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OPEN

Received: 2 June 2017

Accepted: 6 October 2017

Obstetric outcomes in pregnant
women with and without
depression: population-based
comparison
1,2,3 4,5 2 6
Hui-Chun Huang , Fung Chang Sung , Pei Chun Chen , Cherry Yin Yi Chang , Chih-
4 2,7,8 3,9,10 2 11
Hsin Muo , Huei Sheng Shiue , Jian Pei Huang , Tsai Chung Li , Ya Ling Tzeng

9,12
& Shu-I Wu

This study used insurance claims data to evaluate obstetric outcomes in pregnant women with and without
depression because population study for Asian women on the issue is limited We identifed 5,064 women with
depression at pregnancy in 2005 2013, and 20,024 pregnant women without depression, frequency matched
by age, pregnant year and parity Obstetric events during pregnancy and deliveries were evaluated The
depression group had more events than comparisons

for hyperemesis (39 3 vs 35 5 ), abortion (3 3 vs 2 6 ), malpresentation (12 3 vs 10 3 ), C section (40 2 vs 34

6 ) and intrauterine fetal demise (0 7 vs 0 4 ); risks of these events were signifcant for childbearing
depressed women, not for the 35+ years subgroup These incidences were higher in depressed women
taking antidepressant than those without the medication, but were signifcant in childbearing
depressed subgroup for hyperemesis and C section with odds ratios of 1 18 (95 confdence intervals (CI),
1 02 1 36) and 1 29 (95 CI, 1 11 1 49), respectively Incident preterm and low birth weight births were also
higher in the depression group than in comparisons, but weren t

signifcant In conclusion, women with depression during pregnancy may develop more adverse events
than comparisons and are more likely to have a C section delivery

