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

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 years 2. 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 152

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
superior to those in a control group

(7-10)

(13-16)

or placebo

(9,11,12)

, and results have been

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

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.

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

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.

Methodology
Research Design
This study was a Retrospective 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.

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.

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.

10

Figure 1 Study selection process

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.

11

Results

Profile
Age *
Gravida **

Isoxsuprine Hcl

Terbutaline

Associated

n = 47

n = 20

p-value

29.06 4.40

29.80 5.19

0.5825'

0.3576''

Parity **

0.6892''

T **

0.4902''

P **

0.9283''

A **

0.1676''

0.7872''

AOG on Admission (Days) *

L **

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

28 (60%)

10 (50%)

Preterm

19 (40%)

10 (50%)

Term/Preterm ***
0.5916

* mean SD

'Unpaired t test

** median

''Mann-Whitney test

*** Frequency (%)

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

12

(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 Equalvariance 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
0.95003 1213
1213
1.000
0.05000
0.90011 981
981
1.000
0.05000
0.85004 838
838
1.000
0.05000
0.80029 733
733
1.000
0.05000
To attain a study power of at least 80%,

Beta
Mean1
Mean2
S1
S2
0.04997 737.8
812.7
472.3
547.7
0.09989 737.8
812.7
472.3
547.7
0.14996 737.8
812.7
472.3
547.7
0.19971 737.8
812.7
472.3
547.7
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.)

13

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.

14

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

15

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.

16

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.

17

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.

18

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.

19

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.
20

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 Treatment
of 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.

21

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.

22

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 (1 adrenoreceptor),
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 (2 adrenoreceptor),
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.

23

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.

24

Table I
Data Analysis Table

Profile

Isoxsuprine Hcl

Terbutaline

Associated

n = 47

n = 20

p-value

29.06 4.40

29.80 5.19

0.5825'

Gravida **

0.3576''

Parity **

0.6892''

T **

0.4902''

P **

0.9283''

A **

0.1676''

L **

0.7872''

Age *

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

28 (60%)

10 (50%)

Preterm

19 (40%)

10 (50%)

Term/Preterm ***
0.5916

* mean SD

'Unpaired t test

** median

''Mann-Whitney test

*** Frequency (%)

25

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.)

26

Appendix A
Figure 2
Days of Treatment Interval

Days of Treatment Interval

80.00

60.00

40.00

20.00

0.00
G1

G2

Groups
Group 1- Isoxsuprine
Group 2- Terbutaline

27

Appendix B
Figure 3
Tocolysis Duration in hours

Tocolysis Duration in hours

80.00

60.00

40.00

20.00

0.00
G1

G2

Groups

Group 1- Isoxsuprine
Group 2- Terbutaline

28

Appendix C
Figure 4
Delay of Labor in hours

Delay of Labor in hours

2000.00

1500.00

1000.00

500.00

0.00
G1

G2

Groups
Group 1- Isoxsuprine
Group 2- Terbutaline

29