Isoxuprine VS Terbutaline in Pre-term Labor Tocolysis

7/26/2019 Isoxuprine VS Terbutaline in Pre-term Labor Tocolysis

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The Tocolytic Efficacy of Terbutaline versus Isoxsuprine Hydrochloride

among Women presenting with uncomplicated Pre-term Labor

from 2006 to 2011

in Cebu Doctors' University Hospital Department of Obstetrics & Gynecology

(a retrospective therapeutic cohort)

by

Sas Serafica-Hernandez, MD

Department of Obstetrics & Gynecology

Cebu Doctors' University Hospital

Cebu City


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INTRODUCTION

Background/Review of Related Literature

Prematurity, together with its complications, remains to be the most common

underlying cause of neonatal death. In the U.S., the rate of preterm births has

increased by one third over the last 25 years; 9.4 percent in 1981; 10.6 percent in

1990; 12.7 percent in 2005; and, 12.8 percent in 2006 1. Like in the U.S., the preterm

birth rate of our country has increased, with the rate being 14.75 percent during the

last 4 years2

. In the Philippine General Hospital, the average preterm birth rate during

the last 5 years is 21.52 percent and the annual estimated proportion of death

secondary to prematurity is at 37 percent (2,3). Although preterm delivery is defined as

birth before 37 completed weeks, it is babies born before 34 weeks who experience

most mortality and morbidity. Acute morbidities associated with preterm birth include

intraventricular hemorrhage, necrotizing enterocolitis, respiratory distress syndrome,

and patent ductus arteriosus 4. Because of these complications, preterm infants are

mostly admitted at the neonatal intensive care units (NICU) and those infants who do

survive often spend many weeks or months in the hospital. These incur considerable

expenses for the parents, adding further to the stress and the emotional burden,

moreover if the infants survival is accompanied by moderate or severe

neurodevelopmental impairment.

Preterm birth is the result of spontaneous preterm labor in approximately 45-50

percent of cases, follows preterm premature rupture of membranes in 30%, and is

medically indicated (delivery for maternal or fetal complications) in the remaining 15-


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20% (4,5). To date, the etiologies of preterm birth are not completely understood. Our

inadequate knowledge about premature parturition has hampered the ability to predict

its onset, limiting our options to devise improved pharmacologic strategies to control

uterine contractility when indicated.

Tocolytic drugs are the cornerstone in the management of preterm labor. They

are intended to stop uterine contractions during an episode of preterm labor (acute

tocolysis) or maintain uterine quiescence after an acute episode has abated

(maintenance tocolysis). These drugs are used to prolong pregnancy in the hope of

avoiding or ameliorating the sequelae of prematurity. Delaying delivery can allow time

for safe transfer of the mother, enabling the premature infant to be delivered in an

obstetric unit equipped in handling high-risk pregnancies and with supportive neonatal

intensive care facilities. Tocolysis may also buy time long enough for corticosteroid to

take their beneficial effect in enhancing fetal lung maturity possibly decreasing the

chances of severe neonatal complications. At early gestational ages, even a modest 48

to 72 hour prolongation can be greatly beneficial to the fetus and improve neonatal

outcomes. Because of this,attention has centered on efforts to find safe and effective

tocolytic agents. The drugs most commonly used in the United States for the

suppression of preterm labor are the -mimetic agents ritodrine and terbutaline, as well

as magnesium sulfate. Each of these agents have, in clinical trials, been found to be

more effective than either ethanol (7-10) or placebo (9,11,12), and results have been

superior to those in a control group (13-16).