e prevalence of depression has increased in recent years, up to approximately 20% of pregnant women
reported having depressive disorders13. Depressive disorders during pregnancy have been associated with
negative preg-nant outcomes, such
as preeclampsia, preterm delivery,
premature rupture of membranes,
and low infant birth weight. ese
events lead to neonatal and maternal
morbidity and higher healthcare
costs49. ere are more studies on
neonatal outcomes than studies on
other obstetric outcomes associated
with maternal depression during
pregnancy1015.
Studies on whether depression during
pregnancy is associated with increased
adverse events on the mother and
fetus remain inconclusive.
Approximately 15% of women are
classi ed as depressed in a cohort
study of 228,876 singleton
pregnancies in the Tennessee
2
Medicaid population . e risk of
SCiEntifiC RepOrtS | 7: 13937 | DOI:10.1038/s41598 017
12
preterm birth and infant con-vulsions are more common in depressed women who have received medications . A
study in Sweden found that planned Cesarean deliveries are more common in women with depression and/or anxiety
5
during pregnancy .
1 2
Department of Medical Research Mackay Memorial Hospital New Taipei 251 Taiwan. Department of Public Health
3
China Medical University Taichung 404 Taiwan. Center for General Education, MacKay Junior College of Medicine
4
Nursing and Management Taipei 112 Taiwan. Management Ofce for Health Data China Medical University Hospital
5
Taichung 404 Taiwan. Department of Health Services Administration, China Medical University Taichung 404 Taiwan.
6
Department of Obstetrics and Gynecology, China Medical University Hospital,
7 8
Taichung 404 Taiwan. Division of Physical Medicine and Rehabilitation E Da Hospital Kaohsiung 824 Taiwan. School of
9
Medicine for International Students I Shou University Kaohsiung 824 Taiwan. Department of Medicine,
10
Mackay Medical College Taipei 252 Taiwan. Department of Obstetrics and Gynecology, Mackay Memorial
11 12
Hospital Taipei 104 Taiwan. School of Nursing China Medical University Taichung 404 Taiwan. Department of
Psychiatry Mackay Memorial Hospital Taipei 104 Taiwan. Fung Chang Sung and Shu I Wu contributed equally to
this work. Correspondence and requests for materials should be addressed to F. C.S. (email: fcsung1008 yahoo.
com) or S. I.W. (email: shuiwu624 gmail.com)X
14266 3 1
www.nature.com/scientificreports/
County Mental Health System
reported that mental illness was
associated with elevated risk of
A study obstetric complications;
conducted in however, the analysis included
Taiwan several types of mental illnesses,
found that and data on depression was not
women with reported separately.
depression
are less
likely to Findings on adverse events for
have pregnant women with
prenatal care depression are inconsistent. e
but incur inconsistency can be related to
higher the limited sample size of
expenses for studies or the quality of
other types data19,20. A recent systemic
of study analyzed 23 stud-ies
16
healthcare . covering 25 663 women with
Another untreated antenatal depression
follow-up reported that these women
study based were more likely to have low
on a small
birth weight infant and preterm
sample of 21
depressed birth . Among these 23
pregnant studies, a Korean study failed
women to nd an asso-ciation between
failed to pregnant depression and low
observe birth weight22. Information
signicant from a population-based study
unfavorable
with larger samples for Asian
obstetric
17 women is limited. A recent
outcomes . study conducted in China
Women may reported that prenatal
discontinue depression combined with
antide-
anxiety is at a higher risk of
pressant use
prior to
having a low birth weight
23
conception baby . Because of the scarcity
or during the of research for Asian
rst trimester population, it remains both
of pregnancy opportunity and challenges. In
to ensure the present study, we used
safe fetal large insurance claims data to
development investigate whether pregnant
18
. e study of women with depression is
the associated with adverse
California obstetric outcomes and
County neonatal outcomes during
Mental pregnancy and delivery. e
Health obstetric outcomes were
System compared between two groups;
reported that
one group consisted of women
the risk of
obstetric
with depression and the other
complication group had no such disorder
s is lower for before and during pregnancy.
depressed We further assessed whether
women the association between
treated in the depression and obstetric
system than complications diers by
those treated maternal age at birth and
in other antidepressant medication.
settings,
with
adjusted Results
odds ratios Baseline
(aORs) of characteristics of study
1.32 and cohorts Table1 shows
1.72,
that most women in this study
respectively,
compared were mainly low-income
with general population in the age of 2534,
women . e
15 living in the northern Taiwan
study of the
and pregnant for the first time.
California Women in the depression
group were OR =1.33, 95% CI =1.10
more 1.61), malpresentation
prevalent (adjusted OR =1.20, 95% CI
with =1.081.33), and intrauterine
comorbiditi fetal demise (adjusted OR
es than =1.69, 95% CI = 1.12 2.56). e
were the occurrence of Cesarean
non- sections was 6% higher in the
depression depression group than in the
group. comparison group (40.2% vs.
Approximat 34.6%, adjusted OR = 1.25,
ely one h 95% CI =1.161.34). erefore,
depressed women with depression had a
women lower rate of normal
were spontaneous delivery (59.2%
prescribed vs. 65.1%; adjusted OR =0.80,
for 95% CI =0.740.85).
antidepressa Compared to the non-
nt less than depression group, the
6 months depression group had higher
and only rates of preterm delivery (6.4
0.3% vs. 5.4%) and low birth weight
depression births (2.6 vs. 2.4%), but
women dierences were not signicant.
were on the
medications
for longer Table3 shows the adverse
than 6 obstetric events were signicant
months. mainly for younger depressed
groups. e interac-tion between
age and depression was
Incidenc signicant only for Cesarean
e of section use (p =0.03).
obstetric
and Obstetric events
delivery associated with
events antidepressant use
Incident In the depression group, the
maternal
use of antidepres-sant
obstetric medication was associated
complicatio
with slightly increased events
ns were of hyperemesis,
more likely chorioamnionitis, preterm birth
to occur in and Cesarean section use,
the compared non- users, with an
depression adjusted OR of 2.23 (95% CI
group than =1.194.17) for chorio-
in the amnionitis (Table4). Age-
comparison
specic analysis shows that the
group
medication relationship was
(Table2).
signicant in 2534 years old
Signi cant group for only hyperemesis
dierences and Cesarean section use
were (Table5). Interaction between
observed in age and medication was
the
signicant only for Cesarean
multivariabl
section (p =0.04).
e logistic
regression
analysis. e Discussion
depressed
women In the present study, we
were at a observed that the baseline
greater risk comorbidities were more
for prevalent in the depression
hyperemesi group than in the non-
s (adjusted depressed group, and the vast
OR =1.16, majority of depressed women
95% CI were untreated during
=1.08 pregnancy. is study
1.25), demonstrates increased events
abortion of hyperemesis, abortion,
(adjusted malpresentation, Cesarean
Section, and Cesarean Section remained the
intra-uterine risk in the childbearing age
fetal death depressed women with
in women antidepressant medication.
with
depression Although this study presented
during some research feature is
pregnancy. diering characteristics among
Depressed the study groups, as well as
women other studies, the mechanism
aged 25 to of depression associated with
34 had the adverse obstetric outcomes in
higher risk pregnant women remains
of unclear. Women with
hyperemesi depression display
s, abortion, abnormalities in hypothalamic-
malpresenta pituitary-adrenal axis activity
tion, and exhibit high baseline
Cesarean cortisol levels and promoted
Section in response to the arginine
the age vasopressin and corticotropin-
stratied
releasing hormone24.
analysis.
Our data revealed that depressed
When
pregnant women had a higher
examining
risk of hyperemesis gravidarum,
antidepressa the risk remained in the
nt childbearing age women with
medication, antidepressant medication.
we found However, the risk of
depressed hyperemesis grav-idarum among
women withchildbearing age women was
antidepressa similar in those with
nt antidepressants treatment and
medication those without antidepressants
did not treatment. e reported incidence
increase of hyperemesis gravidarum is
much risk at relatively rare, varies across eth-
complicatio nic groups, and is dependent on
25
ns. diagnostic criteria . In our
Hyperemesi study, it is more common
s and because of the diagnostic
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Depressed Monthly Income, NTD

