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Biomedical subjects

David C Bellinger

Publications and source records attributed to David C Bellinger.

At least 37 records · Page 2Linked to original sources
PubMed2004

Intraoperative hyperglycemia during infant cardiac surgery is not associated with adverse neurodevelopmental outcomes at 1, 4, and 8 years.

BACKGROUND: It is unknown whether intraoperative hyperglycemia in infants is associated with worse neurodevelopmental outcomes after low-flow cardiopulmonary bypass (LF), deep hypothermic circulatory arrest (CA), or both. METHODS: In a database review of a prospective trial of 171 infants undergoing arterial switch for D-transposition of the great arteries who were randomly assigned to predominantly LF or CA, glucose was measured after induction (T1), 5 min after cardiopulmonary bypass onset (T2), at the onset of CA or LF (T3), 5 min after CPB resumption (T4), at rewarming to 32 degrees C (T5), 10 min after cardiopulmonary bypass weaning (T6), and 90 min after CA or LF (T7). Outcomes included seizures, electroencephalographic findings, and neurodevelopmental evaluation at 1, 4, and 8 yr. RESULTS: Glucose concentrations were affected by support strategy and age at surgery. Lower glucose in the entire group at T6-T7 tended to predict electroencephalographic seizures (P = 0.06 and P = 0.007) but was not related to clinical seizures. Within the predominantly CA group, higher glucose did not correlate with worse outcomes. Rather, it was associated with more rapid electroencephalographic normalization of "close burst" and "relative continuous" activity at all times except T2 (P < or = 0.03), a finding more pronounced in infants aged 7 days old or younger. Intraoperative serum glucose concentrations were unrelated to neurodevelopmental outcomes at ages 1, 4, and 8 yr. CONCLUSIONS: Low glucose after cardiopulmonary bypass tended to relate to electroencephalographic seizures and slower electroencephalogram recovery, independent of CA duration. High glucose concentrations were not associated with worse neurodevelopmental outcomes. Avoiding hypoglycemia may be preferable to restricting glucose in infants undergoing heart surgery.

Cardiac Surgical Procedures↗
PubMed2004

Effect of prenatal diagnosis on outcomes in D-transposition of the great arteries.

BACKGROUND: By decreasing preoperative morbidity, prenatal diagnosis could improve neurodevelopmental outcomes in infants with critical congenital heart disease. We explored the impact of prenatal diagnosis on perinatal and perioperative variables and on outcomes at 1 year of age. METHODS: We analyzed a database of children enrolled in prospective studies on surgical support techniques from 1988 to 2000. Selection criteria included a diagnosis of D-transposition of the great arteries with intact ventricular septum or ventricular septal defect, no extracardiac congenital anomalies, birth weight >2.3 kg, and repair by arterial switch procedure. RESULTS: Of 346 patients at enrollment, 25 had a prenatal diagnosis, and 321 did not. Children with prenatal diagnosis, compared with those without, had a lower likelihood of birth by spontaneous labor, lower birth weights, lower Apgar 5 scores, a higher rate of preoperative endotracheal intubation, and surgery at a younger age. They tended to have a lower incidence of fetal distress during labor. At 1 year of age, 272 patients were tested with the Psychomotor Development Index and Mental Development Index of the Bayley Scales. Mean z scores were similar in those with and without prenatal diagnosis for both Psychomotor Development Index (-0.92 +/- 0.93 vs -0.88 +/- 1.05) and Mental Development Index (-0.29 +/- 1.13 vs -0.41 +/- 0.93). CONCLUSIONS: Infants with D-transposition of the great arteries with and without prenatal diagnosis differed with respect to perinatal and perioperative variables, but their development at 1 year of age was similar. Future studies should include a greater number of children with prenatal diagnosis and a variety of congenital heart lesions.

Child Development↗
PubMed2004

Lead.

