Diabetes and Depression in Pregnancy:
Is There an Association?
Jodie G. Katon, Ph.C.,1Joan Russo, Ph.D.,2Amelia R. Gavin, Ph.D.,3
Jennifer L. Melville, M.D., M.P.H.,4and Wayne J. Katon, M.D.2
Background: Prior studies have reported inconsistent findings regarding the association of antenatal depression
with pregnancy-related diabetes. This study examined the association of diabetes and antenatal depression.
Methods: We conducted a cross-sectional analysis of baseline data from a prospective cohort study of pregnant
women receiving prenatal care at a single University of Washington Medical Center clinic between January 2004
and January 2009. The primary exposure was diabetes in pregnancy (no diabetes, preexisting diabetes, or
gestational diabetes [GDM]). Antenatal depression was defined by the Patient Health Questionnaire-9 (PHQ-9)
score or current use of antidepressants. Antenatal depression was coded as (1) any depression (probable major or
minor depression by PHQ-9 or current antidepressant use) and (2) major depression (probable major depression
by PHQ-9 or current antidepressant use). Logistic regression was used to quantify the association between
diabetes in pregnancy and antenatal depression.
Results: The prevalences of preexisting diabetes, GDM, any antenatal depression, and major antenatal
depression were 9%, 18%, 13.6%, and 9.8%, respectively. In the unadjusted analysis, women with pre-
existing diabetes had 54% higher odds of any antenatal depression compared to those without diabetes
(odds ratio [OR] 1.54, 95% confidence interval [CI] 1.08-2.21). After adjusting for important covariates the
association was attenuated (OR 1.16, 95% CI 0.79-1.71). Results were similar for antenatal major depres-
sion. GDM was not associated with increased odds for any antenatal depression or antenatal major
Conclusions: Neither preexisting diabetes nor GDM was independently associated with increased risk of an-
burden of disease by 2030.1The prevalence of major depres-
sion in women peaks during childbearing years, with recent
estimates indicating that approximately 8%–12% of pregnant
women may meet diagnostic criteria for major depression.2
Antenatal major depression is associated with adverse con-
sequences for offspring during the perinatal period and over
the life course.3Antenatal depression is also associated with
experiencing more discomfort from pregnancy-related phys-
ical symptoms,4increased functional impairment, and greater
marital conflict.5Additionally, antenatal depression is a
lobally, major depressive disorder (MDD) is pro-
jected to be one of the three leading contributors to
strong risk factor for postpartum depression (PPD),5which is
associated with poor maternal-infant bonding6and may have
adverse effects on infant development.3Despite these find-
ings, depressive disorders continue to be underdetected and
undertreated in pregnancy.4
The prevalence of diabetes in pregnancy has risen 122% in
the last 20 years,7largely due to increased prevalence of
gestational diabetes (GDM),8defined as glucose intolerance
with first onset or recognition in pregnancy. There is evidence
of a bidirectional link between depression and diabetes.9
Depression earlier in life increases the risk for development of
type 2 diabetes,9and diabetes-specific complications are as-
sociated with a higher risk of subsequent depression.9,10One
study in a large Medicaid population found that diabetes that
1Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
2Department of Psychiatry & Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington.
3School of Social Work, University of Washington, Seattle, Washington.
4Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, Washington.
JOURNAL OF WOMEN’S HEALTH
Volume 20, Number 7, 2011
ª Mary Ann Liebert, Inc.
precedes pregnancy is associated with depression among
pregnant women,11although the findings with respect to
GDM are less clear.11–14Three earlier studies found that the
mood profile of women with GDM did not differ significantly
from that of women without diabetes in pregnancy.12–14
These were relatively small studies that measured antenatal
depressive symptoms rather than using diagnostic criteria for
major depression. In contrast, using a large sample of preg-
nant women enrolled in Medicaid, Kozhimannil et al.11re-
ported a 2-fold increase in odds of receiving a diagnosis of
perinatal depression (defined as depression in the 6 months
before delivery and in the first year postpartum) among wo-
men with prepregnancy diabetes and GDM compared to
women with no diabetes. Because major depression is un-
likely to remit without treatment, understanding whether or
not diabetes, in particular GDM, is associated with antenatal
major depression is paramount.
