Neurodevelopmental Outcome In Preterm Infants Research Articles

Caffeine, Bronchopulmonary Dysplasia and Neurodevelopmental Outcomes in Premature Infants

Caffeine, Bronchopulmonary Dysplasia and Neurodevelopmental Outcomes in Premature Infants

Serum neurotrophins at birth correlate with respiratory and neurodevelopmental outcomes of premature infants.

Preterm birth is a significant cause of infant morbidity and mortality, which are primarily the result of respiratory and neurodevelopmental complications. However, no objective biomarker is currently available to predict at birth the risk and severity of such complications. Thus, we sought to determine whether serum neurotrophins concentrations measured at birth correlate with risk for later development of bronchopulmonary dysplasia (BPD) and long-term neurodevelopmental outcomes. This study prospectively included 223 newborns admitted to neonatal intensive care units (NICU) and divided into three groups: (i) preterm infants who developed BPD; (ii) preterm infants who did not develop BPD; (iii) term infants. An exploratory cohort was enrolled in West Virginia, followed by a validation cohort recruited in four NICUs in Ohio. Specimens for serum and tracheal neurotrophins concentrations were collected within 48 h of admission. Infants requiring a fraction of inspired oxygen >0.21 for at least 28 days were diagnosed with BPD. Neurodevelopmental outcomes were extrapolated from Bayley Scales of Infant Development-Third Edition (BSID-III) administered at the 24-month follow-up visit. Serum brain-derived neurotrophic factor (BDNF) concentration at birth had significant negative correlation with later diagnosis of BPD (P = 0.011) and with duration of invasive ventilation and oxygen supplementation (P = 0.009 and 0.015, respectively). Serum nerve growth factor (NGF) concentration at birth had significant positive correlation with BSID-III cognitive and language composite scores at 24 months (P < 0.001 and 0.010, respectively). These data suggest that serum neurotrophins concentrations measured at birth provide prognostic information on subsequent respiratory and neurodevelopmental outcomes.

MRI at term equivalent age for predicting long-term neurodevelopmental outcome in preterm infants – a cohort study

Purpose: Preterm infants are at increased risk of adverse neurodevelopmental outcome (NDO). Cranial ultrasound has limited predictability. The purpose of the study is to evaluate whether magnetic resonance imaging (MRI) done at term equivalent age (TEA) predicts NDO at 18–22 months of corrected gestational age (CGA).Materials and methods: This cohort study of preterm infants born at ≤32 weeks of gestation and/or birth weight <1500 grams between April 2011 and August 2012 was conducted in a tertiary care institute in India. MRI done at TEA was reported using objective scoring. NDO at 18–22-month CGA was assessed using Bayley Scale of Infant Development (BSID) version III. Composite score (CS) < 85 in motor, language, or cognition domain was taken as adverse NDO. Association between individual MRI subscores and NDO was evaluated using multiple linear regressions by backward elimination method. Validity of MRI abnormality in predicting adverse NDO was assessed.Results: Out of 94 infants who had MRI at TEA, 56 (60%) underwent BSID III. Mean gestational age was 29.8 ± 2.1 weeks. Median CS of all domains was lower with higher total MRI score. Predictive accuracy for various subscores ranged from 55 to 73%. By multiple regression analysis, signal abnormality was associated with motor delay (β −8.4; p .02) and cystic white matter (WM) changes with motor delay (β −7.3; p .003) and cognitive delay (β −6.1; p .005).Conclusions: Although specificity and negative predictive value were moderate to high across all subscores in MRI to predict the NDO, the accuracy has been only low to moderate, which limits its use as sole predictor.

Impact of mode of conception on neonatal and neurodevelopmental outcomes in preterm infants.

