Association of epidural analgesia with maternal and neonatal outcomes in preterm vaginal delivery: a single-center retrospective study

Association of epidural analgesia with maternal and neonatal outcomes in preterm vaginal delivery: a single-center retrospective study | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 25 April 2025 V1 Latest version Share on Association of epidural analgesia with maternal and neonatal outcomes in preterm vaginal delivery: a single-center retrospective study Authors : Jing Sun [email protected] , Yu Lin , Guanxiong Wu , Li Luo , Jingjing Deng , Xiaojing Fang , Yuting Hu , and Yuantao Li 0000-0003-4531-7864 Authors Info & Affiliations https://doi.org/10.22541/au.174558982.22040264/v1 226 views 117 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract [1]¿p#1 Objective: To determine whether epidural analgesia is associated with maternal and neonatal outcomes in preterm vaginal delivery. Design: Retrospective cohort study. Setting: Deliveries in Shenzhen Maternity & Child Healthcare Hospital, China. Population or Sample: Preterm parturients with singleton pregnancies and vaginal delivery in 2020-2024. Methods: The association of epidural analgesia with outcomes were examined. Propensity score matching and entropy balancing were used to eliminate potential confounders. Main Outcome Measures: Duration of first, second and third stages of labor, hemorrhage during vaginal delivery and postpartum hemorrhage (and ≥500mL), Apgar scores (and <7) at 1, 5 and 10 minutes, assisted ventilation, NICU admission, neonatal intraamniotic infection, neonatal sepsis, neonatal asphyxia and neonatal respiratory distress syndrome. Results: The study comprised 853 parturients, 564 (66.12%) received epidural analgesia. After propensity score matching, 567 parturients remained, 339 (59.79%) received epidural analgesia. Duration of first and second stages of labor were longer in epidural group than non-epidural group (difference: 6 [95% CI: 4 to 9], difference: 6 [95% CI: 4 to 9], respectively). Epidural analgesia was associated with Apgar score <7 at 1 minute (OR: 0.355 [95% CI: 0.161-0.783], P = 0.010), but not after adjusted covariates (OR: 0.453[ 95% CI: 0.166-1.233], P = 0.121). Conclusions: Use of epidural analgesia in preterm vaginal delivery may increase duration of first and second stages of labor, but associations with other outcomes were not observed. 1 Introduction Epidural analgesia is currently one of the most effective and commonly used analgesic modalities in labor. It is recommended for healthy pregnant women requesting pain relief during labor, depending on a woman’s preferences by WHO.[1] In China, up to 30% of women who undergo vaginal delivery receive epidural analgesia.[2] Although the associations of epidural with maternal and neonatal outcomes have been researched in many literatures, most studies focused on safety and efficacy of epidural drugs in the full-term (>37 weeks of gestation) delivery. Parturients who were experiencing premature delivery (gestational age <37 weeks) were often excluded from studies. Little is known about the association of epidural analgesia with maternal and neonatal outcomes in preterm parturients, especially those who had undergone vaginal delivery. In recent years, a single-center retrospective study with 147 parturients reported that the durations of both the first and second stages of labor were significantly longer in the epidural group in preterm. Neonatal outcomes did not differ between groups, which included an Apgar score <7 at 1 and 5 minutes, assisted ventilation (CPAP, bag and mask resuscitation, intubation, or chest compression), duration of oxygen therapy, and hospital stay.[3] A population based study with 567216 women and 39601 (7.0%) preterm women reported more marked reductions in severe maternal morbidity (SMM) were seen in women delivering preterm compared with those delivering at term or post term, but lacked association of epidural analgesia with maternal and neonatal outcomes such as durations of stages of labor, Apgar scores, assisted ventilation and NICU admission.[4] In fact, for a preterm parturient epidural analgesia may be particularly challenging. First, preterm births occur in 5-13% of pregnancies, which is a small population.