Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months

CONTEXT: Despite more than 2 decades of outcomes research after very preterm birth, clinicians remain uncertain about the extent to which neonatal morbidities predict poor long-term outcomes of extremely low-birth-weight (ELBW) infants. OBJECTIVE: To determine the individual and combined prognostic effects of bronchopulmonary dysplasia (BPD), ultrasonographic signs of brain injury, and severe retinopathy of prematurity (ROP) on 18-month outcomes of ELBW infants. DESIGN: Inception cohort assembled for the Trial of Indomethacin Prophylaxis in Preterms (TIPP). SETTING AND PARTICIPANTS: A total of 910 infants with birth weights of 500 to 999 g who were admitted to 1 of 32 neonatal intensive care units in Canada, the United States, Australia, New Zealand, and Hong Kong between 1996 and 1998 and who survived to a postmenstrual age of 36 weeks. MAIN OUTCOME MEASURES: Combined end point of death or survival to 18 months with 1 or more of cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness. RESULTS: Each of the neonatal morbidities was similarly and independently correlated with a poor 18-month outcome. Odds ratios were 2.4 (95% confidence interval [CI], 1.8-3.2) for BPD, 3.7 (95% CI, 2.6-5.3) for brain injury, and 3.1 (95% CI, 1.9-5.0) for severe ROP. In children who were free of BPD, brain injury, and severe ROP the rate of poor long-term outcomes was 18% (95% CI, 14%-22%). Corresponding rates with any 1, any 2, and all 3 neonatal morbidities were 42% (95% CI, 37%-47%), 62% (95% CI, 53%-70%), and 88% (64%-99%), respectively. CONCLUSION: In ELBW infants who survive to a postmenstrual age of 36 weeks, a simple count of 3 common neonatal morbidities strongly predicts the risk of later death or neurosensory impairment.

Conductive hearing loss in preterm infants with bronchopulmonary dysplasia

Objective: To determine the risk of conductive hearing loss in preterm infants with bronchopulmonary dysplasia (BPD) and preterm controls. Methodology: The study population consisted of 78 infants with BPD of 26-33 weeks gestation and 78 controls of similar gestational age matched for broad-based birthweight categories. An auditory brainstem response (ABR) audiology was performed shortly before hospital discharge. Visual reinforcement orientation audiometry (VROA) and impedance audiometry were performed at 8-12 months corrected for prematurity. Infants with persistent audiological abnormalities were referred for evaluation to paediatric ENT surgeons. Results: Infants with BPD had a significantly higher rate of ABR abnormalities (BPD: 22%, controls: 9%; P = 0.028). On VROA and impedance audiometry, the infants with BPD also had a higher rate of persistent abnormalities. Following ENT assessment, 22.1% of infants with BPD and 7.7% of controls had persistent conductive dysfunction requiring myringotomy and grommet tube insertion (P = 0.03). Most of these infants had normal ABR audiometry at hospital discharge. Conclusions: Preterm infants with BPD are at high risk of persistent conductive hearing loss late in the first year of life compared to controls. An ABR audiology conducted at the time of hospital discharge does not predict accurately later conductive hearing problems. Infants with BPD should have routine audiological evaluation toward the end of the first year of life.

Psychoeducational outcome at school age of preterm infants with bronchopulmonary dysplasia

Objective: To investigate the cognitive performance and educational attainment at school-age of children with bronchopulmonary dysplasia (BPD), compared with a preterm control group of children. Methods: Seventy preterm infants with BPD and 61 birth weight matched controls were prospectively followed-up to school-age. The Weschler Intelligence Scale for Children - III (WISC), the Wide Range Achievement Test (WRAT) and the Developmental Test of Visual Motor Integration (VMI) were administered. The results were compared between the two groups and multiple regression analyses were performed to determine the effect of confounding variables. Results: The children in the BPD group performed less well on the Full Scale IQ (mean 86.7 vs 93.5; 95% CI, 1.9-11.7), Verbal IQ (mean 87.1 vs 94.1; 95% CI, 2.0-12.0) and the Performance IQ (mean 88.6 vs 95.2; 95% CI, 2.0-11.2) of the WISC, the reading component of the WRAT (mean 93.8 vs 98.9; 95% CI, 0.3-9.8) and the VMI (mean 88.9 vs 93.3; 95%, CI 1.1-7.8). Despite controlling for social and biological variables, statistical differences persisted for Full Scale and Verbal IQ and reading. A Verbal IQ >1 SD below the mean was found in 41% of BPD children compared to 21% of controls, while on the reading component of the WRAT a greater proportion of BPD children also had scores>1 SD below the mean. Conclusion: Impaired psychoeducational performance was found in preterm children with BPD compared to controls, especially in the areas of language abilities and reading skills. This supports a greater need for special educational services and counseling for parents for these children.

