Double Jeopardy: A Distinct Mortality Pattern Among Preterm Infants with Congenital Heart Disease.

Contemporary United States (US) data on the survival of preterm infants with congenital heart disease (CHD) are unavailable despite the over-representation of CHD and improving surgical outcomes in the preterm population. The aim of this study is to use population-based data to compare 1-year survival and early mortality (< 3 days) by gestational age (GA) between preterm infants with and without cyanotic CHD (CCHD) in the US. This national retrospective cohort included all liveborn, preterm infants between 21 and 36 weeks GA with a birth certificate indicating the presence or absence of CCHD (n = 2,654,253) born between 2014 and 2019 in the US. Data were provided by the US Center for Disease Control database linking birth and death certificates. Of liveborn preterm infants, 0.13% (n = 3619) had CCHD. 1-year survival was significantly lower in infants 23-36 weeks with CCHD compared to those without. The greatest survival gap occurred between 28 and 31 weeks (28 weeks adjusted risk difference 37.5%; 95% CI 28.4, 46.5; 31 weeks 37.9%; 30.5, 45.3). Early mortality accounted for more than half of deaths among infants 23-31 weeks with CCHD (23 weeks-68%, CI 46.7, 83.7; 31 weeks-63.9%, 52.9, 73.6). Survival trends demonstrated worsened 1-year survival in infants 35-36 weeks with CCHD over the study period. The pattern of mortality for preterm infants with CCHD is distinct from those without. The significant survival gap in the very preterm population and notably high rate of early death in the infants with CCHD calls for renewed attention to early neonatal intensive care for this dually affected population.

Single-Center Comparison of Outcomes Following Cardiac Surgery in Low Birth Weight and Standard Birth Weight Neonates.

OBJECTIVE: To compare outcomes between low birth weight (LBW; <2.5 kg) and standard birth weight neonates undergoing cardiac surgery. STUDY DESIGN: A single-center retrospective study of neonates undergoing cardiac surgery with cardiopulmonary bypass from 2012 to 2018. LBW neonates were 1:2 propensity score-matched to standard birth weight neonates (n = 93 to n = 186) using clinical characteristics. The primary and secondary outcomes were survival to hospital discharge and postoperative complications, respectively. After matching, regression analyses were conducted to compare outcomes. RESULTS: The LBW group had a higher proportion of premature neonates than the standard birth weight group (60% vs 8%; P < .01) and were less likely to survive to hospital discharge (88% vs 95%; OR, 0.39; 95% CI, 0.15-0.97). There was no difference in unplanned cardiac reoperations or catheter-based interventions, cardiac arrest, extracorporeal membrane oxygenation, infection, and end-organ complications between the groups. Among LBW infants, survival was improved at weight >2 kg. CONCLUSIONS: LBW is a risk factor for decreased survival. LBW neonates weighing >2 kg have survival comparable to those weighing >2.5 kg.

Attenuation of oxidative damage by targeting mitochondrial complex I in neonatal hypoxic-ischemic brain injury.

BACKGROUND: Establishing sustained reoxygenation/reperfusion ensures not only the recovery, but may initiate a reperfusion injury in which oxidative stress plays a major role. This study offers the mechanism and this mechanism-specific therapeutic strategy against excessive release of reactive oxygen species (ROS) associated with reperfusion-driven recovery of mitochondrial metabolism. AIMS AND METHODS: In neonatal mice subjected to cerebral hypoxia-ischaemia (HI) and reperfusion, we examined conformational changes and activity of mitochondrial complex I with and without post-HI administration of S-nitrosating agent, MitoSNO. Assessment of mitochondrial ROS production, oxidative brain damage, neuropathological and neurofunctional outcomes were used to define neuroprotective strength of MitoSNO. A specificity of reperfusion-driven mitochondrial ROS production to conformational changes in complex I was examined in-vitro. RESULTS: HI deactivated complex I, changing its conformation from active form (A) into the catalytically dormant, de-active form (D). Reperfusion rapidly converted the D-form into the A-form and increased ROS generation. Administration of MitoSNO at the onset of reperfusion, decelerated D→A transition of complex I, attenuated oxidative stress, and significantly improved neurological recovery. In cultured neurons, after simulated ischaemia-reperfusion injury, MitoSNO significantly reduced ROS generation and neuronal mortality. In isolated mitochondria subjected to anoxia-reoxygenation, MitoSNO restricted ROS release during D→A transitions. CONCLUSION: Rapid D→A conformation in response to reperfusion reactivates complex I. This is essential not only for metabolic recovery, but also contributes to excessive release of mitochondrial ROS and reperfusion injury. We propose that the initiation of reperfusion should be followed by pharmacologically-controlled gradual reactivation of complex I.