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Biomedical subjects

K B Nelson

Publications and source records attributed to K B Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1991

How much of neonatal encephalopathy is due to birth asphyxia?

In the literature on neonatal encephalopathy, the pervasive assumption is that once infants with major malformations or infections have been excluded, most of the remaining cases are due to birth asphyxia. Assessing the proportion of neonatal encephalopathy that is due to asphyxia during birth is difficult because of problems in defining asphyxia and neonatal encephalopathy and in recognizing the cause of neonatal neurologic illness. Available evidence indicates that neonatal neurologic signs are not strongly related to obstetric complications, signs of fetal distress, or biochemical markers usually considered to indicate perinatal asphyxia. Most studies that have sought positive evidence of independent markers of intrapartum asphyxia have found them to be absent in a large majority of neurologically symptomatic neonates. We conclude that the proportion of neonatal encephalopathy that is asphyxial in origin is not known but warrants examination, especially in view of the probable need in the near future to identify, on the basis of evidence available in the first hour or so of life, suitable candidates for clinical trials of powerful but risky treatments of birth asphyxia.

Asphyxia Neonatorum↗
PubMed1991

Analysis of clinical trials by treatment actually received: is it really an option?

The primary analysis of a randomized clinical trial should compare patients in their randomly assigned treatment groups (intention to treat analysis). When a substantial number of subjects fail to take a prescribed medication or are switched to a different study medication, it is tempting to consider treatment comparisons using only those subjects with treatment as actually received rather than as prescribed. There are several arguments against this approach: the prognostic balance brought about by randomization is likely to be disturbed; sample size will be reduced; and the validity of the statistical test procedures will be undermined. Further, results of analysis by treatment actually received may suffer from a bias introduced by using compliance, a factor often related to outcome independently of the treatment received, to determine the groups for comparison. The extent and nature of this bias will be related to the definition of compliance in an as treated analysis, a definition which could be unintentionally self-serving. We have investigated the problem of the definition of actual treatment in the context of a recent clinical trial. We used several definitions to classify patients as having received or not received treatment as prescribed. These definitions, when used in as treated analyses, provided results that were at times inconsistent or counter-intuitive, and which neither helped to confirm nor further explain the intention to treat analysis.

Child, Preschool↗
PubMed1991

Intelligence at six years in relation to neonatal bilirubin levels: follow-up of the National Institute of Child Health and Human Development Clinical Trial of Phototherapy.

Results of the National Institute of Child Health and Human Development Randomized Controlled Trial of Phototherapy were examined for the relationship of neonatal bilirubin level to neurological and developmental outcome at 6-year follow-up. This analysis focused on 224 control children with birth weight of less than 2000 g. Bilirubin levels were maintained below previously specified levels by the use of exchange transfusion only (24%). Rates of cerebral palsy were not significantly higher for children with elevated maximum bilirubin level than for those whose level remained low. No association was evident between maximum bilirubin level and IQ (Full Scale, Verbal, or Performance) by simple correlation analysis (r = -.087, P = .2 for Full Scale) or by multiple linear regression adjusting for factors that covary with IQ (beta = -.15, P = .58). IQ was not associated with mean bilirubin level, time and duration of exposure to bilirubin, or measures of bilirubin-albumin binding. Thus, over the range of bilirubin levels permitted in this clinical trial, there was no evidence of bilirubin toxicity to the central nervous system. Measures used to control the level of bilirubin in low birth weight neonates appear to prevent effectively the risk of bilirubin-induced neurotoxicity.

Bilirubin↗
PubMed1990

Phenobarbital for febrile seizures--effects on intelligence and on seizure recurrence.

Phenobarbital is widely used in the treatment of children with febrile seizures, although there is concern about possible behavioral and cognitive side effects. In 217 children between 8 and 36 months of age who had had at least one febrile seizure and were at heightened risk of further seizures, we compared the intelligence quotients (IQs) of a group randomly assigned to daily doses of phenobarbital (4 to 5 mg per kilogram of body weight per day) with the IQs of a group randomly assigned to placebo. After two years, the mean IQ was 7.03 [corrected] points lower in the group assigned to phenobarbital than in the placebo group (95 percent confidence interval, -11.52 to -2.5, P = 0.0068 [corrected]). Six months later, after the medication had been tapered and discontinued, the mean IQ was 5.2 points lower in the group assigned to phenobarbital (95 percent confidence interval, -10.5 to 0.04, P = 0.052). The proportion of children remaining free of subsequent seizures did not differ significantly between the treatment groups. We conclude that phenobarbital depresses cognitive performance in children treated for febrile seizures and that this disadvantage, which may outlast the administration of the drug by several months, is not offset by the benefit of seizure prevention.

Child, Preschool↗
PubMed1990

Prenatal and perinatal antecedents of febrile seizures.