Effects of tidal volume and positive end-expiratory pressure during resuscitation of very premature lambs

Background: Guidelines recommend neonatal resuscitation without controlling tidal volume or positive end-expiratory pressure (PEEP). However, these may improve gas exchange, lung volume and outcome. Aim: To investigate resuscitation of very premature lambs with a Laerdal bag without PEEP versus volume guarantee ventilation with PEEP. Methods: Anaesthetized lambs (n = 20) delivered at 125 d gestation were randomized to three groups receiving 15 min resuscitation: (1) Laerdal bag and no PEEP; (2) ventilation with a tidal volume of 5 ml/kg and 8 cm H2O PEEP; (3) ventilation with 10 ml/kg and 8 cm H2O PEEP. They were then all ventilated for 2 h with tidal volumes of 5 or 10 ml/kg, and 8 cm H2O PEEP. Ventilation parameters and blood gases were recorded. Results: Different tidal volumes affected PaCO2 within minutes, with 10 ml/kg causing severe hypocarbia. PEEP had little effect on PaCO2. Oxygenation improved significantly with PEEP of 8 cm H2O, irrespective of tidal volume. Conclusion: Very premature lambs can be resuscitated effectively using volume-guarantee ventilation and PEEP. Tidal volumes affected PaCO2 within minutes but had little effect on oxygenation. PEEP halved the oxygen requirement compared with no PEEP. Resuscitating premature babies with controlled tidal volumes and PEEP might improve their outcome.

Neutrophil dysplasia characterised by a pseudo-Pelger-Huet anomaly occurring with the use of mycophenolate mofetil and ganciclovir following renal transplantation: a report of five cases

Aim: The pseudo-Pelger-Huet (PH) anomaly has been associated with a variety of primary haematological disorders, infections and drugs. Recently, the development of dysgranulopoiesis characterised by a pseudo-PH anomaly has been reported in two patients with the use of mycophenolate mofetil (MMF) in the setting of heart and/or lung transplantation. We present a further five cases of MMF-related dysgranulopoiesis characterised by a pseudo-PH anomaly occurring after renal transplantation. Methods: All patients were receiving standard immunosuppression protocols for renal transplantation, including a combination of MMF, steroids and either cyclosporin or tacrolimus. Oral ganciclovir was also used for cytomegalovirus prophylaxis in each case. Results: Development of dysplastic granulopoiesis occurred a median of 96 days (range 66-196 days) after transplantation. Moderate or severe neutropaenia (

Clinical and molecular genetics of myoclonic-astatic epilepsy and severe myoclonic epilepsy in infancy (Dravet syndrome)

The majority of severe epileptic encephalopathies of early childhood are symptomatic where a clear etiology is apparent. There is a small subgroup, however, where no etiology is found on imaging and metabolic studies, and genetic factors are important. Myoclonic-astatic epilepsy (MAE) and severe myoclonic epilepsy in infancy (SMEI), also known as Dravet syndrome, are epileptic encephalopathies where multiple seizure types begin in the first few years of life associated with developmental slowing. Clinical and molecular genetic studies of the families of probands with MAE and SMEI suggest a genetic basis. MAE was originally identified as part of the genetic epilepsy syndrome generalized epilepsy with febrile seizures plus (GEFS(+)). Recent clinical genetic studies suggest that SMEI forms the most severe end of the spectrum of the GEFS(+). GEF(+) has now been associated with molecular defects in three sodium channel subunit genes and a GABA subunit gene. Molecular defects of these genes have been identified in patients with MAE and SMEI. Interestingly, the molecular defects in MAE have been found in the setting of large GEFS(+) pedigrees, whereas, more severe truncation mutations arising de novo have been identified in patients with SMEI. It is likely that future molecular studies will shed light on the interaction of a number of genes, possibly related to the same or different ion channels, which result in a severe phenotype such as MAE and SMEI. (C) 2001 Elsevier Science B.V. All rights reserved.

