Nifedipine Compared to Atosiban for Treating Preterm Labor

• drugs side effects [ Time Frame: within the first 48 hours after treatment ] [ Designated as safety issue: Yes ]
• obstetrical (number of days to delivery, gestational age at delivery, mode of delivery) [ Time Frame: within 24 hours after delivery ] [ Designated as safety issue: No ]
• neonatal (Apgar score, sepsis, IVH, NEC, RDS, DEATH) [ Time Frame: within 30 days from delivery ] [ Designated as safety issue: Yes ]

The purpose of this study is to investigate the efficacy and the safety of nifedipine compared to atosiban for treating preterm labor.

• Drug: Atosiban
  Atosiban group will receive an atosiban bolus (6.75 mg) over 1 min then an intravenous infusion of 300mcg/min for 3 h followed by 100mcg/min for another 45h. If contractions continue or recur within 48 hours or the dilatation of the cervix progresses by 1 cm or more within 48 hours, atosiban will be stopped and the women will receive nifedipine as a 2nd line (see arm 2). If the second line fails and gestational age is less than 28 weeks, indomethacin will be administered as a 3rd line.
• Drug: Nifedipine
  Nifedipine group: the initial dose will be 20 mg (one tab) orally every 20 min for 3 doses. If the contractions is inhibited, a maintenance dose of 20 - 40 mg every 6 h up to 48 h will be followed. If contractions continue or recur within 48 hours or the dilatation of the cervix progresses by 1 cm or more within 48 hours, nifedipine will be stopped and the women will receive atosiban as a 2nd line (see arm 2). If the second line fails and gestational age is less than 28 weeks, indomethacin will be administered as a 3rd line.

• Experimental: 1
  Intervention: Drug: Atosiban
• Experimental: 2
  Intervention: Drug: Nifedipine

• King JF, Flenady V, Papatsonis D, Dekker G, Carbonne B. Calcium channel blockers for inhibiting preterm labour; a systematic review of the evidence and a protocol for administration of nifedipine. Aust N Z J Obstet Gynaecol. 2003 Jun;43(3):192-8. Review.
• Papatsonis DN, Van Geijn HP, Adèr HJ, Lange FM, Bleker OP, Dekker GA. Nifedipine and ritodrine in the management of preterm labor: a randomized multicenter trial. Obstet Gynecol. 1997 Aug;90(2):230-4.
• Moutquin JM, Sherman D, Cohen H, Mohide PT, Hochner-Celnikier D, Fejgin M, Liston RM, Dansereau J, Mazor M, Shalev E, Boucher M, Glezerman M, Zimmer EZ, Rabinovici J. Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study. Am J Obstet Gynecol. 2000 May;182(5):1191-9.
• Salim R, Garmi G, Nachum Z, Zafran N, Baram S, Shalev E. Nifedipine compared with atosiban for treating preterm labor: a randomized controlled trial. Obstet Gynecol. 2012 Dec;120(6):1323-31. doi: http://10.1097/AOG.0b013e3182755dff.

Inclusion Criteria:

1. Gestational age between 24 to 34 weeks which had been documented by a definite LMP and sonography up to 20 weeks.

2. All women fulfilled the criteria of preterm labor. The diagnosis of preterm labor required the presence of 4 uterine contractions or more over 30 minutes, each lasting at least 30 seconds, and documented cervical change. The cervical criteria were met when either of the following was present:

   1. Nulliparous women: a single cervical examination demonstrating dilatation of 0 cm to 4 cm and effacement of at least 50%
   2. Multiparous women: a single cervical examination demonstrating dilatation of 1 cm to 4 cm and effacement of at least 50%.
3. Provision of written informed consent

Exclusion Criteria:

1. Chorioamnionitis
2. Preterm rupture of membranes
3. Vaginal bleeding
4. Major fetal malformations
5. Severe hypertensive disorders
6. Intrauterine growth restriction (< 5th percentile).
7. Non-reassuring fetal heart rate

8. Maternal contraindications

   1. Chronic hypertension
   2. Systolic blood pressure < 90 mmHg
   3. Cardiovascular disease
   4. Elevated hepatic enzymes
9. Congenital or acquired uterine malformation