Neurodevelopmental outcome following hypoxic ischaemic encephalopathy and therapeutic hypothermia is related to right ventricular performance at 24-hour postnatal age.

OBJECTIVE: Our aim was to determine whether right ventricular (RV) dysfunction at 24-hour postnatal age predicts adverse developmental outcome among patients with hypoxic ischaemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). DESIGN: Neonates≥35 weeks with HIE/TH were enrolled in a physiological study in the neonatal period (n=46) and either died or underwent neurodevelopmental follow-up at 18 months (n=43). The primary outcome was a composite of death, diagnosis of cerebral palsy or any component of the Bayley Scores of Infant Development III<70. We hypothesised that tricuspid annulus plane systolic excursion (TAPSE) <6 mm and/or RV fractional area change (RV-FAC) <0.29 would predict adverse outcome. RESULTS: Nine patients died and 34 patients were followed up at a mean age of 18.9±1.4 months. Both indices of RV systolic performance were abnormal in 15 (35%) patients, TAPSE <6 mm only was abnormal in 4 (9%) patients and RV-FAC <0.29 only was abnormal in 5 (12%) patients (19 had with normal RV function). Although similar at admission, neonates with RV dysfunction had higher cardiovascular and neurological illness severity by 24 hours than those without and severe MRI abnormalities (70% vs 53%, p=0.01) were more common. On logistic regression, TAPSE <6 mm (OR 3.6, 95% CI 1.2 to 10.1; p=0.017) and abnormal brain MRI [OR 21.7, 95% CI 1.4 to 336; p=0.028) were independently associated with adverse outcome. TAPSE <6 mm predicted outcome with a 91% sensitivity and 81% specificity. CONCLUSIONS: The role of postnatal cardiovascular function on neurological outcomes among patients with HIE who receive TH merits further study. Quantitative measurement of RV function at 24 hours may provide an additional neurological prognostic tool.

Resilience and Vulnerability: Neurodevelopment of Very Preterm Children at Four Years of Age.

Children born very preterm (VPT) are at high-risk for altered brain development and impaired neurodevelopmental outcomes but are not well-studied before school-age. We investigated 64 four-year-olds: 37 VPT children [<32 weeks gestational age [GA]; 22 males; mean GA: 28.8 weeks ± 1.6], 25 full-term (FT) children (12 males), plus two VPT cases with ventriculomegaly and exceptionally resilient outcomes. All children underwent high-resolution structural magnetic resonance imaging and developmental assessments. Measures of brain volume, cortical thickness, and surface area were obtained. Children born VPT demonstrated reduced cerebral and cerebellar white matter volumes yet increased cerebral gray matter, temporal lobe, occipital lobe and ventricle volumes after adjusting for total brain volume. Cortical thickness was greater in the VPT children compared to FT children across all lobes. On developmental assessments, the VPT children scored lower on average than FT children while the two cases had intact cognitive abilities. In addition to larger ventricle volumes, the two cases had white matter and gray matter volumes within the ranges of the FT children. The VPT children displayed distinct differences in structural brain volumes at 4 years of age, consistent with delayed maturation. The cases with persistent ventriculomegaly and good cognitive outcomes displayed typical gray matter and increased white matter volumes, indicating a potential protective developmental phenomenon contributing to their intact cognitive abilities.

Procedural Interventions and Stabilization Times During Interfacility Neonatal Transport.

OBJECTIVE: Transport teams perform multiple procedural interventions during the stabilization of critically ill neonates. The setting of this study was a national cohort of interfacility neonatal transports from nontertiary centers. METHODS: A retrospective cohort study of neonatal transports having interventional procedures using the Canadian Neonatal Transport Network database during 2014 to 2016. Demographics and procedures associated with stabilization times ≤ 120 versus > 120 minutes were analyzed. Predictors of stabilization time were evaluated using multivariable logistic regression analysis. RESULTS: Among 3,350 neonatal transports analyzed, the 3 most frequently performed procedures were peripheral intravenous insertion, arterial blood gas sampling, and endotracheal tube insertion, with success rates of 85.2%, 89.1%, and 95.3%, respectively. The frequency of procedures varied across gestational age subgroups, and success rates were lower for umbilical arterial catheter insertions. After adjustment for confounders, more invasive procedures and a higher number of interventions were associated with longer stabilization times. CONCLUSION: The type and frequency of procedures performed had a significant impact on stabilization time. Any procedures that are nonessential for stabilization at the nontertiary center, such as umbilical arterial catheter insertion, could be minimized to promote timely admission to tertiary centers. The demonstrated variations in procedural success among teams provide useful information for benchmarking and promote the sharing of training practices.