Children differ from adults in the relative importance of lead sources and pathways, lead metabolism, and the toxicities expressed. The central nervous system effects of lead on children seem not to be reversible. Periods of enhanced vulnerability within childhood have not consistently been identified. The period of greatest vulnerability might be endpoint specific, perhaps accounting for the failure to identify a coherent "behavioral signature" for lead toxicity. The bases for the substantial individual variability in vulnerability to lead are uncertain, although they might include genetic polymorphisms and contextual factors. The current Centers for Disease Control and Prevention screening guideline of 10 micro g/dL is a risk management tool and should not be interpreted as a threshold for toxicity. No threshold has been identified, and some data are consistent with effects well below 10. Historically, most studies have concentrated on neurocognitive effects of lead, but higher exposures have recently been associated with morbidities such as antisocial behavior and delinquency. Studies of lead toxicity in experimental animal models are critical to the interpretation of nonexperimental human studies, particularly in addressing the likelihood that associations observed in the latter studies can be attributed to residual confounding. Animal models are also helpful in investigating the behavioral and neurobiological mechanisms of the functional deficits observed in lead-exposed humans. Studies of adults who have been exposed to lead are of limited use in understanding childhood lead toxicity because developmental and acquired lead exposure differ in terms of the maturity of the organs affected, the presumed mechanisms of toxicity, and the forms in which toxicities are expressed.

Adult↗
PubMed2003

The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants.

BACKGROUND: We hypothesized that cognitive impairment and hemodynamic instability after infant cardiac surgery with cardiopulmonary bypass might be exacerbated by hemodilution. METHODS: In a single-center randomized trial with blinded assessment of outcomes, we compared use of 2 hemodilution protocols during hypothermic cardiopulmonary bypass with infant cardiac surgery. The primary perioperative end point was lowest cardiac index in the first 24 hours postoperatively, and primary end points at age 1 year were scores on the Psychomotor Development Index and Mental Developmental Index of the Bayley Scales. RESULTS: Among 147 subjects, 74 were assigned to the lower-hematocrit strategy (21.5% +/- 2.9%, mean +/- SD at onset of low-flow bypass) and 73 to the higher-hematocrit strategy (27.8% +/- 3.2%). In intent-to-treat analyses the lower-hematocrit group had lower nadirs of cardiac index (P =.02), higher serum lactate levels 60 minutes after cardiopulmonary bypass (P =.03), and a greater percentage increase in total body water on the first postoperative day (P =.006). Blood product use and adverse events were similar in the 2 groups. At age 1 year (113 children), the lower-hematocrit group had worse scores on the Psychomotor Development Index (81.9 +/- 15.7 vs 89.7 +/- 14.7, P =.008), as well as more Psychomotor Development Index scores at least 2 SDs below the population mean (16/56 [29%] vs 5/53 [9%], P =.01). The groups had similar Mental Developmental Index scores and findings on neurologic examination. Inferences using hematocrit as a continuous variable were similar to those based on intent-to-treat analyses. CONCLUSIONS: Hemodilution to a hematocrit level in wide use for cardiopulmonary bypass and thought to be safe is associated with adverse perioperative and developmental outcomes in infants.

Cardiac Surgical Procedures↗
PubMed2003

Motor sequence learning and reading ability: is poor reading associated with sequencing deficits?

Although it is widely assumed that children with learning disabilities have "sequencing problems," these have not been well specified. A non-verbal serial reaction time (SRT) paradigm was used to evaluate motor sequence learning in 422 children between ages 7 and 11 in relation to reading, cognitive ability level, and attention problems. The children demonstrated the response profile typically associated with motor sequence learning, but the component of the profile indicative of implicit sequence learning was not reliably associated with any of the predictors. Cognitive ability predicted overall response time; cognitive ability, reading, and attention problems each predicted overall accuracy. Explicit learning was predicted by cognitive ability, but not by reading or attention problems. Thus, we found no evidence that poor reading is preferentially associated with a domain general deficit in sequential learning.

Aptitude↗
PubMed2003

Length of stay after infant heart surgery is related to cognitive outcome at age 8 years.

