Efficacy and safety of oral and vaginal administration of misoprostol for induction of labor in high-risk obese pregnant women with hypertension or diabetes mellitus

Abstract

Objective

This study aims to compare the safety and efficacy of misoprostol administered orally and vaginally in obese pregnant women at term with either gestational hypertension or diabetes.

Methods

A total of 264 pregnant women were enrolled and categorized into two groups based on their primary condition: hypertension (134 cases) or diabetes mellitus (130 cases) and were further divided into subgroups for misoprostol administration: orally (Oral group) or vaginally (Vaginal group). The primary outcomes measured were changes in the Bishop score following treatment, induction of labor (IOL) success rates, requirement for oxytocin augmentation, duration of labor, mode of delivery, and cesarean section rates.

Results

Significant enhancements in Bishop scores, decreased cesarean section rates and increased success rates of IOL were noted in both administration groups. The incidence of vaginal delivery within 24 h was significantly higher in the Vaginal group compared to the Oral group. Adverse effects, including nausea, uterine overcontraction, hyperfrequency of uterine contraction and uterine hyperstimulation without fetal heart rate deceleration, were significantly more prevalent in the Vaginal group than in the Oral group.

Conclusion

Misoprostol administration, both orally and vaginally, proves effective for labor induction in obese pregnant women with hypertension or diabetes. However, the oral route presents a lower risk of adverse maternal and neonatal outcomes, suggesting its preference for safer labor induction in this demographic.

Keywords:

• Misoprostol
• vaginal administration
• oral administration
• induction of labor
• high-risk obese pregnant women

Introduction

Induction of labor (IOL) refers to an artificial intervention by clinicians to initiate uterine contractions before the onset of natural labor to facilitate childbirth [1]. This procedure is indicated when the continuation of pregnancy poses a significant health risk to either the mother or the fetus, making IOL a preferable option [2]. The prevalence of IOL has been increasing, influenced by factors such as the rising number of pregnancies in older women and advancements in medical technology that improve the detection of maternal comorbidities or complications and fetal developmental issues. A study conducted in California, USA, reported that approximately 47% of pregnant women underwent IOL [3], while in some European countries, the rate of IOL has surpassed 30% [4]. These statistics not only reflect the growing commonality of IOL as a clinical procedure but also emphasize the critical need for selecting safe and effective methods for IOL to safeguard the health and life of the pregnant woman and/or the fetus. Currently, clinical practice for IOL incorporates two main approaches: mechanical and pharmacological. Mechanical methods include procedures such as the incision of the amniotic membrane, cervical dilation with instruments, and the insertion of a catheter [5]. On the other hand, pharmacological methods involve the administration of drugs like oxytocin, and prostaglandins [6], each chosen for their efficacy in inducing labor or preparing the cervix for childbirth.

Misoprostol, a synthetic analog of prostaglandin E1 (PGE1), has emerged as a prominent agent for the IOL. Initially approved for the management of gastric and duodenal ulcers due to its ability to inhibit gastric acid secretion, enhance mucosal repair, and exert mild anti-inflammatory effects [7]. Compared with other prostaglandin analogs, misoprostol exhibits higher activity, longer duration of action, and stability at room temperature [8]. Its utility was expanded upon the discovery of its direct action on the uterine musculature. Misoprostol facilitates uterine contractions and promotes cervical softening and dilation [9]. These attributes have positioned misoprostol as an increasingly preferred first-line pharmacological option for IOL globally, and lead to its FDA approval in 2002 for cervical ripening and IOL [10].

Oral and vaginal routes are the primary methods for administering misoprostol for IOL. Vaginal administration has been shown to offer higher bioavailability compared to the oral route, though it may carry increased safety risks [11,12]. Over the past decade, numerous clinical studies have explored the efficacy and safety of misoprostol administered orally versus vaginally for IOL, yielding contradictory and controversial outcomes [13]. Consequently, there is no established consensus among healthcare professionals regarding the most effective route of misoprostol administration for IOL [14]. Earlier studies grouped pregnant women with various health conditions without distinguishing between their differing health statuses and failed to address the distinct considerations necessary for high-risk obese pregnant women with comorbid conditions such as hypertension or diabetes mellitus. These women face more complex health challenges and an elevated risk during labor, indicating a critical need for research and clinical protocols that specifically target their unique healthcare requirements. Thus, to address the limitations of earlier work, we designed this study to assess the impact of oral versus vaginal misoprostol administration on the outcomes of IOL in a high-risk population to obtain a more solid foundation for selecting the optimal administration route for misoprostol in high-risk obese pregnant women with hypertension or diabetes mellitus.