[5] Second, not all centers are adequately equipped with resources and staff, making both providing adequate care and carrying out clinical trials difficult. Overall, this population remains to be studied extensively. This study evaluates whether exposure to epidural analgesia is associated with maternal and neonatal outcomes in preterm vaginal delivery. It aims to focus on safe anaesthesia practices to follow in these vulnerable parturients, and to develop strategies that ensure parturients in preterm labor of vaginal delivery, have access to comprehensive information and support about the use of epidural analgesia. 2 Methods 2.1 Study population and data source We retrospectively investigated parturients at Shenzhen Maternity & Child Healthcare Hospital between November 2018 and January 2024 whether epidural analgesia is associated with maternal and neonatal outcomes in preterm vaginal delivery. This study was approved by the Institutional Ethics Committee of the Shenzhen Maternity & Child Healthcare Hospital, in Shenzhen, China [approval number: (2022)81]. Data obtained from electronic medical records included maternal age, maternal pre-pregnancy BMI (determined within 7 days before delivery), gestational weeks, parity, gestational diabetes, hypertensive disorders complicating pregnancy (HDCP), post-ablative hypothyroidism (PH hypothyroidism), premature rupture of membranes (PROM), induction of labor, oxytocin use, lateral episiotomy, duration of first, second and third stages of labor, hemorrhage during vaginal delivery, postpartum hemorrhage, neonate birth weight, Apgar scores (at 1, 5 and 10 minutes after delivery) and neonatal assisted ventilation (CPAP, HigFi, nCPAP/nIMV, HHHFNC), neonatal intensive care unit (NICU) admission and diagnosis. Neonatal data reported in the medical record were also collected. We reported this study in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. 2.2 Inclusion and exclusion criteria All parturients with preterm vaginal delivery of a singleton infant (<37 weeks of gestation) were included. Medical records without baseline characteristics (ie, age, weight, and height) or no recorded labor summaries were excluded. (see Supplementary Appendix 1 for details) [1]¿p#1 2.3 Epidural analgesia After entering the delivery room, preterm parturients who requested epidural analgesia for pain were placed in the left lateral position with opened peripheral venous access. Then, epidural puncture (AS-E epidural puncture package) was performed through L2-L3 intervals, and the epidural catheter was inserted at a depth of 3–4 cm. Then, an experimental dose (a total of 3 mL of 1:200,000 adrenaline+ 1.5% lidocaine) was injected. If there was no local anesthetic poisoning or other abnormal reactions, the catheter was fixed and the multiparas were placed in the supine position. For pain relief, 10 mL of 0.1% ropivacaine mixed solution was injected once through the epidural catheter. If there were no obvious adverse reactions such as hypotension, nausea and vomiting or local anesthetic poisoning symptoms after 30 min of observation, an analgesia pump (ZZB-I impulse type, 200 mL) was connected, with a ready to use solution of 0.08% ropivacaine and sufentanil 0.4 μg/ml. Parameter setting: pulse frequency once/h, dose 10 mL, infusion rate 400 ml/h, PCA dose 8 ml, locking time 30 min. Epidural labor analgesia continued until the baby was delivered. Preterm parturients could terminal their epidural infusion at the request of the obstetric care provider for clinical indications. There was no standardization of the indication for termination nor was there a specific requirement other than obstetric request. Blood pressure was measured every 5 min during the first 20 min and hourly during the continuous of patient-controlled analgesia usage. Meanwhile, Visual analog scale (VAS) pain scores was recorded 30 min after the epidural loading dose. (see Supplementary Appendix 2 for details) 2.4 Outcomes Maternal outcomes included duration of first, second and third stages of labor, hemorrhage during vaginal delivery, postpartum hemorrhage, hemorrhage during vaginal delivery≥500 mL and postpartum hemorrhage ≥500 mL. Neonatal outcomes included Apgar score at 1, 5 and 10 minutes, Apgar score <7 at 1, 5 and 10 minutes, assisted ventilation, NICU admission, neonatal intraamniotic infection, neonatal sepsis, neonatal asphyxia and neonatal respiratory distress syndrome (NRDS). 2.5 Exposure and confounders Exposure was receiving and not receiving epidural analgesia. Confounders included maternal age, maternal pre-pregnancy BMI, gestational weeks, parity, gestational diabetes, HDCP, PH hypothyroidism, PROM, induction of labor, oxytocin use, lateral episiotomy and neonate birth weight. 