Arch Womens Ment Health (2015) 18:473–483
DOI 10.1007/s00737-014-0474-z
ORIGINAL ARTICLE
Associations of anxiety disorders, depressive disorders and body
weight with hypertension during pregnancy
Susanne Winkel & Franziska Einsle & Lars Pieper &
Michael Höfler & Hans-Ulrich Wittchen & Julia Martini
Received: 14 May 2014 / Accepted: 18 October 2014 / Published online: 25 November 2014
# Springer-Verlag Wien 2014
Abstract The purpose of this study was to prospectively
examine the relationships between maternal DSM-IV-TR anx-
iety disorders, depressive disorders, and body mass index
(BMI) with arterial hypertension and blood pressure during
pregnancy. In the Maternal Anxiety in Relation to Infant
Development (MARI) study, N=306 women were enrolled
in early pregnancy and repeatedly assessed during peripartum
period. DSM-IV-TR anxiety and depressive disorders prior to
pregnancy, lifetime anxiety/depression liability, and BMI dur-
ing early pregnancy were assessed with the Composite Inter-
national Diagnostic Interview for Women (CIDI-V). Based on
their prepregnancy status, all participants were assigned to one
of the following initial diagnostic groups: no anxiety nor
depressive disorder (no AD), pure depressive disorder (pure
D), pure anxiety disorder (pure A), and comorbid anxiety and
depressive disorder (comorbid AD). Blood pressure measure-
ments were derived from medical records. Arterial hyperten-
sion during pregnancy was defined by at least two blood
pressure values ≥140 mmHg systolic and/or ≥90 mmHg dia-
stolic. N=283 women with at least four documented blood
pressure measurements during pregnancy were included in the
analyses. In this sample, N=47 women (16.6 %) were identi-
fied with arterial hypertension during pregnancy. Women with
comorbid AD (reference group: no AD) had a significantly
higher blood pressure after adjustment for age, parity,
smoking, occupation, household income, and education (sys-
tolic: linear regression coefficient [β]=3.0, 95 % confidence
interval [CI]=0.2–5.7; diastolic, β=2.3, 95 % CI=0.1–4.4).
Anxiety liability was associated with an increased risk of
hypertension (odds ratio [OR]=1.1, 95 % CI=1.0–1.3) and a
S. Winkel (*) : F. Einsle : L. Pieper : M. Höfler : H.<U. Wittchen :
J. Martini
Institute for Clinical Psychology and Psychotherapy, Technische
Universität Dresden, Chemnitzer Straße 46, 01187 Dresden,
Germany
e-mail: winkel@psychologie.tu-dresden.de
higher systolic blood pressure (β=0.4, 95 % CI=0.0–0.7).
The adjusted interaction model revealed a significant interac-
tion between the diagnostic group pure A and BMI for hyper-
tension (ORIT =1.5, 95 % CI=1.1–2.1). Especially, women
with a lifetime history of comorbid anxiety and depression and
obese pregnant women with a lifetime history of pure anxiety
disorder should be informed about their heightened risk of
hypertension, monitored with regular blood pressure measure-
ments, and provided with strategies for prevention and early
intervention such as changes in diet and physical activity.
Keywords Pregnancy . Anxiety disorder . Depressive
disorder . Hypertension . BMI
Background
Arterial hypertension during pregnancy (defined by at least
two blood pressure values ≥140 mmHg systolic and/or
≥90 mmHg diastolic; Regitz-Zagrosek et al. 2011) affects up
to 15 % of all women and is associated with a range of
pregnancy-related complications such as pre-eclampsia
(Regitz-Zagrosek et al. 2011; Roberts et al. 2003; Sibai et al.
2005). The main impact on the fetus may be undernutrition as
a result of utero-placental vascular insufficiency and an asso-
ciated growth retardation, low infant birth weight, and preterm
delivery (Churchill et al. 1997; Regitz-Zagrosek et al. 2011;
Roberts et al. 2003; Sibai et al. 2005). The long-term conse-
quences of hypertension during pregnancy for the mother can
be chronic hypertension after delivery and an overall increase
in lifetime cardiovascular risk (Bellamy et al. 2007;
Lindheimer et al. 2008).
Studies of the general (nonpregnant) community have
shown that hypertension is associated with mental disorders
(Davies et al. 1999; Grimsrud et al. 2009; Patten et al. 2009;
Players and Peterson 2011). In particular, individuals with
474
anxiety and depressive disorders may be more prone to hy-
pertension because of a presumed unhealthy lifestyle (Bonnet
et al. 2005; Strine et al. 2008) and associated changes in the
autonomic nervous system, the hypothalamic-pituitary-
adrenal axis, and the immune system (McCabe et al. 2009;
Scott et al. 2009). It is certainly possible that similar associa-
tions exist in pregnant women, but it may also be that the
associations differ from the general community, because dur-
ing pregnancy, the blood pressure regulation is substantially
changed (Ganzevoort et al. 2004; Regitz-Zagrosek et al.
2011). The normal course of blood pressure during pregnancy
includes a fall in the first trimester and a rise after
midpregnancy with the highest values immediately preceding
birth (Lindheimer et al. 2008). One study has shown that
women with anxiety or depressive disorder prior to pregnancy
have a 1.7 higher risk of the hypertensive disorder pre-
eclampsia (Qiu et al. 2009). Accordingly, Kurki et al. (2000)
showed a significantly increased chance for pre-eclampsia if
women were affected by depression (odds ratio [OR]=2.5),
anxiety (OR=3.2), or both (OR=3.1) during early pregnancy.
However, results of further studies on the association of anx-
iety and depression with pre-eclampsia (Andersson et al.
2004; Banhidy et al. 2006; Jablensky et al. 2005) were het-
erogeneous due to differing methods and the fact that mental
disorder diagnoses were mostly ascertained from medical
records as opposed to being diagnosed by structured clinical
interviews, leaving many women with undiagnosed mental
disorders (Wittchen et al. 2011). Apart from studies on the link
between mental disorders and pre-eclampsia, the relationship
between anxiety and depressive disorders with hypertension
during pregnancy has to our knowledge not yet been
investigated.
Thus, the first aim of the present study is to investigate the
associations of anxiety and/or depressive disorders prior to
pregnancy with blood pressure and arterial hypertension in
pregnancy. Because it is known from studies in the general
community that individuals with severe or comorbid anxiety
and depressive disorders (compared to pure anxiety or pure
depressive disorders) are at a higher risk of hypertension
(Carroll et al. 2010; Grimsrud et al. 2009; Scott et al. 2007),
the hypothesis is that an elevated risk is present in pregnant
women with comorbid anxiety and depressive disorders and
also in women with a more severe disorder.
As outlined above, an unhealthy, and in particular over-
weight, lifestyle may also be linked to hypertension. Given the
fact that obesity is one of the major risk factors of hyperten-
sion during pregnancy (Bodnar et al. 2007; Zhang et al. 1997)
and is also related to psychiatric disorders (Petry et al. 2008), it
is investigated whether the associations between anxiety and
depressive disorders (and their severity) vary in relation to the
body mass index (BMI) of early pregnancy. All associations
of anxiety and depression and BMI with hypertension during
pregnancy are additionally adjusted for age, parity, smoking,
S. Winkel et al.
occupation, household income, and education. This was done
because studies show that hypertension during pregnancy
occurs more often in older women (Ayala and Hermida
2001; Zhang et al. 1997), during first pregnancies (Kaur and
Kaur 2012; Zhang et al. 1997), and in women with lower
socioeconomic status (Roblin et al. 2010) and is associated
with smoking (England et al. 2002; Zhang et al. 1997).
Methods
Procedure
In the prospective longitudinal Maternal Anxiety in Relation
to Infant Development (MARI) study (Martini et al. 2013),
N=306 women were investigated from early pregnancy (base-
line: 10–12 weeks of gestation) until four months postpartum in
approximately two-monthly intervals and additionally one year
later. Participants were assessed via standardized interviews,
questionnaires, and observations by trained assessors. All par-
ticipants provided written informed consent after the study aims
and procedures were fully explained. The MARI study was
carried out in accordance with the APA ethical standards and
has been approved by the Ethics Committee of the Medical
Faculty of the Technische Universität Dresden (No. EK
94042007). Further information on the procedure of the main
study is published elsewhere (Martini et al. 2013).
Participants of the MARI study
A total of N=533 pregnant women from gynecological out-
patient settings (January 2009 to June 2010) in the area of
Dresden (Germany) were screened for exclusion criteria (ges-
tational age >12 weeks, younger than 18 or older than
40 years, multiple pregnancy, history of more than 3 sponta-
neous abortions/(induced) terminations of pregnancy/still
births or infant impairment, invasive fertility treatment, severe
physical disease/microsomia/skeletal malformation, sub-
stance abuse or heroin substitution during the preceding
6 months, severe psychiatric illness, expectation to leave the
area of Dresden, insufficient mastery of German language).
Overall, N=306 women were eligible and recruited for the
MARI study. Sociodemographic characteristics of the sample
of the main study were reported by Martini et al. (2013).
Sample for the present analyses
Out of the N=306 women of the MARI sample, N=283
women were included in the presented post hoc analyses
(92.5 %). N=20 women did not participate until the end of
pregnancy (N = 8 women due to spontaneous abortion/
termination of pregnancy, N=2 moved away from Dresden,
N=3 could not be reached anymore, N=7 reported lack of
Associations of anxiety disorders 475

