Relationships between Adaptive Behaviours, Personal Factors, and Participation of Young Children.

AIM: To examine the extent to which personal factors (age, socioeconomic grouping, and preterm birth) and adaptive behaviour explain the participation patterns of young children. METHODS: 65 Children 2-5 years old with and without a history of preterm birth and no physical or intellectual disability were selected by convenience sampling from Galway University Hospital, Ireland. Interviews with parents were conducted using the Adaptive Behaviour Assessment System, Second Edition (ABAS-II) and the Assessment of Preschool Children's Participation (APCP). Linear regression models were used to identify associations between the ABAS-II scores, personal factors, and APCP scores for intensity and diversity of participation. RESULTS: Adaptive behaviour explained 21% of variance in intensity of play, 18% in intensity of Skill Development, 7% in intensity of Active Physical Recreation, and 6% in intensity of Social Activities controlling for age, preterm birth, and socioeconomic grouping. Age explained between 1% and 11% of variance in intensity of participation scores. Adapted behaviour (13%), Age (17%), and socioeconomic grouping (5%) explained a significant percentage of variance in diversity of participation controlling for the other variables. CONCLUSIONS: Adaptive behaviour had a unique contribution to children's intensity and diversity of participation, suggesting its importance.

The impact of preterm birth on participation in childhood occupation.

UNLABELLED: Outcome studies of premature babies have focused their assessments predominately on neurodevelopmental impairments without relating these deficits to the impact they have on a child's everyday life. This study aims to determine whether very 'preterm birth alone' impacts on a child's ability to participate in and carry out childhood activities. Forty-four former premature infants between 6 months and 5 years 6 months, born in Galway University Hospital, Ireland, without physical or intellectual disability, were compared with 51 age-matched term-born infants. Study infants had an average gestation of 29 weeks and birth weight of 1,145 g. Functional skills were assessed using the Adaptive Behavior Assessment Scale-II and the Assessment of Preschool Children's Participation. Premature infants had significantly lower mean scores in overall adaptive behaviour compared to term infants, regardless of whether chronological (difference = 13.6, 95% (CI) = [8.2, 19.1]) or corrected (difference = 6.6, 95% CI = [1.4, 11.8]) age was used. Premature infants had lower mean scores in conceptual, social and practical skills, but no difference was found between the groups in intensity or diversity of participation. CONCLUSION: Premature infants had significantly lower scores in adaptive behaviour than term infants. This measurable effect of preterm birth on 'childhood occupations' merits further investigation.

De novo interstitial deletion 2q14.1q22.1: is there a recognizable phenotype?

In this report we describe a male patient with a rare de novo interstitial deletion of chromosome 2q14.1-q22.1. His karyotype was reported as 46,XY,del(2)(q13q21) but subsequent array comparative genomic hybridization (array CGH) analysis redefined the deletion breakpoints as 2q14.1 and 2q22.1. Eight patients have been reported with deletions either within or spanning the region 2q13 or 2q14 to 2q22.1. In five patients the diagnosis was made by karyotype analysis alone and in three reported patients and the proband array CGH analysis was also performed. When the proband was compared with the eight previously reported patients it was apparent that they shared many clinical findings suggesting that patients with a de novo interstitial deletion involving 2q13 or 2q14 to 2q21 or 2q22 may have a recognizable phenotype. There are 14 known disease-associated genes in the deleted region of 2q14.1-q22.1 and their possible phenotypic effects on the proband and the eight previously reported patients are discussed.

Platelet transfusions in infants with necrotizing enterocolitis.

Severe thrombocytopenia (< 50 x 10(9)/L) frequently accompanies advanced necrotizing enterocolitis (NEC). In premature infants with severe thrombocytopenia, despite a paucity of evidence to support the practice, platelet transfusions are commonly used to maintain arbitrary levels of platelet counts in an effort to prevent hemorrhage. However, platelet transfusions contain a variety of bioactive factors, including platelet activating factor (PAF), which can augment systemic inflammatory processes. A growing body of evidence that incriminates PAF in the pathogenesis of NEC has emerged over the past few decades from both animal and human data. Both severe thrombocytopenia and multiple platelet transfusions have been associated with increased mortality, but it is admittedly difficult to differentiate between the effects of the underlying disease and the effects, if any, of the platelet transfusions. In this report, we review the roles of PAF and platelet transfusions in infants with severe NEC.

