Comparison of the effect of simultaneous administration of magnesium sulfate and indomethacin with the administration of magnesium sulfate alone in inhibiting premature birth.

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Masoumeh Dadashaliha, Shiva Hoorshad, Somayeh Fallah This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5226675/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Premature birth is one of the most significant complications observed in pregnancies, which can lead to consequences such as preterm birth and its associated complications. The aim of this research is to compare the effectiveness of tocolytics with magnesium sulphate alone and the combination of magnesium sulphate and indomethacin in preventing premature birth at Kowsar Hospital in 2019-2020. Materials and Methods : This clinical trial was conducted on 200 pregnant women with gestational age of 24 to 32 weeks referred to Kowsar Hospital in Qazvin; Iran. Patients were divided into two equal groups, receiving treatment with magnesium sulphate and indomethacin (Group A) and magnesium sulphate alone (Group B). Then, the data were analysed using SPSS statistical software and appropriate statistical tests. Results: According to the research findings, the mean time interval from drug administration to delivery in Group A was 505.91 ± 774.71 hours, and in Group B, it was 545.77 ± 503.32 hours, with this difference being statistically significant (p 0.05). On the other hand, the type of intervention had a significant relationship with the number of deliveries within 7 days after starting drug administration (p < 0.05). Conclusion: The results indicate a greater impact of tocolytics with the combination of magnesium sulphate and indomethacin compared to magnesium sulphate alone in preventing premature birth and delaying it. There were similarities in our study findings compared to other studies. Trial registration: This clinical study was approved by the Iranian Registry of Clinical Trials ( http://www.irct.ir ) with the with the IRCT ID: IRCT20190819044568N1, Registration date was 2020-05-08 . Premature birth magnesium sulphate Iindomethacin Figures Figure 1 Figure 2 Figure 3 Introduction Preterm birth, or preterm Labour, is used to describe babies born much earlier than expected. Preterm birth is divided into two subgroups: births before 33 weeks and 6 days are considered early preterm, while births between 34 and 36 weeks are termed late preterm, constituting over 70% of all preterm births. Deliveries occurring between weeks 37 to 38 and 6 days are considered early term, and those between weeks 39 to 40 and 6 days are considered full term, encompassing a range of fetal maturity that completes later in pregnancy than previously thought ( 1 ) Overall, the incidence of preterm birth has gradually increased from 9.57% in 2014 to 9.36% in 2015. Various factors contribute to premature birth, often with multiple interacting characteristics and environmental influences. Causes may include unjustifiable preterm Labor, premature rupture of membranes, obstetric and maternal conditions, and multiple pregnancies. Spontaneous preterm Labor alone accounts for approximately 40–45% of preterm births( 2 ) The undesirable consequences of infant immaturity in cases where birth occurs before 39 completed weeks of gestation are significant and notable. The survival of infants born preterm before 32 weeks’ gestation depends on two factors: birth weight and gestational age, with survival rates reaching up to 95% after reaching a weight of 1000 grams and achieving a gestational age of 28 weeks in female fetuses or 30 weeks in male fetuses. Preterm birth is the most common cause of infant mortality, accounting for 75% of neonatal deaths. Preterm birth affects various fetal organs, including the brain, leading to complications such as hypoxic-ischemic encephalopathy (HIE), intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), weak cerebral growth, hydrocephalus, cerebral palsy, and decreased neurological function including impaired hearing. Among pulmonary complications, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and gastrointestinal complications such as hyperbilirubinemia, feeding intolerance, and necrotizing enter colitis (NEC) are notable. Multiple immunological complications can arise, including hospital-acquired infections (HAP), and haematological and endocrinological complications such as hypoglycaemia, insulin resistance, and cortisol deficiency are also common. Additionally, ophthalmological complications such as retinopathy of prematurity (ROP), nocturnal enuresis, and cardiovascular complications such as hypertension (HTN), pulmonary hypertension (PHTN), patent ductus arteriosus (PDA), as well as various renal, haematological, and endocrinological complications including hypoglycaemia, insulin resistance, and cortisol deficiency, can occur ( 3 ) Among the risk factors for preterm birth, maternal age or being too young, poverty and malnutrition, tobacco and drug use, genetic factors, periodontal diseases, and infections are mentioned. There are various therapeutic methods for preventing preterm birth, including the use of different types of progesterone formulations, either systemic or vaginal, or surgical interventions like cerclage, all aimed at delaying preterm labour and reducing neonatal complications. Nowadays, despite concerns about maternal hydration, tocolytics, along with bed rest and the use of tranquilizers, have found wide application in preventing preterm birth and are considered the mainstay of treatment ( 4 ). Medications used for Tocolysis, which aim to inhibit uterine contractions, have their most significant effect in delaying labour for at least 48 hours to administer steroids to the mother for accelerating fetal lung maturity and transferring the mother to a facility equipped with a neonatal intensive care unit (NICU). Examples of Tocolytic drugs used in the treatment of preterm labour include beta-adrenergic agonists such as Ritodrine, magnesium sulphate, prostaglandin inhibitors like indomethacin, nitric oxide donors such as nitro-glycerine, calcium channel blockers like Nifedipine, and oxytocin Analogs such as Atosiban. However, determining the most effective treatment in this area requires conducting comprehensive comparative studies through clinical trials. In this regard, the effectiveness of magnesium sulphate in Tocolysis has been clearly demonstrated ( 5 – 7 ). Hormonal interventions like oral or injectable progesterone and the use of vasodilator drugs such as Nifedipine are commonly used methods ( 8 , 9 ). However, determining the most effective treatment in this area requires conducting comprehensive comparative studies through clinical trials. In the past, the efficacy in reducing fetal mortality in preterm labour was our concern; however, nowadays with the identification of these pregnancies and appropriate care for both the mother and fetus, fetal mortality in these pregnancies has been reduced. Nevertheless, cases that arise still require further investigation and attention ( 10 , 11 ). The birth of a premature infant poses significant economic and psychosocial burdens on the family, leading to the loss of emotional and financial investments and resources ( 12 ). Premature infants are among the vulnerable groups in society and experience considerable physical, emotional, and psychological challenges compared to full-term infants, requiring proper care to sustain life and achieve normal growth and development ( 13 ). Among these, hospitalization in the neonatal intensive care unit (NICU) for several days to months (depending on the level of prematurity or infant's condition) ( 14 ) is common. Since hospitalization is often a stressful and overwhelming experience for both the infant and the parents, particular attention has been given to it in recent years( 15 , 16 ). With the understanding that reducing infant mortality signifies an improvement in public health, measures to reduce preterm births have gained special significance( 17 , 18 ). Bed rest, hydration, tocolytic medications to reduce uterine activity, and corticosteroids for fetal lung maturation and prevention of neonatal respiratory distress syndrome, as well as interventions to prevent infections such as Group B Streptococcus and neonatal sepsis, are among the important actions taken in the care of pregnant women at risk of preterm birth ( 19 , 20 ). Nowadays, magnesium sulphate therapy has been well established for many years. The medication magnesium sulphate, known in English as sulphate magnesium and chemically represented as MgSO4, is a therapeutic agent with various clinical applications, including prevention of seizures in preeclampsia, preterm Labor, and as an adjunct in the treatment of cardiac arrhythmias. Its parenteral and oral forms are used in the treatment of hypomagnesemia, and intravenously as a bronchodilator and smooth muscle relaxant. Its cellular mechanism of action is attributed to the inhibition of acetylcholine release at the neuromuscular junction, consequently inhibiting calcium influx into cells due to intracellular magnesium displacement. Its anticonvulsant effect is through the blockade of neuronal calcium channels via glutamate channels (these channels are only present in the CNS), producing an anticonvulsant effect on the maternal cortex without causing CNS depression in the mother and fetus. Some of the side effects of this drug include: Loss of deep tendon reflexes, respiratory depression, nausea and vomiting, sweating, tingling sensation, hypotension, drowsiness, and dizziness, muscular weakness, bradycardia, and even coma. In case of overdose with this drug, initially the patellar reflexes disappear, and at higher concentrations, respiratory depression, respiratory paralysis, and ultimately cardiac arrest occur. Its treatment involves intravenous calcium gluconate along with discontinuation