time or interest), and for N=3 women, no blood pressure Table 1 Sociodemographic and selected gynecological variables at base-
line assessment in early pregnancy as well as outcome measures of
documentation was available (lost their Mutterpass or repeat-
included women from the MARI sample (N=283)
edly forgot their Mutterpass at the MARI assessments).
Sociodemographic variables and selected gynecological infor- Sociodemographic and gynecological variables
mation on the included (N=283) women are presented in Age in years (mean, SD) 28.2 4.4
Table 1. Excluded women (N=23) were significantly younger Current occupation (N, %)
(M=26.2, SD=4.3 vs M=28.2, SD=4.4 years, p=0.041) and Unemployed 23 8.2
more often unemployed (N=7, 30.4 % vs N=23, 8.2 %, Employed 166 58.7
p<0.001). For other variables, no systematic differences were Housewife 16 5.6
apparent (all p>0.05). Student 62 21.9
Other 16 5.6
Diagnostic assessments Marital status (N, %)
married 104 36.7
DSM-IV-TR anxiety and depressive disorders were assessed never married 168 59.4
with the Composite International Diagnostic Interview for separated/ divorced/ widowed 11 3.9
Women (CIDI-V; Martini et al. 2009), a modified version of Number of pregnancies (incl. current pregnancy) (N, %)
the WHO-CIDI that comprises very good psychometric prop- 1 141 49.8
erties (Kessler and Ustün 2004). At T1, the lifetime version of 2 75 26.5
the CIDI-V was conducted to assess diagnostic status prior to 3 41 14.5
pregnancy. Importantly, diagnoses with an onset four weeks 4–5 26 9.2
prior to baseline interview—around the time when pregnancy is Smoking (number of cigarettes in past 12 month) (mean, SD) 2.9 6.2
confirmed by a pregnancy test or by a gynecologist—were not Education (N, %)
incorporated in the following initial diagnostic groups (but No degree 2 0.7
considered as affected during pregnancy first): no AD (refer- 9th grade 15 5.3
ence), no anxiety nor depressive disorder prior to pregnancy; 10th grade 69 24.4
pure D: pure depressive disorder(s) prior to pregnancy; pure A: Abitur (German university entrance certificate) 104 36.8
pure anxiety disorder(s) prior to pregnancy; and comorbid AD: University 93 32.9
comorbid anxiety and depressive disorders prior to pregnancy. Monthly household income after taxes (N, %)
In addition, two dimensional indices were constructed in
Less than 500 € 20 7.1
order to reflect the severity of the respective disorders. These
500 to 1,500 € 96 33.9
indices are based on baseline (prior to pregnancy) diagnostic
1,500 to 2,500 € 89 31.5
information (criteria were coded as 0 “not present” or 1
2,500 to 3,500 € 53 18.7
“present”). The anxiety liability index incorporated diagnostic
3,500 to 4,500 € 18 6.4
information about the occurrence of (1) any anxiety disorder
More than 4,500 € 7 2.5
prior to pregnancy (panic disorder, agoraphobia, social pho-
Outcome measures:
bia, specific phobia, phobia not otherwise specified, obsessive
Initial diagnostic groups (N, %)
compulsive disorder, generalized anxiety disorder), (2) any
No AD 98 34.6
anxiety disorder 12 months prior to pregnancy, (3) the pres-
Pure D 46 16.3
ence of panic attacks prior to pregnancy, (4) panic attacks
Pure A 78 27.6
during the past 12 months prior to pregnancy, (5) comorbidity
Comorbid AD 61 21.6
of anxiety disorders prior to pregnancy, and (6) comorbid
Severity of anxiety and depression (mean, SD)
anxiety disorders 12 months prior to pregnancy. Further
criteria were (7) early onset (median split of earliest onset; 1, Anxiety liability (range 0–10) 2.5 2.7
≤10 years) and (8) interference with daily life (1 “a lot” or Depression liability (range 0–9) 2.6 2.5
“very much”), (9) the presence of at least three lifetime spe- BMI (mean, SD) 23.6 4.3
cific phobias prior to pregnancy, and (10) at least one “severe” BMI classification according to WHO (N, %)
anxiety disorder (1, any anxiety disorder excl. specific phobia) Underweight (BMI <18.5) 6 2.1
prior to pregnancy. The depression liability index was gener- Normal weight (BMI ≥18.5≤25) 204 72.1
ated accordingly, using information about (1) diagnosis of Overweight (BMI >25) 73 25.8
major depressive disorder or dysthymia prior to pregnancy, Number of blood pressure measurements (mean, SD) 11.8 2.8
(2) 12-month diagnosis of major depressive disorder or dys- Blood pressure (mean, SD)
thymia prior to pregnancy, (3) frequency (1, ≥2 episodes) and Mean systolic 113.8 8.6
(4) duration of episodes (median split of longest episode;
476
Table 1 (continued)
Mean diastolic 69.1
1st trimester: systolic 112.4
1st trimester: diastolic 67.9
2nd trimester: systolic 111.8
2nd trimester: diastolic 66.7
3rd trimester: systolic 115.5
3rd trimester: diastolic 70.8
Arterial hypertension (N, %) 47
No AD no anxiety nor depressive disorder prior to pregnancy, Pure D pure
depressive disorder(s) prior to pregnancy, Pure A pure anxiety disorder(s)