The consequences of comorbid diabetes and antenatal de-
pression are still poorly understood. Among women with
GDM, poor glycemic control may be associated with greater
psychologic distress,12and poor glycemic control is, in turn,
associated with increased maternal and neonatal morbidity.15
In the nonpregnant population, comorbid depression has
been shown to be associated with decreased adherence to
diabetes self-care regimens (i.e., diet, exercise, cessation of
smoking, and taking medication as prescribed),16which may
explain in part the increased risk of macrovascular and mi-
crovascular complications and mortality among patients with
comorbid depression and diabetes.17Therefore, understand-
may potentially improve care of women with diabetes in
pregnancy and reduce associated maternal and neonatal
The objective of this study was to examine whether pre-
existing diabetes or GDM was associated with a higher
prevalence of antenatal depression than is found in women
without diabetes in pregnancy. To address these questions,
we conducted a cross-sectional analysis of baseline data from
an ongoing prospective cohort study in a large community-
based sample of pregnant women receiving prenatal care at a
single University of Washington Medical Center clinic be-
tween January 2004 and January 2009.
Materials and Methods
Study design and population
The participants in this study were patients receiving pre-
natal care at a single University of Washington Medical
Center clinic from January 2004 to January 2009. Ques-
tionnaires assessing mood and psychosocial factors were in-
as part of routine clinical care to all patients during preg-
nancy. All women receiving ongoing obstetrical care and
completing at least one clinical questionnaire in either the
second or third trimester during the study time period were
eligible for inclusion in the study. Exclusion criteria included
age <15years at thetimeofdelivery andinability tocomplete
the clinical questionnaire because of mental incapacitation or
language difficulties (i.e., no interpreter available). Clinic staff
were asked to contact and obtain consent from potentially
eligible subjects for study enrollment at the time of screen
completion. Among patients providing written informed
consent, questionnaires were linked to automated medical
records. All procedures were approved by the University of
Washington’s Institutional Review Board.
During the study period, 3347 women completed at least
one psychosocial screening questionnaire at 4 months’ ges-
tation, during the third trimester, or postpartum (Fig. 1). Staff
were present to obtain consent from 2577 (77%) for study
enrollment. A total of 227 (6.8%) declined to participate in this
part of the study, and 543 (16.2%) left the clinic before they
could consent. Of the 2577 women who consented, 2398
(93.1%) completed the psychosocial screen before delivery.
Study variables and measures
The primary exposure in our study was diabetes in preg-
nancy (no diabetes, preexisting diabetes, and GDM). Diag-
of 648.8 in the automated medical record. GDM is clinically
defined as glucose intolerance with first recognition or onset
in pregnancy18; therefore, this diabetes category could po-
tentially include women with previously unrecognized type 2
diabetes. Preexisting diabetes (type 1 or type 2 diabetes) was
defined by a physician ICD-9 diagnosis of 250.x in the auto-
mated medical record. A subset of patients had both an ICD-9
diagnosis of preexisting diabetes and GDM, and these were
reassigned as preexisting diabetes if there was a self-report on
the screening questionnaire of being diagnosed with diabetes
within the previous 3 years, excluding a diagnosis only in
pregnancy, or if there was evidence on self-report of use of
patients with both ICD-9 diagnoses were reassigned as hav-
record and the questionnaire included demographic charac-
teristics, general health history, prior pregnancy complica-
tions, and social history. Maternal age (measured in years)
was obtained from the automated medical record. Women
were asked about their current marital status, which was
analyzed as a categorical variable (married or living with a
partner or not currently partnered). Self-reported race/eth-
nicity was categorized as non-Hispanic white and nonwhite.
Employment status was defined as either employed (full-time
or part-time) or unemployed (in school, retired, homemaker,
unemployed, disabled, other).
Tobacco use was assessed using the Smoke-Free Families
Prenatal Screen, which was specifically developed to maxi-
mize disclosure of smoking status during pregnancy.19Wo-
men with any current smoking were classified as smokers.
