Tocolytic Therapy Research Articles

MiR-203 modulates pregnant myometrium contractility via transient receptor potential vanilloid 4 channel expression.

Preterm labor is the leading cause of neonatal death and major morbidity but remains a poorly understood process with no effective tocolytic therapies. Recent work has identified the transient receptor potential vanilloid 4 (TRPV4) channel, a membrane calcium channel upregulated in uterine smooth muscle through gestation, as integral in the transition from quiescence to contraction in the gravid uterus. The present study builds upon these findings and investigates regulation of the TRPV4 channel during pregnancy in the murine and human uterus by micro-RNA 203 (miR-203). We find a progressive decrease in miR-203 expression during gestation, accompanied by a reciprocal increase in TRPV4 mRNA and protein expression. In human uterine smooth muscle cells (UtSMC), miR-203 overexpression reduces, and si-RNA-mediated silencing increases, TRPV4 expression. Studies using murine UtSMC demonstrate that miR-203 expression modulates TRPV4-mediated cytosolic calcium entry and contractility. Consistent with these findings, the response to pharmacologic TRVP4 agonists is increased in myometrial tissue from miRNA203 -/- mice compared to control mice. Moreover, we demonstrate that miR-203 binds specifically on the promoter region of TRPV4 to decrease expression. In murine inflammatory models of preterm labor, miR-203 overexpression prolongs pregnancy. Estradiol (E2) decreases miR-203 and increases TRPV4 expression, providing a potential physiologic link for the unique reciprocal relationship in UtSMC. Taken together, these findings provide evidence that miR-203 modulates uterine contractility during pregnancy via negative regulation of TRPV4. These findings support the hypothesis that targeting miR-203 holds the promise of an entirely novel approach to prevent prematurity and treat preterm labor.

Current possibilities and prospects of tocolytic therapy

The urgency of the problem of preterm birth (PB) is because of its high prevalence and neonatal mortality. The effects of PB on the fetus are often fatal, and PB accounts for 70% of neonatal mortality and 36% of infant mortality. Severe neurological deficits (e.g., cerebral palsy, epilepsy, intraventricular hemorrhages, retinopathy, blindness, hearing loss, delayed neuropsychiatric and motor development) occur in 68% of surviving premature infants. Additionally, children born prematurely have a high risk for purulent septic diseases. The metabolic consequences of prematurity cause diseases such as metabolic syndrome and hypertension. Thus, tocolytic therapy is a crucial therapeutic measure in obstetrics. However, most known and actively used tocolytic drugs induce insufficient effect for long-term prolongation of pregnancy or have serious side effects. Currently, there is a search for new tocolytics to obtain safe, adequate, and long-term effects. This review examines promising and relevant drugs that may be used in routine obstetric practice. Scientific articles, meta-analyses, and systematic reviews from the databases PubMed, Embase, Web of Science, and Google Scholar, and RSCI were analyzed. For the analysis, publications in English and posted no more than 5 years before the study was conducted were selected, except for fundamental works with a longer publication period.

Effects of nationwide adjustment of tocolysis protocol in the Netherlands on neonatal outcomes in women with threatened preterm birth and delivery at 30-32 weeks of gestation: A cohort study