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Beta-adrenergic agonists include terbutaline, ritodrine, salbutamol and

isoxsuprine hydrochloride. In our institution, the two most commonly used beta

agonists are Isoxsuprine hydrochloride and Terbutaline Sulfate. All are adrenaline-like

drugs that cause beta-2 adrenergic relaxation of the uterus, although all have some

beta-1 adrenergic side effect. The first beta-mimetic agents proposed for treatment of

preterm contractions was isoxsuprine in 1961. Its clinical use was subsequently limited

due to its non-selective beta-adrenergic side effects. Terbutaline, on the other hand, is

a beta-2 selective beta-adrenergic agonist also used for the management of premature

uterine contractions. Presently, only ritrodrine for intravenous administration is

approved by the United States FDA for use in pregnancy as a tocolytic.

The study of Giorgino et al revealed a beneficial effect of isoxsuprine in

prolonging pregnancy in 54.5 percent of women at risk of abortion and in 82.3 percent

of women at risk of premature delivery. Combination of individual and general data

revealed a beneficial effect of isoxsuprine in 77.3 percent of cases at risk of abortion

and 89 percent for risk of premature delivery. These findings provide preliminary

evidence in favor of the effectiveness of isoxsuprine in prolonging pregnancy in women

at risk of abortion or premature delivery 17.

There is a large body of literature on the pharmacological effects of beta-mimetic

drugs, but most of it is based on observational study and very little information is

derived from trials documenting their efficacy and safety. Because of this, the off-label

use of drugs is fairly common among physicians since scientific studies and clinical trials

support such use. Therefore, this study took a 5 year systemic review of patients


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records for supportive evidence of the efficacy of the two most commonly used tocolytic

agents in Cebu Doctors University Hospital, Isoxsuprine hydrochloride and Terbutaline

sulfate, and evaluated the perinatal outcomes in these women. This study intended to

prove the superiority of one drug over the other in delaying or prolonging preterm

labor.


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OBJECTIVES

General Objective:

The primary endpoint of this study was to compare the efficacy of Isoxsuprine

Hydrochloride versus Terbutaline Sulfate in pregnancy prolongation among women with

early preterm labor admitted at Cebu Doctors University Hospital (CDUH).

Specific Objectives: this study:

1. Determined the number of patients in early preterm labor at Cebu Doctors

University Hospital

2. Determined the mean duration of tocolysis quantified in hours needed to delay

preterm labor on both Isoxsuprine and Terbutaline group.

3. Determined the delay in labor, quantified in days, from the time tocolysis was

started up to the time of delivery of the fetus on both Terbutaline and

Isoxsuprine group.

4. Compared the duration of tocolysis and days interval from the time of treatment

to the time of delivery between the Isoxsuprine group and the Terbutaline group.

5. Compared the percentage of term or preterm neonates on each study arm.

6. Compared the neonatal outcome in terms of Apgar score, Ballard score and

birthweight between the two groups.

Scope and Limitations:

The study compiled information of all patients admitted at Cebu Doctors

University Hospital from January 2006 to August 2011, diagnosed with premature


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uterine contractions or those who fit the criteria of early preterm labor (age of gestation

from 28 to 33 completed weeks). Pregnant women with age of gestation at 34 to 36

weeks or those below 28 weeks were not included in the study. The research subjects

were given either parenteral Isoxsuprine hydrochloride or Terbutaline as sole agent for

acute tocolysis. Patient records were followed from the point of treatment until the time

of delivery. Patients who have pre-existing medical conditions or conditions arising from

pregnancy such as hypertension, diabetes mellitus, cardiac or renal problems were also

excluded. Pregnant women with multiple gestations, fetuses with congenital anomalies

or those with abnormal obstetric conditions were also excluded from the study.

Pregnant women with premature uterine contractions who were given tocolytic agents

other than the above mentioned tocolytic drugs were not included in the study as well

as those who received combination tocolytic agents.


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Methodology

Research Design

This study was aRetrospective Cohort Study

Research Locale

The study was conducted at Cebu Doctors University Hospital from January 01,

2006 to August 31, 2011.

