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BMC Pregnancy and Childbirth Sep 2022Various methods are used for cervical ripening during the induction of labor. Mechanical and pharmacological methods are commonly used for cervical ripening. A... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Various methods are used for cervical ripening during the induction of labor. Mechanical and pharmacological methods are commonly used for cervical ripening. A double-balloon catheter was specifically developed to ripen the cervix and induce labor; however, the efficacy of the double-balloon catheter in cervical ripening compared to other methods is unknown.
METHODS
We searched five databases and performed a Bayesian network meta-analysis. Six interventions (double-balloon catheter, Foley catheter, oral misoprostol, vaginal misoprostol, dinoprostone, and double-balloon catheter combined with oral misoprostol) were included in the search. The primary outcomes were cesarean delivery rate and time from intervention-to-birth. The secondary outcomes were as follows: Bishop score increment; achieving a vaginal delivery within 24 h; uterine hyperstimulation with fetal heart rate changes; need for oxytocin augmentation; instrumental delivery; meconium staining; chorioamnionitis; postpartum hemorrhage; low Apgar score; neonatal intensive care unit admission; and arterial pH.
RESULTS
Forty-eight randomized controlled trials involving 11,482 pregnant women were identified. The cesarean delivery rates of the cervical ripening with a double-balloon catheter and oral misoprostol, oral misoprostol, and vaginal misoprostol were significantly lower than cervical ripening with a Foley catheter (OR = 0.48, 95% CI: 0.23-0.96; OR = 0.74, 95% CI: 0.58-0.93; and OR = 0.79, 95% CI: 0.64-0.97, respectively; all P < 0.05). The time from intervention-to-birth of vaginal misoprostol was significantly shorter than the other five cervical ripening methods. Vaginal misoprostol and oral misoprostol increased the risk of uterine hyperstimulation with fetal heart rate changes compared to a Foley catheter. A double-balloon catheter with or without oral misoprostol had similar outcomes, including uterine hyperstimulation with fetal heart rate changes compared to a Foley catheter.
CONCLUSION
Double-balloon catheter did not show superiority when compared with other single method in primary and secondary outcomes of labor induction. The combination of double-balloon catheter with oral misoprostol was significantly reduced the rate of cesarean section compared to Foley catheter without increased risk of uterine hyperstimulation with fetal heart rate changes, which was shown in oral or vaginal misoprostol.
Topics: Administration, Intravaginal; Bayes Theorem; Cervical Ripening; Cesarean Section; Female; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Network Meta-Analysis; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic; Urinary Catheters
PubMed: 36068489
DOI: 10.1186/s12884-022-04988-2 -
BioMed Research International 2022To compare the maternal and neonatal outcomes of pregnant women who had labor induction with intravaginal misoprostol or had spontaneous labor in our clinic. . The...
PURPOSE
To compare the maternal and neonatal outcomes of pregnant women who had labor induction with intravaginal misoprostol or had spontaneous labor in our clinic. . The records of 213 pregnant women, who were followed up in Acibadem Maslak University Hospital for vaginal delivery between June 2021 and December 2021, were retrospectively evaluated. The pregnant women, who gave birth, were divided into 3 groups as follows: spontaneous labor (SL), those induced by a single dose of misoprostol (SDM), and those induced by multiple doses of misoprostol (MDM). The groups were compared in terms of delivery type, the vaginal birth rate within 12 hours, need for intervention, duration of the second stage of labor, cesarean section ratio due to fetal distress, time from the last dose to delivery, and 1st and 5th minute APGAR scores.
RESULTS
Among the primiparous pregnant women, 84.7% of SL group, 65.2% of SDM group, and 37% MDM group delivered vaginally within 12 hours ( < 0.05). The time from the last misoprostol dose to delivery was also statistically significantly shorter in pregnant women, who received a single dose of misoprostol (483 vs. 720 min, respectively). When the hospitalization time was evaluated, in the SDM group, the MDM group, and the SL group, it was found to be 611, 831, and 379 min, respectively. In multiparous pregnant women, the hospitalization time was 735 min in the SDM group, 494 min in the MDM group, and 261.5 min in the SL group ( < 0.05). Other than the hospitalization time, when the aforementioned variables were studied in multiparous pregnant women, no statistically significant difference among groups was observed ( > 0.05).
