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Just Accepted by The Journal of Maternal-Fetal & Neonatal Medicine

Is antenatal depression associated with adverse obstetric and perinatal outcomes?

M Yedid Sion, A Harlev, AY Weintraub, R Sergienko, E Sheiner

doi: 10.3109/14767058.2015.1023708

Abstract

Objective:

To examine whether a pre-gestational diagnosis of depression is a risk factor for adverse obstetric and neonatal outcome.

Study design:

A retrospective cohort study investigating maternal characteristics, obstetrical and perinatal outcomes in singleton pregnancies of women with and without a diagnosis of depression was conducted. A pre-gestational diagnosis of depression was made by a psychiatrist or family physician and was recorded in the patients' chart. Multiple logistic regression models were used to control for possible confounders.

Results:

During the study period, 256312 deliveries occurred. Out of which, 221 women (0. %) had a pre-gestational diagnosis of depression. When examining obstetric outcomes, women with a diagnosis of depression were

older (32.05±5.772 VS 28.56±5.851) and smokers (7.2% VS 1.1%), had a higher rate of preterm deliveries

(37.99±2.989 VS 39.02±2.249) and cesarean sections (28.5% VS 13.6%) in comparison to the control group. When examining neonatal outcomes, neonates of women diagnosed with depression had a lower birth mean weight (3.038.47±649.6 VS 3183.44±551.8) and increased rates of perinatal mortality (3.2% VS 1.3%). Using a multiple logistic regression model, with perinatal mortality as the outcome variable to control for cofounders such as maternal age, preterm birth, chronic hypertension and gestational diabetes mellitus, a diagnosis of depression was not found to be an independent risk factor for perinatal mortality. Another multiple logistic regression model found advanced maternal age, smoking, preterm birth and labor induction to be associated with a diagnosis of depression.

Conclusion:

Pregnant women diagnosed with depression are at an increased risk for preterm birth, low birth weight, and cesarean sections. However, it was not associated with increased rates of perinatal mortality.

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Is antenatal depression associated with adverse

obstetric and perinatal outcomes?

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Is antenatal depression associated with adverse obstetric and perinatal

outcomes?

Yedid Sion M1, Harlev A

1, Weintraub AY

1, Sergienko R

2, Sheiner E

1

1 Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University

Medical Center, Ben-Gurion University of the Negev, Israel.

2 Department of Epidemiology and Health Services Evaluation, Faculty of Health Sciences,

Soroka University Medical Center, Ben-Gurion University of the Negev, Israel.

Key words:

Antenatal depression, risk factor, low birth weight

Corresponding author: Eyal Sheiner, MD, PhD

Department of Obstetrics and Gynecology

Soroka University Medical Center

POB 151

Beer Sheva 84101

Israel

sheiner@bgu.ac.il

Abstract

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Objective:

To examine whether a pre-gestational diagnosis of depression is a risk factor for adverse obstetric and

neonatal outcome.

Study design:

A retrospective cohort study investigating maternal characteristics, obstetrical and perinatal outcomes in

singleton pregnancies of women with and without a diagnosis of depression was conducted. A pre-

gestational diagnosis of depression was made by a psychiatrist or family physician and was recorded in

the patients' chart. Multiple logistic regression models were used to control for possible confounders.

Results:

During the study period, 256312 deliveries occurred. Out of which, 221 women (0. %) had a pre-

gestational diagnosis of depression. When examining obstetric outcomes, women with a diagnosis of

depression were older (32.05±5.772 VS 28.56±5.851) and smokers (7.2% VS 1.1%), had a higher rate of

preterm deliveries (37.99±2.989 VS 39.02±2.249) and cesarean sections (28.5% VS 13.6%) in

comparison to the control group. When examining neonatal outcomes, neonates of women diagnosed with

depression had a lower birth mean weight (3.038.47±649.6 VS 3183.44±551.8) and increased rates of

perinatal mortality (3.2% VS 1.3%). Using a multiple logistic regression model, with perinatal mortality

as the outcome variable to control for cofounders such as maternal age, preterm birth, chronic

hypertension and gestational diabetes mellitus, a diagnosis of depression was not found to be an

independent risk factor for perinatal mortality. Another multiple logistic regression model found

advanced maternal age, smoking, preterm birth and labor induction to be associated with a diagnosis of

depression.