Materials and methods

Study design

This retrospective cross-sectional study comprised 264 high-risk obese pregnant women who underwent IOL via either oral or vaginal misoprostol administration at the Department of Obstetrics and Gynecology, Haidian District Maternal and Child Health Hospital, from January 2021 to June 2023. The study inclusion criteria were based on one or more indications for IOL, such as gestational hypertension, preeclampsia, chronic hypertension or gestational diabetes mellitus [15]. The study protocol was approved by the Ethics Committee of Haidian District Maternal and Child Health Hospital (approval number ZS2023001), adhering to the ethical standards outlined in the Declaration of Helsinki. Before IOL, all participants provided written informed consent.

Inclusion criteria

The inclusion criteria for participants were as follows: (1) primigravidae with a full-term, singleton pregnancy in cephalic presentation, eligible for vaginal delivery; (2) meeting the World Health Organization (WHO) diagnostic criteria for obesity and either hypertension or diabetes mellitus [16], with a Body Mass Index (BMI) ≥ 30 kg/m²; (3) presenting a cervical Bishop score of less than 6 before IOL; (4) having intact fetal membranes; (5) lacking contraindications to prostaglandin use; (6) absence of vaginal inflammation; and (7) possessing complete clinical data.

Exclusion criteria

The exclusion criteria were: (1) a history of uterine or cervical surgery; (2) the presence of placenta praevia; (3) severe preeclampsia associated with impairment of organ function; (4) diabetes mellitus classified as class B or above according to the White classification; (5) abnormal volume of amniotic fluid; (6) abnormal fetal heart rate patterns or abnormal systolic/diastolic (S/D) ratios in the umbilical artery or middle cerebral artery before IOL as assessed by Doppler ultrasound; (7) presence of any known contraindications to prostaglandins, such as a history of asthma exacerbated by NSAIDs or previous cesarean delivery; (8) presence of vaginal inflammation (i.e. vaginal discharge, itching, or pain) by pelvic examination; and (9) a definitive diagnosis of fetal growth restriction before IOL.

Definitions, groupings and interventions

Participants with gestational hypertension or preeclampsia were diagnosed according to the American College of Obstetricians and Gynecologists (ACOG) criteria. The included participants with gestational diabetes mellitus were diagnosed by oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Fetal Growth Restriction (FGR) was defined as estimated fetal weight below the 10th percentile for gestational age, indicating the fetus is not growing as expected.

The study cohort was categorized into two groups based on comorbid conditions: a hypertension group (134 cases) and a diabetes mellitus group (130 cases). None of the participants had concurrent diagnoses of both hypertension and diabetes mellitus. In each disease-specific group, the participants were further stratified based on the route of misoprostol administration for IOL: an oral misoprostol group (Oral group) and a vaginal misoprostol group (Vaginal group). Overall, the study included 67 cases of high-risk obese pregnant women with hypertension in both the Oral and Vaginal groups and 65 cases of those with diabetes mellitus in each of these administration groups.

For participants in the Oral group, 200 μg of misoprostol was dissolved in 200 ml of purified water, creating a solution with a concentration of 1 μg/ml. Initially, these pregnant women received 25 ml of this solution orally, followed by the same dose every 2 h until the onset of regular contractions. In the Vaginal group, a 25 μg misoprostol tablet, uncrushed, was inserted into the posterior vaginal fornix following vulvar disinfection. In the absence of contractions 6 h post-administration, a vaginal examination was conducted to evaluate cervical ripeness and to check whether the misoprostol had dissolved and been absorbed. If the tablet had not fully dissolved and been absorbed, no additional dose was administered; however, if the tablet was fully absorbed but there was no improvement in cervical condition, another 25 μg of misoprostol was administered until regular contractions commenced. The maximum daily dosage of misoprostol did not exceed 50 μg. Throughout the misoprostol administration process for induction of labor, clinical professionals meticulously monitored all participants for fetal heart rate and the intensity and frequency of uterine contractions. In cases where contractions were excessively frequent, an immediate vaginal examination was conducted, and any residual drug was removed. Additional oxytocin could be administered no sooner than 4 h following the last dose, contingent upon a vaginal examination confirming drug absorption. Moreover, if these methods did not induce spontaneous labor and the Bishop score reached or exceeded 6, labor induction proceeded with manual rupture of membranes and oxytocin administration by a clinical healthcare professional in the delivery room. The misoprostol dosage and administration intervals in this study adhered to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO) [17]. The medication flow is shown in Figure 1.

