Effect of peripheral IV based blood collection on catheter dwell time, blood collection, and patient response.

AIM: To evaluate the effect of daily PIV-based phlebotomy using the PIVO device on PIVC dwell times and replacement rates, as well as the reliability of blood sample collection, and patient response to this method of blood collection. BACKGROUND: Blood draws which are also known as phlebotomy for laboratory analyses are one of the most common experiences for hospitalized patients. When performed by venipuncture, they are often associated with pain and anxiety for patients. Most hospitals avoid phlebotomy from peripheral IV catheters due to sample hemolysis, sample dilution by fluids in PIVC line or infused medications, PIVC dislodgement or infiltration, and increased rates of phlebitis. METHODS: A prospective, randomized- controlled study of 160 GI surgery patients was enrolled. Patients were randomized to either control evaluation of PIVC dwell or to receive daily PIVO blood collections in addition to evaluation of PIVC dwell. RESULTS: Daily PIVO blood collections did not negatively affect PIVC dwell or replacement rates. Overall 81% of blood collection attempts were successful and the likelihood of success was strongly associated with PIVC condition. Patients reported 0.7/10 pain for PIVO blood collection on a 0-10 pain scale and a 9.1/10 preference for PIVO on a 0 (strongly prefer needle) to 10 (strongly prefer PIVO) preference scale. Results suggest that use of a PIV based blood collection was a reliable and valid approach and was superior to routine phlebotomy in self-reported responses from patients.

Factor Structure of the Eating Disorder Examination-Questionnaire in a Clinical Sample of Adult Women With Anorexia Nervosa.

An exploratory factor analysis on the Eating Disorder Examination-Questionnaire (EDE-Q) is presented for a clinical sample of women with anorexia nervosa. THE EDE-Q was completed by 169 participants after admission to an inpatient unit for eating disorders. Results of the current study did not support the four-factor model presented by the EDE-Q. A new four-factor solution was obtained with two factors showing similarity to the Restraint and Eating Concern subscales of the original model. The Shape and Weight Concern items primarily loaded together on one factor, along with preoccupation with food and fear of losing control over eating, two Eating Concern items. Finally, an appearance factor was obtained that supports the results of prior research. [Journal of Psychosocial Nursing and Mental Health Services, 56(5), 33-39.].

Trajectories of Change in Body Weight During Inpatient Treatment for Anorexia Nervosa.

BACKGROUND: Identifying distinct trajectories of change in body weight during inpatient treatment for anorexia nervosa (AN) may provide knowledge about the process of weight restoration and may help detect optimal body weight response patterns among individuals who are at risk for not achieving weight restoration or leaving treatment prematurely. OBJECTIVE: This study explored the extent to which distinct trajectories of change in body weight existed among individuals during inpatient treatment for AN. DESIGN: Group-based trajectory modeling was used to identify distinct trajectories of change in body weight among 500 individuals receiving inpatient treatment for AN. RESULTS: Four distinct trajectories were identified: weight gain ( n = 197), treatment resistant ( n = 177), weight plateau ( n = 82), and weight fluctuate ( n = 44). CONCLUSION: Clinically, it is important to consider the heterogeneity of changes in body weight during inpatient treatment to help guide interventions and outcomes.

Improving End-of-Life Care: Palliative Care Embedded in an Oncology Clinic Specializing in Targeted and Immune-Based Therapies.

PURPOSE: Patients with advanced cancer benefit from early involvement of palliative care. The ideal method of palliative care integration remains to be determined, as does its effectiveness for patients treated with targeted and immune-based therapies. MATERIALS AND METHODS: We studied the impact of an embedded palliative care team that saw patients in an academic oncology clinic specializing in targeted and immune-based therapies. Patients seen on a specific day accessed the embedded model, on the basis of automatic criteria; patients seen other days could be referred to a separate palliative care clinic (usual care). We abstracted data from the medical records of 114 patients who died during the 3 years after this model's implementation. RESULTS: Compared with usual care (n = 88), patients with access to the embedded model (n = 26) encountered palliative care as outpatients more often ( P = .003) and earlier (mean, 231 v 109 days before death; P < .001). Hospice enrollment rates were similar ( P = .303), but duration was doubled (mean, 57 v 25 days; P = .006), and enrollment > 7 days before death-a core Quality Oncology Practice Initiative metric-was higher in the embedded model (odds ratio, 5.60; P = .034). Place of death ( P = .505) and end-of-life chemotherapy (odds ratio, 0.361; P = .204) did not differ between the two arms. CONCLUSION: A model of embedded and automatically triggered palliative care among patients treated exclusively with targeted and immune-based therapies was associated with significant improvements in use and timing of palliative care and hospice, compared with usual practice.

