Search

Objective: To reevaluate at age 8 years children who had participated during the first 3 years of life in a randomized clinical trial of special services for low-birthweight (LBW) premature infants.Design: Follow-up of a randomized controlled trial of premature infants (< or = 37 weeks' gestation), stratified by 2 LBW groups (lighter [< or = 2000 g] and heavier [2001-2500 g]) and divided into intervention (n=377) and follow-up only (n=608) groups.Setting: Eight sites serving diverse populations.Participants: At age 8 years, 874 children were assessed: 336 in the intervention group and 538 in the follow-up only group.Intervention: The 3-year intervention consisted of home visits (birth to 3 years), child development center services (ages 1 to 3 years), and parent group meetings (ages 1 to 3 years).Primary Outcome Measures: Cognitive functioning (Weschler Intelligence Scale for Children-III; Peabody Picture Vocabulary Test-Revised); academic achievement (Woodcock-Johnson Tests of Achievement-Revised); and parental reports of school performance, behavior (Child Behavior Checklist), and health (Child General Health Survey).Results: At age 8 years, in the entire cohort and in the lighter LBW stratum, the intervention and follow-up only groups were similar on all primary outcome measures. Differences favoring the intervention group were found within the heavier LBW group: full-scale IQ score (4.4 points higher, P=.007), verbal IQ score (4.2 points higher, P=.01), performance IQ score (3.9 points higher, P=.02), mathematics achievement score (4.8 points higher, P=.04), and receptive vocabulary score (6.7 points higher, P=.001). On a physical functioning subscale, the whole intervention group received less favorable ratings, while the lighter LBW intervention group had lower maternal ratings assessing social limitations caused by behavior.Conclusion: Although at age 8 years there were modest intervention-related differences in the cognitive and academic skills of heavier LBW premature children, attenuation of the large favorable effects seen at 3 years was observed in both the heavier and lighter LBW groups. This indicates a need to develop additional intervention strategies for LBW premature children that can provide sustained benefits. [ABSTRACT FROM AUTHOR]

Stimulant medications have been used to manage the associated symptoms of ADHD including inattention, developmentally inappropriate levels of activity, distractibility, and impulsivity. To date, clinical trials clearly have established the efficacy of the stimulants on the core symptoms of ADHD and associated aggression. Although the stimulants improve classroom productivity and behavior, few data have demonstrated the effectiveness of the stimulants on academic achievement. Finally, there has been a paucity of data on the long-term efficacy and safety of stimulants. Recommendations are made for future research studies that examine the integration of stimulant medication with other psychosocial therapies, particularly behavior management.

Maternal exposures to aminopterin and methotrexate have been associated with a pattern of malformation which includes prenatal-onset growth deficiency, severe lack of ossification of the calvarium, hypoplastic supraorbital ridges, small, low-set ears, micrognathia, and limb abnormalities. We report on a patient whose mother received methotrexate during the first trimester of pregnancy and who, in addition to the structural anomalies typical of maternal methotrexate exposure, has significant developmental delay. This is the third patient exposed to folic acid antagonists with mental retardation, providing further evidence that developmental delay is one feature of fetal aminopterin-methotrexate syndrome. Therefore, it is recommended that formal developmental testing be performed in all patients prenatally exposed to methotrexate.

Objective: To identify parents' perceptions of helpful vs unhelpful types of social support received in managing the care of preadolescents with chronic conditions., Design: Multimethod cohort study with 1-year follow-up., Setting: General community., Participants: Volunteer, consecutive sample of parents of 124 preadolescents with a variety of chronic conditions., Methods: In-depth, in-home interviews conducted with parents. Quantitative data from the Social Support Assessment questionnaire was used to assess and compare sources and types of helpful support at baseline and 1 year later. Content analytic methods were used to categorize unsupportive behaviors described by parents during the first interview., Results: Both mothers and fathers reported that other family members were the primary source of helpful emotional and tangible support, while health care providers were the primary source of helpful informational support. The amount of perceived support from family members, community members, and service providers stayed relatively stable over time, except that fathers reported a significant increase in helpful emotional and informational support from extended family members from baseline to 1 year later. Also, 388 incidents of unsupportive behaviors were identified; the majority of these behaviors were attributed to health professionals and extended family members., Conclusion: While patterns of perceived support remained relatively stable over a 1-year period, reports of unsupportive behaviors suggest gaps in service and problems that must be addressed to improve the care that children with chronic conditions and their families receive.