of magnesium sulphate( 21 ) . However, the use of NSAIDs alongside it and the role of this issue in enhancing the effectiveness of tocolytic therapy warrants further investigation. Indomethacin, known in English as Indomethacin, belongs to the category of nonsteroidal anti-inflammatory drugs (NSAIDs) and is available in tablet, capsule, and suppository forms. Indomethacin is a potent analgesic and anti-inflammatory drug, used as a medication to inhibit uterine contractions. Indomethacin primarily inhibits the enzyme cyclooxygenase, thereby preventing the conversion of arachidonic acid to prostaglandins. Prostaglandins play a crucial role in labour induction and preterm labour. Indomethacin's tocolytic effects are achieved by inhibiting cyclooxygenase, suppressing prostaglandin synthesis, and consequently reducing uterine contractions. Cyclooxygenase inhibitors are divided into two subgroups: non-selective COX-1 and COX-2 inhibitors, and selective COX-2 inhibitors. COX-1 is found in human decidua, myometrium, and fetal membranes, while COX-2 expression in the uterus plays a role in preterm labour and preterm birth, with no significant effects on the decidua and myometrium. Indomethacin is a non-selective COX-2 inhibitor. This drug is available in the market in the form of 25 mg capsules, 75 mg slow-release tablets, and 50 and 100 mg suppositories. Its suppository form is used as a tocolytic. Among its side effects are gastrointestinal ulcers, nausea and diarrhoea, severe morning headaches, drowsiness, vertigo, visual disturbances, and ringing in the ears( 22 ). However, despite extensive studies, indomethacin alone has not been established as the primary drug for tocolysis, and the choice of medication depends on factors such as drug availability, efficacy, maternal and neonatal side effects, and cost. This study compares the effects of magnesium sulphate alone versus magnesium sulphate and indomethacin in inhibiting preterm labour. The management of preterm labour remains a crucial focus in obstetrics due to its significant impact on neonatal outcomes. Various tocolytic agents have been explored to delay delivery and improve outcomes, with magnesium sulphate and indomethacin being among the most commonly used. Studies have provided differing perspectives on the effectiveness of these treatments, influenced by factors such as dosage, administration route, and concurrent therapies. Jayaram et al. (2018) highlighted the neuroprotective and tocolytic benefits of magnesium sulphate in preterm labour. However, variability in recommendations arises due to contextual factors such as maternal age and dosage ( 23 ). In contrast, Crowther et al. (2014) found no significant difference in delivery timing between magnesium sulphate and a control group, despite administering a regimen of 4 grams initially followed by 2 grams per hour for 48 hours ( 24 ). Klauser et al. (2014) conducted a randomized controlled trial; pregnancy between 24–32 weeks of gestation; comparing Nifedipine, magnesium sulphate, and indomethacin in preterm labour cases. The study revealed similar gestational age at delivery and labour cessation among the groups, though Nifedipine was linked with higher incidences of hypotension and tachycardia, while indomethacin was associated with more uterine contractions and oligohydramnios. Overall, no major differences in efficacy or safety were noted among the tocolytics ( 25 ). Abbassalizadeh et al. (2014) compared indomethacin and magnesium sulphate in women with singleton pregnancies between 28 to 32 weeks of gestation. The duration from onset of pain to delivery was similar between the two groups, suggesting no significant difference in efficacy ( 26 ). Nia et al. (2012) further confirmed this finding, showing no significant differences in delivery timing or maternal adverse effects between magnesium sulphate and indomethacin ( 27 ). Taj et al. (2012) found indomethacin more effective than magnesium sulphate in delaying Labor, with 76.9% of magnesium sulphate recipients delivering within 72 hours compared to 37% in the indomethacin group( 28 ). Conversely, Barana and Saeidi (2007) found no significant difference between Nifedipine and magnesium sulphate in delaying delivery beyond 48 hours ( 29 ). Lastly, Vermillion et al. (2000) and Lewis et al. (1995) explored combined therapies. Vermillion found no significant difference between indomethacin and control groups, while Lewis demonstrated that combining magnesium sulphate with indomethacin extended tocolysis duration significantly compared to magnesium sulphate alone ( 30 , 31 ). These findings underscore the complexity of choosing an optimal tocolytic regimen, highlighting the need for individualized treatment approaches based on specific clinical circumstances. Methods In this study, an intervention conducted in the form of a randomized double-blind clinical trial involved 200 women with symptoms of preterm labour who presented to Kowsar Hospital in Qazvin during the years 2022 and 2023. Eligible participants were selected and evaluated, and their data were collected and entered into the study. Inclusion criteria: Singleton pregnancies Gestational age between 24 and 32 weeks, having at least 4 uterine contractions in 20 minutes or 8 contractions in 1 hour causing changes in dilatation and effacement of the cervix, Cervical dilatation more than 2 and less than 4 centimetres, Cervical effacement more than 80%. Exclusion criteria: Multiple pregnancies, Recognized maternal medical conditions (such as cardiac, pulmonary, renal, rheumatologic diseases, kidney failure, history of gastrointestinal ulcers, etc.), Premature rupture of membranes, Vaginal bleeding, Cervical dilatation of 4 centimetres or more Intrauterine fetal demise (IUFD), Intrauterine growth restriction (IUGR), Hypersensitivity to indomethacin. Among the 200 pregnant women referred to Kowsar Hospital with singleton pregnancies, aged between 24 and 32 weeks, experiencing preterm labour contractions with cervical dilatation less than 4 centimetres, without vaginal bleeding, premature rupture of membranes, or history of kidney and gastrointestinal diseases, those who agreed to participate in the study were selected. Their demographic characteristics including sonography, gravidity, BMI, maternal age, and history of previous preterm labour were recorded. Considering the protocol of preterm labour management in Kowsar Hospital, all participants received the following protocol: slow intravenous loading dose of 4 grams of magnesium sulphate followed by 2 grams per hour for a maximum of 48 hours or 12 hours after cessation of contractions. 200 bags labelled as A and B were prepared, where A represented indomethacin and B represented placebo suppositories, stored in the labour room refrigerator, and administered randomly according to allocation using computerized randomization. The individuals were divided into the following two groups: Group 1: Pregnant women with preterm Labor pains received intravenous magnesium sulphate along with indomethacin suppositories 100 milligrams rectally every 12 hours for up to 12 hours after cessation of uterine contractions (contractions were monitored every 2 hours for 20 minutes by cardiotocography) or for a maximum of 48 hours. Group 2: Pregnant women with preterm Labor pains received intravenous magnesium sulphate along withl placebo suppositories rectally every 12 hours for up to 12 hours after cessation of uterine contractions (contractions were monitored every 2 hours for 20 minutes by cardiotocography) or for a maximum of 48 hours. During the medication administration period, patients were monitored for vital signs, blood pressure, headache, nausea, vomiting, shortness of breath, dizziness, and drowsiness. Signs of magnesium sulphate toxicity were also evaluated through urine output volume, deep tendon reflexes (DTR), and respiratory rate. Fetal heart rate was regularly monitored using cardiotocography, and uterine contractions were recorded every 2 hours for 20 minutes by this device. Data including gestational age, time interval between drug administration and delivery, history of preterm Labor, neonatal Apgar score, and if the neonate was admitted to the NICU, as well as drug side effects, were recorded on the questionnaire form. The primary outcome was the time interval after receiving uterine contraction-inhibiting drugs to delivery (in hours), and the secondary outcome was neonatal Apgar score at 1st and 5th minutes, neonatal weight, and whether they were admitted to the NICU. The study was double-blinded, meaning both the researcher and the patient were unaware of the type of suppository. Only the Labor room midwife, who recorded it for the patient, knew its nature, and at the end of the study period, she reported the cases to the researcher. Data analysis will be performed using the statistical software SPSS version 25, and descriptive statistics such as mean and standard deviation for quantitative variables, and frequency and percentage for qualitative variables, will be reported. The significance level for interpreting the results is considered as 0.05. A comparison between the two groups' primary outcomes will be conducted using independent samples t-test (or Mann-Whitney U test if assumptions are violated), and the frequency of outcomes between the two groups will be compared using the chi-square test (or Fisher's exact test if assumptions are violated). Additionally, side effects of drugs on mothers and fetuses between the two groups will be compared using the chi-square test (or Fisher's exact test if assumptions are violated). Results Determination and Comparison of Demographic Characteristics of Study Participants Table 1 displays the demographic characteristics including age, gravity, and BMI of the attendees. Characteristics MgSO4 Group Mean ± SD Indomethacin Group Mean ± SD P-value Maternal Age 26.71 ± 5.79 27.53 ± 5.05 0.245 Maternal BMI 