2.6 Statistical analysis Normal numerical variables were presented as mean ± standard deviation, and t-test was used for comparison between groups. Non-normal numerical variables were presented as median (first quartile, third quartile), and Wilcoxon rank-sum test was used for comparison between groups, differences and 95% confidence intervals (CIs) in medians were calculated using Hodges-Lehmann estimator. Shapiro-Wilk test was used to test for normal distribution. Categorial variables were presented as number (percentage), and Fisher’s exact test or Chi-square test was used for comparison between groups, odd ratios (ORs) and 95% CIs were estimated using Fisher’s exact test. Quantile regression analysis was used to explore the effect of variables. Univariate quantile regression was used with the outcomes as dependent variables, exposure of epidural analgesia and baseline characteristics as independent variables. All independent variables with P-value < 0.05 were included for further multivariate quantile regression analysis, and a stepwise selection were subsequently used to preserve variables base on Akaike information criterion (AIC), except variable of epidural analgesia was forced to preserve. All models were built with 50th percentiles. Difference in median between epidural group and non-epidural group corresponds to the coefficient of variable of epidural analgesia, which was estimated in the quantile regression.[6] Logistic regression analysis was also used. Univariate logistic regression analysis was performed with the outcomes as dependent variables, exposure of epidural analgesia and baseline characteristics as independent variables. After that, independent variables with P-value < 0.05 were all included for multivariate logistic regression analysis, and a stepwise selection was used to preserve variables base on the AIC, except variable epidural analgesia were forced to preserve. Odds ratios (ORs) and 95% CIs of variable of epidural analgesia for the outcomes were estimated by using logistic regression. All statistical analyses were conducted using R software (version: 4.2.2). A two-sided P-values < 0.05 were considered statistically significant. The quantile regression analysis was performed using the R package ‘quantreg’. 2.6.1 Propensity score matching As there were potential confounding variables in this study, propensity score matching (PSM) was used to assess the association between epidural analgesia and outcomes by constructing a subset cohort of parturients with and without receiving epidural analgesia but similar in base characteristics before labor delivery. The propensity score was estimated using a multivariate logistic regression with exposure of epidural analgesia as dependent variable, and covariates included year of delivery, maternal age, maternal pre-pregnancy BMI, gestational weeks, parity, gestational diabetes, HDCP, PROM, induction of labor and neonate birth weight. Matching was performed using a 2:1 nearest neighbor (NN) algorithm without replacement with a caliper equal to 0.05 using the R package ‘MatchIt’.[7] 2.6.2 Post-hoc power analysis and minimum sample size determination Since this study was a single-center retrospective observational study, the estimated sample size could not be included, post-hoc power analysis was performed instead, which can be useful when a statistically non-significant result is obtained in a small study. For example, a null finding may stem from low power or a truly small effect. A post hoc power analysis can help distinguish these findings.[8] For continuous outcomes, post-hoc power analysis was used to determine statistical powers on Wilcoxon rank sum test at a two-tailed 5% alpha level and estimate minimum sample size would be sufficient to detect present effect size with 80% or more power at a two-tailed 5% alpha level. For categorical outcomes, statistical powers were determined on two-sample proportion test at two-sided 5% alpha level and the minimal sample size were estimated with 80% or more power at two-sided 5% alpha level.[9] 2.6.3 Exploratory subgroup analysis All parturients were divided into subgroups by preterm birth: late preterm (34 to <37 weeks) gestations, moderate preterm (32 to gestations and extremely preterm (<28 weeks) to explore the associated with maternal and neonatal outcomes and estimated differences and 95% CIs in medians between groups and ORs and 95% CIs of epidural analgesia for the outcomes. Furthor, all parturients were also divided into subgroups by neonate birth weight: normal birth weight (2500 to <4000g), low birth weight (1500g to <2500g), extremely low birth weight (1000g to For each subgroup, propensity score matching was used to maintain baseline balance between epidural and non-epidural groups. After propensity score matching, the differences and 95% CIs in medians and ORs and 95% CIs for the outcomes were estimated between groups. 