The T-ACE was used to assess substance use in the 12 months
before pregnancy.20The T-ACE was developed to identify
risk drinkers and has been validated in a pregnant popula-
tion.20Women were considered to have a history of alcohol
use if they met the criteria for risk drinking in the 12 months
before their current pregnancy.
Women were considered to have a medical comorbidity if
they reported one or more prepregnancy health condi-
tions(excluding diabetes). Prepregnancy health conditions
included asthma, hypertension, arthritis, thyroid disorders,
migraines, gastrointestinal disorders, cancer, seizure disor-
ders, heart failure, other heart disease, or a chronic physical
at depression screening was calculated based on a woman’s
984 KATON ET AL.
expected date of delivery and the date the depression screen
was administered. A history of pregnancy complications was
recorded for women self-reporting one or more significant
complications in a prior pregnancy, including GDM, hyper-
tension or preeclampsia, eclampsia, preterm labor, preterm
delivery, preterm rupture of the membranes, placental
abruption, oligohydramnios, or hemorrhage. Women with no
prior pregnancy were categorized as having no history of
There were two primary study outcomes: any antenatal
depression and antenatal major depression. Any antenatal
depression was defined by a positive diagnosis of probable
major or minor depression on the Patient Health Ques-
tionnaire-9 (PHQ-9)21or use of any antidepressants during
the current pregnancy. Antenatal major depression was de-
fined by a positive diagnosis of probable major depression by
the PHQ-9 or use of any antidepressants during the current
pregnancy. The PHQ-9 identifies major and minor depression
based on Diagnostic and Statistical Manual of Mental Disorders
IV (DSM-IV) criteria.21The DSM-IV criteria for major de-
weeks, five or more depressive symptoms present for more
than half of the days, with at least one of these symptoms
being depressed mood or anhedonia. The criteria for minor
depression require the subject to have, for at least 2 weeks,
two to four depressive symptoms present for more than half
of the days, with at least one of these symptoms being de-
pressed mood or anhedonia. The PHQ-9 has been validated
for diagnosis of major depression among obstetrics/gyne-
cology patients and has a sensitivity of 73% and specificity of
98% for diagnosis of major depression based on the Struc-
tured Clinical Interview for DSM-IV (SCID).21Information on
antidepressant usage was obtained by patient self-report.
Selective serotonin reuptake inhibitors (SSRI) included ser-
traline, fluoxetine, fluvoxamine, paroxetine, citalopram, and
escitalopram. All non-SSRI antidepressants were included in
the other antidepressant category. Self-report of antidepres-
sant use in pregnancy has reasonable agreement with phar-
macy records when it is collected during pregnancy.22In the
final analysis, SSRIs and other antidepressants were com-
bined in the any antidepressant category. Figure 1 shows the
prevalence of antenatal major and minor depression by PHQ-
9 and the use of antidepressants.
Characteristics of women were summarized for the total
sample and by diabetes in pregnancy status. Means and 95%
Study population, depression status by Patient Health Questionnaire-9 (PHQ-9) and antidepressant use.
DIABETES AND DEPRESSION IN PREGNANCY985
and percentages, and 95% CIs are reported for categorical
variables. Means or proportions and 95% CIs of each com-
ponent of our specified antenatal depression outcomes (PHQ-
9 score, probable major and minor depression by PHQ-9
score, and antidepressant medication use) were also reported
for the entire sample and by diabetes in pregnancy status.
The associations between diabetes and any antenatal de-
pression and diabetes and antenatal major depression were
estimated using logistic regression. Four models were fit se-
quentially. The first model included only the primary expo-
sure of diabetes status (none, preexisting diabetes, GDM). The
second model adjusted for demographic characteristics (ma-
ethnicity, education, and employment). The third model ad-
justed for demographic characteristics and the presence of
other chronic medical conditions. The fourth model adjusted
for demographic characteristics, other chronic medical con-
ditions, and pregnancy variables (prior pregnancy, gesta-
tional week at depression screening, and prior pregnancy
complications). Odds ratios (OR) and 95% CIs are reported.
All analysis were completed using STATA 9 (StataCorp,
College Station, TX).
As antenatal depressive symptoms may result from poor
control of GDM, we ran a sensitivity analysis including only
women who had a depression screen at 4 months of gestation.