Periventricular Hemorrhagic Infarction in Very Preterm Infants: Characteristic Sonographic Findings and Association with Neurodevelopmental Outcome at Age 2 Years.

OBJECTIVE: To describe the sonographic characteristics of periventricular hemorrhagic infarction (PVHI) and their association with mortality and neurodevelopmental disability in very preterm infants born in 2008-2013. STUDY DESIGN: Retrospective multicenter observational cohort study. Diagonal PVHI size was measured and severity score assessed. PVHI characteristics were scored and temporal trends were assessed. Neurodevelopmental outcome at 2 years of corrected age was assessed using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales. Multigroup analyses were applied as appropriate. RESULTS: We enrolled 160 infants with median gestational age of 26.6 weeks. PVHI was mostly unilateral (90%), associated with an ipsilateral grade III intraventricular hemorrhage (84%), and located in the parietal lobe (51%). Sixty-four (40%) infants with PVHI died in the neonatal period. Of the survivors assessed at 2 years of corrected age, 65% had normal cognitive and 69% had normal motor outcomes. The cerebral palsy rate was 42%. The composite outcome of death or severe neurodevelopmental disability was observed in 58%, with no trends over the study period (P = .6). Increasing PVHI severity score was associated with death (P < .001). Increasing PVHI size and severity score were negatively associated with gross motor scores (P = .01 and .03, respectively). Trigone involvement was associated with cerebral palsy (41% vs 14%; P = .004). Associated posthemorrhagic ventricular dilation (36%) was an independent risk factor for poorer cognitive and motor outcomes (P < .001 for both). CONCLUSIONS: Increasing PVHI size and severity score were predictive of less optimal gross motor outcome and death in very preterm infants.

Impaired Right Ventricular Performance Is Associated with Adverse Outcome after Hypoxic Ischemic Encephalopathy.

Rationale: Asphyxiated neonates with hypoxic ischemic encephalopathy (HIE) are at risk of myocardial dysfunction; however, echocardiography studies are limited and little is known about the relationship between hemodynamics and brain injury.Objectives: To analyze the association between severity of myocardial dysfunction and adverse outcome as defined by the composite of death and/or abnormal magnetic resonance imaging.Methods: Neonates with HIE undergoing therapeutic hypothermia were enrolled. Participants underwent echocardiography at 24 hours, 72 hours (before rewarming), and 96 hours (after rewarming). Cerebral hemodynamics were monitored by near-infrared spectroscopy and middle cerebral artery Doppler.Measurements and Main Results: Fifty-three patients with a mean gestation and birthweight of 38.8 ± 2.0 weeks and 3.33 ± 0.6 kg, respectively, were recruited. Thirteen patients (25%) had mild encephalopathy, 27 (50%) had moderate encephalopathy, and 13 (25%) had severe encephalopathy. Eighteen patients (34%) had an adverse outcome. Severity of cardiovascular illness (P < 0.001) and severity of neurologic insult (P = 0.02) were higher in neonates with adverse outcome. Right ventricle (RV) systolic performance at 24 hours was substantially lower than published normative data in all groups. At 24 hours, lower tricuspid annular plane systolic excursion (P = 0.004) and RV fractional area change (P < 0.001), but not pulmonary hypertension, were independently associated with adverse outcome on logistic regression. High brain regional oxygen saturation (P = 0.007) and low middle cerebral artery resistive index (P = 0.04) were associated with RV dysfunction on post hoc analysis.Conclusions: RV dysfunction is associated with the risk of adverse outcome in asphyxiated patients with HIE undergoing hypothermia. Echocardiography may be a valuable diagnostic and prognostic tool in this vulnerable population.