CONCLUSION
Intravaginal misoprostol seems to be a promising medical agent for labor induction due to its high delivery rates within 12 hours and the absence of negative fetal outcomes, its ease of storage, and affordable cost.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Misoprostol; Oxytocics; Cesarean Section; Retrospective Studies; Pregnancy Outcome; Administration, Intravaginal; Labor, Induced
PubMed: 36531654
DOI: 10.1155/2022/2826927 -
Obstetrics and Gynecology Jul 2019To evaluate whether cervical ripening with oral misoprostol increases cesarean delivery risk and prolongs time to vaginal delivery compared with vaginal misoprostol in a... (Comparative Study)
Comparative Study
OBJECTIVE
To evaluate whether cervical ripening with oral misoprostol increases cesarean delivery risk and prolongs time to vaginal delivery compared with vaginal misoprostol in a predominantly overweight population.
METHODS
This single center, retrospective cohort study was performed at a tertiary care academic medical center and compared labor induction outcomes with vaginal misoprostol to outcomes with oral misoprostol after a complete institutional shift to oral misoprostol. Labor induction using 25 micrograms vaginal misoprostol in 2013-2014 was compared with 50 micrograms oral misoprostol in 2014-2015. The primary outcome was cesarean delivery. Secondary outcomes included time to vaginal delivery, uterine tachysystole, maternal hemorrhage, and composite adverse neonatal outcomes. Demographics and outcomes were analyzed using standard statistical tests. Multivariable regression models accounting for potential confounders were created for the primary and secondary outcomes with adjusted odds ratios (aOR) as the measures of effect.
RESULTS
There were 138 women in the oral and 138 women in the vaginal misoprostol groups. In the overall cohort, the median (interquartile range) body mass index was 31.7 (28.2-36.8) and most women (72%) were of either black or Hispanic race or ethnicity. The frequency of cesarean delivery was higher in the oral than the vaginal misoprostol group (32% vs 21%; P=.04). The adjusted odds of cesarean was higher with oral misoprostol (aOR 2.01; 95% CI 1.07-3.76). Among nulliparous women, the frequency of cesarean delivery was 41% in the oral and 28% in the vaginal misoprostol groups (aOR 2.79; 95% CI 1.26-6.19). Women had a longer time to vaginal delivery in the oral compared with vaginal misoprostol group (41 vs 31 hours respectively, P=.01). Tachysystole occurred more frequently with vaginal misoprostol (20% vs 11%; P=.04).
CONCLUSION
Compared with vaginal misoprostol, oral misoprostol may be associated with increased risk of cesarean delivery and longer time to vaginal delivery.
Topics: Administration, Intravaginal; Administration, Oral; Adult; Cesarean Section; Cohort Studies; Delivery, Obstetric; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 31188317
DOI: 10.1097/AOG.0000000000003274 -
Nigerian Journal of Clinical Practice Apr 2023Despite using a tourniquet to reduce bleeding during abdominal myomectomy, the procedure is still complicated by significant intraoperative bleeding. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Despite using a tourniquet to reduce bleeding during abdominal myomectomy, the procedure is still complicated by significant intraoperative bleeding.
AIM
To determine whether misoprostol and tourniquet compared with tourniquet alone would significantly reduce bleeding during abdominal myomectomy at two tertiary hospitals in Enugu.
MATERIALS AND METHODS
This study is an open-label randomized controlled trial. A total of 126 consenting participants were recruited from women booked for abdominal myomectomy at the study centers over 7 months. They were randomized into groups A (vaginal misoprostol 400 μg) and B (no misoprostol) one hour before surgery. Intraoperatively, all participants had a tourniquet application. Intraoperative and postoperative blood loss was compared between the two groups. Descriptive and inferential analyses were carried out using IBM SPSS Version 22.0. A P- value of < 0.05 was considered statistically significant.