OBJECTIVE: To test the hypothesis that postoperative length of stay (LOS) after infant heart surgery might be an easily measured surrogate marker for various events that culminate in later adverse cognitive outcome. METHODS: Among 160 eligible patients with D-transposition of the great arteries undergoing reparative surgery in infancy, 155 (97%) were reevaluated at age 8 years with IQ and achievement testing. We explored whether LOS quartiles were associated with these outcomes when adjusting for perioperative and sociodemographic variables. RESULTS: Longer cardiac intensive care unit (CICU) LOS quartiles were associated at age 8 years with lower full-scale IQ (P=.02), lower verbal IQ (P=.02), and with tendencies toward lower performance IQ (P=.08) and math achievement (P=.08) in adjusted models. Compared with patients in the first quartile of CICU LOS, those in the fourth quartile had mean scores for full-scale IQ that were lower by 7.2 points (P=.01); verbal IQ, 7.3 points (P=.02); performance IQ, 5.8 points (P=.05); and math achievement, 6.0 points (P=.07). Analyses on hospital LOS quartile were similar. CONCLUSIONS: Longer postoperative LOS is associated with worse later cognitive function, even when adjusted for perioperative events, perfusion times, and sociodemographic variables. Further research is necessary to determine the mechanisms underlying this relation.

Cardiac Surgical Procedures↗
PubMed2003

Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial.

OBJECTIVES: Our goal was to determine which of the two major methods of vital organ support used in infant cardiac surgery, total circulatory arrest and low-flow cardiopulmonary bypass, results in better neurodevelopmental outcomes at school age. METHODS: In a single-center trial, infants with dextrotransposition of the great arteries underwent the arterial switch operation after random assignment to either total circulatory arrest or low-flow cardiopulmonary bypass. Developmental, neurologic, and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children (97%). RESULTS: Treatment groups did not differ in terms of most outcomes, including neurologic status, Full-Scale or Performance IQ score, academic achievement, memory, problem solving, and visual-motor integration. Children assigned to total circulatory arrest performed worse on tests of motor function including manual dexterity with the nondominant hand (P =.003), apraxia of speech (P =.01), visual-motor tracking (P =.01), and phonologic awareness (P =.003). Assignment to low-flow cardiopulmonary bypass was associated with a more impulsive response style on a continuous performance test of vigilance (P <.01) and worse behavior as rated by teachers (P =.05). Although mean scores on most outcomes were within normal limits, neurodevelopmental status in the cohort as a whole was below expectation in many respects, including academic achievement, fine motor function, visual-spatial skills, working memory, hypothesis generating and testing, sustained attention, and higher-order language skills. CONCLUSIONS: Use of total circulatory arrest to support vital organs during heart surgery in infancy is generally associated with greater functional deficits than is use of low-flow cardiopulmonary bypass, although both strategies are associated with increased risk of neurodevelopmental vulnerabilities.

Boston↗
PubMed2003

The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: the Boston Circulatory Arrest Trial.

OBJECTIVES: Despite the technical advantages of total circulatory arrest for vital organ support during infant heart surgery, many centers have moved away from its use because of the demonstrated effects of circulatory arrest of long duration on neurodevelopmental outcomes. Our goal was to determine the functional form of the association between duration of circulatory arrest and risk of neurodevelopmental dysfunction. METHODS: From 1988 to 1992, in a single-center trial, infants with d-transposition of the great arteries underwent the arterial switch operation after random assignment to circulatory arrest or low-flow bypass. The alpha-stat method was used, and hematocrit on bypass was maintained at 20%. Developmental, neurologic, and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children (97%). Outcomes selected for analysis were Full-Scale, Verbal, and Performance IQ, Reading and Mathematics Composite, time to complete the Grooved Pegboard (dominant hand), and the Mayo Test for Apraxia. RESULTS: Nonparametric regression and piecewise linear models indicated that neurodevelopmental outcomes were generally not adversely affected unless the duration of circulatory arrest exceeded a threshold of 41 minutes (95% 1-sided lower confidence limit of 32 minutes). CONCLUSIONS: We found that the effect of duration of total circulatory arrest on later neurodevelopmental outcomes is nonlinear, with little influence at shorter durations and with steadily worsening outcomes after longer durations of circulatory arrest. Because the effects of duration of circulatory arrest may vary according to diagnosis, age at surgery, and other bypass and perioperative variables, this study cannot ascertain a universally "safe" duration of total circulatory arrest.