White matter injury predicts disrupted functional connectivity and microstructure in very preterm born neonates.

OBJECTIVE: To determine whether the spatial extent and location of early-identified punctate white matter injury (WMI) is associated with regionally-specific disruptions in thalamocortical-connectivity in very-preterm born neonates. METHODS: 37 very-preterm born neonates (median gestational age: 28.1 weeks; interquartile range [IQR]: 27-30) underwent early MRI (median age 32.9 weeks; IQR: 32-35), and WMI was identified in 13 (35%) neonates. Structural T1-weighted, resting-state functional Magnetic Resonance Imaging (rs-fMRI, n = 34) and Diffusion Tensor Imaging (DTI, n = 31) sequences were acquired using 3 T-MRI. A probabilistic map of WMI was developed for the 13 neonates demonstrating brain injury. A neonatal atlas was applied to the WMI maps, rs-fMRI and DTI analyses to extract volumetric, functional and microstructural data from regionally-specific brain areas. Associations of thalamocortical-network strength and alterations in fractional anisotropy (FA, a measure of white-matter microstructure) with WMI volume were assessed in general linear models, adjusting for age at scan and cerebral volumes. RESULTS: WMI volume in the superior (ß = -0.007; p = .02) and posterior corona radiata (ß = -0.01; p = .01), posterior thalamic radiations (ß = -0.01; p = .005) and superior longitudinal fasciculus (ß = -0.02; p = .001) was associated with reduced connectivity strength between thalamus and parietal resting-state networks. WMI volume in the left (ß = -0.02; p = .02) and right superior corona radiata (ß = -0.03; p = .008), left posterior corona radiata (ß = -0.03; p = .01), corpus callosum (ß = -0.11; p < .0001) and right superior longitudinal fasciculus (ß = -0.02; p = .02) was associated with functional connectivity strength between thalamic and sensorimotor networks. Increased WMI volume was also associated with decreased FA values in the corpus callosum (ß = -0.004, p = .015). CONCLUSIONS: Regionally-specific alterations in early functional and structural network complexity resulting from WMI may underlie impaired outcomes.

Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?

OBJECTIVE: To compare neurodevelopmental outcomes of preterm infants with and without intervention for posthemorrhagic ventricular dilatation (PHVD) managed with an "early approach" (EA), based on ventricular measurements exceeding normal (ventricular index [VI] <+2 SD/anterior horn width <6 mm) with initial temporizing procedures, followed, if needed, by permanent shunt placement, and a "late approach" (LA), based on signs of increased intracranial pressure with mostly immediate permanent intervention. METHODS: Observational cohort study of 127 preterm infants (gestation <30 weeks) with PHVD managed with EA (n = 78) or LA (n = 49). Ventricular size was measured on cranial ultrasound. Outcome was assessed at 18-24 months. RESULTS: Forty-nine of 78 (63%) EA and 24 of 49 (49%) LA infants received intervention. LA infants were slightly younger at birth, but did not differ from EA infants for other clinical measures. Initial intervention in the EA group occurred at younger age (29.4/33.1 week postmenstrual age; p < 0.001) with smaller ventricles (VI 2.4/14 mm >+2 SD; p < 0.01), and consisted predominantly of lumbar punctures or reservoir taps. Maximum VI in infants with/without intervention was similar in EA (3/1.5 mm >+2 SD; p = 0.3) but differed in the LA group (14/2.1 mm >+2 SD; p < 0.001). Shunt rate (20/92%; p < 0.001) and complications were lower in EA than LA group. Most EA infants had normal outcomes (>-1 SD), despite intervention. LA infants with intervention had poorer outcomes than those without (p < 0.003), with scores <-2 SD in 81%. CONCLUSION: In preterm infants with PHVD, those with early intervention, even when eventually requiring a shunt, had outcomes indistinguishable from those without intervention, all being within the normal range. In contrast, in infants managed with LA, need for intervention predicted worse outcomes. Benefits of EA appear to outweigh potential risks. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for preterm infants with PHVD, an EA to management results in better neurodevelopmental outcomes than a LA.