Non-depressed

(N =5,064)
(N =20,024)
0.07

n
(%)
n
(%)
p value
*
Age, years

<15,840
4452
(87.9)
17641
(88.1)
0.22
<25
578
(11.4)
2311
(11.5)

15,841 to 25,000
445
(8.8)
1620
(8.1)

25 to 34
3698
(73.0)
14792
(73.9)

>25,000
167
(3.3)
763
(3.8)

>=35
788
(15.6)
2921
(14.6)

Geographic region

Mean (SD)
30.5
(4.7) 0.0005
30.3
(4.58)
0.02
 (0.99)

North
2069
(40.9)
8726
(43.6)

No
4999
(98.7)
19825
(99.0)

Central
1216
(24.0)
4336
(21.7)

Previous parity

South
1326
(26.2) 0.99
5145
(25.7)

0
4372
(86.3)
17268
East (86.2)
453
(9.0)
1817
(9.1)

1
600
(11.9)
2389
Multiple (11.9)
pregnancy

0.07

2
84
(1.7)
336
(1.7)

Yes
65
(1.3)
199
 Anemia
603
(11.9)
1643
(8.2)
<0.0001

3
8
(0.2)
31
(0.2)

Prenatal care visits

Comorbidity

7
676
(13.4)
2661
(13.3)
0.08

Diabetes
13
(0.26)
41
(0.20)
0.48

8 to 9
1472
(29.1)
5514
(27.5)

Chronis
hypertension
108
(2.1)
279
(1.4)
0.0001

10
2916
(57.6)
11849
(59.2)

Hyperthyroidis
m
197
(3.9)
409
(2.0)
<0.0001

Antidepressant medication
 30.034.0 NTD, recently 30.3
NTD.

criteria also included excessive

vomiting during pregnancy. A
None meta-analysis of 59 studies
4015
(79.3)
estimated that near 70% of
pregnant women experience
nausea and/or vomiting and
1.1% with hyperemesis
gravidarum26 . Hyperemesis
gravidarum is a primary reason
for sick leave and
hospitalization during
pregnancy27,28. Nausea and
vomiting of pregnancy (NVP)
cause a substantial negative
eect on the quality of life for
<6 months
women29,30. Wood et al. indi-
1034 cated that the eects of NVP are
(20.4) amplied with increased
severity of NVP symptoms30.
Finding in this study echo
previous studies investigating
the association between
depression and
hyperemesis25,31,32. Bearing in
mind that both depression and
hyperemesis gravidarum leads
to uncomfortable experience
among pregnant women.
Considerable support should
6 months or be considered and provided.
longer
15
(0.3) Our study also found an
increased odds ratio of
abortion among the depressed
women. e abortion risk may be
explained by the decreased
levels of Nerve Growth Factor
(NGF). Recent studies found
that NGF levels are sig-
nicantly lower among
depressed women33 and lower
NGF level is associated with
abortion34. NGF is involved in
pregnancy maintenance35, with
Table 1. an aberrant distribution in
Comparison placental tissue relevant to
in pregnancy failure36. ere have
demographi been several studies focused
c on the association between
characteristi antidepressant and abortion,
cs and yet the study ndings are
comorbiditi controversial. Most of studies
es between indicated that antidepressants
depressed associated with increased risk
women and of abortion37 39. A recent
non- review found that there was no
depressed statistically signicant impact of
women. SD,antidepressant exposure on
standard 14
deviation; rates of spontaneous abortion
NTD, new . Similarly, our study observed
Taiwan no signi cantly increased risk
dollar, one among depressed women
USD is without antidepressant. ese
controversia residual confounding by
l nding may depression severity and
reect adverse lifestyle38,40,41.
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Depressed Abortion
Non-depressed 165
Odds ratio (3.3)
(95% 514
confdence (2.6)
interval) 1.28
(1.071.53)**
1.33
(1.101.61)**
N =5064
N =20024 Intrauterine growth retardation
19
(0.4)
64
(0.3)
1.18
n (0.701.96)
(%) 1.12
n (0.641.97)
(%)
Crude
Adjusted

