Low-Dose Oral Misoprostol Versus Oxytocin Infusion For Induction Of Labor In Pregnant Women With Term Premature Rupture Of Membranes in China: A retrospective Nested Case-Control Study

doi:10.21203/rs.3.rs-4328098/v1

While the use of oral misoprostol for labor induction in premature rupture of membrane (PROM) women is not prevalent in China, the main aim of this study was to validate the efficacy and safety of low-dose oral misoprostol solution compared to oxytocin infusion for labor induction in term PROM women with unfavorite cervix conditions. A retrospective nested case-control study was conducted at a tertiary general hospital in China from March 2020 to February 2024, comparing the efficacy of oxytocin infusion and oral misoprostol for labor induction in term PROM women with a Bishop score < 6. A total of 449 mothers were included, with 282 assigned to the oxytocin group and 167 assigned to the misoprostol group. The duration of total labor time was shorter in the misoprostol group. There was a markedly higher incidence of postpartum hemorrhage (PPH) and severe PPH observed in oxytocin group. Logistic regression analysis revealed that misoprostol administration demonstrated a negative relationship (aOR: 0.46; 95%CI: 0.21–0.95) with failed labor induction outcomes and occurrence of PPH (aOR: 0.49; 95% CI: 0.27–0.85). Oral low-dose misoprostol has demonstrated both safe and superior efficacy to oxytocin infusion for labor induction and may potentially reduce the incidence of failed induction and associated with a decreased risk of PPH were observed in the misoprostol group in term PROM pregnant women with unfavorable cervical condition.

Health sciences/Medical research/Outcomes research

Health sciences/Risk factors

Premature rupture of membrane

Oxytocin infusion

Oral low-dose misoprostol

Vaginal delivery

Failed induction of labor

Postpartum hemorrhage

Premature rupture of membranes (PROM) refers to the rupture of fetal membranes before the onset of labor¹. Occurrence of term PROM complicates approximately 8% of pregnancies, and its most significant maternal consequence is the increased risk of intrauterine infection, which aggravates the prolonged membrane rupture. Compared to expectant management for term PROM patients, induction process is the preferred treatment option^2,3.

Labor induction is determined based on the cervix conditions which are evaluated using the Bishop score. In cases where the cervix is deemed favorable, oxytocin is administered intravenously to initiate labor. Conversely, if the cervix is considered unfavorable (Bishop score < 6), prostaglandin or Foley's balloon are commonly administered to cause cervical ripening. However, in patients with PROM, such vaginal manipulations may increase the risk of infection and potentially result in uterine hyperstimulation, fetal distress, and emergency cesarean section (C-section).

Oxytocin is the most extensively applied agent and the recommended drug in cases of PROM by the American College of Obstetricians and Gynecologists, primarily due to its good safety profile 1. However, in term PROM patients with an unripened cervix, its efficacy appears to be limited.

Misoprostol, a prostaglandin E1 drug utilized for cervical ripening, is cost-effective, efficient, and global accessibility. Although vaginal administration has been extensively researched, there is limited data regarding its oral administration. Nonetheless, recent evidence indicates that low-dose oral misoprostol results in higher rates of vaginal delivery compared to oxytocin, vaginal misoprostol, and dinoprostone PGE2. Furthermore, it is associated with fewer occurrences of abnormal fetal heart rate changes and uterine tachysystole ^4–6. Similar results were obtained in patients with term PROM^7–9.

Although it is widely used globally, the utilization of oral low-dose misoprostol for labor induction in China is relatively low. Since March 2022, our department has applied oral low-dose misoprostol for cervical ripening in late gestational women who do not exhibit favorable cervix conditions. Studies comparing vaginal misoprostol with oral low-dose misoprostol demonstrates that the oral route may have higher efficacy and safety profile, and thus higher rate of vaginal delivery and a lower incidence of fetal stress and uterine hyperstimulation¹⁰. In the last two years, we administered oral low-dose misoprostol to PROM pregnant women who did not exhibit cervical ripening. In this study, we compared the efficacy and safety of oral low-dose misoprostol with traditional oxytocin for term PROM mothers.