Sodium channel alpha 1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms

Background: Mutations in SCN1A, the gene encoding the alpha1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS(+)). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS(+) in a significant proportion of patients with SMEI Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy. Method: The authors screened SCN1A in 24 patients with SMEI and 23 with IS. Results: Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI. Conclusions: The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS(+) could interact with other loci to cause SMEI in cases with a family history of GEFS(+). This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.

The assessment of oral cytology utilizing ploidy analysis and virtual microscopy for the early detection of epithelial dysplasia and neoplasia in oral mucosal lesions

Oral squamous cell carcinoma (OSCC) is associated with high morbidity and mortality which is due, at least in part, to late detection. Precancerous and cancerous oral lesions may mimic any number of benign oral lesions, and as such may be left without investigation and treatment until they are well advanced. Over the past several years there has been renewed interest in oral cytology as an adjuvant clinical tool in the investigation of oral mucosal lesions. The purpose of the present study was to compare the usefulness of ploidy analysis after Feulgen stained cytological thin-prep specimens with traditional incisional biopsy and routine histopathological examination for the assessment of the pre-malignant potential of oral mucosal lesions. An analysis of the cytological specimens was undertaken with virtual microscopy which allowed for rapid and thorough analysis of the complete cytological specimen. 100 healthy individuals between 30 and 70 years of age, who were non-smokers, non-drinkers and not taking any medication, had cytological specimens collected from both the buccal mucosa and lateral margin of tongue to establish normal cytology parameters within a control population. Patients with a presumptive clinical diagnosis of lichen planus, leukoplakia or OSCC had lesional cytological samples taken prior to their diagnostic biopsy. Standardised thin preparations were prepared and each specimen stained by both Feuglen and Papanicolau methods. High speed scanning of the complete slide at 40X magnification was undertaken using the Aperio Scanscope TM and the green channel of the resultant image was analysed after threshold segmentation to isolate only nuclei and the integrated optical density of each nucleus taken as a gross measure of the DNA content (ploidy). Preliminary results reveal that ploidy assessment of oral cytology holds great promise as an adjunctive prognostic factor in the analysis of the malignant potential of oral mucosal lesions.

A 1-year longitudinal study of severe traumatic brain injury in Australia using the Sickness Impact Profile

Objective: To document outcome and to investigate patterns of physical and psychosocial recovery in the first year following severe traumatic brain injury (TBI) in an Australian patient sample. Design: A longitudinal prospective study of a cohort of patients, with data collection at 3, 6, 9, and 12 months post injury. Setting: A head injury rehabilitation unit in a large metropolitan public hospital. Patients: A sample of 55 patients selected from 120 consecutive admissions with severe TBI. Patients who were more than 3 months post injury on admission, who remained confused, or who had severe communication deficits or a previous neurologic disorder were excluded. Interventions: All subjects participated in a multidisciplinary inpatient rehabilitation program, followed by varied participation in outpatient rehabilitation and community-based sen ices. Main Outcome Measures: The Sickness impact Profile (SIP) provided physical, psychosocial, and total dysfunction scores at each follow-up. Outcome at 1 year was measured by the Disability Rating Scale. Results: Multivariate analysis of variance indicated that the linear trend of recovery over time was less for psychosocial dysfunction than for physical dysfunction (F(1,51) = 5.87, P < .02). One rear post injury, 22% of subjects had returned to their previous level of employability, and 42% were able to live independently. Conclusions: Recovery from TBI in this Australian sample followed a pattern similar to that observed in other countries, with psychosocial dysfunction being more persistent. Self-report measures such as the SIP in TBI research are limited by problems of diminished self-awareness.

Effects of sampling opportunities on preference for adults with severe disabilities

A variable that appears to affect preference development is the exposure to a variety of options. Providing opportunities for systematically sampling different options is one procedure that can facilitate the development of preference, which is indicated by the consistency of selections. The purpose of this study was to evaluate the effects of providing sampling opportunities on the preference development for two adults with severe disabilities. Opportunities for sampling a variety of drink items were presented, followed by choice opportunities for selections at the site where sampling occurred and at a non-sampling site (a grocery store). Results show that the participants developed a definite response consistency in selections at both sites. Implications for sampling practices are discussed.