Platelet transfusions in infants with necrotizing enterocolitis do not lower mortality but may increase morbidity.

OBJECTIVE: Necrotizing enterocolitis (NEC), a serious multisystemic inflammatory disease most commonly seen in premature neonates, is often associated with thrombocytopenia. Infants with severe forms of NEC commonly have platelet counts of less than 50,000/mm(3), occasionally less than 10,000/mm(3). Despite an absence of data to support the practice, platelet transfusions are commonly used to maintain a certain arbitrary platelet count in an effort to prevent bleeding. As platelet transfusions contain a variety of bioactive factors including pro-inflammatory cytokines, we hypothesized that a higher number and volume of platelet transfusions would not be associated with an improvement in mortality or morbidity. STUDY DESIGN: A retrospective cohort analysis was conducted of the medical records of all infants between 1997 and 2001 with Bell's Stage 2 or 3 NEC associated with platelet counts of <100,000/mm(3). The medical records were evaluated for the following variables: platelet counts, number and volume of platelet transfusions, symptoms of bleeding, and hospital course. Mortality and development of short bowel syndrome and/or cholestasis were correlated to the total number and volume (total ml and ml/kg) of platelet transfusions. Differences between the outcome groups were compared using the independent t-test, Fisher's exact test and Mann-Whitney tests. RESULTS: A total of 46 infants met the study criteria (gestational age 28+/-4 weeks and birth weight 1166+/-756 g, mean+/-SD). There were a total of 406 platelet transfusions administered to the study population. Of these, 151 (37.2%) were given in the presence of active bleeding, with 62% of these resulting in the cessation of bleeding within 24 hours. Other listed indications for platelet transfusions were hypovolemia and severe thrombocytopenia. On analysis of the entire cohort, there was no statistical improvement in either mortality or morbidity (short bowel syndrome and cholestasis) with greater number and/or volume of platelet transfusions. Furthermore, we found that infants who developed short bowel syndrome and/or cholestasis had been given a significantly higher number and volume of platelet transfusions when compared to those who did not have these adverse outcomes [median (minimum - maximum) - number of transfusions : 9 (0 to 33) vs 1.5 (0 to 20), p=0.010; volume of transfusions (ml/kg): 121.5 (0 to 476.6) vs 33.2 (0 to 224.3), p=0.013]. CONCLUSION: This retrospective analysis suggests that greater number and volume of platelet transfusions in infants with necrotizing enterocolitis are associated with greater morbidity in the form of short bowel syndrome and/or cholestasis without the benefit of lower mortality.

Severe thrombocytopenia predicts outcome in neonates with necrotizing enterocolitis.

OBJECTIVE: Necrotizing enterocolitis (NEC) is a common and serious gastrointestinal disorder that predominately affects premature infants. Few prognostic indices are available to guide physicians through the expected course of the disease. We hypothesized that the degree and timing of onset of severe thrombocytopenia (platelet count <100,000/mm(3)) would be a predictor of adverse outcome and an indication for surgical intervention in infants with NEC. STUDY DESIGN: The clinical presentation and outcome of all infants with Bell stage II or III NEC treated at Texas Children's Hospital between 1997 and 2001 were retrospectively reviewed. Patients were stratified into two groups based on the presence (Group1) or absence (Group 2) of severe thrombocytopenia (platelet count <100,000/mm(3)) within 3 days of a diagnosis of NEC. Differences between groups were compared using logistic regression to estimate adjusted odds ratios. RESULTS: A total of 91 infants met inclusion criteria (average birth weight 1288+/-135 g; average gestational age 29.0+/-3.0 weeks). Compared to infants in Group 2, infants in Group 1 were more premature (28.0+/-4.1 vs 30.0+/-4.2 weeks; p=0.02), more likely to have received postnatal steroids (42.5% vs 20.4%; p=0.02), and more likely to require laparotomy for gangrenous bowel (adjusted OR 16.33; p<0. 001). The presence of severe thrombocytopenia was also a predictor of mortality (adjusted OR 6.39; p=0.002) and NEC-related gastrointestinal complications including cholestatic liver disease and short bowel syndrome (adjusted OR 5.47; p=0.006). CONCLUSION: Severe thrombocytopenia within the first 3 days after a diagnosis of NEC suggests a higher likelihood of bowel gangrene, morbidity, and mortality. Prospective studies of infants with early and severe thrombocytopenia may help determine the optimal timing of laparotomy in infants with NEC.