27.95 ± 3.82 26.88 ± 3.13 0.031 Gravidity 1.84 ± 0.92 1.85 ± 0.92 0.867 Age at Pregnancy Upon Admissionn 31.61 ± 1.84 30.75 ± 2.23 0.007 History of Preterm Delivery 8 (8%) 14 (14%) 0.129 Upon observation of Table 1 , it was noted that there was no statistically significant difference between the two groups regarding baseline characteristics such as maternal age, Gravidity, and history of preterm delivery. However, the two groups significantly differed in terms of BMI and age at pregnancy upon admission, where individuals in the MgSO4 recipient group alone exhibited higher BMI and older age at pregnancy upon admission compared to the group receiving MgSO4 and indomethacin. Specifically, for BMI upon admission during pregnancy, the age was statistically significant at P = 0.031, with 26.88 ± 3.13 compared to 27.95 ± 3.82 and for gestational age at admission, it was (31.61 ± 1.84 compared to 30.75 ± 2.23, P = 0.007) Determining and Comparing the Time Interval from Drug Administration to Delivery in 2 Groups as Primary Outcome Comparison of Mean Time Interval from Drug Administration to Delivery in Two Groups in Hours Based on the findings, the mean time interval from drug administration to delivery in Group A (MgSO4 + Indomethacin) was 774.18 ± 505.91 hours, equivalent to 32.28 days, whereas in Group B (MgSO4), it was 545.78 ± 503.32 hours, equivalent to 22.74 days. The Mann-Whitney U test revealed a statistically significant relationship between the type of intervention and the time interval from drug administration to delivery, with a p-value of 0.001. (Fig. 1 ) According to the above figure, 15% of individuals in the MgSO4 recipient group delivered compared to 8% of individuals in the MgSO4 and Indomethacin recipient group within 48 hours after the initiation of medication. Based on the results obtained from the Chi-square test, this difference was not statistically significant (P = 0.174).(Fig. 2 ) According to the above figure, 31% of individuals in the MgSO4 recipient group delivered spontaneously compared to 15% of individuals in the MgSO4 and Indomethacin recipient group within 7 days after receiving tocolytic medication. Based on the results obtained from the Chi-Square test, this difference was statistically significant (P = 0.007). (Fig. 3 ) Determining and Comparing Secondary Outcomes in Two Groups Table 2 Determination and Comparison of Secondary Outcomes in Two Groups Secondary Outcomes MgSO4 Group Mean ± SD Indomethacin Group Mean ± SD P-value Gestational age at delivery time. 35.03 ± 2.65 35.30 ± 2.50 0.438 First Minute Apgar Score 8.01 ± 1.22 8.02 ± 1.03 0.502 Fifth Minute Apgar Score 9.23 ± 0.89 9.16 ± 0.85 0.120 NICU Admission 14 (14%) 10 (10%) 0.384 Occurrence of Drug Side Effects NO 75 (75%) 63 (63%) 0.139 YES Constriction 17 20 Dyspnoea Nausea 3 6 Nausea and vomiting 5 9 Hypotension 0 2 Based on the data presented in the above table, no significant difference was observed between the two groups in any of the secondary outcomes. (Table 2 ) Table 3 Results obtained from logistic regression for identifying predictor variables of childbirth within 7 days after the initiation of Tocolytic medication. B S.E. Exp(B) Sig Intervention .735 .371 2.085 .048 Mothers Age − .008 .036 .992 .816 Gestational age at initial visit − .291 .103 .747 .005 Gravid .283 .223 1.327 .204 BMI − .062 .051 .939 .224 constant 10.783 3.908 48189.1 40 .006 Based on the results of logistic regression, and according to the data presented in the above table, among the variables of mother's age, gestational age at initial visit, gravidity, BMI, and type of intervention, only the variables of type of intervention and gestational age at the time of the visit were able to predict the occurrence of spontaneous labour within 7 days of starting the tocolytic drug. After adjustment for the variable of gestational age at initial visit, the type of intervention remained significantly associated with the occurrence of spontaneous labour within 7 days of starting the tocolytic drug (Exp(B) = 2.08, P = 0.048). Discussion The aim of this research was to compare the effect of simultaneous administration of magnesium sulphate with indomethacin versus magnesium sulphate alone in inhibiting preterm labour at Kowsar Hospital. Based on the findings, no statistically significant differences were observed in the demographic characteristics such as maternal age, gravidity, and history of preterm delivery. The average age of the women was 12.27 ± 43.5 years, and the average gravidity was 85.1 ± 92.0 Twenty-two women (11%) had a history of preterm delivery. However, there were significant differences between the two groups in terms of BMI and gestational age at admission. Women in the magnesium sulphate alone group had a higher BMI (p = 0.031) and a later gestational age at admission (p = 0.007) compared to the magnesium sulphate plus indomethacin group. The average time interval from drug administration to delivery in group A (magnesium sulphate + indomethacin) was 71.774 ± 91.505 hours, whereas in group B (magnesium sulphate alone), it was 77.545 ± 32.503 hours. This indicates that the intervention in group A was more effective in prolonging labour inhibition. There was a statistically significant relationship between the type of intervention and the time interval from drug administration to delivery. Among the variables of maternal age, gestational age at admission, gravidity, BMI, and type of intervention, only the type of intervention and gestational age at admission were significant predictors of spontaneous delivery within seven days of drug administration. After secondary adjustment, the type of intervention still had a significant relationship with spontaneous delivery within seven days of drug administration. This result supports that simultaneous administration of magnesium sulphate and indomethacin has a more positive impact in this context. This finding is consistent with Jayaram et al. (2018), who recommended magnesium sulphate for preterm labour inhibition due to its neuroprotective and tocolytic effects. However, in various studies, factors like gestational age, dosage, duration of treatment, and use of other tocolytics, including indomethacin, have shown differing recommendations for its use (Jayaram et al., 2018).( 23 ) According to Klauser et al. (2014), there was no significant difference in gestational age at delivery among groups treated with Nifedipine, magnesium sulphate, or indomethacin. Overall, there was no significant difference in the efficacy or safety of these major tocolytics ( 25 ). Abbasside et al. (2014) found no significant difference in the overall rate of preterm delivery between groups treated with magnesium sulphate and indomethacin, although differences in study criteria might explain the variance in results. Abbasside’s study included women with gestational ages between 28 and 32 weeks and dilation less than 6 cm, while our study included women with gestational ages between 24 and 32 weeks and dilation less than 4 cm ( 26 ). Contrary to our findings, Mosoodagh and colleagues (2012) observed similar effects in both groups treated with indomethacin and magnesium sulphate for preterm labour inhibition, with no preterm delivery observed within 48 hours of admission ( 27 ). TAJ ARAMESH et al. (2012) also reported significant differences in delaying preterm labour, with more effective results for indomethacin within the first 72 hours compared to magnesium sulphate alone. In contrast, in our study, this difference was significant over a seven-day period following drug administration ( 28 ). There were no significant differences in adverse maternal outcomes, NICU admissions, gestational age at delivery, and neonatal Apgar scores between the two groups. This is consistent with Vermillion et al. (2000), who reported no significant difference in gestational age at delivery between groups treated with indomethacin and controls ( 30 ). Lewis et al. (1995) found that the combined treatment (magnesium sulphate and indomethacin) prolonged tocolytic effects significantly more (368 hours) compared to magnesium sulphate alone (70.9 hours), which is consistent with our study results (Lewis et al., 1995). In conclusion, although there were no significant differences in the first 48 hours, the combined treatment showed a significant effect over a seven-day period in delaying preterm labour ( 31 ). Conclusion Preventing and treating preterm labour to reduce adverse neonatal outcomes and improve survival and quality of life is crucial. The primary goal in controlling preterm labour is not only to prolong pregnancy but also to improve neonatal outcomes and reduce mortality. This perspective significantly impacts long-term health and social care. The findings of this study indicate that simultaneous administration of magnesium sulphate and indomethacin is more effective in inhibiting and delaying preterm labour compared to magnesium sulphate alone. Considering other parameters such as neonatal Apgar scores, drug side effects, and gestational age at delivery, which showed minor differences, the combined treatment proved to be significantly effective in prolonging the time to delivery. Recommendations for future research it is recommended to conduct larger intervention studies controlling all influencing variables to achieve more precise results. Separate studies on the impact of different interventions on other delivery parameters, such as type of delivery, maternal complications, and pain perception, should be conducted. Combining these findings with current study results would provide a more comprehensive understanding of the effectiveness of different treatment protocols. Declarations Ethics approval and consent to participate This study has been approved by the Clinical Research Ethics Committee of Qazvin University of medical science. http://ethics.research.ac.ir/ IR.QUMS.REC.2019.102 , date approval 2019.3.13 . Each patient signed an informed consent regarding data collection for scientific purpose prior to their admission to the study. Consent for publication Not applicable. Availability of data and materials The dataset used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research received no external funding. Authors' contributions M.D conceived and designed the study. And S.F critically evaluated the manuscript. Sh.H performed the examination samplings and following pregnant women during delivery, S. F was a major contributor in writing the manuscript and M.D analyzed and interpreted the patient data regarding the labor progress. All authors significantly contributed to the development and implementation of the protocol. All authors read and approved the final manuscript. Acknowledgements The researchers express their gratitude from respected all participants in research, and all who made precious contributions to this study. Publisher’s Note Springer, Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References Slattery MM, Morrison JJ. Preterm delivery. Lancet. 