prior to pregnancy, Comorbid AD comorbid anxiety and depressive dis-
orders prior to pregnancy, N number, % percentage, SD standard deviation
1, ≥12 weeks) prior to pregnancy, (5) early onset (median split
of earliest onset; 1, ≤23 years), and (6) degree of interference
with daily activities (1, “a lot” or “very much”). Further
criteria were (7) number of symptoms (1, at least 5 out of 9
symptoms, according to DSM-IV-TR), (8) somatic syndrome
according to ICD-10 definition, and (9) inpatient treatment
prior to pregnancy (see also Martini et al. 2013).
Blood pressure Medical data about blood pressure during
pregnancy were derived from the medical documentation in
the German “Mutterpass.” The Mutterpass is a medical record
book that is kept by all pregnant women in Germany and
includes medical information about pregnancy, delivery, and
postpartum period. At every medical examination during
pregnancy, the blood pressure is measured and recorded by
the gynecologist or the midwife. Based on the European
Society of Cardiology Guidelines on the management of
cardiovascular diseases during pregnancy, hypertension dur-
ing pregnancy was defined as blood pressure values
≥140 mmHg systolic and/or 90 mmHg diastolic (Regitz-
Zagrosek et al. 2011). For an increased reliability, two mea-
surements must have been above this threshold. Participants
with at least four documented blood pressure measurements
during pregnancy were included in the analyses. In the present
sample, the number of documented blood pressure measure-
ments during pregnancy per woman ranged from 4 to 30
(mean 11.8; SD=2.8) measurements. The earliest documented
blood pressure measurement of a woman was in the fifth week
and the latest during the 41st week of gestation. During the
first pregnancy trimester, ten women had no documented
blood pressure values, possibly because they did not receive
their Mutterpass from the gynecologist during the first trimes-
ter. Hence, analyses for the first trimester were based on N=
273 women. During second and third trimester, all 283 wom-
en had at least two documented blood pressure measurements.
Body mass index At baseline assessment, women were asked
about their current weight and height to calculate their BMI
S. Winkel et al.
[weight (kg)/height (m)2] (World Health Organization, 2000).
6.5 Women were classified into three groups according to World
11.4 Health Organization: BMI<18.5 was classified as under-
9.0
weight, BMI≥18.5≤25 as normal weight, and BMI>25 as
9.7
7.3 overweight. However, for significance tests, the group of
9.4 women with underweight (N=6) was too small and therefore
7.2 combined with women with normal weight.
16.6
Statistical analyses
Frequencies, mean values, and standard deviations were ana-
lyzed descriptively. As the dependent variable (hypertension)
was binary, logistic regression analyses were used to compare
the odds of having hypertension in different risk groups. To
analyze if BMI predicts the association of psychopathology
with hypertension, interaction terms between BMI and diag-
nostic status (coded with three dummy variables) were calcu-
lated. Model-based risk estimates by diagnostic status and
BMI are illustrated graphically. For dimensional dependent
variables (systolic and diastolic blood pressure, anxiety/
depression liability), linear regressions were applied. Multiple
logistic and linear regression analyses were performed in
order to adjust for the possible confounding variables age,
parity, smoking during the past 12 months prior to pregnancy,
occupation, monthly household income after taxes, and edu-
cation. Statistical tests were conducted at the 5 % significance
level. All analyses were performed using STATA 12.1
(StataCorp 2013).
Results
The distribution of the initial diagnostic groups and the de-
scription of anxiety and depression liability, body weight, and
blood pressure are presented in the lower part of Table 1.
In this sample, N=47 women (16.6 %) were identified with
arterial hypertension during pregnancy. Only eight women
with hypertension reported that they were treated with antihy-
pertensive drugs (woman without hypertension did not re-
ceive antihypertensive drugs).
Associations of anxiety and depressive disorders and BMI
with blood pressure during pregnancy
Univariate analyses were endorsed to identify unadjusted asso-
ciations with hypertension during pregnancy. As displayed in
Table 2, women with comorbid AD had hypertension signifi-
cantly more often than women with no AD (26.2 vs 13.3 %).
Anxiety liability was significantly higher in women with hyper-
tension (mean=3.2, SD=3.0) as compared to women without
hypertension (mean=2.3, SD=2.7). Also, the BMI was signif-
icantly higher in women with hypertension (26.1 for women
Associations of anxiety disorders 477