Figure 1 shows the flowchart of participant selection. From March 2020 to February 2024, 24,484 deliveries were recorded, with 18,680 involving singleton pregnant women. A total of 282 and 167 cases of PROM met the inclusion criteria, where either oxytocin or oral low-dose misoprostol was used for labor induction. Prenatal data, delivery details, and birth outcomes were compared between the oxytocin and misoprostol groups, and the results are shown in Tables 1–3.

Table 1

Prenatal information compared between two groups
Prenatal information	Oxytocin	Misoprostol	P-value	Sig
	(n = 282)	(n = 167)
	Mean ± SD	Mean ± SD
	N (%)	N (%)
Age (years)	31.9 ± 3.2	32.3 ± 3.0	0.25	NS
Advanced age (over 35 years)	56(19.9)	24(14.4)	0.16	NS
Hight (cm)	162.6 ± 4.8	163.3 ± 5.2	0.15	NS
Body weight (kg)	71.25 ± 9.3	71.8 ± 10.0	0.58	NS
Body weight gain (kg)	12.9 ± 4.1	12.9 ± 4.4	0.91	NS
Pregestational BMI	22.1 ± 3.1	22.1 ± 3.2	0.96	NS
Underweight (BMI < 18.5)	26(9.2)	15(9.0)	> 0.99	NS
Obesity (BMI ≥ 28)	14(5.0)	14(8.4)	0.16	NS
Gravidity	1(1 ~ 2)	1(1 ~ 1)	0.01	**
Gestational weeks (weeks)	39.1 ± 1.0	39.2 ± 1.0	0.35	NS
Bishop score	4.1 ± 0.9	3.5 ± 0.9	< 0.01	**
IVF	45(16.0)	35(21.0)	0.20	NS
GBS +	19(6.7)	23(13.8)	0.02	*
GDM	49(17.4)	31(18.6)	0.80	NS
Abbreviation: BMI: body mass index; IVF-ET: in vitro fertilization-embryo transfer; GBS: Group B streptococcus.

Comparison of delivery information between two groups

Regarding delivery information, there were no significant differences in hospitalization days, labor onset rate, vaginal delivery rate, and failed induction labor rate between the oxytocin and misoprostol groups (Table 2). However, the duration of PROM to induction was longer in the misoprostol group than in the oxytocin administration group, potentially prolonging the duration from PROM to labor onset and delivery. Nevertheless, there were no significant differences in the time from PROM to labor onset or delivery, as well as the time from administration to labor onset or delivery between the two groups. Moreover, the rates of 24-hour deliveries were comparable between the two groups.

Regarding vaginal delivery, oral misoprostol induction in pregnant women with PROM was associated with shorter duration of the first stage of labor and overall labor time compared to oxytocin induction. The incidence rates of precipitate labor, episiotomy, and delivery within 24 hours were similar between the two groups. For cesarean section deliveries, there was no significant difference in the rate of operative interventions during labor or abnormal progression of labor between the two groups.