ObjectiveIn 2019 the Dutch national prevention of preterm birth (PTB) protocol was adjusted to withhold tocolysis for threatened PTB above 30 weeks of gestation due to insufficient evidence regarding its effectiveness on improving perinatal outcomes. The aim of this study is to evaluate neonatal outcomes of children born in the Netherlands between 30 and 32 weeks of gestation before and after the national protocol change. Study designWe performed a nationwide retrospective cohort study comparing outcomes of births in the years 2018 (tocolysis) and 2020 (no tocolysis). Tocolytic therapy consisted of either nifedipine or atosiban. Data were extracted from the national Perinatal Registry (PERINED). Women with a spontaneous PTB from 30 + 0 to 31 + 6 weeks of gestation were included. The primary outcome was a composite of mortality, severe intraventricular hemorrhage, severe necrotizing enterocolitis, cystic periventricular leukomalacia, and retinopathy of prematurity needing therapy. Secondary outcomes included additional neonatal outcomes. The odds ratio (OR) with corresponding 95 % confidence interval (CI) was calculated by logistic regression analysis for the year 2020 compared with 2018. ResultsComposite neonatal outcome did not differ between 2018 compared to 2020 (8.4 % (18/215) vs 8.2 % (25/306), OR 0.95; 95 % CI 0.51–1.77). No difference in composite neonatal outcome was found when analyzing groups as singletons (7.1 % vs 9.3 %, OR 1.35; 95 % CI 0.64–2.87), and multiples (13.3 % vs 5.9 %, OR 0.41; 95 % CI 0.13–1.26). ConclusionThere was no significant difference in composite neonatal outcome in pregnancies resulting in spontaneous PTB between 30 and 32 weeks of gestation in 2018 (with tocolysis) compared to 2020 (no tocolysis). These results support the protocol adjustment to withhold tocolytic treatment in women with threatened PTB above 30 weeks of gestation.

To Assess The Role Of Vaginal Micronised Progesterone As A Tocolytic Therapy In Arrested Preterm Labour

To Assess The Role Of Vaginal Micronised Progesterone As A Tocolytic Therapy In Arrested Preterm Labour

Cooperation of aquaporin 5 and the adrenergic system in the initiation of birth in rat model

Aquaporins (AQPs) are involved in the process of implantation, regulate myometrial contractions and cervical ripening, and maintain appropriate placental functioning. The molecular mechanism of these functions is not fully understood. Our study aimed to investigate the physiological significance of AQP5 during pregnancy and to determine the cooperation between the adrenergic system and the AQP5 in uterine contraction in the late-pregnant rat uterus.After administering AQP5 siRNA intraperitoneally to Sprague-Dawley rats, the length of the gestational period was determined and the changes in uterine contractions were measured in an isolated organ bath system. Pharmacological influence on AQP5 expression and uterine contraction was investigated by treatment with terbutaline (10 mg/kg, subcutaneously) and doxazosin (5 mg/kg, orally) in vivo; and mercuric chloride (HgCl2), in vitro. Moreover, the levels of cAMP response element binding protein (CREB) were measured in the uterus by an ELISA kit.The gestational period became shorter, AQP5 expression significantly decreased and rat uterus contraction increased after AQP5 siRNA treatment compared to the control. Treatment with terbutaline significantly increased AQP5 mRNA and protein expression after 30 min and continuously reduced it until 90 min, whereas doxazosin treatment did not significantly alter AQP5 expression. Treatment with the AQP5 antagonist HgCl2 increased spontaneous uterus contraction and decreased norepinephrine-induced uterus contraction with decreasing AQP5 expression in pregnant rat uterus. Moreover, the tocolytic effect through the adrenergic system was amplified in the presence of an AQP5 antagonist, presumably via the changes in cAMP level.In conclusion, our findings elucidate the collaborative role of aquaporin 5 (AQP5) and adrenergic systems in the regulation of uterine contractions in late-pregnant rats. Our findings suggest this may be a good starting point for developing a new tocolytic therapy.

Pheophorbide-a, a chlorophyll derivative, inhibits myometrial contractility ex vivo via blockade of extracellular and intracellular Ca2+−entry

