Comparative Study of Nifedipine and Isoxpurine As Tocolytics For Preterm Labor
Comparative Study of Nifedipine and Isoxpurine As Tocolytics For Preterm Labor
Comparative Study of Nifedipine and Isoxpurine As Tocolytics For Preterm Labor
DOI 10.1007/s13224-011-0080-1
ORIGINAL ARTICLE
Received: 13 April 2009 / Accepted: 21 June 2011 / Published online: 29 October 2011
Federation of Obstetric & Gynecological Societies of India 2011
Abstract
Objectives This study was done to compare isoxpurine
hydrochloride and nifedipine as tocolytic drugs for preterm
labor.
Methods A prospective cohort study of 832 antenatal
women with preterm labor was conducted in the Department of Obstetrics & Gynecology. Out of 400 women
found eligible for tocolysis, 200 were given isoxpurine
hydrochloride while the other 200 were given nifedipine
randomly. The data obtained was statistically analyzed on
SPSS 10.0 of Windows 2003.
Results Incidence of preterm labor was 22% while the
incidence of preterm delivery was 20.9%. Nifedipine was
twice more effective than isoxpurine hydrochloride as a
tocolytic agent as a tocolytic agent (P value 0.006) while
side effects were comparable (P value 0.133). In earlydiagnosed preterm labor, nifedipine had higher efficacy
than isoxpurine (P value 6.45 9 10-6) and also higher
efficacy than its own in late diagnosed preterm labor
(P value 2.08 9 10-5).
Conclusions There is a high incidence of preterm labor in
India. Nifedipine is a better tocolytic drug than isoxpurine
hydrochloride, especially when started with the earliest
signs of preterm labor.
Introduction
Preterm labor & delivery is one of the biggest challenges
for obstetricians and so are the preterm babies for the
pediatricians. Preterm delivery affects 11% in U.S. [1] or
even greater in developing countries (23.3% in India) [2]
and it accounts for 4075% of neonatal deaths. Incidence
of preterm labor and delivery shows increasing trends in
countries where data is available [14]. It could be due to
assisted reproductive techniques, psychosocial stress, or
medically induced prematurity.
Prediction and prevention of preterm labor is not
possible despite extensive research on the subject. So, we
have to face preterm labor and manage our patients
according to their gestational age. Preterm labor before
34 weeks needs to be arrested for at least 48 h so that
fetal pulmonary maturity is attained using betamethasone. Delivery between 34 and 37 weeks reduces the risk
of respiratory distress syndrome but does not exempt the
baby from other complications of prematurity. Thus
tocolytic agents are frequently used in obstetric practice.
b-adrenergic receptor blocking agent isoxsuprine hydrochloride and calcium channel blocker nifedipine are two
commonly used tocolytic agents in India. This study was
done to compare their efficacy and analyze the overall
123
123
Results
Out of total 3,768 antenatal admissions during the study
period, 832 (22%) were admitted for preterm labor. Total
live births in the same duration were 3,228 out of which
676 were preterm deliveries giving an incidence of preterm
delivery of 20.9%. Out of 832 cases of PTL, 400 were
given tocolysis.
Gestational age wise distribution of cases and their final
outcome is shown in Table 1. There was no significant
difference in various confounding factors between the two
groups as shown in Table 2.
Table 3 shows the overall effect of the two types of
tocolytic therapy. Overall success rate of tocolysis was
74%. Successful tocolysis was achieved in 80% cases of
nifedipine group and 68 % cases of isoxpurine group
showing a statistically significant (P value 0.006) advantage in nifedipine group.
Out of 400 cases of PTL, 244 belonged to subgroup A
and 156 belonged to subgroup B. Analysis of the tocolytic
effect in the two subgroups showed that subgroup A has
better success rate (P value 2.08 9 10-5) as compared to
subgroup B. The success rate of nifedipine (112/124) was
significantly higher (P value 6.45 9 10-60) than that of
isoxpurine (80/120) in subgroup A. The comparative efficacy of the two drugs was similar in subgroup B (P value
0.09).