Longitudinal Study of White Matter Development and Outcomes in Children Born Very Preterm.

Identifying trajectories of early white matter development is important for understanding atypical brain development and impaired functional outcomes in children born very preterm (<32 weeks gestational age [GA]). In this study, 161 diffusion images were acquired in children born very preterm (median GA: 29 weeks) shortly following birth (75), term-equivalent (39), 2 years (18), and 4 years of age (29). Diffusion tensors were computed to obtain measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), which were aligned and averaged. A paediatric atlas was applied to obtain diffusion metrics within 12 white matter tracts. Developmental trajectories across time points demonstrated age-related changes which plateaued between term-equivalent and 2 years of age in the majority of posterior tracts and between 2 and 4 years of age in anterior tracts. Between preterm and term-equivalent scans, FA rates of change were slower in anterior than posterior tracts. Partial least squares analyses revealed associations between slower MD and RD rates of change within the external and internal capsule with lower intelligence quotients and language scores at 4 years of age. These results uniquely demonstrate early white matter development and its linkage to cognitive functions.

Longitudinal cerebellar growth following very preterm birth.

PURPOSE: To measure cerebellar growth in a longitudinal cohort of very preterm infants to identify early predictors of subsequent brain growth. Although the cerebellum grows rapidly during late gestation, the rate and variability of growth following premature birth, and the effects of associated injury, are largely unknown. MATERIALS AND METHODS: In all, 105 very-preterm born infants (24-32 weeks GA) were imaged using magnetic resonance imaging (MRI) at birth, term-equivalent, 2, and 4 years of age. Cerebellar and total cerebral volumes were estimated from 1 mm isotropic T1 -weighted scans acquired at 1.5T and 3T, using an atlas-based approach. Linear models were used to analyze cerebellar volume as cross-sectional and longitudinal functions of age, clinical, and radiological correlates. Linear models were also used to test for associations between volume and cognitive outcome. RESULTS: Cerebellar volume increased rapidly with age-at-scan during both the preterm (0.7 mL/wk, P < 0.001) and term periods (1.8 mL/wk, P < 0.001). Infants with grade 3 or 4 germinal matrix hemorrhage (GMH) had smaller cerebellar volumes as a percentage of total brain volume starting at birth and continuing to 4 years of age (-0.43%, -0.57%, -1.09% at preterm, term, and 4 years, respectively, P < 0.01). Irrespective of age-at-scan, early cerebellar volume was predictive of volume at 4 years of age (slope = 1.3, P < 0.001). Cerebellar volumes were not found to predict cognitive outcome at 4 years of age; P < 0.2. CONCLUSION: High-grade GMH and small perinatal cerebellar size is predictive of cerebellar development up to 4 years of age. These findings suggest that it is possible to identify individuals at high risk of reduced cerebellar volumes at an early age. J. Magn. Reson. Imaging 2016;43:1462-1473.

Associations of Perinatal Clinical and Magnetic Resonance Imaging Measures with Developmental Outcomes in Children Born Very Preterm.

OBJECTIVE: To identify perinatal risk factors associated with long-term neurocognitive and behavioral impairments in children born very preterm using a multivariate, partial least squares approach. STUDY DESIGN: Twenty-seven perinatal clinical and magnetic resonance imaging measures were collected at birth and during the neonatal intensive care stay for 105 neonates born very preterm (≤ 32 weeks gestational age). One-half of the children returned for neuropsychological assessments at 2 and 4 years of age. Parent-reported behavioral measures were also obtained at 4 years of age. Three partial least squares analyses were performed to determine associations between clinical and radiologic measures with cognitive outcomes at 2 and 4 years of age, as well as with behavioral measures at 4 years of age. RESULTS: Within the first components of each analysis, only intrauterine growth restriction, male sex, and absence of antenatal corticosteroid use were associated with poorer cognitive and language ability at 2 and 4 years of age, accounting for 79.6% and 71.4% of the total variance, respectively. In addition, white matter injury at term-equivalent age contributed to more problematic internalizing behaviors, behavioral symptoms, and impaired executive function at 4 years of age, accounting for 67.9% of the total variance. CONCLUSIONS: Using this data-driven multivariate approach, specific measures in prenatal and early postnatal life are shown to be selectively and significantly associated with cognitive and behavioral outcomes in children born very preterm. Early detection of risk factors can help inform prognoses of children at greatest risk of long-term impairments.