Free radicals and diseases in premature infants.

Free radicals have been implicated in the pathogenesis of a wide spectrum of human diseases. Premature infants are probably developmentally unprepared for extrauterine life in an oxygen-rich environment and exhibit a unique sensitivity to oxidant injury. Diseases associated with premature infants, including bronchopulmonary dysplasia, periventricular leukomalacia, intraventricular hemorrhage, retinopathy of prematurity, and necrotizing enterocolitis, have been linked to free radical-mediated cell and tissue injury. With the advent of therapies designed to combat the injurious effects of free radicals, the role of these highly reactive chemical molecules in the pathogenesis of neonatal diseases needs to be fully determined.

Necrotizing enterocolitis and gastrointestinal complications after indomethacin therapy and surgical ligation in premature infants with patent ductus arteriosus.

BACKGROUND: Indomethacin is the most frequently used pharmacological agent for closure of a patent ductus arteriosus (PDA) in premature infants. However, reports of complications, particularly, necrotizing enterocolitis (NEC) and isolated gastrointestinal perforation have generated concerns about the use of this medication. OBJECTIVES: A retrospective study to compare the incidence of NEC, NEC-related gastrointestinal complications and isolated gastrointestinal perforation among premature infants treated for a PDA with either, indomethacin alone (I), surgical ligation alone (L), or indomethacin followed by surgical ligation (I-L). METHODS: The medical records of 224 infants that underwent treatment, either pharmacological or surgical, for a PDA, confirmed by echocardiography, over a 4-year period (1995 to 1998) were analyzed. Treatment history and gastrointestinal complications were reviewed. RESULTS: Of the 224 infants, 108 (48.2%) were treated with I, 50 (22.3%) by L, 66 (29.5%) with I-L. The clinical characteristics of the three treatment groups were similar and no differences in the incidence of NEC were observed between groups. NEC occurred in 14 (13%) of the I group, seven (14%) of the L group, and eight (12%) of the I-L group. The rate of NEC related gastrointestinal complications and isolated gastrointestinal perforation were also similar among groups. CONCLUSION: In this large retrospective study, indomethacin treatment for a significant PDA in premature infants was not associated with a greater risk for NEC or NEC-related gastrointestinal complications than surgical ligation.

Transcutaneous bilirubin--comparing the accuracy of BiliChek® and JM 103® in a regional postnatal unit.

OBJECTIVE: Transcutaneous bilirubin (TcB) has the potential to reduce serum bilirubin sampling. During a recent survey on the use of TcB in postnatal units in the Republic of Ireland, we identified that only 58% of the 19 units were using TcB and that only two devices were in use, the BiliChek® and JM 103®. We aimed to evaluate and compare these two devices in a regional postnatal unit. METHODS: To evaluate and compare the accuracy of the BiliChek® and JM 103®, we studied simultaneous TcB and total serum bilirubin (TSB) measurements from a population of jaundiced term and near term infants. We evaluated each device with regard to correlation with TSB and potential to safely reduce serum bilirubin testing. RESULTS: Both TcB devices strongly correlated with TSB (r = 0.88 for BiliChek® and r = 0.70 for JM 103®. The BiliChek® and JM 103® were accurate up to cut-off values of 200 µmol/L and 180 µmol/L, respectively. Using Bhutani's nomogram, 100% sensitivity was achieved using the 75th percentile for BiliChek® and the 40th percentile for JM 103®. CONCLUSION: Both TcB devices correlated closely with moderately increased TSB levels and are suitable screening tools to identify jaundiced infants that require a serum bilirubin, with upper limit cut-off values. Both devices reduced the need for TSB levels. We found the BiliChek® slightly more accurate than the JM 103® for our study population. TcB however, is not in widespread use.

