Relationship between painless delivery and postpartum depression: The Japan Environment and Children’s Study (JECS)

Postpartum depression is one of the most commonly experienced psychological disorders for women after childbirth, usually occurring within one year. This study aimed to clarify whether women with painless delivery, including epidural analgesia, spinal-epidural analgesia, and paracervical block, had a decreased risk of postpartum depression after giving birth in Japan. Methods The Japan Environment and Children’s Study (JECS) was a prospective cohort study that enrolled registered fetal records (n = 104,065) in 15 regions nationwide in Japan. Binomial logistic regression analyses were performed to calculate the adjusted odd ratios (aORs) for the association between mode of delivery with or without analgesia and postpartum depression at one-, six- and twelve-months after childbirth.


Methods
The Japan Environment and Children's Study (JECS) was a prospective cohort study that enrolled registered fetal records (n = 104,065) in 15 regions nationwide in Japan. Binomial logistic regression analyses were performed to calculate the adjusted odd ratios (aORs) for the association between mode of delivery with or without analgesia and postpartum depression at one-, six-and twelve-months after childbirth.

Results
At six months after childbirth, painless vaginal delivery was associated with a higher risk of postpartum depression (aOR: 1.218, 95% con dence interval: 1.067-1.391), compared with vaginal delivery without analgesia or cesarean section. Nevertheless, the risk disappeared one year after delivery. Among the pregnant women who requested painless delivery, 5.1% had a positive Kessler-6 scale (K6) score for depression before the rst trimester (p < 0.0001), which was signi cantly higher than the proportions in the vaginal delivery without analgesia (3.5%) and cesarean delivery (3.5%) groups.

Conclusions
Our data suggested that the risk of postpartum depression at six months after childbirth tended to be increased after painless vaginal delivery, compared with vaginal delivery without analgesia or cesarean section. Requests for painless delivery continue to be relatively uncommon in Japan, and women who make such requests might be more likely to experience postpartum depressive symptoms because of underlying personality characteristics, including a tendency to worry.

Background
Analgesia during delivery is the most common and widely accepted method of pain relief during labor [1][2][3]. Although the proportion of pregnant women requesting painless delivery with analgesia varies internationally between 20%-70% [2,3], the proportion in Japan continues to be relatively low.
Nevertheless, the use of analgesia has recently been growing in popularity, and the proportion of women who use analgesia during labor reportedly increased from 4.6% in 2014 to 6.1% in 2016 [4]. Since a common maternal myth in Japan is that labor pains are conducive to forming a strong maternal instinct [5], we assumed that this belief might be one of the reasons why delivery with analgesia is uncommon in Japan, compared with other countries.
Giving birth in a more relaxed state through the use of analgesia during delivery can be expected to confer bene ts to both mother and baby. Even in healthy mothers, suppressing hyperventilation arising from pain and suppressing the deterioration in blood ow to the placenta as a result of the release of stress hormones are possible merits of epidural delivery. Analgesia and the accompanying reduction in childbirth stress might be particularly bene cial to mothers with chronic diseases, such as cardiovascular disease.
On the other hand, a recent report suggested increased risks in obstetric and neonatal outcomes among pregnant women with combined spinal-epidural analgesia during labor, compared with women without analgesia; these risks included a prolonged duration of labor, instrumental delivery, lower Apgar scores, and an umbilical arterial blood gas pH of less than 7.10 [4]. In contrast, several lines of evidence suggest that epidural analgesia is associated with a decreased risk for postpartum depression [6][7][8], although the sample sizes of some prospective cohorts were limited.
Severe labor pains are a risk factor of postpartum depression in pregnant women, and early depression is associated with an increased risk of long-term depression [9]. Postpartum depression affects women who have given birth and is a common disorder for new mothers. Almost 10-15% of mothers may suffer from postpartum depression within the rst year after delivery [9]. Multiple factors may be involved in postpartum depression, and the causes have been di cult to understand.
The present study aimed to clarify whether the mode of delivery, particularly the use of analgesia during delivery, decreased the risk of postpartum depression after childbirth in Japan.