Despite improvements in survival rates for low birthweight (LBW) infants, the prevalence among survivors of major neurodevelopmental impairment seems relatively stable. Cerebral palsy, the most common major impairment, can usually be ruled out by 18 months corrected age. Minor impairments such as learning disabilities cannot be ruled out until much later. The efficacy of interventional services in this population was addressed by a national randomized trial. The intervention produced large treatment effects for heavier LBW infants and moderate effects for lighter infants. Five years later, modest residual effects were found for heavier LBW infants, but not for the lighter, suggesting that 0 to 3 services alone are not sufficient to prevent scholastic disadvantage in this population.

Human dermatitis-involving cytotoxic interaction between effector lymphocytes and epithelial target cells has thus far been documented in vivo only as naturally occurring disease or as an iatrogenic complication of organ engraftment. In this report, we reproduce human cytotoxic dermatitis via local microinjection of heterologous human lymphocytes into human skin xenografted to mice with severe combined immune deficiency syndrome. Injection sites develop progressive T cell epidermotropism culminating in cytotoxic dermatitis resembling human lichen planus within 4 weeks. Effector T cells express a CD8+, TIA-1+ phenotype, proliferate locally, express interleukin-2 surface receptors, and demonstrate interferon-gamma mRNA induction after microinjection. Migration of these T cells into the epidermis is closely linked to experimental induction and coincident expression of intercellular adhesion molecule by keratinocytes. T cell apposition to keratinocytes is associated with endonuclease-mediated DNA fragmentation (apoptosis) in the latter cell type. Intraepidermal T cell migration and related lesion formation is partially abrogated by systemic administration of antisense oligonucleotide to ICAM-1 mRNA. These findings demonstrate that human cytotoxic tissue injury directed against epithelial targets can be produced and modulated in chimeric mice.

Purpose: Our objective was to determine the effect of experience on the results with intracytoplasmic sperm injection., Methods: The quarterly outcome with both ICSI and traditional in vitro fertilization (IVF) in 1994 was analyzed in 475 patients under age 40 undergoing 595 oocyte retrievals. The data represent 307 patients undergoing 379 retrievals for IVF and 165 patients undergoing 216 retrievals for ICSI., Results: Fertilization rates with ICSI improved significantly each quarter (52.96, 62.17, 70.17, and 74.87% in Q-I, Q-II, Q-III, and Q-IV, respectively), while the rate with IVF improved significantly between Q-I (69.9%) and Q-II (80.10%) and slightly but significantly between Q-II and Q-IV (82.88%). The implantation rate per embryo after ICSI improved significantly after Q-I (6.17%) compared to Q-II (10.70%) and Q-IV (12.14%). The pregnancy rate per transfer with ICSI increased steadily after Q-I (13.79, 21.88, 23.53, and 25.00% in Q-I through Q-IV), reaching statistical significance between Q-I and Q-III and between Q-I and Q-IV., Conclusions: Although acceptable results can be obtained with ICSI after a relatively short period of time, optimum results require substantial experience.

Low-birth-weight (LBW) premature infants are at increased risk for abnormal development. It is unclear whether intervention programs designed to prevent the disabilities in preterm children are efficacious. This paper reviews the settings in which interventions take place (e.g. nursery, home) and to whom they are directed (e.g. infant, parent). One intervention program, the Infant Health and Development Program (IHDP) is reviewed in detail. The IHDP was a multisite randomized clinical trial to evaluate the efficacy of combining developmental and support services along with paediatric follow-up to reduce the developmental problems seen among LBW preterm infants. Results from all studies suggest that preventive developmental interventions for LBW, premature infants have thus far demonstrated only modest success. Future research endeavours should investigate the type, duration, critical age onset, and intensity of the intervention as well as which subgroups of LBW infants most benefit from such programs.