Boston↗
PubMed2003

Visual-spatial skills in children after open-heart surgery.

This study was part of a randomized clinical trial comparing the central nervous system effects of the two vital organ-support methods used in infant cardiac surgery: total circulatory arrest and low-flow cardiopulmonary bypass. The extent to which visual-spatial deficits are (1). associated with surgical and perioperative variables, (2). attributable to visual-perceptual, motor control, or metacognitive deficits, and (3). associated with adaptive difficulties at home or school was evaluated. The subjects were 155 8-year-old children with D-transposition of the great arteries who underwent the arterial switch operation before 3 months of age. As part of a comprehensive evaluation, the Rey-Osterrieth Complex Figure (ROCF) was administered. ROCF copy productions were classified as having a Basal Organization Level of 1 (low) or 2 or greater. A five-category clinical rating was also assigned. More than half of the children in the cohort (52%) had copy productions scored at Level 1, more than twice the expected frequency. The risk of having a low score was not associated with vital organ support method or other surgical variables. On the basis of comparisons of the relative fits of nested logistic regression models, poor visual-perceptual abilities were more predictive of having a Level 1 score than either motor control or metacognitive deficits. Children with poor copy production scores had lower mathematics scores, but not lower reading scores or poorer parent and teacher ratings of adaptive competence. The percentage of children receiving remedial school services was associated with ROCF clinical rating, ranging from 58% in the worst category to 8% in the best category. Visual-spatial deficits are common among children after infant heart surgery and seem to reflect visual-perceptual rather than motor control or metacognitive deficits. In addition, these deficits do not seem to be clearly associated with the intraoperative methods or postoperative events evaluated.

Cardiac Surgical Procedures↗
PubMed2003

An approach to assessment of endocrine disruption in the National Children's Study.

In this article we consider the importance of assessing endocrine disruption in a large new cohort that has been proposed, the National Children's Study (NCS). We briefly review evidence that endocrine disruption is a potentially important hypothesis for human studies and weigh the need to assess endocrine disruption in the NCS. We note the salient features of earlier, similar cohort studies that serve as reference points for the design of the NCS. Finally, we discuss features of the NCS that would allow or enhance assessment of endocrine disruption, even if endocrine disruption were not a primary hypothesis motivating the study. At this time, the evidence supporting endocrine disruption in humans with background-level exposures is not strong. Thus, a compelling rationale for the NCS will probably need to be based on core hypotheses that focus on other issues. Nonetheless, if properly designed, the NCS could serve as an excellent resource for investigating future hypotheses regarding endocrine disruption.

Adolescent↗
PubMed2003

Perspectives on incorporating human neurobehavioral end points in risk assessments.

Three topics are addressed: (1) measurement issues (e.g., the reliability and validity of neurobehavioral test scores), (2) general principles of assessment, including test selection, and (3) interpretation of scores. Psychological tests generally perform as well as medical tests in terms of reliability and validity. Test manuals, assessment textbooks, and psychologists are useful resources to the risk assessor. The variety of different tests employed in neurobehavioral studies complicates interstudy comparisons. In addition, tests that ostensibly assess the same general domain of function might assess somewhat different abilities within that domain. Although a uniform battery for use in all studies seems desirable, the battery appropriate for a specific study depends on study goals, knowledge about the mechanism(s) of neurotoxicity, nature of the study population, and pattern of exposure. Exposure-related neurobehavioral deficits are generally indicators of "altered function" rather than of "clinical disease." Limiting concern to end points corresponding to clinical disease might not be appropriate. Many neurobehavioral diagnoses are phenomenological and a neurotoxicant might cause a unique pattern of deficits for which no label has been created. The concern that a small shift in the central tendency of a distribution of test scores has no significance for the individual should be reexamined in light of the prevention paradox, formulated on the basis of epidemiologic studies of chronic disease. Poor performance on a neurobehavioral test does not necessarily map clearly onto underlying behavioral or neural substrate. The absence of such linkages, given current knowledge about brain-behavior relationships, should not reduce confidence in neurobehavioral end points. Use of neurobehavioral test scores involves considerations that differ little from those that the risk assessor routinely addresses in using end points commonly used in research on other topics in environmental epidemiology.

