major and minor de- pressive episodes that occur during pregnancy or within 1 year after childbirth. Prevalence estimates of perinatal de- pression in the general population range from 8.5% to 11% during pregnancy and from 6.5% to 12.9% during the first year postpartum depending on the assessment method (i.e., self-report measures, clinical interview), timing of the as- sessment (i.e., first, second, or third trimester of pregnancy or number of weeks after delivery), and population character- istics.14 Depressive symptoms that occur during this specific reproductive time are a serious mental health problem in the general population, and the consequences have critical im- plications for the mother; mother-infant relationship15; the emotional, behavioral, and cognitive development of the child16,17; and marital and family relationships.18 Early diag- nosis and treatment interventions are critical to ensure the welfare of the mother, child, and family.

Only a few studies have examined the prevalence and risk factors of perinatal depression in high-risk populations, such as HIV-infected women and at-risk HIV-uninfected women. To our knowledge, only one study has examined the rate of perinatal depression among HIV-infected women. That study was a retrospective cohort design and involved 273 pre- dominantly minority HIV-infected women from Los Angeles between 1997 and 2006.19 Perinatal depression was based on medical records or multidisciplinary chart notes indicating an onset of depression during pregnancy and/or within 4 weeks after delivery. The overall prevalence of perinatal depression was 30.8%, of depression during pregnancy was 22%, and of depression within 4 weeks postpartum was 18.3%. Estimates of the rate of perinatal depressive symptoms in HIV-infected women were not presented in the study.

There is also limited research on potential risk factors for perinatal depression in HIV-infected women. Only one study in HIV-infected women specifically examined correlates of depression in both the pregnancy and postpartum periods.

Kapetanovic et al.19 reported that past history of a psychiatric illness, substance use during pregnancy, social stress during pregnancy, and lower CD4 + pregnancy nadir were associ- ated with an increased risk of perinatal depression as defined by medical records and multidisciplinary notes in their sam- ple of HIV-infected women (n = 273). Other studies have at- tempted to elucidate the predictors of depressive symptoms in HIV-infected women during either pregnancy or postpar- tum but not both time periods. One study (n = 307) examined correlates of depression during pregnancy as defined by the Center of Epidemiological Studies—Depression scale (CES-D) (interval measure with somatic items removed) in a sample of young, pregnant ( ‡ 24 weeks), HIV-infected women who were predominantly low-income, low-education ( < 12 years), and minority women (71% African American, 20% Hispan- ic).20 Depression during pregnancy was significantly associ- ated with ineffective coping styles, stress, social isolation, and drug and alcohol use. Another study (n = 245) examined postpartum depressive symptoms operationally defined by the CES-D (median split of ‡ 15 was used to define depres- sion) in a sample of young, low-income, low-education ( < 12 years), unmedicated, asymptomatic HIV-infected patients who had recently given birth (18–24 months postpartum) in Thailand.21 Postpartum depression was related to broken relationships, ineffective coping strategies, having an HIV- infected infant, and nondisclosure of HIV status to others. Taken together, these studies help to elucidate some of the determinants of depression during pregnancy and the post- partum period in HIV-infected women.

The primary objective of the present investigation was to assess the prevalence of elevated perinatal depressive symp- toms in a sample of HIV-infected vs. at-risk HIV-uninfected women. The study design involved prospective evaluations of depressive symptoms as measured by the CES-D scale during preconception, pregnancy, and postpartum. Based on previous findings, we hypothesized that perinatal depressive symptoms would be increased in HIV-infected compared to at-risk HIV- uninfected women. The secondary objective was to examine risk factors for elevated perinatal depressive symptoms in HIV- infected and at-risk HIV-uninfected women. Given demon- strations that risky health behaviors7,12 (e.g., drug use, multiple sexual partners), sociodemographic factors12 (e.g., ethnicity, education, income), and service features6 (e.g., insurance sta- tus, use of mental health services) related to depressive symptoms in past studies of HIV-infected women, we exam- ined these factors as risk factors of elevated perinatal depres- sive symptoms. We also examined unintended pregnancy as an additional risk factor, given that unintended pregnancy is associated with an increase in smoking, illicit drug use, and alcohol use compared with intended pregnancy.22

Materials and Methods

Study population

WIHS is a longitudinal, multicenter study of the natural and treated history of HIV in women and includes six clinical sites: Bronx/Manhattan and Brooklyn, NY; Chicago, IL; Washington, DC; and San Francisco and Los Angeles, CA.23,24

Starting in 1994–1995 and again in 2001–2002 and with insti- tutional review board approval, HIV-infected and at-risk uninfected women matched by age, race/ethnicity, level of education, recruitment site, and risk factors, including history

1288 RUBIN ET AL.

of injection drug use and number of sexual partners were enrolled into WIHS.23,24 The HIV-uninfected women are considered at-risk because they are low income and they en- gage in high rates of risky behaviors (e.g., drug use, multiple sex partners), which are risk factors for HIV.