Indomethacin therapy for patent ductus arteriosus in premature infants: efficacy of a dosing strategy based on a second-dose peak plasma indomethacin level and estimated plasma indomethacin levels.

The objective of this study was to determine the rate of patent ductus arteriosus (PDA) closure in premature infants using an adjustable indomethacin (INDO) dosing strategy, based on a second-dose peak plasma INDO level. We conducted a retrospective review of the medical records of premature infants that were treated with INDO for a PDA, had a second dose peak plasma NDO levels, and followed predetermined guidelines for INDO dosing adjustments, over a 4-year period (1995 to 1998). Of 103 infants treated with the adjustable INDO dosing strategy, 66 (64%) achieved PDA closure whereas 37 (36%) did not. No differences in the second-dose peak plasma INDO levels (830 +/- 339 versus 702 +/- 381 ng/mL), day of life treatment was started (4 +/- 3 versus 4 +/- 2 days), or the number of doses of INDO received (4 +/- 1 versus 5 +/- 2 dose) were observed between responders and nonresponders. However, fourth-dose peak plasma INDO levels, which were available from 38 of 66 (57%) of the responders and 20 of 37 (54%) of the nonresponders, were lower in nonresponders (1553 +/- 413 versus 1829 +/- 609 ng/mL, p < 0.05). Patient demographics, including birth weight and gestational age, were similar between these groups. Using an adjustable INDO dosing strategy, based on a second-dose peak plasma INDO level and estimated plasma levels, PDA closure rates of 64% can be achieved. Although a clear relationship between INDO plasma levels and PDA closure was evident form this study, the rate of PDA closure in our study was lower than has been observed in studies with serial plasma INDO level monitoring.

CoASH and CoASSG levels in lungs of hyperoxic rats as potential biomarkers of intramitochondrial oxidant stresses.

Coenzyme A (CoASH) is compartmentalized preferentially in the mitochondria, and CoASH and its mixed disulfide with glutathione (CoASSG) undergo thiol/disulfide exchange reactions with glutathione (GSH) and glutathione disulfide (GSSG) in vitro. We measured CoASH and CoASSG in freeze-clamped lung tissues from Fischer-344 and Sprague-Dawley rats maintained in room air or exposed to >95% O(2) for 48 h to test the hypothesis that oxidant stresses on lung thiol status would be observed in the CoASH/CoASSG redox couple, suggesting oxidant stress responses in the mitochondria. Lung tissue concentrations of CoASSG in the Fischer-344 rats declined from 0.89 +/- 0.15 to 0.51 +/- 0.13 nmol/g of lung after 48 h of hyperoxia. CoASH levels declined from 6.40 +/- 0.84 to 3.0 +/- 0.65 nmol/g of lung, and acetyl CoA levels also were lower in the lungs of animals exposed to hyperoxia. CoASH/CoASSG ratios were lower in animals exposed to hyperoxia, satisfying our previously defined criteria for an oxidant stress on this thiol/disulfide redox couple, but absolute CoASSG levels were not increased, as would be expected for oxidant stresses driven simply by increases in reactive oxygen species or other oxidants. Pulmonary edema was observed in the hyperoxic rats and accounted for some of the declines in CoASH concentrations, but CoASH contents per total lung also declined. Lung mitochondrial succinate dehydrogenase activities were not diminished in rats exposed to hyperoxia, indicating that the decreases in CoASH concentrations are not attributable to general destruction of lung mitochondria. Lung GSSG contents were greater in the hyperoxia animals, but GSH/GSSG ratios, which are dominated by extramitochondrial pools, did not decrease in these animals. The mechanisms responsible for, and the possible pathophysiologic consequences of, the decreases in lung CoASH concentrations are not evident from the data available at the present time, but the loss of more than half the tissue contents of CoASH is likely to generate additional metabolic effects that could have significant pathophysiologic consequences.