Table 2 Description and logistic regression between maternal anxiety and depressive disorders prior to pregnancy and BMI with arterial hypertension
during pregnancy

No hypertension Hypertension Crude logistic regression analyses Adjusteda logistic regression analyses
(N=235) (N=48)
N (%) N (%) OR 95 % CI p OR 95 % CI p

Initial diagnostic groups

No AD (N=98) 85 (86.7) 13 (13.3) reference reference
Pure D (N=46) 38 (82.6) 8 (17.4) 1.4 0.5–3.6 0.514 0.7 0.3–2.0 0.979
Pure A (N=78) 68 (87.2) 10 (12.8) 1.0 0.4–2.3 0.931 0.9 0.4–2.2 0.813
Comorbid AD (N=61) 45 (73.8) 16 (26.2) 2.3 1.0–5.3 0.043 2.1 0.9–4.9 0.089
Anxiety liability 2.3 (2.7) 3.2 (3.0) 1.1 1.0–1.2 0.048 1.1 1.0–1.3 0.044
Depression liability 2.5 (2.5) 2.9 (2.6) 1.1 0.9–1.2 0.341 1.0 0.9–1.2 0.814
BMI (dimensional) 23.1 (3.6) 26.1 (6.3) 1.1 1.1–1.2 <0.001 1.1 1.1–1.2 <0.001
BMI groups
Normal or underweight (N=210) 183 (87.1) 27 (12.9) reference reference
Overweight (N=73) 53 (72.6) 20 (27.4) 2.6 1.3–4.9 0.005 2.7 1.3–5.4 0.006

No AD no anxiety nor depressive disorder prior to pregnancy, Pure D pure depressive disorder(s) prior to pregnancy, Pure A pure anxiety disorder(s) prior
to pregnancy, Comorbid AD comorbid anxiety and depressive disorders prior to pregnancy, N number, % percentage, SD standard deviation, OR odds
ratio, 95 % CI 95 % confidence interval
p-values equal or below 0.05 are presented in bold
a
Adjusted for age, parity, smoking, occupation, household income, and education

with vs 23.1 for women without hypertension). Considering the
BMI classes shows that women with overweight had with
27.4 % (N=20) significantly more often hypertension compared
to women with normal or underweight 12.9 % (N=27).
In the multiple models (right part of Table 2), all associa-
tions were adjusted for the possible confounding variables:
age, parity, smoking, education, occupation, and household
income. The anxiety liability remained significantly associat-
ed with hypertension (OR=1.1) as well as the BMI (OR=1.1).
The women with overweight still had a significantly higher
chance for hypertension compared to women with normal or
underweight (OR=2.7).
Analyses of changes in blood pressure during pregnancy
(difference between the first blood pressure value and the
highest value during pregnancy and differences between mean
first trimester and mean second trimester, between mean sec-
ond and mean third trimester, and between mean first mean
third trimester) revealed that the changes were not significant-
ly different between the initial diagnostic groups.
With the dimensional blood pressure measurements as the
dependent variable (displayed in Table 3), again the crude anal-
yses and the analyses adjusted for possible confounding variables
(age, parity, smoking, occupation, household income, and edu-
cation) were performed. In the crude and the adjusted analyses,
women with comorbid AD had the significantly highest systolic
and diastolic blood pressure measurements (115.5 mmHg sys-
tolic, 70.5 mmHg diastolic) compared to women with no AD
(112.5 mmHg systolic, 68.2 mmHg diastolic). Also, the BMI
was in the crude and the adjusted analyses significantly
associated with the systolic and diastolic blood pressure (β=
0.9 and β=0.5, respectively). Women with overweight had
significantly higher systolic and diastolic blood pressure com-
pared to women with normal or underweight (crude: β=6.3 and
β=4.5; adjusted: β=6.2 and β=4.6). The anxiety liability was in
the crude and adjusted regression analysis significantly associat-
ed with the systolic blood pressure (β=0.4).
Blood pressure per trimester
As it is normal that the blood pressure substantially changes
during course of pregnancy, the blood pressure per trimester
was analyzed. As expected, the blood pressure decreased from
the first to the second trimester and increased again in the third
trimester in all diagnostic groups (see Fig. 1). Differences
between the diagnostic groups were apparent as at any trimes-
ter, women with no AD had the lowest blood pressure values
and women with comorbid AD had the highest values. Crude
linear regression analyses revealed the following significant
differences: Women with pure A had a significant higher
systolic blood pressure during first trimester compared to
women with no AD (M=113.4, SD=9.8 vs M=109.7, SD=
12.9; β=3.7, 95 % confidence interval (CI)=0.2–7.2, p=
0.037). Compared to no AD, women with comorbid AD had
a significantly higher systolic blood pressure during the first
trimester (M=114.9, SD=12.4 vs M=109.7, SD=12.9; β=
5.2, 95 % CI=1.5–8.9, p=0.006) and a significantly higher
systolic (M=117.6, SD=9.9 vs M=114.2, SD=9.0, β=3.4
95 % CI 0.4–6.4, p=0.027) and diastolic (M=72.8, SD=8.1
478 S. Winkel et al.