Antidepressants may be prescribed for conditions other than
excluding women with self-reported antidepressant use and
used PHQ-9 alone to define any antenatal depression and
antenatal major depression.
Missing data and multiple imputation
Although data were complete for the primary outcome and
exposure, there were missing data for many of the covariates;
<10% of data were missing for any individual covariate.
However, use of complete-case analysis would have caused
the exclusion of 476 women. Additionally, when data are
missing at random, use of complete-case analysis biases re-
sults and decreases efficiency.23Therefore, we used multiple
imputation to create five complete datasets (m=5), and the
regression coefficients from each dataset were combined us-
ing the rules described by Little and Rubin.23To impute the
missing covariate values, we specified individual equations
based on the selection rules recommended by van Buuren
et al.24Among the variables considered for each imputation
equation were all demographic, pregnancy, and clinical var-
iables in addition to the outcomes of probable antenatal ma-
jor, minor, or any depression; preterm delivery; very preterm
delivery; low birth weight; and very low birth weight. All
results presented in tables are from the multiple imputation.
Results from complete-case analysis (results not shown) were
similar to those from the multiple imputation.
In this study, women with preexisting diabetes compared
to women without diabetes in pregnancy were older, more
likely to belong to a nonwhite race/ethnicity group, and had
an increased prevalence of chronic medical conditions (Table
1). Compared to women without diabetes in pregnancy, wo-
men with GDM were also older, more likely to be of nonwhite
race/ethnicity, and more likely to have at least one other
chronic medical condition. Among women with other chronic
medical conditions, migraines (37%) and asthma (28%) were
the most frequently reported. A higher percentage of women
with preexisting diabetes or GDM had a history of pregnancy
In our final study sample, the prevalence of preexisting
diabetes was 9%, and the prevalence of GDM was 18%; 327
(13.6%) women met our criteria for any antenatal depression,
The prevalenceofantenatalmajordepression (probable major
depression by PHQ-9 or antidepressant use) and any ante-
natal depression (probable major or minor depression by
PHQ-9 or antidepressant use) was highest among women
with preexisting diabetes (Table 2). Women with GDM had a
Table 1. Characteristics and Prevalence of Risk Factors for Antenatal Depression
Among Respondents in Total Sample (n=2398) and by Diabetes Status
No diabetes PreexistingGDM
Married or partnered, %
Nonwhite race/ethnicity, %
Some college, %
Current smoker, %
History of alcohol use, %
‡1 chronic medical condition, %
Prior pregnancy, %
Gestational week at depression screen
‡1 Prior pregnancy complication, %
86 (84.4- 87.8)
33 (30.9- 35.4)
56 (53.2- 57.9)
72 (70.2- 74.4)
49 (42.1- 55.6)
20.8 (19.9- 21.7)
31.9 (31.3- 32.4)
54 (49.1- 59.0)
aData are mean (95% confidence interval [CI]) or percentage (95% CI) using imputed data (m=5).
GDM, gestational diabetes mellitus.
986 KATON ET AL.
similar prevalence of antenatal major depression and any
antenatal depression compared towomenwithout diabetes in
pregnancy. These findings were consistent for each compo-
nent of our specified antenatal depression outcomes (PHQ-9
score, probable major and minor depression by PHQ-9 score,
and antidepressant medication use).
In the unadjusted analysis, women with preexisting dia-
betes, compared to those with no diabetes, had 54% higher
odds (OR 1.54, 95% CI 1.08-2.21) for any antenatal depression
(probable minor or major depression by PHQ-9 or antide-
for antenatal major depression (probable major depression by
PHQ-9 or antidepressant use) (Table 3). Adjustment for de-
mographic characteristics had little effect on these findings.
After adjusting for demographic and chronic medical condi-
tions, the associations between preexisting diabetes and any
antenatal depression (OR 1.26, 95% CI 0.86-1.84) and ante-
natal major depression (OR 1.18, 95% CI 0.76-1.82) were at-
tenuated and no longer statistically significant. Controlling
for demographic characteristics, chronic medical conditions,
and pregnancy variables further attenuated the association of
antenatal depression with preexisting diabetes. GDM was not
associated with increased odds of any antenatal depression or
antenatal major depression in either the unadjusted or ad-
justed analysis. The results remained unchanged when only
women who were screened for depression by 4 months of
gestation were included in the analysis or when women with
self-reported antidepressant use were excluded.
