Pamela K. Donohue

The Limit of Viability -- Neonatal Outcome of Infants Born at 22 to 25 Weeks' Gestation

Background With improved survival of preterm infants, questions have been raised about the limit of viability. To provide better information and counseling for parents of infants about to be delivered after 22 to 25 weeks gestation, we evaluated the mortality and neonatal morbidity of preterm infants born at these gestational ages. Methods We studied retrospectively all 142 infants born at 22 to 25 weeks gestation (as judged by best obstetrical estimate) from May 1988 through September 1991 in a single hospital. Mortality in the first six months, including stillbirths, and neonatal morbidity (i.e., the presence of intracranial pathologic conditions, chronic lung disease, and retinopathy of prematurity) were analyzed. Results Fifty-six infants (39 percent) survived for six months. Survival improved with increasing gestational age; none of 29 infants born at 22 weeks gestation survived, as compared with 6 of 40 (15 percent) born at 23 weeks, 19 of 34 (56 percent) born at 24 weeks, and 31 of 39 (79 percen...

Pediatric diffusion tensor imaging: Normal database and observation of the white matter maturation in early childhood

Recent advances in diffusion tensor imaging (DTI) have made it possible to reveal white matter anatomy and to detect neurological abnormalities in children. However, the clinical use of this technique is hampered by the lack of a normal standard of reference. The goal of this study was to initiate the establishment of a database of DTI images in children, which can be used as a normal standard of reference for diagnosis of pediatric neurological abnormalities. Seven pediatric volunteers and 23 pediatric patients (age range: 0-54 months) referred for clinical MR examinations, but whose brains were shown to be normal, underwent anatomical and DTI acquisitions on a 1.5 T MR scanner. The white matter maturation, as observed on DTI color maps, was described and illustrated. Changes in diffusion fractional anisotropy (FA), average apparent diffusion constant (ADC(ave)), and T2-weighted (T2W) signal intensity were quantified in 12 locations to characterize the anatomical variability of the maturation process. Almost all prominent white matter tracts could be identified from birth, although their anisotropy was often low. The evolution of FA, shape, and size of the white matter tracts comprised generally three phases: rapid changes during the first 12 months; slow modifications during the second year; and relative stability after 24 months. The time courses of FA, ADC(ave), and T2W signal intensity confirmed our visual observations that maturation of the white matter and the normality of its architecture can be assessed with DTI in young children. The database is available online and is expected to foster the use of this promising technique in the diagnosis of pediatric pathologies.

White and gray matter development in human fetal, newborn and pediatric brains

Brain anatomy is characterized by dramatic growth from the end of the second trimester through the neonatal stage. The characterization of normal axonal growth of the white matter tracts has not been well-documented to date and could provide important clues to understanding the extensive inhomogeneity of white matter injuries in cerebral palsy (CP) patients. However, anatomical studies of human brain development during this period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor magnetic resonance imaging (DTMRI) can reveal detailed anatomy of white matter. We acquired diffusion tensor images (DTI) of postmortem fetal brain samples and in vivo neonates and children. Neural structures were annotated in two-dimensional (2D) slices, segmented, measured, and reconstructed three-dimensionally (3D). The growth status of various white matter tracts was evaluated on cross-sections at 19-20 gestational weeks, and compared with 0-month-old neonates and 5- to 6-year-old children. Limbic, commissural, association, and projection white matter tracts and gray matter structures were illustrated in 3D and quantitatively characterized to assess their dynamic changes. The overall pattern of the time courses for the development of different white matter is that limbic fibers develop first and association fibers last and commissural and projection fibers are forming from anterior to posterior part of the brain. The resultant DTMRI-based 3D human brain data will be a valuable resource for human brain developmental study and will provide reference standards for diagnostic radiology of premature newborns.

Multi-Contrast Human Neonatal Brain Atlas: Application to Normal Neonate Development Analysis

MRI is a sensitive method for detecting subtle anatomic abnormalities in the neonatal brain. To optimize the usefulness for neonatal and pediatric care, systematic research, based on quantitative image analysis and functional correlation, is required. Normalization-based image analysis is one of the most effective methods for image quantification and statistical comparison. However, the application of this methodology to neonatal brain MRI scans is rare. Some of the difficulties are the rapid changes in T1 and T2 contrasts and the lack of contrast between brain structures, which prohibits accurate cross-subject image registration. Diffusion tensor imaging (DTI), which provides rich and quantitative anatomical contrast in neonate brains, is an ideal technology for normalization-based neonatal brain analysis. In this paper, we report the development of neonatal brain atlases with detailed anatomic information derived from DTI and co-registered anatomical MRI. Combined with a diffeomorphic transformation, we were able to normalize neonatal brain images to the atlas space and three-dimensionally parcellate images into 122 regions. The accuracy of the normalization was comparable to the reliability of human raters. This method was then applied to babies of 37-53 post-conceptional weeks to characterize developmental changes of the white matter, which indicated a posterior-to-anterior and a central-to-peripheral direction of maturation. We expect that future applications of this atlas will include investigations of the effect of prenatal events and the effects of preterm birth or low birth weights, as well as clinical applications, such as determining imaging biomarkers for various neurological disorders.