Table 3 Associations of maternal anxiety and depressive disorders prior to pregnancy and BMI with mean systolic and diastolic blood pressure during
pregnancy

Systolic Diastolic

Crude linear Adjusteda linear Crude linear Adjusteda linear

regression analyses regression analyses regression analyses regression analyses

M (SD) β 95% CI p β 95% CI p M (SD) β 95% CI p β 95% CI p

Initial diagnostic groups

No AD (N=98) 112.5 (7.9) reference reference 68.2 (6.0) reference reference
Pure D (N=46) 113.9 (8.9) 1.3 −1.7–4.4 0.391 1.4 −1.2–4.0 0.296 69.0 (6.3) 0.7 −1.6–3.0 0.531 0.4 −1.9–2.8 0.717
Pure A (N=78) 114.1 (8.2) 1.5 −1.0–4.1 0.237 1.4 −2.3–3.9 0.612 69.1 (6.3) 0.9 −1.1–2.8 0.374 1.0 −1.0–2.9 0.332
Comorbid AD (N=61) 115.5 (9.9) 3.0 0.2–5.8 0.035 3.0 0.2–5.7 0.039 70.5 (7.6) 2.3 0.2–4.4 0.033 2.3 0.1-4.4 0.037
Anxiety liability 0.4 0.0–0.8 0.039 0.4 0.0–0.7 0.050 0.2 −0.3–0.5 0.086 0.3 −0.2–0.5 0.074
Depression liability 0.0 −0.4–0.4 0.915 −0.2 −0.4–0.6 0.910 0.1 −0.2–0.4 0.409 0.1 −0.2−0.4 0.494
BMI (dimensional) 0.9 0.7–1.1 <0.001 0.9 0.7–1.1 <0.001 0.5 0.3–0.7 <0.001 0.5 0.4–0.7 <0.001
BMI groups
Normal or underweight 112.2 (8.0) reference reference 67.9 (6.2) reference reference
(N=210)
Overweight (N=73) 118.5 (8.8) 6.3 4.1–8.5 <0.001 6.2 3.9–8.4 <0.001 72.4 (6.5) 4.5 2.8–6.1 <0.001 4.6 2.9–6.4 <0.001

No AD no anxiety nor depressive disorder prior to pregnancy, Pure D pure depressive disorder(s) prior to pregnancy, Pure A pure anxiety disorder(s) prior
to pregnancy, Comorbid AD comorbid anxiety and depressive disorders prior to pregnancy, M mean, SD standard deviation, β linear regression
coefficient, 95 % CI 95 % confidence interval
p-values equal or below 0.05 are presented in bold
a
Adjusted for age, parity, smoking, occupation, household income, and education

vs M=69.8, SD =6.8, β=2.9 95 % CI 0.6–5.2, p=0.012)
blood pressure during the third trimester. Multiple linear
regression analyses adjusted for BMI and other possible
confounding variables (age, parity, smoking, occupation,
household income, and education) revealed the following
significant results: Compared to no AD, women with pure
A (M= 113.4, SD = 9.8 vs M = 109.7, SD = 12.9, β = 3.4,
95 % CI=0.1-6.7, p=0.041) and also women with comor-
bid AD (M=114.9, SD =12.4 vs M=109.7, SD=12.9; β=
4.3, 95 % CI = 0.8–7.8, p = 0.016) had a significantly
higher systolic blood pressure during the first trimester.
The adjusted association between anxiety liability and
systolic blood pressure during first trimester (β = 0.6,
95 % CI = 0.1–1.1, p = 0.010) was also significant. All
other adjusted associations between diagnostic groups or
anxiety/depression liability were not significant (tables on
request).
Associations of anxiety/depressive disorders and BMI
with hypertension during pregnancy
As presented in Table 4, in the crude linear regression
analysis, women with comorbid AD had a significantly
higher BMI compared to women with no AD (M=24.3,
SD = 4.3 vs M = 22.8, SD = 3.3; OR = 1.4). Adjusted for
possible confounding variables, the association between
comorbid AD and BMI was attenuated to nonsignificance
(OR=1.3; p=0.053). The BMI was not different in wom-
en with pure D and pure A and not significantly associ-
ated with anxiety liability and depression liability. Com-
paring the percentage of overweight women across the
four diagnostic groups revealed no significant differences
between the groups (logistic regression: all p>0.05; re-
sults on request), and no significant associations of over-
weight with anxiety liability and depression liability were
apparent (linear regression: all p > 0.05; results on
request).
Interaction between anxiety/depressive disorders and BMI
for hypertension during pregnancy
The crude interaction model revealed significant interactions
between the diagnostic group pure A and the BMI for hyper-
tension (ORIT =1.5, 95 % CI=1.1–2.0, p=0.007). Hence, the
model predicts that the OR for the association between pure A
(compared to no AD) and hypertension increases by 1.5 per unit
increase in BMI. The interaction was also significant for comor-
bid AD (ORIT =1.3, 95 % CI=1.0–1.7, p=0.048) indicating that
the OR for the association between comorbid AD (compared to
no AD) and hypertension increases by 1.3 per unit increase in
BMI. The interaction between pure D and BMI on hypertension
was not significant (ORIT =1.2, 95 % CI=0.95–1.5, p=0.130).
Associations of anxiety disorders 479

