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 Table of Contents  
Year : 2021  |  Volume : 5  |  Issue : 1  |  Page : 23-29

Risk of adverse perinatal outcomes and antenatal depression based on the zung self-rating depression scale

1 Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China
2 Shanghai Mental Health Center, Shanghai 200030, China
3 Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090; 3Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai 200011, China

Date of Submission30-Aug-2020
Date of Decision08-Oct-2020
Date of Acceptance20-Nov-2020
Date of Web Publication16-Apr-2021

Correspondence Address:
Xian Xia
Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200090
Xiao-Tian Li
Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200090
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2096-2924.313683

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Objective: The aim of the study is to investigate the relationship between antenatal depression and adverse perinatal outcomes.
Methods: This prospective cohort study enrolled pregnant women between gestational ages of 12–20 weeks to complete the Chinese version of the Zung Self-Rating Depression Scale (SDS) and followed them for delivery from September 2015 to September 2016. Participants were classified into mild, moderate, and severe depression groups according to the SDS scores. Logistic regression was performed to assess the association between antenatal depression and perinatal outcomes including preterm birth (PTB), cesarean section use, hypertension disorders, gestational diabetes, and thyroid diseases during pregnancy. An age-stratified analysis was performed.
Results: A total of 4,663 pregnant women were analyzed. As a result, 13.8%, 1.7%, and 0.2% of women were classified as mild, moderate, and severe depression, respectively. Severely depressed mothers were at higher risk for PTB (adjusted odds ratio [OR] =11.31, 95% confidence interval [CI] 2.13–60.03), especially spontaneous PTB. Moderate-depressed women were at higher risk for hyperthyroidism during pregnancy (adjusted OR = 3.67, 95% CI 1.10–12.27), while women with mild depression tended to choose cesarean sections (OR = 1.24, 95% CI = 1.04–1.49). Age-stratified analysis indicated an elevated risk of adverse outcomes associated with depression in women aged <25 years, but the association was not significant.
Conclusions: Antenatal depression was associated with PTB, hyperthyroidism, and cesarean use. Studies with large sample sizes should verify the relationship between PTB and antenatal depression to avoid casual events.

Keywords: Antenatal Depression; Cesarean Section; Preterm Birth; Zung Self-Rating Depression Scale

How to cite this article:
Chen XN, Hu Y, Hu WH, Xia X, Li XT. Risk of adverse perinatal outcomes and antenatal depression based on the zung self-rating depression scale. Reprod Dev Med 2021;5:23-9

How to cite this URL:
Chen XN, Hu Y, Hu WH, Xia X, Li XT. Risk of adverse perinatal outcomes and antenatal depression based on the zung self-rating depression scale. Reprod Dev Med [serial online] 2021 [cited 2021 Jun 22];5:23-9. Available from: https://www.repdevmed.org/text.asp?2021/5/1/23/313683

  Introduction Top

Pregnancy is a period in which there are significant changes in women's lifestyles, social roles, and psychology. Associations between maternal–emotional disorders and neonatal outcomes have been well investigated but inconsistent. Studies have revealed that depressed or anxious mothers were at elevated risk of adverse fetal outcomes such as preterm birth (PTB), low birth weight, and intrauterine growth retardation,[1],[2],[3],[4],[5],[6],[7] while numerous studies did not detect a significant correlation.[8],[9],[10],[11],[12],[13] These conflicting results are due to differences in the study population, sample size, measuring time, measuring scales, and confounding factors. Moreover, several studies failed to distinguish the severity of depression, so it was unknown whether the negative result was due to mild depression. Additional studies have focused on the association between depression and obstetrical complications.[14],[15],[16],[17] However, these studies did not consider the fundamental disease in prepregnancy, such as hypertension or diabetes, and the case–control studies failed to conclude the causal relationship between depression and gestational complications.

Women in developing countries have a higher prevalence of antenatal depression according to epidemiological studies.[18],[19],[20] However, mental health has been neglected in developing countries in the literature.[21],[22],[23] We expected that antenatal depression in developing countries had a stronger association with adverse perinatal outcomes since they have less access to mental care or professional psychological treatment. In China, psychological assessments of pregnant women were not routine. The change of family policy resulted in the elevated incidence of advanced-aged women and multipara in China, leading to the epidemics of psychological stress. This study aimed to fill this gap by focusing on the mental status of pregnant Chinese women.

Our study aimed to explore the association between antenatal depression and adverse obstetric outcomes in the Chinese population and the specific mental status of women of advanced age.