Figure 1. The different treatment way of misoprostol for oral group and vaginal group.

Data collection

In this study, data on pregnant women and their newborns was collected from electronic and paper medical records, comprising age, BMI, obesity classification (class I, II, III), gestational age, number of miscarriages, parity, history of curettage and the incidence of premature rupture of membranes. Additionally, medical conditions like gestational hypertension and gestational diabetes mellitus were recorded. Information related to the IOL included its success rate, labor duration (first, second, third stages, and total), delivery method (vaginal delivery, instrumental vaginal delivery, cesarean section), Bishop’s score before and after misoprostol intervention, requirement for oxytocin, IOL failure rate, and complications such as fetal distress, chorioamnionitis, meconium-stained amniotic fluid. Other data collected were the onset of action of misoprostol, time from drug administration to delivery, rate of vaginal delivery within 24 h, frequency and intensity of contractions, postpartum hemorrhage incidence (≥ 500 ml for vaginal delivery within 24 h or ≥ 1000 ml during cesarean section), adverse drug reactions (nausea, vomiting, diarrhea), and cases of uterine hyperstimulation with or without fetal heart deceleration. Neonatal data encompassed birth weight, 1-min and 5-min Apgar scores, incidence of neonatal asphyxia, cord arterial pH below 7.2, neonatal infections, and the necessity for intensive care.

Outcome indicators

We evaluated the impact of various misoprostol administration routes on IOL outcomes. Primary outcomes included the success rate of IOL (i.e. the percentage of women who achieve vaginal delivery following the initiation of labor induction methods, measured from the time of the first intervention [misoprostol administration] to the occurrence of labor that leads to vaginal delivery, within a defined period, typically 24 to 48 h), labor duration (i.e. the sums these three stages, providing an overall measure of the time from the onset of labor to the delivery of the placenta), delivery method (i.e. vaginal delivery and cesarean section), Bishop’s score following misoprostol intervention, the requirement for oxytocin (i.e. percentage of women needing oxytocin augmentation to achieve successful labor induction), and the incidence of indications leading to cesarean section (i.e. the frequency of specific clinical conditions or labor complications that necessitate delivery by cesarean section, such as strong contractions, failure of inductions [labor dystocia], fetal distress and maternal health conditions that contraindicate vaginal delivery [e.g. maternal failure]). Strong contractions is defined as the occurrence of uterine contractions lasting more than one minute each, with a gap of less than two minutes. Failure of inductions is defined as failure to achieve vaginal delivery within 48 h of induced labor.

Statistical analysis

Data were analyzed using SPSS 25.0 software (IBM Corp., Armonk, NY, USA). The normality of data distribution was assessed with the Kolmogorov-Smirnov test. Quantitative data were presented as mean ± standard deviation, while qualitative data were expressed in frequencies (%). Comparisons of quantitative data between two groups were conducted using the independent samples t-test, qualitative data comparisons were made with the chi-square test or Fisher’s exact test, and hierarchical data were analyzed using the rank sum test. Relative risk (RR) and 95% confidence intervals (CI) were calculated. A P-value of < 0.05 was considered statistically significant.

Results

Baseline demographic characteristics

A total of 264 pregnant women were included in this study, divided into two cohorts: those with hypertension (134 women) and those with diabetes (130 women) (Figure 2). In the hypertension cohort, the oral and vaginal groups showed no significant differences in baseline characteristics such as age, BMI, gestational age, obesity classification, Bishop’s score, miscarriage history, parity, and history of curettage. The oral group’s average age was 30 years with a BMI of 38.58, while the vaginal group’s average age was 29 years with a BMI of 38.88. Similarly, in the diabetes cohort, both medication groups were comparable across metrics like age, BMI, gestational age, Bishop score, and obstetric history, with the oral group having an average age of 29 years and a BMI of 37.85, and the vaginal group with an average age of 29 years and a BMI of 38.11. These findings highlight that, among high-risk obese pregnant women either with hypertension or diabetes, the choice between oral and vaginal medication does not significantly affect basic maternal characteristics, indicating a potential for flexible treatment approaches based on patient and provider preferences (Table 1).

Figure 2. Screening flow of the study participants.

Table 1. Basic information of patients.