Study Population

Inclusion criteria

Pregnant women who were admitted for premature uterine contractions or

who were experiencing preterm labor with age of gestation at 28 weeks to 33

completed weeks were included in the study. The study subjects fulfilled the American

College of Obstetrics and Gynecology (ACOG) criteria of preterm labor: 1. Contractions

of four in 20 minutes or eight in 60 minutes with progressive change in the cervix, 2.

Cervical dilatation greater than 1 cm, 3. Cervical effacement of 80% or greater. The

subjects were tocolysed with either parenteral Isoxsuprine hydrochloride or Terbutaline

according to the accepted practice guidelines and did not receive any tocolytic agents at

or before their admission.

Exclusion criteria: This study excluded:

1. Women with multiple gestation

2. The presence of abnormal obstetric conditions, such as premature rupture of

membranes, intrauterine growth retardation, congenital genetic diseases,

placenta previa, placental abruption, or prolapse of umbilical cord.


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3. History of fever within 1 week prior to admission

4. Patients who received tocolytic agents other than Isoxuprine hydrochloride

and Terbutaline Sulfate.

5. Pregnant women with pregnancy induced or pre-existing medical conditions

such as hypertensive disorders, diabetes mellitus, cardiac and renal problems.

6. Patients with incomplete data of the interval from the start of treatment to

the end of tocolysis, time of delivery and the outcome of the neonates.


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Data Collection Procedure

Records of all patients that qualified the disease indexes; preterm delivery and

premature uterine contractions were assessed individually from the medical records

computer database. Logbooks at the Neonatal Intensive Care Unit were also carefully

reviewed. All pregnant women admitted at Cebu Doctors University Hospital from

January 2006 to August 2011 who were diagnosed with premature uterine contractions

with age of gestation from 28 to 33 completed weeks were included in the study. We

extracted details from the intervention such as choices of tocolytics, aim, dosage, route,

duration and routine use of corticosteroids. Data extracted from the qualified pregnant

patients (based on the inclusion-exclusion criteria) included maternal age, parity,

gestational age on admission and at the time of delivery, cervical dilation and

effacement on admission. Neonatal outcome were analyzed using Apgar score at 1 and

5 minutes, ballard score and birthweight.

Out of the total 451 preterm deliveries and premature uterine contraction

admissions (Figure 1), 67 subjects qualified for the study. 19 patients were given

Terbutaline as their sole tocolytic agent whereas 48 patients were given Isoxsuprine

hydrochloride drip. The mean duration of tocolysis needed to delay preterm labor and

the interval of days from the time the treatment was started to the time of delivery

were recorded and analyzed for results.


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Numerical data were summarized using mean standard deviation. In

comparing between the Isoxsuprine and Terbutaline groups, the Unpaired t test was

used for numerical data while Mann-Whitney U test was used for non-parametrical

continuous or non-normal data. An associated p-value less than 0.05 were considered

significant. Microsoft Excel and various open ware statistical tools were used to process

and analyse data.

Figure 1 Study selection process


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Results

Sixty-nine patients qualified for our study. The Isoxsuprine and Terbutaline

groups are essentially the same or statistically equivalent in relation to maternal age,

parity, age of gestation on admission and at delivery. It was found out that in using the

tocolytic treatment on the mother; on average, Isoxsuprine (Figure 2) was used for

significantly longer time compared to Terbutaline (Figure 3) (30.75 hours versus 21.35

hours). However, Isoxsuprine (Figure 4) timed a shorter average duration of labor delay

Isoxsuprine Hcl Terbutaline AssociatedProfile

n = 47 n = 20 p-valueAge * 29.06 4.40 29.80 5.19 0.5825'

Gravida ** 2 2 0.3576''

Parity ** 1 1 0.6892''

T ** 0 1 0.4902''

P ** 0 0 0.9283''

A ** 0 0 0.1676''

L ** 1 1 0.7872''

AOG on Admission (Days) * 225.57 10.80 228.50 10.47 0.3064'

AOG at Delivery (Days) * 257.32 14.69 256.45 18.78 0.8550'