Table 2

Delivery information compared between two groups
Delivery information	Oxytocin	Misoprostol	P-value	Sig
	(n = 282)	(n = 167)
	Mean ± SD	Mean ± SD
	N (%)	N (%)
Hospitalization days	3(2 ~ 5)	3(2 ~ 4)	0.32	NS
Labor onset	236(83.7)	146(87.4)	0.34	NS
Vaginal delivery	178(63.1)	109(65.3)	0.39	NS
forceps delivery	12(4.3)	11(6.6)
C-Section delivery	92(32.6)	47(28.1)
Failed induction labor	36(12.8)	13(7.8)	0.12	NS
Duration of PROM to labor (h)	19.6 ± 11.2	21.5 ± 9.2	0.09	NS
Duration of administration to labor (h)	12.6 ± 10.1	12.9 ± 8.4	0.82	NS
Duration of PROM to delivery (h)	32.1 ± 13.6	32.1 ± 11.2	1.00	NS
Duration of administration to delivery (h)	25.1 ± 12.4	23.6 ± 10.7	0.19	NS
Delivery in 24h from administration	137(48.6)	86(51.5)	0.56	NS
Vaginal delivery
First stage of labor (h)	10.5 ± 5.1	9.0 ± 5.0	0.02	*
Second stage of labor (h)	0.8 ± 0.7	0.7 ± 0.7	0.05	NS
Total labor time (h)	11.5 ± 5.2	10.0 ± 5.2	0.01	**
Precipitate labor	0(0.0)	0(0.0)	> 0.99	NS
Duration of prom to vaginal delivery (h)	31.4 ± 13.6	30.7 ± 11.2	0.65	NS
Duration of administration to vaginal delivery (h)	24.5 ± 12.2	22.2 ± 10.9	0.10	NS
Vaginal delivery in 24h^a	98(51.6)	72(60.0)	0.16	NS
Episiotomy^a	77(40.5)	57(47.5)	0.24	NS
C-Section delivery
C-section delivery during the course of labor^b	46(19.5)	26(17.8)	0.79	NS
C-section delivery due to abnormal progression of labor^b	26(11.0)	10(6.8)	0.21	NS
^a The number of vaginal deliveries was 190 in the oxytocin group and 120 in the misoprostol group.
^b The number of labor onset was 236 in the oxytocin group and 146 in the misoprostol group.

Comparison of delivery outcomes between two groups

In terms of delivery outcomes, there were no statistically significant differences observed in the rates of uterine hyperstimulation, fetal distress, suspected intrauterine infection, pathological placental abnormalities, newborn body weight, cord blood pH, or postpartum blood loss between the two groups (Table 3). However, the incidence of postpartum hemorrhage (PPH) >500ml within 24 hours after delivery and severe PPH (blood loss ≥1000ml within 24 hours after delivery) was significantly higher in the oxytocin administration group compared to the oral misoprostol group. Furthermore, a higher incidence of postpartum urinary retention (PPUR) was observed in the misoprostol group.

Table 3

Delivery outcomes compared between two groups
Delivery outcomes	Oxytocin	Misoprostol	P-value	Sig
	(n = 282)	(n = 167)
	Mean ± SD	Mean ± SD
	N (%)	N (%)
Uterine hyperstimulation	6(3.6)	7(2.5)	0.56	NS
Fetal stress	27(9.6)	25(15.0)	0.09	NS
Suspected intrauterine infection	11(3.9)	5(3.0)	0.79	NS
Uterine hyperstimulation	7(2.5)	6(3.6)	0.56	NS
Newborn body weight (g)	3244 ± 368	3233 ± 349	0.75	NS
Macrosomia	5(1.8)	4(2.4)	0.73	NS
PH of cord blood	7.32 ± 0.06	7.32 ± 0.05	0.42	NS
PH < 7.20	5(1.8)	1(0.6)	0.42	NS
Neonatal asphyxia	3(1.1)	0(0.0)	0.30	NS
Postpartum blood loss in 24 hours	370(290 ~ 500)	370(308 ~ 450)	0.88	NS
PPH > 500ml^a	71(25.2)	28(16.8)	< 0.05	*
Severe PPH^a	7(2.5)	0(0.0)	< 0.05	*
Postpartum urinary retention	6(2.1)	12(7.2)	0.01	**
Pathological abnormality of placenta	20(7.1)	6(3.6)	0.15	NS
^a The case count of PPH > 500ml included both vaginal and C-section deliveries, while severe PPH was defined as PPH ≥ 1000ml
Abbreviation: PPH: postpartum hemorrhage

Logistic analysis of vaginal delivery, failed induction of labor and postpartum hemorrhage