RESULTS
An intention-to-treat analysis was carried out. All 63 participants (100%) and 56 (90%) completed the study according to the protocol in groups A and B, respectively. Socio-demographic characteristics were not significantly different in both groups. The mean intraoperative blood loss in the "misoprostol group" (522.6 ± 127.91 ml) was significantly lower than in the "no-misoprostol group" (583.5 ± 186.20 ml), with P = 0.028. The difference in mean hemoglobin (g/dl) was lower in the "misoprostol group" than in the "no-misoprostol group" (1.3 ± 0.79 vs. 1.9 ± 0.89, P < 0.001). The mean 48 hours postoperative blood loss (ml) between the two groups was 323.8 ± 221.44 vs. 549.4 ± 519.72), with P = 0.001.
CONCLUSION
Among women receiving tourniquet during myomectomy in Enugu, the additional use of vaginal misoprostol 400 μg significantly reduced intraoperative blood loss.
Topics: Female; Humans; Uterine Myomectomy; Misoprostol; Blood Loss, Surgical; Leiomyoma; Nigeria; Postoperative Hemorrhage
PubMed: 37203110
DOI: 10.4103/njcp.njcp_526_22 -
Nursing Open Sep 2021To develop and validate the nomogram for risk estimation of Caesarean delivery and to compare the effect of cervical ripening balloon, evening primrose oil (EPO) and...
Developing and validating the Caesarean risk assessment nomogram and comparing the effect of cervical ripening balloon, evening primrose oil and misoprostol on childbirth outcomes in term pregnancies: A study protocol.
AIM
To develop and validate the nomogram for risk estimation of Caesarean delivery and to compare the effect of cervical ripening balloon, evening primrose oil (EPO) and misoprostol on Bishop Score and duration of the first stage of labour.
DESIGN
The first phase is a prospective study, and the second phase is a randomized controlled trial.
METHODS
In the first phase, the nomogram will be developed and validated over 300 participants, and in the second phase, the 90 participants will be allocated to three groups: vaginal 25mcg misoprostol, vaginal 4000mg EPO and double-balloon catheter, through block randomization method. The Bishop score will be evaluated every 4 hr, and if required the same dose will be repeated. Maximum waiting time for balloon is 12 hr if not effective, the catheter will be removed, and other interventions will be done according to guidelines.
DISCUSSION
The nomogram will help informed decision-making for women undergoing an induction with an unfavourable cervix and introducing effective low-complication methods of labour induction can improve the pregnancy outcomes.
Topics: Cervical Ripening; Cesarean Section; Female; Humans; Labor, Induced; Linoleic Acids; Misoprostol; Nomograms; Oenothera biennis; Oxytocics; Plant Oils; Pregnancy; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; gamma-Linolenic Acid
PubMed: 33689238
DOI: 10.1002/nop2.846 -
The Lancet. Global Health Oct 2022To address the knowledge gaps in the provision of post-abortion care by midwives for women in the second trimester, we investigated the effectiveness and safety of... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the effectiveness and safety of treatment of incomplete second trimester abortion with misoprostol provided by midwives and physicians: a randomised, controlled, equivalence trial in Uganda.
BACKGROUND
To address the knowledge gaps in the provision of post-abortion care by midwives for women in the second trimester, we investigated the effectiveness and safety of treatment for incomplete second trimester abortion with misoprostol, comparing care provision by midwives with that provided by physicians in Uganda.
METHODS
Our multicentre, randomised, controlled, equivalence trial undertaken in 14 health facilities in Uganda recruited women with incomplete abortion of uterine size 13-18 weeks. We randomly assigned (1:1) women to clinical assessment and treatment by either midwife or physician. The randomisation sequence was computer generated, in blocks of four to 12, and stratified for study site. Participants received sublingual misoprostol (400 μg once every 3 h for up to five doses). The study was not concealed from the health-care providers and study participants. Primary outcome was complete abortion within 24 h that did not require surgical evacuation. Analysis was per-protocol and intention to treat; the intention-to-treat population consisted of women who were randomised, received at least one dose of misoprostol, and reported primary outcome data, and the per-protocol population excluded women with unexplained discontinuation of treatment. We used generalised mixed-effects models to obtain the risk difference. The predefined equivalence range was -5% to 5%. The trial was registered at ClinicalTrials.gov, NCT03622073.