Hours of Tocolysis * 30.81 16.19 21.35 10.92 0.7725'

Total Delay Time (Hrs) * 720.66 469.98 812.65 547.73 0.5170'

Birthweight (grams) * 2607.74 467.04 2520.55 560.22 0.5454'

Apgar Score 1 min. * 8.70 0.81 8.00 1.52 0.0631'

Apgar Score 5 min. * 9.85 0.51 9.55 0.83 0.1427'

Ballard score (weeks) * 36.98 1.69 36.65 2.35 0.5750'

Term/Preterm ***

Term 28 (60%) 10 (50%)

Preterm 19 (40%) 10 (50%)

0.5916

* mean SD 'Unpaired t test

** median ''Mann-Whitney test*** Frequency (%)


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(737.77 hours) than Terbutaline (812.65 hours) with a mean of 74.87 hours in favor of

Terbutaline. This time difference in delay of labor was not statistically significant. The

mean Apgar score at 1 minute proved to show any valid statistical detectable difference

in favor of Isoxsuprine (8.7 points, versus Terbutaline's 8 points). Using the Equal-

variance t-Test, it would seem that Isoxsuprine registers a better 5-minute Apgar score

than Terbutaline. However, the t-Test is not the ideal statistical test for the data, since

the data is not normally distributed, and since variances between 5-min APGAR scores

for the Isoxsuprine group versus the Terbutaline group are not equal. Comparison of

Ballard score, birthweight and the percentage of term and preterm infant on each group

has shown no significant difference.

Two-Sample T-Test Power Analysis

Table 2 Numeric Results for Two-Sample T-Test

Power N1 N2 Ratio Alpha Beta Mean1 Mean2 S1 S2

0.95003 1213 1213 1.000 0.05000 0.04997 737.8 812.7 472.3 547.70.90011 981 981 1.000 0.05000 0.09989 737.8 812.7 472.3 547.7

0.85004 838 838 1.000 0.05000 0.14996 737.8 812.7 472.3 547.7

0.80029 733 733 1.000 0.05000 0.19971 737.8 812.7 472.3 547.7

To attain a study power of at least 80%, a sample size of at least 1,466 should be met.

Null Hypothesis: Mean1 = Mean2.

Alternative Hypothesis: Mean1 Mean2 (2-tailed, which doesnt assume any drug to be better than the

other.)


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Discussion

A healthy body of literature is available concerning the efficacy and safety of

most, if not all tocolytic agents. However, deciding which tocolytic agent to use as the

first-line drug is a difficult decision to make. Despite the wealth of information, no sole

tocolytic agent is considered gold standard for treatment of premature labor. Hence,

the need for continuing research on this area remains paramount.

This study primarily compared Isoxsuprine hydrochloride to Terbutaline Sulfate in

delaying early preterm labor among pregnant women presenting with premature

uterine contractions. The Isoxsuprine and Terbutaline groups are essentially the same

or statistically equivalent in relation to maternal age, parity, age of gestation on

admission and at delivery. However, it was found in the study that parenteral

Isoxsuprine hydrochloride was given at considerably longer periods of time compared to

parenteral Terbutaline during tocolysis. Isoxsuprine hydrochloride took approximately 8

to 9 hours more, as opposed to Terbutaline, in controlling or ceasing premature uterine

contractions before maintenance tocolysis was initiated. The Isoxsuprine group also

timed a shorter duration of pregnancy prolongation from the point of tocolysis to the

point of delivery, averaging at 31 days. Conversely, Terbutaline on average has delayed

pregnancy to approximately 3 days (812 hours or 33 days) more than the Isoxsuprine

group. This time difference in pregnancy prolongation did not register as significant

statistically since the analysis showed that the study needs more data to detect such a

difference in labor delay.


