The only trial that failed to show its effectiveness used a subtherapeutic dose. 9 Evidence for preventing IVH seemed so compelling that use of antenatal phenobarbital became a standard of care in many institutions. Despite the apparent effectiveness of antenatal phenobarbital treatment, it is no longer employed in clinical practice. This is mainly due to two recent RCTs that have shed more light on phenobarbital s preventive effect. Both trials showed that phenobarbital has no significant protective effect, thus contradicting previous results.
Several explanations are possible.
Not all RCTs were blinded, so a preferential bias toward treatment groups could exist. In some studies, treatment groups had more exclusion criteria, again possibly causing a bias in favour of treatment groups. The similarity in results of early studies suggests an uncontrolled confounding factor. Because antenatal corticosteroid use has significantly increased over the last two decades, its possible confounding effect would cause an apparent decrease in the effectiveness of antenatal phenobarbital. If studies using antenatal phenobarbital are scrutinized in chronologic order, we see a clear trend toward decreasing effect of phenobarbital over time.