Postpartum depression (PPD) is a major depressive episode that begins within 6 weeks after delivery [
This disorder may be caused by multiple risk factors, including the history of depression, preterm delivery, poor marital relationship, and low social income [
As reported, hypertensive disorder in pregnancy (HDP) is a risk factor for depression, and the prevalence is about 20%-30% [
Our previous study demonstrated that PE patients had nearly 3-fold increased odds for PPD compared to normal women, and patients with severe PE had a more than 4-fold higher risk of screening positive for PPD [
Herein, we aimed to compare the incidence rate of PPD in PE and normal women by employing the EPDS and to comprehensively evaluate the association between PPD and PE, especially its severity and complications. In addition, it has been previously reported that pelvic floor symptoms, urinary incontinence, and pain would affect postpartum moods [
In this two-center retrospective cohort study, patients who delivered between October 1, 2018, and August 30, 2019, were enrolled from the First Affiliated Hospital of Chongqing Medical University and Qinghai Red Cross Hospital. All patients were asked to independently complete the questionnaires within about 6 weeks after delivery. With informed consent, the answers of the patients can be used here.
The inclusion criteria were (1) diagnosis of PE by elevated blood pressure (systolic
The exclusion criteria were as follows: (1) presence of other complications, such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and hyperthyroidism; (2) preterm (gestational age less than 36+6 weeks) not caused by PE; (3) preexisting mental diseases, history of depression; and (4) stillbirth or giving birth to a malformed fetus (including any minor anomalies).
All details of maternal and neonatal conditions during pregnancy and delivery were obtained from the hospital information systems. After applying the inclusion and exclusion criteria, we invited mothers for a clinical visit within 6 weeks after delivery and encouraged them to participate in our questionnaires, including EPDS, Leakage Index Questionnaire, and pain scale (numerical rating scales).
EPDS is the most commonly used PPD scale worldwide and is one of the most authoritative self-evaluation scales to screen for PPD [
The Leakage Index Questionnaire (involving 3 items with multiple choices) and pain scale were used to evaluate the recovery of muscles in the pelvic floor and the degree of postpartum pain in mothers, respectively. The scores of the former range from 0 to 6 and from 0 to 10 in the latter. The higher scores on the Leakage Index Questionnaire predict poorer recovery of pelvic floor muscles. Moreover, educational background, annual family income, and milk feeding methods were also investigated in our questionnaire (details are shown in Figure
Besides, severe PE was diagnosed as (1) systolic
This study was designed to detect a 15% absolute difference between groups with 90% power and a 5% type I error rate. We assume that the incidence of PPD was about 30% in the PE group and 15% in the control group. Therefore, a sample size of 380 (88 in the PE group and 292 in the control group) was needed. The MedSci Sample Size Tools (MSST, version 5.7.15, copyright 2020 MedSci.cn) were applied for calculating. We recruited 130 PE patients and 295 healthy women.
Variables following normal distribution were compared via an independent
A total of 130 PE patients met the inclusion and exclusion criteria. We randomly selected 295 normal women who met the inclusion criteria during the same period. In the PE group, 74 patients were diagnosed with mild PE, the others with severe PE. Clinical characteristics were compared between the normal and PE groups in Table
Comparison of baseline characteristics between normal and PE women.
Variables | PE ( | Normal ( | |
---|---|---|---|
Age (y) | 0.135a | ||
18-24 | 9 (6.92) | 24 (8.13) | |
25-34 | 104 (80.0) | 250 (84.75) | |
35-45 | 17 (13.08) | 21 (7.12) | |
Prepregnant BMI (kg/m2) | 0.005a | ||
<18.5 | 20 (15.4) | 59 (20.0) | |
18.5-23.9 | 86 (66.2) | 215 (72.9) | |
24.0-27.9 | 21 (16.1) | 17 (5.7) | |
≥28.0 | 3 (2.3) | 4 (1.4) | |
BMI increment | 0.792b | ||
Gravidity | 2 (1-3) | 2 (1-3) | 0.942c |
Parity | 1 (1-2) | 1 (1-2) | 0.777c |
Primipara | 91 (70.0) | 213 (72.20) | 0.643a |
Cesarean section | 121 (93.08) | 98 (33.22) | <0.001a |
Gestational weeks (d) | 260 (251.75-269.00) | 277 (272.00-282.00) | <0.001c |
Male baby | 65 (50.0) | 167 (56.61) | 0.245a |
Neonatal weight (g) | 2960 (2197.50-3362.50) | 3255 (3035.00-3560.00) | <0.001c |
Education background | 4 (3-4) | 4 (3-4) | 0.451c |
Annual income | 3 (2-3) | 3 (2-3) | 0.839c |
Leakage Index | 0 (0-1) | 0 (0-2) | 0.713c |
Pain scale | 1 (1-1) | 1 (1-1) | 0.268c |
Exclusive breastfeeding | 43 (33.08) | 170 (57.63) | <0.001a |
aThe
All participants were asked to finish EPDS, and the scores were compared between the normal and PE groups. No differences in clinical characteristics were found between PPD and non-PPD mothers in the normal group (Table
Comparison of baseline characteristics between PPD and non-PPD women in the normal group.