Environmental Pollutants↗
PubMed2002

Neurodevelopmental outcome after congenital heart surgery: results from an institutional registry.

OBJECTIVE: Increased survival in children with critical congenital heart disease (CHD) has raised interest in the neurodevelopmental sequelae of these lesions. This investigation is part of an institutional effort to examine the neurodevelopment of 5-year-old children following repair or palliation of CHD. METHODS: We performed a battery of neuropsychological tests on a sample of 243 children between 1998 and 2001. RESULTS: In the sample as a whole, mean full-scale (FSIQ), verbal (VIQ), and performance (PIQ) IQ scores were in the normal range (96.8+/-15.9, 97.8+/-14.6, and 96.3+/-17.1, respectively). Anatomic, demographic, and perioperative factors were assessed for impact on neurodevelopment. In multiple regression analysis, lower socioeconomic status (SES) and the diagnosis of velocardiofacial syndrome (VCFS) predicted a lower FSIQ (P=0.01, and P=0.001, respectively). A single ventricle diagnosis (P=0.06), longer postoperative ICU stay (P=0.08), and cumulative duration of hypothermic circulatory arrest (HCA) (P=0.09) approached significance as predictors of lower FSIQ. CONCLUSION: Children with CHD, on the whole, appear to be performing within the average range in terms of intellectual abilities. Lower SES and VCFS are associated with lower IQ scores. Trends toward worse outcomes were observed in single ventricle patients, biventricular patients with longer postrepair ICU stays, and patients subjected to longer periods of HCA.

Child↗
PubMed2002

Neurologic outcome of choreoathetoid encephalopathy after cardiac surgery.

Postoperative encephalopathy with choreoathetosis is a serious neurologic complication of childhood cardiac surgery. An inadequate understanding of the long-term outcome has limited family counseling and the institution of intervention strategies. Our objective was to define the long-term neurologic, cognitive, and behavioral outcome in this group of patients. By retrospective review we identified all cases of choreoathetosis in our cardiac intensive care unit from 1986 through 1995. During this decade we described a sudden transient increase in postoperative choreoathetosis that disappeared as we modified treatment strategies in perioperative care. These children underwent a comprehensive battery of neurologic, cognitive, and behavioral tests to determine in detail their long-term outcome. Of the 36 cases identified of which three were deceased, four were abroad, and eight were lost to follow-up, 21 families were approached, and 15 of the 21 (71%) consented to testing. We found pervasive deficits in memory, attention, and language, with a median full-scale IQ of 67 (range = 40-122), as well as in motor function, including persistent dyskinesia in seven of 15 (47%). The pervasive and enduring cognitive and motor deficits in survivors of postoperative choreoathetosis caution for guarded predictions of outcome and highlight the need for careful neurologic and cognitive evaluation in all children with choreoathetosis after open heart surgery.

Athetosis↗
PubMed2002

Neurodevelopmental outcomes after biventricular repair of congenital heart defects.

