Changes in the Treatment and Outcomes of Different Severities of Neonatal Hypoxic Ischemic Encephalopathy in California: A Retrospective Cohort Study.

OBJECTIVE: Evaluate the changes in management and outcomes of Californian infants with hypoxic ischemic encephalopathy (HIE). STUDY DESIGN: Infants with HIE were identified from a California administrative birth cohort using ICD codes and divided into two epochs, Epoch 1 (2010-2015) and Epoch 2 (2016-2019). Risk ratios (RR) for therapeutic hypothermia (TH) in each epoch and their outcomes were calculated using log-linear regression. RESULTS: In this cohort, 4779 infants with HIE were identified. Incidence of HIE in California increased yearly from 0.5/1,000 California births to a peak of 1.5/1,000 births in 2018. The use of TH in infants with mild HIE increased in Epoch 2 compared to Epoch 1. There was no significant difference in outcomes between epochs for infants with mild HIE that received TH. CONCLUSION: Significantly more infants with mild HIE received TH since 2015 in California, but no difference in outcomes was found for these patients.

Early identification of SOX17 deficiency in infants to guide management of heritable pulmonary arterial hypertension using PDA stent to create reverse Potts shunt physiology.

Heritable pulmonary arterial hypertension (HPAH) is a rare progressive condition that includes patients with an identified genetic cause of pulmonary arterial hypertension (PAH). HPAH and idiopathic PAH (IPAH) have an estimated combined incidence of 0.5-0.9 cases per million children-years. Several pathogenic variants have been associated with HPAH in children and adults, including genes BMPR2, TBX4, and ACVRL1, and more rarely with variants in genes such as SOX17. HPAH is often difficult to manage and has poor prognosis despite advances in medical therapy with many patients progressing to lung transplantation, right heart failure and death. Surgical and transcatheter Potts shunt creation can reduce systolic burden and has shown reduction in morbidity and mortality in children. Early genetic testing can provide both diagnostic and prognostic value in managing and counseling children with severe PAH and it can guide transcatheter or surgical management in refractory cases despite maximal medical therapies. We describe a patient with HPAH (SOX17 mutation) who underwent percutaneous patent ductus arteriosus stent for right ventricle decompression at 2 months of age with clinical management guidance by genetic testing results.

Racial and Ethnic Inequities in Therapeutic Hypothermia and Neonatal Hypoxic-Ischemic Encephalopathy: A Retrospective Cohort Study.

OBJECTIVE: To investigate racial inequities in the use of therapeutic hypothermia (TH) and outcomes in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We queried an administrative birth cohort of mother-baby pairs in California from 2010 through 2019 using International Classification of Diseases codes to evaluate the association between race and ethnicity and the application of TH in infants with HIE. We identified 4779 infants with HIE. Log-linear regression was used to calculate risk ratios (RR) for TH, adjusting for hospital transfer, rural location, gestational age between 35 and 37 weeks, and HIE severity. Risk of adverse infant outcome was calculated by race and ethnicity and stratified by TH. RESULTS: From our identified cohort, 1338 (28.0%) neonates underwent TH. White infants were used as the reference sample, and 410 (28.4%) received TH. Black infants were significantly less likely to receive TH with 74 (20.0%) with an adjusted risk ratio (aRR) of 0.7 (95% CI 0.5-0.9). Black infants with any HIE who did not receive TH were more likely to have a hospital readmission (aRR 1.36, 95% CI 1.10-1.68) and a tracheostomy (aRR 3.07, 95% CI 1.19-7.97). Black infants with moderate/severe HIE who did not receive TH were more likely to have cerebral palsy (aRR 2.72, 95% CI 1.07-6.91). CONCLUSIONS: In this study cohort, Black infants with HIE were significantly less likely to receive TH. Black infants also had significantly increased risk of some adverse outcomes of HIE. Possible reasons for this inequity include systemic barriers to care and systemic bias.

Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury.

BACKGROUND: There is evidence from various models of hypoxic-ischemic injury (HII) that nitric oxide (NO) is protective. We hypothesized that either inhaled NO (iNO) or nitrite would alleviate brain injury in neonatal HII via modulation of mitochondrial function. METHODS: We tested the effects of iNO and nitrite on the Rice-Vannucci model of HII in 7-day-old rats. Brain mitochondria were isolated for flow cytometry, aconitase activity, electron paramagnetic resonance, and Seahorse assays. RESULTS: Pretreatment of pups with iNO decreased survival in the Rice-Vannucci model of HII, while iNO administered post-insult did not. MRI analysis demonstrated that pre-HII iNO at 40 ppm and post-HII iNO at 20 ppm decreased the brain lesion sizes from 6.3±1.3% to 1.0±0.4% and 1.8±0.8%, respectively. Intraperitoneal nitrite at 0.165 µg/g improved neurobehavioral performance but was harmful at higher doses and had no effect on brain infarct size. NO reacted with complex IV at the heme a3 site, decreased the oxidative stress of mitochondria challenged with anoxia and reoxygenation, and suppressed mitochondrial oxygen respiration. CONCLUSIONS: This study suggests that iNO administered following neonatal HII may be neuroprotective, possibly via its modulation of mitochondrial function.

Association of a Delayed Cord-Clamping Protocol With Hyperbilirubinemia in Term Neonates.

OBJECTIVE: To evaluate the implementation of a delayed cord-clamping protocol at an academic medical center, and its short-term associations on term neonates. METHODS: This was a retrospective cohort study of women aged 18 years or older delivering a term neonate at an academic medical center before and 5-7 months after implementation of a universal delayed cord-clamping protocol (October-December 2015 and October-December 2016, respectively). The primary outcome measure was the mean peak neonatal transcutaneous bilirubin level, with secondary outcome measures including mean initial transcutaneous bilirubin levels, mean serum bilirubin levels, number of serum bilirubin levels drawn, incidence of clinical jaundice, and phototherapy. RESULTS: Protocol adherence was 87.8%. Data are presented on 424 neonates. The mean peak neonatal transcutaneous bilirubin levels were significantly higher among neonates in the postprotocol group (10.0±3.4 mg/dL vs 8.4±2.7 mg/dL, P<.01). More neonates in the postprotocol group were diagnosed with jaundice (27.2% vs 16.6%; odds ratio [OR] 1.88; 95% CI 1.17-3.01) and required serum blood draws (43.7% vs 29.4%; OR 1.86; 95% CI 1.25-2.78). However, there were no differences in mean peak serum bilirubin levels between groups (9.7±3.0 mg/dL vs 9.1±3.1 mg/dL, P=.17) or need for phototherapy (5.2% vs 6.6%, OR 1.28; 95% CI 0.57-2.89). CONCLUSION: Implementation of a delayed cord-clamping protocol for term neonates was associated with significantly higher mean transcutaneous bilirubin levels, an increased number of serum blood draws, and more clinical diagnoses of jaundice, although there was no increase in the incidence of phototherapy.