2.6.4 Sensitivity analysis Similar to the inverse probability of treatment weighting method, entropy balancing to assign an optimized set of weights to the parturients in the cohort to generate balanced cohorts. It produced a series of appropriate weights to achieve the highest possible balance between groups. The potential confounding effects of year of delivery, maternal age, maternal pre-pregnancy BMI, gestational diabetes, HDCP, PH hypothyroidism, PROM, induction of labor and neonate birth weight were considered in the cohort. Maximum standardized mean differences (SMD) between groups were examined with the maximum differences being smaller than 0.1 for all covariates indicating a balance between groups.[10][11] Entropy balancing was performed using the R package ‘WeightIt’. 3 Results [1]¿p#1 3.1 Baseline characteristics Only a small proportion of preterm delivery (7494 [9.0%]) (Figure 1) and a total of 853 preterm parturients on vaginal delivery were identified who matched inclusion and exclusion criteria. Of these, 564 parturients receiving and 289 parturients not receiving epidural analgesia were divided into epidural group and non-epidural group. Epidural group was more younger compared with non-epidural group (median age: 31 [IQR: 28-34] years vs median age: 33 [IQR: 29-36] years, P < 0.001). The baseline characteristics were shown in Table 1. The characteristics differed between groups except maternal pre-pregnancy BMI, gestational diabetes, HDCP and oxytocin use. After propensity score matching, there were 339 parturients in epidural group and 228 parturients in non-epidural group. All differences between groups became no significance. The details were shown in Table 2. [1]¿p#1 3.2 Association of epidural analgesia with maternal outcomes after propensity score matching The duration of the first and second stages of labor were significantly longer in the epidural group than non-epidural group (difference: 6 [95% CI: 4 to 9], difference: 6 [95% CI: 4 to 9], respectively). But the duration of the third stage of labor did not differ between groups (difference: -0.001 to 1]). The hemorrhage during vaginal delivery and postpartum hemorrhage were observed no significance between groups (difference: -0.001 to >-0.001 to <0.001], respectively), and they were almost less than 500mL. Univariate quantile regression analyses indicated that the duration of the first and second stages of labor were significantly longer in the epidural group than non-epidural group (difference: 7 [95% CI: 3.419 to 10.581], difference: 7 [95% CI: 3.419 to 10.581], respectively). The similar results in multivariate quantile regression analyses, the duration of the first and second stages of labor were still significantly longer in the epidural group than non-epidural group (difference: 6.349 [95% CI: 3.505 to 9.193], difference: 6.349 [95% CI: 3.505 to 9.193], respectively). [1]¿p#1 3.3 Association of epidural analgesia with neonatal outcomes after propensity score matching The Apgar score at 1 minute was significantly different between groups (difference: -0.001 to significant between groups (difference: -0.001 to <0.001], difference: -0.001 to <0.001], respectively). Also, the frequency in Apgar score <7 at 1 minute was significantly different between epidural group and non-epidural group (2.95% vs 7.89%, Fisher’s P=0.01). Other frequencies in Apgar score neonatal intraamniotic infection, neonatal sepsis, neonatal asphyxia and neonatal respiratory distress syndrome did not differ between groups. The details were shown in Table 3. In addition, univariate logistic analyses revealed that epidural analgesia were not independently associated with neonatal outcomes except Apgar score <7 at 1 minute and neonatal respiratory distress syndrome (OR: 0.355 [95% CI: 0.161 to 0.783], OR: 0.651 [95% CI: 0.429 to 0.989], respectively). But in multivariate logistic analyses, epidural analgesia was not independently associated with neonatal outcomes after adjusted by covariates (OR: 0.453 [95% CI: 0.166 to 1.233], OR: 1.003 [95% CI: 0.451-2.234], respectively). 