Study population
The design of the Japan Environment and Children's Study (JECS) has been described previously in detail [10][11][12]. The direct web link to the JECS is https://www.env.go.jp/chemi/ceh/en/index.html This study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement for observational studies. Brie y, pregnant women in Japan were recruited for the JECS between January 2011 and March 2014. Women who 1) lived in any of the Study Areas selected by the fteen Regional Centers located in the country at the time of recruitment; 2) had an expected delivery date after August 1, 2011; and 3) were capable of understanding the Japanese language and completing a self-administered questionnaire were included in the study [10,12].
The present study used the "jecs-ag-20180131" dataset, which was released in March 2018 and contains information on 104,065 fetal records (Fig. 1). Among women with multiple pregnancies during the study period, data for the second or third pregnancy was excluded (n =1,003); pregnancies with miscarriages, stillbirths, or missing data (n = 3,860) were also excluded. Overall, 99,202 pregnancies were included in the analysis.
The JECS protocol was approved by the Ministry of the Environment's Institutional Review Board on Epidemiological Studies (no. 100910001) and by the Ethics Committees of all the participating institutions. Written informed consent was obtained from all the study participants.

Data collection
The study participants completed questionnaires throughout their pregnancies and postpartum periods; i.e., during the rst and second/third trimesters (n = 92,550), and at one-, six-and twelve-months after delivery. The medical records at the time of registration and just after vaginal delivery or cesarean section were transcribed by doctors, research coordinators, nurses, or midwives.
Information regarding maternal or paternal demographic factors was obtained from the questionnaires completed during pregnancy. Postpartum information was collected from the questionnaires completed during the six months after delivery.

Outcomes, exposure, and covariates
The primary outcome was the occurrence of postpartum depression. We used the postpartum Edinburgh Postnatal Depression Scores (EPDS) at one and six months after delivery and the postpartum K6 scores within one year after delivery as the primary outcomes [13,14]. The EPDS is a validated, standardized questionnaire consisting of 10 screening items that is commonly used to identify a risk of perinatal or postpartum depression. As the cutoff value for the EPDS, we used a score of ≥9 as a positive result for postpartum depression [15,16].
The K6 self-administered questionnaires were assessed using a ve-category scale (4 = all the time, 3 = most of the time, 2 = some of the time, 1 = a little of the time, 0 = none of the time), with possible scores ranging from 0-24. According to a Japanese validation study for the K6 questionnaire in the general population, the performance of the K6 questionnaire using an optimal cutoff of ≥13 to indicate severe psychological distress was excellent when the performance was examined using an area under the receiver operating characteristic curve (AUC), with values as high as 0.94 (95% con dence interval (CI) = 0.88 to 0.99) [17].
The participants were divided according to mode of delivery into three categories: vaginal delivery without analgesia; painless vaginal delivery, including epidural analgesia, spinal-epidural analgesia, or paracervical block; and cesarean section.

Data analysis
The maternal and postpartum demographic characteristics of the participants were shown with the proportion for discrete data. The Fisher exact test was used to compare the association between the outcome and each variable. Binomial logistic regression analyses were performed by adding all the covariates to calculate the adjusted ORs (aORs) for the association between mode of delivery and postpartum depression. Since missing data can potentially undermine the scienti c credibility of causal conclusions, we applied a multiple imputation method to reduce the potential non-response bias created by missing data and to improve the precision of the estimates when calculating the aORs [18,19]. A total of 20 models, in which all the available variables were used as predictors and outcomes, were created to estimate the aORs. To prevent multiple comparisons possibly yielding false-positive ndings, we adopted the Benjamini-Hochberg method and assessed statistical signi cances by obtaining the q-values adjusted for false discovery rate. All the statistical analyses were performed using IBM SPSS Statistics for Windows, version 24.0 (IBM Corp., Japan).