Achieved Versus Intended Pulse Oximeter Saturation in Infants Born Less Than 28 Weeks' Gestation: The AVIOx Study

OBJECTIVE. The objective of this study was to document pulse oximeter saturation levels achieved in the first 4 weeks of life in infants who were born at <28 weeks gestation, compared with the levels that were targeted by local policy, and examine factors that are associated with compliance with the target range. METHODS. Infants who were <28 weeks gestation and ≤96 hours of age were enrolled in a prospective, multicenter cohort study. Oximetry data were collected with masked signal-extraction oximeters for a 72-hour period in each of the first 4 weeks of life. Data were compared with the pulse oximeter saturation target range prescribed by local institutional policy. Factors that were associated with intended range compliance were identified with hierarchical modeling. RESULTS. Fourteen centers from 3 countries enrolled 84 infants with mean ± SD birth weight of 863 ± 208 g and gestational age of 26 ± 1.4 weeks. Oxygen saturation policy limits ranged between 83% and 92% for lower limits and 92% and 98% for upper limits. For infants who received respiratory support, median pulse oximeter saturation level achieved was 95%. Center-specific medial levels were within the intended range at 12 centers. Centers maintained infants within their intended range 16% to 64% of the time but were above range 20% to 73% of the time. In hierarchical modeling, wider target ranges, higher target range upper limits, presence of a policy of setting oximeter alarms close to the target range limits, and lower gestational age were associated with improved target range compliance. CONCLUSIONS. Success with maintaining the intended pulse oximeter saturation range varied substantially among centers, among patients within centers, and for individual patients over time. Most noncompliance was above the intended range. Methods for improving compliance and the effect of improved compliance on neonatal outcomes require additional research.

Increased morbidity in severe early intrauterine growth restriction.

OBJECTIVE: To determine the relative frequencies of complications in severe early intrauterine growth-restricted (IUGR) infants.METHODS: All infants 32 weeks gestation or less with birth weight less than the fifth percentile admitted from January 1991 to December 1998 were identified retrospectively. Two infants were identified for each IUGR case: the subsequent admission with birth weight ±100u2009g of the case, and the subsequent admission with the same gestational age. Infants with multiple congenital anomalies, congenital infections or admission after 48 hours of age were excluded. Maternal and neonatal demographic data, neonatal morbidity and mortality until discharge were gathered by chart review.RESULTS: A total of 39 IUGR identified infants met criteria, with 41 gestational age infants and 33 birth weight infants. Mean birth weights and gestational ages for the IUGR group, gestational age group, and birth weight group were 744u2009g and 29.6 weeks, 1370u2009g and 29.7 weeks, and 781u2009g and 25.5 weeks respectively. Mortality was higher for IUGR infants than gestational age infants (20.5 vs 0%), but less than the birth weight infants (30%). In surviving infants, total ventilator days, total oxygen days, days to full feeds, and patent ductus arteriosis, were higher for IUGR infants than gestational age infants, but less than birth weight infants. Hypoglycemia, direct hyperbilirubinemia, necrotizing enterocolitis (NEC), thrombo-cytopenia, chronic lung disease and feeding difficulties occurred more frequently in IUGR infants than in both other groups. Length of stay for survivors and incidence of retinopathy of prematurity (ROP) was similar for the IUGR and birth weight infants.CONCLUSIONS: Infants born prematurely who are also severely IUGR have higher neonatal morbidity and mortality when compared to infants of similar gestational age. The surviving IUGR infants had less intraventricular hemorrhage and periventricular leukomalacia than less mature infants of comparable birth weight, but a similar incidence of ROP and length of stay. They had a higher incidence of NEC, direct hyperbilirubinemia and chronic lung disease, probably due to end-organ damage in utero from chronic placental insufficiency. These findings highlight the unique pattern of mortality and morbidity seen in infants with severe early IUGR.