3.4 Exploratory subgroup analyses After propensity score matching in each subgroup, the duration of the first and second stages of labor were significantly longer in the epidural group than non-epidural group in late preterm, normal preterm and low birth weight subgroups. The duration of the third stage of labor did not differ between groups in each subgroup. The hemorrhage during vaginal delivery were observed no significance between groups except in very preterm subgroup. The postpartum hemorrhage was observed no significance between groups in each subgroup. The Apgar score at 1, 5 and 10 minutes was nearly no significantly different between the epidural group and non-epidural group in each subgroup. Epidural analgesia was not associated with maternal outcomes and outcomes with Apgar score <7 at 1, 5 and 10 minutes, assisted ventilation, neonatal intraamniotic infection, neonatal sepsis, neonatal asphyxia and neonatal respiratory distress syndrome in each subgroup. NICU admission was observed no association with epidural analgesia except in late preterm subgroup. The details were presented in Figure 2 and Figure 3. [1]¿p#1 3.5 Robustness of results and sensitivity analysis Similar results were seen after the entropy balancing with standardized mean difference (SMD) of less than 10% (see Supplementary Table S2). The duration of the first and second stage of labor were still significantly longer in the epidural group than non-epidural group (median: 26.00 [IQR: 12.00-50.00] vs 15.00 [IQR: 8.00-28.00], p < 0.001). The duration of the third stage of labor, hemorrhage during vaginal delivery and postpartum hemorrhage were observed no significance between groups. The Apgar score at 1, 5 and 10 minutes were not significantly different between groups. The frequency in Apgar score <7 at 1 and 5 minutes, assisted ventilation, NICU admission, neonatal intraamniotic infection, neonatal sepsis, neonatal asphyxia and neonatal respiratory distress syndrome were no significant between the groups except Apgar score <7 at 10 minutes. Univariate and multivariate quantile regression analyses indicated that the duration of the first second and third stage of labor were significantly longer in the epidural group than non-epidural group (see Supplementary Table S3). Univariate and multivariate logistic regression analyses indicated that epidural analgesia were not independently associated with Apgar score neonatal intraamniotic infection, neonatal sepsis, neonatal asphyxia and neonatal respiratory distress syndrome except postpartum hemorrhage ≥500 mL (see Supplementary Table S4). 4 Discussion 4.1 Main Findings In this study, epidural analgesia in preterm vaginal delivery was associated with longer duration of first and second stages of labor, but not with duration of third stage of labor, hemorrhage during vaginal delivery and postpartum hemorrhage, as well as neonatal outcomes, which included Apgar scores at 1, 5 and 10 minutes, Apgar scores <7 at 1, 5 and 10 minutes, assisted ventilation, NICU admission, neonatal intraamniotic infection, neonatal sepsis, neonatal asphyxia and neonatal respiratory distress syndrome. Additional explore subgroup analysis showed the associations of epidural with longer duration of first and second stages of labor in late preterm, normal birth weight and low birth weight subgroups . Duration of third stage of labor, hemorrhage during vaginal delivery and postpartum hemorrhage, neonatal outcomes were likely no association in all subgroups. Sensitivity analyses with a weighted cohort had similar effect size estimates. These findings may provide reassurance to parents and health care professionals regarding the safety of epidural analgesia. 4.2 Interpretation Current literatures are too scarce to reflect the comprehensive outcomes. Our study contrasted with the single-center retrospective study that contained 147 women with preterm vaginal delivery of a singleton infant (23-36 weeks of gestation) in Tokyo between January 2014 and October 2016, which showed the same results with longer durations of both the first and second stages of labor in the epidural use, and no association between epidural use and Apgar score <7 at 1 and 5 minutes, assisted ventilation.[3] Another retrospective study from May 2014 until May 2021 with 962 late preterm and 9476 term vaginal deliveries found that epidural use among multiparous women may extended the duration of second stage of labor in late preterm period.