	Hypertension group			Diabetes mellitus group
Variables	Oral group (n = 67)	Vaginal group (n = 67)	p	Oral group (n = 65)	Vaginal group (n = 65)		p
Age	30.30 ± 3.22	29.55 ± 3.38	0.193	29.51 ± 2.87	29.65 ± 3.11		0.792
BMI	38.58 ± 2.02	38.88 ± 1.32	0.323	37.85 ± 2.73	38.11 ± 2.34		0.554
Obesity class			0.138				0.439
I	6 (9.0)	1 (1.7)		10 (15.4)	6 (9.2)
II	51 (78.5)	57 (85.1)		47 (72.3)	53 (81.5)
III	10 (13.8)	10 (14.9)		8 (12.3)	6 (9.2)
Gestational age	245.76 ± 5.58	246.79 ± 6.15	0.319	246.88 ± 6.59	245.02 ± 5.88		0.092
Bishop’s score before intervention	3.46 ± 1.16	3.42 ± 1.12		0.820	3.45 ± 1.08	3.51 ± 1.09	0.747
Number of miscarriage			0.125				0.184
0	48 (71.6)	52 (77.6)		52 (80.0)	49 (75.4)
1	15 (22.4)	15 (22.4)		9 (13.8)	15 (23.1)
2	4 (6.0)	0 (0.0)		4 (6.2)	1 (1.5)
Parity			0.125				0.184
1	48 (71.6)	52 (77.6)		52 (80.0)	49 (75.4)
2	15 (22.4)	15 (22.4)		9 (13.8)	15 (23.1)
3	4 (6.0)	0 (0.0)		4 (6.2)	1 (1.5)
History of curettage			0.829				0.108
No	54 (80.6)	53 (79.1)		57 (87.7)	50 (76.9)
Yes	13 (19.4)	14 (20.9)		8 (12.3)	15 (17.7)
Premature rupture of membranes	1 (1.49)	2 (2.99)	0.559	0 (0.00)	1 (1.54)		0.315

Note. *p < 0.05 indicates a statistical difference between the Oral and Vaginal groups. BMI: body mass index.

Effects of two misoprostol administration routes on the main outcome indicators of induction of labor in high-risk obese pregnant women with hypertension

In the cohort of high-risk obese pregnant women with hypertension, the IOL success rate in the Vaginal group was marginally higher compared to the Oral group (74.6% vs. 64.2%) but not statistically significant (p > 0.05). The incidence of spontaneous vaginal delivery was significantly greater in the Vaginal group (43.4%) than in the Oral group (26.9%, p < 0.05), while the rates of instrumental vaginal delivery and cesarean section were somewhat lower, with no statistical significance in these differences (p > 0.05). Furthermore, post-intervention comparisons of Bishop’s score, labor duration, IOL failure rate, fetal distress, chorioamnionitis, and meconium-stained amniotic fluid incidence between the Vaginal and Oral groups showed no significant differences (p > 0.05). Importantly, the requirement for oxytocin was substantially lower in the Vaginal group (7.5%) compared to the Oral group (28.4%, p < 0.05), indicating a notable difference in labor-management between the two groups (Table 2).

Table 2. Effect of oral and vaginal administration of misoprostol on the main outcome indicators of IOL in high-risk obese pregnant women with hypertension.

Variables	Oral group (n = 67)	Vaginal group (n = 67)	RR	95%CI	p
Success rate of IOL	43 (64.2)	50 (74.6)	1.642	0.781–3.451	0.189
Duration of labor
first (min)	645.56 ± 43.74	655.7 ± 40.01	1.006	0.998–1.014	0.163
second (min)	52.97 ± 14.84	49.33 ± 16.51	0.986	0.965–1.007	0.194
third (min)	12.01 ± 4.70	11.75 ± 4.76	0.988	0.919–1.062	0.741
total (min)	710.55 ± 45.92	716.78 ± 43.84	1.003	0.996–1.011	0.421
Bishop’s score after intervention	6.49 ± 1.35	6.40 ± 1.50	0.956	0.753–1.215	0.715
Need for oxytocin	19 (28.4)	5 (7.5)	0.204	0.071–0.585	0.002*
Mode of delivery
Spontaneous vaginal delivery	18 (26.9)	29 (43.3)	2.077	1.006–4.289	0.046*
Instrumental vaginal delivery	24 (35.8)	18 (26.9)	0.658	0.315–1.374	0.264
Cesarean section	25 (37.3)	20 (29.9)	0.715	0.348–1.469	0.360
Indications for cesarean section
Failure of IOL	5 (20.0)	6 (30.0)	0.583	0.148–2.294	0.438
Fetal distress	2 (8.0)	0 (0.0)	–		0.196
Chorioamnionitis	3 (12.0)	2 (10.0)	1.227	0.185–8.161	0.832
Meconium-staining amniotic fluid	2 (8.0)	0 (0.0)	–	–	0.196

Note. *p < 0.05 indicates a statistical difference between the Oral and Vaginal groups.