Limitations of routine neuroimaging in predicting outcomes of preterm infants.

INTRODUCTION: Preterm births are increasing in number and while the rates of cerebral palsy have declined, there are increasing numbers of infants who survive with handicaps. In some studies, up to 50 % of children will have morbidity when followed up to school age. METHODS: A review of current literature was conducted to determine the validity of routine cranial ultrasound scans (CUS) to predict neurodevelopmental outcomes, including motor and cognitive deficits. We also reviewed the additional benefit offered by including MRI scans in scanning protocols to enhance the reliability in predicting the neurodevelopmental sequelae of prematurity. RESULTS: CUS is valuable as a screening tool to determine significant brain injury when conducted regularly over the first weeks of life in preterm infants. Subtle changes on CUS are difficult to interpret and more precise information is offered by performing MRI scans. These are most often carried out at term equivalent age but earlier scans may be just as useful in predicting neurocognitive outcomes. When MRI scans are either normal or seriously abnormal, there is a very clear correlation with outcome to 2 years of age. Mild and moderate degrees of injury defined on MRI need more sophisticated scanning sequences to determine the likelihood of associated sequelae. Follow-up to school age is essential to diagnose more subtle cognitive delays. CONCLUSION: CUS provides a good screening tool to detect serious brain injury resulting in motor handicaps but MRI scans are complementary and necessary to accurately predict the outcomes of preterm infants, especially cognitive delays.

Quantitative MRI in the very preterm brain: assessing tissue organization and myelination using magnetization transfer, diffusion tensor and T1 imaging.

Magnetization transfer ratio (MTR), diffusion tensor imaging (DTI) parameters and T(1) relaxometry values were used to create parametric maps characterizing the tissue microstructure of the neonatal brain in infants born very premature (24-32 gestational weeks) and scanned at preterm and term equivalent age. Group-wise image registration was used to determine anatomical correspondence between individual scans and the pooled parametric data at the preterm and term ages. These parametric maps showed distinct contrasts whose interrelations varied across brain regions and between the preterm and term period. Discrete patterns of regional variation were observed for the different quantitative parameters, providing evidence that MRI is sensitive to multiple independent aspects of brain maturation. MTR values showed a marked change in the pattern of regional variation at term equivalent age compared to the preterm period such that the ordinal ranking of regions by signal contrast changed. This was unlike all other parameters where the regional ranking was preserved at the two time points. Interpreting the data in terms of myelination and structural organization, we report on the concordance with available histological data and demonstrate the value of quantitative MRI for tracking brain maturation over the neonatal period.

Visual functional magnetic resonance imaging of preterm infants.

AIM: The aim of this study was to determine the feasibility of undertaking visual functional magnetic resonance imaging (fMRI) in very preterm children. METHOD: Forty-seven infants born at less than 32 weeks gestational age (25 males, 22 females; mean (SD) age at birth 28.8 wks [1.9]) were scanned using 1.5 T MRI as part of a longitudinal neuroimaging study. These infants were scanned at preterm age (within 2 wks of birth) and at term-equivalent age. Quantitative T2* data and fMRI in response to visual stimuli (flashing strobe) were acquired in this population. T2* values were compared at preterm age and at term-equivalent age using a two-tailed t-test. A general linear model was used to evaluate occipital lobe response to visual stimuli. RESULTS: T2* values were significantly higher at preterm age than at term-equivalent age in both the medial and lateral occipital lobes (preterm infants: 187.2 ms and 198.4 ms respectively; term infants: 110.9 ms and 133.2 ms respectively; p<0.002). Significant positive occipital lobe activation (q<0.01) was found in 3 out of 65 (5%) fMRIs carried out at preterm age and in 19 out of 26 (73%) scans carried out at term-equivalent age. INTERPRETATION: Visual stimuli do not elicit a reliable blood oxygen level-dependent (BOLD) response in very preterm infants during the preterm period. This suggests that BOLD fMRI may not be the appropriate modality for investigating occipital lobe function in very preterm infants.

