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Biomedical subjects

David C Bellinger

Publications and source records attributed to David C Bellinger.

At least 19 recordsLinked to original sources
PubMed2026

Prenatal exposure to indoor PM2.5 and children's cognitive performance at 4 years of age: an observational analysis from the UGAAR randomized controlled trial.

Outdoor fine particulate matter (PM2.5) concentrations during pregnancy are linked to reduced cognitive performance in children. We previously reported that portable HEPA filter air cleaners use during pregnancy improved children's mean full-scale IQ (FSIQ), but no previous studies have evaluated the relationship between indoor PM2.5 during pregnancy and FSIQ in childhood. We conducted an observational analysis using data from the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) randomized controlled trial. Using a previously developed model of weekly indoor PM2.5 concentrations, we estimated the average concentrations in participants' homes over the full pregnancy and in each trimester. When the children were four years old, we measured FSIQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV). We used multiple linear regression to assess the adjusted relationships between interquartile range (IQR) contrasts in indoor PM2.5 during pregnancy and FSIQ among 475 mother-child dyads. An 8.8 μg/m3 increase in indoor PM2.5 concentration over the full pregnancy was associated with a reduction of 1.4 points (95% CI: -3.4, 0.6) in mean FSIQ. The strongest association between PM2.5 concentrations and FSIQ was in the first trimester, when a 19.1 μg/m3 contrast was associated with a 2.8-point reduction (95% CI: -5.7, 0.2) in mean FSIQ. Indoor PM2.5, particularly during early pregnancy, may impair brain development, leading to lower mean FSIQ scores in four-year old children. These results, combined with our previous analysis of HEPA filter air cleaners, indicate that reducing PM2.5 exposure during pregnancy has beneficial effects on children's cognitive performance.

Humans↗
PubMed2005

Neuropsychological correlates of hair arsenic, manganese, and cadmium levels in school-age children residing near a hazardous waste site.

A pilot study was conducted to explore the potential associations between hair metal levels and the neuropsychological function and behavior of school-aged children. Thirty-two children, 11-13 years old, were administered a battery of tests that assessed general intelligence, visual-motor skills, receptive language, verbal memory, nonverbal problem-solving, and behavior problems. Parents and teachers rated the children's attention, executive functions, and behavior problems. The concentrations of manganese (Mn), arsenic (As), and cadmium (Cd) were measured in hair samples provided by 31 of the children. The mean hair metal levels were: Mn, 471.5 parts per billion (ppb); As, 17.8 ppb; Cd, 57.7 ppb. Children's general intelligence scores, particularly verbal IQ scores, were significantly related, inversely, to hair Mn and As levels, as were scores on tests of memory for stories and a word list. In some cases, a significant Mn-by-As interaction was found. It appeared that it was the low scores of children for whom both Mn and As levels were above the median values in the sample that were responsible for the main effects observed for each metal. No other significant relationships were found. These results suggest the need to study further the neuropsychological correlates of developmental exposure to Mn and As, particularly as a mixture.

Arsenic↗
PubMed2005

Teratogen update: lead and pregnancy.

This review focuses on the impacts of lead exposure on reproductive health and outcomes. High levels of paternal lead exposure (>40 microg/dl or >25 microg/dl for a period of years) appear to reduce fertility and to increase the risks of spontaneous abortion and reduced fetal growth (preterm delivery, low birth weight). Maternal blood lead levels of approximately 10 microg/dl have been linked to increased risks of pregnancy hypertension, spontaneous abortion, and reduced offspring neurobehavioral development. Somewhat higher maternal lead levels have been linked to reduced fetal growth. Some studies suggest a link between increased parental lead exposure and congenital malformations, although considerable uncertainty remains regarding the specific malformations and the dose-response relationships. Common methodological weaknesses of studies include potential exposure misclassifications due to the frequent unavailability of exposure biomarker measurements at biologically appropriate times and uncertainty regarding the best exposure biomarker(s) for the various outcomes. A special concern with regard to the pregnant woman is the possibility that a fetus might be exposed to lead mobilized from bone stores as a result of pregnancy-related metabolic changes, making fetal lead exposure the result of exposure to exogenous lead during pregnancy and exposure to endogenous lead accumulated by the woman prior to pregnancy. By reducing bone resorption, increased calcium intake during the second half of pregnancy might reduce the mobilization of lead from bone compartments, even at low blood lead levels. Subgroups of women who incurred substantial exposures to lead prior to pregnancy should be considered to be at increased risk.