Women eligible for WIHS were aged ‡ 13 years and were able to provide informed consent and complete an interview in either English or Spanish. Although enrollment has been closed since the end of 2002, participants continue to undergo a clinical examination and extensive interview and provide biologic specimens every 6 months. Study methodology, training, and quality assurance procedures and the cohort’s baseline characteristics have been reported previously.23,24

The study sample for this analysis was restricted to WIHS participants who experienced one or more pregnancies be- tween October 1994 and May 2005 (n = 531), experienced a live birth (n = 474), had a known delivery date on file (n = 447), and had CES-D scores across three reproductive stages: precon- ception ( > 10 months before delivery), pregnancy ( £ 10 months before delivery), and postpartum ( £ 12 months after delivery)(N = 244). The primary reason why only 244 of the 447 with known delivery dates had CES-D scores available for each of the three stages was that WIHS administered the CES-D annually from 1994 until October 1998 and then began more frequent administrations, every 6 months, from October 1998 until the present. In the Results section we compare the characteristics of women who were included in this analysis and those who were excluded. CES-D scores at all three time points were necessary because (1) the primary outcome measure (i.e., perinatal depression) was operationally defined as elevated depressive symptoms during pregnancy and/or within 1 year postpartum and (2) the predictor variables, in- cluding elevated depressive symptoms before pregnancy, were from the preconception study visit.

Measures

Depressive symptoms. Elevated perinatal depressive symptoms were assessed with the CES-D,25 a 20-item self- report measure. In accordance with standard definitions of perinatal depression,14 elevated perinatal depressive symp- toms were defined as a CES-D score ‡ 16 during pregnancy ( £ 10 months before delivery) and/or postpartum ( £ 12 months after delivery). In secondary analyses, we examined a more stringent cutoff of 23 and an interval-level version of the sub- scale that excluded somatic items (i.e., fatigue, poor appetite, lack of energy, restlessness, poor concentration) similar to HIV symptoms. The CES-D has excellent reliability, validity, and factor structure25 and is commonly used in studies of HIV,12

including women with HIV.26 Its sensitivity for the DSM diag- nosis of major depression is excellent, in the range of 80%–90%, with a somewhat lower specificity, in the range of 70%–80%.27– 29 The Black Women’s Health Study has demonstrated that the CES-D is a valid measure in African American women.30

Independent measures/potential risk factors of perinatal depressive symptoms. Potential predictors of perinatal de- pression were obtained from the preconception visit, which was defined as the most recent visit at least 10 months before delivery. WIHS participants are asked about health-related variables in the 6 months since their last visit, so these pre- conception variables represent status/exposure in the 6 months preceding the preconception visit (e.g., drug use

represents drug use within the 6 months preceding the pre- conception visit). In addition to HIV status, we examined risky health behaviors, including current smoking status, alcohol—abstainer, light ( < 3 drinks/week), moderate (3–13 drinks/week), heavy ( ‡ 14 drinks/week)—marijuana/hash use, crack, cocaine, and/or heroin use, and current number of sexual partners (male and/or female, < 2, ‡ 2). The socio- demographic factors examined included age, race (Hispanic, African American, Caucasian), level of education ( < high school education, ‡ high school education), average house- hold income ( £ $12,000, > $12,000), employment status, marital status (married/partner, all others). We also exam- ined intention of getting pregnant, depression during pre- conception (CES-D ‡ 16 greater than 10 months before delivery), and service features, including current insurance and use of mental health services. Interactions were also ex- amined between HIV status and risky health behaviors, so- ciodemographic factors, service features, and intention of getting pregnant. In analyses restricted to HIV-infected wo- men, additional variables included HAART use (yes, no), HAART adherence ( ‡ 95% of the time considered adherent, < 95% of the time considered nonadherent), CD4 + cell count (an indicator of the progress of HIV infection where lower counts indicate more severe disease) ( < 200, 200–500, > 500 cells/lL), and viral load (a measurement of the amount of HIV in the blood where higher counts indicate more severe disease) (HIV RNA using cutoffs of 500 and 10,000 copies/mL).

Statistical analysis

Differences between HIV-infected and uninfected women in characteristics measured at preconception were examined using independent t tests for continuous variables and chi- square tests for categorical variables. To compare the preva- lence of perinatal depression (i.e., ‡ 16 on the CES-D during pregnancy and/or postpartum) in HIV-infected vs. uninfected women, chi-square analyses were conducted. To compare the prevalence on the interval-level version of the subscale that excluded somatic items, an independent t test was conducted. Next, logistic regression models were used to identify signif- icant predictors (i.e., serostatus, risky health behaviors, so- ciodemographic factors, service features, intention to get pregnant as well as interactions with serostatus) of elevated perinatal depressive symptoms first in the entire sample and then separately for HIV-infected and at-risk uninfected wo- men. Forward and backward selection procedures were used to determine the best predictors of elevated perinatal depres- sive symptoms. Likelihood ratio tests were used to compare models, and the most parsimonious model was selected. All p values were two-sided. The statistical significance level was set at p = 0.10 in order to examine marginally significant results/ trends (standard criteria in the literature). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each of the significant predictor variables using maximum likelihood estimates from logistic regression models. All analyses were conducted using SAS (version 9.2 for Windows, Cary, NC).