Deep gray matter maturation in very preterm neonates: regional variations and pathology-related age-dependent changes in magnetization transfer ratio.

PURPOSE: To elucidate the relationship between gestational age, pathologic findings, and magnetic resonance (MR) imaging measures of tissue maturation-myelination in deep gray matter areas in very preterm neonates imaged at birth. MATERIALS AND METHODS: The study was approved by the research ethics board. Written informed consent was given by the infants' parents. Forty-two preterm neonates (19 boys; median gestational age, 28.7 weeks) with normal-appearing gray matter structures at presentation underwent MR imaging within 2 weeks of birth that included T1- and T2-weighted, magnetization transfer, and T1 relaxometry sequences. Neonates were separated into the following groups: those with normal findings (n = 23), those with white matter injury (WMI) (n = 9), those with grade I germinal matrix hemorrhage (GMH) (n = 3), and those with grade II GMH and WMI (n = 7). Analysis of covariance was used to determine regional effects of age and pathologic findings on magnetization transfer ratio (MTR) and to assess the relationship between MTR and T1. RESULTS: MTR increased linearly with age (P ≤ .0265), with a similar rate of change of 0.32% per week (95% confidence interval [CI]: 0.16, 0.49) in the basal ganglia (BG) and thalami. A lower trend (0.11% per week; 95% CI: -0.05, 0.28) was seen in the pons. Higher MTRs were seen in the thalami and pons than in the BG (P < .05), indicating earlier maturation. Accordingly, higher T1 values were observed in the BG relative to the thalami (P < .0001). Higher MTRs in the BG were observed in the group of neonates with normal findings at presentation than in the group with WMI (P = .02). CONCLUSION: MTR measurements can be used to monitor early myelination in the developing brain and to help detect changes in tissue that are not shown on T1- and T2-weighted MR images.

Optimized T1- and T2-weighted volumetric brain imaging as a diagnostic tool in very preterm neonates.

BACKGROUND: T1- and T2-W MR sequences used for obtaining diagnostic information and morphometric measurements in the neonatal brain are frequently acquired using different imaging protocols. Optimizing one protocol for obtaining both kinds of information is valuable. OBJECTIVE: To determine whether high-resolution T1- and T2-W volumetric sequences optimized for preterm brain imaging could provide both diagnostic and morphometric value. MATERIALS AND METHODS: Thirty preterm neonates born between 24 and 32 weeks' gestational age were scanned during the first 2 weeks after birth. T1- and T2-W high-resolution sequences were optimized in terms of signal-to-noise ratio, contrast-to-noise ratio and scan time and compared to conventional spin-echo-based sequences. RESULTS: No differences were found between conventional and high-resolution T1-W sequences for diagnostic confidence, image quality and motion artifacts. A preference for conventional over high-resolution T2-W sequences for image quality was observed. High-resolution T1 images provided better delineation of thalamic myelination and the superior temporal sulcus. No differences were found for detection of myelination and sulcation using conventional and high-resolution T2-W images. CONCLUSION: High-resolution T1- and T2-W volumetric sequences can be used in clinical MRI in the very preterm brain to provide both diagnostic and morphometric information.

Impact of oxygen saturation targets and oxygen therapy during the transport of neonates with clinically suspected congenital heart disease.

