Early Hyperoxemia and 2-year Outcomes in Infants with Hypoxic-ischemic Encephalopathy: A Secondary Analysis of the Infant Cooling Evaluation Trial.

OBJECTIVE: To determine the causal relationship between exposure to early hyperoxemia and death or major disability in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We analyzed data from the Infant Cooling Evaluation (ICE) trial that enrolled newborns ≥35 weeks' gestation with moderate-severe HIE, randomly allocated to hypothermia or normothermia. The primary outcome was death or major sensorineural disability at 2 years. We included infants with arterial pO2 measured within 2 hours of birth. Using a directed acyclic graph, we established that markers of severity of perinatal hypoxia-ischemia and pCO2 were a minimally sufficient set of variables for adjustment in a regression model to estimate the causal relationship between arterial pO2 and death/disability. RESULTS: Among 221 infants, 116 (56%) had arterial pO2 and primary outcome data. The unadjusted analysis revealed a U-shaped relationship between arterial pO2 and death or major disability. Among hyperoxemic infants (pO2 100-500 mmHg) the proportion with death or major disability was 40/58 (0.69), while the proportion in normoxemic infants (pO2 40-99 mmHg) was 20/48 (0.42). In the adjusted model, hyperoxemia increased the risk of death or major disability (adjusted risk ratio 1.61, 95% CI 1.07-2.00, P = .03) in relation to normoxemia. CONCLUSION: Early hyperoxemia increased the risk of death or major disability among infants who had an early arterial pO2 in the ICE trial. Limitations include the possibility of residual confounding and other causal biases. Further work is warranted to confirm this relationship in the era of routine therapeutic hypothermia.

Cardiac Morphology and Function in Preterm Growth Restricted Infants: Relevance for Clinical Sequelae.

OBJECTIVES: To assess cardiac morphology and function in preterm infants with fetal growth restriction (FGR) compared with an appropriate for gestational age cohort, and to ascertain clinical correlation with neonatal sequelae. STUDY DESIGN: With informed consent, 20 infants born between 28 and 32 weeks of gestational age and birthweight (BW) <10th percentile were compared using conventional and tissue Doppler echocardiography with 20 preterm appropriate for gestational age infants. Total duration of respiratory support was recorded. RESULTS: The gestational age and BW of the infants with FGR and appropriate for gestational age infants were 29.8 ± 1.3 weeks vs 30 ± 0.9 weeks (P = .78) and 923.4 ± 168 g vs 1403 ± 237 g (P < .001), respectively. Preterm infants with FGR had significantly greater interventricular septal hypertrophy, greater free wall thickening, and lower sphericity indices (1.53 ± 0.15 vs 1.88 ± 0.2; P < .001), signifying globular and hypertrophied hearts. The transmitral E/A ratio and isovolumic relaxation time, markers of diastolic function, were significantly increased in the FGR cohort (0.84 ± 0.05 vs 0.78 ± 0.03 [P < .001] and 61.4 ± 4.1 ms vs 53.2 ± 3.2 ms [P < .001], respectively). Ejection fraction, as measured by the rate corrected mean velocity of circumferential fiber shortening was reduced (1.93 ± 0.4 circ/second vs 2.77 ± 0.5 circ/second; P < .001) in the FGR cohort. On follow-up, the total duration of respiratory support was significantly longer in the FGR cohort, and correlated with tissue Doppler E/E' (r = 0.65; P = .001), mean velocity of circumferential fiber shortening (r = -0.64; P = .001) and mitral annular peak systolic excursion (r = -0.57; P = .008). CONCLUSIONS: Preterm infants with FGR have altered cardiac function evident within days after birth, which is associated with respiratory sequelae.