Variables | PPD group ( | Non-PPD group ( | |
---|---|---|---|
Age | 0.126b | ||
Prepregnant BMI | 0.387b | ||
BMI increment | 0.284b | ||
Gravidity | 2 (1-3) | 2 (1-3) | 0.450c |
Parity | 1 (1-2) | 1 (1-2) | 0.242c |
Primipara | 28 (65.12) | 185 (73.41) | 0.173a |
Cesarean section | 13 (30.23) | 85 (33.73) | 0.397a |
Gestational weeks (d) | 276 (273-283) | 277 (272-282) | 0.611c |
Male baby | 26 (60.47) | 141 (55.95) | 0.352a |
Neonatal weight (g) | 3240.00 (3040.00-3700.00) | 3260.00 (3030.00-3530.00) | 0.352c |
Education background | 3 (3-4) | 4 (3-4) | 0.290c |
Annual income | 3 (2-3) | 3 (2-3) | 0.851c |
Leakage Index Score | 1 (0-2) | 0 (0-2) | 0.419c |
Pain scale | 1 (1-2) | 1 (1-1) | 0.209c |
Exclusive breastfeeding | 21 (48.84) | 149 (59.13) | 0.137a |
aThe
Comparison of baseline characteristics between PPD and Non-PPD women in the PE group.
Variables | PPD group ( | Non-PPD group ( | |
---|---|---|---|
Severe PE | 16 (40.0) | 30 (33.3) | 0.295a |
FGR | 17 (42.5) | 21 (23.3) | 0.024a |
Age | 0.783b | ||
Prepregnant BMI | 0.684b | ||
BMI increment | 0.396b | ||
Gravidity | 2 (1-3) | 2 (1-3) | 0.514c |
Parity | 1 (1-2) | 1 (1-2) | 1.000c |
Primipara | 28 (70.0) | 63 (70.0) | 0.578a |
Cesarean section | 39 (97.5) | 82 (91.1) | 0.173a |
Gestational weeks (d) | 259.00 (247.25-265.75) | 261.00 (252.75-269.00) | 0.368c |
Male baby | 21 (52.5) | 44 (48.9) | 0.425a |
Neonatal weight (g) | 2415.00 (1822.50-3187.50) | 3065.00 (2352.50-3442.50) | 0.007c |
Education background | 4 (3-4) | 4 (3-4) | 0.891c |
Annual income | 3 (2-3) | 3 (2-3) | 0.651c |
Leakage Index Score | 1 (0-2) | 0 (0-1) | 0.208c |
Pain scale | 1 (1-2) | 1 (1-1) | 0.012c |
Exclusive breastfeeding | 11 (27.5) | 32 (35.5) | 0.244a |
NICU | 11 (27.5) | 19 (21.11) | 0.280a |
aThe
We tried to explore the associations between PPD and PE. The average EPDS score in the normal group was significantly lower than that of the mild PE subgroup (
Comparison of EPDS scores in each subgroup.
Variables | Samples ( | EPDS scores | ||
---|---|---|---|---|
Normal | 295 | Reference | Reference | |
Mild PE | 74 | -2.690 | 0.008 | |
Severe PE | 46 | -4.170 | <0.001 | |
PE+FGR | 38 | -5.031 | <0.001 |
aAll of the
The average EPDS score in the normal group was significantly lower than that of the mild PE subgroup. The
There was a higher cesarean section rate among PE patients than normal women (93.08%
Comparison of characteristics between two different delivery modes in normal women.