Hyperemesis
1988
(39.3)
7117
(35.5)
1.17
(1.101.25)***
1.16
(1.081.25)***

Gestational
diabetes
629
(12.4)
Antepartum hemorrhage
2440
459
(12.2)
(9.1)
1.02
1734
(0.931.12)
(8.7)
1.00
1.05
(0.901.11)
(0.941.17)
1.03
(0.921.17)

Preeclampsia/e
clampsia
112
Placental previa
(2.2)
745
439
(14.7)
(2.2)
2851
1.01
(14.2)
(0.821.25)
1.04
0.92
(0.951.13)
(0.731.17)
0.99
(0.901.10)
 Postpartum Hemorrhage
185
(3.7)
688
(3.4)
1.07
(0.901.26)
Placental 1.11
abruption (0.931.32)
54
(1.1)
191
(1.0)
1.12
(0.831.52)
1.05
(0.751.47)

Preterm labor /delivery

325
(6.4)
1080
(5.4)
1.20
(1.061.37)**
1.12
Premature (0.971.29)
rupture
membranes
395 Malpresentation
(7.8) 622
1491 (12.3)
(7.5) 2101
1.05 (10.5)
(0.941.18) 1.20
1.08 (1.071.31)***
(0.951.22) 1.20
(1.081.33)***

Low birth weight

130
(2.6)
488
(2.4)
1.06
(0.871.28)
0.97
(0.781.21)

Chorioamnionit
is
30
(0.6)
99
(0.5)
1.20
(0.801.81)
0.94
(0.581.54)

Normal spontaneous delivery

3000
(59.2)
13033
(65.1)
0.78
(0.730.83)***
0.80
(0.740.85)***

Cesarean Section
2036
(40.2)
6924
(34.6)
1.27
(1.191.36)***
1.25 found that depressed women
(1.161.34)***
had a higher odds ratio of
malpresentation, particularly
Vacuum
Extraction/Forc
in those aged 25 to 34.
eps Malpresentation is an
430 important cause of dystocia
(8.5) leading to a risky delivery, and
1768
(8.8) especially for primiparous
0.96 women42. Research on
(0.861.07)
0.92
malpresentation is scarce, the
(0.811.04) etiology is still unclear. Known
possible risks include a large
baby, polyhydramnios,
multiple pregnancy, low-lying
placenta, preterm labor, and
anomalies of the fetus, uterus
or pelvis43. When
malpresentations occur,
primiparous women are at a
greater risk for oper-ative
delivery than are multiparous
women42. However, we cannot
nd out the cause of
malpresentation among
depressed women in our study,
Intrauterine it remains unanswered for the
fetal death future study.
37
(0.7)
87 Consistent with previous
(0.4)
1.69 studies, pregnant women with
depression in our study were at
(1.152.48)**
1.69 a higher risk of Cesarean
(1.122.56)*
delivery5,6,17,4447. e signicant
risk still remained in the
childbearing age depressed
Table 2. women with anti-depressant
Odds ratios medication in the age strati ed
of maternal analysis. e operation is
obstetric performed generally for
and deliveryreducing the pain threshold,
complicatio increasing pain perception,
ns in impairing uterine contractility
relation to and psychological distress44 .
depression.
While expe-riencing pain,
Adjusted
pregnant women with
odds ratio
depression had difculty to
was
function and cooperate
estimated
properly during labor.
using
Obstetricians may intentionally
logistic
or unintentionally prefer other
regression
operative deliveries due to
controlling
for age, symptoms of depres-sion44. In
geographic addition, women might feel
region, anxiety and fear of childbirth
chronic and request Cesarean
5
hypertensio delivery .
n,
hyperthyroi In this study, around 80% of
dism, depression women are
anemia and unmedicated during the
medication. pregnancy, one h depressed
*p <0.05, women took antidepressants for
**p <0.01, a short period. is observation is
***p consistent with a large cohort
<0.001. study which shows that most
women discontinued
antidepressants before the
12
second trimester of pregnancy .
Patients who discontinue
e present medications may experience
study also more serious depression
symptoms women and non-depressed
before women. We were also capable
conception to stratify data to observe the
or recurrent variation of outcomes by age
depression and antidepressant. is
during circumstance allowed us not
pregnancy
48,49 only to investigate the role of
.e depression itself, but also
potential risk consider the eect of
to the infant
antidepressant medication. In
of
addition, our study focused on
antidepressa
nt use during pregnancy related outcomes
pregnancy is within the pregnancy pathway,
con- rather than delivery or neonatal
14 outcomes. It provided
troversial .
complete information for
In our study,
the risk of depressed women and health
medicated care professionals to weigh
group benets and risks.
resembled
with un- is study also has some
medicated limitations. Demographic data
group. A such as education level, lifestyle
careful history, and mar-ital status, are
treatment not available in the data analysis.
plan is However, the study sample is
essential for unlikely to be a ected by these
women potential confounders because
under Chinese pregnant women not
antidepressa only avoid unhealthy behaviors
nt treatment but also withdraw the treatment
who plan to that might harm the fetus.
conceive or Although our study did not
become provide the education level of
pregnant. the study sample, levels of
income is associated with
e present education. Our data was unable
study is to show a signi cant dierence in
strengthene income between our study
d by using a groups and the potential eect is
large reduced. e second limitation is
population that information on mental
data, disorders before 1996 was not
allowing a available, but we were able to
ascertain caseness and outcomes
high
based on medical contacts during
statistical the follow -up window.
power to However, such measurement
capture errors in both exposure and out-
multiple come ascertainments are
pregnant obscured instead of exaggerated
outcomes to the association of interest. e third
be limitation is that among
compared depression group only 15 (0.3%)
between women had the medications for
depressed longer than 6 months. We were
unable
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Depressed
Non-depressed
Odds ratio
(95%
confdence
interval)

