Effects of Neonatal Hypoxic-Ischemic Injury on Brain Sterol Synthesis and Metabolism.

BACKGROUND: Neonatal hypoxic-ischemic brain injury (HIBI) results from disruptions to blood supply and oxygen in the perinatal brain. The goal of this study was to measure brain sterol metabolites and plasma oxysterols after injury in a neonatal HIBI mouse model to assess for potential therapeutic targets in the brain biochemistry as well as potential circulating diagnostic biomarkers. METHODS: Postnatal day 9 CD1-IGS mouse pups were randomized to HIBI induced by carotid artery ligation followed by 30 minutes at 8% oxygen or to sham surgery and normoxia. Brain tissue was collected for sterol analysis by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Plasma was collected for oxysterol analysis by LC-MS/MS. RESULTS: There were minimal changes in brain sterol concentrations in the first 72 hours after HIBI. In severely injured brains, there was a significant increase in desmosterol, 7-DHC, 8-DHC, and cholesterol 24 hours after injury in the ipsilateral tissue. Lanosterol, 24-dehydrolathosterol, and 14-dehydrozymostenol decreased in plasma 24 hours after injury. Severe neonatal HIBI was associated with increased cholesterol and sterol precursors in the cortex at 24 hours after injury. CONCLUSIONS: Differences in plasma oxysterols were seen at 24 hours but were not present at 30 minutes after injury, suggesting that these sterol intermediates would be of little value as early diagnostic biomarkers.

MicroRNA therapeutic targets in neonatal hypoxic-ischemic brain injury: a narrative review.

Neonatal hypoxic-ischemic brain injury (HIBI) is a devastating injury resulting from impaired blood flow and oxygen delivery to the brain at or around the time of birth. Despite the use of therapeutic hypothermia, more than one in four survivors suffer from major developmental disabilities-an indication of the critical need for more effective therapies. MicroRNAs (miRNA) have the potential to act as biomarkers and/or therapeutic targets in neonatal HIBI as a step toward improving outcomes in this high-risk population. This review summarizes the current literature around the use of cord blood and postnatal circulating blood miRNA expression for diagnosis or prognosis in human infants with hypoxic-ischemic encephalopathy, as well as animal studies assessing endogenous brain miRNA expression and potential for therapeutic targeting of miRNA expression for neuroprotection. Ultimately, the lack of knowledge regarding brain specificity of circulating miRNAs and the temporal variability in expression currently limit the use of miRNAs as biomarkers. However, given their broad effect profile, ease of administration, and small size allowing for effective blood-brain barrier crossing, miRNAs represent promising therapeutic targets for improving brain injury and reducing developmental impairments in neonates after HIBI. IMPACT: The high morbidity and mortality of neonatal hypoxic-ischemic brain injury (HIBI) despite current therapies demonstrates a need for developing more sensitive biomarkers and superior therapeutic options. MicroRNAs have been evaluated both as biomarkers and therapeutic options after neonatal HIBI. The limited knowledge regarding brain specificity of circulating microRNAs and temporal variability in expression currently limit the use of microRNAs as biomarkers. Future studies comparing the neuroprotective effects of modulating microRNA expression must consider temporal changes in the endogenous expression to determine appropriate timing of therapy, while also optimizing techniques for delivery.

Direct hyperbilirubinemia and cholestasis in trisomy 13 and 18.

Trisomy 13 and 18 are common chromosomal abnormalities that affect multiple organ systems. There is a paucity of published data, however, on the hepatic complications seen in these patient populations. One of the most common pathologic hepatobiliary issues seen in the newborn period is direct hyperbilirubinemia (DH). Thus, this study sought to estimate the incidence and evaluate possible etiologies of DH in neonates with trisomy 13 or 18. This retrospective cohort study included all infants admitted to our two neonatal intensive care units between 2012 and 2020 with the diagnosis of trisomy 13 or 18. DH is most commonly diagnosed as a direct bilirubin >1 mg/dl but a cutoff of >2 mg/dl is more specific for cholestasis, so both cutoffs were evaluated. Continuous data were compared using Fisher's exact test and categorical variables by the Mann-Whitney U test. Thirty-five patients met inclusion: 13 with trisomy 13 and 22 with trisomy 18. DH of >2 mg/dl was seen in seven (53.8%) patients with trisomy 13 and five (22.7%) with trisomy 18. Using a cutoff of >1 mg/dl, the rate of trisomy 13 was unchanged, but the rate in trisomy 18 increased to 9/22 (40.9%). There was a trend toward more DH in trisomy 13 patients (p = 0.079) versus trisomy 18 and higher rates in infants who received total parenteral nutrition (TPN) (50.0 vs. 13.3%, p = 0.026). The presence of cardiac or ultrasound-defined hepatobiliary abnormalities was not correlated with DH. Due to the high rates of DH in hospitalized neonates with trisomy 13 and 18, we recommend screening newborns with trisomy 13 or 18 for DH starting in the first week of life and continuing at least weekly until 4 weeks of life or until completion of TPN, whichever comes later. Future studies should further evaluate possible etiologies of DH in this population.