2002;360(9344):1489–97. Wex J, Connolly M, Rath W. 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Klauser CK, Briery CM, Martin RW, Langston L, Magann EF, Morrison JC. A comparison of three tocolytics for preterm labor: a randomized clinical trial. J Maternal-Fetal Neonatal Med. 2014;27(8):801–6. Abasalizadeh S, Fakhraei MA, Ghojazadeh M, Abasalizadeh F, Raouf S, Javadi EHS. Compare the efficacy of Indomethacin and magnesium Sulphate in prevention of preterm labor. Int J Curr Res Aca. 2014;2(8):244–51. Mesdaghinia E, Mesdaghinia A, Hashemi T, Sooky Z, Mousavi SGA. Comparing the effects of Indomethacin and Magnesium-sulfate in the treatment of preterm labor. Feyz Med Sci J. 2012;16(2):95–101. Aramesh S, GHAFFARIAN SH, Ghaffari P, Noorian K, Hosseinian Z, Moghimi M. Coparative efficacy of Indomethacin and Magnesium Sulfate in management of Preterm Labor. 2012. Borna S, Saeidi FM. Celecoxib versus magnesium sulfate to arrest preterm labor: randomized trial. J Obstet Gynecol Res. 2007;33(5):631–4. Vermillion ST, Newman RB. Recent indomethacin tocolysis is not associated with neonatal complications in preterm infants. Am J Obstet Gynecol. 1999;181(5):1083–6. Lewis DF, Grimshaw A, Brooks G, Dunnihoo DR, Otterson WN. A comparison of magnesium sulfate and indomethacin to magnesium sulfate only for tocolysis in preterm labor with advanced cervical dilation. South Med J. 1995;88(7):737–40. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5226675","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":366755315,"identity":"6c4f8dc4-a132-461d-9d5e-5c51266936a6","order_by":0,"name":"Masoumeh Dadashaliha","email":"","orcid":"","institution":"Qazvin University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Masoumeh","middleName":"","lastName":"Dadashaliha","suffix":""},{"id":366755320,"identity":"d65d4a7f-3bb1-4cbe-818d-24b5cdeab5a0","order_by":1,"name":"Shiva Hoorshad","email":"","orcid":"","institution":"Qazvin University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shiva","middleName":"","lastName":"Hoorshad","suffix":""},{"id":366755321,"identity":"5b1a6515-b2a8-4390-b13a-0d3aa76934da","order_by":2,"name":"Somayeh Fallah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYBAC+RmMDQwMNgwyDBLMB4B8CRmCWgxugLSkMfAwSLAlgLTwENYiASLBWngMQEwitEg3t274kWDHwz+755vUjRoLHgb2w0c34NMiP+dg282ehGQeiTtnt0nnHAM6jCct7QZea24ktt3g/cHMw3AjF6iFTQLkQjOCWm7+Sajnkb+R80w65x+RWm7zJBzmMbiRwyad20aEFgOQFpmE4zyGN9KMrXP7JHjYCPlFfkb6s5tvEqrl5G4kP7yd861Ojp/98DH8DkMCLOA4YiNWOQgwfyBF9SgYBaNgFIwcAACjlUjydrSuGgAAAABJRU5ErkJggg==","orcid":"","institution":"University of Sharjah","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Somayeh","middleName":"","lastName":"Fallah","suffix":""}],"badges":[],"createdAt":"2024-10-08 15:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5226675/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5226675/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":68654830,"identity":"cfe3064e-8a66-4db8-9113-55e779915e34","added_by":"auto","created_at":"2024-11-10 13:56:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21486,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of the Mean Time Interval between Drug Administration and Delivery in Two Groups in Hours\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5226675/v1/e64c3b5a66a33113ec73a541.png"},{"id":68655337,"identity":"7b810f3a-8b98-47ec-904e-129934342070","added_by":"auto","created_at":"2024-11-10 14:04:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":26349,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the Frequency of Deliveries within 48 Hours After the Initiation of Medication in Two Groups\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5226675/v1/e6b2f212aa63a7eb57d2a0fd.png"},{"id":68654833,"identity":"fd159ba9-5bab-4964-a64a-94957a1266c1","added_by":"auto","created_at":"2024-11-10 13:56:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":26599,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the Frequency of Deliveries within 7 Days After the Initiation of Medication in Two Groups\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5226675/v1/6d65a7856a66f5e70f22de0a.png"},{"id":70318136,"identity":"1d2fe4be-1421-46c7-8f1d-2c7d34d96917","added_by":"auto","created_at":"2024-12-02 06:09:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":525713,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5226675/v1/5b7f595a-4805-4838-8cb2-b3936d089dcd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of the effect of simultaneous administration of magnesium sulfate and indomethacin with the administration of magnesium sulfate alone in inhibiting premature birth.","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePreterm birth, or preterm Labour, is used to describe babies born much earlier than expected. Preterm birth is divided into two subgroups: births before 33 weeks and 6 days are considered early preterm, while births between 34 and 36 weeks are termed late preterm, constituting over 70% of all preterm births. Deliveries occurring between weeks 37 to 38 and 6 days are considered early term, and those between weeks 39 to 40 and 6 days are considered full term, encompassing a range of fetal maturity that completes later in pregnancy than previously thought (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOverall, the incidence of preterm birth has gradually increased from 9.57% in 2014 to 9.36% in 2015. Various factors contribute to premature birth, often with multiple interacting characteristics and environmental influences. Causes may include unjustifiable preterm Labor, premature rupture of membranes, obstetric and maternal conditions, and multiple pregnancies. Spontaneous preterm Labor alone accounts for approximately 40\u0026ndash;45% of preterm births(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe undesirable consequences of infant immaturity in cases where birth occurs before 39 completed weeks of gestation are significant and notable. The survival of infants born preterm before 32 weeks\u0026rsquo; gestation depends on two factors: birth weight and gestational age, with survival rates reaching up to 95% after reaching a weight of 1000 grams and achieving a gestational age of 28 weeks in female fetuses or 30 weeks in male fetuses. Preterm birth is the most common cause of infant mortality, accounting for 75% of neonatal deaths. Preterm birth affects various fetal organs, including the brain, leading to complications such as hypoxic-ischemic encephalopathy (HIE), intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), weak cerebral growth, hydrocephalus, cerebral palsy, and decreased neurological function including impaired hearing.\u003c/p\u003e \u003cp\u003eAmong pulmonary complications, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and gastrointestinal complications such as hyperbilirubinemia, feeding intolerance, and necrotizing enter colitis (NEC) are notable. Multiple immunological complications can arise, including hospital-acquired infections (HAP), and haematological and endocrinological complications such as hypoglycaemia, insulin resistance, and cortisol deficiency are also common. Additionally, ophthalmological complications such as retinopathy of prematurity (ROP), nocturnal enuresis, and cardiovascular complications such as hypertension (HTN), pulmonary hypertension (PHTN), patent ductus arteriosus (PDA), as well as various renal, haematological, and endocrinological complications including hypoglycaemia, insulin resistance, and cortisol deficiency, can occur (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAmong the risk factors for preterm birth, maternal age or being too young, poverty and malnutrition, tobacco and drug use, genetic factors, periodontal diseases, and infections are mentioned. There are various therapeutic methods for preventing preterm birth, including the use of different types of progesterone formulations, either systemic or vaginal, or surgical interventions like cerclage, all aimed at delaying preterm labour and reducing neonatal complications. Nowadays, despite concerns about maternal hydration, tocolytics, along with bed rest and the use of tranquilizers, have found wide application in preventing preterm birth and are considered the mainstay of treatment (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Medications used for Tocolysis, which aim to inhibit uterine contractions, have their most significant effect in delaying labour for at least 48 hours to administer steroids to the mother for accelerating fetal lung maturity and transferring the mother to a facility equipped with a neonatal intensive care unit (NICU). Examples of Tocolytic drugs used in the treatment of preterm labour include beta-adrenergic agonists such as Ritodrine, magnesium sulphate, prostaglandin inhibitors like indomethacin, nitric oxide donors such as nitro-glycerine, calcium channel blockers