IOL: induction of labor: RR: relative risk; CI: confidence interval.

Effects of two misoprostol administration routes on the main outcome indicators of induction of labor in high-risk obese pregnant women with diabetes mellitus

In the subgroup of high-risk obese pregnant women with diabetes mellitus, the IOL success rates between the Vaginal and Oral groups showed no significant difference (76.9% vs. 78.5%, p > 0.05). Additionally, there were no significant differences observed in the rates of spontaneous vaginal delivery, instrumental vaginal delivery, cesarean section, the Bishop’s scores before and after intervention, the necessity for oxytocin, the duration of labor, the IOL failure rate, and the incidences of fetal distress, chorioamnionitis, and meconium-stained amniotic fluid between the two groups (p > 0.05) (Table 3).

Table 3. Effect of oral and vaginal administration of misoprostol on the main outcome indicators of IOL in high-risk obese pregnant women with diabetes mellitus.

Variables	Oral group (n = 65)	Vaginal group (n = 65)	RR	95%CI	p
Success rate of IOL	51(78.5)	50(76.9)	0.915	0.401–2.091	0.833
Duration of labor
First (min)	653.15 ± 43.52	663.80 ± 41.69	1.006	0.998–1.014	0.156
Second (min)	53.28 ± 16.24	50.91 ± 16.15	0.991	0.970–1.012	0.403
Third (min)	12.17 ± 4.84	11.91 ± 4.93	0.989	0.921–1.062	0.759
Total (min)	718.60 ± 47.51	726.62 ± 44.01	1.004	0.996–1.012	0.318
Bishop’s score after intervention	6.35 ± 1.45	6.52 ± 1.29	1.095	0.851–1.411	0.480
Need for oxytocin	10(15.4)	8(12.3)	0.772	0.284–2.100	0.612
Mode of delivery
Spontaneous vaginal delivery	21(32.3)	18(27.7)	0.802	0.378–1.702	0.566
Instrumental vaginal delivery	23(35.4)	31(47.7)	1.665	0.824–3.366	0.154
Cesarean section	21(32.3)	16(24.6)	0.684	0.318–1.474	0.331
Indications for cesarean section
Failure of IOL	5(23.8)	5(31.3)	0.688	0.160–2.55–	0.614
Fetal distress	3(14.3)	2(12.5)	1.167	0.171–7.963	0.875
Chorioamnionitis	1(4.8)	1(6.3)	0.750	0.043–12.985	0.843
Meconium-staining amniotic fluid	1(4.8)	1(6.3)	0.750	0.043–12.985	0.843

Note. *p < 0.05 indicates a statistical difference between the Oral and Vaginal groups.

IOL: induction of labor: RR: relative risk; CI: confidence interval.

Effect of two misoprostol administration routes on secondary outcome indicators of induction of labor in high-risk obese pregnant women with hypertension

In the group of high-risk obese pregnant women with hypertension, the Vaginal group showed significantly higher rates of vaginal delivery within 24 h (62.7% vs. 41.8%), frequent contractions (34.3% vs. 10.4%), strong contractions (28.4% vs. 3.0%), and nausea (53.7% vs. 34.3%) compared to the Oral group (p < 0.05). Additionally, the incidence of uterine hyperstimulation without fetal heart deceleration was significantly higher in the Vaginal group (17.9% vs. 0%, p < 0.05). There were no significant differences in the action time of misoprostol, the time from administration to delivery, postpartum hemorrhage, and the rates of uterine hyperstimulation with fetal heart deceleration, vomiting, and diarrhea between the two groups (p > 0.05). Regarding neonatal outcomes, there was no significant difference in weight, 1-min Apgar score, 5-min Apgar score, rate of neonatal asphyxia, rate of cord arterial pH < 7.2, rate of neonatal infection, and rate of neonatal intensive care unit admission between the Vaginal and Oral groups (p > 0.05) (Table 4).

Table 4. Effect of oral and vaginal administration of misoprostol on secondary outcome indicators of IOL in high-risk obese pregnant women with hypertension.