Temporal brain microRNA expression changes in a mouse model of neonatal hypoxic-ischemic injury.

BACKGROUND: Neonatal hypoxic-ischemic brain injury (HIBI) results in significant morbidity and mortality despite current standard therapies. MicroRNAs (miRNAs) are a promising therapeutic target; however, there is a paucity of data on endogenous miRNA expression of the brain after HIBI during the primary therapeutic window (6-72 h after injury). METHODS: Postnatal day 9 mouse pups underwent unilateral carotid ligation+hypoxia (HIBI), sham surgery+hypoxia, or sham surgery+normoxia (controls). miRNA sequencing was performed on the ipsilateral brain of each of the three groups plus the contralateral HIBI brain at 24 and 72 h after injury. Findings were validated in eight key miRNAs by quantitative polymerase chain reaction. RESULTS: Hypoxia resulted in significant differential expression of 38 miRNAs at both time points. Mir-2137, -335, -137, and -376c were significantly altered by neonatal HIBI at 24 and 72 h, with 3 of the 4 demonstrating multiphasic expression (different direction of differential expression at 24 versus 72 h). CONCLUSIONS: Our global assessment of subacute changes in brain miRNA expression after hypoxia or HIBI will advance research into targeted miRNA-based interventions. It will be important to consider the multiphasic miRNA expression patterns after HIBI to identify optimal timing for individual interventions. IMPACT: This study is the first to comprehensively define endogenous brain microRNA expression changes outside of the first hours after neonatal hypoxic-ischemic brain injury (HIBI). Mir-2137, -335, -137, and -376c were significantly altered by neonatal HIBI and therefore deserve further investigation as possible therapeutic targets. The expression profiles described will support the design of future studies attempting to develop miRNA-based interventions for infants with HIBI. At 24 h after injury, contralateral HIBI miRNA expression patterns were more similar to ipsilateral HIBI than to controls, suggesting that the contralateral brain is not an appropriate "internal control" for miRNA studies in this model.

Biogenesis, physiological functions and potential applications of extracellular vesicles in substance use disorders.

Substance use disorder (SUD) is a growing health problem that affects several millions of people worldwide, resulting in negative socioeconomic impacts and increased health care costs. Emerging evidence suggests that extracellular vesicles (EVs) play a crucial role in SUD pathogenesis. EVs, including exosomes and microvesicles, are membrane-encapsulated particles that are released into the extracellular space by most types of cells. EVs are important players in mediating cell-to-cell communication through transfer of cargo such as proteins, lipids and nucleic acids. The EV cargo can alter the status of recipient cells, thereby contributing to both physiological and pathological processes; some of these play critical roles in SUD. Although the functions of EVs under several pathological conditions have been extensively reviewed, EV functions and potential applications in SUD remain less studied. In this review, we provide an overview of the current knowledge of the role of EVs in SUD, including alcohol, cocaine, heroin, marijuana, nicotine and opiate abuse. The review will focus on the biogenesis and cargo composition of EVs as well as the potential use of EVs as biomarkers of SUD or therapeutic targets in SUD.