In this study of 2398 women, there was an increased risk of
any antenatal depression associated with preexisting diabetes
in the unadjusted analysis; however, this association was
Table 2. Prevalence of Antenatal Depression, Antidepressant Use, and Use of Other Psychiatric Medications,
by Diabetes Status (n=2398)
Total sampleNo diabetes PreexistingGDM
Depression by PHQ-9
Mean PHQ-9 score
Probable major depression
Probable minor depression
Other psychiatric medication
Depression by PHQ-9 and medication use
2398 1747226 425
4.0 (2.1- 5.9)
13.2 (11.6- 14.8)
Data are mean (95% CI) or percentage (95% CI).
aProbable major or minor depression by Patient Health Questionnaire-9 (PHQ-9) or antenatal antidepressant use.
bProbable major depression by PHQ-9 or antenatal antidepressant use.
SSRI, selective serotonin reuptake inhibitors.
Table 3. Odds Ratio (95% Confidence Interval) for Any Antenatal Depression and Major
Antenatal Depression Among Pregnant Women After Multiple Imputation (m=5)
Any antenatal depressiona
Major antenatal depressionb
Covariate adjustment Preexisting diabetesGDMPreexisting diabetes GDM
Demographic characteristicscand chronic
medical conditions,dand pregnancy variablese
1.26 (0.86-1.84)0.95 (0.68-1.32)1.18 (0.76-1.82) 0.89 (0.60-1.30)
1.16 (0.79-1.71)0.95 (0.68-1.33) 1.12 (0.72-1.74)0.90 (0.61-1.32)
Odds ratios for antenatal depression compare those with preexisting diabetes or GDM to those without any diabetes.
aProbable major depression or minor depression by PHQ-9, or antidepressant use vs. no depression.
bProbable major depression by PHQ-9 or antidepressant use vs. no depression or probable minor depression by PHQ-9.
cDemographic characteristics: maternal age at depression screen (years), marital status (married or partnered, single), nonwhite race/
ethnicity, education (some college, high school or less), employment (yes, no).
dOne or more other chronic medical condition (yes, no).
ePregnancy variables: prior pregnancy (yes, no), gestational week at depression screen (weeks), ‡1 prior pregnancy complication (yes, no).
DIABETES AND DEPRESSION IN PREGNANCY987
attenuated and no longer statistically significant after ad-
justing for demographic, clinical, and pregnancy characteris-
tics. There was no independent association between GDM
and either measure of antenatal depression in the unadjusted
or adjusted analyses.
Our findings differ from some of those reported in prior
studies. Kozhimannil et al.,11in a study of 11,024 pregnant
9 code for perinatal depression (depression 6 months before 1
year after delivery) or a prescription for antidepressants
among women with preexisting diabetes and women with
GDM. Although in the unadjusted analysis, we found a
similar association of preexisting diabetes and any antenatal
depression, this association was largely accounted for by the
greater percentage of women with preexisting diabetes who
also had other chronic medical conditions. Type 2 diabetes is
often associated with comorbid illnesses, such as hyperten-
sion. Thus, the burden of chronic illness, and not diabetes
alone, may be more likely to be associated with depression.