FINDINGS
Between Aug 14, 2018, and Nov 16, 2021, 1191 eligible women were randomly assigned to each group (593 women to the midwife group and 598 to the physician group). 1164 women were included in the per-protocol analysis, and 530 (92%) of 577 women in the midwife group and 553 (94%) of 587 women in the physician group had a complete abortion within 24 h. The model-based risk difference for the midwife versus physician group was -2·3% (95% CI -4·4 to -0·3), and within our predefined equivalence range (-5% to 5%). Two women in the midwife group received blood transfusion.
INTERPRETATION
Clinical assessment and treatment of second trimester incomplete abortion with misoprostol provided by midwives was equally effective and safe as when provided by physicians. In low-income settings, inclusion of midwives in the medical management of uncomplicated second trimester incomplete abortion has potential to increase women's access to safe post-abortion care.
FUNDING
Swedish Research Council and THRiVE-2.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Incomplete; Abortion, Induced; Female; Humans; Midwifery; Misoprostol; Physicians; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Uganda
PubMed: 36030801
DOI: 10.1016/S2214-109X(22)00312-6 -
Acta Obstetricia Et Gynecologica... Apr 2021The safety and acceptability of medical abortion using mifepristone and misoprostol at home at ≤9 weeks' gestation is well established. However, the upper... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The safety and acceptability of medical abortion using mifepristone and misoprostol at home at ≤9 weeks' gestation is well established. However, the upper gestational limit at which the procedure remains safe and acceptable at home is not known. To inform a national guideline on abortion care we conducted a systematic review to determine what gestational limit for expulsion at home offers the best balance of benefits and harms for women who are having medical abortion.
MATERIAL AND METHODS
We searched Embase, MEDLINE, Cochrane Library, Cinahl Plus and Web-of-Science on 2 January 2020 for prospective and retrospective cohort studies with ≥50 women per gestational age group, published in English from 1995 onwards, that included women undergoing medical abortion and compared home expulsion of pregnancies of ≤9 weeks' gestational age with pregnancies of 9 -10 weeks or >10 weeks' gestational age, or compared the latter two gestational age groups. We assessed risk-of-bias using the Newcastle-Ottowa scale. All outcomes were meta-analyzed as risk ratios (RR) using the Mantel-Haenszel method. The certainty of the evidence was assessed using GRADE.
RESULTS
Six studies (n = 3381) were included. The "need for emergency care/admission to hospital" (RR = 0.79, 95% confidence interval [CI] 0.45-1.4), "hemorrhage requiring transfusion/≥500 mL blood loss" (RR = 0.62, 95% CI 0.11-3.55), patient satisfaction (RR = 0.99, 95% CI 0.95-1.03), pain (RR = 0.91, 95% CI 0.82-1.02), and "complete abortion without the need for surgical intervention" (RR = 1.03, 95% CI 1-1.05) did not differ statistically significantly between the ≤9 and >9 weeks' gestation groups. The rates of vomiting (RR = 0.8, 95% CI 0.69-0.93) and diarrhea (RR = 0.85, 95% CI 0.73-0.99) were statistically significantly lower in the ≤9 weeks group but these differences were not considered clinically important. We found no studies comparing pregnancies of 9 -10 weeks' gestation with pregnancies of >10 weeks' gestation. The certainty of this evidence was predominantly low and mainly compromised by low event rates and loss to follow up.
CONCLUSIONS
Women who are having a medical abortion and will be taking mifepristone up to and including 10 weeks' gestation should be offered the option of expulsion at home after they have taken the misoprostol. Further research needs to determine whether the gestational limit for home expulsion can be extended beyond 10 weeks.