Inhaled Corticosteroid Exposure in Hospitalized Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: The objective of this paper was to determine inhaled corticosteroid (IC) use in infants with bronchopulmonary dysplasia (BPD), define the interhospital variation of IC administration to infants with BPD, and compare clinical, demographic, and hospital factors associated with IC use. STUDY DESIGN: Using the Pediatric Health Information System database, a retrospective multicenter cohort of 4,551 infants born at <32 weeks of gestation with developing BPD was studied. The clinical, demographic, and hospital characteristics of infants exposed and not exposed to ICs were compared. RESULTS: IC use varied markedly between hospitals, ranging from 0 to 66% of infants with BPD exposed to ICs. Increased annual BPD census was not associated with IC use. In total, 25% (1,144 out of 4,551) of patients with BPD and 43% (536 out of 1,244) of those with severe BPD received ICs. Increased IC exposure was associated with lower birth weight and gestational age, days on respiratory support, need for positive pressure ventilation at 36-week postmenstrual age, need for tracheostomy, and increased use of systemic steroids, bronchodilators, and diuretics. CONCLUSION: IC exposure is common in infants with BPD, with substantial interhospital variability. IC use was associated with more severe disease. Hospital experience did not account for the wide variability in IC use by the hospital. Further research into the effects of ICs use is urgently needed to help guide their use in this vulnerable population. KEY POINTS: · The risks and benefits of IC use in infants with BPD are incompletely understood.. · IC use is common in infants with BPD (25%) and severe BPD (43%) varies widely by hospital (0-66% of patients with BPD received an IC).. · Hospital experience did not account for the wide interhospital variation in IC use..

Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children's Hospital Neonatal Consortium.

OBJECTIVE: This study was aimed to describe utilization of therapeutic hypothermia (TH) in neonates presenting with mild hypoxic-ischemic encephalopathy (HIE) and associated neurological injury on magnetic resonance imaging (MRI) scans in these infants. STUDY DESIGN: Neonates ≥ 36 weeks' gestation with mild HIE and available MRI scans were identified. Mild HIE status was assigned to hyper alert infants with an exaggerated response to arousal and mild HIE as the highest grade of encephalopathy recorded. MRI scans were dichotomized as "injury" versus "no injury." RESULTS: A total of 94.5% (257/272) neonates with mild HIE, referred for evaluation, received TH. MRI injury occurred in 38.2% (104/272) neonates and affected predominantly the white matter (49.0%, n = 51). Injury to the deep nuclear gray matter was identified in (10.1%) 20 infants, and to the cortex in 13.4% (n = 14 infants). In regression analyses (odds ratio [OR]; 95% confidence interval [CI]), history of fetal distress (OR = 0.52; 95% CI: 0.28-0.99) and delivery by caesarian section (OR = 0.54; 95% CI: 0.31-0.92) were associated with lower odds, whereas medical comorbidities during and after cooling were associated with higher odds of brain injury (OR = 2.31; 95% CI: 1.37-3.89). CONCLUSION: Majority of neonates with mild HIE referred for evaluation are being treated with TH. Odds of neurological injury are over two-fold higher in those with comorbidities during and after cooling. Brain injury predominantly involved the white matter. KEY POINTS: · Increasingly, neonates with mild HIE are being referred for consideration for hypothermia therapy.. · Drift in clinical practice shows growing number of neonates treated with hypothermia as having mild HIE.. · MRI data show that 38% of neonates with mild HIE have brain injury, predominantly in the white matter..

Ferroptosis: A Promising Therapeutic Target for Neonatal Hypoxic-Ischemic Brain Injury.

Ferroptosis is a type of programmed cell death caused by phospholipid peroxidation that has been implicated as a mechanism in several diseases resulting from ischemic-reperfusion injury. Most recently, ferroptosis has been identified as a possible key injury mechanism in neonatal hypoxic-ischemic brain injury (HIBI). This review summarizes the current literature regarding the different ferroptotic pathways, how they may be activated after neonatal HIBI, and which current or investigative interventions may attenuate ferroptotic cell death associated with neonatal HIBI.

Surveillance guidelines for children with trisomy 18.

Trisomy 18 is the second most common aneuploidy syndromes in live born infants. It is associated with high mortality rates, estimated to be 75%-95% in the first year of life, as well as significant morbidity in survivors. The low survival is largely due to the high prevalence of severe congenital anomalies in infants with this diagnosis. However, interventions to repair or palliate those life-threatening anomalies are being performed at a higher rate for these infants, resulting in increased rates of survival beyond the first year of life. While it is well documented that trisomy 18 is associated with several cardiac malformations, these patients also have respiratory, neurological, neoplastic, genitourinary, abdominal, otolaryngologic, and orthopedic complications that can impact their quality of life. The goal of this review is to present a comprehensive description of complications in children with trisomy 18 to aid in the development of monitoring and treatment guidelines for the increasing number of providers who will be caring for these patients throughout their lives. Where the evidence is available, this review presents screening recommendations to allow for more rapid detection and documentation of these complications.

Surveillance guidelines for children with trisomy 13.