Mean systolic blood pressure Mean diastolic blood pressure

120
74

118
72

116

β=4.3* 70
114

112 68
β=3.4*

110 66

108
64

106

62
104 1st trimester (N=273) 2nd trimester (N=283) 3rd trimester (N=283)
1st trimester (N=273) 2nd trimester (N=283) 3rd trimester (N=283)

comorbid AD pure A pure D no AD

Fig. 1 Mean systolic and diastolic blood pressure by pregnancy trimester depressive disorder(s) prior to pregnancy, Pure A pure anxiety disorder(s)
and diagnostic group. Note: Asterisk Significant difference, adjusted for prior to pregnancy, Comorbid AD comorbid anxiety and depressive
age, parity, smoking, occupation, household income, and education, No disorders prior to pregnancy, β linear regression coefficient
AD no anxiety nor depressive disorder prior to pregnancy, Pure D pure

After adjustment for possible confounders (age, parity,
smoking, education, occupation, and household income), the
interaction between pure A and BMI for hypertension remained
significant (ORIT =1.5, 95 % CI=1.1–2.1, p=0.006). The asso-
ciation of comorbid AD and BMI was attenuated to
nonsignificance (ORIT =1.3, 95 % CI=1.0–1.7, p=0.072). In
Fig. 2, the interaction between the diagnostic group and BMI on
the risk for hypertension is illustrated. All control variables (age,
parity, smoking, education, occupation, and household income)
were fixed at their average in the sample. Additionally, the
interaction model adjusted for the control variables revealed no
significant interactions between anxiety liability and BMI for
hypertension (ORIT =1.1, 95 % CI=0.99–1.0, p=0.154) and
between depression liability and BMI for hypertension
(ORIT =1.0, 95 % CI=0.97–1.0, p=0.483).
Discussion
In this prospective longitudinal study, the associations of
anxiety and depression prior to pregnancy and BMI with
hypertension during pregnancy were analyzed extensively
for the first time. Pregnant women with a lifetime comorbid

Table 4 Description and linear regression between maternal anxiety and depressive disorders prior to pregnancy and BMI

BMI Crude linear regression analyses Adjusteda linear regression analyses

M (SD) β 95 % CI p β 95 % CI p

Initial diagnostic groups

No AD (N=98) 22.8 (3.3) reference reference
Pure D (N=46) 24.1 (5.9) 1.2 −0.3–2.7 0.103 1.1 −0.4–2.6 0.153
Pure A (N=78) 23.7 (4.2) 0.9 −0.4–2.2 0.156 0.7 −0.6–1.9 0.286
Comorbid AD (N=61) 24.3 (4.3) 1.4 0.1–2.8 0.039 1.3 0.0–2.7 0.053
Anxiety liability 0.1 −0.1–0.3 0.228 0.1 −0.1–0.3 0.344
Depression liability 0.2 −0.4–0.4 0.119 0.1 −0.1–0.3 0.199