Results

Sample characteristics at preconception

Of the 244 participants, 139 were HIV-infected women and 105 were at-risk HIV-uninfected women. Each woman was

PERINATAL DEPRESSIVE SYMPTOMS AND HIV 1289

included in the analysis only once and was included for the first birth in WIHS only. Overall, the 244 women included in the analysis were similar across most sociodemographic and clinical variables to the 230 women who experienced a live birth but did not have a known delivery date on file or CES-D scores for each of the three reproductive stages. The exception was that women included in the analysis more frequently reported crack, cocaine, and/or heroin use during precon- ception (15%) compared to women not included in the anal- ysis (5%); chi-square (1, n = 474) = 11.31, p < 0.001.

Table 1 provides demographic information at preconcep- tion for both HIV-infected (n = 139) and uninfected (n = 105) women and for the two groups combined (n = 244). The sample ranged in age from 17 to 44 years (mean = 29.38, standard deviation [SD] = 5.70). Notably, our sample was largely representative of HIV-infected women in the United States in terms of ethnicity (62% African American), educa- tion (55% high school graduates or equivalent), employment status (39% employed), and household income (54% with < $12,000/year).31 Among HIV-infected women, the median CD4 + lymphocyte count was 423 cells/lL (range 0–1608, median 423), and 8% had CD4 + cell counts < 200 cells/lL. Fifty percent had been prescribed antiretroviral (ARV) ther- apy, and 77% were treatment adherent.32 Plasma viral load was undetectable for 31%, above the lower limit of quantita- tion (LLQ) but < 10,000 copies/mL for 42% and > 10,000 copies/mL for 27% of HIV-infected women.

Overall, HIV-infected and uninfected women were similar across many sociodemographic, clinical, and behavioral var- iables, although there were significant differences between HIV-infected and uninfected women in mean age (30.37 vs. 28.08 years, p = 0.002), health insurance status (80% vs. 64% insured, p = 0.01), and current number of sex partners (17% vs. 38% with ‡ 2 partners, p = 0.001). There were also trends for HIV-infected and uninfected women to differ on marijuana/ hash use (20% vs. 31%, p = 0.07) and use of mental health services (17% vs. 10%, p = 0.095) during preconception.

Prevalence of perinatal depressive symptoms

Table 2 provides the frequency of clinically significant depressive symptoms during preconception, pregnancy, postpartum, and perinatal for HIV-infected women, HIV- uninfected at-risk women, and for the two groups combined. The overall prevalence of elevated perinatal depressive symptoms across the two groups combined was 46%. There were no significant differences in overall prevalence as a function of HIV serostatus ( p = 0.44). There were no signifi- cant differences between HIV-infected and HIV-uninfected women in the prevalence of depressive symptoms during preconception ( p = 0.44), pregnancy ( p = 0.50; first trimester, p = 0.51; second trimester, p = 0.40; third trimester, p = 0.98), or postpartum ( p = 0.49).

In some studies of HIV-infected women, probable depres- sion is defined with a more stringent cutoff of 23 or with an interval-level version of the subscale that excludes somatic items that overlap with symptoms of HIV.6,20 Notably, the prevalence of elevated perinatal depressive symptoms did not differ by HIV serostatus using the more stringent cutoff of 23 (HIV-infected 26%, HIV-uninfected 31%, p = 0.47). There were also no differences between HIV-infected and HIV-uninfected women on the interval level version of the scale excluding

somatic items during preconception ( p = 0.91), pregnancy ( p = 0.26; first trimester, p = 0.25; second trimester, p = 0.82; third trimester, p = 0.92), or postpartum ( p = 0.43).

Risk factors of perinatal depressive symptoms

Table 3 provides the significant predictors from the final logistic regression models examining predictors of perinatal depressive symptoms (CES-D ‡ 16) in the entire sample (n = 244) and in HIV-infected (n = 139) and HIV-uninfected (n = 105) women separately. In the overall sample, precon- ception depression ( p < 0.001), education (less than high school, p = 0.03), current number of sexual partners precon- ception ( ‡ 2 partners, p = 0.02), and mental health service use preconception ( p = 0.04) were significant predictors of peri- natal depressive symptoms (i.e., during pregnancy and/or postpartum); crack, cocaine, and/or heroin use preconception was a marginally significant predictor ( p = 0.08). Serostatus was not a significant predictor of perinatal depressive symptoms in the overall sample and, thus, was not included in the final model. Among HIV-infected women, preconcep- tion elevated perinatal depressive symptoms ( p < 0.001) was a significant predictor of perinatal depression, and crack, co- caine, and/or heroin use almost reached statistical signifi- cance ( p = 0.058). Among at-risk HIV-uninfected women, preconception depression ( p < 0.001) and current number of sexual partners preconception ( ‡ 2 partners, p = 0.01) were significant predictors of perinatal depressive symptoms, and having less than a high school education almost reached sta- tistical significance ( p = 0.08).