Trisomy 13 is one of the three most common aneuploidy syndromes in live-born infants. It is associated with mortality rates as high as 90% within the first year of life, in large part, due to the high prevalence of severe congenital abnormalities that increase mortality and morbidity. However, life-saving and life-prolonging medical interventions are being performed at a higher rate for these infants, resulting in increased rates of survival. Although cardiac complications have been well described in infants with trisomy 13, these patients also experience other complications such as respiratory, neurological, genitourinary, abdominal, otolaryngologic, and orthopedic complications that can impact their quality of life. The goal of this review is to present a comprehensive description of complications in children with trisomy 13 to aid in the development of monitoring and treatment guidelines for the increasing number of providers who will be caring for these patients throughout their lives. Where the evidence is available, this review presents screening recommendations to allow for more rapid detection and documentation of these complications.

Cholesterol metabolism and brain injury in neonatal encephalopathy.

Neonatal encephalopathy (NE) results from impaired cerebral blood flow and oxygen delivery to the brain. The pathophysiology of NE is complex and our understanding of its underlying pathways continues to evolve. There is considerable evidence that cholesterol dysregulation is involved in several adult diseases, including traumatic brain injury, stroke, Huntington's disease, and Parkinson's disease. Although the research is less robust in pediatrics, there is emerging evidence that aberrations in cholesterol metabolism may also be involved in the pathophysiology of neonatal NE. This narrative review provides an overview of cholesterol metabolism in the brain along with several examples from the adult literature where pathologic alterations in cholesterol metabolism have been associated with inflammatory and ischemic brain injury. Using those data as a background, the review then discusses the current preclinical data supporting the involvement of cholesterol in the pathogenesis of NE as well as how brain-specific cholesterol metabolites may serve as serum biomarkers for brain injury. Lastly, we review the potential for using the cholesterol metabolic pathways as therapeutic targets. Further investigation of the shifts in cholesterol synthesis and metabolism after hypoxia-ischemia may prove vital in understanding NE pathophysiology as well as providing opportunities for rapid diagnosis and therapeutic interventions. IMPACT: This review summarizes emerging evidence that aberrations in cholesterol metabolism may be involved in the pathophysiology of NE. Using data from NE as well as analogous adult disease states, this article reviews the potential for using cholesterol pathways as targets for developing novel therapeutic interventions and using cholesterol metabolites as biomarkers for injury. When possible, gaps in the current literature were identified to aid in the development of future studies to further investigate the interactions between cholesterol pathways and NE.

Clinical risk factors for the development of late-onset circulatory collapse in premature infants.

BACKGROUND: Very low birth weight (VLBW) infants may be at risk for late-onset circulatory collapse (LCC) where otherwise stable infants develop hypotension resistant to vasoactive agents. The risk factors for LCC development are poorly defined, and it has been theorized that it may be in part due to withdrawal from exogenous prenatal steroids. The goal of this study was to define the clinical characteristics of LCC and investigate its association with antenatal steroid administration. METHODS: This is a retrospective cohort study of infants born ≤1500 g. LCC was retrospectively diagnosed in infants requiring glucocorticoids for circulatory instability at >1 week of life. Demographic and clinical characteristics were compared between groups using Mann-Whitney test. RESULTS: Three hundred and ten infants were included; 19 (6.1%) developed LCC. Infants with LCC were born at a median 4.6 weeks' lower gestation, 509 g lower birth weight than those without LCC. There was no difference in antenatal steroid delivery between the groups. CONCLUSIONS: LCC occurs in a distinct subset of VLBW infants, suggesting the need for monitoring in this high-risk population. Antenatal steroids did not significantly increase the risk of LCC development in this study. IMPACT: Late-onset circulatory collapse (LCC) is a life-threatening clinical entity occurring in around 6% in VLBW infants and is likely underdiagnosed in the United States. Targeting specific demographic characteristics such as birth weight (<1000 g) and gestational age at birth (<26 weeks) may allow for early identification of high-risk infants, allowing close monitoring and prompt treatment of LCC. No significant association was found between antenatal steroid administration and LCC development, suggesting that the theoretical risks of antenatal steroids on the fetal HPA axis does not outweigh the benefits of antenatal steroids in fetal lung maturity. To date, no studies characterizing LCC have originated outside of Asia. Therefore, providing a description of LCC in a U.S.-based cohort will provide insight into both its prevalence and presentation to inform clinicians about this potentially devastating disorder and foster early diagnosis and treatment. This study validates LCC characteristics and prevalence previously outlined by Asian studies in a single-center U.S.-based cohort while also identifying potential risk factors for LCC development. This manuscript will provide education for U.S. physicians about the risk factors and clinical presentation of LCC to facilitate early diagnosis and treatment, potentially decreasing neonatal mortality. With prompt recognition and treatment of LCC, infants may have decreased exposure to vasoactive medications that have significant systemic effects.