Variables | C-sections ( | Vaginal delivery ( | |
---|---|---|---|
Age | 0.011b | ||
Prepregnant BMI | 0.239b | ||
BMI increment | 0.381b | ||
Gravidity | 2 (1-3) | 2 (1-2) | 0.257c |
Parity | 1 (1-2) | 1 (1-2) | 0.270c |
Primipara | 67 (68.37) | 146 (74.11) | 0.335a |
Gestational weeks (d) | 276 (272-282) | 277 (272-282) | 0.635c |
Male baby | 54 (55.10) | 113 (57.36) | 0.803a |
Neonatal weight (g) | 3252.5 (3050.0-3600.0) | 3260.0 (3020.0-3535.0) | 0.275c |
Education background | 4 (3-4) | 4 (3-4) | 0.120c |
Annual income | 2 (2-3) | 3 (2-3) | 0.024c |
Leakage Index | 0 (0-1) | 1 (0-2) | <0.001c |
Pain scale | 1 (1-1) | 1 (1-1) | 0.025c |
Exclusive breastfeeding | 54 (55.10) | 116 (58.88) | 0.617a |
EPDS score | 0.337b | ||
PPD | 13 (13.27) | 30 (15.23) | 0.728a |
aThe
Comparison of baseline characteristics in normal and PE women who suffered cesarean section.
Variables | PE ( | Normal ( | |
---|---|---|---|
Age | 0.488b | ||
Prepregnant BMI | 0.316b | ||
BMI increment | 0.576b | ||
Gravidity | 2 (1-3) | 2 (1-3) | 0.240c |
Parity | 1 (1-2) | 1 (1-2) | 0.623c |
Primipara | 85 (70.25) | 67 (68.37) | 0.770a |
Gestational weeks (d) | 260 (251-269) | 276 (272-282) | <0.001c |
Male baby | 60 (49.59) | 54 (55.10) | 0.497a |
Neonatal weight (g) | 2960.0 (2170.0-3400.0) | 3252.5 (3050.0-3600.0) | <0.001c |
Education background | 4 (3-4) | 4 (3-4) | 0.141c |
Annual income | 3 (2-3) | 2 (2-3) | 0.172c |
Leakage Index | 0 (0-1) | 0 (0-1) | 0.073c |
Pain scale | 1 (1-1) | 1 (1-1) | 0.240c |
Exclusive breastfeeding | 40 (33.06) | 54 (55.10) | 0.002a |
EPDS score | <0.001b | ||
PPD | 39 (32.23) | 13 (13.27) | 0.001a |
aThe
We compared the rate of positive screening of PPD in each subgroup (Table
Comparison of the incidence of PPD between normal and PE women.
Variables | PPD (%) | Non-PPD (%) | |
---|---|---|---|
Normal ( | 43 (14.58) | 252 (85.42) | Reference |
Total PE ( | 40 (30.77) | 90 (69.23) | <0.001 |
Mild PE ( | 20 (27.03) | 54 (72.97) | 0.014 |
Severe PE ( | 16 (36.96) | 30 (63.04) | 0.002 |
PE+FGR ( | 17 (44.74) | 21 (52.26) | <0.001 |
NICU ( | 11 (36.66) | 19 (63.33) | 0.004 |
PE+preterm ( | 20 (32.79) | 41 (67.21) | 0.001 |
aAll of the
We also tried to explore the associations between PE complications and PPD development. In the PE+FGR subgroup, the incidence of PPD was the highest among all the subgroups (44.74%). Thirty newborns were extremely weak and had to be sent to the neonatal intensive care unit (NICU). Obviously, when the babies were sent to NICU, their mothers tended to develop PPD. PPD incidence among these mothers increased dramatically (36.66%), which was extremely high. Preterm, one of the common complications in PE, occurred in almost half of PE mothers (61 of 130). PPD occurrence was 32.79% in the PE+preterm subgroup.
Then, multiple logistic regression was performed to evaluate the independent risk factors for PPD. With PPD as the dependent variable, PE, severe PE, FGR, and NICU admission were regarded as independent variables individually, while age, BMI, gestational days, baby weight, delivery model, Leakage Index Score, milk-feeding ways, and pain scale were analyzed as confounding factors. Women with mild PE demonstrated 2-fold higher odds of PPD (
Multivariable logistic regression analysis for PPD in PE and normal patients.
Variables | OR (95% CI) | Adjusted OR (95% CI)a |
---|---|---|
Age | 0.987 (0.925-1.052) | |
Prepregnant BMI | 1.006 (0.917-1.103) | |
Gestational weeks (d) | 0.985 (0.851-1.139) | |
Baby weight | 0.999 (0.999-1.000) | |
Leakage Index | 1.137 (0.952-1.358) | |
Educational background | 0.953 (0.731-1.241) | |
Annual income | 1.020 (0.741-1.403) | |
Cesarean section | 1.758 (1.074-2.887) | 1.177 (0.620-2.232)# |
Exclusive breastfeeding | 0.558 (0.342-0.911) | 0.752 (0.445-1.270)## |
Pain scale | 1.581 (1.151-2.174) | 1.509 (1.078-2.114) |
Mild PE | 2.171 (1.184-3.981) | 2.117 (1.001-4.479) |
Severe PE | 3.126 (1.527-6.216) | 2.759 (1.206-6.315) |
FGR | 4.744 (2.317-9.713) | 3.450 (1.596-7.458) |
NICU | 2.597 (1.184-5.696) | 2.809 (1.258-6.270) |
aThe adjusted ORs were calculated by multifactor logistic regression models. #Adjusted factors: age, BMI, and PE. ##Adjusted factors: age, BMI, PE, and cesarean section.