[13] Our study had same results in late preterm subgroup analysis for preterm women. A population based study with 567216 women in labor at 24+0 to 42+6 weeks’ gestation between 1 January 2007 and 31 December 2019, show a 47% reduction in severe maternal morbidity (SMM) in those delivering prematurely (39 601 women, 7.0%) when the primary outcome of SMM defined as a composite outcome of ≥1 of 21 conditions according to the US CDC criteria for SMM or a critical care admission.[4] In our study, there was no difference between epidural and non-epidural use in NICU admission, but it may be not comparable because our study did not contain other composite outcomes of SMM. A case-control study with 206 cases and 206 matched controls singleton infants born during January 2006 to December 2010 showed that late-preterm infants exposed to maternal epidural analgesia in labor were more likely to develop respiratory distress in the immediate neonatal period.[14] But we found no difference for respiratory distress syndrome in our study. As other large observational studies focused on the association of epidural analgesia in full-term delivery, these studies may not be comparable to our study. A Cochrane review included epidural versus placebo/no‐treatment (seven trials involving 897 women) founded that there was no clear difference between the groups for length of first and second stage of labor (minutes).[15] A retrospective study found that Apgar scores at 1 and 5 minutes were slightly but significantly lower in neonates whose mothers had received epidural analgesia, as well as NICU admission was significantly more frequent in the epidural.[16] These different findings in our study showed the difference between full-term and preterm vaginal delivery, but it might not be generalizable unless more evidence provided. [1]¿p#1 4.3 Strengths and Limitations We acknowledged that our study had some potential limitations: First, this study was a single-center retrospective observational study, selection and recall biases might affect the results for differences in receiving epidural or not between parturients and cause-effect relationship can not be ascertained and may lead to bias.[17] Second, as we depend on review of medical records that were originally not designed to collect data for research, maternal fever in labor was missing, which might affect the neonatal outcomes, such as neonatal sepsis. A retrospective cohort study show that in preterm patients an epidural was associated with a decreased risk for neonatal sepsis (5.7% vs. 10.0%, p = 0.04), 5-minute Apgar score <7 (23.5% vs. 33.6%, p = 0.006), and NICU admission (66.6% vs. 76.5%, p = 0.008) compared to those born in the setting of a fever without an epidural.[18] The contradicting results might be affect by the maternal fever or low statistical power with small sample size. Third, our study did post-hoc power analysis, but some studies indicated that power analysis should always be considered before any research study in order to choose an ideal sample size and/or to examine the feasibility of properly evaluating study aims, but it should never be used in order to help interpret the results of an already completed study. Alternatively, 95% confidence intervals for odds ratio, mean difference or other relevant parameter estimates should be used when attempting to draw conclusions from results.[19][20] Although we performed post-hoc power analysis (see Table 4), it may be helpless for the interpretation of results. At the same time, we provided 95% CIs for effect sizes, but selection bias could not be avoided. 5 Conclusion In conclusion, this study of 857 parturients in China suggest that use of epidural analgesia in preterm vaginal delivery may increase the duration of first and second stages of labor, but association with duration of third stage of labor, hemorrhage during vaginal delivery and postpartum hemorrhage, as well as neonatal outcomes, which included Apgar scores at 1, 5 and 10 minutes, Apgar scores <7 at 1, 5 and 10 minutes, assisted ventilation, NICU admission, neonatal intraamniotic infection, neonatal sepsis, neonatal asphyxia and neonatal respiratory distress syndrome, were not observed. This results may be used to help decision-making for parturients considering epidural analgesia. It may also be helpful for further study design of preterm vaginal delivery in prospective studies. Author contribution Jing Sun conceived, collected data and helped to interpret the results. Yu Lin performed data analysis and drafted the manuscript. Guanxiong Wu, Li Luo, Jingjing Deng, Xiaojing