Conclusion:

Pregnant women diagnosed with depression are at an increased risk for preterm birth, low birth weight,

and cesarean sections. However, it was not associated with increased rates of perinatal mortality.

Introduction

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The onset of depression is reported to peak during childbearing years and it is approximately twice more

common in women than in men [1]. Traditionally, pregnancy is considered a period of wellbeing and

happiness, and was once thought to protect women from depression [2]. However, this period can also be

emotionally stressful, despite the positive expectation of an offspring.

Antenatal depressive symptoms are frequent and prevalent in developed as well as in developing

countries. Recent estimates regarding the prevalence of major depression during pregnancy show that

8.3% to 12.7% of US women experience depression [3, 4]. Studies conducted in other countries, have

shown an average prevalence of around 20% and according to one study, depressed mood in pregnancy

was reported to be as high as 39% [5-7]. Though the prevalence of antenatal depression varies in severity,

it is still unquestionably a widespread condition among pregnant women.

The association between depressive symptoms and pregnancy complications and adverse pregnancy

outcomes is controversial. While some studies have found an association between antenatal depression

and pregnancy complications and adverse outcomes such as preeclampsia, preterm delivery, low birth

weight and cesarean delivery [2-3, 8-11], others have not [12-14]. The present study was aimed to

examine whether a diagnosis of pre-gestational maternal depression is a risk factor during pregnancy for

adverse obstetrical and neonatal outcomes.

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Materials and methods

A retrospective population-based cohort study was conducted at the Soroka University Medical Center

including deliveries that occurred between the years 1988 and 2011. Soroka University Medical center is

the sole tertiary hospital in the southern region of Israel, serving the entire population of the region.

Included were all singleton pregnancies of women who gave birth during the study period. The study

population was divided into two groups: women with and without an existing diagnosis of depression

prior to gestation. Data regarding the diagnosis of depression were recorded by the admitting physician

from the referral information. The diagnosis was made according to the patients' charts, by psychiatrist or

family physician. All depressive disorders diagnoses were included. Data regarding pregnancy

complications and adverse outcomes were retrieved from a computerized perinatal database that consists

of information, recorded directly following delivery, by an obstetrician. The database includes

information regarding antepartum, intrapartum and postpartum characteristics. Skilled medical secretaries

routinely reviewed the information prior to entering it into the database. Coding was performed after

assessing the medical prenatal care records together with the routine hospital documents.

The following maternal clinical characteristics were analyzed: maternal age, ethnicity, gestational age,

gravidity, parity and smoking. Pre-gestational and gestational complications that were assessed:

gestational diabetes mellitus (GDM), anxiety, chronic hypertension, previous cesarean delivery, recurrent

pregnancy loss, fertility treatments, pre-eclampsia, premature rupture of membranes (PROM) and preterm

birth. The following delivery characteristics and complications were assessed: epidural use, cesarean

section (CS), tubal ligation and fetal distress. The neonatal characteristics and outcomes that were

assessed were: Apgar score, birth weight and perinatal mortality.

Statistical analysis was performed using SPSS software (SPSS, Chicago IL). The categorical variables

were compared and their statistical significance was tested using the chi square test or the Fisher exact

test. For continuous variables, significance was tested using the T test or one way analysis of variance

(ANOVA). Multivariable logistic regression models were constructed in order to control confounders.

Odds ratio and their 95% confidence intervals (CI) were computed. P<0.05 was considered statistically

significant.

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Results

A total of 256,312 births met the inclusion criteria during the study period. Of these, 221 patients were

diagnosed with depression prior to gestation. The rest were regarded as a control group. Clinical and

demographic characteristics of patients differed between the two groups. Women belonging to the case

group were more likely to be older, Jewish, with lower gestational age at delivery, higher gravidity albeit

similar parity, as compared to the control group. They also had higher smoking rates (table 1).