Self-report of eating disorder symptoms among women with and without infertility.

OBJECTIVE: To compare eating disorder (ED) symptoms in women seeking treatment for infertility to women receiving routine primary care. DESIGN: A cross-sectional comparative design. SETTING: Women were recruited from two infertility centers and a general hospital primary care setting. PARTICIPANTS: Participants included 51 women seeking treatment for ovulatory and unexplained infertility and 34 women attending routine primary care. MEASURES: Participants completed a battery of standardized rating scales measuring self-reported ED symptoms, drive for thinness, bulimic symptoms, body dissatisfaction, and related clinical characteristics. RESULTS: Multivariate analysis of covariance confirmed that women seeking treatment for infertility had significantly greater scores on measures of drive for thinness (p = .001) and bulimic symptoms (p = .002) than those receiving routine primary care. However, the comparison group had significantly greater scores on measures of body dissatisfaction (p < .001) and dietary restraint (p = .001) than the infertility group. Both groups had elevated rates of lifetime ED diagnoses compared to national prevalence rates. CONCLUSIONS: Results demonstrated that women seeking treatment for ovulatory and unexplained infertility have greater drive for thinness and bulimic symptoms but not body dissatisfaction or dietary restraint compared to women seeking primary care. The results suggest that infertility and routine health care visits may provide opportunities for early identification and treatment of women with ED symptomatology. Future studies may benefit from further elucidation of the potential role of ED symptoms in the etiology and maintenance of infertility in, particularly, normal-weight women.

Impaired language pathways in tuberous sclerosis complex patients with autism spectrum disorders.

The purpose of this study was to examine the relationship between language pathways and autism spectrum disorders (ASDs) in patients with tuberous sclerosis complex (TSC). An advanced diffusion-weighted magnetic resonance imaging (MRI) was performed on 42 patients with TSC and 42 age-matched controls. Using a validated automatic method, white matter language pathways were identified and microstructural characteristics were extracted, including fractional anisotropy (FA) and mean diffusivity (MD). Among 42 patients with TSC, 12 had ASD (29%). After controlling for age, TSC patients without ASD had a lower FA than controls in the arcuate fasciculus (AF); TSC patients with ASD had even a smaller FA, lower than the FA for those without ASD. Similarly, TSC patients without ASD had a greater MD than controls in the AF; TSC patients with ASD had even a higher MD, greater than the MD in those without ASD. It remains unclear why some patients with TSC develop ASD, while others have better language and socio-behavioral outcomes. Our results suggest that language pathway microstructure may serve as a marker of the risk of ASD in TSC patients. Impaired microstructure in language pathways of TSC patients may indicate the development of ASD, although prospective studies of language pathway development and ASD diagnosis in TSC remain essential.

Recovering from early deprivation: attachment mediates effects of caregiving on psychopathology.

OBJECTIVE: Children exposed to early institutional rearing are at risk for developing psychopathology. The present investigation examines caregiving quality and the role of attachment security as they relate to symptoms of psychopathology in young children exposed to early institutionalization. METHOD: Participants were enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal intervention study of children abandoned and placed in institutions at or shortly after birth. Measures included observed caregiving when children were 30 months of age, observed attachment security at 42 months, and caregiver reports of children's psychopathology at 54 months. At 54 months, some children remained in institutions, others were in foster care, others had been adopted domestically, and still others had been returned to their biological families. Thus, the children had experienced varying amounts of institutional rearing. RESULTS: After controlling for gender, quality of caregiving when children were 30 months old was associated with symptoms of multiple domains of psychopathology at 54 months of age. Ratings of security of attachment at 42 months mediated the associations between quality caregiving at 30 months and fewer symptoms of psychopathology at 54 months. CONCLUSIONS: Among deprived young children, high-quality caregiving at 30 months predicted reduced psychopathology and functional impairment at 54 months. Security of attachment mediated this relationship. Interventions for young children who have experienced deprivation may benefit from explicitly targeting caregiver-child attachment relationships.