Fang, Yuting Hu and Yuantao Li helped to collect data and revised it critically for important intellectual content. All authors approved the version to be published. [1]¿p#1 Funding Shenzhen Science and Technology Innovation Commission grants [grant number: JCYJ20230807120302004]. Acknowledgement The authors have nothing to report. Ethical statement This study was approved by the Institutional Ethics Committee of the Shenzhen Maternity & Child Healthcare Hospital, in Shenzhen, China [approval number: (2022)81]. Conflicts of interests The authors declare that they have no conflicts of interest. References 1. WHO recommendations: Intrapartum care for a positive childbirth experience. Geneva: World Health Organization; 2018. Executive summary. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513802/ 2. 1.Qiao, J., et al., A Lancet Commission on 70 years of women’s reproductive, maternal, newborn, child, and adolescent health in China. The Lancet, 2021. 397(10293): p. 2497-2536. 3. Mori Y, Toyama S, Sato M, Yamashita Y, Suzuki Y, Sago H. Influence of preterm labour epidural analgesia on neonatal and maternal outcomes: a single-centre retrospective study. Br J Anaesth. 2021 Nov;127(5):e154-e156. doi: 10.1016/j.bja.2021.07.017. Epub 2021 Aug 20. PMID: 34420683. 4. Kearns RJ, Kyzayeva A, Halliday LOE, Lawlor DA, Shaw M, Nelson SM. Epidural analgesia during labour and severe maternal morbidity: population based study. BMJ. 2024 May 22;385:e077190. doi: 10.1136/bmj-2023-077190. PMID: 38777357; PMCID: PMC11109902. 5. Halliday L, Nelson SM, Kearns RJ. Epidural analgesia in labor: A narrative review. Int J Gynaecol Obstet. 2022 Nov;159(2):356-364. doi: 10.1002/ijgo.14175. Epub 2022 Mar 21. PMID: 35277971. 6. Staffa SJ, Kohane DS, Zurakowski D. Quantile Regression and Its Applications: A Primer for Anesthesiologists. Anesth Analg. 2019 Apr;128(4):820-830. doi: 10.1213/ANE.0000000000004017. PMID: 30649075. 7. Chen JW, Maldonado DR, Kowalski BL, Miecznikowski KB, Kyin C, Gornbein JA, Domb BG. Best Practice Guidelines for Propensity Score Methods in Medical Research: Consideration on Theory, Implementation, and Reporting. A Review. Arthroscopy. 2022 Feb;38(2):632-642. doi: 10.1016/j.arthro.2021.06.037. Epub 2021 Sep 20. PMID: 34547404. 8. Madjarova, S.J., Pareek, A., Eckhardt, C.M. et al. Fragility Part I: a guide to understanding statistical power. Knee Surg Sports Traumatol Arthrosc 30, 3924–3928 (2022). https://doi.org/10.1007/s00167-022-07188-9 9. Ye, T., & Yi, Y. (2017). Sample size calculations in clinical research, third edition, by Shein-Chung Chow, Jun Shao, Hansheng Wang, and Yuliya Lokhnygina: Chapman & Hall/CRC Biostatistics Series, New York, Taylor & Francis, 2017, 510 pp., $99.95 (hardback), ISBN: 978-1-138-74098-3. Statistical Theory and Related Fields, 1(2), 265–266. https://doi.org/10.1080/24754269.2017.1398000 10. Harvey RA, Hayden JD, Kamble PS, Bouchard JR, Huang JC. A comparison of entropy balance and probability weighting methods to generalize observational cohorts to a population: a simulation and empirical example. Pharmacoepidemiol Drug Saf. 2017 Apr;26(4):368-377. doi: 10.1002/pds.4121. Epub 2016 Nov 13. PMID: 27859943. 11. Hainmueller J. Entropy balancing for causal effects: a multivariate reweighting method to produce balanced samples in observational studies. Political Analysis. 2012: 25–46. 12. Kearns RJ, Shaw M, Gromski PS, Iliodromiti S, Lawlor DA, Nelson SM. Association of Epidural Analgesia in Women in Labor With Neonatal and Childhood Outcomes in a Population Cohort. JAMA Netw Open. 2021 Oct 1;4(10):e2131683. doi: 10.1001/jamanetworkopen.2021.31683. PMID: 34709386; PMCID: PMC8554639. 13. Gutzeit O, Justman N, Zvi DB, Siegler Y, Khatib N, Ginsberg Y, Beloosesky R, Weiner Z, Vitner D, Liberman S, Zipori Y. Late preterm delivery has a distinctive second-stage duration and characteristics. Am J Obstet Gynecol MFM. 2023 Mar;5(3):100845. doi: 10.1016/j.ajogmf.2022.100845. Epub 2022 Dec 23. PMID: 36572106. 14. Kumar M, Chandra S, Ijaz Z, Senthilselvan A. Epidural analgesia in labour and neonatal respiratory distress: a case-control study. Arch Dis Child Fetal Neonatal Ed. 2014 Mar;99(2):F116-9. doi: 10.1136/archdischild-2013-304933. Epub 2013 Oct 29. PMID: 24170528. 15. Anim-Somuah M, Smyth RM, Cyna AM, Cuthbert A. Epidural versus non-epidural or no analgesia for pain management in labour. Cochrane Database Syst Rev. 2018 May 21;5(5):CD000331. doi: 10.1002/14651858.CD000331.pub4. PMID: 29781504; PMCID: PMC6494646. 