BACKGROUND: Although guidelines for mechanical ventilation, cardiovascular support and intravenous prostaglandin are well established, there is a lack of consensus regarding SpO(2) targets and safety of oxygen administration during transport of neonates with suspected congenital heart disease (CHD). In many centers, an SpO(2) range of 75-85% is targeted but there is no published evidence of the clinical consequences of this approach. OBJECTIVE: To determine the effect of average SpO(2) range and oxygen administration during neonatal transport on clinical markers of cardiovascular instability. METHODS: A retrospective study was conducted on neonates with suspected CHD who presented at community hospitals. Based on average SpO(2) during transport, neonates were categorized into three distinct groups: group I (SpO(2) <75%), group II (SpO(2) 75-85%), group III (SpO(2) >85%). The severity and proportion of neonates with hypoxemia, metabolic and lactic acidosis on arrival at level III NICU were compared. A comparison was also made between oxygen requirement and indicators of cardiorespiratory instability. RESULTS: Seventy-five neonates were studied and 14 (19%), 38 (50%) and 23 (31%) neonates were allocated to groups I, II and III, respectively. Therapeutic interventions during the transport stabilization process included oxygen (n = 53, 71%), mechanical ventilation (n = 56, 75%) and prostaglandin E1 (n = 63, 84%). The severity or proportion of neonates with hypoxemia, elevated lactate or metabolic acidosis was similar between the groups. Neonates receiving an oxygen requirement of FiO(2) >70% had lower arterial SpO(2) on arrival. A provisional diagnosis of CHD and/or PPHN (p = 0.01) and neonates receiving inotropes (p = 0.005) were independent risk factors for cardiovascular instability. CONCLUSION: If congenital heart disease is strongly suspected oxygen should be cautiously weaned to maintain a minimum SpO(2) >75%. Neonates receiving >70% oxygen are at greatest risk of metabolic acidosis or critical hypoxemia and may benefit from expedited transfer to a cardiac center.

Accuracy of clinical diagnosis and decision to commence intravenous prostaglandin E1 in neonates presenting with hypoxemia in a transport setting.

BACKGROUND: Setting goals for monitoring and initiating life-saving interventions such as prostaglandins (prostaglandin E(1) [PGE(1)]) during transport stabilization are dependent on establishing an accurate clinical diagnosis. OBJECTIVE: The aim of this study was to determine the accuracy of clinical diagnosis of suspected congenital heart disease (CHD) and the decision to initiate PGE(1) in neonates presenting with hypoxemia. METHODS: A retrospective cohort study (2002-2004) on hypoxemic neonates who were transported to an outborn neonatal intensive care unit (NICU) was conducted. Provisional diagnosis established by the transport team was categorized as suspected CHD (group 1), suspected persistent pulmonary hypertension of the newborn (group 2), and suspected CHD and/or persistent pulmonary hypertension of the newborn (group 3) based on history, physical examination, laboratory test, chest radiograph, and initial response to treatment. A definitive diagnosis was established on arrival to NICU by echocardiography. RESULTS: A total of 115 neonates were included in the study. The mean gestational age at birth, median age at admission to NICU, and the mean stabilization time were 38.2 (2.4) weeks, 1 (1-26) days, and 217 (108) hours, respectively. The interventions provided during transport stabilization included mechanical ventilation (n = 86, 75%), PGE(1) (n = 70, 61%), inotropes (n = 41, 36%), and fluid bolus (n = 50, 43%). The accuracy of a provisional diagnosis of CHD by transport team was 87.7% and the positive predictive value was 88.1%. Sixty neonates (88%) received PGE(1) appropriately. Eight neonates (12%) with duct-dependent CHD (n = 68) did not receive PGE(1) and were considered as missed opportunities. Ventilated neonates in groups 1 and 3 were identified as the groups that can potentially benefit from more liberal use of PGE(1) and without any adverse effects. CONCLUSION: Although the accuracy of a diagnosis of CHD and the decision to initiate PGE(1) was high, 12% of neonates with a duct-dependent CHD were transported without commencement of PGE(1). Lower thresholds for PGE(1) administration to hypoxemic neonates may potentially improve preoperative stabilization and minimize neonatal morbidity.

The hemodynamically significant ductus arteriosus in critically ill full-term neonates. Two case reports?