Effect of treatment of obstructive sleep apnea on seizure outcomes in children with epilepsy.

A retrospective review of children with epilepsy and obstructive sleep apnea, treated surgically for their obstructive sleep apnea from January 2008-October 2010, was performed for age, sex, type of epilepsy, antiseizure medications, sleep-study data, and changes in seizure frequency. Twenty-seven subjects (median age, 5 years) with no adjustment to their medications around their time of surgery were identified. Three months after surgery, 10 (37%) patients became seizure-free, three (11%) demonstrated >50% seizure-reduction, and six (22%) exhibited an amelioration of seizure frequency. Two (7%) demonstrated unchanged seizure-frequency, and six (22%) manifested a worsening of seizure frequency. Median seizure frequency before surgery was 8.5 (interquartile range, 2-90), and after surgery, three (interquartile range, 0-75), with a 53% median seizure reduction. Multivariate analysis demonstrated a trend toward seizure freedom with each percentile increase in body mass index and early age of surgery. We conclude that obstructive sleep apnea surgery may decrease seizure frequency, especially in children with elevated body mass index scores and younger age at time of surgery.

Diurnal and sleep/wake patterns of epileptic spasms in different age groups.

PURPOSE: Epileptic spasms are seizures that occur predominantly in children and are characterized by clusters of brief axial movements. Epileptic spasms may occur in the context of a variety of syndromes. Previous research has found that epileptic spasms occur in a sleep/wake and diurnal rhythm. The purpose of this study was to identify these patterns in different age groups. METHODS: Charts of 2,021 patients with epilepsy undergoing video-electroencephalography (EEG) monitoring over a 10-year period were reviewed for presence of epileptic spasms and analyzed for their occurrence during the day (6 a.m. to 6 p.m.) or night, out of wake or sleep, and in 3-h time-blocks throughout the day. Exact epileptic spasm time, EEG localization, and the presence or absence of magnetic resonance imaging lesion were also recorded. Patients were separated into two age groups: A ages 3 and under, and over age 3. Statistical analysis of seizure occurrence in time bins was carried out using binomial calculations. p-Values <0.05 were taken as significant. Using exact seizure times, a generalized linear mixed model of the Poisson-family with a square root link function was used to calculate mean seizure times. Age, as a binary variable, and time, as a categorical variable, was treated as fixed effect predictors, and individual effects were modeled as random effects. For comparison between the two age groups, over age 3 and under age 3, seizure times were transformed into circular variables. A circular analysis of variance test was used to assess for the difference in mean seizure time, assuming a von Mises distribution of the circle. KEY FINDINGS: We analyzed 219 clusters of epileptic spasms in 51 patients (15 girls; mean age 2.15 ± 2.22 years). Forty-two patients younger than 3 years of age had 163 seizures and nine patients older than 3 years had 56 seizures. Epileptic spasms occurred predominantly during wakefulness (p < 0.001) and during daytime (p < 0.001). Epileptic spasms occurred most frequently between 9 a.m. and noon (p < 0.05) and between 3 p.m. and 6 p.m. (p < 0.001). Patients without magnetic resonance imaging lesions had most seizures between 9 a.m. and noon (p < 0.01) and 3 p.m. and 6 p.m. (p < 0.001). Thirty-seven patients had 157 epileptic spasms (71.2%) with generalized EEG patterns and 14 patients had 62 epileptic spasms (28.8%) with focal EEG patterns. Generalized EEG seizures occurred more frequently than focal EEG seizures (p < 0.001). Following age stratification, patients younger than 3 years had most epileptic spasms between 9 a.m. and noon (p < 0.05) and 3 p.m. and -6 p.m. (p < 0.01) and patients older than 3 years had most epileptic spasms between 6 a.m. and -9 a.m. (p < 0.05) and a second peak between 3 p.m. and 6 p.m., although the difference was not statistically significant due to insufficient numbers. Using continuous time analysis, the mean seizure time in the under age 3 and the over age 3 groups was 2:24 p.m. and 11:40 a.m. Using a circular analysis of variance test, the difference between mean seizure times in these groups was found to be statistically significant (p = 0.038). SIGNIFICANCE: Epileptic spasms occur more frequently in the waking state and daytime. Younger patients have epileptic spasms mostly between 9 a.m. and noon and 3 p.m. and -6 p.m., and older patients have epileptic spasms mostly between 6 a.m. and 9 a.m. These findings emphasize age-related changes in epileptic spasm pathophysiology or potentially evolution of disease with age.