Is assisted conception associated with neonatal morbidity and mortality and with neurodevelopmental impairment at 2 years of corrected age in preterm infants born before 34 weeks of gestational age? Assisted conception is not associated with an increase in neonatal morbidity and mortality and is even significantly associated with a better 2-year neurodevelopmental outcome in preterm infants. Assisted conception appears to increase the rate of preterm births, though few studies have analysed outcomes for these preterm infants. This prospective observational study included 703 preterm infants born between January 2009 and December 2013 and 573 of them were assessed at 2 years of corrected age. All infants born alive between 24+0 and 33+6 weeks of gestational age and hospitalised at the Angers University Hospital were eligible as long as the mode of conception was known for neonatal outcome assessment. They were enroled in the Loire Infant Follow-up Team (LIFT) prospective longitudinal cohort and included for neurodevelopmental outcome assessment. Neonatal morbidity and mortality were evaluated during hospitalisation based on a composite score including death, intraventricular haemorrhage Grade ≥3, periventricular leukomalacia, treated patent ductus arteriosus and bronchopulmonary dysplasia at 36 weeks of gestational age. The neurodevelopmental outcome at 2 years of corrected age was determined by a physical examination, a neuropsychological test and a parental questionnaire. In order to ensure comparability, infants were matched 1:1 according to maternal age, twin status and propensity score,calculated from variables usually associated (positively or negatively) with assisted conception, including gestational age, z-score of birth weight, antenatal corticosteroids and magnesium sulphate treatments, gender, parity, maternal body mass index, tobacco consumption, outborn delivery (i.e. not at a tertiary-care medical centre) and maternal socio-economic status. There were 703 preterm infants included in the analysis of neonatal morbidity and mortality, including 137 born after assisted conception. After matching, 184 preterm infants were included for neonatal morbidity and mortality analysis. There was no significant association between assisted conception and neonatal morbidity and mortality (aOR 0.67, 95% CI [0.25, 1.77], P = 0.422). 573 infants were assessed at 2 years, including 121 born after assisted conception. After matching, 154 preterm infants were included for neurodevelopmental outcome analysis. Assisted conception was significantly associated with a reduction in the probability of non-optimal neurological development at 2 years (aOR 0.26, 95% CI [0.09, 0.80], P = 0.019). Further studies remain necessary to fully confirm these results. This was a monocentric study and 14% of enroled infants were lost to follow up at 2 years of corrected age. These findings are relevant for providing appropriate information to parents considering assisted conception, and more importantly for those with a preterm infant following a pregnancy achieved by assisted conception. The authors report external funding and no conflicts of interest for this work. N/A.

Health, Physical Growth, and Neurodevelopmental Outcomes in Preterm Infants of Women With Hypertensive Disorders of Pregnancy

ObjectiveTo compare the health, physical growth, and developmental outcomes in preterm infants of women with and without hypertensive disorders of pregnancy (HDP). DesignCross-sectional analysis of health outcomes; physical growth (head circumference, height, and weight) collected at birth and 2 months, corrected for prematurity; and cognitive, language, and motor skills of preterm infants of women with and without HDP. SettingFour NICUs in the United States. ParticipantsWomen (n = 221) and their preterm infants who weighed less than 1,750 g were enrolled in a multicenter, randomized trial of two interventions administered by each infant’s mother when the infant was no longer critically ill. MethodsWomen and their preterm infants were categorized into groups with (n = 80) and without (control, n = 141) HDP. Data were extracted from infants’ medical records, and the women completed questionnaires. ResultsThe infants of women with HDP were more likely to be small for gestational age than the infants of women without HDP (31.7% vs. 10.6%, p < .002). The proportion of infants with greater neurologic risk, patent ductus arteriosus, intraventricular hemorrhage, and days on a ventilator did not differ between the groups. Although mean infant height at 2 months was less in the HDP group than the control group, other growth and neurodevelopmental outcomes did not differ between the groups. ConclusionAmong preterm infants admitted to NICUs, those born to women with HDP were more likely to be small for gestational age than those born to normotensive women. Additional research is needed to optimize care for infants born to women with HDP.