Variables	Oral group (n = 67)	Vaginal group (n = 67)	RR	95%CI	p
Action time of misoprostol	54.73 ± 6.67	55.94 ± 6.95	1.027	0.976–1.080	0.304
Time from administration to delivery	6.40 ± 0.65	6.24 ± 0.65	0.677	0.398–1.150	0.149
Vaginal delivery within 24 h	28 (41.8)	42 (62.7)	2.340	1.170–4.681	0.015*
Frequent contractions	7 (10.4)	23 (34.3)	0.223	0.088–0.566	0.001*
Strong contractions	2 (3.0)	19 (28.4)	0.078	0.017–0.350	0.000*
Postpartum hemorrhage (bleeding volume > 1000 ml)	10 (14.9)	22 (32.8)	2.787	1.199–3.256	6.478
Uterine hyperstimulation with fetal heart deceleration	2 (3.0)	3 (4.5)	1.523	0.246–9.423	0.649
Uterine hyperstimulation without fetal heart deceleration	0 (0.00)	12 (17.9)	0.069	0.009–0.551	0.001*
Epidural anesthesia	7 (10.4)	9 (13.4)	1.330	0.465–3.807	0.594
Adverse drug reactions
nausea	23 (34.3)	36 (53.7)	2.222	1.107–4.458	0.024*
vomiting	16 (23.9)	9 (13.4)	0.495	0.201–1.216	0.121
diarrhea	7 (10.4)	4 (6.0)	0.544	0.152–1.954	0.266
Neonatal weight	3.68 ± 0.35	3.78 ± 0.34	2.292	0.847–6.206	0.103
Neonatal intensive care	4 (6.0)	4 (6.0)	1.000	0.239–4.175	1.000
1-min Apgar score ≤ 7	2 (3.0)	3 (4.5)	1.523	0.246–9.423	0.649
5-min Apgar score ≤ 7	5 (7.5)	4 (6.0)	0.787	0.202–3.070	0.730
Cord arterial pH < 7.2	1 (1.5)	1 (1.5)	1.000	0.061–16.325	1.000
Neonatal infection	3 (4.5)	1 (1.5)	0.323	0.033–3.189	0.310
Neonatal asphyxia	1 (1.5)	1 (1.5)	1.000	0.061–16.325	1.000

Note: *p < 0.05 indicates a statistical difference between the Oral and Vaginal groups.

IOL: induction of labor: RR: relative risk; CI: confidence interval.

Effect of two misoprostol administration routes on secondary outcome indicators of induction of labor in high-risk obese pregnant women with diabetes mellitus

In the study of high-risk obese pregnant women with diabetes mellitus, the Vaginal group showed a significantly higher rate of vaginal delivery within 24 h (46.2% vs. 24.6%), increased occurrence of frequent contractions (43.1% vs. 7.7%), strong contractions (41.5% vs. 15.4%), and nausea (70.8% vs. 49.2%), as well as a higher incidence of uterine hyperstimulation without fetal heart deceleration (23.1% vs. 1.54%, p < 0.05), compared to the Oral group. The study found no significant differences between the groups in terms of the onset action of misoprostol, the duration from administration to delivery, incidences of postpartum hemorrhage, nausea, vomiting, diarrhea, and the rate of uterine hyperstimulation with fetal heart deceleration (p > 0.05). Regarding neonatal outcomes, there were no significant differences in weight, 1-min Apgar score, 5-min Apgar score, rates of neonatal asphyxia, neonatal infection, and admission to the neonatal intensive care unit between the two groups (p > 0.05). However, the rate of cord arterial pH less than 7.2 was significantly higher in the Vaginal group compared to the Oral group (18.5% vs. 6.2%, p < 0.05) (Table 5).

Table 5. Effect of oral and vaginal administration of misoprostol on secondary outcome indicators of IOL in high-risk obese pregnant women with diabetes mellitus.