Prenatal lead levels, plasma amyloid ß levels, and gene expression in young adulthood.

BACKGROUND: Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer's disease (AD). OBJECTIVES: We attempted to assess the relationship between early-life lead exposure and potential biomarkers for AD among young men and women. We also attempted to assess whether early-life lead exposure was associated with changes in expression of AD-related genes. METHODS: We used sandwich enzyme-linked immunosorbent assays (ELISA) to measure plasma concentrations of amyloid ß proteins Aß40 and Aß42 among 55 adults who had participated as newborns and young children in a prospective cohort study of the effects of lead exposure on development. We used RNA microarray techniques to analyze gene expression. RESULTS: Mean plasma Aß42 concentrations were lower among 13 participants with high umbilical cord blood lead concentrations (≥ 10 µg/dL) than in 42 participants with lower cord blood lead concentrations (p = 0.08). Among 10 participants with high prenatal lead exposure, we found evidence of an inverse relationship between umbilical cord lead concentration and expression of ADAM metallopeptidase domain 9 (ADAM9), reticulon 4 (RTN4), and low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1) genes, whose products are believed to affect Aß production and deposition. Gene network analysis suggested enrichment in gene sets involved in nerve growth and general cell development. CONCLUSIONS: Data from our exploratory study suggest that prenatal lead exposure may influence Aß-related biological pathways that have been implicated in AD onset. Gene network analysis identified further candidates to study the mechanisms of developmental lead neurotoxicity.

Iron deficiency in infancy is associated with altered neural correlates of recognition memory at 10 years.

OBJECTIVE: To determine the long-term effects of iron deficiency on the neural correlates of recognition memory. STUDY DESIGN: Non-anemic control participants (n=93) and 116 otherwise healthy formerly iron-deficient anemic Chilean children were selected from a larger longitudinal study. Participants were identified at 6, 12, or 18 months as iron-deficient anemic or non-anemic and subsequently received oral iron treatment. This follow-up was conducted when participants were 10 years old. Behavioral measures and event-related potentials from 28 scalp electrodes were measured during an new/old word recognition memory task. RESULTS: The new/old effect of the FN400 amplitude, in which new words are associated with greater amplitude than old words, was present within the control group only. The control group also showed faster FN400 latency than the formerly iron-deficient anemic group and larger mean amplitude for the P300 component. CONCLUSIONS: Although overall behavioral accuracy is comparable in groups, the results show that group differences in cognitive function have not been resolved 10 years after iron treatment. Long-lasting changes in myelination and energy metabolism, perhaps especially in the hippocampus, may account for these long-term effects on an important aspect of human cognitive development.

Loss of white matter microstructural integrity is associated with adverse neurological outcome in tuberous sclerosis complex.

RATIONALE AND OBJECTIVES: Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome in which cognitive and social-behavioral outcomes for patients vary widely in an unpredictable manner. The cause of adverse neurologic outcome remains unclear. The aim of this study was to investigate the hypothesis that disordered white matter and abnormal neural connectivity are associated with adverse neurologic outcomes. MATERIALS AND METHODS: Structural and diffusion magnetic resonance imaging was carried out in 40 subjects with TSC (age range, 0.5-25 years; mean age, 7.2 years; median age, 5 years), 12 of whom had autism spectrum disorders (ASD), and in 29 age-matched controls. Tractography of the corpus callosum was used to define a three-dimensional volume of interest. Regional averages of four diffusion scalar parameters of the callosal projections were calculated for each subject. These were the average fractional anisotropy (AFA) and the average mean, radial, and axial diffusivity. RESULTS: Subjects with TSC had significantly lower AFA and higher average mean, radial, and axial diffusivity values compared to controls. Subjects with TSC and ASD had significantly lower AFA values compared to those without ASD and compared to controls. Subjects with TSC without ASD had similar AFA values compared to controls. CONCLUSION: Diffusion tensor scalar parameters provided measures of properties of the three-dimensional callosal projections. In TSC, changes in these parameters may reflect microstructural changes in myelination, axonal integrity, or extracellular environment. Alterations in white matter microstructural properties were associated with TSC, and larger changes were associated with TSC and ASD, thus establishing a relationship between altered white matter microstructural integrity and brain function.