The odds ratio of PPD for each characteristic. The line segment represents the odds ratio and 95% confidence interval for each variable. It shows that the pain scale, mild PE, severe PE, FGR, and NICU were risk factors with OR and
Besides PE, postpartum pain was another independent risk factor for PPD (
Among the general population, hypertension has already been proved to be an independent risk factor for depressive disorder [
As reported, PPD occurred in 20.5% of PE patients in Tanzanian and in about 21% of PE mothers in Greek [
For PE mothers, besides the unfavorable experience of hypertension, other conditions such as additional costs and concerns of the newborns with complications also increase mothers’ psychological burden [
Whether the cesarean section will increase the risk of PPD is still controversial. In China, some healthy pregnant women would like to choose a cesarean section due to social-psychological factors. In this research, mothers with PE preferred to have a cesarean section to avoid possible adverse outcomes. This can explain why the rate of operative delivery in China among PE patients is so high. First of all, to figure out the effect of the cesarean section for PPD, we compared delivery models among normal women. Patel et al. demonstrated that operative delivery would not increase the incidence of PPD in 14,633 women [
However, in the PE group, we found that both EPDS score and PPD incidence were much higher in mothers suffering from the operation. It could be inferred that PE directly increased the risk of PPD rather than cesarean section. Then, we applied subgroup analysis to find the reason. In the PE+FGR subgroup, the incidence of PPD was the highest among all the subgroups. Obviously, mothers tended to show anxiety when babies were sent to NICU. Another common complication is preterm. Almost half of PE mothers occurred preterm. As expected, mothers in the PE+preterm group experienced higher psychological distress than others. Weigl et al. pointed out that new mothers of preterm infants exhibited higher scores of depression, anxiety, and stress than parents of term infants [
Postpartum pain, urinary incontinence, and feeding methods were also evaluated in the regression model. Postpartum pain was an independent risk factor for PPD, increasing the odds by 1.5-fold. A few trials showed that untreated pain is associated with a risk of PPD [
Hullfish et al. have demonstrated a correlation between urinary incontinence and PPD [
Although the connection between PE and PPD is still unclear, some mechanisms, such as clinical symptoms, inflammation, and genetic changes, have been used as hypotheses for the reason between PE and PPD. The pathogenesis for PE, a placenta disease, can be explained by the “two-stage theory” [
We must admit that there are some limitations in our study. As a retrospective study, it suffered from bias and case limitations. Firstly, patients were recruited from 2 hospitals, and the local bias may be relatively reduced, but there is still a need for a study involving multiple centers. Secondly, it was hard to control the operation rate in the PE group, although this delivery mode was not found to be a risk factor in our regression model. Thirdly, EPDS was a preliminary screening tool, not the gold standard for the diagnosis of PPD. In the future, we would like to initiate larger randomized controlled trials and more in-depth mechanistic studies.
PE can be an independent risk factor for PPD. Moreover, its severity and complications exacerbate the development of PPD. Severe PE, FGR, and NICU admission all increased nearly 3-fold risk for PPD-positive screening. Patients with PE should be offered suitable interventions, such as pain management, more cognitive-behavioral therapies (CBT), and interpersonal psychotherapies (IPT) to prevent the development of PPD.
The data used and analyzed during the current study are available from the corresponding authors on reasonable request.
The study was approved by the ethics committee of the First Affiliated Hospital of Chongqing Medical University on 1 December 2019 (No. 20198101).
Electronic informed consent was obtained before completing the questionnaire.
This manuscript has been submitted as a preprint; here is the website link:
None is declared. Completed disclosure of interest forms are available to view online as supporting information.
The authors would like to acknowledge support from the “111 program” of the Ministry of Education of PRC and the State Administration of Foreign Experts Affairs PRC. This work was financially supported by the National Key Research and Development Program of Reproductive Health & Major Birth Defects Control and Prevention (No. 2016YFC1000407), the National Natural Science Foundation of China for Youth (81601304), the Key Program of International Cooperation of NSFC (81520108013), the Ph.D. Programs Foundation of the Ministry of Education of China (2013550311003), and the General Program of the National Natural Science Foundation of China (81471472).
Figure S1: the questionnaires were used in the study, including EPDS, Leakage Index Questionnaire, and pain scale.