Results
Characteristics of prenatal, neonatal, and postpartum statuses and maternal postpartum outcomes Table 1 summarizes the characteristics of the prenatal, neonatal, and postpartum statuses and the maternal postpartum outcomes. Among the 99,202 pregnancies who were included in the analysis, the mode of delivery was vaginal delivery without analgesia in 78.7% (n = 78,082), painless vaginal delivery in 2.4% (2,337), and cesarean section in 18.8% (18,657). The mode of delivery was unknown in 126 cases (0.1%).
As for the outcomes, a signi cant difference in the incidence of postpartum depression at one month after delivery was observed according to the mode of delivery (vaginal delivery without analgesia: 14.0%, painless vaginal delivery: 16.7%, and cesarean section: 15.0%, p < 0.0001). A similar trend was observed at six months after delivery (11.5%, 14.1% and 11.9%, respectively, p = 0.0007). The K6 scores for postpartum depression at one year after childbirth, however, did not differ signi cantly according to delivery mode (p = 0.5599).
With respect to the covariates, the distribution of categorized maternal ages was as follows: 1.1% with an age of <20 years, 37.1% with an age of 20-29 years, 52.2% with an age of 30-39 years, and 3.3% with an age of ≥40 years. All the evaluated demographic characteristics differed signi cantly according to the mode of delivery (p < 0.0001). Regarding the prenatal and neonatal statuses, among the women who requested painless delivery, 5.1% had a positive K6 score for depression during the rst trimester, compared with 3.5% in each of the vaginal delivery without analgesia and cesarean delivery groups (p < 0.0001). A similar trend was found during the second/third trimesters, with 5.2% of the women in the painless delivery, 3.1% of the women in the vaginal delivery without analgesia, and 3.7% of the women in the cesarean delivery groups having a positive K6 score for depression (p < 0.0001). All the prenatal and neonatal status variables except for the child's sex differed signi cantly according to the mode of delivery (p = 0.0049). As for the postpartum and childcare variables, the breast-feeding method, frequency of infant crying, and partner's cooperation with nurturing at one month after delivery differed signi cantly among the three groups (all p < 0.0001), whereas no signi cant differences in marriage status at six months after delivery (p = 0.371) and partner's cooperation with nurturing at one year after delivery (p = 0.431) were seen.

Association between painless delivery and postpartum depression
The association between painless vaginal delivery and postpartum depression is shown in Fig. 2. In addition, the supplemental gure shows the estimated association without using the multiple imputation method (Suppl Fig. 1). At six months after delivery, women who requested analgesia for painless delivery had a higher risk of postpartum depression (aOR: 1.218, 95% CI: 1.067-1.391, q = 0.022), compared with vaginal delivery without analgesia. Nevertheless, the association disappeared at one year after delivery. Although no signi cant difference in the point estimates with or without using the multiple imputation method was seen, the con dence intervals for the aORs calculated using multiple imputation were narrower than those calculated without multiple imputation.

Discussion
The present study found an increased risk of postpartum depression at six months among women who requested painless vaginal delivery in Japan. Little consensus exists regarding the effect of painless delivery on postpartum depression, since the results of previous studies are inconsistent. A recent report suggested that epidural analgesia during labor is not associated with a decreased risk of developing postpartum depression [20]. In contrast, Riazanova et al. reported that postpartum depression was diagnosed at six weeks after delivery in 4.67% of women who requested epidural analgesia, compared with 6.79% among women without analgesia during delivery [21]. Several lines of evidence have suggested that the risk of postpartum depression is reduced in women who receive epidural analgesia, compared with those without analgesia [22,23]. Liu et al. reported that the use of neuraxial analgesia during labor was associated with a reduced risk of postpartum depression at two years after delivery [9].
One possible reason for the con icting reports mentioned above might be due to the nature of the evaluation period for assessing postpartum depression. Postpartum depression is de ned as a form of major depression beginning within 4 weeks after delivery and potentially lasting for months or years. In previous studies, the association between postpartum depression and mode of delivery was assessed at time points ranging from a few weeks to as long as two years after delivery. An assessment of the temporal trajectory of postpartum depression using a longitudinal study, rather than cross-sectional assessments at speci c time periods, is thus needed.
Another explanation might be the use of different screening tools to evaluate postpartum depression in the previous studies. Both the K6 and the EPDS are commonly used universal screening tools for the diagnosis of postpartum depression. A systematic review validating the EPDS in postpartum women reported that the sensitivity of the tool ranged widely from 34% to 100%, while the speci city ranged from 44% to 100% [24]. A study comparing the performances of mental health screening tools showed that the EPDS had the highest area under the curve value [25], meaning a high sensitivity for the detection of postpartum depression, while the K6 showed a good balance between sensitivity (74%) and speci city (85%), reaching a su cient positive predictive value. However, the cutoff values depended on the language of translation, and such differences might be responsible for the discrepant results.
Next, special attention should be paid to the personality traits of women or the presence of psychological distress before or during early pregnancy and the relations between such factors and the selection of painless delivery. In Japan, the number of women who request painless delivery is relatively small, whereas the rates of painless delivery with analgesia range between 20% and 70% internationally [7]. Thus, we think that the results of the present study may differ from those of comparable international studies. As mentioned in the Introduction, labor with analgesia is uncommon in Japan because of the popular belief that enduring the pain of labor is virtuous. Recently, however, both the number of elderly pregnancies and the number of pregnant women requesting painless delivery have been increasing in Japan. In the present study, the proportion of women with a positive K6 score during their rst trimester was higher in the painless vaginal delivery group (5.1%) than in the vaginal delivery without analgesia (3.5%) and cesarean delivery (3.5%) groups. This nding suggests that women with high levels of anxiety might have been more likely to request epidural analgesia. However, the current study adjusted for the possibility of such an effect on the association between the mode of delivery and postpartum depression using logistic regression analyses (Fig. 2). Additionally, as a practical implication, it should be noted that pregnant women who requested painless delivery had higher K6 scores for depression during the rst trimester, compared with women in the other two delivery groups.
Depression is the most common psychological disorder in women after childbirth, occurring in 9.0% of pregnant women in Japan (Ministry of Health, Labour and Welfare, 2015 [26]). A national project to prevent postpartum depression has been started in Japan, and postpartum depression is regarded as an essential health issue. Olieman et al. reported that women who underwent elective cesarean sections had signi cantly higher symptom levels of posttraumatic stress disorder and depression than women undergoing vaginal delivery without analgesia [27]. Such discrepancies persist, and health professionals should pay careful attention to all postpartum women, regardless of the mode of delivery or the use of analgesia.