BackgroundPreterm delivery is associated with neonatal complications such as neurological impairment and necrotising enterocolitis. Thus, suppression of early myometrial contractility in pre-term labor (PTL) delays delivery and reduces maternal adverse outcomes associated with PTL. However, most tocolytics exert varied efficacies and untoward outcomes such as maternal cardiovascular and respiratory effects creating a need for novel efficacious and safe tocolytics. We previously reported that chlorophyll derivatives including Pheophorbide-a (PBa) isolated from the leaves of the plant Ficus exasperata, effectively inhibited non-pregnant mouse myometrial contractility ex vivo. Therefore, the current study explores the mechanisms involved in PBa-induced myometrial contractility inhibition in both non-pregnant and pregnant mouse uterus. MethodWe carried out contractility studies by inducing isometric tension on isolated myometrial strips of mice following ex vivo exposure to PBa. The uterine strips were mounted in organ baths containing oxygenated physiological saline maintained at pH 7.4 and 36.8 ± 0.2 °C. ResultsPBa (0.02–206.19 µM) produced concentration-dependent decreases in the amplitude and frequency of pregnant and non-pregnant uterine contractions. In addition, PBa (87.74 μM) significantly inhibited the amplitude (P = 0.0026) and frequency (P = 0.0178) of OT-induced uterine contractility in Ca2+−free solution and in the presence of high KCl (80 mM) (P = 0.005). Furthermore, our study showed that the uterine relaxant effect of PBa occurred through the blockade of l-type voltage-gated Ca2+channels (VGCCs) and through inhibition of Ca2+ mobilization from intracellular stores which are common downstream pathways specific to tocolytics and relevant for uterine relaxation. ConclusionThese findings reveal that PBa effectively attenuates uterine contractions via interaction with Ca2+−entry and shows potential as a promising candidate as a tocolytic therapy for PTL. Further investigations on PBa are encouraged to elucidate molecular and cellular mechanisms of PBa uterine relaxation activity including assessment of efficacy and off-target effects.

Evaluation between Serum Level CRP and Maternal Outcomes that includes Preterm Delivery: A Prospective Analysis

Background and Aim: C-reactive protein is commonly employed as a biomarker to track the development ofinflammatory and infectious disorders. There aren’t many researches that have investigated the link between maternal serum CRP concentrations early in pregnancy and preterm birth or neonatal outcomes. The aim of this study was to evaluate the correlation between serum level CRP and maternal and neonatal adverse outcomes including preterm delivery and Small for gestational age (SGA).Material and Methods: This prospective study was conducted on 400 pregnant women who delivered at theObstetrics and Gynecology Department of a medical college and affiliated hospital for the period of one year.Pregnant women who met the inclusion and exclusion criteria were enrolled after giving their informed consent, and the serum C-reactive protein levels were measured at the gestational age (GA) of 14 to 20 weeks. Pregnant women were then followed up to delivery, and based on the GA at delivery, they were divided into preterm and non-preterm groups. A reference level of 1.5 mg/dl is used. Therefore, pregnancies with high maternal serum C - reactive protein were those in which the maternal serum level was above 1.5 mg/dl.Results: A total of 296 individuals in group A and 104 individuals in group B had CRP levels below 1.5 mg/dl,respectively. This study’s average gestational age was 18.8 weeks. The minimum and maximum gestational ages were 12+1 and 21+3 weeks, respectively. In this study, 316 individuals delivered at term, while 84 people delivered preterm. In the population under study, 114 individuals underwent LSCS, while the remaining 286 women gave birth vaginally. 400 patients in total were included in the study; 316 had CRP levels under 1.5; of these, 272 had term deliveries, while 24 had preterm births. The remaining 84 individuals had a CRP of greater than 1.5; of these, 60 had preterm deliveries and 24 had term births.Conclusion: Assessment of maternal concentrations of CRP can be used as suitable biomarker for predictingpreterm labor, and also despite the limitation in the number of patients, response to tocolytic therapy in our study was predictable by the evaluation concentrations of CRP of these women.

The Usage of Tocolytic Drugs in Pregnant Women With the Threat or Preterm Labor in PKU Muhhamadiyah Gamping Hospital Yogyakarta