Accelerated Small-World Property of Structural Brain Networks in Preterm Infants at Term-Equivalent Age

Background: The prediction of neurodevelopmental outcomes in preterm infants is one of the clinical challenges of pediatrics. Despite the recent interest in brain development and white matter connectivity using a network-based analysis, very little is known about the brain network of at term-equivalent age in preterm infants. Objective: We aimed to investigate the structural brain network using diffusion MRI following preterm delivery at term-equivalent age compared with term infants and explored the influence of gestational age (GA) and clinical factors. Method: Diffusion tensor imaging data were acquired prospectively from 55 preterm neonates without apparent brain abnormalities (mean gestational age: 29.43 weeks) and 21 full-term infants at term-equivalent age. The global structural brain networks were produced by probabilistic white matter tractography in combination with the Johns Hopkins University neonate atlas to quantify connectivity between different cortical regions. Results: Compared with full-term infants, preterm infants had significantly lower global efficiency (p = 0.048) and increased small worldness (p = 0.012) after correcting for sex and age at MRI scan. The increased small worldness in the brain network at term-equivalent age was significantly linearly correlated with lower GA after adjusting for sex and the effects of postmenstrual age at MRI scan on the data in preterm infants (β = –0.020, p = 0.037). In multivariate analysis, infants with chronic lung disease had significantly decreased changes in clustering (p = 0.014) and local efficiency (p = 0.027). Conclusion: The accelerated small worldness in preterm infants suggests that the structural brain network after preterm birth is reorganized in maximizing integrated and segregated processing, implying resilience against prematurity-associated pathology.

Reducing Brain Injury of Preterm Infants in the Delivery Room.

Cerebrovascular injury is one of the major detrimental consequences of preterm birth. Recent studies have focused their attention on factors that contribute to the development of brain lesions immediately after birth. Among those factors, hypothermia and lower cerebral oxygen saturation during delivery room resuscitation and high tidal volumes delivered during respiratory support are associated with increased risk of severe neurologic injury. In preterm infants, knowledge about causes and prevention of brain injury must be applied before and at birth. Preventive and therapeutic approaches, including correct timing of cord clamping, monitoring of physiological changes during delivery room resuscitation using pulse oximetry, respiratory function monitoring, near infrared spectroscopy, and alpha EEG, may minimize brain injury, Furthermore, postnatal administration of caffeine or other potential novel treatments (e.g., proangiogenic therapies, antioxidants, hormones, or stem cells) might improve long-term neurodevelopmental outcomes in preterm infants.

A review on the relationship between mitochondrial dysfunction and white matter injury in preterm infants

White matter injury in preterm infants has a complex etiology and can lead to long-term neurocognitive and behavioral deficits, but there are still no specific treatment methods for this disease at present. More and more studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of white matter injury in preterm infants and might be a common subcellular mechanism of white matter developmental disorder, which involves oxidative stress, reduced ATP synthesis, and disequilibrium of calcium homeostasis. This article reviews the role of mitochondria in brain development and the mechanism of mitochondrial dysfunction, with a hope to perform early intervention of white matter injury in preterm infants by protecting mitochondrial function, so as to provide a reference for improving the neurodevelopmental outcome of preterm infants who survive.

Influence of Maternal Preeclampsia on Neurodevelopmental Outcomes of Preterm Infants

Objective: The aim of this study was to determine the neurodevelopmental outcome of preterm infants born to mothers with preeclampsia and to compare them with preterm controls.Study design: This was a retrospective, observational study in a large, tertiary, neonatal intensive care unit. Neurodevelopmental evaluations using Bayley Scales of Infant Development II were performed in 226 two-year-old infants with birth weight ≤1500 g and gestational age ≤32 weeks who were born to mothers with preeclampsia and in 493 infants who were born after normotensive pregnancies, matched for gestational age and gender.Results: The mean gestational ages of the infants in the preeclampsia and control groups were 29.9±2.3 weeks and 28.7±4.1 weeks, respectively (p&lt;0.001). A total of 372 infants with a mean age of 19.2±3.2 months were assessed for long-term outcome. The mean mental developmental index score was significantly higher, and the percentage of infants with cerebral palsy was significantly lower, in the preeclampsia group compared with the control group (p=0.03 and p=0.02, respectively). However, no overall significant differences in neurodevelopmental impairment rates were found between the two groups (p=0.08).Conclusion: Maternal preeclampsia seems to be a protector factor for the development of cerebral palsy in preterm infants.

Prediction of long-term neurodevelopmental outcome in preterm infants using trajectories of general movement assessments.