  Methods Top

Data source and study population

This was a prospective cohort study conducted at the Obstetrics and Gynecology (ObGyn) Hospital of Fudan University, Shanghai. The inclusion criteria were (1) pregnant women willing to participate, (2) with singleton gestation, (3) older than 18 years, (4) Han ethnicity, and (5) complete mental measurement questionnaire during 12–20 weeks of gestation. In total, 6,923 pregnant women at the antenatal outpatient visit completed the questionnaire from September 2015 to September 2016. Among them, 6,149 participants completed scales between 12 and 20 weeks of gestational age. After excluding 110 twin gestations, 15 with induced abortion in the early second trimester, and 1,361 due to loss of follow-up due to unknown reasons such as transfer, 4,663 women were finally included for analysis. The study flow is illustrated in [Figure 1]. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional (Obstetrics and Gynecology Hospital of Fudan University) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants included in the study.
Figure 1: Study flow. After recruitment, 110 cases of twin gestation, 15 cases having induced abortion, and 1,361 cases who loss of follow-up were excluded from the study. 4,663 women were finally analyzed. Among them, 643 (13.8%), 81 (1.7%), and 7 (0.1%) mothers were classified into mild, moderate, and severe depression group, respectively, according to Zung SDS score. IUD: Intrauterine death; SDS: Self-Rating Depression Scale.

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Assessment of antenatal depression

Pregnant women were asked to complete the Chinese version of the Zung Self-Rating Depression Scale (SDS). SDS has 20 items, and each item was ranked by scoring from 1 (none or a little of the time) to 4 (most or all of the time), leading to a raw score ranging from 20 to 80.[24],[25],[26] In this scale, 10 items were worded positively and scored reversely. The final index score of SDS was converted by multiplying the raw score by 1.25 and then rounding down decimal places. The severity of emotional disorder was categorized based on the index score: nil depression (index score <50), mild depression (index score 50–60), moderate depression (index score 60–70), and severe depression (index score >70). Participants were guaranteed that all responses would be confidential and anonymous. This study obtained ethical approval from the Fudan Institute's Ethics Committee.

Assessment of perinatal outcomes and confounders

All perinatal outcomes were obtained from the medical records. Gestational age was calculated according to the last menstrual period and/or crown–rump length based on ultrasound in the first trimester. PTB (<37 weeks) was further divided into spontaneous PTB and medically indicated preterm delivery. The former included spontaneous preterm labor or preterm premature rupture of the membranes, and the latter began with induction or cesarean section but did not initiate spontaneous labor or rupture of the membrane. Additional obstetric events included hyperthyroidism, hypothyroidism, gestational diabetes mellitus (GDM), hypertension in pregnancy, and cesarean section use, all obtained from medical records. Hypothyroidism included subclinical (abnormal thyroid-stimulating hormone [TSH] and normal free thyroxin [FT4]) and clinical hypothyroidism (elevated TSH and decreased FT4), while hyperthyroidism only referred to elevated FT4 and normal TSH levels. GDM excluded diabetes diagnosed before pregnancy and pre-GDM diagnosed at the first antenatal visit. Hypertension disorder in pregnancy was analyzed separately according to the severity of gestational hypertension (the transient hypertension of pregnancy or chronic hypertension identified in the latter half of pregnancy) and preeclampsia/eclampsia.[27],[28]

Various potential confounders were obtained from the first outpatient visit, including maternal age, body mass index (BMI), parity, previous abnormal pregnancy, artificial reproductive technology, preexisting hypertension, or vaginal bleeding in the first trimester.

Statistical analysis

Statistical tests included the Kolmogorov–Smirnov test, Levene's test, Student's t-test, and Chi-square test were conducted to compare the characteristics of pregnant women with or without a mood disorder. The number and incidence rates of each perinatal outcome were calculated, including PTB, cesarean use, and obstetric comorbidities including hyperthyroidism, hypothyroidism, hypertension, and diabetes. Univariate and multivariate logistic regression analyses were performed to assess the association between each outcome and mood status categorized from normal to severe.

A sensitivity analysis was performed to analyze the correlation between depression and perinatal outcomes. Two different adjusted models were constructed. First, we adjusted for maternal age, BMI, and parity for the basic model because these covariates were significantly correlated with all adverse perinatal outcomes in the univariable regression. Subsequently, we adjusted for GDM and gestational hypertension disorders in the second adjusted model because they were theoretically correlated with the outcomes. Age-stratified analyses were also performed for several perinatal outcomes since the interaction between age and depression was significant in the logistic regression model.