In models using a more stringent CES-D cutoff of 23, many of the same variables were significant. In the overall sample, serostatus was not a significant predictor and, thus, was not included in the final models. Significant predictors in the overall sample included preconception depression (OR 4.78, 95% CI 2.51-9.08, p < 0.001), current number of sexual partners preconception ( ‡ 2 partners, OR 2.05, 95% CI 1.06-3.96, p = 0.03), and average household income ( £ $12,000, OR 2.19, 95% CI 1.16-4.14, p = 0.02). Among HIV-infected women, the only significant predictors of elevated perinatal depressive symptoms were preconception depressive symptoms (OR 7.50, 95% CI 3.05-18.41, p < 0.001) and average household income ( £ $12,000, OR 2.79, 95% CI 1.13-6.89, p = 0.03). Among at-risk HIV-uninfected women, preconception depression (OR 3.38, 95% CI 1.33-8.56, p < 0.001), and current number of sexual partners preconception ( ‡ 2 partners, OR 3.18, 95% CI 1.29- 7.83, p = 0.01) were significant predictors.

In models using the interval-level version of the subscale, serostatus was not a significant predictor of elevated de- pressive symptoms during the perinatal period (pregnancy or postpartum) (Table 4). Significant predictors in the overall sample included preconception depression ( p < 0.001), cur- rent number of sexual partners preconception ( p < 0.01), having less than a high school education ( p = 0.02), and crack, cocaine, and/or heroin use ( p = 0.01). Among HIV-infected women, the only significant predictors of perinatal depressive symptoms were preconception depression ( p < 0.001) and being of Hispanic origin ( p = 0.02); mental health service use preconception ( p = 0.05) and average household income ( £ $12,000, p = 0.05) were marginally significant predictors. Among at-risk HIV-uninfected women, preconception de- pression ( p < 0.001) and current number of sexual partners

1290 RUBIN ET AL.

preconception ( p < 0.03) were significant predictors. Crack, cocaine, and/or heroin use was a marginally significant pre- dictor ( p = 0.09) during pregnancy and significant during postpartum ( p = 0.03).

Discussion

The aim of this article was twofold: first, to assess the prevalence of clinically significant perinatal depressive

symptoms in a sample of HIV-infected vs. uninfected women and, second, to examine risk factors for elevated perinatal depressive symptoms in both HIV-infected and uninfected women. Consistent with previous findings,19 the proportion of women with elevated perinatal depressive symptoms was high in our sample before conception (39%) and in the peri- natal period (46%). There were no differences between HIV- infected and uninfected women in likelihood of clinically significant depressive symptoms. HIV-infected women were

Table 1. Demographics at Preconception ( > 10 Months Before Delivery) for HIV-Infected Women, HIV-Uninfected Women, and the Two Groups Combined (n = 244)

HIV status

HIV-infected n = 139 HIV-uninfected n = 105 Overall sample n = 244 Variables n (%) n (%) n (%)

Age (mean, SD)** 30.37 (5.37) 28.08 (5.90) 29.38 (5.71) Race

African American 90 (65) 60 (57) 150 (62) Hispanic 37 (27) 38 (36) 75 (31) White 27 (19) 16 (15) 43 (18)

At least high school graduate or equivalent 75 (54) 58 (55) 133 (55) Currently employed 52 (37) 43 (41) 95 (39) Currently married 57 (41) 39 (37) 96 (39) Average household Income ( £ $12,000/year) 77 (55) 54 (51) 131 (54) Carrying insurance** 111 (80) 67 (64) 178 (73) Current number of sex partners ( ‡ 2)*** 24 (17) 40 (38) 64 (26) Trying to get pregnant 88 (63) 76 (72) 164 (67) Mental health services{ 24 (17) 10 (10) 34 (14) Recent usea

Smoking 66 (48) 46 (44) 112 (46) Alcohol

Abstainer 70 (50) 41 (39) 111 (46) Light ( < 3 drinks/week) 46 (33) 41 (39) 87 (36) Moderate (3–13 drinks/week) 18 (13) 13 (12) 31 (12) Heavy ( ‡ 14 drinks/week) 5 (4) 10 (10) 15 (6)

Marijuana/hash{ 28 (20) 32 (31) 60 (25) Crack/freebase cocaine 15 (11) 11 (11) 26 (11) Cocaine 7 (5) 8 (8) 15 (6) Heroin 3 (2) 7 (7) 10 (4) Composite crack, cocaine, and/or heroin 19 (14) 18 (17) 37 (15)

Disease CD4 number > 500 59 (42) - - ‡ 200 and £ 500 69 (50) - - < 200 11 (8) - - Viral load (HIV RNA, copies/mL)

Undetectable 43 (31) - - < 10,000 58 (42) - - ‡ 10,000 38 (27) - -

Medication use HAART 47 (34) - - Non-HAART 22 (16) - - ARV naive 70 (50) - -

Medication compliance ( ‡ 95%)b 36 (77) - - Intervals (days: Mean, SD)