Bone and Bones↗
PubMed2005

A quantitative analysis of prenatal methyl mercury exposure and cognitive development.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper quantifies the impact of prenatal MeHg exposure on cognitive development. Other papers quantify the beneficial impact of prenatal intake of n-3 PUFAs on cognitive function and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults. This analysis aggregates results from three major prospective epidemiology studies to quantify the association between prenatal MeHg exposure and cognitive development as measured by intelligence quotient (IQ). It finds that prenatal MeHg exposure sufficient to increase the concentration of mercury in maternal hair at parturition by 1 microg/g decreases IQ by 0.7 points. This paper identifies important sources of uncertainty influencing this estimate, concluding that the plausible range of values for this loss is 0 to 1.5 IQ points.

Central Nervous System↗
PubMed2005

A quantitative analysis of prenatal intake of n-3 polyunsaturated fatty acids and cognitive development.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of prenatal n-3 intake on cognitive development. Other papers quantify the negative impact of prenatal exposure to MeHg on cognitive development, and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults. This paper aggregates eight randomized controlled trials (RCTs) comparing cognitive development in controls and in children who had received n-3 PUFA supplementation (seven studies of formula supplementation and one study of maternal dietary supplementation). Our analysis assigns study weights accounting for statistical precision, relevance of three endpoint domains (general intelligence, verbal ability, and motor skills) to prediction of IQ, and age at evaluation. The study estimates that increasing maternal docosahexaenoic acid (DHA) intake by 100 mg/day increases child IQ by 0.13 points. The paper notes that findings were inconsistent across the RCTs evaluated (although our findings were relatively robust to changes in the weighting scheme used). Also, for seven of the eight studies reviewed, effects are extrapolated from formula supplementation to maternal dietary intake.

Central Nervous System↗
PubMed2005

A quantitative risk-benefit analysis of changes in population fish consumption.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish, while recommendations encourage fish consumption among the general population because of nutritional benefits. To investigate the aggregate impacts of hypothetical shifts in fish consumption, the Harvard Center for Risk Analysis convened an expert panel (see acknowledgements). Effects investigated include prenatal cognitive development, coronary heart disease mortality, and stroke. Substitution of fish with high MeHg concentrations with fish containing less MeHg among women of childbearing age yields substantial developmental benefits and few negative impacts. However, if women instead decrease fish consumption, countervailing risks substantially reduce net benefits. If other adults (mistakenly and inappropriately) also reduce their fish consumption, the net public health impact is negative. Although high compliance with recommended fish consumption patterns can improve public health, unintended shifts in consumption can lead to public health losses. Risk managers should investigate and carefully consider how populations will respond to interventions, how those responses will influence nutrient intake and contaminant exposure, and how these changes will affect aggregate public health.

Adolescent↗
PubMed2005

Low-level environmental lead exposure and children's intellectual function: an international pooled analysis.

Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 microg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 microg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5-10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 microg/dL and declined to 9.4 microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 microg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 microg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were 3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 microg/dL was significantly greater than that observed for those with a maximal blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is associated with intellectual deficits.

Child↗
PubMed2005

Helminth infection and cognitive impairment among Filipino children.