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In reviewing the results, Terbutaline would seem to be the better choice of drug

for acute tocolysis since its effect is immediate as evidenced by the shorter hours of

tocolysis needed to suppress uterine contractions. Theoretically, this shorter time period

of exposure to Terbutaline would also decrease the discomfort and untoward side

effects (hypokalemia and pulmonary edema) caused by the beta mimetic class of drugs.

The 3 day advantage of Terbutaline in prolonging pregnancy as compared to

Isoxsuprine will greatly benefit the fetus by affording more time for organ maturation,

presumably decreasing the incidence of complications of prematurity. Albeit the findings

were deemed to be non-significant statistically, these data might still be of clinical use

in considering the choice of tocolytic agent. A study done by Kosasa et al compared 99

women who were assigned to either a terbutaline or ritodrine treatment for preterm

labor. Delivery was delayed 25.8 days in terbutaline subjects and 13.0 days in ritodrine

subjects. Babies of terbutaline subjects weighed more than those of ritodrine subjects;

more women (60%) achieved 36 weeks gestation on terbutaline than on ritodrine

(39%) 18. The findings of this study also reflected the study done by Caritis et al. The

study compared women experiencing preterm labor who were randomly assigned to

receive either terbutaline or ethanol. Terbutaline was found to work better than ethanol

in preventing further cervical dilation during the first 36 hours after treatment was

started. Pregnancy was prolonged longer in the terbutaline group (15 plus or minus 4

days) than in the ethanol group (10 plus or minus 3 days) 19.

Recently, the role of terbutaline in the treatment and prevention of preterm

labor has been questioned by the FDA; however, numerous studies still demonstrate


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the drugs efficacy and safety particularly in prolonging pregnancy. Practicing physicians

should not be restricted in the use of terbutaline for acute tocolysis since it continues to

be one of the remaining few therapeutic options in the battle against preterm birth.

In assessing neonatal outcome, the Isoxsuprine group had better Apgar score

than the terbutaline group, although, this did not register as statistically significant. The

observed difference in birthweight of 100.85 grams in favour of Isoxsuprine also did not

detect statistical significance. Nonetheless, an increase in birthweight as a possible

reflection of pregnancy prolongation can very much benefit the fetus clinically. No

difference was found out in terms of the percentage of term or preterm infants on each

treatment group.

Like most retrospective study, the collection of data in this study was not

standardized and uniform which could lead to biases. The researcher had no control

over the data extracted leading to the inclusion of less high-quality subjects. Another

limitation to the study was the sample size and effect size, which was not large enough

to adequately power the study. In the two-sample t-test power analysis (Table 2), to

attain a power of at least 80 percent, a sample size of 1,466 subjects must be achieved.

A longer period of time for review and a large number of subjects might yield results

more reflective of the difference in the efficacy for both tocolytic agents. Despite these

limitations, the result of this study is valuable and can contribute immensely to the pool

of information in the search for the ideal tocolytic that can finally put an end to

premature delivery.


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Conclusion

Isoxsuprine hydrochloride took longer periods of time, compared to Terbutaline

Sulfate in controlling or suppressing uterine contractions in women experiencing

preterm labor. Furthermore, Terbutaline had an approximately three day advantage

over Isoxsuprine in pregnancy prolongation. Although these findings were statistically

non-significant, this can guide clinicians in choosing their first-line tocolytic drug.

Moreover, this three day advantage of terbutaline over Isoxsuprine can afford more

time for immature fetal organs to further develop avoiding severe neonatal

complications and possibly, even death.

To prevent preterm labor, one should not only depend on the application of

uterine contraction inhibitors, but understand the etiology, risk factors, and the

pathologic process, so that one can predict, diagnose and take direct and effective

measures.


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Recommendations

Additional research is recommended on the pharmacologic management of

preterm labor. Despite the wealth of clinical literature on this area, the first line drugs

that arrests preterm labor remains to be discovered. The researcher recommends

including more test subjects which can be achieved by increasing the time period of

review or having multi-hospital collaboration. As the number of test subject increase,

the more significant the observation becomes thereby reducing the margin of error.