Subsequently, we established a logistic regression model with vaginal delivery and failed induction of labor as the dependent variables, while oral misoprostol administration, age, pregnancy weight gain, pregestational BMI, gravidity, gestational weeks, IVF-ET status, GDM, infection of GBS, Bishop score and newborn body weight were included as independent variables. Data shown in Table 4 indicate that in terms of vaginal delivery outcomes, pregestational BMI (aOR: 0.93, 95% CI: 0.87~0.99) and IVF-ET status (aOR: 0.30, 95% CI: 0.17~0.52) were negatively associated with successful vaginal delivery. In contrast, for failed labor induction outcomes, misoprostol administration showed a negative relationship (aOR 0.46, 95% CI: 0.21~0.95), while IVF-ET showed a positive association (aOR: 3.12, 95%CI: 1.49~6 .43). These findings indicate that induction of labor using oral misoprostol for term PROM may decrease the likelihood of failed labor induction compared to IVF-ET, which is associated with increased risk of failed labor induction.

Furthermore, PPH is a major complication during delivery which varies with different drugs used for induction. Consequently, we developed a logistic regression model with the occurrence of PPH>500ml as the dependent variable and independent variables including oral misoprostol or oxytocin administration along with basic information. Table 5 shows that there were positive associations between age (aOR: 1.17, 95%CI: 1.07~1.27), gestational weeks (aOR: 1.35, 95%CI: 1.02~1.80), IVF-ET (aOR:2.43, 95%CI:1.32~4.48), and PPH incidence rates. Conversely, a negative correlation was observed between misoprostol administration and PPH occurrence (aOR=0.49, 95%CI:0 .27~0 .85). These findings indicate that advanced age, prolonged gestational weeks, and IVF-ET increase the risk of PPH, while oral misoprostol may potentially reduce the prevalence of PPH in patients with PROM.

Table 4. Association between perinatal information and vaginal delivery or failed induction of labor

Variable	Vaginal delivery			Failed induction of labor
Variable	aOR^a	95%CI^b	P value	aOR	95%CI	P-value
Misoprostol administration	1.51	0.93 ~ 2.47	0.10	0.46	0.21 ~ 0.95	0.04
Age	0.94	0.87 ~ 1.01	0.11	0.96	0.86 ~ 1.06	0.42
Body weight gain	1.02	0.97 ~ 1.08	0.43	0.93	0.86 ~ 1.01	0.09
Pregestational BMI	0.93	0.87 ~ 0.99	0.04	1.06	0.96 ~ 1.16	0.27
Gravidity	0.86	0.63 ~ 1.19	0.36	0.85	0.49 ~ 1.34	0.51
Gestational weeks	0.82	0.64 to 1.1	0.12	0.87	0.60 ~ 1.24	0.43
IVF-ET	0.30	0.17 ~ 0.52	<0.01	3.12	1.49 ~ 6.43	<0.01
GDM	1.74	0.95 ~ 3.28	0.08	0.94	0.39 ~ 2.10	0.88
GBS positive	0.59	0.29 ~ 1.24	0.15	1.48	0.46 ~ 3.94	0.47
Bishop score	1.09	0.86 ~ 1.39	0.46	0.85	0.60 ~ 1.20	0.35
Newborn body weight	1.00	0.99 ~ 1.00	0.35	1.00	1.00 ~ 1.00	0.01

^aaOR: adjusted odd ratio

^b 95%CI: 95% confidence intervals

Table 5

Association between perinatal information and postpartum hemorrhage
Variable	aOR	95%CI	P value
Misoprostol administration	0.49	0.27 ~ 0.85	0.01
Vaginal delivery	1.66	0.96 ~ 2.94	0.08
Age	1.17	1.07 ~ 1.27	< 0.01
Body weight gain	1.05	0.98 ~ 1.11	0.14
BMI	1.06	0.98 ~ 1.14	0.17
Gravidity	0.96	0.67 ~ 1.36	0.83
Gestational weeks	1.35	1.02 ~ 1.80	0.04
IVF-ET	2.43	1.32 ~ 4.48	< 0.01
GDM	1.19	0.62 ~ 2.22	0.59
GBS positive	1.65	0.70 ~ 3.64	0.23
Bishop score	1.10	0.85 ~ 1.45	0.48
Newborn body weight	1.00	0.99 ~ 1.00	0.24

