AL-Qadisiya Medical Journal Vol.11 No.20 2015 Effectiveness and safety of the oxytocin antagonist( atosiban) versus beta-adrenergic agonists (salbutamol) in the treatment of preterm labor. Yasamin H. Sharif Al-Shibany* ,Saba M. Swadi Al- Thuwainy * *Obstetrics and Gynecology Department Medical college / Al-Qadisia University ,Email: [email protected] , Email: [email protected] (Received 7 / 4 /2015 , Accepted 19 / 4 / 2015) الخﻻصة : التأثيرات و اﻻعراض الجانبية ﻻستتداا عاتاا اﻻسيستيبا و عتي عاضتد ضﻻتاس لووينيتيستيي الب تر عنتا ضنتتابوت الدةيتتة قالنااانتة ضتتا عاتاا النتتالبييساضي وعتي عاضتتد ضالتي لننتتتابوت البيتتا تت الدةيتة الب تتر ة لعوج حاﻻت اليﻻسة النبكرة. الطر اة: أجر ت الاااسة ضنت لى اليﻻسة و اﻷطلا التعةين الا يانية-العراق , لةلترة ضتي هت ر يتاني الثان /4102 و لغا ة ه ر ياني الثان /4102 ( عةى 011 اضرأة حاضد قعنر 01-52 ستنة( و اسلةتي التى نت الطتياا ضتتا اعتتراض لةتتيﻻسة النبكتترة و يانتتت تتترة الانتتد ضتتي 42-52 أستتبي ( ضتتا وجتتيس انابالتتات لةتترح سنتغرق 51 ثانية قنعا ≤ أاقعة انابالات لو 01 س ياة و يا اسنا عنق الرح ضي 0الى 5 س (و 1التى 5 س (لةنياات عا نة اليﻻسة وسرعة نبض الجنيي طبيعية , س ساني النر ﻻات الى ضجنيعتيي: النجنيعة اﻷولتى و عاسعا 21 ضر ﻻتة عيلجتت قعاتاا النتالبييساضي عتي طر تق ضاةتي الااتي اليا تا و النجنيعتة الثانيتة 21 ضر ﻻة عيلجت قعااااﻻسيسيبا اليا ا ضا ضرا بة هاة اﻻنابالات و اﻻعراض الجانبية لكد عااا عةى اﻻ و الجنيي لغرض سألير اليﻻسة النبكرة و ساةيد النﻻاعلات النر ر ة و الي يات لاى النياليا الداج حا ث اليﻻسة. النتتتا: : لتت كتتي عنتتاف التتتو تت ستتألير حتتاﻻت التتيﻻسة النبكتترة لنتتاة 21 ستتاعة 22% ضااقتتد20%( و 7 أ تتا 41% ضااقتتد 54%( قتتيي النجنيعتتة اﻷولتتى و الثانيتتة عةتتى التتتيال و لكتتي اﻻعتتراض الجانبيتتة ضثتتد سنتتاا نبﻻات ةب اﻻ يانت ايثر عنا النجنيعة اﻷولى الت عيلجت قعاتاا النتالبييساضي 44% ضااقتد 1%(.لت سكتي عناف التو ات النتا: اﻹحصا:ية لةنﻻاعلات النر ر ة لاى النياليا الداج حا ث اليﻻسة قيي النجنيعتيي. اﻻستتتنتاج: استتتداا عاتتاا اﻻسيستتيبا لتتا نتتتا: ضاااقتتة ﻻستتتداا عاتتاا النتتالبييساضي تت ستتألير حتتاو التتيﻻسة النبكرة و لكي لا أعنية سر ر ة ا ﻻد ضي النالبييساضي قنب ةة اﻻعراض الجانبية لاى اﻻ و الجنيي و ننصت قاستتتدااضا يتتأو لتت عوجتت لاتتاﻻت التتيﻻسة النبكتترة لتاةيتتد النﻻتتاعلات و ننتتب الي يتتات لتتاى الدتتاج حتتا ث اليﻻسة. Abstract: Background and Objectives: preterm labor complicates 5-10% of pregnancies and is a leading cause of neonatal morbidity and mortality worldwide and 70-80% of perinatal deaths occur in preterm infants. The aim of this study is to compare the effectiveness, safety and adverse effects of the oxytocin antagonist medication(atosiban) with those of beta-adrenergic agonist (salbutamol) in the treatment of patients with preterm labor. Patients and Methods: one hundred pregnant women with preterm labor were enrolled in this study from the period of( January 2014 – January 2015) at Al- Diwaniya Maternity and Pediatrics Teaching Hospital-Iraq with a gestational age of 24-34 weeks, they were randomly assigned to receive tocolytics either salbutamol (n=50) or atosiban (n=50).Salbutamol was given by(intravenous infusion 10-50 microgram)for up to 48 hour. Atosiban was given by (intravenous bolus dose of 6.75 mg then 300microgram/minute for 3 hour and 100microgram/minute for up to 48hour). Retreatment with the study drugs or alternative tocolytic agents was allowed. Main outcome measures included were tocolytic effectiveness, which was assessed in terms of number of women undelivered after 48hour and 7 days. Tocolytic safety was assessed in terms of maternal and fetal side effects and neonatal morbidity. Results: there were no significant differences between the salbutamol and the atosiban group in prolongation of pregnancy for 48 hour (44% versus 671 AL-Qadisiya Medical Journal Vol.11 No.20 2015 46%;p=0841)and 7 days(20% versus 32%;p=0.171) ,respectively. Maternal adverse events , including tachycardia occurred more frequently in the salbutamol group(22% versus 8%;p=0.050).Neonatal outcomes and complications were comparable between the two study groups(42% versus 32%;p=0.30). Conclusions: the oxytocin antagonist (atosiban) was as effective as beta- agonist(salbutamol) in delaying threatened preterm birth , and found to be better tolerated by both the mother and fetus than salbutamol , with a comparable neonatal safety profil.This study supports the clinical use of atosiban as a first line tocolytic in the treatment of preterm labor. Key words: preterm labor ,tocolytics, salbutamol , atosiban ,pregnancy outcome ,neonatal outcome. Introduction: agents act through a variety of mechanisms Preterm labor refers to the onset of uterine to decrease the availability of intracellular contractions of sufficient strength and calcium ions leading to inhibition of actin- frequency to effect progressive dilatation and myosin interaction(7).Their effectiveness in