Efficacy and safety of oral nifedipine with or without vaginal progesterone in the management of threatened preterm labor


Background: Preterm labor (PTL) is a serious emergency wherein robust management is imperative for achieving improved outcome.

Objective: To evaluate the efficacy and safety of nifedipine alone vs nifedipine with vaginal progesterone in managing threatened PTL.

Materials and Methods: This comparative study was carried out at the Pakistan Institute of Medical Sciences, Islamabad over a 2-year’ period, from September, 2013 to August, 2015. The study included 276 patients with threatened PTL. Half of them were allocated to nifedipine alone group whereas the remainder half to the additional progesterone group. In nifedipine alone group (group A), all the patients were given 20mg of rapid release nifedipine orally. If uterine contraction continued, a 10mg dose was repeated every 20 min with a maximum of 40mg within the first hour. After completing the first hour, 20mg was given every 4–6 hr for 72 hr. In the additional vaginal progesterone group (group B), following successful tocolysis with nifedipine, additional - maintenance tocolysis was ensured with vaginal progesterone 200mg daily.

Results: Successful acute tocolysis was achieved with nifedipine among 86.23% patients. Mean pregnancy prolongation was 11.13 ± 5.08 days in group A while 29.73 ± 3.10 days in group B. (p0.001).

Conclusion: Acute tocolytic therapy with nifedipine was successful in the majority of our patients. The additional daily use of vaginal progesterone suppositories resulted in significant prolongation of pregnancy as well as reduction in the rate of low birth weight and neonatal ICU admissions.

Key words: Preterm labor, Tocolytics, Nifedipine, Progesterone.

[1] Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller AB, et al. Born too soon: the global epidemiology of 15 million preterm births. Reprod Health 2013; 10: S2.

[2] Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med 2010; 362: 529–535.

[3] Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ 2010; 88: 31–38.

[4] Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2011; 38: 18–31.

[5] Conde-Agudelo A, Romero R, Kusanovic JP. Nifedipine in the management of preterm labor: a systematic review and meta analysis. Am J Obstet Gynecol 2011; 204: 134: e1–20.

[6] Romero R, Yeo L, Chaemsaithong P, Chaiworapongsa T, Hassan SS. Progesterone to prevent spontaneous preterm birth. Semin Fetal Neonatal Med 2014; 19: 15–26.

[7] Moramezi F, Barati M, Saadati N, Masihi S, Hemadi M. A comparative study between the efficacy of 17-alpha hydroxyl progesterone caproate plus salbutamol with magnesium sulfate in treatment of preterm labor. Int J Pharmacol 2011; 7: 130–134.

[8] Beigi A, Esmailzadeh A, Pirjani R. Comparison of risk of preterm labor between vaginal progesterone and 17-alpha-hydroxy-progesterone Caproate in women with threatened abortion: A randomized clinical trial. Int J Fertil Steril 2016; 10: 162–168.

[9] Yassaee F, ShekarrizFoumani R, Afsari S, Fallahian M. The effect of progesterone suppositories on threatened abortion: A randomized clinical trial. J Reprod Infertil 2014; 15: 147–151.

[10] Ragunath MP, Sasmal D, Dhanaraj M. A study of nifedipine in the treatment of preterm labor of south Indian origin. Int J Pharm Res Scholar 2012; 1: 34–38.

[11] Klauser CK, Briery CM, Martin RW, Langston L, Magann EF, Morrison JC. A comparison of three tocolytics for preterm labor: a randomized clinical trial. J Matern Fetal Neonatal Med 2014; 27: 801–806.

[12] Sharami SH, Zahiri Z, Shakiba M, Millani F. Maintenance therapy by vaginal progesterone after threatened idiopathic preterm labor: A randomized placebo controlled double blind trial. Int J Fertil Steril 2010; 4: 45–50.

[13] SalehGargari S, Habibolahi M, Zonobi Z, Khani Z, Sarfjoo FS, KazemiRobati A, et al. Outcome of vaginal progesterone as a tocolytic agent: Randomized clinical trial. ISRN Obstet Gynecol 2012; 2012: 607906. 1–5.

[14] Kashanian M, Bahasadri S, Zolali B. Comparison of the efficacy and adverse effects of nifedipine and indomethacin for the treatment of preterm labor. Int J Gynecol Obstet 2011; 113: 192–195.

[15] Khan K, Zamora J, Lamont RF, Van Geijn Hp H, Svare J, Santos-Jorge C, et al. Safety concerns for the use of calcium channel blockers in pregnancy for the treatment of spontaneous preterm labour and hypertension: a systematic review and meta-regression analysis. J Matern Fetal Neonatal Med 2010; 23: 1030–1038.

[16] Flenady V, Wojcieszek AM, Papatsonis DN, Stock OM, Murray L, Jardine LA, et al. Calcium channel blockers for inhibiting preterm labour and birth. Cochrane DB Syst Rev 2014; 6: CD002255.

[17] Ga´ spa´ r R, Hajagos-To´ th J. Calcium channel blockers as tocolytics: principles of their actions, adverse effects and therapeutic combinations. Pharmaceuticals 2013; 6: 689–699.

[18] Bomba-Opon DA, Kosinska-Kaczynska K, Kosinski P, Wegrzyn P, Kaczynski B, Wielgos M. Vaginal progesterone after tocolytic therapy in threatened preterm labor. J Matern Fetal Neonatal Med 2012; 25: 1156–1159.

[19] Arikan I, Barut A, Harma M, Harma IM. Effect of progesterone as a tocolytic and in maintenance therapy during preterm labor. GynecolObstet Invest 2011; 72: 269–273.

[20] Bafghi AS, Bahrami E, Sekhavat L. Comparative study of vaginal versus intramuscular progesterone in the prevention of preterm delivery: A randomized clinical trial. Electron Physician 2015; 7: 1301–1309.