Increasing Skin-to-Skin in a Level IV NICU: A Quality Improvement Project.

PURPOSE: To evaluate the effect of a bundled intervention on the number of skin-to-skin ("kangaroo care") events occurring in a level IV NICU. DESIGN: A quality improvement effort centering around the introduction of an intervention bundle intended to safely increase the rate of skin-to-skin holding. Rates of unplanned extubations were recorded as a balancing measure to estimate safety. SAMPLE: All infants admitted to the NICU from December 2017 through September 2019 were included. The "preintervention" period was the 6 months prior to the initiation of the intervention bundle (December 2017-May 2018). RESULTS: The absolute number of skin-to-skin holds increased from the preintervention phase (range 7-28 holds/month, median 11 holds/month) to the postintervention phase (range 16-100 holds/month, median 55 holds/month). The total unplanned extubations showed no significant change between the preintervention and postintervention periods.

Neonatal Vitamin D Status Is Associated with the Severity of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy: A Pilot Study.

OBJECTIVE: The primary aim of this study was to evaluate the association between 25-hydroxyvitamin D (25OHD) concentration at birth and the short-term outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). Our secondary aim was to evaluate the effect of postnatal vitamin D supplementation on outcomes in the perinatal period after hypoxic injury. STUDY DESIGN: This retrospective cohort study included all infants ≥35 weeks gestation admitted to a regional level IV neonatal intensive care unit and diagnosed with moderate or severe HIE. Spearman correlation coefficients were used to evaluate associations between clinical outcomes including standardized brain magnetic resonance imaging (MRI) scores and either 25OHD concentrations in the first 48 hours of life or total vitamin D supplementation. RESULT: A total of 43 infants met inclusion criteria; 22 had 25OHD concentrations drawn within the first 48 hours. There was a significant inverse association between 25OHD concentration and brain injury on MRI (p = 0.017). There was a trend toward decreased ventilator days in infants receiving higher doses of vitamin D in the first week of life (p = 0.062), but there was no association between vitamin D dosing and MRI injury. CONCLUSION: These results support an association between lower vitamin-D levels and early adverse outcomes in HIE, including radiographic severity of brain injury.

Combined Treatment with Insulin-Like Growth Factor 1 and AMD3100 Improves Motor Outcome in a Murine Model of Neonatal Hypoxic-Ischemic Encephalopathy.

Stem cell transplantation is a promising intervention for neonatal hypoxic-ischemic encephalopathy (HIE); however, universal feasibility and safety have not been thoroughly evaluated. AMD3100 and insulin-like growth factor 1 (IGF1) mobilize progenitor cells into peripheral circulation. The objective of this study was to assess the short-term efficacy of inducing endogenous stem cell mobilization after injury in a model of neonatal HIE. Postnatal day 9 CD1 pups received sham surgery or unilateral carotid artery ligation and 30 min of hypoxia followed by saline, AMD3100, IGF1, or both agents. Intraperitoneal injections of 5-ethynyl-2'-deoxy-uridine (EdU) and 5-bromo-2'-deoxyuridine were used to -label replicating progenitor cells. At P14, animals underwent rotarod testing, and the brains were sectioned for area measurements and immunofluorescence staining. Comparisons were made using one-way analysis of variance. Spearman's rho was calculated to assess correlation between rotarod results and markers of brain injury. Pups treated with both agents had improved rotarod performance (p = 0.02) and increased EdU+ progenitor cells in the subgranular zone (SGZ) compared to injured controls (p = 0.10). An increase in active cells within the SGZ was correlated with improved rotarod performance (r = 0.84, p = 0.04). There were no differences in overall injury score or in brain area or number of activated cells in the subventricular zone between the treatment groups. Combined treatment with AMD3100 and IGF1 shows promise for decreasing brain injury and improving motor function in pups after HIE which correlated with changes in the number of active progenitor cells in the SGZ.

From cord to caudate: characterizing umbilical cord blood stem cells and their paracrine interactions with the injured brain.