Strengths And Limitations
The JECS, with 100,000 participants, is the largest nationwide birth cohort study to be conducted in Japan and is considered to be representative of the general population [10,28]. The outcome measurements were reliable because pregnancy and delivery information were based on medical records transcribed by doctors, research coordinators, nurses, and midwives. Furthermore, the risk estimates for the effect of painless delivery on postpartum depression were calculated using multiple imputations, providing a high level of scienti c credibility and reducing the potential non-response bias created by missing data.
The present study had some limitations. As stated above, two different indexes, the EPDS and the K6 score, were used to evaluate postpartum depression. Since the researchers were unable to implement the use of appropriate indicators for individual studies in their own surveys, the same screening tool could not be used at each measurement point. Although previous studies have shown that the cutoff values for both indicators were appropriate [25], this may have created a potential for systematic bias.

Conclusion
Painless delivery was associated with an increased risk of postpartum depression at six months after delivery among pregnant women in Japan. Social support after delivery for mothers who select painless delivery is thus necessary. Further analysis of maternal personality types and environmental statuses and comparing older and younger women who request painless vaginal delivery are needed to determine in which situations might epidural delivery be desirable. Because of prevailing maternal myths, Japan may represent a special environment where painless deliveries are extremely rare and are selected mainly by women who are susceptible to depression. Unlike in other countries, a higher proportion of women with postpartum depression at six months after delivery was seen among women requesting painless delivery; continuous postnatal care is thus important for these women.
Abbreviations EPDS: Edinburgh Postnatal Depression Scores; JECS: The Japan Environment and Children's Study; K6: Kessler-6 scale Declarations should be sent to: jecs-en@nies.go.jp. The person responsible for handling enquiries sent to this e-mail address is Dr Shoji F. Nakayama, JECS Programme O ce, National Institute for Environmental Studies.

Ethics approval and consent to participate
The study protocol was approved by the ethics committee of the JECS. The JECS protocol was approved by the Ministry of the Environment's Institutional Review Board on Epidemiological Studies (no. 100910001) and by the Ethics Committees of all the participating institutions.

Consent for publication
Not applicable.   Association between painless delivery and postpartum depression. Adjusted for maternal age, maternal body mass index, maternal educational status, annual income, recurrent miscarriage, mode of pregnancy, parity, drinking history, maternal smoking history, pre-K6 ( rst trimester and second/third trimesters), marriage status (at second/third trimester and at 6 months after birth), sex of child, Apgar score at 1 min and at 5 min, inborn error of metabolism, neonatal anomalies, breast-or bottle-feeding, frequency of infant crying and partner's cooperation with nurturing (at 1 month and at 1 year after birth). * q = 0.022, obtained by Benjamini-Hochberg method. Error bars showed 95% CI.

Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download. Painlessdelivery2021.1Tables.docx