Hyperglycemia and Retinopathy of Prematurity in Very Low Birth Weight Infants

OBJECTIVE: Retinopathy of prematurity (ROP) remains a leading cause of morbidity in the very low-birth-weight (VLBW) infant. This study investigates a possible association between serum/blood glucose and the development of ROP.METHODS: A retrospective case–control study of all infants born between 1992 and 1997 at the Johns Hopkins Hospital with birth weights less than 1000u2009g who developed Stage 3 or 4 ROP was conducted. Controls either had Stage 1 ROP or no eye disease and were matched 2:1 with ROP patients for gestational age, birth weight and year of birth. Odds ratios (ORs) of ROP were calculated for multiple exposures over the first month after birth, including oxygen concentration (FiO2), blood glucose levels, vitamin E, mean airway pressure and mean blood pressure.RESULTS: In a simple logistic regression analysis, we found an increased ROP risk for: (1) each 10u2009mg/dl increase of mean glucose (OR 1.96; 95% CI 1.13 to 3.42), (2) each 1% increase of mean FiO2 (OR 1.06; 95% CI 1.004 to 1.13), (3) history of dopamine infusion (OR 5.4; 95% CI 1.16 to 25.2) and (4) intraventricular hemorrhage Grade 3 or 4 (OR 7.3; 95% CI 1.53 to 34.7). Using a multiple regression model, we found an increased ROP risk for each 10u2009mg/dl increase of mean glucose (OR 2.7; 95% CI 1.003 to 7.27). Each IU/kg/day of vitamin E supplementation reduced ROP risk (OR 0.37; 95% CI 0.16–0.86).CONCLUSION: In this study, we could demonstrate that glucose levels in the first month of life are associated with the development of ROP. Further studies have to determine if this association is causal or if hyperglycemia is just an expression of severity of illness.

Neonatologist training to guide family decision making for critically ill infants.

OBJECTIVESnTo assess neonatology fellow training in guiding family decision making for high-risk newborns and in several critical communication skills for physicians in these scenarios.nnnDESIGNnA Web-based national survey.nnnSETTINGnNeonatal-perinatal training programs in the United States.nnnPARTICIPANTSnGraduating fellows in their final month of fellowship.nnnMAIN OUTCOME MEASURESnFellows perceived training and preparedness to communicate with families about decision making.nnnRESULTSnThe response rate was 72%, representing 83% of accredited training programs. Fellows had a great deal of training in the medical management of extremely premature and dying infants. However, they reported much less training to communicate and make collaborative decisions with the families of these infants. More than 40% of fellows reported no communication training in the form of didactic sessions, role play, or simulated patient scenarios and no clinical communication skills training in the form of supervision and feedback of fellow-led family meetings. Fellows felt least trained to discuss palliative care, families religious and spiritual needs, and managing conflicts of opinion between families and staff or among staff. Fellows perceived communication skills training to be of a higher priority to them than to faculty, and 93% of fellows feel that training in this area should be improved.nnnCONCLUSIONSnGraduating neonatology fellows are highly trained in the technical skills necessary to care for critically ill and dying neonates but are inadequately trained in the communication skills that families identify as critically important when facing end-of-life decisions.

Burnout and Resilience Among Nurses Practicing in High-Intensity Settings

BACKGROUNDnThe high level of stress experienced by nurses leads to moral distress, burnout, and a host of detrimental effects.nnnOBJECTIVESnTo support creation of healthy work environments and to design a 2-phase project to enhance nurses resilience while improving retention and reducing turnover.nnnMETHODSnIn phase 1, a cross-sectional survey was used to characterize the experiences of a high-stress nursing cohort. A total of 114 nurses in 6 high-intensity units completed 6 survey tools to assess the nurses characteristics as the context for burnout and to explore factors involved in burnout, moral distress, and resilience. Statistical analysis was used to determine associations between scale measures and to identify independent variables related to burnout.nnnRESULTSnMoral distress was a significant predictor of all 3 aspects of burnout, and the association between burnout and resilience was strong. Greater resilience protected nurses from emotional exhaustion and contributed to personal accomplishment. Spiritual well-being reduced emotional exhaustion and depersonalization; physical well-being was associated with personal accomplishment. Meaning in patient care and hope were independent predictors of burnout. Higher levels of resilience were associated with increased hope and reduced stress. Resilience scores were relatively flat over years of experience.nnnCONCLUSIONSnThese findings provide the basis for an experimental intervention in phase 2, which is designed to help participants cultivate strategies and practices for renewal, including mindfulness practices and personal resilience plans.

Evidence of slow maturation of the superior longitudinal fasciculus in early childhood by diffusion tensor imaging.

While the majority of axonal organization is established by birth in mammalian brains, axonal wiring and pruning processes, as well as myelination, are known to extend to the postnatal periods, where environmental stimuli often play a major role. Normal axonal and myelin development of individual white matter tracts of human in this period is poorly understood and may have a major role in cognitive development of human. In this study, we applied diffusion tensor imaging and normalization-based population analyses to 44 preteen children and 30 adult images. We observed highly significant changes of fiber orientations at regions that correspond to the superior longitudinal fasciculus during the first 5 years. The result is attributed to slow axonal and/or myelin maturation of this tract, which is believed to be involved in language functions.