Klauser 2012.
| Methods | Multi‐arm RCT (NCT00811057). | |
| Participants | 301 women (90 magnesium sulphate; 114 nifedipine; 97 indomethacin). Inclusion criteria: women between 20 and 32 weeks' gestation, confirmed to be in preterm labour (regular uterine contractions, 5 mins apart or less, cervical dilatation of at least 1 cm or a change from the previous vaginal examination); with intact membranes; singleton or twin pregnancy, vertex presentation, with cervical dilatation from 1 ‐ 6 cm and sufficient effacement and decrease in station. Only women with 'idiopathic' preterm labour were included. Exclusion criteria: women with triplet or quad pregnancies, women with significant medical and surgical reasons for early delivery (severe pre‐eclampsia, placental abruption, fetal malformations inconsistent with life, chorioamnionitis, IUGR, nonreassuring fetal heart tracing. Setting: Obstetrics Dept, University of Mississippi Medical Center, USA. |
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| Interventions |
MAGNESIUM VS CALCIUM CHANNEL BLOCKERS VS PROSTAGLANDIN INHIBITORS 1) Magnesium sulphate (n = 85 women; 95 infants (10 twins)): 6 g IV loading dose of magnesium sulphate over 20 mins followed by 4‐6 g/hr until contractions had ceased for 1‐2 hr, and then discontinued. 2) Nifedipine (n = 104 women; 119 infants (15 twins)): 30 mg loading dose orally followed by 20‐30 mg every 4‐6 hrs until contractions stopped. 3) Indomethacin (n = 87 women; 103 infants (103 twins)): women received 100 mg rectal suppository which could be repeated once, 2 hrs after the initial dose if contractions continued. This was followed by 50 mg indomethacin by mouth every 6 hrs until contractions had ceased for 12 hrs. Only used for 48 hrs as a total treatment cycle. (Pepcid 20 mg was given orally twice a day to minimise GI irritation.) No tocolytics were given as maintenance therapy. |
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| Outcomes | Women who had not given birth after 48 hrs; neonatal mortality; gestational age at birth; nausea/vomiting; hypotension; tachycardia; fetal ductal constriction; oligohydramnios; birthweight; cord pH; neonatal morbidity (RDS, PDA, sepsis, NEC, IVH, PVL), days on ventilation, days in NICU. Serious infant outcome (able to compile a composite of death and PVL). |
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| Notes | Antenatal corticosteroid use: all women.
Surfactant use: not reported. Sample‐size calculation: yes. Funding: no external sources; "no declarations of interest". No antibiotics were given. Drugs could be switched for treatment failure or adverse effects, but women were analysed according to their original group allocation. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Only reported as "generated by random generation". |
| Allocation concealment (selection bias) | Low risk | Not entirely clear, but probably secure third party "After enrolment a disinterested third party (UMC Pharmacy Service) ..... selected the next in a series of opaque envelopes, containing a card generated by random selection, assigning the patient to one of the three study groups.. and the appropriate medication was sent to the labor/delivery suite." |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Blinding was not possible for women or study personnel given the 3 different regimens. |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Not reported. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | 25/301 (8%) women lost to follow‐up or results not analysed:
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| Selective reporting (reporting bias) | Unclear risk | Events were not reported for the neonatal morbidity composite (only reported as P = 0.504). |
| Other bias | Unclear risk | No other obvious sources of bias identified, although more women were randomised to nifedipine (114 vs 90 magnesium sulphate vs 97 indomethacin) and no adjustment made for twins. |