To assess the predictive value of trajectories and individual assessment of quality of general movements (AQGM) for identification of neurodevelopmental impairment (NDI) at 18-24 months corrected age (CA) in infants <30 weeks gestational age and/or birth weight <1500 g. In this retrospective cohort study, AQGM at 6 weeks and 3 months CA were scored and categorized as normal (N) or abnormal (A). AQGM measures were compared with degree of NDI and Bayley Scales of Infant Development, Third Edition (BSID-III) composite motor and cognitive scores. 'Persistently abnormal' AQGM included both mildly abnormal (MA) and definitely abnormal (DA) assessments. A "modified AQGM" where MA assessments were considered normal variant/transient injury was used to conduct post-hoc analysis. Across 244 cases, persistently abnormal AQGM trajectory predicted the level of NDI (OR 2.5, 95% CI 1.2, 5.1) compared to AQGM trajectory that normalized. However, using the "modified AQGM", persistently DA trajectories were associated with significantly lower BSID-III composite motor and cognitive scores (p < 0.001 and p = 0.039, respectively). Categorizing MA assessments as transient injury increased the predictive value of AQGM trajectories and significantly predicted lower cognitive and motor scores at 18-24 months CA.

Low-grade intraventricular hemorrhage and neurodevelopment at 24 months of age

AIMS: To evaluate the impact of low-grade intraventricular hemorrhage on neurodevelopmental outcome in preterm infants at 24 months of age.METHODS: We conducted a retrospective case-control study of infants with gestational age less than 34 weeks, admitted to a Neonatal Intensive Care Unit between January/2006 and December/2015. Cases were defined as those with low-grade intraventricular hemorrhage (grades I or II), diagnosed by cranial ultrasonography. For each case, a control with the same gestational age but without intraventricular hemorrhage was selected. Follow-up examinations of neurodevelopment were performed at 24 months of age in cases and controls using the Griffiths Mental Development Scale. Cerebral palsy, neurodevelopmental delay (developmental quotient &lt;2 side deviations below the mean), hearing impairment and/or blindness were considered as severe neurodevelopmental impairment.RESULTS: The study included 172 preterm infants: 86 cases and 86 controls. In the univariate analysis, a difference between the two groups was identified for the following clinical findings: antenatal corticosteroid complete cycle (57% in cases vs. 80% in controls; p=0.001; OR: 0.33, 95%CI 0.17-0.64); male gender (63% cases vs. 41% controls; p=0.004; OR: 2.45, 95%CI 1.3-4.5); outborn (26% cases vs. 9% controls; p=0.005; OR: 3.3 95%CI 1.4-8.0); Clinical Risk Index for Babies higher than 5 (24% in cases vs. 12% in controls; p=0.029; OR: 2.4 95%CI 1.1-5.6); intubation in the delivery room (47% cases vs. 27% controls; p=0.007; OR: 2.38 95%CI 1.3-4.5); and neonatal sepsis (34% in cases vs. 20% in controls; p=0.039; OR: 2.1 95%CI 1.03-4.1). After logistic regression, differences were only maintained for antenatal corticosteroid (p=0.005; OR 0.34, 95%CI 0.16-0.72) and male gender (p=0.002; OR 2.9, 95%CI 1.4-5.8). A severe neurodevelopmental deficit was present in three cases (3.5%) and one control (1.2%). No statistically significant differences in outcome were found between cases and controls.CONCLUSIONS: In this sample, preterm infants with low-grade intraventricular hemorrhage diagnosed by cranial ultrasonography had no difference in early neurodevelopmental outcome when compared with controls.

Late neuroimaging predicts neurodevelopmental outcomes in preterm infants.

