A randomized controlled trial of oropharyngeal therapy with mother's own milk for premature infants.

OBJECTIVE: To determine if oropharyngeal therapy with mother's own milk (OPT-MOM) reduces late-onset sepsis (L-OS; primary outcome), NEC, death, length of stay, time to full enteral nutrition (FEN) and full oral feeds in preterm infants (BW < 1250 g). DESIGN: Infants (N = 220) were randomized to Group A (milk) or B (placebo) and received 0.2 mL every 2 h for 48 h, then every 3 h until 32 weeks CGA. RESULTS: There were no significant differences in L-OS, NEC or death. Group A trended towards an 8-day reduction in stay, 8-day reduction in time to FEN and a 6-day reduction in time to full oral feeds, compared to B. While clinically relevant, due to large variability in outcomes and lack of power, p values were > 0.05. CONCLUSION: OPT-MOM did not reduce L-OS, NEC or death. Group A trended towards a reduced stay and better nutritional outcomes, but results were not statistically significant. CLINICALTRIALS: GOV: NCT02116699.

Early provision of oropharyngeal colostrum leads to sustained breast milk feedings in preterm infants.

BACKGROUND: Oropharyngeal colostrum (OC) application strategies have been shown to be feasible and safe for very low birth weight (VLBW) infants. Evidence to support the nutritional and clinical advantages of OC care remains somewhat theoretical. The objectives of this study were to a) confirm the feasibility and safety of OC application in preterm infants and b) determine if OC application is associated with improved nutritional and clinical outcomes from birth to discharge. We hypothesized that OC application in the first few days would promote sustained breast milk feedings through discharge. METHODS: An observational longitudinal study was conducted in 133 VLBW infants during 2013-14, after an OC protocol was adopted. Maternal and infant characteristics, infant vital signs during administration, nutritional outcomes, and common neonatal morbidities were assessed and compared to 85 age- and weight-matched VLBW infants from a retrospective control cohort from 2012, prior to the implementation of the OC protocol. RESULTS: There were no adverse events or changes in vital signs during the application of OC. VLBW infants who received OC continued to receive the majority of their enteral feeds from human breast milk at six 6 of age and through discharge (p < 0.01). There was no difference in maternal characteristics known to affect breast milk production, and rates of common neonatal morbidities were statistically similar between groups. CONCLUSION: OC application for VLBW infants is safe and practical in a neonatal intensive care unit setting and is associated with increased rates of breast milk feeding.

Effects of intermittent nebulization of NONOate, DPTA/NO, on group B Streptococcus-induced pulmonary hypertension in newborn piglets.

BACKGROUND: A single dose of NONOate attenuates pulmonary hypertension (PH) induced by group B Streptococcus (GBS) infusion and this is accompanied by a decrease in systemic vascular resistance (SVR). OBJECTIVE: The objective of the study was to determine whether two doses of the NONOate sustain the attenuation in GBS-induced PH without further systemic compromise. METHODS: 15 anesthetized newborn piglets were randomized to receive placebo (n = 8) or two doses of nebulized DPTA/NO (n = 7) at 15 and 75 min after GBS-induced PH. Pulmonary artery (Ppa) and systemic (Psa) pressures, cardiac output (CO) and arterial blood gases were obtained at baseline and every 15 min until 180 min during GBS infusion. RESULTS: Ppa and pulmonary vascular resistance (PVR) decreased significantly after the first dose of nebulized DPTA/NO and this effect was maintained after the second dose. Psa and SVR decreased after the first dose of DPTA/NO to values close to baseline and no further changes in systemic circulation were observed with repeated treatment. PVR/SVR increased with GBS infusion, but decreased after the first dose of DPTA/NO and remained significantly lower for 180 min. CO was significantly higher in the DPTA/NO group. Changes in Ppa, PVR, Psa, SVR, and CO with GBS infusion were not modified by placebo infusion. PaCO(2), base deficit, and pH did not differ between groups. PaO(2) was significantly lower in the DPTA/NO group after the second dose. CONCLUSION: These data demonstrated that GBS-induced PH is attenuated with two doses of DPTA/NO without significant systemic effect. The vasodilatory effect is more pronounced in the pulmonary than in the systemic vasculature, as suggested by lower PVR/SVR in the DPTA/NO group. We speculate that NONOates may have a clinical application in the management of PH in neonates.

Ventilatory response to hypoxia during endotoxemia in young rats: role of nitric oxide.