Future researchers can also take on a randomized prospective approach of this topic. In

this manner, the collection of data would be standardized thereby reducing confounding

bias.

Future researchers may also focus on the maternal side effect of tocolytic

agents. The researcher recommends use of survival analyses to present continuous

birth outcomes by gestational age at enrolment. Doing so helps to clarify whether (and

if so, to what extent) even a small delay in birth at a particular gestational age might be

clinically significant.

Lastly, the researcher recommends that the hospitals medical record section

accurately classify premature uterine contractions under the International Classification

of Disease code of early or threatened labor for ease of data retrieval.


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Acknowledgements

I would like to extend her sincerest gratitude to the following persons who made the

completion of this research possible: Dr. Henry David N. Dimaano, current chair of the

Committee for Research Development of the Central Visayas Consortium for Health

Research & Development (DOST-7), for serving as main technical contributor on the

aspects of research design, data analysis and interpretation -- and whose guidance and

support from the initial to the final level enabled me to have an understanding of

medical research; Dr. Amethyst R. Ypil, for the conceptual support and for making me

realize the pressing need for further research in the area concerning preterm labor; Dr.

Ma. Victoria Larrazabal, our department chairperson, for the much needed support and

encouragement in every endeavor we take; Dr. Josefina Ebao-Zabate, our training

officer, for her valuable advises and teachings; Dr. Charisse Sharon E. Tan, for sharing

her vast knowledge and expertise in the field of medical research; Ms. Iris Petralba, for

her patience and guidance in dealing with statistical issues involving this study; the staff

of the Medical Records Section of Cebu Doctors University Hospital, for lending the

much helping hand in the data gathering process. Lastly, to Dr. Joseph Lester

Hernandez, for the much needed love and support.


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References:

1. Iams, JD, R Romero, et.al. Preterm labor and birth. In: Creasy and Resniks

Maternal Fetal Medicine. 6th Edition. 2009:545-582.

2. POGS Committee on Nationwide Statistics 1995-2008.

3. Philippine General Hospital Perinatal Statistics 2005-2009

4.AIger LS, Crenshaw MC. Preterm labor and delivery of the preterm infant. In:

Turnbill, Chamberlain, eds, Obstetrics. London: Churchill Livingstone, 1990; pp

749-770.

5. Haas DM. Preterm birth in clinical evidence. London: BMJ Publishing Group;

2006.

6. Pennell CE, Jacobsson B, Williams SM, Buus RM, Muglia LJ, Dolan SM, et al., et

al. Genetic epidemiologic studies of preterm birth: guidelines for research. Am J

Obstet Gynecol 2007; 196: 107-18 doi: 10.1016/j.ajog.2006.03.109 pmid:

17306646.

7. Steer CM, Petrie RH. A comparison of magnesium sulfate and alcohol for the

prevention of premature birth. Am J Obstet Gynecol 1977;129:1.

8. Lauersen NH, Merkatz IR, Tejani Net al. Inhibition of premature labor: A

multicenter comparison of ritodrine and ethanol. Am J Obstet Gynecol

1977;127:837.

9. Merkatz IR, Peter JB, Barden TP. Ritodrine hydrochloride: A beta-mimetic agent

for use in preterm labor. II. Evidence of efficacy. Obstet Gynecol 1980;56:7.

10.Cariris SN, Carson D, Greebon D et al. A comparison of terbutaline and ethanol in

the treatment of preterm labor. Am J Obstet Gynecol 1982;142:183.

11.Wesselius-DeCasparis A, Thiery M, Yo Le Sian A et al. Results of double-blind,

multicenter study with ritodrine in premature labor. Br Med J 1971;3:144.

12. Ingemarsson I. Effect of terbutaline on premature labor. Am J Obstet Gynecol

1976; 125:520.