All data and calculations were stored and performed using SPSS version 20.0 (Chicago, IL, USA). Statistical significance was set at P < 0.05, and all P values were two-tailed.

  Results Top

In total, 4,663 pregnant women were analyzed. [Supplementary Table 1] indicates that mothers lost to follow-up tended to be younger and nulliparous compared with analyzed mothers. There was no difference in BMI, previous history, artificial reproductive technology use, or SDS scores between the missing mothers and analyzed mothers, which explained the random loss of participants. Among the 4,663 mothers analyzed, 20 (0.4%) had a miscarriage, 6 (0.1%) had intrauterine death or delivered dead fetus, 191 (4.1%) had PTB, and 1,557 (33.4%) had a cesarean section. The average index score of SDS was 41.96 ± 9.16, resulting in a prevalence of 15.7% for antenatal depression. Furthermore, 643 (13.8%), 81 (1.7%), and 7 (0.2%) women were categorized into mild, moderate, and severe depression group, respectively. [Table 1] summarizes the baseline characteristics of women with or without emotional disorders. Mothers younger than 25 years (P = 0.001), who had a history of abnormal pregnancy (P = 0.004), who had chronic hypertension (P = 0.026), and who experienced vaginal bleeding in the first trimester (P = 0.023) were more likely to suffer from depression.

Table 1: Comparison of baseline characteristics between depressed and nondepressed women

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[Table 2] presents the incidence of obstetric events and the correlation between the events and maternal depression. Depressed mothers had a higher incidence of these obstetric events. The severely depressed mothers were at a higher risk for PTB (adjusted odds ratio [OR] =9.04, 95% confidence interval [CI] 1.70–48.04), and the risk was elevated to 11.31-fold (95% CI 2.13–60.03) even in the fully adjusted model. However, severe depression was correlated with spontaneous PTB (adjusted OR = 11.43, 95% CI 2.10–62.32) but not with medically induced PTB. The mothers with moderate depression were more likely to have hyperthyroidism (OR = 3.67, 95% CI 1.10–12.27), while mothers with mild depression were more likely to choose a cesarean section (OR = 1.24, 95% CI 1.04–1.49). Hypertension, GDM, and hypothyroidism had no statistically significant correlation with maternal emotional status after adjustment. No increasing trend in the OR value was observed with depression.
Table 2: Incidence and odds ratio of perinatal outcomes in relation to antenatal depression

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A significant interaction was observed between age and depression for GDM (P < 0.000), hypertension disorder (P = 0.021), PTB (P = 0.023), and use of cesarean section (P < 0.000). [Table 3] presents the age-stratified analysis. A vertical comparison indicated an age-dependent increase in the prevalence of GDM and cesarean section use in women with normal emotional status but not in women with depression. While the horizontal comparison revealed the prevalence of hypertension disorder, PTB, and cesarean section were higher in women with depression in the subgroup aged <25 years, the association was not significant.
Table 3: Age-stratified analysis of adverse perinatal outcomes in relation to maternal depression/anxiety

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  Discussion Top

Our study revealed that women with severe depression had a risk of more than 11-fold of PTB, which might be concluded casually due to the limited number of cases. Women with moderate depression were at a higher risk for hyperthyroidism during pregnancy, while women with mild depression tended to choose a cesarean section. There was no correlation between maternal depression and hypertension or GDM. The age-stratified analysis noted an elevated risk of adverse outcomes associated with depression in women <25 years of age, but the association was not significant.

Our results contribute to the limited research conducted in developing countries about mood disorders and adverse perinatal outcomes. A prospective cohort study with a large sample size made the result credible. We divided pregnant women into four groups: normal, mild, moderate, and severe levels of depression according to the SDS scale. This procedure allowed us to not only analyze the circumstances but also obtain more information from the severity trend. An age-stratified analysis had a certain reference value for China since there was an increasing number of advanced-aged pregnant women whose emotional status was uncounted before.

There were several limitations to our study. The obvious limitation was that the Zung SDS was only a screening tool instead of the golden diagnosis since we lacked professional psychologists to conduct the psychological interview. Therefore, we only reported the screening positive rate instead of the incidence of depression. Second, demographic data such as education level, occupation, and income level were not obtained. Third, we did not obtain the baseline characteristics of thyroid dysfunction before pregnancy due to a lack of prepregnancy assessment. Moreover, we evaluated emotional status during 12–20 weeks of gestation, while the use of medication or mental support in the late second or third trimester was blank. However, the results would not be influenced dramatically because the proportion of pregnant women under psychological treatment was low because of neglecting mental health.