Commentary on: Hintz S, Barnes P, Bulas D, Slovis T, Finer N, Wrage L, et al. Neuroimaging and neurodevelopmental outcome in extremely preterm infants. Pediatrics 2015; 135: e32–42. Neurodevelopmental outcomes are a crucial part of prognosis and are pivotal in ongoing conversations between neonatologists and parents 1, 2. Recent studies show greater predictive value in near-term cranial ultrasound (CUS) and MRI versus traditional CUS performed in the first few weeks of life 1-3. MRI detects white matter injury more accurately while US detects intraventricular haemorrhages, ventriculomegaly and cystic periventricular leukomalacia 2, 4, 5. However, studies have found former preterm infants with developmental impairments despite normal NICU ultrasounds, and, importantly, others have reported transient findings of cystic periventricular leukomalacia (resolving by near-term) are associated with developmental impairments 2, 6, 7. The NEURO prospective study by Hintz et al. 8 analysed the predictive ability of early CUS, near-term CUS and near-term MRI in a cohort of 480 extremely preterm neonates, born at 24–27 weeks. Negative outcomes were defined as neurodevelopmental impairment, significant gross motor impairment or death. The authors provided multivariable modelling to consider perinatal and neonatal demographic and clinical risk factors. Results were presented as OR and AUC of ROC curves. Further statistical calculations of Tables 2–5 show sensitivity and specificity of 0.27 and 0.92, respectively, for the association between major findings in early CUS and negative outcomes of neurodevelopmental impairment or death, compared to sensitivity of 0.28 and specificity of 0.97 for major findings in late CUS. The calculated sensitivity and specificity of MRI WMA are similar to that reported by Woodward et al. 4 in 2006 (92% vs 84% and 23% vs 34%, respectively), demonstrating that MRI has potential for higher sensitivity than CUS. The major findings of the NEURO study were that early CUS is not predictive of future neurodevelopmental outcomes, despite taking into account perinatal and neonatal demographic and clinical risk factors. The ability to predict outcomes is only mildly enhanced by the addition of MRI to late CUS. Therefore, in environments where MRI is not easily available, late CUS may be sufficient in predicting prognosis. The strengths of the NEURO study included large population size, blinded imaging evaluations, required temporal proximity of late CUS and MRI. Limitations included that CUS was obtained by local centre protocol with possibility for technical inconsistencies, and there were low rates of adverse outcomes, leading to wide confidence intervals. While multivariable modelling taking into account neonatal risk factors scrutinises results, a drawback is potential over-analysis. Near-term CUS and MRI have been shown to be more reliable alternatives to early CUS in predicting outcomes, but imaging is only mildly effective in formulating predictions of neurodevelopmental outcomes in extremely premature neonates 2, 4, 9. There is still considerable uncertainty regardless of imaging modality or combination of imaging modalities used. Studies have shown that MRI before discharge is too early to detect posterior limb internal capsule myelination abnormalities, which have been shown to be associated with gross motor deficits 3, 5. Extending outcomes to include cognitive and behavioural difficulties of school-age ex-premature neonates will detect deficits not fully appreciated on Bayley or GMFCS testing 2, 9. https://ebneo.org/2018/06/late-neuroimaging-predicts-neurodevelopmental-outcomes-in-preterm-infants/ None. None.

Relationship between brain function (aEEG) and brain structure (MRI) and their predictive value for neurodevelopmental outcome of preterm infants

To improve the prediction of neurodevelopmental outcome in very preterm infants, this study used the combination of amplitude-integrated electroencephalography (aEEG) within the first 72 h of life and cranial magnetic resonance imaging (MRI) at term equivalent age. A single-center cohort of 38 infants born before 32 weeks of gestation was subjected to both investigations. Structural measurements were performed on MRI. Multiple regression analysis was used to identify independent factors including functional and structural brain measurements associated with outcome at a corrected age of 24 months. aEEG parameters significantly correlated with MRI measurements. Reduced deep gray matter volume was associated with low Burdjalov Score on day 3 (p < 0.0001) and day 1–3 (p = 0.0012). The biparietal width and the transcerebellar diameter were related to Burdjalov Score on day 1 (p = 0.0111; p = 0.0002). The final multiple regression analysis revealed independent predictors of neurodevelopmental outcome: intraventricular hemorrhage (p = 0.0060) and interhemispheric distance (p = 0.0052) for mental developmental index; Burdjalov Score day 1 (p = 0.0201) and interhemispheric distance (p = 0.0142) for psychomotor developmental index.Conclusion: Functional aEEG parameters were associated with altered brain maturation on MRI. The combination of aEEG and MRI contributes to the prediction of outcome at 24 months.What is Known:• Prematurity remains a risk factor for impaired neurodevelopment.• aEEG is used to measure brain activity in preterm infants and cranial MRI is performed to identify structural gray and white matter abnormalities with impact on neurodevelopmental outcome.What is New:• aEEG parameters observed within the first 72 h of life were associated with altered deep gray matter volumes, biparietal width, and transcerebellar diameter at term equivalent age.• The combination of aEEG and MRI contributes to the prediction of neurodevelopmental outcome at 2 years of corrected age in very preterm infants.