N =5064
N =20024

Malpresentation
53
(9.2)
Age, years 154
n
(%)
n (6.7)
1.41
(1.021.96)*
(%) 1.48
Crude (1.032.13)*
Adjusted

Normal spontaneous
<25 yr N 399
578 (69.0)
1779
2311
(77.0)
0.67
(0.550.82)***
0.63
(0.500.78)***

delivery

Hyperemesis
265
(45.9)
904

(39.1)
1.31
(1.091.57)**
1.29
(1.051.59)*

Abortion
18
(3.1)
62

(2.7)
1.17
(0.681.99)
1.16
(0.632.13)
 1.15
(1.071.24)***
1.14
(1.051.23)**

Abortion
Cesarean 127
Section (3.4)
175 370
(30.3)
528
(2.5)
1.39
(22.9) (1.131.70)**
1.47 1.46
(1.201.80)*** (1.171.82)***
1.58
(1.261.98)***
Malpresentation
460
Intrauterine (12.4)
fetal death 1536
3
(0.5)
(10.4)
6
1.23
(1.101.37)***
(0.3) 1.25
2.00 (1.111.41)***
(0.508.04)
1.72
(0.348.61) Normal spontaneous
2237
(60.5)
9831

(66.5)
0.77
(0.720.83)***
0.79
(0.720.85)***

delivery

2534 yr N
3698

14792

Hyperemesis
1471
(39.8)
5391

(36.5)
 (1.011.42)*
1.17
(0.971.40)

Abortion
Cesarean
Section 20
(2.5)
1448
(39.2) 82
4914
(2.8)
(33.2) 0.90
(0.551.48)
1.29
(1.201.39)*** 0.93
(0.551.56)
1.27
(1.171.38)***

Intrauterine
fetal death
24
(0.7)
61

(0.4)
1.58
(0.982.53)
1.63
(0.982.71)

Malpresentation
109
(13.8)
411

(14.1)
0.98
(0.781.23)
0.99
(0.771.26)

>=35 yr N
788

2921

Normal spontaneous
364
(46.2)
1423

(48.7)
0.90
(0.771.06)
0.92
(0.771.09)

delivery

Hyperemesis
252
(32.0)
822

(28.1)
1.20
 Table 3. Age-specic odds
ratios of maternal obstetric
complications in relation to
depression. Adjusted odds ratio
was estimated using logistic
regression controlling for
geographic region,
hypertension, hyperthyroidism,
anemia and medication.
Interaction between age and
depression was signicant for
Cesarean section (p =0.03), but
not for hyperemesis (p =0.44),
abortion (p =0.25),
malpresentation (p =0.12),
normal spontaneous delivery
(p =0.06) and intrauterine fetal
death (p =0.90).