Low-level environmental lead exposure in childhood and adult intellectual function: a follow-up study.

BACKGROUND: Early life lead exposure might be a risk factor for neurocognitive impairment in adulthood. OBJECTIVES: We sought to assess the relationship between early life environmental lead exposure and intellectual function in adulthood. We also attempted to identify which time period blood-lead concentrations are most predictive of adult outcome. METHODS: We recruited adults in the Boston area who had participated as newborns and young children in a prospective cohort study that examined the relationship between lead exposure and childhood intellectual function. IQ was measured using the Wechsler Abbreviated Scale of Intelligence (WASI). The association between lead concentrations and IQ scores was examined using linear regression. RESULTS: Forty-three adults participated in neuropsychological testing. Childhood blood-lead concentration (mean of the blood-lead concentrations at ages 4 and 10 years) had the strongest relationship with Full-Scale IQ (ß = -1.89 ± 0.70, p = 0.01). Full-scale IQ was also significantly related to blood-lead concentration at age 6 months (ß = -1.66 ± 0.75, p = 0.03), 4 years (ß = -0.90 ± 0.41, p = 0.03) and 10 years (ß = -1.95 ± 0.80, p = 0.02). Adjusting for maternal IQ altered the significance of the regression coefficient. CONCLUSIONS: Our study suggests that lead exposure in childhood predicts intellectual functioning in young adulthood. Our results also suggest that school-age lead exposure may represent a period of increased susceptibility. Given the small sample size, however, the potentially confounding effects of maternal IQ cannot be excluded and should be evaluated in a larger study.

Validity of evidence-derived criteria for reactive attachment disorder: indiscriminately social/disinhibited and emotionally withdrawn/inhibited types.

OBJECTIVE: This study examined the validity of criteria for indiscriminately social/disinhibited and emotionally withdrawn/inhibited reactive attachment disorder (RAD). METHOD: As part of a longitudinal intervention trial of previously institutionalized children, caregiver interviews and direct observational measurements provided continuous and categorical data used to examine the internal consistency, criterion validity, construct validity, convergent and discriminant validity, association with functional impairment, and stability of these disorders over time. RESULTS: As in other studies, the findings showed distinctions between the two types of RAD. Evidence-derived criteria for both types of RAD showed acceptable internal consistency and criterion validity. In this study, rates of indiscriminately social/disinhibited RAD at baseline and at 30, 42, and 54 months were 41/129 (31.8%), 22/122 (17.9%), 22/122 (18.0%), and 22/125 (17.6%), respectively. Signs of indiscriminately social/disinhibited RAD showed little association with caregiving quality. Nearly half of children with indiscriminately social/disinhibited RAD had organized attachment classifications. Signs of indiscriminately social/disinhibited RAD were associated with signs of activity/impulsivity and of attention-deficit/hyperactivity disorder and modestly with inhibitory control but were distinct from the diagnosis of attention-deficit/hyperactivity disorder. At baseline, 30, 42, and 54 months, 6/130 (4.6%), 4/123 (3.3%), 2/125 (1.6%), and 5/122 (4.1%) of children met criteria for emotionally withdrawn/inhibited RAD. Emotionally withdrawn/inhibited RAD was moderately associated with caregiving at the first three time points and strongly associated with attachment security. Signs of this type of RAD were associated with depressive symptoms, although two of the five children with this type of RAD at 54 months did not meet criteria for major depressive disorder. Signs of both types of RAD contributed independently to functional impairment and were stable over time. CONCLUSIONS: Evidence-derived criteria for indiscriminately social/disinhibited and emotionally withdrawn/inhibited RAD define two statistically and clinically cohesive syndromes that are distinct from each other, shows stability over 2 years, have predictable associations with risk factors and attachment, can be distinguished from other psychiatric disorders, and cause functional impairment.

Placental pathology in asphyxiated newborns meeting the criteria for therapeutic hypothermia.