Table 2 describes pre-gestational and gestational complications. Women in the case group were more

likely to have a history of CS, higher rates of chronic hypertension, anxiety and anemia diagnosis.

Delivery and neonatal complications and characteristics are presented in table 3. An increased prevalence

of preterm deliveries, low birth weight, low Apgar scores (<7), and CS was noted. Moreover, a significant

increase in perinatal mortality was observed. Women with depression were more likely to undergo labor

induction, as well as epidural anesthesia. Higher rates of tubal sterilization were performed during CS in

the depression group as compared to the control group.

While using a multiple logistic regression model with perinatal mortality as the outcome variable, to

control for cofounders such as maternal age, preterm birth, chronic hypertension and gestational diabetes

mellitus (GDM), a pre-gestational diagnosis of depression was not noted as an independent risk factor for

perinatal mortality (OR 1.361, CI 95%: 0.63-3.105; P=0.45).

In another multiple logistic regression model with depression prior to gestation as the outcome variable,

the following factors were found to be associated with a diagnosis of depression: advanced maternal age

(OR 1.093, CI 1.069-1.118), smoking (OR 5.324, CI 3.163-8.96), preterm birth (OR 2.305, CI 1.620-

3.280) and labor induction (OR 1.391, CI 1.035-1.869).

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Discussion

Based on previous studies that have demonstrated a correlation between psychiatric morbidity and

pregnancy outcome [18-20], in the current study, we aimed to examine whether a pre-gestational

diagnosis of depression is associated with adverse obstetrical and neonatal outcome. The major finding of

our study is that women with a pre-gestational diagnosis of depression were found to exhibit higher rates

of pregnancy complications and adverse perinatal outcomes. When examining maternal demographic and

clinical characteristics, we found several factors to be associated with a diagnosis of maternal depression.

In our study, women diagnosed with depression were significantly older and had a higher gravidity. They

were more likely to be smokers, suffer from anemia, anxiety and chronic hypertension and had higher

rates of a previous CS. These findings were further reinforced by the results of our multivariate analysis

and are consistent with previous studies marking smoking [15], anemia [16] and hypertension [4] as more

prevalent amongst women suffering from depression in comparison to control groups.

Previous studies have reported an association between antenatal depression and preeclampsia [2, 8]. One

study found that depression was associated with a 2.5-fold increased risk for preeclampsia as compared to

the control group [8]. In a study from Finland, no increased risk of preeclampsia was found among

women suffering from mild depression as compared to the control group; however, those with moderate

depression had a 2.3-fold increased risk of preeclampsia, while moderate-severe depression was

associated with a 3.2-fold increased risk of preeclampsia [2]. In contrast to these reports, in our study, no

significant association was found between antenatal depression and preeclampsia [2, 8]. There was also

no significant association between antenatal depression and GDM, which is consistent with the findings

of Katon et al. [17].

Controversy exists regarding the association between antenatal depression and preterm birth or low birth

weight [18-19].In our study antenatal depression was significantly associated with preterm birth and low

birth weight. Likewise, a meta-analysis that covered 29 studies examining the effect of antenatal

depression on pregnancy outcome concluded that women suffering from depression during pregnancy had

an increased risk of preterm birth and low birth weight [3]. This study emphasized an association between

depression during pregnancy and perinatal outcomes. In our study however, women had a pre-gestational

diagnosis of depression. In contrast, other studies revealed no differences in neonatal outcome as

compared to the control group [12-13].

A biologic mechanism can be suggested in order to explain the association between pre-gestational

depression and preterm birth. As previously reported and partially reinforced in our results, pre-

gestational depression is associated with an increase in smoking, alcohol consumption and substance

abuse. Hence, the relation between depression and preterm birth was previously suggested to be mediated

by these behaviors [20]. However, while adjusting for smoking, drug and alcohol use, in some of these

previous studies, the association between depression and preterm birth was persevered, proposing an

independent association between depression and preterm birth. The previously described association

between depression and altered immune reaction as reflected by a reduction in natural killer cell activity

and higher plasma concentrations of pro-inflammatory cytokines might serve as the missing link [21-22].