Cesarean
to observe whether women
Section with antidepressant are at a
413 higher risk for complications
(52.4) because of the small sample
1482
size. To bridge this gap with
adverse outcome, future
(50.7)
1.07
studies will need to provide
(0.911.25) enough subjects to evaluate
1.04 (0.88 outcomes related to
1.24) medication.

is population-based
retrospective cohort study
presented that pregnant women
with depression are asso-ciated
with higher risk of
hyperemesis, abortion,
malpresentation, and Cesarean
Section. ese ndings have
important clinical implications
for pregnant women and health
care professionals. To make a
decision about care during
pregnancy, depressed women
Intrauterine and clinicians must weigh risks
fetal death
10 and benets of treatment options
(1.3) against the consequence
20 associated with untreated
illness. e underlying
(0.7) mechanisms on severity of
1.86
(0.874.00)
depression, comorbidi-ties, and
1.88 (0.84 obstetric outcomes still require
4.20) further explorations.

Methods

Data source and study

population The
Department of Health of
Taiwan launched a single-
payer National Health
Insurance 2013 for one million persons
(NHI) randomly selected from all
program in insured people. Diagnoses were
March coded with the International
1995. Classication of Disease, 9th
Approximat Revision, Clinical Modication
ely 99% of (ICD-9-CM). From the 2005
the 23 2013 claims data, we identied
million pregnant women who had the
people in diagnosis of depression during
pregnancy (ICD-9-CM codes of
Taiwan
depression: 296.2, 296.20 to
registered in296.25, 296.2, 296.30 to 296.35,
this 296.82, 300.4, 309.0, 309.1,
program by 309.28, and 311). Only pregnant
2000. With women with the depression
the diagnosis for at least 3 times in
authorizatio the outpatient records or for at
n from the least once depression diagnosis
Bureau of in the inpatient records were
National included in the depression
Health cohort. Depressed women with
Insurance, the history of schizophrenia
the National (ICD-9-CM 295), bipolar
Health disorders (ICD-9-CM 296,
Research 296.2, and 296.3) and/or anxiety
Institutes of (ICD-9-CM 300) were excluded.
Taiwan ere were 5,064 women eligible
established for inclusion in the depression
group. For each depressed
several data
woman, we identied 4 pregnant
les of women without the history of
reimbursem depression, schizophrenia,
ent claims bipolar disorders and anxiety as
publicly the comparison group, frequency
available matched by age, parity and
for pregnancy year. Overall, 20,024
research. women were identied for the
We obtained non- depressed group. e
from the Research Ethics Committee of
National China Medical University and
Health Hospital approved this study
Research (CMUH-104-REC2115). e
Institutes the original identication number of
Longitudinal each person in this secondary
Health database has been encrypted and
Insurance replaced with surrogate
Database, identication. e study popula-tion
contain-ing was waived from informed
claims data consent process because there
from 1996 to was no breach of privacy.
tifiC RepOrtS | 7: 98 017 14266 3
13937 | 5
SCiEn
DOI:10.1038/s415
www.nature.com/scientificreports/

Preeclampsia/eclampsia
439
(2.2)
89
Non-
(2.2)
0.93
Depression (0.731.17)
without 23
Odds ratio (2.2)
(95% 0.84
Depression (0.541.31)
with
Odds ratio
(95%

depressed

confdence
medication
confdence

N =20024
medication N
=4015
interval)
N =1049
interval)
Abortion
514
(2.6)
n 137
(%) (3.4)
n 1.33
(%) (1.101.61)**
Adjusted 28
n (2.7)
(%) 1.04
Adjusted (0.701.52)

Hyperemesis Intrauterine growth retardation

7117 64
(35.5) (0.3)
1565 15
(39.0) (0.4)
1.16 1.12
(1.081.25)*** (0.641.97)
422 4
(40.2) (0.4)
1.19 1.11
(1.051.35)** (0.403.05)

Gestational
diabetes
2440
(12.2)
501
(12.5)
1.00
(0.901.11)
128
(12.2)
1.04
(0.861.26)

Antepartum hemorrhage
1734
(8.7)
364
(9.1)
1.03
(0.921.17)
95
(9.1)
1.06
(0.851.31)
 1.08
(0.951.22)
75
(7.2)
0.98
(0.771.25)

Placental previa
2851
(14.2)
580
(14.5)
0.99
(0.901.10)
165
(15.7) Chorioamnionitis
1.13 99
(0.951.34) (0.5)
19
(0.5)
0.94
(0.581.54)
11
(1.1)
2.23
(1.194.17)*

Postpartum Hemorrhage
688
(3.4)
155
(3.9)
1.11
(0.931.32)
30
(2.9)
0.81
(0.561.17)