Preconception ( > 300 days before delivery) 440.30 (88.49) 453.81 (123.66) 446.11 (105.05) Pregnancy ( £ 300 days before delivery) 116.76 (74.32) 111.66 (76.58) 114.57 (75.19) Postpartum ( £ 365 days after delivery) 146.92 (82.10) 143.29 (83.83) 145.36 (82.70) aRecent use refers to within 6 months of the preconception Women’s Interagency HIV Study (WIHS) visit. bData were only available on 47 of the 69 women taking medication because this information was not collected until October 1998 in the

WIHS. Therefore, the percentage of women who were medication compliant is based on 36 of 47 women. ***p < 0.001; **p < 0.01. {p > 0.05 and p < 0.10. ARV, antiretroviral; HAART, highly active antiretroviral therapy; SD, standard deviation.

PERINATAL DEPRESSIVE SYMPTOMS AND HIV 1291

at increased risk for perinatal depression if they had a history of elevated depressive symptoms preconception or used crack, cocaine, and/or heroin preconception, although the substance use effect just missed statistical significance (p = 0.06). Additional risk factors for perinatal depressive symptoms across the combined sample of HIV-infected and

uninfected women included lower education, current number of sexual partners before pregnancy, and mental health ser- vice use before pregnancy.

Our data suggest that the occurrence of clinically signifi- cant depressive symptoms before pregnancy is a strong pre- dictor of perinatal depression in both HIV-infected and

Table 2. Frequency of Depressive Symptoms ( ‡ 16) as Measured by Center for Epidemiologic Studies-Depression Scale as Function of Stage of Pregnancy for HIV-Infected Women,

At-Risk HIV-Uninfected Women, and the Two Groups Combined (n = 244)

HIV Status

Infected (n = 139) Uninfected (n = 105) Overall sample n = 244 Stage of pregnancy n (%) n (%) n (%)

Preconception 58 (42) 38 (36) 96 (39) Pregnancya 47 (34) 40 (38) 87 (36)

First trimester 7 (35) 7 (47) 14 (40) Second trimester 24 (44) 21 (54) 45 (48) Third trimester 30 (47) 24 (47) 54 (47)

Postpartum 43 (31) 37 (35) 80 (33) Perinatalb 61 (44) 52 (50) 113 (46)

aThere were no significant differences in elevated depressive symptoms across trimesters in the overall sample ( p = 0.72), HIV-infected women ( p = 0.65), or HIV-uninfected women ( p = 0.79).

bPerinatal depression was defined as ‡ 16 on the CES-D during pregnancy ( £ 10 months before delivery) and/or postpartum ( £ 12 months following delivery). Perinatal depression was the primary outcome variable in the regression analyses.

Table 3. Significant Predictors from the Final Logistic Regression Models Examining Predictors of Perinatal Depressive Symptoms ( ‡ 16 on Center for Epidemiologic Studies-Depression Scale

During Pregnancy and/or Postpartum) in the Overall Sample (n = 244) and in HIV-Infected (n = 139) and HIV-Uninfected (n = 105) Women Separately

Sample Significant predictors OR 95% CI p value

Overall sample (n = 244) Preconception depression <0.001 No, CES-D < 16 (n = 148) 1.00 Reference Yes, CES-D ‡ 16 (n = 96) 5.62 3.08-10.27

Education 0.03 At least high school or equivalent (n = 133) 1.00 Reference Less than high school (n = 111) 1.92 1.06-3.46

Crack, cocaine, and/or heroin use preconception 0.08 No use (n = 207) 1.00 Reference Any use (n = 37) 2.24 0.92-5.46

Current number of sexual partners 0.02 < 2 (n = 180) 1.00 Reference ‡ 2 (n = 64) 2.20 1.12-4.32

Mental health services used preconception 0.04 No use of services (n = 210) 1.00 Reference Use of services (n = 34) 2.51 1.03-6.13

HIV-infected (n = 139) Preconception depression <0.001 No, CES-D < 16 (n = 78) 1.00 Reference Yes, CES-D ‡ 16 (n = 61) 5.71 2.67-12.19

Crack, cocaine, and/or heroin use preconception 0.06 No use (n = 120) 1.00 Reference Any use (n = 19) 3.10 0.96-10.01

HIV-uninfected (n = 105) Preconception depression <0.001 No, CES-D < 16 (n = 67) 1.00 Reference Yes, CES-D ‡ 16 (n = 38) 8.96 3.26-24.65

Education 0.08 At least high school or equivalent (n = 58) 1.00 Reference Less than high school (n = 47) 2.31 0.91-5.84

Current number of sexual partners <0.01 < 2 (n = 65) 1.00 Reference ‡ 2 (n = 40) 3.54 1.38-9.10

CI, confidence interval; OR, odds ratio.