Partus Prematurus Imminens (PPI) is a threat to pregnancy caused by contractions in the uterus at a gestational age that has not reached 37 weeks, or what is commonly called preterm labour. According to the WHO, there are around 10-11% of preterm births in the world each year, while in Indonesia, the WHO explains that there are around 16% of preterm deliveries, which places Indonesia in fifth place with the largest preterm deliveries in the world. Management and prevention efforts with tocolytic therapy is a therapy used to suppress uterine contractions. This research used analytic descriptive observational with a cross-sectional approach where these observations were made within the past 5 years. The sample in this study was conducted on pregnant women who experienced the threat of preterm labour. This research found that most of the samples recovered as many as 23 (95.8%) people, and the most used drug was Nifedipine, with a recovery status of 12 (50.0%) people, while the rest were Hystolan. However, there was no significant relationship between drug use and recovery in pregnant women with imminent premature labour, as shown by the Fisher Exact Test, p value> 0.05. Tocolytic drugs are effective to be given to pregnant women with Partus Prematurus Imminens (PPI). However, there was no significant relationship between the drug (Nifedipine and Hystolan) and the recovery of pregnant women with imminent preterm labour (PPI) at PKU Muhammadiyah Gamping Hospital, Yogyakarta.

The Effect of Magnesium Sulfate on Contraction of Pregnant Women with Cases of Partus Premature Imminent in District General Hospitals Mentawai Islands

In 2020, it was recorded that the number of neonatal deaths in West Sumatra was 104, with 18 cases being the cause of prematurity, where the Mentawai Islands district had the highest ranking of neonate deaths with 44 deaths and 10 cases being the cause of prematurity. This research aims to determine the effect of administering magnesium sulfate therapy on contractions of pregnant women in cases of imminent premature labour at the Mentawai Islands District Hospital in 2021. This type of research is pre-experimental with a Grup Pretest-Post Test design because in this study a random sample was not carried out by taking samples from secondary data retrospectively. Data taken came from medical records of inpatients who had a diagnosis of premature labour (ICD Total sampling was taken with a total sample size of 48, and statistical data analysis using the McNemar test. Data from 48 research subjects experienced contractions and received magnesium sulfate therapy. During monitoring after administering magnesium sulfate, 3 subjects still experienced contractions and 45 subjects did not experience contractions. Uterine contractions occurred significantly more before magnesium sulfate therapy than after magnesium sulfate therapy (P<0.005). There is a significant relationship between administering magnesium sulfate to patients with preterm labour to stop uterine contractions at the Mentawai Islands District Hospital. Apart from being a tocolytic therapy, magnesium sulfate also has a neuroprotectant effect so it is highly recommended for therapy in cases of premature parturition.

THU316 Relatively Rare And Increasingly Fatal; A Case Of Euglycemic DKA In A Patient With Gestational Diabetes

Abstract Disclosure: C. Dimech: None. E. Rabiei-Flori: None. P.L. Bononi: None. Diabetic ketoacidosis (DKA) is an endocrine emergency and can be a catastrophic event during pregnancy, increasing both maternal and fetal mortality. Euglycemic DKA (EDKA) during pregnancy is a rare, acute, life-threatening emergency characterized by euglycemia, metabolic acidosis and ketosis. EDKA has been reported in pregnancies complicated by Type 1 diabetes, Type 2 diabetes and gestational diabetes. Unlike DKA, the diagnosis of EDKA is often overlooked because of the absence of hyperglycemia. The incidence of DKA and EDKA are higher during pregnancy due to physiologic changes of increasing insulin resistance from human placental lactogen, placental insulinase, and progesterone which result in a relative insulin deficiency as the pregnancy progresses. Additionally, tocolytic therapy to delay preterm labor and antenatal corticosteroids given to promote fetal lung development, pose unique triggering factors in pregnancy which can further precipitate DKA. We report a case of EDKA in a 37-year-old G2P0010 Caucasian female at 29 week 6 day gestation with recently diagnosed gestational diabetes on diet therapy (HbA1c 6.3%), who was admitted for atypical preeclampsia. Initial laboratory studies revealed an anion gap metabolic acidosis (anion gap=24, arterial pH 7.242) with euglycemia (blood glucose 123mg/dL). She underwent emergent C-section 24 hours after admission due to development of pre-eclampsia with severe features. Despite delivery, she had persistent and worsening high anion gap metabolic acidosis (HAGMA). The Endocrinology service was consulted and ordered a beta hydroxybutyrate level which was elevated at 6.18mmol/L (0.02-0.30mmol/L) with 3+ ketonuria. Intravenous insulin and dextrose were instituted with gradual improvement in acidosis. EDKA is an easily missed diagnosis that should always be considered during pregnancy in a patient with high anion gap metabolic acidosis. Prompt recognition and treatment is essential to minimize complications to mother and fetus. Presentation: Thursday, June 15, 2023

Study Based on the Alliance Between Serum Magnesium Levels and Preterm Labor: An Inclusive Review.