Placental
abruption
191
(1.0)
43
(1.07)
1.05
(0.751.47)
11
(1.05)
1.03
(0.561.88)

Preterm labor/delivery
1080
(5.4)
250
(6.2)
1.12
(0.971.29)
75
(7.2)
1.33
(1.041.70)*

Malpresentation
Premature 2101
rupture (10.5)
membranes 507
1491 (12.6)
(7.5) 1.20
320 (1.081.33)***
(8.0) 115
(11.0)
1.05
(0.861.28)

Low birth
weight
488
(2.4)
101 Intrauterine fetal death
(2.5) 87
0.97 (0.4)
(0.781.21) 31
29 (0.8)
(2.8) 1.69
1.11 (1.122.56)*
(0.761.63) 6
(0.6)
1.28
(0.562.94)

Table 4. Odds ratios of

obstetric and delivery
complications in relation to
depression with and without
antidepressant medication.
Adjusted odds ratio was
estimated using logistic
regression controlling for age,
geographic region, chronic
hypertension, hyperthyroidism,
and anemia. *p <0.05, **p
<0.01, ***p <0.001.
Normal
spontaneous
delivery
13033
(65.1)
2366
(58.9) Non-
0.80 Depression without
(0.740.85)*** Odds ratio (95% confdence
634 Depression with
(60.4) Odds ratio (95%
0.80
(0.710.92)**

Cesarean depressed
Section medication
6924 interval)
(34.6)
1625
(40.5)
1.25 medication
(1.161.34)***
confdence interval)
411
(39.2)
1.24 Age, years
(1.091.42)** n
(%)
n
Vacuum (%)
Extraction/Forc
eps
1768 Adjusted
(8.8) n
328 (%)
(8.2) Adjusted
0.92
(0.811.04)
102 <25 yr N
(9.7) 2311
1.10 438
(0.891.36)

140
 0.63
(0.500.78)***
104
(74.3)
0.86
(0.581.28)

delivery

Hyperemesis
904
(39.1)
201
(45.9)

1.29
(1.051.59)**
63
(45.0)
1.26 (0.89
1.77)

Abortion
62
(2.68)
13
(2.97)

1.16
(0.632.13)
5
(3.57)
1.34 (0.53
3.40)

Malpresentatio
n
154 Cesarean Section
(6.66) 528
42 (22.9)
(9.59) 141
(32.2)
1.48
(1.032.13)* 1.58
11 (1.261.98)***
(7.86) 34
1.18 (24.3)
(0.622.23) 1.08
(0.731.62)

Normal
spontaneous Intrauterine fetal death
1779 6
(77.0) (0.26)
295 2
(67.4) (0.46)
 1.46
(1.171.82)***
1.72 21
(0.348.61) (2.66)
1 1.06
(0.71) (0.681.66)
2.99
(0.3525.2)
Malpresentation
1536
(10.4)
372
(12.8)

1.25
(1.111.41)***
88
(11.2)
1.07
(0.851.34)

Normal spontaneous
9831
(66.5)
1762
(60.6)

0.79
(0.720.85)***
475
2534 yr N (60.3)
14792 0.78
(0.670.90)**
2910
delivery

788

Hyperemesis
5391
(36.5)
1152
(39.6)

1.14
(1.051.23)**
319
(40.5)
1.18
(1.021.36)*

Abortion
370
(2.50)
106
(3.64)
Cesarean Hyperemesis
Section 822
4914 (28.1)
(33.2) 212
1137 (31.8)
(39.1)
1.17
1.27 (0.971.40)
(1.171.38)*** 40
311 (33.1)
(39.5) 1.24
1.29 (0.841.83)
(1.111.49)***

Intrauterine
fetal death
61
(0.41)
20
(0.69)

1.63
(0.982.71)
4
(0.51)
1.17
(0.423.24)

Abortion
82
(2.81)
18
(2.70)

0.93
(0.551.56)
2
(1.65)
0.55
(0.132.27)

>=35 yr N
2921

667

121

Malpresentation
411
(14.1)
93
(13.9)

0.99 (0.771.26)
16
(13.2)
0.91 (0.531.56)
 Section
1482
(50.7)
347
(52.0)

1.04 (0.881.24)
66
(54.6)
1.14 (0.791.64)

Normal
spontaneous
1423
(48.7)
309
(46.3)

0.92 (0.77
1.09)
55
(45.5)
0.91 (0.63
1.31) Intrauterine fetal death
20
(0.68)
delivery 9
(1.35)

1.88 (0.844.20)
1
(0.83)
1.13 (0.158.56)