Objective: To develop recommendations for effectively informing families about their child's chronic illness or disability., Methods: The sample included 43 families of infants with Down syndrome and/or congenital heart disease who were participating in Project Resilience, which is a multisite longitudinal research project. Family interviews were transcribed verbatim and coded by two raters. Qualitative techniques were used to identify the factors that influenced family caregivers' reactions to learning that their child had been diagnosed as having a chronic condition., Results: Family caregivers clearly distinguished their personal emotional reactions to the diagnosis from their reactions to how providers informed them about their child's condition. Families emphasized the quality of information that they received as well as the manner in which they were told about the condition. Although two thirds of the informing incidents were positive, families also reported negative reactions to outdated and inadequate information as well as to professionals who were insensitive to their needs., Conclusions: Resident and continuing education programs need to prepare physicians who can sensitively and effectively "break the news" to diverse families who have children with chronic conditions. At the time of diagnosis, clinicians need to PACE the news by (1) planning the setting, (2) assessing the family's background knowledge and experience, (3) choosing strategies that best fit the family's particular situation, and (4) evaluating the family's understanding of the information.

Objective: Mortality and neurodevelopmental morbidity among infants weighing less than 800 g at birth are compared in three separate studies from the same intensive care nursery during an almost 15-year period., Methods: The survival and neurodevelopmental outcome of 210 infants with birth weights less than 800 g admitted to the University of Washington neonatal intensive care unit between 1986 and 1990 are compared with those of two previous cohorts (1977 through 1980 and 1983 through 1985) of extremely low birth weight (ELBW) infants from the same nursery., Results: Annual admissions of these ELBW infants nearly doubled from 1977 to 1990, whereas nursery survival rose from 20% between 1977 and 1980, to 36% between 1983 and 1985, to 49% in this current study of births between 1986 and 1990. The greatest increase in survival among the three studies occurred among infants with birth weights less than 700 g. Female survival was 20% higher than male survival in each of the time periods. The prevalence of major neurosensory impairments did not differ significantly among the three study groups (19%, 21%, and 22% respectively); male survivors were more commonly affected across time periods. There were no differences in mean cognitive test scores between the current 1986 through 1990 birth cohort (94) and the two previous cohorts (1977 through 1980, 98; 1983 through 1985, 89)., Conclusions: The experience of our center with these ELBW infants over time seems reassuring to the extent that progressive increases in nursery survival have not resulted in increased neurodevelopmental morbidity.

The outcome literature on low birthweight (LBW) premature children indicates that they are at risk for a variety of neurodevelopmental impairments throughout childhood. To prevent such disabilities, numerous interventions have been initiated with LBW children. Nineteen intervention programs designed for LBW preterms that have published study results dating from 1971 are reviewed. Included are interventions in the neonatal nursery, at home, and at centers as well as interventions that are both child-focused and parent-focused. One randomized clinical trial evaluating comprehensive intervention services, the Infant Health and Development Program, is described in detail. Conclusions from the studies reviewed indicate that intervention programs have had only modest success in altering neurodevelopmental outcomes, although parent-child interaction has often been facilitated. Future research on the effects of preventive intervention needs to examine long-term developmental competencies and to replicate positive findings in multiple settings.

Objective: To evaluate the persistence of effects on health and development at age 5 years of the Infant Health and Development Program, an early childhood intervention that was provided to low-birth-weight (LBW) premature infants from neonatal discharge through age 3 years., Design: Randomized, controlled, multicenter trial, stratified by two LBW groups: lighter (< or = 2000 g) and heavier (2001 to 2500 g)., Setting: Eight socioeconomically heterogeneous clinical sites., Participants: Of 985 eligible infants weighing 2500 g or less and at 37 weeks' or less gestational age, 377 infants were randomly assigned to the intervention group and 608 to the follow-up only group. About two thirds of the infants in each group were in the lighter LBW stratum, and one third were in the heavier LBW stratum., Intervention: The intervention group received home visits (from neonatal discharge through age 3 years) as well as center-based schooling (from 1 to 3 years of age). Children in both groups received pediatric surveillance., Main Outcome Measures: Cognitive development, behavioral competence, and health status., Results: At age 5 years, the intervention group had full-scale IQ scores similar to children in the follow-up only group. However, in the heavier LBW stratum, children in the intervention group had higher full-scale IQ scores (3.7 points higher; P = .03) and higher verbal IQ scores (4.2 points higher; P = .02). No significant differences between intervention and follow-up only groups in cognitive measures at age 5 years were noted in the lighter LBW infants. The intervention and follow-up groups were similar in behavior and health measures regardless of LBW stratum., Conclusion: The early childhood intervention provided in the first 3 years of life had effects on heavier LBW premature infants' IQ and verbal performance at age 5 years that were not observed for lighter LBW premature infants. The intervention did not affect health or behavior at age 5 years in either LBW stratum.