effacement of the cervix with a gestational suppression of preterm labor has been age between 24 weeks and less than 37 controversial and many of these agents are weeks of gestation , before 24 weeks the associated with serious side effects to both correct term is miscarriage rather than mother and her fetus(7).However, tocolytics preterm labor (1).Preterm labor complicates should be considered if the few days gained 5-10% of pregnancies and is a leading cause would be put to good use such as completing of neonatal morbidity and mortality a course of corticosteroids which greatly worldwide ,and 70-80% of perinatal deaths accelerate fetal lung maturity and reduce the occur in preterm infants (2).It is a major risk of respiratory distress syndrome and its public health problem in terms of loss of life sequelae as well as intraventricular from respiratory distress syndrome(RDS) and hemorrhage ,but it takes one to two days to intraventricular hemorrhage(IVH) ,long term work ,and also give time for in-utero transfer disability (cerebral palsy ,blindness ,deafness of the fetus to a tertiary center equipped for ,chronic lung disease and health care cost) high risk pregnancies with neonatal intensive both in developing and developed care unit(8). world(1,2).Preterm labor precedes about 50% Beta-adrenergic agonist drugs such as of preterm birth , but approximately 30% of salbutamol are the commonly used tocolytic preterm labor spontaneously resolves, less drugs (9).It acts through c-GMP to inhibit than 10% of women presenting with preterm uterine contractions by inhibiting the entry of contractions give birth within seven days and calcium ions into the smooth muscle of the 50% of patients hospitalized for preterm uterus and produce uterine relaxation in most labor give birth at term (3,4).For patients instance, but the onset is variable and with true preterm labor ,tocolytic therapy depends on the dosage. (9).Salbutamol is often abolishes contractions temporarily , but known to cross the placental barrier as does not remove the underlying stimulus that evidenced by the increase in fetal heart rate initiated the process of parturitions or reverse (10). It has been shown that these agents parturition changes in the uterus , and the net postpone the delivery for 24,48hours and result is that a single course of tocolytics may even 7 days, however ,such a delay has not delay delivery by hours or days ,but not been associated with a significant reduction weeks or months(5). in either perinatal mortality or Tocolytics (also called anticontraction morbidity(9,10).They are associated with medications ) are pharmacological agents serious maternal side effects such pulmonary used to suppress premature labor, and they edema ,myocardial ischemia, arrhythmia are given when delivery would result in ,chest pain and death(9).Although premature birth(6).These pharmacological hyperglycemia and hypokalemia are 677 AL-Qadisiya Medical Journal Vol.11 No.20 2015 recognized complications ,so the drug used 34 weeks of pregnancy (determined by the cautiously in patients with diabetes mellitus date of the last menstrual period when known or who require surgery(9,10). or by early ultrasound)with preterm labor Atosiban is a new class of tocolytics, it is an which is defined as the persistence of ≥4 oxytocin antagonist licensed for the symptomatic uterine contractions of at least management of preterm labor (11).Oxytocin 30 second period during the 60-minutes after is believed to initiate uterine contractility by admission and despite bed rest, in the increasing the intracellular calcium presence of cervical dilatation between (0 concentration of myometrium cells through a and 3 cm ) for primigravida and between( 1 direct effect on membrane bound oxytocin and 3 cm) for multigravida , with cervical receptors. Oxytocin further stimulates uterine effacement of more than 50% with a normal contractility and initiates cervical ripening by fetal heart rate. Exclusion criteria: gestational stimulating the release of prostaglandins in age below 24 weeks or over 34 weeks the decidual and fetal membranes ,cervical dilatation greater than 3 cm (12).Atosiban is a synthetic peptide which is ,premature rupture of membranes a competitive antagonist of human oxytocin ,intrauterine growth retardation abnormal at receptor level in the uterus and potentially fetal heart rate, antepartum uterine bleeding, also in the decidual and fetal membranes and eclampsia and sever pre-eclampsia requiring administration result in a dose dependent delivery, intrauterine fetal death suspected inhibition of uterine contractility with a intrauterine infection multiple pregnancy reduction in oxytocin mediated prostaglandin ,fetal anomaly, maternal diabetes mellitus, release (13).As an antagonist