1292 RUBIN ET AL.

uninfected women. This logical finding stresses the impor- tance of screening and treatment of depression in the pre- conception period that may lead to depression in the perinatal period. Additionally, our findings stress the need for contin- ued monitoring and management of depression in HIV- infected women and in at-risk HIV-uninfected women during pregnancy and the postpartum period. Substance use (crack, cocaine, and/or heroin) was a marginally significant predictor of perinatal depressive symptoms, particularly among HIV- infected women ( p = 0.06). Substance abuse, like HIV disease, has been associated with depression12 and has been shown to affect treatment adherence.6,7 Thus, consideration of sub- stance use among HIV-infected women remains of particu- lar importance when studying depression in general. Having multiple sex partners was a significant predictor of peri- natal depressive symptoms, particularly among at-risk HIV-uninfected women. Risky sexual behaviors, specifically having multiple sex partners, has also been associated with depression in a number of samples including both African American and white women,33 impoverished women,34 and inner-city drug users.35 Continued reinforcement needs to be placed on the negative consequences of risky sexual behaviors in at-risk HIV-uninfected women, which may help to reduce depression as well as HIV transmission.

HIV-infected women in our study did not show elevated perinatal depressive symptoms when compared to at-risk HIV-uninfected women. Factors, such as having multiple sexual partners, low education, mental health service use, and drug use (crack, cocaine, and/or heroin), were more important than serostatus in predicting perinatal depression in WIHS women overall. Although HIV-infected women may have a presumed vulnerability to perinatal depression because of their medical status, there are four possible reasons why the prevalence rates did not differ. First, HIV-infected women in our study and in the community frequently have greater ac- cess to medical care and social services compared with at-risk HIV-uninfected women,36 and this may mitigate against ele-

vated depressive symptoms. Second, women are living longer with HIV; thus, there are fewer concerns about low life ex- pectancy in the context of raising a child. Third, the risk of mother-to-child transmission of HIV has been significantly reduced from rates of 25%–30%37 to < 1%38 given routine HIV screening of pregnant women, use of ARV drugs and zido- vudine therapy, avoidance of breastfeeding, and use of ce- sarean deliveries. Fourth, this sample, like the larger WIHS sample from which it was drawn, has a high background rate of depression6,7,28,39 in part because of prevalence of other factors, including high rates of substance abuse. Those factors appear to have a stronger link to depression than pregnancy. However, this finding may be unique to the WIHS cohort and, thus, our findings need to be replicated in other prospective cohorts of pregnant women with HIV.

The present study is limited by several factors. First, we focused on elevated depressive symptoms as a marker of clinically relevant perinatal depression because we did not have clinical diagnoses. A better approach would have been to use a diagnostic interview, such as the Structured Clinical Interview for the DSM (SCID), to measure clinical depres- sion.6 Second, we did not have data on obstetric factors that may be associated with depression (e.g., preeclampsia, ges- tational diabetes, prematurity, HIV transmission to the infant, neonatal intensive care unit admissions, or other maternal or infant complications). We also lacked data on potential psy- chosocial predictors, including coping style, social stress, and broken relationships, as well as antidepressant use. Although these variables were not available for all the women in this study, these variables are currently being collected in WIHS and can be examined in future studies. Third, we did not have complete data for all women with live births in the WIHS, and this may have introduced biases. The primary reason CES-D scores were missing was because the CES-D was only ad- ministered annually at the onset of WIHS compared to once every 6 months later on. There was an overrepresentation of crack, cocaine, and/or heroin use among HIV-infected women

Table 4. Significant Predictors from the Final Regression Models Examining Predictors of Perinatal Depressive Symptoms (Interval-Level Subscale on Center for Epidemiclogic Studies-Depression

Scale During Pregnancy and Postpartum) in the Overall Sample (n = 244) and in HIV-Infected (n = 139) and HIV-Uninfected (n = 105) Women Separately

Stage

Pregnancy Postpartum

Sample b p b p

Overall sample (n = 244) Preconception depression 0.60 <0.001 0.47 <0.001 Current number of sexual partners ‡ 2 0.14 0.01 - - Having less than a high school education 0.12 0.02 - - Crack, cocaine, and/or heroin use preconception - - 0.14 0.01

HIV-infected (n = 139) Preconception depression 0.65 <0.001 0.55 <0.001 Hispanic origin 0.16 0.02 - - Mental health service use preconception - - 0.14 0.05 Average household income £ $12,000 - - 0.14 0.05

HIV-uninfected (n = 105) Preconception depression 0.53 <0.001 0.36 <0.001 Current number of sexual partners ‡ 2 0.19 0.02 - - Crack, cocaine, and/or heroin use preconception 0.14 0.09 0.20 0.03

PERINATAL DEPRESSIVE SYMPTOMS AND HIV 1293

who become pregnant in WIHS but an underrepresentation of use among HIV-infected women regardless of pregnancy status.7,40 Thus, the present results may still not be general- izable to the broader population of HIV-infected women who become pregnant. Our findings with respect to illicit sub- stances as a predictor of perinatal depression particularly among HIV-infected women are important, however, as this factor seems to have a stronger link to perinatal depression than serostatus.