The objective of this study was to examine the independent effect of infection with each of four helminths (Ascaris lumbricoides, Schistosoma japonicum, Necator americanus, and Trichuris trichiura) on cognitive function after adjusting for the potential confounders nutritional status, socioeconomic status (SES), hemoglobin, sex, and the presence of other helminthes. This cross-sectional study was carried out in a rural village in Leyte, The Philippines in 319 children 7-18 years old. Three stools were collected and read in duplicate by the Kato Katz method. Infection intensity was defined by World Health Organization criteria. Cognitive tests were culturally adapted and translated. Learning and memory cognitive domains were each defined by three subscales of the Wide Range Assessment of Memory and Learning, which had an inter-rater reliability >/= 0.92 and test-retest reliabilities ranging from 0.61 to 0.89. A household SES questionnaire was administered. A logistic regression model was used to quantify the association between performance in different cognitive domains (learning, memory, verbal fluency, and the Philippine Non-Verbal Intelligence Test) and helminth infections. After adjusting for age, sex, nutritional status, hemoglobin, and SES, S. japonicum infection was associated with poor performance on tests of learning (odds ratio [OR] = 3.04, 95% confidence interval [CI] = 1.1-6.9), A. lumbricoides infection was associated with poor performance on tests of memory (OR = 2.2, 95% CI = 1.04-4.7), and T. trichiura infection was associated with poor performance on tests of verbal fluency (OR = 4.5, 95% CI = 1.04-30). Helminth infection was associated with lower performance in three of the four cognitive domains examined in this study. These relationships remained after rigorous control for other helminths and important confounding covariates.

Adolescent↗
PubMed2004

Prediction of IQ and achievement at age 8 years from neurodevelopmental status at age 1 year in children with D-transposition of the great arteries.

OBJECTIVE: Studies of developmental outcomes in children with congenital heart disease (CHD) frequently use assessments conducted in infancy as primary endpoints. Whether test scores of CHD patients in infancy are predictive of status at school age has not been evaluated, however. METHODS: In the Boston Circulatory Arrest Study, 135 children with D-transposition of the great arteries repaired by arterial switch operation were administered the Bayley Scales of Infant Development and the Fagan Test of Infant Intelligence at 1 year of age and the Wechsler Intelligence Scale for Children, Third Edition and the Wechsler Individual Achievement Test at 8 years. RESULTS: Although most 1-year test scores were significantly associated with 8-year test scores, the amounts of shared variance were modest (<10%). All 1-year test scores had poor sensitivity (16%-32%) and poor positive predictive value (35%-42%) but good specificity (80%-93%) and negative predictive value (78%-79%). More than half of the children with low scores at 8 years (< or =85) had had scores >84 at 1 year. CONCLUSION: This pattern suggests that although test scores at 1 year are modestly associated with test scores at 8 years, many children who are at risk for poor late outcomes will not be identified on the basis of 1-year test scores. Long-term follow-up of children with CHD is necessary to draw inferences about the developmental sequelae of preoperative, intraoperative, and postoperative factors.

Cardiac Surgical Procedures↗
PubMed2004

Early postoperative body temperature and developmental outcome after open heart surgery in infants.

BACKGROUND: Experimental data have suggested that early postoperative temperature management after cerebral ischemia may alter neurologic outcome. We explored whether minor deviations in early postoperative body temperature after infant heart surgery affects developmental outcome. METHODS: In a study of infants undergoing repair of congenital heart disease, 95% of whom had a period of deep hypothermic circulatory arrest, postoperative temperature data were collected following cardiac surgery. Subjects were infants who had been enrolled in one of two prospective randomized single-center trials. Development was tested at age one year (the Bayley Scales of Infant Development) and at four years (Wechsler Preschool and Primary Scale of Intelligence, including Full Scale IQ, a Verbal IQ, and a Performance IQ). RESULTS: Perioperative temperature data were reviewed in 329 patients, of whom 244 (74%) were evaluated at age one year and 156 (48%) were evaluated at four years. The temperature profile was recorded during the rewarming phase and for 36 hours postoperatively on the Intensive Care Unit. There were no significant associations between postoperative temperature and any of the neurodevelopmental tests at age one or four years. A further analysis assessing the percentage of time over specific temperature cutoff points of 37.5 degrees C, 38 degrees C, 38.5 degrees C, and 39 degrees C, revealed no significant effect. CONCLUSIONS: Neurodevelopmental outcome at one and four years after repair of complex congenital heart disease was not significantly affected by the early postoperative body temperature profile of the infant when a management strategy aiming for normothermia is employed.

Body Temperature↗
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↗