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Introduction: Early skin-to-skin contact (ESSC) is associated with rare, sudden, unexpected postnatal collapse episodes. Placing the newborn in ESSC closer to an upright position may reduce the risk of airway obstruction and improve respiratory mechanics. This study assessed whether a greater inclination of the mother’s bed during ESSC would reduce the proportion of healthy term newborns (HTNs) who experienced episodes of pulse oximeter saturation (SpO 2 ) <91%. Methods: We conducted a multicenter randomized controlled trial comparing the effect of the mother’s bed incline, 45° versus 15°, on desaturation in HTNs during ESSC. Before delivery on 1,271 dyads, randomization was conducted, and stringent criteria to select healthy mothers and term newborns were monitored until after birth. Preductal SpO 2 was continuously monitored between 10 min and 2 h after birth. The primary outcome was the occurrence of at least one episode of SpO 2 <91%. Results: 254 (20%) mother-infant dyads were eligible for analysis (45°, n = 126; 15°, n = 128). Overall, 57% (95% confidence interval [CI]: 51%–63%) of newborns showed episodes of SpO 2 <91%. The proportion of infants with SpO 2 <91% episodes was 52% in 45° and 62% in 15° (relative risk: 0.80; 95% CI: 0.6–1.07). Conclusions: We did not show that a high mother bed inclination during ESSC led to significantly fewer HTNs who experienced episodes of SpO 2 <91%. Desaturation episodes from 10 min to 2 h after birth occurred in more than half of HTNs.