Table 5. Age-speci c odds

ratios of maternal obstetric and
delivery complications in
relation to depression with and
without antidepressant
medication. Adjusted odds
ratio was estimated using
logistic regression controlling
for geographic region, chronic
hypertension, hyperthyroidism,
and anemia. *p <0.05, **p
<0.01, ***p <0.001 Interaction
between age and medication
was signi cant for Cesarean
section (p =0.04), but not for
hyperemesis (p =0.77),
abortion (p =0.44),
malpresentation (p =0.33),
normal spontaneous delivery
(p =0.09) and intrauterine fetal
Cesarean death (p =0.97).
SCiEntifiC 98 017 14266 3
RepOrtS | 7:
6
13937 |
DOI:10.1038/s415
www.nature.com/scientificreports/
this study. e Chi-square test was
used to examine the dierences
between the depression group
Outcome and the comparison group for the
measure baseline sociodemographic
s We characteristics, including age
examined (<25, 2534 and 35 years),
obstetric geographic region of residence
adverse (Northern, Central, Southern,
and Eastern), monthly income
outcomes
(<15,840 NTD [one USD is
occurred
equivalent to 3034 NTD, which
during is 30.3 NTD recently],
pregnancy 15,841~25,000 NTD and
and post- 25,001 NTD), pregnancy
delivery in history, and comorbidities.
both Comorbidity was considered if
groups. We the woman was diagnosed at
evaluated least twice in the outpatient
incident claims or once in the inpatient
events of claims. Diabetes, hypertension,
hyperemesi hyperthyroidism, and anemia
s, were the comorbidities included
gestational in this study. We measured the
diabetes, number and incidence rate of
each of aforementioned
preeclampsi
pregnancy events for both the
a/ depression and comparison
eclampsia, groups. Univariate and multiple
abortion, logis-tic regression analyses
intrauterine assessed the odds ratio (OR) of
growth each obstetric event associated
retardation, with the depression status. Both
antepartum crude OR and adjusted OR with
hemorrhage 95% condence intervals (CI)
, placenta were presented. Age, geographic
previa, region, par-ity, and comorbidity
placental were included in the
abrup-tion, multivariable analysis. Age-
premature specic analyses were further
rupture of performed to identify high-risk
membranes, age group if the obstetric event
chorioamni appeared signicant. Interactions
onitis, between age and depression
postpartum were examined for these events.
Further data analysis compared
hemorrhage
the controls against depression
, preterm with and with-out medication.
delivery, Age-specic analyses were also
low birth performed to identify high-risk
weight, age group if the obstetric event
malpresenta appeared signicant. Interactions
tion, normal between age and anti-depressant
spontaneous medication were examined for
delivery, these events.
Cesarean
section,
vacuum
Data availability e data
extraction that support the ndings of this
delivery andstudy were obtained from
intra-uterine National Health Research
fetal death. Institutes (NHRI) of the
Ministry of Health and Welfare
in Taiwan but restrictions
Statistica apply to the availa-bility of
l these data, which were used
analyses under license for our study, and
We used so are not publicly available
SAS soware for duplication. Data can be
version 9.4 requested only from the
(SAS Ministry of Health and
Institute Welfare.
Inc., Carey,
USA) to
perform data References
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clinical Medical University Hospital;
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CMU under the Aim for Top
University Plan of the Ministry
72, 9941001 of Education, Taiwan. e
(2011).
funding agencies had no role in
study design, data collection
Acknowl and analysis, decision to
edgemenpublish, or preparation of the
manuscript. No additional
ts external funding received for
this study. FC Sung and SI Wu
is study is have equal contribution for this
supported instudy.
part by
Taiwan
Author Contributions
Ministry of
Health and
Welfare Study concept development:
Clinical H.C.H., C.Y.Y.C. and H.S.S.;
Trial Center study design: H.C.H.,
(MOHW10 C.Y.Y.C., F.C.S. and P.C.C.;
6-TDU- B- designed and performed the
212- studys data analysis: H.C.H.,
113004); C.H.M. and J.P.H.; data
Academia interpretation: all authors; dra
Sinica manuscript and literature
Taiwan study: H.C.H., F.C.S., P.C.C.,
Biobank, T.C.L., Y.L.T. and S.I.W.; nal
Stroke approval of the version to be
Biosignatur published: F.C.S. and S.I.W.
e Project
(BM105010
10037);
Additional Information
NRPB Competing Interests: e
Stroke authors declare that they have
Clinical no competing interests.
SCiEntifiC DOI:10.1038/s41598
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