Objective To evaluate the safety and short-term outcomes of preterm neonates born at 34–35 weeks gestation with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Study design Medical records of preterm neonates born at 34–35 weeks gestational age with HIE treated with therapeutic hypothermia were retrospectively reviewed. Short-term safety outcomes and the presence, severity (mild, moderate, severe) and patterns of brain injury on magnetic resonance imaging (MRI) were reviewed using a standard scoring system, and compared with a cohort of term neonates with HIE treated with therapeutic hypothermia. Results Thirty-one preterm and 32 term neonates were identified. Therapeutic hypothermia-associated complications were seen in 90% of preterm infants and 81.3% of term infants (p=0.30). In the preterm infants, hyperglycemia (58.1% vs.31.3%, p=0.03) and rewarming before completion of therapeutic hypothermia (19.4% vs. 0.0%, p=0.009) were more likely compared with term infants. All deaths occurred in the preterm group (12.9% vs. 0%, p=0.04). Neuroimaging showed the presence of injury in 80.6% of preterm infants and 59.4% of term infants (p=0.07), with no differences in injury severity. Injury to the white matter was more prevalent in preterm infants compared with term infants (66.7% vs. 25.0%, p=0.001). Conclusions Therapeutic hypothermia in infants born at 34–35 weeks gestational age appears feasible. Risks of mortality and side effects warrant caution with use of therapeutic hypothermia in preterm infants.

Improvements in clinical management of the preterm infant have reduced the rates of the two most common forms of brain injury, such as severe intraventricular hemorrhage and white matter injury, both of which are contributory factors in the development of cerebral palsy. Nonetheless, they remain a persistent challenge and are associated with a significant increase in the risk of adverse neurodevelopment outcomes. Repeated episodes of ischemia–reperfusion represent a common pathway for both forms of injury, arising from discordance between systemic blood flow and the innate regulation of cerebral blood flow in the germinal matrix and periventricular white matter. Nevertheless, establishing firm hemodynamic boundaries, as a part of neuroprotective strategy, has challenged researchers. Existing measures either demonstrate inconsistent relationships with injury, as in the case of mean arterial blood pressure, or are not feasible for long-term monitoring, such as cardiac output estimated by echocardiography. These challenges have led some researchers to focus on the mechanisms that control blood flow to the brain, known as cerebrovascular autoregulation. Historically, the function of the cerebrovascular autoregulatory system has been difficult to quantify; however, the evolution of bedside monitoring devices, particularly near-infrared spectroscopy, has enabled new insights into these mechanisms and how impairment of blood flow regulation may contribute to catastrophic injury. In this review, we first seek to examine how technological advancement has changed the assessment of cerebrovascular autoregulation in premature infants. Next, we explore how clinical factors, including hypotension, vasoactive medications, acute and chronic hypoxia, and ventilation, alter the hemodynamic state of the preterm infant. Additionally, we examine how developmentally linked or acquired dysfunction in cerebral autoregulation contributes to preterm brain injury. In conclusion, we address exciting new approaches to the measurement of autoregulation and discuss the feasibility of translation to the bedside.

Background Deep nuclear gray matter injury in neonatal hypoxic-ischemic encephalopathy (HIE) is associated with worse neurodevelopmental outcomes. We previously published a qualitative MRI injury scoring system utilizing serial T1-weighted, T2-weighted and diffusion-weighted imaging (DWI), weighted for deep nuclear gray matter injury. Objectives To establish the validity of the MRI scoring system with neurodevelopmental outcome at 18–24 months. Materials and methods MRI scans from neonates with moderate to severe HIE treated with therapeutic hypothermia were evaluated. Signal abnormality was scored on T1-weighted, T2-weighted and DWI sequences and assessed using an established system in five regions: (a) subcortical: caudate nucleus, globus pallidus and putamen, thalamus and the posterior limb of the internal capsule; (b) white matter; (c) cortex,(d) cerebellum and (e) brainstem. MRI injury was graded as none, mild, moderate or severe. Inter-rater reliability was tested on a subset of scans by two independent and blinded neuroradiologists. Surviving infants underwent the Bayley Scales of Infant and Toddler Development-III (Bayley-III) at 18–24 months. Data were analyzed using univariate and multivariate linear and logistic regression. Results Fifty-seven eligible neonates underwent at least one MRI scan in the first 2 weeks of life. Mean postnatal age at scan 1 was 4±2 days in 50/57 (88%) neonates and 48/54 (89%) surviving infants underwent scan 2 at 10±2 days. In 54/57 (95%) survivors, higher MRI injury grades were significantly associated with worse outcomes in the cognitive, motor and language domains of the Bayley-III. Conclusion A qualitative MRI injury scoring system weighted for deep nuclear gray matter injury is a significant predictor of neurodevelopmental outcome at 18–24 months in neonates with HIE.

Objective: To evaluate the association between early (within 10d) pRBC transfusion and the development of severe ROP. Study Design and Methods: This was a single-center retrospective study. Inclusion criteria were preterm infants born ≤ 32 weeks gestation or weighing ≤ 1500g. Severe ROP was defined as infants requiring retinal laser ablation or bevacizumab injection. Logistic regression was used to identify the association between transfusions and severe ROP. Results: A total of 1635 infants were included in the final analysis. The severe ROP incidence was 8% (126/1635). Ninety-one percent (115/126) of infants who developed severe ROP received a pRBC transfusion in the first 10d. Early transfusion was associated with severe ROP; adjusted odds ratio of 3.8 (95% CI: 1.8-8.1). Conclusion: pRBC transfusions in the first 10 days of life are associated with an almost four-fold increased risk of severe ROP, independent of gestational age at birth or bronchopulmonary dysplasia (BPD) status.