13.Wallace RL, Caldwell DL, Ausbacher R et al. Inhibition of premature labor by

terbutaline. Obstet Gynecol 1978;51:387.


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14.Spasso KR, Harbert GM, Thiagarajah S. The use of magnesium sulfate as the

primary tocolytic agent to prevent premature delivery. Am J Obstet Gynecol

1982;142:840.

15.Stubblefield PG, Heyl PS. Treatment of premature labor with subcutaneous

terbutaline. Obstet Gynecol 1982;59:457.

16.Elliott JP. Magnesium sulfate as a tocolytic agent. Am J Obstet Gynecol

1983;147:277.

17.Giorgino FL, Egan CG. Use of isoxsuprine hydrochloride as a tocolytic agent in

the treatment of preterm labour: a systematic review of previous literature.

http://www.ncbi.nlm.nih.gov/m/pubmed/20712130/

18.Kosasa, Thomas et al.,"Ritodrine and Terbutaline Compared for the Treatmentof Preterm Labor," Acta Obsetrics Gynecology Scandinavia, 1985, Vol. 64, pp.

421-425.

19.Caritis, Steve et al., "A Comparison of Terbutaline and Ethanol in the Treatment

of Preterm Labor," American Journal of Obstetrics and Gynecology, 1982, Vol.

183, pp. 183-190.


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Definition of Terms

1. Preterm Labor- defined as regular contractions associated with cervical change

before the completion of 37 weeks gestation.

2. Preterm Birth- birth before 259 days or 37weeks from the first day of the last

normal menstrual period or 245 days after conception. The lower limit for

considering a birth to be preterm varies from 24 weeks or earlier in the United

States to 23 to 24 weeks in Europe.

3. Preterm- refers to fetus, a pregnancy or a neonate, that is less than 38 weeks

(or 37 weeks gestation based on WHO definition) and more than 20 weeks age

of gestation.

4. Neonate- a newborn infant, especially one less than four weeks old.

5. Tocolysis- inhibition of uterine contractions.

6. Tocolytic agent- A medication that can inhibit labor, slow down or halt the

contractions of the uterus. Tocolytic agents are widely used today to treat

premature labor and permit pregnancy to proceed and so let the fetus gain in

size and maturity before being born.

7. Beta-Sympathomimetic agents- commonly used oral and parenteral tocolytic that

acts on beta-2 receptors located in the uterus, bronchioles, and blood vessels.

Their stimulation leads to uterine relaxation, bronchodilation, and vasodilation.


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8. Isoxsuprine hydrochloride- a sympathetic amine with potent inhibitory effects on

vascular, uterine, and other smooth muscles. Used as a vasodilator in various

vascular diseases and as a uterine relaxant.

9. Terbutaline- a beta2-adrenergic receptor agonist used as a bronchodilator; it has

also been used as a tocolytic agent.

10.Beta-1 adrenergic receptor- The beta-1 adrenergic receptor (1adrenoreceptor),

also known as ADRB1, is a beta-adrenergic receptor, and also denotes the

human gene encoding it. It is a G-protein coupled receptor associated with the

Gs heterotrimeric G-protein which increases cardiac output, release renin from

juxtaglomerular cells and increases lipolysis in adipose tissue.

11.Beta-2 adrenergic receptor- The beta-2 adrenergic receptor (2adrenoreceptor),

also known as ADRB2, is a beta-adrenergic receptor, and also denotes the

human gene encoding it. It causes smooth muscle relaxation of the uterus and

causes minor degree increase in cardiac output

12. APGAR score a scoring system clinically used to identify those neonates who

require resuscitation as well as to assess effectiveness of any resuscitative

measures.

13.Ballard score- a system of newborn assessment of gestational maturation. It

provides a valid estimation of postnatal maturation for preterm infants with

gestational ages greater than 20 weeks and covers a dozen categories, including

posture, arm recoil, popliteal angle, skin, plantar surface, and genitals.