Although misoprostol is utilized off-label for late gestational induction of labor in China and various other regions, it is now being increasingly used in the field of obstetrics. According to the national guidelines on labor induction published in 2014, vaginal administration is the most recommended route for misoprostol usage. However, this route has been associated with numerous complications such as uterine hyperstimulation, fetal heart rate changes, placental abruption, emergency operations, and amniotic fluid embolism. Meanwhile, the national guideline recommends that misoprostol should only be used in pregnant women with intact membranes, which restricts its administration via vaginal route to mothers with premature rupture of membranes. After the 37th week of gestation, the American College of Obstetricians and Gynecologists (ACOG) suggests the administration of oxytocin to induce labor in cases of PROM. However, clinical experience has shown suboptimal efficacy and unsatisfactory maternal outcomes associated with oxytocin use. This calls for the development of alternative and more effective methods to induce labor, particularly in women with an unripe cervix condition.

Although the national guideline for labor induction has not been updated, numerous publications have indicated that oral low-dose misoprostol may be superior to vaginal administration. However, data on the use of oral route in China is limited. In this study, we aimed to evaluate the effectiveness and safety of oral low-dose misoprostol for term PROM mothers with an unripe cervix condition.

To date, numerous comparative studies have explored the application of oral misoprostol in labor induction among term PROM pregnant women. A study by Leila Pourali et al⁸ found that sublingual administration of 25 μg misoprostol every 4 hours for labor induction in PROM cases improved neonatal outcomes with better efficacy compared to oxytocin. Elsewhere, Rania et al.⁹ administered oral misoprostol tablets at a dose of 25 μg every four hours to achieve labor induction in PROM, and observed that women who received oral misoprostol had significantly shorter induction-delivery intervals compared to those who received oxytocin group, particularly among multiparous women. In another study¹¹, oral misoprostol solution at a dosage of 20 μg every 2 hours demonstrated comparable maternal complications and neonatal outcomes relative to standard intravenous oxytocin administration.

In our study, we administered 25 μg misoprostol solution every 2 hours in accordance with the recommendations set forth by the Society of Obstetricians and Gynecologists of Canada (SOGC)¹² and the National Institute for Health and Care Excellence (NICE)¹³. Consistent with previous reports, we found no statistically significant differences in the rates of labor onset and vaginal delivery between groups that received oral misoprostol and those that received oxytocin. Moreover, there were no significant differences in the rates of uterine hyperstimulation, fetal distress, or neonatal asphyxia between the two groups. In contrast, the use of oral misoprostol was linked to a shorter total labor duration. Therefore, our findings indicate that oral misoprostol is both safe and exhibits superior efficacy compared to oxytocin infusion for labor induction in term pregnant women with PROM.

Although few randomized trials has compared the different guidelines for failed labor induction, observational data have consistently suggested that if the maternal and fetal conditions allow, administration of oxytocin should be continued for at least 12 to 18 hours after membrane rupture before considering an induction of labor as unsuccessful due to nonprogression into the active phase¹⁴. In terms of definition, the failed induction cases in our study follows these criteria, even within the misoprostol group, wherein oxytocin perfusion is initiated after 24 hours of misoprostol administration or upon improvement of cervical condition. Notably, we did not find statistically significant differences in the incidence of failed induction between the two groups, and logistic regression analyses suggests that oral misoprostol may potentially mitigate the risk of unsuccessful labor induction. Moreover, high birth weight of the newborn and IVF-ET may contribute to failed induction. Therefore, we hypothesize that infants classified as large for gestational age (LGA) are more likely to necessitate a cesarean section and dystocia. Furthermore, IVF-ET gestation has been linked with advanced maternal age and various social as well as mental factors which affect the success of vaginal deliveries.