Our study confirmed that women with moderate depression had a higher risk of developing hyperthyroidism. It is reasonable to consider the abnormal activity of the sympathetic nervous system[29],[30] induced by stress in life. This association was also verified by Pop et al.[31] and Bunevicius et al.[17] but differed from some studies, suggesting that depression was only associated with elevated TPO-Ab rather than with abnormal thyroid function.[32],[33] However, our study failed to collect information about thyroid function before pregnancy but pooled all the cases during the three trimesters. It was difficult to distinguish the causal connection since mood fluctuation was a symptom of hyperthyroidism.[34]

In this study, we could not prove the correlation between depression and gestational hypertension or preeclampsia/eclampsia. However, we observed that women with pre-existing hypertension were more likely to have depression. This was consistent with a study in the USA with a large sample size.[35] Other studies supposing a higher risk of preeclampsia in the depression or anxiety group[14],[16] neglected the role of pre-existing hypertension. Therefore, we suggest a further cross-sectional study with a large sample size to identify independent contributors to antenatal depression. There is also a need for more attention to mental health for preconception women with physical diseases, which might consequently cause gestational complications.

Our study identified a risk of more than 11-fold of preterm delivery in women with severe depression. However, in the mild and moderate depression subgroup, the OR value decreased and became insignificant. Despite research on mechanisms indicating that stress plays a role in the pathogenesis of PTB via hypothalamic–pituitary–adrenal axis functioning,[36],[37],[38] epidemic studies did not reach an agreement on the relationship between antenatal depression and PTB. The conclusions of Li et al.[39] are similar, suggesting that the risk of PTB elevated as depression exacerbated. They demonstrated a 1.6-fold (95% CI 0.7–3.6) risk of PTB for mild depression and a 2.2-fold (95% CI 1.1–4.7) risk for severe depression according to the Center for Epidemiological Studies Depression Scale. Other studies did not demonstrate the association when combining all subgroups of severity together.[8],[10],[13],[40] Nevertheless, in our study, there were only seven cases in the severe depression subgroup, and whether it was a causal event requires further investigation. When analyzing the mode of PTB separately, no relationship was found between medically induced PTB and depression. Yonkers et al.[41] also proved that depression was only associated with spontaneous PTB. According to our multiple logistic model for medically induced PTB, other factors such as multipara and hypertension were weighted contributors.

Women with mild depression were more likely to have a cesarean section although the OR value of depression was not notably high. Yedid et al. also concluded that depressed women had a 28.5% rate of having a cesarean section compared with 13.6% in the control group.[42] Cephalopelvic disproportion, maternal complications, and malpresentation were the main risk factors for a planned cesarean. However, the nonindication cesarean section was once prevalent in China, and the fear of delivery was the main reason for the nonindication cesarean section. This could explain the correlation between depression and cesarean section, even after adjusting for parity and maternal complications. In contrast, the rate of cesarean section decreased to 33.2% according to our data, reflecting the large process we made in controlling indications.

Contrary to our speculation, depression did not act as a momentous part in adverse outcomes for women older than 35 years. We deduced that advanced maternal age was a riskier factor,[43],[44] which probably concealed the effect of mood disorder because, regardless of being depressed or nondepressed, women aged over 35 years old had a generally higher incidence of adverse outcomes. In contrast, depressed mothers in the younger subgroup faced a higher risk of developing obstetric events, which aligns with a previous study in Taiwan.[45] Unfortunately, in this study, we could not explore the mental health of mothers aged <20 years due to the restriction of the studied population. The mental health of young mothers requires more care and vigilance regarding the complications of advanced-aged mothers.

In conclusion, our study demonstrated the elevated risk of PTB in severely depressed mothers and the risk of hyperthyroidism in moderately depressed mothers. The risk of these events did not increase for women aged over 35 years. However, this result should be interpreted with caution due to the limited number of cases in the subgroups.

Supplementary information is linked to the online version of the paper on the Reproductive and Developmental Medicine website.


We acknowledge the contributions of Prof. Ding Yan and her student Miss. Qian Shuhua in ObGyn Hospital of Fudan University for their kind help during our data collection.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1]

  [Table 1], [Table 2], [Table 3]


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