In premature infants, the clinical effects and management of a hemodynamically significant patent ductus arteriosus (HSDA) are well-described. In full-term neonates the ductus arteriosus (DA) is rarely monitored except in cases of concomitant pulmonary hypertension or duct dependent congenital heart disease. Although systemic-pulmonary shunting commonly occurs in mature infants, coinciding with the normal postnatal fall in pulmonary vascular resistance, cardiac failure in the neonatal period is rarely attributed directly to the DA. In this case series, we report two full-term infants who were initially treated for pulmonary hypertension and myocardial dysfunction but developed clinical, radiographic and two-dimensional echocardiographic evidence of cardiac failure secondary to a large unrestrictive patent DA (PDA). One patient was treated with indomethacin, and, although transductal diameter decreased, there was no clinical benefit. Cardiac failure resolved and myocardial function improved in both cases after PDA ligation. We suggest that PDA be monitored closely in neonates recovering from PPHN who have ongoing oxygenation difficulties or myocardial failure. PDA ligation should be considered an option for full term neonates with cardiac failure secondary to a HSDA when other therapeutic options fail.

Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn.

BACKGROUND: Many neonates with severe persistent pulmonary hypertension of the newborn (PPHN) are nonresponders to inhaled nitric oxide (iNO). Milrinone is a promising adjunctive therapy because of its pulmonary vasodilator properties and cardiotropic effects. DESIGN: Case series of neonates with severe PPHN (defined as oxygenation index [OI] >20, failure of iNO therapy, and echocardiographic confirmation of PPHN). SETTING: Tertiary neonatal intensive care unit. SUBJECTS: Full-term (> or =37 weeks) neonates with severe PPHN who received intravenous milrinone. MEASUREMENTS: The primary end point was the effect of intravenous milrinone on OI and hemodynamic stability over a 72-hour study period. Secondary end points examined included duration of iNO and degree of cardiorespiratory support. RESULTS: Nine neonates at a mean gestation of 39.25 +/- 2.76 weeks, birth weight of 3668 +/- 649.1 g, and baseline OI of 28.1 +/- 5.9 received milrinone treatment after a poor initial response to iNO treatment. Intravenous milrinone was commenced at a median age of 21 hours (range, 18-49 hours), and patients were treated for median of 70 hours (range, 23-136). Oxygenation index was significantly reduced after milrinone treatment, particularly in the immediate 24 hours of treatment (8.0 +/- 6.6, P < .001). There was a significant improvement in heart rate (179 +/- 15.2 vs 149.6 +/- 22.4, P < .001) over the same period. Infants who received milrinone did not develop systemic hypotension; in fact, there was a nonsignificant trend toward improved blood pressure. CONCLUSIONS: Intravenous milrinone produces early improvements in oxygenation without compromising systemic blood pressure.

The importance of head growth patterns in predicting the cognitive abilities and literacy skills of small-for-gestational-age children.

This study evaluated the effects of head growth compromise beginning in utero and continuing, in some cases, through the first 9 months of life on the cognitive and literacy skills of school-age small-for-gestational-age (SGA) children. Seventy-one SGA children, aged 7 to 9 years (gestational ages, 24-41 weeks) and 16 full-term appropriate-for-gestational-age control children of comparable socioeconomic backgrounds and age at testing completed tests assessing intelligence, receptive language, working memory, problem solving, visual-motor integration, phonological awareness, reading, and spelling. SGA children were subdivided into head-growth pattern groups based on their head circumference at birth and at 9 months postterm. Analyses showed that SGA children with poor prenatal and postnatal head growth had the worst outcomes, followed by those with prenatal brain compromise, but good postnatal head growth. SGA children with preserved head growth in utero as well as good head growth after birth demonstrated the best outcomes, although spelling skills were deficient relative to full-term peers. The Verbal and Full Scale IQ ratings of the SGA children who had experienced brain compromise in utero declined significantly from 5 to 8 years of age. We conclude that mild intrauterine growth retardation (IUGR) has a minimal effect on the development of cognitive or academic abilities, providing that brain growth in utero is not affected. IUGR that slows brain growth in utero impairs the acquisition of some cognitive and academic abilities, even when followed by good catch-up head growth after birth, whereas poor brain growth in utero followed by little or no catch-up head growth results in widespread impairments. Findings highlight the limits to brain plasticity and emphasize the importance of optimal prenatal and postnatal brain growth.