Future studies need to examine these variables as potential risk factors of perinatal depression in large samples of HIV- infected women with demographically matched comparison groups. Finally, as previously mentioned, women with HIV in WIHS receive social, medical, and other benefits by partici- pating in WIHS, and these factors might mitigate against depressive symptoms. Therefore, studies are needed to see if HIV influences perinatal symptoms in women who do not benefit from participation in prospective clinical studies.

Conclusions

This is the first study to prospectively compare the preva- lence of perinatal depressive symptoms in HIV-infected and at-risk HIV-uninfected women and to identify predictors of elevated perinatal depressive symptoms in these two groups. The present findings suggest that the risk of elevated peri- natal depressive symptoms (1) does not differ between HIV- infected and at-risk HIV-uninfected women, (2) is associated with a history of depression before conception in both HIV- infected and HIV-uninfected women, and (3) is associated with illicit substances (i.e., crack, cocaine, and/or heroin), particularly among HIV-infected women. Identification and treatment of depression when a woman is trying to conceive may lead to decreased perinatal depression. HIV-infected women who use illicit substances should be monitored for the presence of elevated perinatal depressive symptoms.

Acknowledgments

Data in this article were collected by the Women’s Inter- agency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington, DC, Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Con- sortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Al- lergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI- 42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131). This publication was also made possible by Grant Number K12HD055892 from the National Institute of Child Health and Human Development (NICHD) and the National Institutes of Health Office of Re- search on Women’s Health (ORWH). The contents of this publication are solely the responsibility of the authors and do

not necessarily represent the official views of the National Institutes of Health.

The data were presented at the Society of Biological Psy- chiatry, Vancouver, Canada, May 14–16, 2009.

Disclosure Statement

No competing financial interests exist.

References

1. Gaynes BN, Pence BW, Eron JJ Jr., Miller WC. Prevalence and comorbidity of psychiatric diagnoses based on reference standard in an HIV + patient population. Psychosom Med 2008;70:505–511.

2. Pence BW, Miller WC, Whetten K, Eron JJ, Gaynes BN. Prevalence of DSM-IV-defined mood, anxiety, and substance use disorders in an HIV clinic in the Southeastern United States. J Acquir Immune Defic Syndr 2006;42:298–306.

3. Berger-Greenstein JA, Cuevas CA, Brady SM, Trezza G, Richardson MA, Keane TM. Major depression in patients with HIV/AIDS and substance abuse. AIDS Patient Care STDs 2007;21:942–955.

4. Ciesla JA, Roberts JE. Meta-analysis of the relationship be- tween HIV infection and risk for depressive disorders. Am J Psychiatry 2001;158:725–730.

5. Hartzell JD, Janke IE, Weintrob AC. Impact of depression on HIV outcomes in the HAART era. J Antimicrob Chemother 2008;62:246–255.

6. Cook JA, Cohen MH, Burke J, et al. Effects of depressive symptoms and mental health quality of life on use of highly active antiretroviral therapy among HIV-seropositive wo- men. J Acquir Immune Defic Syndr 2002;30:401–409.

7. Cook JA, Grey DD, Burke-Miller JK, et al. Illicit drug use, depression and their association with highly active anti- retroviral therapy in HIV-positive women. Drug Alcohol Depend 2007;89:74–81.

8. Bangsberg DR, Hecht FM, Charlebois ED, et al. Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population. AIDS 2000;14: 357–366.

9. Ledergerber B, Egger M, Opravil M, et al. Clinical progres- sion and virological failure on highly active antiretroviral therapy in HIV-1 patients: A prospective cohort study. Swiss HIV Cohort Study. Lancet 1999;353:863–868.

10. Paterson DL, Swindells S, Mohr J, et al. Adherence to pro- tease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000;133:21–30.

11. Garcia de Olalla P, Knobel H, Carmona A, Guelar A, Lopez- Colomes JL, Cayla JA. Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients. J Acquir Immune Defic Syndr 2002;30:105–110.

12. Moore J, Schuman P, Schoenbaum E, Boland B, Solomon L, Smith D. Severe adverse life events and depressive symp- toms among women with, or at risk for, HIV infection in four cities in the United States of America. AIDS 1999;13: 2459–2468.

13. Leserman J. Role of depression, stress, and trauma in HIV disease progression. Psychosom Med 2008;70:539–545.

14. Gaynes BN, Gavin N, Meltzer-Brody S, et al. Perinatal de- pression: Prevalence, screening accuracy, and screening outcomes. Evid Rep Technol Assess No. 119. 2005:1–8.

15. Beck CT. The effects of postpartum depression on maternal- infant interaction: A meta-analysis. Nurs Res 1995;44:298–304.

1294 RUBIN ET AL.

16. Beck CT. The effects of postpartum depression on child de- velopment: A meta-analysis. Arch Psychiatr Nurs 1998;12:12–20.

17. Sohr-Preston SL, Scaramella LV. Implications of timing of maternal depressive symptoms for early cognitive and lan- guage development. Clin Child Fam Psychol Rev 2006;9:65–83.