Preterm labor, regarded as the onset of labor before 37 weeks of gestation, is a highly prevalent issue in obstetrics with repercussions for neonatal health. This review article presents an in-depth analysis of the alliance between serum magnesium levels and preterm labor. The review explores the physiological roles of magnesium right through pregnancy, including its significance for energy metabolism, smooth muscle contraction, deoxyribonucleic acid (DNA), and protein synthesis. It addresses cellular transport and the homeostasis of magnesium. The pathophysiological processes encompassing inflammation, oxidative stress, calcium regulation, smooth muscle contractility, and neuroendocrine pathways are investigated. The review evaluates epidemiological studies investigating the alliance between serum magnesium levels and preterm labor. The review incorporates an assortment of study varieties, such as observational studies, case-control studies, prospective cohort studies, and meta-analyses. In the course of reviewing the prognostic relevance of serum magnesium levels in premature labor, therapeutic implications involving diagnostic precision, prognostic significance, and therapeutic response assessment have additionally been addressed. Therapeutic interventions targeting magnesium levels, such as magnesium supplementation, tocolytic therapy, and the role of magnesium in antenatal corticosteroid administration, are explored. This review provides an in-depth evaluation of the correlation between serum magnesium levels and preterm labor, stressing its therapeutic significance and repercussions for future research and treatment strategies.

Laparoscopic management of ovarian cysts during pregnancy under urgent situations.

Majority of adnexal masses are incidental findings during pregnancy and resolve spontaneously. They may complicate pregnancy due to haemorrhage, cyst rupture and ovarian torsion. Laparoscopy is the preferred surgical intervention owing to shorter operative time, quicker recovery and lower post-operative pain. However, safety and feasibility of laparoscopic surgery in the management of ovarian cysts in pregnant women is challenging especially at advanced gestational ages and in urgent situations. In this retrospective study, a total of 48 cases of urgent laparoscopic surgeries were evaluated in the first and second trimesters of pregnancy between March 2018 and March 2021 in Al-Zahra Hospital, Tabriz, Iran. The operations were ended in all patients successfully. The mean operation time was 45 min. There were no foetal maternal complications. All pregnancies had been terminated after 37 weeks of gestation. Oophorectomy had been performed in six patients and six other patients needed blood transfusion. Ovarian torsion was the most common reason for emergency surgery and mature teratoma was the most commonly reported pathology. Tocolytic therapy was required in six patients, and all of the patients were prescribed 50 mg of injectable progesterone twice daily for 10 days after surgery. The mean intra-abdominal pressure was equal to 15 mmHg and the mean end-expiratory carbon dioxide (CO 2 ) pressure was 36 mmHg. Intravenous paracetamol was used to relieve post-operative pain. The mean hospitalisation time was 1.63 days. Most of the ovarian cysts can be managed laparoscopically with ensured safety and lower morbidity even in emergency situations at advanced gestational ages.

Labour as a manifestation of systemic inflammatory reaction (Literature review)

