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The aim of this study was to evaluate the influence of neonatal mandibular distraction osteogenesis (MDO) on cleft dimensions and on early palatoplasty outcomes in patients with Pierre Robin Sequence (PRS). In a prospective cohort study that enrolled 24 nonsyndromic patients with PRS, 12 submitted to the MDO group and 12 patients not treated (non-MDO group), the authors compared patients for cleft palate dimensions through 7 morphometric measurements at the moment of palatoplasty and for early palatoplasty outcomes. At palatoplasty, the MDO group presented a significant shorter distance between the posterior nasal spines (PNS–PNS, P < 0.001) and between uvular bases (UB–UB, P < 0.001), representing a reduction in cleft palate width. They also had significant soft palate lengthening represented by a larger distance between UB and retromolar space (UB–RM, P < 0.001) and UB and PNS (UB–PNS, P = 0.014). Their UB moved away from the posterior wall of the nasopharynx (UB–NPH, P < 0.001). The MDO group had a length of operative time significantly shorter (P < 0.001) and no early palatoplasty complications compared with the non-MDO group. In conclusion, MDO acted as an orthopedic procedure that reduced cleft palate width and elongated the soft palate in patients with PRS. These modifications enabled a reduction of around 11% in the length of operative time of palatoplasty (P < 0.001).