LB2: Opptimum

Abstract

OPPTIMUM aimed to determine whether progesterone prophylaxis to prevent preterm birth in women at risk improves outcomes. In a double blind RCT, 1228 women at risk of preterm birth (due to a positive fetal fibronectin test, or a history of spontaneous preterm birth at ≤ 34+0 weeks gestation, or a cervical length ≤ 25mm) were randomized to vaginal progesterone, 200mg daily, or placebo, taken from 22-24 to 34 weeks gestation. Primary outcomes were (obstetric) preterm birth or fetal death before 34 weeks gestation, (neonatal) death or major morbidity (brain injury or bronchopulmonary dysplasia) and (childhood) Bayley III cognitive scores at 2 years of age, with values imputed for deaths. Analysis was by intention to treat using logistic, proportional hazards or linear regression, adjusting for previous pregnancy of ≥ 14 weeks (where possible), with study centre as a random effect. Progesterone had no statistically significant effect on either the primary obstetric or the childhood outcome (see table). Progesterone prophylaxis reduced the rate of the adverse neonatal composite outcome OR: 0.62 (95% CI 0.41, 0.94). However, following the pre-specified multiple comparisons procedure, this reduction was not statistically significant (adjusted p=0.072). Secondary analysis of the components of the neonatal outcome showed that progesterone reduced the risk of brain injury and neonatal death but not severe chronic lung disease. In the largest study of vaginal progesterone to date, we have not conclusively demonstrated reductions in preterm birth before 34 weeks or in neonatal morbidity. Progesterone appears to confer no long-term benefit or harm on cognitive and/or neurosensory outcomes in children at two years of age.