like Nifedipine, and oxytocin Analogs such as Atosiban. However, determining the most effective treatment in this area requires conducting comprehensive comparative studies through clinical trials. In this regard, the effectiveness of magnesium sulphate in Tocolysis has been clearly demonstrated (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Hormonal interventions like oral or injectable progesterone and the use of vasodilator drugs such as Nifedipine are commonly used methods (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, determining the most effective treatment in this area requires conducting comprehensive comparative studies through clinical trials. In the past, the efficacy in reducing fetal mortality in preterm labour was our concern; however, nowadays with the identification of these pregnancies and appropriate care for both the mother and fetus, fetal mortality in these pregnancies has been reduced. Nevertheless, cases that arise still require further investigation and attention (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe birth of a premature infant poses significant economic and psychosocial burdens on the family, leading to the loss of emotional and financial investments and resources (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Premature infants are among the vulnerable groups in society and experience considerable physical, emotional, and psychological challenges compared to full-term infants, requiring proper care to sustain life and achieve normal growth and development (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Among these, hospitalization in the neonatal intensive care unit (NICU) for several days to months (depending on the level of prematurity or infant's condition) (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) is common. Since hospitalization is often a stressful and overwhelming experience for both the infant and the parents, particular attention has been given to it in recent years(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). With the understanding that reducing infant mortality signifies an improvement in public health, measures to reduce preterm births have gained special significance(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Bed rest, hydration, tocolytic medications to reduce uterine activity, and corticosteroids for fetal lung maturation and prevention of neonatal respiratory distress syndrome, as well as interventions to prevent infections such as Group B Streptococcus and neonatal sepsis, are among the important actions taken in the care of pregnant women at risk of preterm birth (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNowadays, magnesium sulphate therapy has been well established for many years. The medication magnesium sulphate, known in English as sulphate magnesium and chemically represented as MgSO4, is a therapeutic agent with various clinical applications, including prevention of seizures in preeclampsia, preterm Labor, and as an adjunct in the treatment of cardiac arrhythmias. Its parenteral and oral forms are used in the treatment of hypomagnesemia, and intravenously as a bronchodilator and smooth muscle relaxant. Its cellular mechanism of action is attributed to the inhibition of acetylcholine release at the neuromuscular junction, consequently inhibiting calcium influx into cells due to intracellular magnesium displacement. Its anticonvulsant effect is through the blockade of neuronal calcium channels via glutamate channels (these channels are only present in the CNS), producing an anticonvulsant effect on the maternal cortex without causing CNS depression in the mother and fetus. Some of the side effects of this drug include:\u003c/p\u003e \u003cp\u003eLoss of deep tendon reflexes, respiratory depression, nausea and vomiting, sweating, tingling sensation, hypotension, drowsiness, and dizziness, muscular weakness, bradycardia, and even coma.\u003c/p\u003e \u003cp\u003eIn case of overdose with this drug, initially the patellar reflexes disappear, and at higher concentrations, respiratory depression, respiratory paralysis, and ultimately cardiac arrest occur. Its treatment involves intravenous calcium gluconate along with discontinuation of magnesium sulphate(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) .\u003c/p\u003e \u003cp\u003eHowever, the use of NSAIDs alongside it and the role of this issue in enhancing the effectiveness of tocolytic therapy warrants further investigation. Indomethacin, known in English as Indomethacin, belongs to the category of nonsteroidal anti-inflammatory drugs (NSAIDs) and is available in tablet, capsule, and suppository forms. Indomethacin is a potent analgesic and anti-inflammatory drug, used as a medication to inhibit uterine contractions. Indomethacin primarily inhibits the enzyme cyclooxygenase, thereby preventing the conversion of arachidonic acid to prostaglandins. Prostaglandins play a crucial role in labour induction and preterm labour. Indomethacin's tocolytic effects are achieved by inhibiting cyclooxygenase, suppressing prostaglandin synthesis, and consequently reducing uterine contractions. Cyclooxygenase inhibitors are divided into two subgroups: non-selective COX-1 and COX-2 inhibitors, and selective COX-2 inhibitors. COX-1 is found in human decidua, myometrium, and fetal membranes, while COX-2 expression in the uterus plays a role in preterm labour and preterm birth, with no significant effects on the decidua and myometrium. Indomethacin is a non-selective COX-2 inhibitor. This drug is available in the market in the form of 25 mg capsules, 75 mg slow-release tablets, and 50 and 100 mg suppositories. Its suppository form is used as a tocolytic. Among its side effects are gastrointestinal ulcers, nausea and diarrhoea, severe morning headaches, drowsiness, vertigo, visual disturbances, and ringing in the ears(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). However, despite extensive studies, indomethacin alone has not been established as the primary drug for tocolysis, and the choice of medication depends on factors such as drug availability, efficacy, maternal and neonatal side effects, and cost. This study compares the effects of magnesium sulphate alone versus magnesium sulphate and indomethacin in inhibiting preterm labour. The management of preterm labour remains a crucial focus in obstetrics due to its significant impact on neonatal outcomes. Various tocolytic agents have been explored to delay delivery and improve outcomes, with magnesium sulphate and indomethacin being among the most commonly used. Studies have provided differing perspectives on the effectiveness of these treatments, influenced by factors such as dosage, administration route, and concurrent therapies.\u003c/p\u003e \u003cp\u003eJayaram et al. (2018) highlighted the neuroprotective and tocolytic benefits of magnesium sulphate in preterm labour. However, variability in recommendations arises due to contextual factors such as maternal age and dosage (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In contrast, Crowther et al. (2014) found no significant difference in delivery timing between magnesium sulphate and a control group, despite administering a regimen of 4 grams initially followed by 2 grams per hour for 48 hours (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Klauser et al. (2014) conducted a randomized controlled trial; pregnancy between 24\u0026ndash;32 weeks of gestation; comparing Nifedipine, magnesium sulphate, and indomethacin in preterm labour cases. The study revealed similar gestational age at delivery and labour cessation among the groups, though Nifedipine was linked with higher incidences of hypotension and tachycardia, while indomethacin was associated with more uterine contractions and oligohydramnios. Overall, no major differences in efficacy or safety were noted among the tocolytics (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAbbassalizadeh et al. (2014) compared indomethacin and magnesium sulphate in women with singleton pregnancies between 28 to 32 weeks of gestation. The duration from onset of pain to delivery was similar between the two groups, suggesting no significant difference in efficacy (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Nia et al. (2012) further confirmed this finding, showing no significant differences in delivery timing or maternal adverse effects between magnesium sulphate and indomethacin (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Taj et al. (2012) found indomethacin more effective than magnesium sulphate in delaying Labor, with 76.9% of magnesium sulphate recipients delivering within 72 hours compared to 37% in the indomethacin group(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Conversely, Barana and Saeidi (2007) found no significant difference between Nifedipine and magnesium sulphate in delaying delivery beyond 48 hours (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Lastly, Vermillion et al. (2000) and Lewis et al. (1995) explored combined therapies. Vermillion found no significant difference between indomethacin and control groups, while Lewis demonstrated that combining magnesium sulphate with indomethacin extended tocolysis duration significantly compared to magnesium sulphate alone (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThese findings underscore the complexity of choosing an optimal tocolytic regimen, highlighting the need for individualized treatment approaches based on specific clinical circumstances.