The depression associated activation of the immune system affects the mother, fetus, placenta, decidua

and myometrium, eventually resulting in the initiation of early parturition process. Therefore,

inflammation might mediate the relation between depression and preterm birth [20]. The same mechanism

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can explain the increased early pre-term delivery (<34 weeks) during stress states, as seen during military

operations and wars [23].

The contradicting results of the different studies regarding the adverse effects of depression could be

partly explained by differences in the tested populations, differences in the criteria used to establish a

diagnosis of depression and the fact that many of the studies were small-scaled and examined limited

perinatal parameters. Other psychiatric conditions such as schizophrenia, anxiety and eating disorders

were also proved to be associated with pregnancy complications and adverse perinatal outcome in recent

literature [24-26]. Hizkiyahu et al. found that schizophrenia and schizoaffective disorders are independent

risk factors for low birth weight (<2500 g) [24]. Pasternak et al. reported that pregnancies of women with

eating disorders are associated with higher rates of adverse maternal and perinatal outcomes, such as

fertility treatments, preterm delivery, low birth weight, IUGR, and CS [25]. A recent study found that

anxiety disorders are an independent risk factor for spontaneous preterm delivery and CS [26]. These

findings coincide with the hypothesis that all mental illnesses, including maternal depression, pose as risk

factors for adverse obstetrical and perinatal outcomes.

Controversy also exists regarding the association between depressive disorders and the mode of delivery.

While several studies found higher rates of CS (either elective or emergency) in patients with a diagnosis

of anxiety disorders [9-10], other studies did not demonstrate this correlation [27-28]. In our study

patients with a diagnosis of depression were characterized by higher rates of previous CS as well as

higher rates of a cesarean mode of delivery. The higher incidence of elective CS might be explained at

least in part by a co- variation of depression with fear of experiencing pain and fear of childbirth [9],

whereas the higher incidence of emergency CS can be credited in part to a difficulty of depressed women

to function properly and cooperate during labor, while experiencing pain. There is general agreement

regarding the extended use of epidural analgesia by patients with depressive disorders [9-10, 29]. Our

data is in agreement with previous studies. Likewise, patients with anxiety show a similar trend [26]. This

also can be explained by fear of experiencing pain.

This study offers several strengths. Our large sample size allowed studying several clinically important

outcomes in women with a diagnosis of pre-gestational depression in our population. Additionally, the

comprehensive database allowed us to access pregnancy outcome information that was obtained in a

prospective manner. It should also be noted that a large number of obstetrical and perinatal outcomes

were examined. Our study has several inherent weaknesses, mostly due to its retrospective nature. One

potential weakness is that some undiagnosed women with a diagnosis of pre-gestational depression are

included in the general population group, an assumption that is reinforced by the fact that the prevalence

of diagnosed antenatal depression is smaller than described in the literature. The categorization of women

as suffering from pre-gestational depression was made only if the women had a previous diagnosis by a

psychiatrist or family physician. It could be expected that only the most severe cases were included, and it

is therefore, likely that a proportion of patients with milder or untreated depression were missed. We did

not discriminate our analysis according to the status of the disease (severity) or whether they were treated

during pregnancy or not. Because the diagnosis of pre-gestational depression was usually known to the

physicians, at the time of labor and delivery, caregiver bias cannot be ruled out; however this represents

real life thus increasing the clinical utility of our findings.

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Another limitation of our study was derived from its focus. The focus of our study was the obstetrical and

perinatal outcomes in a population of women with pre-gestational depression and not on the

characteristics of the depressive disorder itself. Therefore, some information that is related to

characterization of patients with pre-gestational depression, such as duration of symptoms, psychiatric co-

morbidities, suicide attempts, alcohol and drug abuse and antidepressant treatment was not available and

therefore is not presented in the study. No information was available regarding the scope of psychiatric

inpatient and outpatient admission during pregnancy, which may have influenced outcome measures. In

addition, there are confounding variables that were out of our reach, such as social class, that could have

contributed to the analysis.