Stem cells are proving to be a promising therapy for a wide range of pediatric disorders, from neonatal hypoxic-ischemic encephalopathy to pediatric leukemia. Owing to their low immunogenicity and ease of availability, umbilical cord blood (UCB) progenitor cells are increasingly replacing fetal- and adult-derived cells in therapeutic settings. Multiple environmental and demographic factors affect the number and type of stem cells extracted from UCB, and these differences have been associated with disparities in outcomes after transplantation. To avoid variations in efficacy, as well as the potential adverse effects of stem cell transplantation, evaluation of the stem cell secretome is critical to identify key paracrine signals released by the stem cells that could be used to provide similar neuroprotective effects to stem cell transplantation. This article describes the cell types found in UCB and reviews the available literature surrounding the effects of collection timing and volume, maternal risk factors, delivery characteristics, and neonatal demographics on the cellular composition of UCB. In addition, the current findings regarding the stem cell secretome are discussed to identify factors that could be used to supplement or replace stem cell transplantation in pediatric neuroprotection.

Evaluating a Targeted Bedside Measure of Cerebral Perfusion in a Nonhuman Primate Model of Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: To compare ultrasound-derived resistive indices (RIs) obtained at the level of the thalamus via fast Doppler ultrasound with traditional anterior cerebral artery measures in a model of neonatal hypoxic-ischemic encephalopathy and to correlate each with clinical outcomes. METHODS: Nine nonhuman primate neonates underwent no umbilical cord occlusion (n = 3), umbilical cord occlusion without hypothermia (n = 3), or umbilical cord occlusion with hypothermia (n = 3). The RI was measured in the anterior cerebral artery and thalamus on days 0, 1, and 4 of life. Magnetic resonance imaging with spectroscopy was performed on day 4. RESULTS: Mean thalamus and anterior cerebral artery RI values in the first 36 hours of life were statistically different in neonates who died (+0.13; P = .019) or developed cerebral palsy (-0.08; P = .003). Thalamic RI values showed stronger associations with serum and spectroscopic lactate values than those in the anterior cerebral artery. The umbilical cord occlusion-with-hypothermia group showed a significant increase in the RI in the thalamus but not the anterior cerebral artery. CONCLUSIONS: Resistive index measurements in the thalamus may eventually supplement other bedside measures for predicting outcomes in the HIE population, but further studies need to differentiate the effect of hypothermia from illness severity on thalamic perfusion.

Fast Doppler as a novel bedside measure of cerebral perfusion in preterm infants.

BACKGROUND: Altered cerebral perfusion from impaired autoregulation may contribute to the morbidity and mortality associated with premature birth. We hypothesized that fast Doppler imaging could provide a reproducible bedside estimation of cerebral perfusion and autoregulation in preterm infants. METHODS: This is a prospective pilot study using fast Doppler ultrasound to assess blood flow velocity in the basal ganglia of 19 subjects born at 26-32 wk gestation. Intraclass correlation provided a measure of test-retest reliability, and linear regression of cerebral blood flow velocity and heart rate or blood pressure allowed for estimations of autoregulatory ability. RESULTS: The intraclass correlation when imaging in the first 48 h of life was 0.634. We found significant and independent correlations between the systolic blood flow velocity and both systolic blood pressure and heart rate (P = 0.015 and 0.012 respectively) only in the 26-28 wk gestational age infants in the first 48 h of life. CONCLUSION: Our results suggest that fast Doppler provides reliable bedside measurements of cerebral blood flow velocity at the tissue level in premature infants, acting as a proxy for cerebral tissue perfusion. Additionally, autoregulation appears to be impaired in the extremely preterm infants, even within a normal range of blood pressures.

Evaluating an Association between Ampicillin and Intraventricular Hemorrhage in Preterm Infants.

Intraventricular hemorrhage (IVH) is a common and potentially devastating adverse outcome affecting up to 30% of preterm infants. ß-Lactam antibiotics affect platelet activation through interaction with platelet surface receptors. The objective of this study was to evaluate an association between ampicillin use and the development of IVH in preterm infants. This was a single-center and a retrospective case-control study of preterm low-birth-weight infants diagnosed with IVH and matched controls without IVH. Conditional logistic regression was performed on 10 clinical features from the first week of life to evaluate the association with IVH. Data were obtained for 174 subjects with no significant differences between groups in demographic factors and level of illness indicators. Earlier administration of the first dose of ampicillin was associated with increased odds of developing IVH (odds ratio [OR]: 0.95, p = 0.028) when controlling for other common associations. Longer courses of ampicillin were not significantly associated with the development of IVH (OR: 1.13, p = 0.089). The odds of developing IVH in our population increased with earlier, but not longer initial courses of ampicillin. Further research into the associations with IVH should include the assessment of ampicillin dose, timing, and duration.