Solid-state 1H, 13C, 14N, and 31P NMR spectroscopy was used to study the effects of the bee venom peptide, melittin, on aligned multilayers of dimyristoyl-, dilauryl- and ditetradecyl-phosphatidylcholines above the gel to liquid-crystalline transition temperature, Tc. Both 31P spectra from the lipid headgroups and 1H resonances from the lipid acyl chain methylene groups indicate that the peptide does not affect the mosaic spread of the lipid molecules at lipid:peptide molar ratios of 10:1, or higher. None of the samples prepared above Tc showed any evidence of the formation of hexagonal or isotropic phases. Melittin-induced changes in the chemical shift anisotropy of the headgroup phosphate and the lipid carbonyl groups, and in the choline 14N quadrupole splittings, show that the peptide has effects on the headgroup order and on the molecular organization in the sections of the acyl chains nearest to the bilayer surface. The spin-lattice relaxation time for the lipid acyl chain methylene protons was found to increase and the rotating-frame longitudinal relaxation time to markedly decrease with the addition of melittin, suggesting that motions on the nanosecond time scale are restricted, whereas the slower, collective motions are enhanced in the presence of the peptide.

The effects of ethanol, monofluoro- and trifluoroethanol on the hydrolysis of ATP and coupled Ca2+ translocation by sarcoplasmic reticulum Ca(2+)-ATPase (EC 3.6.1.38) were measured. All three alcohols had parallel effects on the enzyme activities at concentrations up to 200 mM, suggesting a similar mechanism of action. 19F nuclear magnetic resonance spectroscopy was used to investigate their site of action in the purified enzyme.

Developmental intervention in the first 5 years of life is an expanding, complex enterprise. Documenting efficacy by traditional scientific methods has proven to be elusive for a number of practical reasons, e.g., target population heterogeneity, methodology variability, inadequate outcome measures, and cost of longitudinal cohort designs. Nevertheless, despite these shortcomings, there is accumulating research information as to which types of intervention approaches are likely to be most beneficial to specific groups of infants and children and their families. It is quite clear that preventive strategies for at-risk children and families are different than ameliorative strategies for children with established disabilities. It is also clear that comprehensive evaluation of effectiveness must include consideration of both functional child gains (e.g., social, communication, mobility, and adaptive skills) and enhancement of family function. It is the pediatrician's responsibility to be adequately informed about contemporary developmental interventions in order to balance parental hopes and needs with potential benefits.

In infants with bronchopulmonary dysplasia, the influence of the severity of their pulmonary disease on neurodevelopmental outcome is unknown. Neurodevelopmental outcomes at a mean age of 36 months were assessed in 27 premature subjects who had bronchopulmonary dysplasia. Subjects had a mean birth weight of 940 g (range, 540 to 1690 g) and a mean gestational age of 27 weeks (range, 25 to 31 weeks). The duration of mechanical ventilation ranged from 22 to 128 days, and the duration of requirement of supplemental oxygen ranged from 34 to 1033 days. No significant correlations were found between duration of mechanical ventilation or oxygen therapy and overall neurodevelopmental outcome. In contrast, cranial ultrasound findings of intracranial hemorrhage and/or periventricular echodensity related specifically to poorer cognitive outcome. By age 3 years, severity of bronchopulmonary dysplasia is not a sufficient predictor of neurodevelopmental outcome. Intracranial hemorrhage and periventricular echodensity continue to be important predictors.

Mortality and neurodevelopmental morbidity were compared in two cohorts of neonates with birth weights of less than 800 g. The neonates, born in the years 1977 through 1980 (original cohort) and 1983 through 1985 (current cohort), were patients in the same university intensive care nursery. Mortality was 80% in the original cohort and 64% in the current cohort (P = .01). In the current cohort, survival was significantly better for neonates with birth weights of more than 749 g (58% vs 27%; P = .001). Survival was also significantly associated with gender and with gestation number (female survival was 48% and male survival was 23%, P = .003; singleton survival was 41% and twin survival was 21%, P = .03). Prevalence of major central nervous system handicaps did not significantly differ between the two study groups, but severity of handicap was worse for the current study group. Morbidity in the current cohort was most severe for twins (67% with a major central nervous system handicap) and was least severe for singleton girls (4% with a major central nervous system handicap, P = .002). Delivery mode appeared to affect outcome. Although there were more nursery admissions and more survivors among neonates with birth weights of less than 800 g during the period 1983 through 1985 compared with the period 1977 through 1980, overall neurodevelopmental morbidity worsened.