The study focused on women with a pre-gestational diagnosis of depression. Our database includes only

immediate perinatal outcome and postpartum depression is not routinely recorded. However, farther

prospective studies should investigate this important issue.

Finally, a weakness inherent to retrospective cohort studies is the potential for missing data. However, the

data in our study were reported by an obstetrician directly after delivery. Skilled medical secretaries

routinely reviewed the information before entering it into the database. Coding was done after assessing

the medical prenatal care records together with the routine hospital documents. This makes this potential

source of information bias less likely.

In conclusion, in the current study we found that pregnant women that were diagnosed with pre-

gestational depression are at an increased risk for preterm birth, low birth weight, and CS. Nevertheless,

pre-gestational depression was not associated with an increased rate of perinatal mortality

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content of this article

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Table 1: Maternal demographic and obstetric characteristics:

* Median (abnormally distributed)

Depression No depression P value

N= 221

N= 256091

Maternal age (year ± SD) 32.05±5.772 28.56±5.851 <0.001

Gestational age (week ±

SD)

37.99±2.989 39.02±2.249 <0.001

Gravidity* 4 3 <0.001

Parity * 3 3 0.011

Smoking 7.2% 1.1% <0.001

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Table 2: Pre gestational and gestational complications:

Depression No depression P value

N= 221

N= 256091

Anxiety 5.9% 0.1% <0.001

Recurrent Pregnancy loss 7.7% 5.2% 0.101

Previous CS 19.5% 12.2% 0.001

Fertility treatments 2.3% 1.7% 0.552

chronic hypertension 5% 1.5% <0.001

Pre-eclampsia 5% 4.3% 0.682

GDM 6.3% 5.7% 0.663

Anemia 41.2% 28.2% <0.001

PROM 7.7% 8% 0.860

CS, cesarean section; PROM, premature rapture of membranes; GDM, gestational diabetes mellitus

Table 3: Labor and neonatal characteristics and complications:

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Depression No depression P value

N= 221 (0.1%)

N= 256091 (99.9%)

Labor induction 32.6% 26.6% 0.044

Caesarian section 28.5% 13.6% 0.001

Epidural use 22.2% 14.1% 0.001

Tubal ligation 5% 1.5% <0.001

Pre- term birth

(<37 weeks)

5.9% 2.2% <0.001

Apgar 1 min <7

(%)

12.2% 6.5% 0.001

Apgar 5 min <7

(%)

5.9% 3% 0.012

Low birth Wt

(<=2500gr)

14.5% 8% <0.001

Very low birth Wt

(<=1500gr)

3.6% 1.3% 0.003

Perinatal

mortality

3.2% 1.3% 0.019

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Table 4. Multiple logistic regression models of risk factors for perinatal mortality

Characteristics OR 95% CI p value

Depression 1.361 0.612- 3.025 0.450

Maternal age 1.021 1.016- 1.027 <0.001

Preterm birth 29.092 27.013- 31.330 <0.001

Ethnicity 0.577 0.536-0.621 <0.001

Chronic hypertension 0.813 0.716- 0.923 0.001

GDM 0.522 0.435- 0.625 <0.001

GDM, gestational diabetes mellitus

CI, confidence interval; OR, odds ratio

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Table 5: Multiple logistic regression model of factors associated with antenatal depression

Characteristics OR 95% CI p Value

Maternal age 1.093 1.069- 1.118 <0.001

Ethnicity 1.339 1.008- 1.778 0.044

Smoking 5.324 3.163- 8.960 <0.001

Labor induction 1.391 1.035- 1.869 0.029

Preterm birth 2.305 1.620- 3.280 <0.001

Previous CS 1.408 0.996- 1.992 0.053

Chronic hypertension 1.284 0.808- 2.041 0.289

GDM 0.655 0.377- 1.139 0.134

GDM, gestational diabetes mellitus

CI, confidence interval; OR, odds ratio

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