Methods | Placebo‐controlled double‐blind randomised trial Trial conducted in 14 centres by the Maternal‐Fetal Medicine Network, USA From April 2004 until February 2006 |
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Participants | 661 women with a twin pregnancy were randomised. Inclusion criteria: women carrying twins with a gestational age of at least 16 weeks and no more than 20 weeks and 3 days Exclusion criteria: known fetal anomaly, spontaneous fetal death of a fetus after 12 weeks, presumed mono‐amniotic placenta, suspected twin‐twin transfusion syndrome, marked ultrasonographic growth discordance, progesterone or heparin treatment during pregnancy, current or planned cervical cerclage, hypertension, insulin‐dependent diabetes, and twin pregnancies that were the result of intentional fetal reduction |
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Interventions |
Intervention group: weekly intramuscular injection of 250 mg 17‐hydroxyprogesterone caproate from 16 ‐ 20 + 3 weeks until 34 completed weeks’ gestation, or birth if earlier Control group: weekly intramuscular injection of placebo (castor oil) from 16 ‐ 20 + 3 weeks until 34 completed weeks’ gestation, or birth if earlier |
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Outcomes |
Primary outcome: composite of delivery or death prior to 35 weeks’ gestation Secondary outcomes: randomisation to delivery interval; composite adverse outcomes (retinopathy of prematurity, RDS, sepsis, NEC, bronchopulmonary dysplasia, grade III or IV IVH, periventricular leucomalacia), birthweight (less than 2500 g and less than 1500 g), 5‐minute Apgar score < 7, PDA, pneumonia, mechanical ventilation, seizures. Pretermbirth before 37 weeks’ gestation; birthweight less than 2.5 kg; stillbirth; neonatal death; IVH; RDS; bronchopulmonary dysplasia; sepsis; NEC; retinopathy of prematurity |
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Notes | Funding sources: supported by grants (HD27869, HD21410, HD40512, HD34136, HD34208, HD40485, HD27915, HD40544, HD40560, HD27917, HD40500, HD34116, HD40545, HD27860, and HD36801) from the National Institute of Child Health and Human Development Declarations of interest: no potential sources of interest declared |
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Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | “The simple urn method of randomisation with stratification according to clinical center was used by the George Washington University Biostatistical Co‐ordinating Center to create a randomization sequence for each center...” |
Allocation concealment (selection bias) | Low risk | Identical‐appearing treatment packs |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | Women, caregivers and outcome assessors blinded |
Blinding of outcome assessment (detection bias) All outcomes | Low risk | Women, caregivers and outcome assessors blinded |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Outcome data available for 655 of 661 women (less than 1% loss to follow‐up) |
Selective reporting (reporting bias) | Low risk | All expected outcomes reported (delivery or fetal death before 35 weeks’ gestation; other obstetric and neonatal outcomes) |
Other bias | Unclear risk | Other bias not apparent |