Neurodevelopmental Outcomes in Premature Infants with Short Bowel Syndrome

Background: Short bowel syndrome (SBS) is a devastating complication of prematurity. Infants with surgical NEC (sNEC) are at higher risk for neurodevelopmental impairment (NDI). There are limited data on ND outcomes of preterm infants with SBS. Objective: Compare ND and growth outcomes in preterm infants with (1) sNEC or spontaneous intestinal perforation (SIP) + SBS to infants with (2) sNEC or SIP without SBS and to (3) infants with no NEC, SIP or SBS. Design/Methods: Preterm infants born between 22-26 weeks gestational age (GA) in a NICHD Neonatal …

Neurodevelopmental Outcomes in Premature Infants with Short Bowel Syndrome

Neurodevelopmental Outcomes in Premature Infants with Short Bowel Syndrome

Neurodevelopmental Impairment Among Extremely Preterm Infants in the Neonatal Research Network.

Evaluate the spectrum of neurodevelopmental outcome in a contemporary cohort of extremely preterm infants. We hypothesize that the rate of severe neurodevelopmental impairment (NDI) decreases over time. Retrospective analysis of neurodevelopmental outcome of preterm infants ≤27 weeks' gestational age (GA) from a Neonatal Research Network center that completed neurodevelopmental follow-up assessments between April 1, 2011, and January 1, 2015. The Bayley Scales of Infant Development-III (BSID III) and a standardized neurosensory examination were performed between 18 and 26 months' adjusted age. Outcome measures were neurologic examination diagnoses, BSID III cognitive and motor scores, sensory impairment, and the composite outcome of NDI, based on the BSID III cognitive score (analyzed by using a cutoff of <85 or <70), BSID III motor score of <70, moderate or severe cerebral palsy (CP), bilateral blindness, and hearing impairment. Two thousand one hundred and thirteen infants with a mean GA of 25.0 ± 1.0 weeks and mean birth weight of 760 ± 154 g were evaluated. The 11% lost to follow-up were less likely to have private insurance, late-onset sepsis, or severe intraventricular hemorrhage. Neurologic examination results were normal in 59%, suspect abnormal in 19%, and definitely abnormal in 22%. Severe CP decreased 43% whereas mild CP increased 13% during the study. The rate of moderate to severe NDI decreased from 21% to 16% when using the BSID III cognitive cutoff of <70 (P = .07) or from 34% to 31% when using the BSID III cognitive cutoff of <85 (P = .67). Extremely preterm children are at risk for NDI. Over time, the rate of moderate to severe NDI did not differ, but the rates of severe CP decreased, and mild CP increased.

Long-term Neurodevelopmental Outcomes in Preterm Infants with Posthemorrhagic Hydrocephalus Treated with Temporizing Devices (P2.086)

Long-term Neurodevelopmental Outcomes in Preterm Infants with Posthemorrhagic Hydrocephalus Treated with Temporizing Devices (P2.086)

Effects of Intestinal Microbiota on Brain Development in Humanized Gnotobiotic Mice

Poor growth in the Neonatal Intensive Care Unit is associated with an increased risk for poor neurodevelopmental outcomes for preterm infants, however the mechanism is unclear. The microbiome has increasingly been recognized as a modifiable environmental factor to influence host development. Here we explore the hypothesis that the microbiome influences both growth phenotype and brain development. A germ free mouse transfaunation model was used to examine the effects of preterm infant microbiotas known to induce either high growth or low growth phenotypes on postnatal brain development. The microbiome which induced the low growth phenotype was associated with decreases in the neuronal markers NeuN and neurofilament-L as well as the myelination marker MBP when compared to the microbiome associated with the high growth phenotype. Additionally, poor growth phenotype-associated microbiota was associated with increased neuroinflammation marked by increased Nos1, as well as alteration in IGF-1 pathway including decreased circulating and brain IGF-1, decreased circulating IGFBP3, and increased Igfbp3 brain mRNA expression. This study suggests that growth-associated microbiota can influence early neuron and oligodendrocyte development and that this effect may be mediated by effects on neuroinflammation and circulating IGF-1.