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eIn this study, an intervention conducted in the form of a randomized double-blind clinical trial involved 200 women with symptoms of preterm labour who presented to Kowsar Hospital in Qazvin during the years 2022 and 2023. Eligible participants were selected and evaluated, and their data were collected and entered into the study. Inclusion criteria: Singleton pregnancies Gestational age between 24 and 32 weeks, having at least 4 uterine contractions in 20 minutes or 8 contractions in 1 hour causing changes in dilatation and effacement of the cervix, Cervical dilatation more than 2 and less than 4 centimetres, Cervical effacement more than 80%. Exclusion criteria: Multiple pregnancies, Recognized maternal medical conditions (such as cardiac, pulmonary, renal, rheumatologic diseases, kidney failure, history of gastrointestinal ulcers, etc.), Premature rupture of membranes, Vaginal bleeding, Cervical dilatation of 4 centimetres or more Intrauterine fetal demise (IUFD), Intrauterine growth restriction (IUGR), Hypersensitivity to indomethacin.\u003c/p\u003e \u003cp\u003eAmong the 200 pregnant women referred to Kowsar Hospital with singleton pregnancies, aged between 24 and 32 weeks, experiencing preterm labour contractions with cervical dilatation less than 4 centimetres, without vaginal bleeding, premature rupture of membranes, or history of kidney and gastrointestinal diseases, those who agreed to participate in the study were selected. Their demographic characteristics including sonography, gravidity, BMI, maternal age, and history of previous preterm labour were recorded. Considering the protocol of preterm labour management in Kowsar Hospital, all participants received the following protocol: slow intravenous loading dose of 4 grams of magnesium sulphate followed by 2 grams per hour for a maximum of 48 hours or 12 hours after cessation of contractions. 200 bags labelled as A and B were prepared, where A represented indomethacin and B represented placebo suppositories, stored in the labour room refrigerator, and administered randomly according to allocation using computerized randomization.\u003c/p\u003e \u003cp\u003eThe individuals were divided into the following two groups: Group 1: Pregnant women with preterm Labor pains received intravenous magnesium sulphate along with indomethacin suppositories 100 milligrams rectally every 12 hours for up to 12 hours after cessation of uterine contractions (contractions were monitored every 2 hours for 20 minutes by cardiotocography) or for a maximum of 48 hours. Group 2: Pregnant women with preterm Labor pains received intravenous magnesium sulphate along withl placebo suppositories rectally every 12 hours for up to 12 hours after cessation of uterine contractions (contractions were monitored every 2 hours for 20 minutes by cardiotocography) or for a maximum of 48 hours. During the medication administration period, patients were monitored for vital signs, blood pressure, headache, nausea, vomiting, shortness of breath, dizziness, and drowsiness. Signs of magnesium sulphate toxicity were also evaluated through urine output volume, deep tendon reflexes (DTR), and respiratory rate. Fetal heart rate was regularly monitored using cardiotocography, and uterine contractions were recorded every 2 hours for 20 minutes by this device.\u003c/p\u003e \u003cp\u003eData including gestational age, time interval between drug administration and delivery, history of preterm Labor, neonatal Apgar score, and if the neonate was admitted to the NICU, as well as drug side effects, were recorded on the questionnaire form.\u003c/p\u003e \u003cp\u003eThe primary outcome was the time interval after receiving uterine contraction-inhibiting drugs to delivery (in hours), and the secondary outcome was neonatal Apgar score at 1st and 5th minutes, neonatal weight, and whether they were admitted to the NICU.\u003c/p\u003e \u003cp\u003eThe study was double-blinded, meaning both the researcher and the patient were unaware of the type of suppository. Only the Labor room midwife, who recorded it for the patient, knew its nature, and at the end of the study period, she reported the cases to the researcher.\u003c/p\u003e \u003cp\u003eData analysis will be performed using the statistical software SPSS version 25, and descriptive statistics such as mean and standard deviation for quantitative variables, and frequency and percentage for qualitative variables, will be reported. The significance level for interpreting the results is considered as 0.05. A comparison between the two groups' primary outcomes will be conducted using independent samples t-test (or Mann-Whitney U test if assumptions are violated), and the frequency of outcomes between the two groups will be compared using the chi-square test (or Fisher's exact test if assumptions are violated). Additionally, side effects of drugs on mothers and fetuses between the two groups will be compared using the chi-square test (or Fisher's exact test if assumptions are violated).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDetermination and Comparison of Demographic Characteristics of Study Participants\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003edisplays the demographic characteristics including age, gravity, and BMI of the attendees.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMgSO4 Group Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIndomethacin Group Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal Age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.71\u0026thinsp;\u0026plusmn;\u0026thinsp;5.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.53\u0026thinsp;\u0026plusmn;\u0026thinsp;5.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.245\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal BMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.95\u0026thinsp;\u0026plusmn;\u0026thinsp;3.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.88\u0026thinsp;\u0026plusmn;\u0026thinsp;3.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGravidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.867\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at Pregnancy Upon Admissionn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.75\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of Preterm Delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.129\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eUpon observation of Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, it was noted that there was no statistically significant difference between the two groups regarding baseline characteristics such as maternal age, Gravidity, and history of preterm delivery. However, the two groups significantly differed in terms of BMI and age at pregnancy upon admission, where individuals in the MgSO4 recipient group alone exhibited higher BMI and older age at pregnancy upon admission compared to the group receiving MgSO4 and indomethacin. Specifically, for BMI upon admission during pregnancy, the age was statistically significant at P\u0026thinsp;=\u0026thinsp;0.031, with 26.88\u0026thinsp;\u0026plusmn;\u0026thinsp;3.13 compared to 27.95\u0026thinsp;\u0026plusmn;\u0026thinsp;3.82 and for gestational age at admission, it was (31.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.84 compared to 30.75\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23, P\u0026thinsp;=\u0026thinsp;0.007)\u003c/p\u003e \u003cp\u003e \u003cb\u003eDetermining and Comparing the Time Interval from Drug Administration to Delivery in 2 Groups as Primary Outcome\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eComparison of Mean Time Interval from Drug Administration to Delivery in Two Groups in Hours\u003c/p\u003e \u003cp\u003eBased on the findings, the mean time interval from drug administration to delivery in Group A (MgSO4\u0026thinsp;+\u0026thinsp;Indomethacin) was 774.18\u0026thinsp;\u0026plusmn;\u0026thinsp;505.91 hours, equivalent to 32.28 days, whereas in Group B (MgSO4), it was 545.78\u0026thinsp;\u0026plusmn;\u0026thinsp;503.32 hours, equivalent to 22.74 days. The Mann-Whitney U test revealed a statistically significant relationship between the type of intervention and the time interval from drug administration to delivery, with a p-value of 0.001. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAccording to the above figure, 15% of individuals in the MgSO4 recipient group delivered compared to 8% of individuals in the MgSO4 and Indomethacin recipient group within 48 hours after the initiation of medication. Based on the results obtained from the Chi-square test, this difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.174).(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAccording to the above figure, 31% of individuals in the MgSO4 recipient group delivered spontaneously compared to 15% of individuals in the MgSO4 and Indomethacin recipient group within 7 days after receiving tocolytic medication. Based on the results obtained from the Chi-Square test, this difference was statistically significant (P\u0026thinsp;=\u0026thinsp;0.007). (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDetermining and Comparing Secondary Outcomes in Two Groups\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDetermination and Comparison of Secondary Outcomes in Two Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSecondary Outcomes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eMgSO4 Group\u003c/p\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIndomethacin Group Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGestational age at delivery time.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e35.03\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.30\u0026thinsp;\u0026plusmn;\u0026thinsp;2.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.438\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFirst Minute Apgar Score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e8.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFifth Minute Apgar Score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e9.