Topics: Abortifacient Agents; Abortion, Induced; Female; Gestational Age; Home Care Services; Humans; Mifepristone; Misoprostol; Pregnancy
PubMed: 33063314
DOI: 10.1111/aogs.14025 -
The Cochrane Database of Systematic... Jun 2015Induction of labour is the artificial initiation of labour in a pregnant woman after the age of fetal viability but without any objective evidence of active phase labour... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Induction of labour is the artificial initiation of labour in a pregnant woman after the age of fetal viability but without any objective evidence of active phase labour and with intact fetal membranes. The need for induction of labour may arise due to a problem in the mother, her fetus or both, and the procedure may be carried out at or before term. Obstetricians have long known that for this to be successful, it is important that the uterine cervix (the neck of the womb) has favourable characteristics in terms of readiness to go into the labour state.
OBJECTIVES
To compare Bishop score with any other method for assessing pre-induction cervical ripening in women admitted for induction of labour.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies to identify randomised controlled trials (RCTs).
SELECTION CRITERIA
All RCTs comparing Bishop score with any other methods of pre-induction cervical assessment in women admitted for induction of labour. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and studies using a cross-over design were not eligible for inclusion. Studies published in abstract form were eligible for inclusion if they provided sufficient information.Comparisons could include the following.1. Bishop score versus transvaginal ultrasound (TVUS).2. Bishop score versus Insulin-like growth factor binding protein-1 (IGFBP-1).3. Bishop score versus vaginal fetal fibronectin (fFN).However, we only identified data for a comparison of Bishop score versus TVUS.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the trials for inclusion, extracted the data and assessed trial quality. Data were checked for accuracy.
MAIN RESULTS
We included two trials that recruited a total of 234 women. The overall risk of bias was low for the two studies. Both studies compared Bishop score withTVUS.The two included studies did not show any clear difference between the Bishop score and TVUS groups for the following main outcomes: vaginal birth (RR 1.07, 95% CI 0.92 to 1.25, moderate quality evidence), caesarean delivery (RR 0.81, 95% CI 0.49 to 1.34, moderate quality evidence), neonatal admission into neonatal intensive care unit (RR 1.67, 95% CI 0.41 to 6.71, moderate quality evidence). Both studies only provided median data in relation to induction-delivery interval and reported no clear difference between the Bishop and TVUS groups. Perinatal mortality was not reported in the included studies.For the review's secondary outcomes, the need for misoprostol for cervical ripening was more frequent in the TVUS group compared to the Bishop score group (RR 0.52, 95% CI 0.41 to 0.66, two studies, 234 women, moderate quality evidence). In contrast, there were no clear differences between the Bishop scope and TVUS groups in terms of meconium staining of the amniotic fluid, fetal heart rate abnormality in labour, and Apgar score less than seven. Only one trial reported median data on the induction-delivery interval and induction to active phase interval, the trialist reported no difference between the Bishop group and the TVUS group for this outcome. Neither of the included studies reported on uterine rupture.
AUTHORS' CONCLUSIONS
Moderate quality evidence from two small RCTs involving 234 women that compared two different methods for assessing pre-induction cervical ripening (Bishop score and TVUS) did not demonstrate superiority of one method over the other in terms of the main outcomes assessed in this review. We did not identify any data relating to perinatal mortality. Whilst use of TVUS was associated with an increased need for misoprostol for cervical ripening, both methods could be complementary.The choice of a particular method of assessing pre-induction cervical ripening may differ depending on the environment and need where one is practicing since some methods (i.e. TVUS) may not be readily available and affordable in resource-poor settings where the sequelae of labour and its management is prevalent.The evidence in this review is based on two studies that enrolled a small number of women and there is insufficient evidence to support the use of TVUS over the standard digital vaginal assessment in pre-induction cervical ripening. Further adequately powered RCTs involving TVUS and the Bishop score and including other methods of pre-induction cervical ripening assessment are warranted. Such studies need to address uterine rupture, perinatal mortality, optimal cut-off value of the cervical length and Bishop score to classify women as having favourable or unfavourable cervices and cost should be included as an outcome.