Variables	Oral group (n = 65)	Vaginal group (n = 65)	RR	95%CI	P
Action time of misoprostol	62.14 ± 8.04	62.75 ± 8.23	1.009	0.967–1.053	0.664
Time from administration to delivery	6.54 ± 1.20	6.85 ± 1.12	1.258	0.932–1.699	0.133
Vaginal delivery within 24 h	16(24.6)	30(46.2)	2.625	1.245–5.534	0.010*
Frequent contractions	5(7.7)	28(43.1)	0.110	0.039–0.310	0.000*
Strong contractions	10(15.4)	27(41.5)	0.256	0.111–0.590	0.001*
Postpartum hemorrhage (bleeding volume > 1000 ml)	6(9.2)	7(10.8)	1.187	0.376–3.745	0.770
Uterine hyperstimulation with fetal heart deceleration	3(4.6)	6(9.2)	2.102	0.502–8.791	0.300
Uterine hyperstimulation without fetal heart deceleration	1(1.54)	15(23.1)	0.052	0.007–0.408	0.000*
Epidural anesthesia	6(9.2)	7(10.8)	1.187	0.376–3.745	0.770
Adverse drug reactions
nausea	32(49.2)	46(70.8)	2.497	1.212–5.143	0.012*
vomiting	3(4.6)	6(9.2)	2.102	0.502–8.791	0.300
diarrhea	6(9.2)	4(6.2)	0.645	0.173–2.401	0.372
Neonatal weight	3.43 ± 0.34	3.42 ± 0.38	0.955	0.365–2.497	0.926
Neonatal intensive care	2(3.1)	4(6.2)	2.066	0.365–11.692	0.403
1-min Apgar score ≤ 7	2(3.1)	4(6.2)	2.066	0.365–11.692	0.403
5-min Apgar score ≤ 7	2(3.1)	3(4.6)	1.524	0.246–9.437	0.648
Cord arterial pH < 7.2	4(6.2)	12(18.5)	3.453	1.050–11.349	0.033*
Neonatal infection	2(3.1)	2(3.1)	1.000	0.137–7.322	1.000
Neonatal asphyxia	2(3.1)	3(4.6)	1.524	0.246–9.437	0.648

Note: *p < 0.05, indicates a statistical difference between the Oral and Vaginal groups. IOL: induction of labor: RR: relative risk; CI: confidence interval.

Discussion

This study evaluated the effects of oral versus vaginal misoprostol administration in inducing labor among high-risk obese pregnant women with hypertension or diabetes mellitus. The findings indicate that while the vaginal route slightly improved the success rate of IOL and the rate of spontaneous vaginal deliveries among hypertensive women, these differences were not statistically significant for women with diabetes mellitus. Notably, the vaginal group required significantly less oxytocin support compared to the oral group among hypertensive patients. Adverse outcomes such as uterine hyperstimulation without fetal heart rate deceleration were more common in the vaginal group for both conditions, with the study also noting a higher rate of cord arterial pH less than 7.2 in the vaginal group among women with diabetes mellitus. Overall, the study suggests that the route of misoprostol administration may influence labor outcomes and the need for oxytocin, with the vaginal route showing potential benefits in certain conditions but also associated with specific adverse effects.

Obesity significantly contributes to adverse birth outcomes and is a major factor in the failure of IOL [18]. Research has shown that obese pregnant women exhibit reduced uterine contractility compared to their non-obese counterparts, attributed to pathological changes such as leptin resistance, changes in cholesterol levels, and hormonal imbalances [19,20]. This reduced contractility has been linked to the need for higher doses of oral misoprostol during IOL, increased IOL failure rates, extended labor durations, and a greater likelihood of cesarean delivery, as highlighted by Tolcher et al. [21] and Stefely et al. [22] when comparing outcomes between obese and non-obese pregnant women. Furthermore, conditions like hypertension and diabetes mellitus in pregnant women necessitate careful consideration during IOL. Notably, engaging in routine IOL at term for women with either hypertension or diabetes does not significantly elevate the risks of maternal or neonatal complications. The risk associated with IOL is considerably less than the risk of prolonging pregnancy beyond 41 weeks in these populations [23]. These findings underscore the distinct considerations required for medication choice, administration route, and the decision-making process surrounding IOL in pregnant women who are obese and/or have underlying health conditions. This rationale underpins the study’s focus on this specific patient group.

The uniformity of clinical indicators among the pregnant women in all groups before IOL confirmed the sample’s homogeneity and comparability. The Bishop’s score plays a vital role in assessing the potential success of IOL [24]. In this article, the average Bishop’s score across all groups was below 4 before intervention, indicating a low likelihood of achieving vaginal delivery. This observation highlights the importance of employing targeted interventions to modify cervical conditions, thereby enhancing the chances of successful vaginal delivery. Post-intervention, a significant increase in the mean Bishop’s scores was observed across all groups, with no marked differences between them. Our findings indicate that misoprostol, whether administered orally or vaginally, is comparably effective for inducing labor in high-risk obese pregnant women with hypertension or diabetes mellitus, which is supported by the absence of significant differences in key outcomes, including the success rate of induced labor, labor duration, and the frequency of cesarean deliveries due to failed induction. The effectiveness of both administration routes in this specific population aligns with the findings of Abbassi et al. [24], Langenegger et al. [25], and Prameela et al. [26], who reported similar efficacy between oral and vaginal misoprostol in the broader population of pregnant women, regardless of obesity status.