OBJECTIVE: This study was undertaken to assess neurodevelopment of children after biventricular repair of congenital heart defects. METHODS: Full-scale, performance, and verbal IQs of 69 patients who had undergone biventricular repair were assessed at 5 years of age with the Wechsler Preschool and Primary Scales of Intelligence-Revised. The Wide Range Assessment of Visual-Motor Abilities was used to measure visual-motor skills. Regression analyses adjusting for parental IQ and socioeconomic status were used to evaluate outcome predictors. RESULTS: Median age at repair was 91 days (range 1-1558 days). Hypothermic circulatory arrest was used in 35 cases (mean duration of hypothermic circulatory arrest 33 +/- 17 minutes). Mean full-scale, performance, and verbal IQs for the entire study population were within the reference range (full-scale 96.9 +/- 15.9, performance 96.6 +/- 16.8, verbal 97.7 +/- 15.2). Anatomic diagnosis, age at operation, and use of hypothermic circulatory arrest did not influence full-scale IQ (P =.66, P =.14, and P =.46, respectively), performance IQ (P =.64, P =.36, and P =.73, respectively), or verbal IQ (P =.74, P =.08, and P =.39, respectively). Among patients subjected to hypothermic circulatory arrest, duration of arrest was evaluated as a predictor of outcome. After adjustment for parental IQ, full-scale (P =.12), performance (P =.07), and verbal (P =.22) IQ scores of patients with more than 39 minutes of hypothermic circulatory arrest were not different from those of patients who had arrest periods of 39 minutes or less. After adjustment for socioeconomic status, however, full-scale (P =.05) and performance (P =.03) IQ scores were lower among patients who had more than 39 minutes of hypothermic circulatory arrest. After adjustment for either parental IQ or socioeconomic status, patients with more than 39 minutes of arrest had lower scores on Wide Range Assessment of Visual-Motor Abilities subtests of visual-motor and fine motor abilities and on several performance IQ subtests. CONCLUSIONS: IQs of patients who had undergone biventricular repair of congenital heart defects were within the reference range. However, hypothermic circulatory arrest for longer than 39 minutes was associated with deficits in visual-motor and fine motor skills and possibly in full-scale IQ.

Boston↗
PubMed2002

Influence of parental stress and social support on the behavioral adjustment of children with transposition of the great arteries.

The joint role of parent stress and social support in the emotional adjustment of children was examined prospectively in a group of children with d-transposition of the great arteries (d-TGA). Questionnaires on parent perceptions of stress and social support were administered when children were 1 and 4 years of age (n = 143-153). Parent ratings of child behavior problems were collected at 4 years (n = 152). The findings indicate a favorable outcome for parents and children with congenital heart disease (CHD). Compared with normative samples, parents experienced less stress and more social support, and they rated children as showing fewer behavior problems. Parents with more stress at both ages reported more behavior problems. Families with less social support reported more stress at both 1 and 4 years. Social support, however, did not moderate the relationship between stress and child behavior problems. Early detection of distressed families may assist in alleviating stress and reducing behavior problems.

Child Behavior Disorders↗
PubMed2002

Blood lead level and dental caries in school-age children.

The association between blood lead level and dental caries was evaluated in cross-sectional analyses of baseline data for 543 children 6-10 years old screened for enrollment in the Children's Amalgam Trial, a study designed to assess potential health effects of mercury in silver fillings. Approximately half of the children were recruited from an urban setting (Boston/Cambridge, MA, USA) and approximately half from a rural setting (Farmington, ME, USA). Mean blood lead level was significantly greater among the urban subgroup, as was the mean number of carious tooth surfaces. Blood lead level was positively associated with number of caries among urban children, even with adjustment for demographic and maternal factors and child dental practices. This association was stronger in primary than in permanent dentition and stronger for occlusal, lingual, and buccal tooth surfaces than for mesial or distal surfaces. In general, blood lead was not associated with caries in the rural subgroup. The difference between the strength of the associations in the urban and rural settings might reflect the presence of residual confounding in the former setting, the presence of greater variability in the latter setting in terms of important caries risk factors (e.g., fluoride exposure), or greater exposure misclassification in the rural setting. These findings add to the evidence supporting a weak association between children's lead exposure and caries prevalence. A biologic mechanism for lead cariogenicity has not been identified, however. Our data are also consistent with residual confounding by factors associated with both elevated lead exposure and dental caries.

Boston↗