Childbirth is the result of a rapid biological reaction, in which the humoral and cellular links of immunity take part. Therefore, all attempts to stop the uterine premature contractile activity at the level of the myometrium have only a temporary effect. This review deals with the modern scientific data about the role of immune mechanisms in the labor activity origin from the point of view of the possibilities of predicting its anomalies and pathogenetically based treatment of premature labor.Cytokine balance plays a role already in the process of implantation, during the interaction between the endometrium and the fertilized egg. The increased content of pro-inflammatory cytokines in the endometrium is more typical for the women with normal implantation than for the patients with recurrent reproductive losses. Endometrial decidualization, vascular remodeling occurs under the influence of pro-inflammatory mediators. The traditional view of the preterm labor pathogenesis assumes its infectious nature, which is confirmed by the prevalence of infection in premature newborns and is explained by the activation of pro-inflammatory mediators.Modern opinions regarding the primacy of the inflammatory response in premature rupture of the fetal membranes are outlined. The heterogeneity of the inflammatory response in different patients found an explanation in the polymorphism of genes encoding the main receptors of the immune response – TOLL receptors. The discovery of numerous proteins of the acute inflammation phase led to the search for their role in the implementation of labor activity. So far, the ability to stimulate labor activity has been shown for FCGR3A protein and haptoglobin.Inadequate consideration of the inflammatory reaction role, in particular its systemic nature, in the pathogenesis of premature labor has led to an overestimation of the possibilities of tocolytic therapy. Meta-analyses indicate that the use of tocolytics, despite the effective increase in the duration of pregnancy, does not improve the condition and prognosis of the newborn. Most tocolytic drugs have a point of application of a part of the myocyte, contact with which blocks its contraction. However, all of them, with the exception of indomethacin, do not affect the immunological causes of the development of premature labor, and therefore do not eliminate their effect on the fetus.The inflammatory reaction does not always have an infectious origin, so the management of routinely prescribing antibacterial drugs to prevent premature births has also not spread. At present, it should be recognized that powerful inflammatory processes underlying labor activity, premature in particular, in most cases determine the inevitability of premature birth.Research on finding the regulation of inflammatory mechanisms for the regulation of labor activity can be considered promising, but they are in the early theoretical stages. For a modern doctor, the systemic nature of the inflammatory reaction is of practical importance for understanding the reasons for the rapid generalization of the process in chorioamnionitis, timely diagnosis and response, as well as the features of the course of the early neonatal period.

Tocolytics in obstetric practice

Preterm birth remains a leading cause of perinatal mortality and morbidity in preterm infants and leads to significant annual health care costs. A special role in preventing premature birth belongs to tocolytic therapy, which allows for prolonging pregnancy and avoiding various complications. However, questions arise about the efficacy and safety of this therapy, which can be manifested by various isolated and combined side effects. The aim of the study was to assess the effectiveness and complications of tocolytic therapy. We analyzed the literature on eLibrary, Medline, Scopus, Cochrane Library, PubMed, ScienceDirect, etc.

Delayed interval delivery in a quadruplet pregnancy: a case report and literature review

BackgroundAs the rate of multiple pregnancies increases, delayed interval delivery (DID) is increasingly being implemented to improve perinatal outcomes. But there are no international guidelines for DID in multiple pregnancies. We report a case of DID in a quadruplet pregnancy and review the relevant literature to summarize the management of DID in multiple pregnancies.Case presentationA 22-year-old woman, 22 2/7 weeks' gestation, with quadruplets, was admitted to the hospital for a first cervical cerclage due to cervical dilation. Twenty-five days later, it was found that the cervix was dilated again, so after removing the cervical cerclage, the first quadruplet was delivered vaginally (25 6/7 weeks), and a second cervical cerclage was performed. Four days later, due to re-dilation of the cervix, after removal of the cervical cerclage, the second quadruplet was delivered vaginally (26 3/7 weeks), followed by a third cervical cerclage. Six days later, the pregnancy was terminated by cesarean section due to fetal distress, and the third and fourth quadruplets were delivered (27 2/7 weeks). The patient had no postoperative complications, and all four infants were treated in the neonatal intensive care unit and discharged successfully.ConclusionThis case emphasizes that comprehensive management of delayed interval delivery can improve perinatal outcomes in multiple pregnancies, including anti-infection, tocolytic therapy, practice to promote fetal lung, and cervical cerclage.