Our study found that in high-risk obese pregnant women with hypertension or diabetes mellitus, the rate of vaginal deliveries within 24 h was significantly higher in the group receiving vaginal misoprostol compared to those receiving it orally. This observation aligns with Haas et al. [27], and the underlying mechanism can be attributed to the pharmacokinetics of the drug delivery routes. Specifically, vaginal administration of misoprostol offers direct exposure to the cervix and uterus, leading to quicker onset of contractions and more immediate effects, while the oral administration necessitates a longer pathway for the drug to be absorbed into the bloodstream, circulate, and finally act on the uterus, thereby delaying the onset of labor-inducing effects as outlined by Kerr et al. [12]

In addition, we examined the incidence of various maternal and neonatal adverse events to evaluate the safety of misoprostol administered orally versus vaginally in high-risk obese pregnant women with hypertension or diabetes mellitus. Our findings indicated a significantly higher risk of frequent contractions, strong contractions, and uterine hyperstimulation without fetal heart deceleration in the Vaginal group compared to the Oral group. Moreover, among pregnant women with diabetes mellitus, the likelihood of neonatal cord arterial pH being less than 7.2, indicative of potential acidosis and hypoxia, was significantly greater in neonates born to the Vaginal group. These outcomes align with previous research by Mehrotra et al. [28] and Shetty et al. [29], which suggested an increased risk of contraction abnormalities with vaginal misoprostol, and with Rahimi et al. [13], who found a higher likelihood of neonatal complications following vaginal misoprostol use in a meta-analysis. While oral misoprostol is typically associated with more gastrointestinal side effects like diarrhea, nausea, and vomiting due to its absorption pathway through the gastrointestinal tract before bloodstream entry [13,30], our study interestingly observed a higher incidence of nausea in the Vaginal group. This unexpected result points to the need for further investigation to clarify the underlying causes.

In this study, we also focused on the cesarean section rates across different groups, as cesarean delivery is a common alternative when IOL with misoprostol is unsuccessful. The rate of cesarean section serves as an indirect indicator of IOL failure rates. According to an epidemiological study by Garabedian et al. the cesarean section rate among obese pregnant women with a BMI of 40–49.9 kg/m² was found to be 47.1%, and it increased to 56.1% for those with a BMI greater than 50 kg/m² [31]. However, in our study, the cesarean section rates ranged from 24.6% to 37.3% across the four groups of pregnant women, notably lower than the rates reported in previous data. These findings are in line with Wolfe et al. [32], who reported a roughly 30% IOL failure rate among obese pregnant women, further underscoring the efficacy of misoprostol in facilitating labor.

Based on our reported findings, both oral and vaginal misoprostol administration methods were found to exhibit comparable efficacy in inducing labor among high-risk obese pregnant women with hypertension or diabetes mellitus, with only minor differences observed in certain outcomes. Notably, oral administration of misoprostol was associated with a lower risk of adverse effects, suggesting it may be a safer option for this patient population. However, this study’s retrospective analysis design introduces potential limitations, including selection bias and the possibility of missing clinical information during the enrollment of participants. To validate and expand upon these findings, future studies could aim to conduct prospective, randomized controlled trials.

Conclusion

In conclusion, misoprostol, whether administered orally or vaginally, is equally effective in inducing labor in high-risk obese pregnant women with diabetes mellitus or hypertension. Both administration routes significantly enhance the Bishop’s score, diminish the likelihood of cesarean section, and exhibit high success rates of induced labor. Nonetheless, oral administration emerges as a safer alternative, given that vaginal administration is linked to an increased risk of adverse maternal and neonatal outcomes.

Ethics approval and consent to participate

The study was reviewed and approved by the Ethics Committee of Haidian District Maternal and Child Health Hospital (ZS2023001) and strictly followed the principles of the Declaration of Helsinki. All pregnant women signed an informed consent form before IOL.

Authors’ contributions

ST and LW conceived and designed the study. ST and LW conducted the study. YWH and YNL contributed to data acquisition. FQL and XHJ analyzed the data. ST and FQL interpreted the data. ST and LW edited the manuscript draft. ST and LW reviewed and edited the manuscript. All authors have read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and materials

The datasets used and/or analyzed during the current study can be made available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by High-level Talent Development Program of Health System of Haidian District (project number: 2022HDXD006).