No AD no anxiety nor depressive disorder prior to pregnancy, Pure D pure depressive disorder(s) prior to pregnancy, Pure A pure anxiety disorder(s) prior
to pregnancy, Comorbid AD comorbid anxiety and depressive disorders prior to pregnancy, M mean, SD standard deviation, β linear regression
coefficient, 95 % CI 95 % confidence interval
p-values equal or below 0.05 are presented in bold
a
Adjusted for age, parity, smoking, occupation, household income, and education
480
anxiety and depressive disorder had significantly higher sys-
tolic and diastolic blood pressure values during pregnancy
compared to women without anxiety or depressive disorder.
This is important because hypertension during pregnancy is a
major complication that can cause e.g., premature delivery,
fetal growth retardation, as well as maternal morbidity and
mortality (Zhang et al. 1997; Regitz-Zagrosek et al. 2011).
Long-term studies even showed that hypertensive disorders in
pregnancy were associated with lower intellectual abilities in
the offspring after 20 years (Tuovinen et al. 2012) and with
more frequent subjective complaints of, among others, depres-
sive and anxious symptoms as well as cognitive failures after
70 years (Tuovinen et al. 2013).
Women with comorbid anxiety and depression had a 2.3
higher chance of being affected by arterial hypertension than
women without anxiety and depression. This association was
attenuated to nonsignificance (OR=2.1; p=0.089) after ad-
justment for possible confounding variables (age, parity,
smoking, occupation, household income, and education).
The difference in the odds of 0.2 after adjustment indicates
that the association is in a very small part attributable to the
confounding variables. However, blood pressure values dur-
ing pregnancy were substantially higher if women were af-
fected by anxiety and depressive disorder. Even if the adjusted
regression coefficients of β=3.0 systolic and β=2.3 diastolic
indicate a small mean blood pressure difference of 3.0 mmHg
systolic and 2.3 mmHg diastolic if women were affected by
comorbid anxiety and depression (compared to women with
no anxiety nor depressive disorder), the differences may be
clinically noteworthy. In the general nonpregnant population,
it has been estimated that a 3-mmHg reduction in systolic
blood pressure would reduce the relative risk of stroke mor-
tality by 8%, of coronary artery disease mortality by 5%, and
Model-based risk for hypertension
1
0.9
Normal weight Overweight
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
16 18 20 22 24 26
Fig. 2 Predicted risk for hypertension as a function of the diagnostic
groups and BMI. The confounders in the model (age, parity, smoking,
occupation, household income, and education) were fixed at their average
in the sample. Notes: risk=1 indicates a 100 % probability to have a
hypertension. The displayed BMI ranges from 16 to 37 which are 98.6 %
of the sample. The remaining four women with a higher BMI (39.8, 42.8,
S. Winkel et al.
of all-cause mortality by 4% (Whelton et al. 2002). And,
considering the possible negative effects of hypertension dur-
ing pregnancy for the mother’s and child’s health, any blood
pressure reduction would be beneficial. The greatest differ-
ence between the diagnostic groups was apparent during the
first pregnancy trimester, but also (in the crude analyses) in the
third trimester.
Obesity is a known and important risk factor for hyperten-
sion (Bodnar et al. 2007; Regitz-Zagrosek et al. 2011; Zhang
et al. 1997). Accordingly, in this study the BMI was signifi-
cantly associated with hypertension during pregnancy. The
adjusted regression coefficients of β=6.2 systolic and β=4.6
diastolic indicate a mean increase in blood pressure of
6.2 mmHg systolic and 4.6 mmHg diastolic if women were
overweight (compared to women with normal or underweight).
And therefore, overweight seems somewhat more important for
hypertension compared to anxiety and depression. However,
BMI and diagnostic status prior to pregnancy were not inde-
pendently affecting hypertension, because the higher the BMI
for women with pure anxiety and with comorbid anxiety and
depressive disorders, the higher was their risk elevation for
hypertension.
These results confirm previous studies that found a link
between anxiety and depressive symptoms or disorders and
hypertension in the general population (Carroll et al. 2010;
Grimsrud et al. 2009; Scott et al. 2007) as well as the
hypertensive disorder pre-eclampsia (Kurki et al. 2000; Qiu
et al. 2009). They also indicate the importance of consid-
ering comorbidity of anxiety and depression and to use
standardized diagnostic procedures to confirm diagnostic
status, which has not been considered in studies that did
not find such associations (Banhidy et al. 2006; Jablensky
et al. 2005). The results may be specific for anxiety and
pure A
comorbid AD
pure D
no AD
28 30 32 34 36 BMI
45.9, 49.7) are not displayed. No AD no anxiety nor depressive disorder
prior to pregnancy, Pure D pure depressive disorder(s) prior to pregnancy,
Pure A pure anxiety disorder(s) prior to pregnancy, Comorbid AD co-
morbid anxiety and depressive disorders prior to pregnancy; the line at
BMI=25 indicates the cutoff between normal weight and overweight
according to the World Health Organization
Associations of anxiety disorders
depressive symptoms, because other studies integrated men-
tal disorders that may be independent from hypertension
(e.g., eating disorders) and only found a tendency for a
higher risk of pre-eclampsia in women with mental disor-
ders (3.8 vs 2.4 %) (Andersson et al. 2004).
The specific relevance of anxiety and depression for
hypertension during pregnancy may to some extent be
explained by lifestyle factors such as decreased physical
activity, increased alcohol consumption, smoking, and in
general an unhealthy lifestyle (Bonnet et al. 2005; Strine
et al. 2008). Within the possibilities of the data, the
influence of such potential confounding variables, like
age, parity, and smoking, was controlled for. The adjust-
ment for possible confounders decreased associations of
anxiety and depression with hypertension, underlining
their relevance; however, significant associations
remained even after adjustment.
Another possible explanation for this result is that
hypertension during pregnancy emerges based on a
complex interplay of underlying biological mechanisms
such as alterations in the sympathetic and parasympa-
thetic nervous system, changed immunological process-
es, or an increased hypothalamic–pituitary–adrenal activ-
ity (Patten et al. 2009; Qiu et al. 2009; Scott et al.
2009; Field et al. 2010; Wadhwa et al. 1993). Several
investigators have documented altered plasma cortisol,
β-endorphin corticotrophin releasing hormone, and sero-
tonin concentrations in pregnant women with mood and
anxiety disorders (e.g., Halbreich 2005; Wadhwa 2005).
The special risk elevation for overweight pregnant wom-
en with pure anxiety disorder and with comorbid anxiety
and depressive disorder that this paper documents for the
first time may be explained by chronic inflammation pro-
cesses: First, it has been widely accepted that a chronic
low-grade inflammation under conditions of overweight or
obesity exists (e.g., Purkayastha and Cai 2013). Second, it
