Background: Placebo effect has been largely studied and debated in medicine. Research focused mainly on children and adults but not on newborns. In osteopathy, few studies documented this effect and no research has been conducted in newborns.

Objectives: To assess the presence of placebo effect in newborns using sham osteopathic manipulative treatment.

Design: Randomized control trial.

Setting: Neonatal Intensive Care Unit in Italy.

Interventions: Two groups (103 patients each) of preterm infants aged 29-36 weeks without medical complications received routine pediatric care and osteopathic sham therapy was administrated to the study group only for the entire period of hospitalization.

Main outcome measures: Primary end point was the mean reduction of length of stay at discharge. Secondary objective was the change in daily weight gain.

Results: 206 newborns entered the study. No difference between sham and control group was found for the primary outcome length of stay (30.0±20.3; 28.8±18.9; p=0.70). Multivariate analysis showed no difference between study and control group on length of stay. A negative association was found for gestational age (-2.33; 95% CI -3.81 to -0.85; p=0.002), birth weight (-0.01; 95% CI -0.02 to -0.01; p<0.001) and milk volume at study enrollment (-0.02; 95% CI -0.05 to -0.01; p=0.01).

Conclusions: To the best of our knowledge, this study is the first in the field showing no placebo effect on newborns. Further discussions are opened concerning the age when placebo effect starts.