The study was conducted in the First Affiliated Hospital of Chongqing Medical University between January 2019 and November 2019. The protocol was approved by the ethics committees of the First Affiliated Hospital of Chongqing Medical University (No. 2018-100). This study was registered at the Chinese Clinical Trial Registry on 3/1/2019, number: ChiCTR1900020510.
Subjects
Full-term pregnant women with singleton aged 18 to 45 years old undergoing epidural labor analgesia or elective cesarean section with epidural anesthesia were recruited. Participants were excluded if they were diagnosed with mental illness, cesarean section with general anesthesia, contradiction for epidural anesthesia (including coagulation disorder, infection at the puncture site, lumbar injury), local anesthetics allergy, and severe illness complicating pregnancy (including severe hypertension, diabetes, or other severe heart, hepatic, renal disorders). Participants were also excluded if they were bleeding over 800ml or had a cardiac arrest during birth. To reduce the bias of accidental psychological fluctuation, patients with incomplete epidural anesthesia who needed general anesthesia or those who due to failure of natural childbirth with labor analgesia, turned to cesarean section, were not included in this study.
Groups
On admission to the hospital, all eligible patients were informed about the study, and consent was obtained from each patient. Information about the advantage and disadvantage of labor analgesia and cesarean section were also provided. Combined with the professional suggestions from obstetricians, each patient made her own decision to have labor analgesia (group LA) or cesarean section (group CS). Subjects in group LA received epidural labor analgesia in the delivery room before birth, while subjects in group CS received epidural anesthesia in the operation room before surgery.
Epidural labor analgesia
The cervix was checked by a midwife or obstetrician every 4 hours during the latent phase of the first stage. When the cervix was dilated to 2 cm or more, the epidural labor analgesia was conducted by a senior anesthesiologist (QB Chen). The pregnant woman was placed in a lateral position, and L2-L3 interspace was chosen for puncture and catheterization. An initial loading dose of 5 ml of 1% lidocaine was administrated. After confirming anesthesia's effect and ruling out the adverse event (spinal anesthesia and local anesthetic intoxication), patient-controlled epidural analgesia (PECA) pump was connected to the catheter. The formula of PCEA included 150 mg ropivacaine and 0.25 mg fentanyl with saline added up to a volume of 150 ml in total. The patient received a loading dose of 8 ml when the connection was completed, followed by an infusion rate of 8 ml/h, with a bolus of 8 ml and a lock time of 20 min. The anesthesiologist solved any side effects related to the epidural analgesia. Epidural labor analgesia was canceled when the birth was completed.
Epidural anesthesia for elective cesarean section
Epidural anesthesia was conducted by a senior anesthesiologist (B Wang) for each patient who needed an elective cesarean section. Firstly, Vein puncture and catheterization were conducted by a nurse when the patient was sent to the operation room. Similarly, the patient was placed in a lateral position, and L1-L2 interspace was chosen for puncture and catheterization. An initial loading dose of 3~5 ml of 2% lidocaine was administrated to test the effect of anesthesia and whether there were adverse events related to epidural anesthesia. A dose of 10~15 ml of 2% lidocaine with 1:200,000 epinephrine was subsequently administrated. If the block was insufficient, 5~7 ml of 1% ropivacaine was added via the epidural catheter. The surgery was conducted by a senior obstetrician (FL Peng) when the level of anesthesia ranged from T6 to S3. Cesarean section was conducted through a transverse lower uterine segment incision. The uterine wound was closed in the continuous absorbable suture, and oxytocin or ergometrine was used if necessary. The skin incision was closed with nonabsorbable stitches, which were removed on day 7 ~10 postoperatively. Also, all patients received patient-controlled intravenous analgesia (PCIA) at the end of surgery. The formula of PCIA included tramadol 800 mg, nefopam 40 mg with saline added up to a volume of 80 ml in total. The parameters were set as follows: 5 ml for a loading dose, 1 ml/h for infusion rate, 5 ml for bolus dose, and 20 min for the lock time.
General data collection
The demographic characteristics, including age, body mass index (BMI), education background, and the information on the present pregnancy (including gravidity and parity, perinatal classes about childbirth, present obstetrical and gynecological disease, disease complicating pregnancy) were collected by using a designed information form after receiving written consent from the subject. Perinatal classes were educational courses prepared for expectant mother and father conducted by hospital or birth-feeding institutions, which provided information on perinatal health care, the process of birth, infant feeding, postpartum recovery, and parenting. In addition, the baseline of the numerical rating scale (NRS) scores was collected for each patient. In group LA, the baseline of pain was assessed by NRS before starting epidural labor analgesia, while the baseline NRS scores were evaluated before starting epidural anesthesia in group CS. Besides, antenatal depression was also evaluated using the Edinburgh Postnatal Depression Scale (EPDS). The EPDS is a 10-item questionnaire with maximum scores 30, which is widely used for the detection of postnatal depression [14, 16]Recently, the EPDS has been shown to be an effective screening tool for antenatal depression, where a cutoff score of 10 or 11 is used for the identification of antenatal depression[17, 18]In the present study, antenatal depression was defined as an EPDS score of 10 or higher before birth.
Postpartum follow-up
The EPDS scores were recorded at 3 days and 6 weeks after birth. PPD was diagnosed as EPDS score ≥ 10 at 6 weeks after birth. Additionally, the pain at rest and in motion was assessed by NRS scores at 1, 2, 3 days, and 6 weeks after birth. Pain at rest was defined when the patient was lying in a supine position in bed, and pain in motion was rated when the patient was coughing or walking on level ground. Any adverse event was recorded within 3 days and 6 weeks after birth. Duration of labor and neonatal variables (neonatal gender, body weight, Apgar score 1, 5, 10 min after birth) were also followed. Duration of labor was defined as the time from the beginning of regular contractions (lasting more than 30s with an interval of 5~6 minutes) to the end of birth in group LA, while the duration was calculated as operation time in group CS. In China, mothers are traditionally expected to rest indoors for one full month after birth, so the data on companion during this time (professional maid, patient’s parents or/and parents-in-law) and infant feeding choices (formula milk or/and breast milk) were also recorded.
Sample calculation and statistical analysis
According to the previous report, we assumed that that the incidence of PPD would be 20% for subjects who underwent cesarean section and 14% for pregnant women who received labor analgesia[14, 19]The statistical power of 80% at the 0.05 significance lever required 100 subjects in each group, and the final sample size was 110 subjects considering a 10% dropout rate. The sample size was calculated by two independent proportions of power analyses of PASS 11.
All data were expressed as mean ± standard deviation (normal distribution data) or median (interquartile range) (non-normal distribution data) for continuous variables and total number (percent frequency) for categorical variables. The results of continuous variables were compared using the t-test (normal distribution data) or Wilcoxon rank-sum test (non-normal distribution data). The chi-square test was used to analyze the results of categorical variables. Fisher’s exact test was used for categorical variables when the number of events was less than 5. The predicted factor of PPD was assessed with multivariate logistic regression analysis. All the perinatal variables in this present study, including maternal and neonatal factors, were included in the univariate analysis to screen for potentially predictive factors. To avoid missing some potential important variables, factors with a P-value ≤0.1 in univariate analysis were defined as candidate variables[20]In consideration of a substantial bias of estimated regression coefficients generated using the stepwise method[21]all the potential variables were included in the multivariable model to determine the predictive factors by using the method of enter procedure. P-value < 0.05 was considered as statistically significant.