Effects of caffeine on the preterm brain: An observational study

Background and aimCaffeine improves neurodevelopmental outcome of preterm infants. This study analyses the effects of caffeine on the neonatal brain. We hypothesized that caffeine has a neuroprotective effect through an increase in oxygen metabolism; reflected by increased cerebral oxygen extraction, electrical function, and perfusion. MethodsPreterm infants <32 weeks gestation (GA) receiving their primary dose caffeine-base (10 mg/kg) were included. Ten minutes of stable monitoring were selected before, during, and every hour up to 6 h after caffeine. Near-infrared spectroscopy monitored regional cerebral oxygenation (rScO2) and extraction (FTOE). Amplitude-integrated electroencephalogram (aEEG) monitored minimum, mean and maximum amplitudes. Spontaneous activity transients (SAT) rate and the interval between SATs (ISI) were calculated. Mean arterial blood pressure (MABP), heart rate (HR) and arterial oxygen saturation (SaO2) were monitored. Arterial pCO2's were collected before and 4 h after caffeine. Brain perfusion was assessed 1 h before and 3 h after caffeine by Doppler-measured resistance-index (RI), peak systolic velocity (PSV) and end-diastolic velocity (EDV), in the anterior cerebral artery (ACA) and internal carotid artery (ICA). Results were presented in mean ± SD. Results34 infants, mean GA 28.8 ± 2.1 wk, were included. rScO2 significantly decreased from 69 ± 11 to 63 ± 12 1 h after caffeine, and recovered at 6 h (66 ± 10). FTOE increased correspondingly. MABP and HR increased significantly. PSV in the ACA decreased slightly. Other Doppler variables, aEEG parameters, and SaO2 were unaffected. ConclusionCaffeine increases oxygen extraction, suggesting a (transient) stimulating effect on brain metabolism. However, no substantial changes were found in brain perfusion and in electrical brain activity.

Term-equivalent functional brain maturational measures predict neurodevelopmental outcomes in premature infants

BackgroundTerm equivalent age (TEA) brain MRI identifies preterm infants at risk for adverse neurodevelopmental outcomes. But some infants may experience neurodevelopmental impairments even in the absence of neuroimaging abnormalities. ObjectiveEvaluate the association of TEA amplitude-integrated EEG (aEEG) measures with neurodevelopmental outcomes at 24–36 months corrected age. MethodsWe performed aEEG recordings and brain MRI at TEA (mean post-menstrual age of 39 (±2) weeks in a cohort of 60 preterm infants born at a mean gestational age of 26 (±2) weeks. Forty-four infants underwent Bayley Scales of Infant Development, 3rd Edition (BSID-III) testing at 24–36 months corrected age. Developmental delay was defined by a score greater than one standard deviation below the mean (<85) in any domain. An ROC curve was constructed and a value of SEF90 < 9.2, yielded the highest sensitivity and specificity for moderate/severe brain injury on MRI. The association between aEEG measures and neurodevelopmental outcomes was assessed using odds ratio, then adjusted for confounding variables using logistic regression. ResultsInfants with developmental delay in any domain had significantly lower values of SEF90. Absent cyclicity was more prevalent in infants with cognitive and motor delay. Both left and right SEF90 < 9.2 were associated with motor delay (OR left: 4.7(1.2–18.3), p = 0.02, OR right: 7.9 (1.8–34.5), p < 0.01). Left SEF90 and right SEF90 were associated with cognitive delay and language delay respectively. Absent cyclicity was associated with motor and cognitive delay (OR for motor delay: 5.8 (1.3–25.1), p = 0.01; OR for cognitive delay: 16.8 (3.1–91.8), p < 0.01). These associations remained significant after correcting for social risk index score and confounding variables. ConclusionsaEEG may be used at TEA as a new tool for risk stratification of infants at higher risk of poor neurodevelopmental outcomes. Therefore, a larger study is needed to validate these results in premature infants at low and high risk of brain injury.