OBJECTIVE: We sought to describe placental findings in asphyxiated term newborns meeting therapeutic hypothermia criteria and to assess whether histopathologic correlation exists between these placental lesions and the severity of later brain injury. STUDY DESIGN: We conducted a prospective cohort study of the placentas of asphyxiated newborns, in whom later brain injury was defined by magnetic resonance imaging. RESULTS: A total of 23 newborns were enrolled. Eighty-seven percent of their placentas had an abnormality on the fetal side of the placenta, including umbilical cord lesions (39%), chorioamnionitis (35%) with fetal vasculitis (22%), chorionic plate meconium (30%), and fetal thrombotic vasculopathy (26%). A total of 48% displayed placental growth restriction. Chorioamnionitis with fetal vasculitis and chorionic plate meconium were significantly associated with brain injury (P = .03). Placental growth restriction appears to significantly offer protection against the development of these injuries (P = .03). CONCLUSION: Therapeutic hypothermia may not be effective in asphyxiated newborns whose placentas show evidence of chorioamnionitis with fetal vasculitis and chorionic plate meconium.

Diffusion features of white matter in tuberous sclerosis with tractography.

Normal-appearing white matter has been shown via diffusion tensor imaging to be affected in tuberous sclerosis complex. Under the hypothesis that some systems might be differentially affected, including the visual pathways and systems of social cognition, diffusion properties of various regions of white matter were compared. For 10 patients and 6 age-matched control subjects, 3 T magnetic resonance imaging was assessed using diffusion tensor imaging obtained in 35 directions. Three-dimensional volumes corresponding to the geniculocalcarine tracts were extracted via tractography, and two-dimensional regions of interest were used to sample other regions. Regression analysis indicated lower fractional anisotropy in the splenium of corpus callosum and geniculocalcarine tracts in tuberous sclerosis complex group, as well as lower axial diffusivity in the internal capsule, superior temporal gyrus, and geniculocalcarine tracts. Mean and radial diffusivity of the splenium of corpus callosum were higher in the tuberous sclerosis complex group. The differences in diffusion properties of white matter between tuberous sclerosis complex patients and control subjects suggest disorganized and structurally compromised axons with poor myelination. The visual and social cognition systems appear to be differentially involved, which might in part explain the behavioral and cognitive characteristics of the tuberous sclerosis complex population.

Elevated cerebral pressure passivity is associated with prematurity-related intracranial hemorrhage.

OBJECTIVES: Cerebral pressure passivity is common in sick premature infants and may predispose to germinal matrix/intraventricular hemorrhage (GM/IVH), a lesion with potentially serious consequences. We studied the association between the magnitude of cerebral pressure passivity and GM/IVH. PATIENTS AND METHODS: We enrolled infants <32 weeks' gestational age with indwelling mean arterial pressure (MAP) monitoring and excluded infants with known congenital syndromes or antenatal brain injury. We recorded continuous MAP and cerebral near-infrared spectroscopy hemoglobin difference (HbD) signals at 2 Hz for up to 12 hours/day and up to 5 days. Coherence and transfer function analysis between MAP and HbD signals was performed in 3 frequency bands (0.05-0.25, 0.25-0.5, and 0.5-1.0 Hz). Using MAP-HbD gain and clinical variables (including chorioamnionitis, Apgar scores, gestational age, birth weight, neonatal sepsis, and Score for Neonatal Acute Physiology II), we built a logistic regression model that best predicts cranial ultrasound abnormalities. RESULTS: In 88 infants (median gestational age: 26 weeks [range 23-30 weeks]), early cranial ultrasound showed GM/IVH in 31 (37%) and parenchymal echodensities in 10 (12%) infants; late cranial ultrasound showed parenchymal abnormalities in 19 (30%) infants. Low-frequency MAP-HbD gain (highest quartile mean) was significantly associated with early GM/IVH but not other ultrasound findings. The most parsimonious model associated with early GM/IVH included only gestational age and MAP-HbD gain. CONCLUSIONS: This novel cerebrovascular monitoring technique allows quantification of cerebral pressure passivity as MAP-HbD gain in premature infants. High MAP-HbD gain is significantly associated with GM/IVH. Precise temporal and causal relationship between MAP-HbD gain and GM/IVH awaits further study.