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNICU Admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e14 (14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eOccurrence of Drug Side Effects\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e75 (75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63 (63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.139\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConstriction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDyspnoea Nausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNausea and vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHypotension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBased on the data presented in the above table, no significant difference was observed between the two groups in any of the secondary outcomes. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults obtained from logistic regression for identifying predictor variables of childbirth within 7 days after the initiation of Tocolytic medication.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS.E.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eExp(B)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSig\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.735\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.371\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMothers Age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.992\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.816\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at initial visit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.747\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGravid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.283\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.327\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.204\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.939\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003econstant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.908\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48189.1\u003c/p\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBased on the results of logistic regression, and according to the data presented in the above table, among the variables of mother's age, gestational age at initial visit, gravidity, BMI, and type of intervention, only the variables of type of intervention and gestational age at the time of the visit were able to predict the occurrence of spontaneous labour within 7 days of starting the tocolytic drug. After adjustment for the variable of gestational age at initial visit, the type of intervention remained significantly associated with the occurrence of spontaneous labour within 7 days of starting the tocolytic drug (Exp(B)\u0026thinsp;=\u0026thinsp;2.08, P\u0026thinsp;=\u0026thinsp;0.048).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe aim of this research was to compare the effect of simultaneous administration of magnesium sulphate with indomethacin versus magnesium sulphate alone in inhibiting preterm labour at Kowsar Hospital.\u003c/p\u003e \u003cp\u003eBased on the findings, no statistically significant differences were observed in the demographic characteristics such as maternal age, gravidity, and history of preterm delivery. The average age of the women was 12.27\u0026thinsp;\u0026plusmn;\u0026thinsp;43.5 years, and the average gravidity was 85.1\u0026thinsp;\u0026plusmn;\u0026thinsp;92.0 Twenty-two women (11%) had a history of preterm delivery. However, there were significant differences between the two groups in terms of BMI and gestational age at admission. Women in the magnesium sulphate alone group had a higher BMI (p\u0026thinsp;=\u0026thinsp;0.031) and a later gestational age at admission (p\u0026thinsp;=\u0026thinsp;0.007) compared to the magnesium sulphate plus indomethacin group. The average time interval from drug administration to delivery in group A (magnesium sulphate\u0026thinsp;+\u0026thinsp;indomethacin) was 71.774\u0026thinsp;\u0026plusmn;\u0026thinsp;91.505 hours, whereas in group B (magnesium sulphate alone), it was 77.545\u0026thinsp;\u0026plusmn;\u0026thinsp;32.503 hours. This indicates that the intervention in group A was more effective in prolonging labour inhibition. There was a statistically significant relationship between the type of intervention and the time interval from drug administration to delivery. Among the variables of maternal age, gestational age at admission, gravidity, BMI, and type of intervention, only the type of intervention and gestational age at admission were significant predictors of spontaneous delivery within seven days of drug administration. After secondary adjustment, the type of intervention still had a significant relationship with spontaneous delivery within seven days of drug administration. This result supports that simultaneous administration of magnesium sulphate and indomethacin has a more positive impact in this context.\u003c/p\u003e \u003cp\u003eThis finding is consistent with Jayaram et al. (2018), who recommended magnesium sulphate for preterm labour inhibition due to its neuroprotective and tocolytic effects. However, in various studies, factors like gestational age, dosage, duration of treatment, and use of other tocolytics, including indomethacin, have shown differing recommendations for its use (Jayaram et al., 2018).(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAccording to Klauser et al. (2014), there was no significant difference in gestational age at delivery among groups treated with Nifedipine, magnesium sulphate, or indomethacin. Overall, there was no significant difference in the efficacy or safety of these major tocolytics (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Abbasside et al. (2014) found no significant difference in the overall rate of preterm delivery between groups treated with magnesium sulphate and indomethacin, although differences in study criteria might explain the variance in results. Abbasside\u0026rsquo;s study included women with gestational ages between 28 and 32 weeks and dilation less than 6 cm, while our study included women with gestational ages between 24 and 32 weeks and dilation less than 4 cm (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Contrary to our findings, Mosoodagh and colleagues (2012) observed similar effects in both groups treated with indomethacin and magnesium sulphate for preterm labour inhibition, with no preterm delivery observed within 48 hours of admission (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). TAJ ARAMESH et al. (2012) also reported significant differences in delaying preterm labour, with more effective results for indomethacin within the first 72 hours compared to magnesium sulphate alone. In contrast, in our study, this difference was significant over a seven-day period following drug administration (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere were no significant differences in adverse maternal outcomes, NICU admissions, gestational age at delivery, and neonatal Apgar scores between the two groups. This is consistent with Vermillion et al. (2000), who reported no significant difference in gestational age at delivery between groups treated with indomethacin and controls (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Lewis et al. (1995) found that the combined treatment (magnesium sulphate and indomethacin) prolonged tocolytic effects significantly more (368 hours) compared to magnesium sulphate alone (70.9 hours), which is consistent with our study results (Lewis et al., 1995). In conclusion, although there were no significant differences in the first 48 hours, the combined treatment showed a significant effect over a seven-day period in delaying preterm labour (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePreventing and treating preterm labour to reduce adverse neonatal outcomes and improve survival and quality of life is crucial. The primary goal in controlling preterm labour is not only to prolong pregnancy but also to improve neonatal outcomes and reduce mortality. This perspective significantly impacts long-term health and social care. The findings of this study indicate that simultaneous administration of magnesium sulphate and indomethacin is more effective in inhibiting and delaying preterm labour compared to magnesium sulphate alone. Considering other parameters such as neonatal Apgar scores, drug side effects, and gestational age at delivery, which showed minor differences, the combined treatment proved to be significantly effective in prolonging the time to delivery.\u003c/p\u003e\n\u003ch3\u003eRecommendations for future research\u003c/h3\u003e\n\u003cp\u003eit is recommended to conduct larger intervention studies controlling all influencing variables to achieve more precise results. Separate studies on the impact of different interventions on other delivery parameters, such as type of delivery, maternal complications, and pain perception, should be conducted. Combining these findings with current study results would provide a more comprehensive understanding of the effectiveness of different treatment protocols.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study has been approved by the Clinical Research Ethics Committee of Qazvin University of medical science. http://ethics.research.ac.ir/ IR.QUMS.REC.2019.102\u003cu\u003e,\u0026nbsp;\u003c/u\u003edate approval 2019.3.13\u003cu\u003e.\u003c/u\u003eEach patient signed an informed consent regarding data collection for scientific purpose prior to their admission to the study.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe dataset used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;M.D conceived and designed the study. And S.F critically evaluated the manuscript. Sh.H performed the examination samplings and following pregnant women during delivery, S. F was a major contributor in writing the manuscript and M.D analyzed and interpreted the patient data regarding the labor progress. All authors significantly contributed to the development and implementation of the protocol. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThe researchers express their gratitude from respected all participants in research, and all who made precious contributions to this study.\u003c/p\u003e\n\u003cp\u003ePublisher\u0026rsquo;s Note\u003c/p\u003e\n\u003cp\u003eSpringer, Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSlattery MM, Morrison JJ. Preterm delivery. Lancet. 2002;360(9344):1489\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWex J, Connolly M, Rath W. Atosiban versus betamimetics in the treatment of preterm labour in Germany: an economic evaluation. BMC Pregnancy Childbirth. 2009;9:1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePetrou S. The economic consequences of preterm birth duringthe first 10 years of life. BJOG: Int J Obstet Gynecol. 2005;112:10\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStan CM, Boulvain M, Pfister R, Hirsbrunner-Almagbaly P. Hydration for treatment of preterm labour. Cochrane Database Syst Reviews. 2013(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHusslein P, Quartarolo J. Review of clinical experience with atosiban and the Tractocile Efficacy Assessment Survey in Europe (TREASURE) study protocol. Int J Clin Pract. 2003;57(2):121\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaram K, Mortensen JHS, Wollen A-L. Preterm delivery: an overview. Acta Obstet Gynecol Scand. 2003;82(8):687\u0026ndash;704.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchieve LA, Handler A. Preterm delivery and perinatal death among black and white infants in a Chicago-area perinatal registry. Obstet Gynecol. 1996;88(3):356\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlenady V, Wojcieszek AM, Papatsonis DN, Stock OM, Murray L, Jardine LA et al. Calcium channel blockers for inhibiting preterm labour and birth. Cochrane Database Syst Reviews. 2014(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar P, Magon N, Abdulkareem IH, Mirhosseini SJ, Forouzannia SK, Mirhosseini SA, et al. A PUBLICATION OF NIGERIA MEDICAL ASSOCIATION. Nigerian Med J. 2012;53(4):179.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTan T, Devendra K, Tan L, Tan H. Tocolytic treatment for the management of preterm labour: a systematic review. Singapore Med J. 2006;47(5):361.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchleu\u0026szlig;ner E. The prevention, diagnosis and treatment of premature labor. Deutsches \u0026Auml;rzteblatt international. 2013;110(13):227.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarooqi A, Hagglof B, Sedin G, Gothefors L, Serenius F. Chronic conditions, functional limitations, and special health care needs in 10-to 12-year-old children born at 23 to 25 weeks' gestation in the 1990s: a Swedish national prospective follow-up study. Pediatrics. 2006;118(5):e1466\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalson SK. Preterm birth as a public health initiative. Public Health Rep. 2008;123(5):548\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Rouck S, Leys M. Information needs of parents of children admitted to a neonatal intensive care unit: A review of the literature (1990\u0026ndash;2008). Patient Educ Couns. 2009;76(2):159\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008;371(9608):261\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEscobar GJ, McCormick MC, Zupancic JA, Coleman-Phox K, Armstrong MA, Greene JD, et al. Unstudied infants: outcomes of moderately premature infants in the neonatal intensive care unit. Archives Disease Childhood-Fetal Neonatal Ed. 2006;91(4):F238\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimmons LE, Rubens CE, Darmstadt GL, Gravett MG, editors. Preventing preterm birth and neonatal mortality: exploring the epidemiology, causes, and interventions. Seminars in perinatology. Elsevier; 2010.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang HH, Larson J, Blencowe H, Spong CY, Howson CP, Cairns-Smith S, et al. Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index. Lancet. 2013;381(9862):223\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVause S, Johnston T. Management of preterm labour. Archives Disease Childhood-Fetal Neonatal Ed. 2000;83(2):F79\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTara P, Thornton S, editors. Current medical therapy in the prevention and treatment of preterm labour. Seminars in Fetal and Neonatal Medicine. Elsevier; 2004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChatterjee J, Gullam J, Vatish M, Thornton S. The management of preterm labour. Archives Disease Childhood-Fetal Neonatal Ed. 2007;92(2):F88\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatz VL, Farmer RM. Controversies in tocolytic therapy. Clin Obstet Gynecol. 1999;42(4):802.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJayaram PM, Mohan MK, Farid I, Lindow S. Antenatal magnesium sulfate for fetal neuroprotection: a critical appraisal and systematic review of clinical practice guidelines. J Perinat Med. 2019;47(3):262\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCrowther CA, Brown J, McKinlay CJ, Middleton P, Pregnancy C, Group C. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Reviews. 1996;2014:8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlauser CK, Briery CM, Martin RW, Langston L, Magann EF, Morrison JC. A comparison of three tocolytics for preterm labor: a randomized clinical trial. J Maternal-Fetal Neonatal Med. 2014;27(8):801\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbasalizadeh S, Fakhraei MA, Ghojazadeh M, Abasalizadeh F, Raouf S, Javadi EHS. Compare the efficacy of Indomethacin and magnesium Sulphate in prevention of preterm labor. Int J Curr Res Aca. 2014;2(8):244\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMesdaghinia E, Mesdaghinia A, Hashemi T, Sooky Z, Mousavi SGA. Comparing the effects of Indomethacin and Magnesium-sulfate in the treatment of preterm labor. Feyz Med Sci J. 2012;16(2):95\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAramesh S, GHAFFARIAN SH, Ghaffari P, Noorian K, Hosseinian Z, Moghimi M. Coparative efficacy of Indomethacin and Magnesium Sulfate in management of Preterm Labor. 2012.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBorna S, Saeidi FM. Celecoxib versus magnesium sulfate to arrest preterm labor: randomized trial. J Obstet Gynecol Res. 2007;33(5):631\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVermillion ST, Newman RB. Recent indomethacin tocolysis is not associated with neonatal complications in preterm infants. Am J Obstet Gynecol. 1999;181(5):1083\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLewis DF, Grimshaw A, Brooks G, Dunnihoo DR, Otterson WN. A comparison of magnesium sulfate and indomethacin to magnesium sulfate only for tocolysis in preterm labor with advanced cervical dilation. South Med J. 1995;88(7):737\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Premature birth, magnesium sulphate, Iindomethacin","lastPublishedDoi":"10.21203/rs.3.rs-5226675/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5226675/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e Premature birth is one of the most significant complications observed in pregnancies, which can lead to consequences such as preterm birth and its associated complications. The aim of this research is to compare the effectiveness of tocolytics with magnesium sulphate alone and the combination of magnesium sulphate and indomethacin in preventing premature birth at Kowsar Hospital in 2019-2020.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods\u003c/strong\u003e: This clinical trial was conducted on 200 pregnant women with gestational age of 24 to 32 weeks referred to Kowsar Hospital in Qazvin; Iran. Patients were divided into two equal groups, receiving treatment with magnesium sulphate and indomethacin (Group A) and magnesium sulphate alone (Group B). Then, the data were analysed using SPSS statistical software and appropriate statistical tests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e According to the research findings, the mean time interval from drug administration to delivery in Group A was 505.91 ± 774.71 hours, and in Group B, it was 545.77 ± 503.32 hours, with this difference being statistically significant (p \u0026lt; 0.05). Additionally, the mean gestational age at the time of delivery in Group A was 35.30 ± 2.50 weeks and in Group B was 35.03 ± 2.65 weeks, with no significant difference (p \u0026gt; 0.05). On the other hand, the type of intervention had a significant relationship with the number of deliveries within 7 days after starting drug administration (p \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The results indicate a greater impact of tocolytics with the combination of magnesium sulphate and indomethacin compared to magnesium sulphate alone in preventing premature birth and delaying it. There were similarities in our study findings compared to other studies.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e \u003c/strong\u003eThis clinical study was approved by the Iranian Registry of Clinical Trials (\u003ca href=\"http://www.irct.ir/\" target=\"_blank\"\u003ehttp://www.irct.ir\u003c/a\u003e) with the with the IRCT ID: IRCT20190819044568N1, Registration date was 2020-05-08 .\u003c/p\u003e","manuscriptTitle":"Comparison of the effect of simultaneous administration of magnesium sulfate and indomethacin with the administration of magnesium sulfate alone in inhibiting premature birth.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-10 13:56:45","doi":"10.21203/rs.3.rs-5226675/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8b84cdaf-05df-490b-b289-0dc9a7a67be8","owner":[],"postedDate":"November 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-02T06:08:55+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-10 13:56:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5226675","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5226675","identity":"rs-5226675","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}