Our results further indicated that the incidence of postpartum hemorrhage was lower in women who were administered oral misoprostol. Furthermore, logistic regression analysis demonstrated that oral misoprostol administration efficiently mitigated the risk for PPH. Studies have indicated that prolonged exposure to high doses of oxytocin during labor increases the severity of postpartum hemorrhage (PPH) due to uterine atony¹⁵. A recent study by Braund S, et al.¹⁶ further revealed a strong association between labor induction and the risk of PPH, with the quantity of administered oxytocin found to influence this relationship. Bernitz et al¹⁷ reported increased risk of PPH associated with prenatal administration of high doses of oxytocin infusion. At the molecular level, this phenomenon is referred to as desensitization of oxytocin receptors (OTRs)¹⁸. Another study found that pretreatment with oxytocin attenuated oxytocin-induced contractility in human myometrium, even after a rest period of up to 90 minutes following oxytocin administration¹⁹.

The incidence of postpartum urinary retention (PPUR) was significantly different between the two groups. Several prognostic factors have been linked to increased risk of PPUR^20,21, including the mode and duration of labor, presence of perineal trauma, method of anesthesia or analgesia, patient's BMI, and baby's birth weight. However, few studies have reported on the association between induction of labor and the mode of induction with PPUR. Although the pathophysiology of PPUR is not clear, caution should be exercised regarding the application of oral misoprostol in patients with PROM.

This study several limitations. Firstly, this was a single-center study conducted at a tertiary general hospital in Beijing. The patient population primarily consisted of individuals with perinatal complications and some transfer patients from lower-level hospitals²². Therefore, future multi-center studies and randomized clinical trials are needed to enhance the generalizability of our findings. Secondly, different medical staff members may have varying interpretations of Bishop scores, which can impact the predictive value of successful induction. we propose that the same individuals should consistently assess the Bishop scores to avoid errors. Lastly, we did not record adverse reactions in this study. In future, researchers should comprehensively evaluate drug safety, data on adverse reactions such as rapid heart rate, fever, gastrointestinal reactions etc., should be included in future studies.

In conclusion, oral low-dose misoprostol is safe and has superior efficacy to oxytocin infusion for labor induction. Moreover, it reduces the incidence of failed induction in term PROM pregnant women with unfavorite cervix condition. Low-dose oral misoprostol may decrease the risk of postpartum hemorrhage but increase the rate of postpartum urinary retention.

Study design

This retrospective nested case-control study was conducted in a tertiary maternity unit (6000 deliveries per year) in the Gynecology and Obstetrics Unit of Peking University Third Hospital, in China, from March 2020 to February 2024. A retrospective cohort study was performed over a period of four years, including patients with PROM and unripened cervix after 37 weeks gestation. Oxytocin induction was performed in 282 cases from March 2020 to February 2022, while cervical maturation was achieved using oral low-dose misoprostol solution in 167 cases from March 2022 to February 2024. This study has been approved by the Ethics Committee of Peking University Third Hospital (Approval No. 245-02) in accordance with the Declaration of Helsinki. All participants were adequately informed about the labor procedure and provided signed informed consent.

Participants

Participants were enrolled if they met the following inclusion criteria: singleton, primiparous, cephalic presentation, gestational age ≥37 weeks, PROM without rhythmic contractions, no contraindication to prostaglandins, bishop scores < 6 (unripped cervix) and candidate for vaginal delivery. The exclusion criteria were twin pregnancies, fetuses in the breech or transverse position, intrauterine fetal demise or termination of labor due to severe fetal malformation, history of uterine scarring, those with rhythmic contractions, and refusal to participate in the study. The diagnosis of PROM was confirmed either through clinical assessment or by a pH test paper. According to our departmental protocol, labor induction was initiated after 37 weeks of gestation if there were no signs of spontaneous labor or absence of regular contractions for more than 2 hours following rupture.