Outcomes of nursing monitoring for pregnant women under tocolytic therapies: a comparative study

Background Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality worldwide. Tocolytic drugs had not been shown to improve fetal outcome, but were used to postpone delivery for 48 h to allow for maximal effect of parenteral steroids administered to the mother. The aim of the current study was to evaluate the outcomes of nursing monitoring for the pregnant mother under tocolytic therapy. Design An observational, comparative design was used to achieve the aim of the study. Setting The study was conducted at El Manial University Hosbital and El Galaa Maternity Teaching Hospital. Sample A convenience sample collected throughout one year of 30 preterm pregnant mothers under tocolytic therapy in each hospital. Tools Four tools were used: tool (1) Structured interviewing questionnaire, (2) Tocolytic monitoring, (3) Partograph, and (4) Apgar score. Result The study findings showed that 53.4% of mothers in group A as compared with 63.3% in group B received Epilate as a tocolytic agent. It shows that there were no statistically significant differences among both groups related to mean frequency of uterine contractions and mean duration of U.C, P=(0.329 and 0.189, respectively). It also shows that the side effects of tocolytic drugs in the first 24 h were dizziness, headache, tachycardia, and hypotension in group A (3.3%, 10%, 3.3%, and 6.7, respectively) as compared with (0%, 6.7%, 0%, and 10%, respectively). While only one 3.3% mother in group A had a fetus with bradycardia as a side effect of tocolytic drugs. In all, 93% and 96.7% of mothers in both groups had inhibition of uterine contractions and prolonged their pregnancy for 24 h. Conclusion Based on the results of this study, it could be concluded that tocolytic agents that were administered for 48 h reduced the uterine contractions and increased the period of pregnancy for preterm pregnant mother and improved neonatal outcomes by giving corticosteroids, but they had minimal side effects that occurred for mother and fetus in both groups. Recommendation (1) Close monitoring for all preterm pregnant women who are under tocolytic agents, (2) the newborn for women under tocolytic agents should be under close monitoring, and (3) provide education in the same strain to all nurses working in the maternity hospital with regard to care of women under tocolytic agents.

Progesterone: A Hope to Prevent Preterm Births & Reduce Perinatal Mortality

Objectives: To assess and compare the maintenance of tocolysis in preterm labor by using vaginal and intramuscular progesterone. Study design: Randomized controlled trial. Settings and study duration: Department of Obstetrics & Gynecology, Civil Hospital, Bahawalpur between 12th March 2019 and 11th September 2019 Materials & Methods: A total of 96 women ranging from 18 and 40 years of age presented with threatened preterm labour, at gestational age between 28 to 36 weeks were included. Out of total, Patients having multiple pregnancy, preterm premature rupture of membrane, medical disorders, IUGR and APH were excluded .All patients were given acute tocolytic therapy with oral nifedipine. Then they were divided in 2 groups. In the Group A, vaginal progesterone (Cyclogest 200mg) was given daily while in group B patients, a single intramuscular injection(IM) of 250 mg of 17-alpha-hydroxyprogesterone caproate (17 OHP) was given weekly. All patients in both groups were evaluated upto the delivery and efficacy was documented. Results: The mean age was 29.34 ± .4.92 years. The gestational age was from 28 to 36 weeks with mean age of 30.91 ± 1.44 weeks. Efficacy ( no preterm birth) was seen in 42 (87.50%) in group A (vaginal progesterone) and 34 (70.83%) in group B (intramuscular progesterone) with p-value of 0.044. Conclusion: The verdict of the study is that for preventing preterm birth the efficacy of vaginal progesterone is better than intramuscular. Keywords: vaginal progesterone, preterm birth, perinatal mortality, preterm labour, hydroxyprogesterone, tocolytic maintenance.