18. Manopaiboon C, Shaffer N, Clark L, et al. Impact of HIV on families of HIV-infected women who have recently given birth, Bangkok, Thailand. J Acquir Immune Defic Syndr Hum Retrovirol 1998;18:54–63.

19. Kapetanovic S, Christensen S, Karim R, et al. Correlates of perinatal depression in HIV-infected women. AIDS Patient Care STDs 2009;23:101–108.

20. Blaney NT, Fernandez MI, Ethier KA, Wilson TE, Walter E, Koenig LJ. Psychosocial and behavioral correlates of de- pression among HIV-infected pregnant women. AIDS Pa- tient Care STDs 2004;18:405–415.

21. Bennetts A, Shaffer N, Manopaiboon C, et al. Determinants of depression and HIV-related worry among HIV-positive women who have recently given birth, Bangkok, Thailand. Soc Sci Med 1999;49:737–749.

22. Than LC, Honein MA, Watkins ML, Yoon PW, Daniel KL, Correa A. Intent to become pregnant as a predictor of ex- posures during pregnancy: Is there a relation? J Reprod Med 2005;50:389–396.

23. Barkan SE, Melnick SL, Preston-Martin S, et al. The Wo- men’s Interagency HIV Study. WIHS Collaborative Study Group. Epidemiology 1998;9:117–125.

24. Bacon MC, von Wyl V, Alden C, et al. The Women’s Inter- agency HIV Study: An observational cohort brings clinical sciences to the bench. Clin Diagn Lab Immunol 2005;12: 1013–1019.

25. Radloff LS. The CES-D scale: A self-report depression scale for research in the general population. Appl Psychol Meas 1977;1:385–401.

26. Ickovics JR, Hamburger ME, Vlahov D, et al. Mortality, CD4 cell count decline, and depressive symptoms among HIV- seropositive women: Longitudinal analysis from the HIV Epidemiology Research Study. JAMA 2001;285:1466–1474.

27. Low-Beer S, Chan K, Yip B, et al. Depressive symptoms decline among persons on HIV protease inhibitors. J Acquir Immune Defic Syndr 2000;23:295–301.

28. Richardson J, Barkan S, Cohen M, et al. Experience and covariates of depressive symptoms among a cohort of HIV infected women. Soc Work Health Care 2001;32:93–111.

29. Breslau N. Depressive symptoms, major depression, and generalized anxiety: A comparison of self-reports on CES-D and results from diagnostic interviews. Psychiatry Res 1985; 15:219–229.

30. Williams CD, Taylor TR, Makambi K, et al. CES-D four-factor structure is confirmed, but not invariant, in a large cohort of African American women. Psychiatry Res 2007;150:173–180.

31. Centers for Disease Control and Prevention. MMWR anal- ysis provides new details on HIV incidence in U.S. popula- tions, 2008.

32. Department of Health and Human Services/Henry J. Kaiser Family Foundation Panel on Clinical Practices for the Treatment of HIV infection. Guidelines for the use of anti- retroviral agents in HIV-infected adults and adolescents, 2004 revision. Available at aidsinfo.nih.gov/guidelines/ adult/AA_040705.pdfOctober

33. Khan MR, Kaufman JS, Pence BW, et al. Depression, sexu- ally transmitted infection, and sexual risk behavior among young adults in the United States. Arch Pediatr Adolesc Med 2009;163:644–652.

34. Nyamathi AM, Bennett C, Leake B. Predictors of maintained high-risk behaviors among impoverished women. Public Health Rep 1995;110:600–606.

35. Williams CT, Latkin CA. The role of depressive symptoms in predicting sex with multiple and high-risk partners. J Acquir Immune Defic Syndr 2005;38:69–73.

36. Palacio H, Li X, Wilson TE, et al. Healthcare use by varied highly active antiretroviral therapy (HAART) strata: HAART use, discontinuation, and naivety. AIDS 2004;18:621–630.

37. Lindegren ML, Byers RH Jr., Thomas P, et al. Trends in perinatal transmission of HIV/AIDS in the United States. JAMA 1999;282:531–538.

38. Center for Disease Control and Prevention. Achievements in public health: Reduction in perinatal transmission of HIV infection—United States, 1985–2005. MMWR 2006;55: 592–597.

39. Cook JA, Grey D, Burke J, et al. Depressive symptoms and AIDS-related mortality among a multisite cohort of HIV-positive women. Am J Public Health 2004;94:1133– 1140.

40. Wilson TE, Massad LS, Riester KA, et al. Sexual, contra- ceptive, and drug use behaviors of women with HIV and those at high risk for infection: Results from the Women’s Interagency HIV Study. AIDS 1999;13:591–598.

Address correspondence to: Leah H. Rubin, Ph.D.

Department of Psychiatry (MC 913) University of Illinois at Chicago

Chicago, IL 60612

E-mail: [email protected]

PERINATAL DEPRESSIVE SYMPTOMS AND HIV 1295

Copyright of Journal of Women's Health (15409996) is the property of Mary Ann Liebert, Inc. and its content

may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express

written permission. However, users may print, download, or email articles for individual use.