The study by Kozhimannil et al.11did not adjust for the
presence of other chronic medical conditions. Additionally,
this study used a Medicaid sample and given the higher
prevalence of risk factors for diabetes among low-income
women,25it is possible that a greater proportion of women
diagnosed with GDM in this study had previously unrecog-
Another key difference between the two studies is that we
relied on antenatal diagnostic screening for depression that
was applied to the entire study population independent of
on ICD-9 codes and use of antidepressants in the 6 months
beforeand1year afterdelivery,thusfocusingonwomen with
recognized depression and including PPD in their study
outcome. Only 20%–50% of women meeting the criteria for
major depression in pregnancy are accurately diagnosed, and
physicians are likely to recognize women with more severe
and persistent symptoms of depression.2,4Moreover, if wo-
men with preexisting diabetes or GDM are more likely to be
diagnosed with perinatal depression because of a greater
number of healthcare visits, this might explain the observed
increased odds of depression among women with preexisting
diabetes and GDM in the study by Kozhimannil et al.11
With respect to the lack of association between GDM and
prior smaller studies.12–14However, evidence from the Aus-
tralian Carbohydrate Intolerance Study in Pregnant Women, a
randomized trial of treatment of hyperglycemia in pregnancy,
suggests that treatment of hyperglycemia in pregnancy may
improve mood profile,26and if women with GDM in ourstudy
were screened for depression after beginning treatment for
GDM, this could explain our null findings. Therefore, we con-
ducted a sensitivity analysis excluding women screened for
depression after 4 months of gestation. The results (not shown)
did not differ from the results of our primary analysis.
The current study has several important strengths. We
identified antenatal depression using a diagnostic instrument
(PHQ-9) that was administered independent of a woman’s
diabetes status; therefore, we were able to identify clinically
relevant depression in an unbiased manner. Further, use of
the PHQ-9 also enabled us to distinguish between probable
minor and major depression to further refine our outcome
definition and analysis. We were also able to collect infor-
mation about current use of antidepressants in addition to
detailed demographic, pregnancy, and clinical information.
Finally, this study included a large and diverse population,
making our findings more generalizable to the broader pop-
ulation of pregnant women than previous studies, which had
small sample sizes or studied a Medicaid population.
There are also several limitations to consider. Despite the
diversity of the study population, our study was from a single
large obstetrics clinic in one geographic region of the United
States, thus limiting the generalizability of our findings. This
study examined prevalent antenatal depression and did not
distinguish between preexisting and incident depression or
include information on past history of depression. Depression
is thought to have a bidirectional effect on chronic diseases,
such as diabetes,9and thus is both a risk factor for and a
consequence of diabetes. Therefore, by focusing on prevalent
antenatal depression, this study could not determine the di-
rection of causality. Depression status was determined by the
PHQ-9, not a structured psychiatric interview. Thus, we used
the term ‘‘probable’’ major and minor depression, as clinical
interviews were not done to confirm questionnaire diagnosis.
Although we were able to adjust for a large number of con-
founders, information on prepregnancy BMI was not avail-
able. However, two prior studies that examined the
association of depression and diabetes found that adjusting
for BMI did not appreciably change the measured associa-
tion.27,28Additionally, prepregnancy BMI may have been a
consequence of preexisting depression or management of
preexisting diabetes through weight loss, and, therefore, ad-
justment for prepregnancy BMI would have been inappro-
priate. Finally, a portion of data on important covariates was
missing. Therefore, we used multiple imputation, a technique
shown to decrease bias and increase efficiency when data are
missing at random.23Results using complete-case analysis
were similar to the multiple imputation results.
In this study of 2398 women screened for depression, there
was no detectable independent association of diabetes and
antenatal depression in pregnancy after accounting for the
presence of other chronic medical conditions. Although dia-
betes may not independently increase the risk of antenatal
depression, the presence of one or more chronic medical
conditions significantly increased a woman’s risk of antenatal
depression, highlighting the importance of depression
screening among pregnant women with chronic medical
conditions. Future research needs to replicate these findings
and should also focus on the potential impact of antenatal
control, birth outcomes, and infant health.
J.G.K. is supported by the Reproductive, Perinatal and
Pediatric Training grant number T32 HD052462 from the
Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health, by
the Samuel and Althea Stroum Fellowship, and by a grant
from the Seattle chapter of Achievement Rewards for College
Scientists. A.R.G. is funded under NCRR grant 5 KL2
RR025015. J.G.K.’s time on this project was funded by NIMH
grant K24 MH069741.
988 KATON ET AL.
No competing financial interests exist for any of the
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Address correspondence to:
Jodie G. Katon, Ph.C.
Department of Epidemiology, Box 357236
University of Washington
Seattle, WA 98195
DIABETES AND DEPRESSION IN PREGNANCY989
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