Laboratory Markers in the Prediction of Premature Birth

The problem of premature birth (PB) remains topical for the practicing obstetrician-gynecologist. The study of marker proteins indicating an increased risk of PB is one of the relevant areas of interest in modern obstetrics. The review presents data on laboratory markers of the onset of PB. Information on the importance of laboratory tests in predicting this condition is presented. A literature review on databases Scopus, Web of Science, The Cochrane Library, and Russian Science Citation Index, with a description of the experience of Russian and foreign authors on the use of biochemical indicators in determining risks of PB, is led. The significance of indicators such as fetal fibronectin, placental α-microglobulin-1, phosphorylated insulin-like growth factor-binding protein-1 and other marker proteins, as well as cytokines and hormones in the diagnosis of this condition is described. The experience of using noninvasive rapid tests for the qualitative determination of analytes from cervicovaginal artery emissions is reported. The efficacy of the joint use of medical ultrasound data combined with the determination of the level of one of the laboratory predictors, which choice is reliant on the gestational period and the presence of complications, is estimated. The use of laboratory predictors to determine the risk of PB can significantly reduce the number of unjustifiable hospitalizations as well as the institution of tocolytic and hormonal therapy. Almost all of the predictors which are described have a high negative predictive value, which may help reduce unreasonable hospitalizing.

Tocolytic Therapy Inhibiting Preterm Birth in High-Risk Populations: A Systematic Review and Meta-Analysis

This systematic review aimed to identify the benefits and possible harms of tocolytic therapy for preterm labour management in the context of pregnant women with extremely preterm birth, multiple gestations, or growth-restricted foetuses. A comprehensive search using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO Global Index Medicus databases was conducted from 10 to 15 July 2021. We included randomized controlled trials and non-randomized studies that assessed the effects of tocolysis compared with placebo or no treatment. We found 744 reports and, finally, nine studies (three randomized controlled trials and six cohort studies) pertaining to women with <28 weeks of gestation were included. No eligible studies were identified among women with a multiple pregnancy or a growth-restricted foetus. A meta-analysis of the trial data showed that there were no clear differences in perinatal death nor for a delay in birth. Non-randomized evidence showed that tocolysis delayed birth by 7 days, though there was no clear difference for preterm birth. In summary, it remains unclear whether tocolytic therapy for inhibiting preterm labour is beneficial for these subgroups of women and their newborns. Further well-designed randomized controlled trials and observational studies are needed to address the lack of evidence regarding tocolytic agents in these populations.

Use of Nitroglycerine Patch in the Management of Preterm Labor

Background: Preterm birth is the delivery of the baby before 37 completed weeks of pregnancy. The goal of tocolytic therapy is to reduce neonatal mortality and morbidity by delaying birth, allowing for corticosteroid administration and maternal transfer to the tertiary care center. This study was conducted to observe the tocolytic efficacy of GTN transdermal patches in preterm labor between 28 – 36 weeks of pregnancy. Methods: This cross-sectional study was done in Obstetrics &amp; Gynecology Department at Mufti Mehmood Memorial Hospital, Dera Ismail Khan, from July 2017 to December 2017. Non-probability consecutive samplings of 186 pregnant women with preterm labor were included in the study. Detailed history and examination, routine investigations and ultrasound were performed to confirm viability, gestational age and exclusion of multiple pregnancies, lethal fetal malformation and intrauterine death. Effectiveness of the GTN patch was considered successful if the cessation of uterine contraction occurred within 24 hours of the application of the GTN patch and persisted for 48 hours to achieve the effect of steroids. Results: Tocolytic efficacy of GTN transdermal patch in preterm labor between 28 to 36 weeks of pregnancy was 88.71%. Regarding the parity of the women, 75.8% of women had multipara (parity 2 to 5) and 24.2% had primipara. The average gestational age was 33.15±2.28 weeks. . Two to three uterine contractions per 10 minutes were observed in 75.8% of women while four uterine contractions per 10 minutes were observed in 24.19% of cases. 2cm cervical dilatation was observed in 82 women (44.09%) and 3cm was 75 women (40.32%). Practical implication: The incidence of preterm delivery can be minimized using GTN patch to reduce the uterine contractions and increase the fetal viability inside the womb. Conclusion: There is no better incubator than a mother's womb. The GTN patch appears to be a safe, non-invasive method of suppressing uterine contractions in pre-term labor and also a simple, quicker and cost-effective tocolytic agent. Keywords: Pre-term labor; Tocolytic; Transdermal patch; Uterine contractions.