16. Herrera-Gómez A, García-Martínez O, Ramos-Torrecillas J, De Luna-Bertos E, Ruiz C, Ocaña-Peinado FM. Retrospective study of the association between epidural analgesia during labour and complications for the newborn. Midwifery. 2015 Jun;31(6):613-6. doi: 10.1016/j.midw.2015.02.013. Epub 2015 Mar 11. PMID: 25819707. 17. Talari K, Goyal M. Retrospective studies - utility and caveats. J R Coll Physicians Edinb. 2020 Dec;50(4):398-402. doi: 10.4997/JRCPE.2020.409. PMID: 33469615. 18. Ward C, Caughey AB. Does the presence of epidural analgesia reduce the risk of neonatal sepsis in the setting of an intrapartum fever? J Matern Fetal Neonatal Med. 2022 Jun;35(11):2110-2115. doi: 10.1080/14767058.2020.1779694. Epub 2020 Jun 21. PMID: 32567418. 19. Dziak JJ, Dierker LC, Abar B. The Interpretation of Statistical Power after the Data have been Gathered. Curr Psychol. 2020 Jun;39(3):870-877. doi: 10.1007/s12144-018-0018-1. Epub 2018 Oct 2. PMID: 32523323; PMCID: PMC7286546. 20. Heckman MG, Davis JM 3rd, Crowson CS. Post Hoc Power Calculations: An Inappropriate Method for Interpreting the Findings of a Research Study. J Rheumatol. 2022 Aug;49(8):867-870. doi: 10.3899/jrheum.211115. Epub 2022 Feb 1. PMID: 35105710. Figure 1. Criteria for selection of preterm parturients with vaginal delivery [1]¿p#1 Figure 2. Differences of maternal and neonatal outcomes between epidural and non-epidural groups after propensity score matching Differences of maternal and neonatal outcomes between epidural and non-epidural groups (A) Difference of duration of first stage of labor between groups (B) Difference of duration of second stage of labor between groups (C) Difference of duration of third stage of labor between groups (D) Difference of hemorrhage during vaginal delivery between groups (E) Difference of postpartum hemorrhage between groups (F) Difference of Apgar score at 1 minute between groups (G) Difference of Apgar score at 5 minutes between groups (H) Differences of Apgar score at 10 minutes between groups Inf denotes infinity. NA denotes not applicable. Figure 3. Odds ratios of maternal and neonatal outcomes in epidural compared non-epidural groups after propensity score matching Odds ratios of maternal and neonatal outcomes in epidural compared non-epidural groups. (A) Odds ratios of hemorrhage during vaginal delivery ≥500mL (B) Odds ratios of postpartum hemorrhage ≥500mL (C) Odds ratios of Apgar score <7 at 1 minute (D) Odds ratios of Apgar score <7 at 5 minutes (E) Odds ratios of Apgar score <7 at 10 minutes (F) Odds ratios of assisted ventilation (G) Odds ratios of NICU admission (F) Odds ratios of neonatal intraamniotic infection (H) Odds ratios of neonatal sepsis (I) Odds ratios of neonatal asphyxia (J) Odds ratios of neonatal respiratory distress syndrome Inf denotes infinity. NA denotes not applicable. Supplementary Material File (table_1_20250403.docx) Download 29.69 KB File (table_2_20250403.docx) Download 29.66 KB File (table_3_20250403.docx) Download 28.29 KB File (table_4_20250403.docx) Download 26.12 KB Information & Authors Information Version history V1 Version 1 25 April 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords analgesia: epidural/spinal general obstetrics preterm labour: clinical research Authors Affiliations Jing Sun [email protected] Shenzhen Futian District Maternity & Child Healthcare Hospital View all articles by this author Yu Lin Shenzhen Withsum Technology Limited View all articles by this author Guanxiong Wu Shenzhen Maternity & Child Healthcare Hospital The First School of Clinical Medicine Southern Medical University View all articles by this author Li Luo Shenzhen Futian District Maternity & Child Healthcare Hospital View all articles by this author Jingjing Deng Shenzhen Futian District Maternity & Child Healthcare Hospital View all articles by this author Xiaojing Fang Shenzhen Maternity & Child Healthcare Hospital The First School of Clinical Medicine Southern Medical University View all articles by this author Yuting Hu Shenzhen Maternity & Child Healthcare Hospital The First School of Clinical Medicine Southern Medical University View all articles by this author Yuantao Li 0000-0003-4531-7864 Shenzhen Maternity & Child Healthcare Hospital The First School of Clinical Medicine Southern Medical University View all articles by this author Metrics & Citations Metrics Article Usage 226 views 117 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Jing Sun, Yu Lin, Guanxiong Wu, et al. 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