is assumed that a chronic inflammation is important in the
pathogenesis of comorbid anxiety and depressive disorders,
especially depression (Camacho 2013; Raison et al. 2006).
And third, it is known that a chronic inflammation (which
is often present in overweight individuals) is a risk factor
for hypertension (Purkayastha and Cai 2013; Schiffrin
2013). Hence, it may be that in women with anxiety and/
or depression, synergistic effects of psychopathology and
obesity lead to a special vulnerability for hypertension.
However, this does not explain the finding that a higher
BMI is especially relevant in women with pure anxiety
disorders, because inflammation does not play as important
a role in anxiety disorders as in depressive disorders
(Vogelzangs et al. 2013). Also, during pregnancy, the in-
flammation processes are changed (Challis et al. 2009), and
for this reason, implications from studies in nonpregnant
populations are limited. Further studies with pregnant
481
women designed to assess neuroendocrine, hemodynamic,
and vascular effects of maternal mood and anxiety disor-
ders are required before final conclusions can be drawn
about these hypotheses (Qiu et al. 2009).
Strength and limitations
Major strengths of the study are a prospective design
with multiple assessments, the application of well-
defined categorical diagnoses (DSM-IV-TR) for both ma-
ternal anxiety and depressive disorders prior to pregnan-
cy, the additional consideration of comorbidity and the
widely used definition of hypertension, the adjustment
for possible confounding variables, as well as the con-
sideration of the BMI of the pregnant women. Since we
used an epidemiological sampling design and did not
sample mothers in clinical-psychiatric settings, our re-
sults might be better applicable in general to pregnant
women living in the community.
In this investigation, the hypertension criterion required
at least two independent blood pressure measurements
≥140 mmHg systolic and/or 90 mmHg diastolic to ensure
reliability (Regitz-Zagrosek et al. 2011). However, the
quality of blood pressure measurements in the doctors’
or midwives’ offices is unclear, and it is uncertain wheth-
er the guidelines for the blood pressure measurement were
always followed (e.g., allowing the patient to sit for three
to five minutes prior to the measurement, Mancia et al.
2013). For some women, only a few blood pressure mea-
surements were available; however, an additional analysis
showed that the number of measurements did not differ
significantly and substantively between the diagnostic
groups (tables on request). Therefore, it seems unlikely
that the variation in available measurements has intro-
duced substantial bias into the group comparisons. Anoth-
er limitation may be that an office hypertension (patients
exhibit elevated blood pressure in a clinical setting but not
in other settings) may have an effect on the associations,
because women with anxiety could have a temporarily
increased blood pressure due to stress and tension
(Ogedegbe et al. 2008). However, an isolated office hy-
pertension is also associated with a higher cardiovascular
risk (Mancia et al. 2013).
Finally, based on these data, no conclusion about cau-
sality can be drawn. Even if pre-existing anxiety and
depressive disorders were analyzed, it is unknown which
of the hypertension or the mental disorder was present
first (e.g., women could have suffered from chronic hy-
pertension). However, with this design, it seems unlikely
that hypertension caused in all women the anxiety and
depressive disorders, since most women with hyperten-
sion during pregnancy experience it during pregnancy for
the first time (Zhang et al. 1997).
482
Conclusions
Considering that hypertension during pregnancy is not only
associated with low infant birth weight and other pregnancy
and birth-related complications (Churchill et al. 1997; Regitz-
Zagrosek et al. 2011; Roberts et al. 2003; Sibai et al. 2005),
but also with an overall increase in lifetime cardiovascular risk
(Bellamy et al. 2007; Lindheimer et al. 2008), the findings are
crucial despite the before-mentioned limitations. For preven-
tion, women who are overweight and have pure anxiety
disorder or comorbid anxiety and depressive disorders should
be informed about their heightened risk of hypertension, and
their blood pressure should be carefully monitored during
pregnancy, e.g., with additional measurements at home. The
guidelines on the management of cardiovascular diseases
during pregnancy recommend pharmacological treatments
for hypertension only under certain conditions, as a too low
blood pressure may impair uteroplacental perfusion and there-
fore risk fetal development. Also, not all drugs are recom-
mended, due to fetotoxicity (Regitz-Zagrosek et al. 2011). As
a nonpharmacological management of mild hypertension
(140–150 mmHg systolic and 90–99 mmHg diastolic), the
guidelines recommend, for example, changes in diet, bed rest,
and limitation of activities (Regitz-Zagrosek et al. 2011).
Weight reduction during pregnancy for obese women is ex-
plicitly not recommended as it may lead to reduced neonatal
weight (Regitz-Zagrosek et al. 2011). However, guidelines for
healthy ranges of weight gain during pregnancy have been
established: For pregnant women who are overweight (BMI
25.0–29.9 kg/m2), this is 6.8–11.2 kg, and for obese pregnant
women (BMI≥30 kg/m2), the recommended weight gain is
<6.8 kg (Regitz-Zagrosek et al. 2011). In this context, the
results of the present analysis indicate also that further treat-
ment options for hypertension during pregnancy may be
promising. Physical activity in general and fitness training
could be especially useful in women with no contraindications
since both are significantly associated with a reduced blood
pressure, help to control weight gain, and also improve psy-
chological well-being (Warburton et al. 2006). Other promis-
ing interventions that are recommended for pregnant women
to help reduce blood pressure and improve psychological
well-being could be relaxation training (Little et al. 1984),
yoga (Beddoe et al. 2009), and mindfulness-based interven-
tions (Dunn et al. 2012). Future studies are required to ascer-
tain if such interventions may help these women to reduce
their risk of hypertension and to cope with physical and
psychological challenges that are associated with pregnancy.
Acknowledgments This work is funded by the Institute of Clinical
Psychology and Psychotherapy, Technische Universität Dresden and
supported in part by the Lundbeck Institute Skodsborg, Denmark. Parts
of the field work were additionally supported by the friends and sponsors
(Gesellschaft der Freunde und Förderer) of the Technische Universität
Dresden. Principle investigators are Dr. Julia Martini and Prof. Dr. Hans-
S. Winkel et al.
Ulrich Wittchen. Core staff members of the project are Dipl.-Psych.
Yvonne Hansche, Dr. Michael Höfler, Dipl.-Psych. Julia Niehoff, Dipl.-
Psych. Johanna Petzoldt, Dipl.-Math. Jens Siegert, Dipl.-Psych. Gesine
Wieder, Dipl.-Psych. Susanne Winkel, and Dipl.-Psych. Julia Wittich.
Advisors/consultants to the project are Prof. Dr. Katja Beesdo-Baum,
Prof. Dr. Franziska Einsle, and Dr. Susanne Knappe.
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