Topics: Cervical Ripening; Cervix Uteri; Cesarean Section; Delivery, Obstetric; Female; Hospitalization; Humans; Intensive Care Units, Neonatal; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic; Ultrasonography
PubMed: 26068943
DOI: 10.1002/14651858.CD010762.pub2 -
BioMed Research International 2022The aim of this study was to compare maternal and neonatal outcomes between sublingual misoprostol and oxytocin on stimulating labor in term premature rupture of... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
The aim of this study was to compare maternal and neonatal outcomes between sublingual misoprostol and oxytocin on stimulating labor in term premature rupture of membranes (PROM) in pregnant women. . This randomized single-blind control trial was conducted at Bhumibol Adulyadej Hospital (BAH), Royal Thai Air Force, Bangkok, Thailand, between September 2020 and February 2021. Subjects were term pregnant women who had PROM and came to BAH for delivery. Participants were allocated into study (misoprostol) and control (oxytocin) groups. The study and control groups were, respectively, administered sublingual misoprostol and intravenous oxytocin to induce labor. Induction time and second stage of labor were recorded. Neonatal outcomes and maternal and fetal complications were also recorded and analyzed.
RESULT
A total of 170 women were enrolled and equally divided into study and control groups. Mean maternal age, body mass index, parity, gestational age, and bishop score of both groups were comparable. Induction time of the study group was statistically shorter than the control group (338 and 399 min, respectively). Duration of active phase (450/427 min) and the second stage (19/21 min) of labor between study and control groups were not significantly different. Cesarean section delivery rate of study was lower than the control group (13.3 and 28.8%, = 0.002). Intrapartum complications, neonatal outcomes, and intra- and postpartum complications among both groups were not significantly differentiated. There was no instance of postpartum hemorrhage or uterine rupture in the present study.
CONCLUSION
Induction time and cesarean section rates of sublingual misoprostol group were significantly lower than the intravenous oxytocin group in full-term PROM pregnancy.
Topics: Administration, Intravenous; Administration, Sublingual; Adult; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Pregnancy; Pregnancy Outcome; Single-Blind Method; Thailand
PubMed: 35198639
DOI: 10.1155/2022/9449036 -
Cureus Sep 2023Introduction Induction of labor implies stimulation of contractions before the spontaneous onset of labor, with or without membranes. Augmentation refers to the...
Introduction Induction of labor implies stimulation of contractions before the spontaneous onset of labor, with or without membranes. Augmentation refers to the enhancement of spontaneous contractions that are considered inadequate because of failed cervical and fetal descent. This study compared the effectiveness of intracervical Foley catheter insertion and vaginal misoprostol versus only vaginal misoprostol in the induction of labor and other outcomes relted to it. Methods The present study was a randomized controlled trial that included 148 women divided into two groups: (i) Group A, which received intracervical Foley catheter insertion and vaginal misoprostol (25 µg), and (ii) Group B, which received intravaginal administration of tablet misoprostol (25 µg) alone. We compared the median time from the time of induction to vaginal delivery, incidence of cesarean delivery, chorioamnionitis, puerperal infection, uterine tachysystole, neonatal information at delivery, and discharge status (i.e., birth weight, neonatal intensive care unit (NICU) admission, and neonatal death) between groups. Results We found that the rates of puerperal infection (n=36; 48.6%) and meconium-stained amniotic fluid (n=45; 60.8%) were higher in Group B than in Group A (n=20; 27.0% and n=25; 33.8%, respectively), which were statistically significant differences (p=0.0066 and p=0.0009, respectively). In addition, NICU admission was higher in Group B (n=47; 63.5%) than in Group A (n=30; 40.5%), which was a statistically significant difference (p=0.0051). Conclusion An intracervical Foley catheter with 25 µg of misoprostol was more effective for induction of labor than 25 µg of intravaginal misoprostol alone every six hours for a maximum of four doses in terms of induction to delivery interval, meconium-stained amniotic fluid, mode of delivery, intrapartum complications, and puerperal infection.
PubMed: 37809166
DOI: 10.7759/cureus.44772