There were 216 cases of preterm rupture of membranes,
out of which 156 were allowed spontaneous labor due to
reasons described before, while 62 cases were given tocolysis. Failure rate was reported to be quite high i.e., (28/
62) 45.2% in cases with ruptured membranes compared to
only (76/338) 22.5% in cases with intact membrane. No
significant difference in outcome was noted in nifedipine &
513
Singh et al.
Table 1 Ditribution of preterm
labor cases according to
gestational age (n = 832)
Gestation
age
Preterm labor
cases (no.)
\28 weeks
Isoxsuprine
Preterm
deliveries (no.)
Total
30
10
18
24
2834 weeks
314
100
92
192
222
3436 weeks
404
90
100
190
346
84
84
832
200
200
400
676
[36 weeks
Total number
Nifedipine Isoxsuprine
(200)
(200)
24.7
25.6
Parity
Primigravidae (n)
96
90
Multigravidae (n)
104
110
124
120
Cases in subgroup A
Uterine cont \30 s & Cx
dilatation \2 cm
Discussion
Cases in subgroup B
76
80
62
65
32
30
Total
A (124)
A (120)
B (80)
(n = 400)
24
40
12
B (76)
28
514
112
48
Overall (200)
40 (20%)
Overall (200)
64 (32%)
104 (26%)
72
68
140
88
68
156
160 (80%)
96
40
136 (68%)
P value
296 (74%)
0.006
123
123
Conclusion
Nifedipine has been found to be more effective than
isoxsuprine in this large-scale study. In subgroup A (early
PTL) significant difference can be seen in success rates
among the two tocolytics agents, indicating thereby that
early initiation of tocolysis with nifedipine is definitely
beneficial in cases of preterm labor.
Acknowledgment We acknowledge the contribution of all patients
and doctors of Department of Obstetrics and Gynecology, CSM
Medical University involved in this study.
References
1. Martin JA, Kochank KD, Strobino DM, et al. Annual summary of
vital statistics 2003. Pediatrics. 2005;115:61939.
2. Begum F, Buckshee K, Pande JN. Risk factors associated with
preterm labor. Bangladesh Med Ras Coune Bull. 2003;29:5966.
3. Bibby E, Stewart A. The epidemiology of preterm birth. Neuro
Endocrinol Lett. 2004;25:437.
4. Shingairai AF, Siaban DH, Godfrey BW. Risk factors for prematurity at Harare maternity hospital, Zimbabwe. Int J Epidemiol. 2004;33:1194201.
5. King JF, Flenady VJ, Papatsonis DNM et al. Calcium channel
blockers for inhibiting preterm labor (cochrane review). The
cochrane library. Chichester: Wiley; 2004.
6. Smith CS, Woodland MB. Clinical comparison of oral nifedipine
and subcutaneous terbutaline for initial tocolysis. Am J Perinatol.
1993;10:2804.
7. Jannet D, Abankwa A, Guyard B, et al. Nicardipine versus salbutamol in the treatment of premature labor. Eur J Obstet
Gynecol Reprod Biol. 1997;73:116.
8. Bracero LA, Leikin E, Kirshenbaum N, et al. Comparison of
nifedipine and ritodrine for the treatment of preterm labor. Am J
Perinatol. 1991;8:3659.
9. Papatsonis DN, Van Geijn HP, Ade`r HJ, et al. Nifedipine and
ritodrine in the management of preterm labor: a randomized
multicenter trial. Obstet Gynecol. 1997;90:10234.
10. Kupferminc M, Lessing JB, Yaron Y, et al. Nifedipine versus
ritodrine for suppression of preterm labor. Br J Obstet Gynaecol.
1993;100:10904.
11. Garcia-Velasco JA, Gonzalez AG. Prospective, randomized trial
of nifedipine versus ritodrine in threatened preterm labor. Int J
Gynaecol Obstet. 1998;61:23944.
12. Koks CA, Brolmann HA, de Kleine MJ, et al. A randomized
comparison of nifedipine and ritodrine for suppression of preterm
labor. Eur J Obstet Gynecol Reprod Biol. 1998;77:1716.
13. RCOG. Tocolytic drugs for women in preterm labor. In: Clinical
guideline no. I (B). London: RCOG Press; 2002.
515