Forty-eight low-birth-weight, preterm graduates of the University of Washington's neonatal intensive care unit who had received periodic, serial scanning by means of cranial ultrasonography during the first 4 to 6 weeks of life were longitudinally observed in an interdisciplinary neurodevelopmental follow-up program to a mean corrected age of 18 months. Mean birth weight for the sample was 1286 g; mean gestational age was 29 weeks. Periventricular echodensities were graded from 0 to 3, with 0 indicating no densities and 3 indicating cystic formation. Intracranial hemorrhage was graded in the conventional manner from 0 to IV. Neurodevelopmental outcome was assessed by means of a neurologic examination and the Bayley Scales of Infant Development. To synthesize the results, neurodevelopmental outcome for each subject was classified as normal, demonstrating minor abnormalities, or demonstrating major abnormalities. Multiple statistical analyses with various subgroupings of subjects consistently indicated severe intracranial hemorrhage (grades III and/or IV) to be a better predictor of overall neurodevelopmental outcome than grade of periventricular echodensity, including small cysts. These results suggest a wide range of outcomes after detection of periventricular echodensities and caution against communicating overly pessimistic prognoses in many cases.

In a multicenter, randomized clinical trial, we assessed the early neurologic development of 93 children born prematurely whose heart rates were monitored electronically during delivery and compared it with that of 96 children born prematurely whose heart rates were periodically monitored by auscultation. All the children were singletons with cephalic presentation, and all weighed less than or equal to 1750 g at birth. The mental and psychomotor indexes of the Bayley Scales of Infant Development (standardized mean score +/- SD, 100 +/- 16) and a formal neurologic examination were administered at three follow-up visits (at 4, 8, and 18 months of age, corrected for gestational age). At 18 months, the mean mental-development scores in the groups receiving electronic fetal monitoring and periodic auscultation were 100.5 +/- 2.4 and 104.9 +/- 1.8, respectively (P greater than 0.1). The mean psychomotor-development scores in the two groups at 18 months were 94.0 +/- 2.4 and 98.3 +/- 1.8, respectively (P greater than 0.1). The incidence of cerebral palsy was higher in the electronically monitored group--20 percent as compared with 8 percent in the group that was monitored by auscultation (P less than 0.03). In the electronic-fetal-monitoring group (but not in the periodic-auscultation group), the risk of cerebral palsy increased with the duration of abnormal fetal-heart-rate patterns, as assessed by retrospective review (chi 2 trend = 12.71, P less than 0.001). The median time to delivery after the diagnosis of abnormal fetal-heart-rate patterns was 104 minutes with electronic fetal monitoring, as compared with 60 minutes with periodic auscultation. We conclude that as compared with a structured program of periodic auscultation, electronic fetal monitoring does not result in improved neurologic development in children born prematurely.

The recently introduced dot immunobinding assay is well suited as a rapid and sensitive procedure for the analysis of those hybridoma clones that are producers of a specific antibody. We present a modification of the dot immunobinding assay which utilizes a single nitrocellulose sheet for up to 96 assays. By using a single nitrocellulose sheet, sample manipulation is greatly reduced, reaction conditions can be better standardized and a comparison of background reactivities is provided. Results are presented which demonstrate the effectiveness of this modified dot immunobinding assay.

The relative validities of three clinical assessment methods for estimating gestational age in newborn low birth weight infants were evaluated with reference to estimates based on the date of the mother's last menstrual period. For 1246 infants in eight diverse institutions, estimates based on physical criteria correlated more strongly with dates estimates, yielded estimates more similar on average to dates estimates, and yielded higher proportions of correct classifications of prematurity and small for gestational age than did estimates based on neurologic criteria or neurologic and physical criteria combined. These results support the use of physical criteria rather than neurologic or combined criteria for the clinical assessment of gestational age in low birth weight infants. In a subsample of 511 black and white infants, there were no ethnic differences in mean error of estimate for any of the three methods.