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14.Early preterm labor- labor occurring at 28 weeks to 33 completed weeks of

gestation.

15.Late preterm labor- labor commencing at 34 weeks to 36 completed weeks age

of gestation.

16.Glucocorticoids- adrenocortical steroid hormones that affect glycogenesis in the

liver. They are antiinflammatory, are active in protection against stress, and

carbohydrate and protein metabolism. They are commonly used as adjunctive

therapy in preterm labor to accelerate fetal lung maturity.

17.ACOG- American Congress of Obstetricians and Gynecologists, formerly the

American College of Obstetricians and Gynecologists, is a professional association

of medical doctors specializing in obstetrics and gynecology in the United States.

Founded in 1951 in Chicago, Illinois, ACOG has over 55,000 members and is the

nation's leading group of professionals providing health care for women. Now

based in Washington, DC, it is a private, voluntary, non-profit membership

organization.


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Table I

Data Analysis Table

Isoxsuprine Hcl Terbutaline AssociatedProfile

n = 47 n = 20 p-value

Age * 29.06 4.40 29.80 5.19 0.5825'

Gravida ** 2 2 0.3576''

Parity ** 1 1 0.6892''

T ** 0 1 0.4902''

P ** 0 0 0.9283''

A ** 0 0 0.1676''

L ** 1 1 0.7872''

AOG on Admission (Days) * 225.57 10.80 228.50 10.47 0.3064'AOG at Delivery (Days) * 257.32 14.69 256.45 18.78 0.8550'

Hours of Tocolysis * 30.81 16.19 21.35 10.92 0.0075'

Total Delay Time (Hrs) * 720.66 469.98 812.65 547.73 0.5170'

Birthweight (grams) * 2607.74 467.04 2520.55 560.22 0.5454'

Apgar Score 1 min. * 8.70 0.81 8.00 1.52 0.0631'

Apgar Score 5 min. * 9.85 0.51 9.55 0.83 0.1427'

Ballard score (weeks) * 36.98 1.69 36.65 2.35 0.5750'

Term/Preterm ***

Term 28 (60%) 10 (50%)

Preterm 19 (40%) 10 (50%)

0.5916

* mean SD 'Unpaired t test

** median ''Mann-Whitney test

*** Frequency (%)


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Table 2

Two-Sample T-Test Power Analysis

Numeric Results for Two-Sample T-Test Allocation

Power N1 N2 Ratio Alpha Beta Mean1 Mean2 S1 S2

0.95003 1213 1213 1.000 0.05000 0.04997 737.8 812.7 472.3 547.7

0.90011 981 981 1.000 0.05000 0.09989 737.8 812.7 472.3 547.7

0.85004 838 838 1.000 0.05000 0.14996 737.8 812.7 472.3 547.7

0.80029 733 733 1.000 0.05000 0.19971 737.8 812.7 472.3 547.7

To attain a study power of at least 80%, you need a sample size of at least 1,466.

Null Hypothesis: Mean1 = Mean2.

Alternative Hypothesis: Mean1 Mean2 (2-tailed, which doesnt assume any drug to be better than the other.)


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Appendix A

Figure 2

Days of Treatment Interval

0.00

20.00

40.00

60.00

80.00

G1 G2

Groups

DaysofTre

atmentInterval

Group 1- IsoxsuprineGroup 2- Terbutaline


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Appendix B

Figure 3

Tocolysis Duration in hours

0.00

20.00

40.00

60.00

80.00

G1 G2

Groups

TocolysisDuratio

ninhours

Group 1- Isoxsuprine

Group 2- Terbutaline


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Appendix C

Figure 4

Delay of Labor in hours

0.00

500.00

1000.00

1500.00

2000.00

G1 G2

Groups

DelayofLaborinhours

Group 1- IsoxsuprineGroup 2- Terbutaline

Documents

Isoxuprine VS Terbutaline in Pre-term Labor Tocolysis