Administration of Escherichia coli endotoxin attenuates the ventilatory response to hypoxia (VRH) in newborn piglets, but the mechanisms responsible for this depression are not clearly understood. Nitric oxide (NO) production increases during sepsis and elevated NO levels can inhibit carotid body function. The role of endothelial NO on the VRH during endotoxemia was evaluated in 26 young rats. Minute ventilation (VE) and oxygen consumption (VO2) were measured in room air (RA) and during 30 min of hypoxia (10% O2) before and after E. coli endotoxin administration. During endotoxemia, animals received placebo (PL, n = 8); a nonselective nitric oxide synthase (NOS) inhibitor (NG-nitro-L-arginine methyl ester, L-NAME, n = 9), or a neuronal NOS (nNOS) inhibitor (7-nitroindazole, 7-NI, n = 9). During endotoxemia, a larger increase in VE was observed only during the first min of hypoxia in the L-NAME group when compared with PL or 7-NI (p < 0.001). VRH was similar in the PL and 7-NI groups. A larger decrease in VO2 at 30 min of hypoxia was observed in L-NAME and 7-NI groups when compared with PL (p < 0.03). These data demonstrate that the attenuation of the early VRH during endotoxemia is in part mediated by an inhibitory effect of endothelial NO on the respiratory control mechanisms.

Effects of a nebulized NONOate, DPTA/NO, on group B streptococcus-induced pulmonary hypertension in newborn piglets.

NONOates are chemical compounds that are stable as solids but generate nitric oxide (NO) in aqueous solutions. When nebulized or instilled intratracheally, NONOates can attenuate pulmonary hypertension in adult animals with lung injury. To assess the effect of a nebulized NONOate, DPTA/NO, on group B Streptococcus (GBS)-induced pulmonary hypertension in newborn piglets, we studied 20 anesthetized and mechanically ventilated piglets (4-10 d). They were randomly assigned to receive nebulized placebo solution or DPTA/NO (100 mg) 15 min after sustained pulmonary hypertension. Pulmonary artery and wedge, systemic, and right atrial pressures; cardiac output; and arterial blood gases were obtained at baseline and every 15 min during 120 min of continuous GBS infusion (6 x 10(8) CFU/min). Methemoglobin levels were measured at baseline and 60 min. A significant decrease in pulmonary artery pressure, pulmonary vascular resistance (PVR), systemic arterial pressure, and systemic vascular resistance (SVR) was observed after DPTA/NO nebulization (p <0.001). Whereas the increase in PVR/SVR observed after GBS infusion was sustained for 120 min in the placebo group, this ratio decreased after DPTA/NO nebulization and remained significantly lower throughout the study period (p <0.01). Cardiac output, arterial blood gases, and methemoglobin values did not differ between groups. These data demonstrate that the pulmonary hypertension induced by GBS infusion is markedly attenuated by DPTA/NO nebulization. The lower PVR/SVR observed in the treated group indicates that the vasodilatory effect of NONOate is more pronounced in the pulmonary than systemic vasculature. Therefore, NONOates may have clinical application in the management of pulmonary hypertension secondary to sepsis in neonates.

The effect of a nebulized NO donor, DPTA/NO, on acute hypoxic pulmonary hypertension in newborn piglets.

NONOates, novel NO donors, are complexes of NO with nucleophiles which spontaneously and nonenzymatically release NO in aqueous solution. This study sought to determine the cardiopulmonary effects of the nebulized NONOate dipropylenetriamine (DPTA)/NO in newborn piglets with acute hypoxia-induced pulmonary hypertension. Twenty sedated and mechanically ventilated piglets (4-10 days old) exposed to hypoxia (Fi(O2) = 0.14) were randomly assigned to receive nebulized saline as placebo (PL) or DPTA/NO (75 mg) after 30 min of hypoxia. Pulmonary artery (P(pa)) and wedge pressures, systemic (P(sa)) and right atrial pressures, cardiac output (CO) and arterial blood gas were measured at baseline and every 15 min for 2 h. Methemoglobin levels were measured at baseline and 1 h after drug nebulization. Data (means +/- SD) were analyzed by repeated-measures analysis of variance. Acute hypoxia resulted in an increase in P(pa) and pulmonary vascular resistance (PVR), which was significantly attenuated by DPTA/NO nebulization as compared to the PL group (p < 0.0001). Changes in P(sa), CO, systemic vascular resistance (SVR), arterial blood gas and methemoglobin levels were not different between groups. In contrast to the increase in PVR/SVR observed during hypoxia in the PL group, there was a significant decrease in this ratio after NONOate administration (p < 0.0001). These data show that acute hypoxic pulmonary hypertension in newborn piglets is markedly attenuated by NONOate nebulization. This response is predominantly in the pulmonary vasculature as the PVR/SVR was significantly lower in the treated group. We speculate that NONOates may have clinical application in the treatment of persistent pulmonary hypertension of the newborn.

The effect of Escherichia coli endotoxin infusion on the ventilatory response to hypoxia in unanesthetized newborn piglets.

To determine the effects of endotoxemia on the neonatal ventilatory response to hypoxia, 17 chronically instrumented and unanesthetized newborn piglets (