Drugs administration

Oral misoprostol solution: Pregnant women who met the inclusion criteria were transferred to the delivery room. Before drug administration, confirmation of fetal heart monitoring response type was conducted again to ensure there were no contraindications. The drug was administered by both the midwife and physician, starting with an initial dose of 25 μg followed by subsequent doses of 25 μg every 2 hours. In cases where contraction frequency exceeded 2 times per 10 minutes, administration of the drug was delayed, and daily dosage did not exceed 200 μg. Once the cervical Bishop score reached ≥6 points, oxytocin infusion was initiated if deemed appropriate. For the specific drug preparation, a 200 μg tablet of misoprostol was dissolved in 200 ml of warm water, ensuring thorough mixing to achieve a well-blended solution with a concentration of 1 μg/ml. This solution was then orally administered to pregnant women at a dosage of 25 ml.

Oxytocin intravenous: In the oxytocin group, cervical ripening and induction of labor were achieved through oxytocin perfusion. A serum pump was used to administer 0.5% low-dose oxytocin at a rate of 0.5 mL/min, and was doubled every 15 minutes until the number of contractions was 3 times or more in 10 minutes with the duration of 40 seconds and appropriate force.

Data collection

The following clinical data were collected: prenatal information like age, height, pregestational body mass index (BMI), gravidity, gestational weeks, cervical Bishop score, whether complicated with in vitro fertilization-embryo transfer (IVF-ET), gestational diabetes mellitus (GDM) and infection of Group B streptococcus (GBS+); delivery information like mode of delivery, failed induction of labor, duration from rupture or administration to labor or delivery, duration of labor, delivery outcomes like adverse pregnancy outcomes such as fetal distress, intrauterine infection, postpartum hemorrhage (PPH), postpartum urinary retention. In addition, the rate of episiotomy, birth weight, Apgar score at 1 minute, and umbilical cord blood pH value were recorded.

Outcome indicators

The primary and secondary outcomes were compared between the two groups to evaluate the efficacy and safety of misoprostol. Primary outcomes were the number of vaginal deliveries and failed induction of labor. Failed induction of labor was defined as a prolonged latent phase or the absence of labor following the administration of oxytocin for a minimum of 12 hours²³. Secondary outcomes were delivery complications like fetal stress and PPH.

Statistical analysis

Statistical analyses were performed using GraphPad Prism 9 (GraphPad Software, San Diego, CA). Measurement data with a normal distribution were presented as Mean±SD, and the Student T-test was employed to compare two groups. Measurement data that did not follow a normal distribution were described as M (P25-P75), and comparison between groups was performed using the Mann-Whitney U test. Count data were expressed as the number and percentage, and the comparison between groups was conducted using Fisher's exact probability. Logistic regression models were adjusted for prenatal information and utilized to analyze induced labor failure and PPH. Statistical significance was defined as a P-value <0.05.

PROM

premature rupture of membranes

PPH

Postpartum Hemorrhage

C-section

cesarean section

IVF-ET

in vitro fertilization-embryo transfer

GDM

gestational diabetes mellitus

GBS+

infection of Group B streptococcus

PPUR

postpartum urinary retention

Funding The project was funded by the National Key Research and Development Program of China (2021YFC2701500)

Data availability The data from this study can be requested by contacting Yike Yang ([email protected]).

Author contributions YANG Yike: project design, data collection, data sorting, statistical analysis, thesis writing; YU Zhiheng: project design, data analysis, thesis modification; SHI Huifeng: statistical analysis and guidance; WANG Yan and ZHAO Yangyu: project design, research guidance. All authors approved the submission.

AcknowledgementsThe authors would like to acknowledge support from the National Key Research and Development Program of China. The authors would like to thank all the reviewers who participated in the review, as well as MJEditor (www.mjeditor.com) for providing English editing services during the preparation of this manuscript.

Competing interests The authors declare no competing interests.

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No competing interests reported.

Low-Dose Oral Misoprostol Versus Oxytocin Infusion For Induction Of Labor In Pregnant Women With Term Premature Rupture Of Membranes in China: A retrospective Nested Case-Control Study

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Introduction

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Discussion

Methods and materials

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Version 1