We examined prenatal and perinatal characteristics as possible risk factors for febrile seizures in a large pediatric population. Family history was among the few identified factors that made an important contribution to vulnerability to febrile seizures; however, no more than 6% of febrile seizures could be attributed to a characteristic of family history. Maternal illness, smoking history, and a few rare neonatal characteristics were associated with increases in risk. No complication of labor or delivery was an important risk factor for febrile seizures.

Anticonvulsants↗
PubMed1990

Phototherapy for neonatal hyperbilirubinemia: six-year follow-up of the National Institute of Child Health and Human Development clinical trial.

The National Institute of Child Health and Human Development Randomized, Controlled Trial of Phototherapy for Neonatal Hyperbilirubinemia was conducted to determine whether phototherapy used to control serum bilirubin is safe and is as effective in preventing brain injury as exchange transfusion. The study, conducted at six neonatal care centers, randomly assigned 1339 newborn infants to phototherapy or control groups by the following subgroups: (1) birth weight less than 2000 g; (2) birth weight 2000 to 2499 g and bilirubin level greater than 171 mumol/L (10 mg/dL); or (3) birth weight greater than or equal to 2500 g and bilirubin level greater than 222 mumol/L (13 mg/dL). Phototherapy was administered for 96 hours, and exchange transfusion was used to control hyperbilirubinemia at the same predetermined levels in both groups. Neurological and developmental examinations were conducted at 1 and 6 years of age, with follow-up rates of 83% and 62%, respectively. The two groups did not differ in mortality or diagnosed medical conditions. The phototherapy and control groups had similar rates of cerebral palsy (5.8% vs 5.9%), other motor abnormalities including clumsiness and hypotonia (11.1% vs 11.4%), and sensorineural hearing loss (1.8% vs 1.9%). The Wechsler Intelligence Scale for Children-Revised scores overall were not significantly different for the two groups (Verbal, 96.8 vs 94.8; Performance, 95.8 vs 95.1 for phototherapy and control groups, respectively). Phototherapy effectively controlled neonatal hyperbilirubinemia without evidence of adverse outcome at 6 years of age and was at least as effective as management with exchange transfusion alone.

Birth Weight↗
PubMed1989

Developmental enamel defects in primary teeth in children with cerebral palsy, mental retardation, or hearing defects: a review.

Developmental enamel defects in primary teeth have been found at least twice as frequently in children with cerebral palsy or mental retardation as in control children, and frequently also in children with sensori-neural hearing deficits. The developing tooth germ is sensitive to a range of systemic disturbances, some of which may also affect neurologic development. Because the enamel cannot recover once it is damaged, it may provide a repository of information on the timing and nature of insults potentially affecting other ectodermally derived structures, including the brain. This paper reviews the literature on developmental defects of enamel in primary teeth, asking whether these might be useful as biological markers of the timing and in some cases the nature of insults. Among systemic factors related to development of enamel that might also have implications for neurologic development are certain genetic disorders including tuberous sclerosis, premature birth, neonatal nutritional disturbances (especially hypocalcemia), viral infections (such as rubella and cytomegalovirus during gestation), thyroid disorders, and maternal diabetes. It is concluded that further research is warranted concerning whether developmental defects of dental enamel can be useful markers for the timing of intra-uterine or perinatal events associated with certain neurologic and sensory disorders of children.

Cerebral Palsy↗
PubMed1989

Relationship of intrapartum and delivery room events to long-term neurologic outcome.

Our current ability to predict neurologic outcome based on intrapartum information is very limited. Adding information on neurologic state during the first days of life adds powerfully to the ability to predict long-term outcome. Further enhancement of predictive abilities will require putting together into single studies the kinds of information on predictors that is now reported in scattered and variously selected small series. Although prediction of outcome requires looking forward from information available in the delivery room to include observations on neonatal encephalopathy and its biochemical and other correlates, an understanding of causation requires looking backward from immediate perinatal and delivery room events to consider the contribution of prenatal factors, known and unknown. Many characteristics commonly labeled as indicators of "neonatal hypoxia," for example, may be the first evidence in the infant of earlier-established abnormality. Birth events appear to contribute only a small proportion of CP and much less of other chronic neurologic disabilities. There is a possibility that the addition of new agents to our therapeutic armamentarium may be capable of reducing that number still further. Prediction and causation as related to chronic neurologic disability gain fresh relevance in view of the need to prepare for clinical trials of new therapies in perinatal medicine.

Apgar Score↗
PubMed1989

Lack of stability in enamel defects in primary teeth of children with cerebral palsy or mental retardation.

The Developmental Defects of Enamel (DDE) index was used to study the reliability across time of assessment of enamel defects in primary teeth in neurologically handicapped children. Fourteen of the 48 children originally examined were available for re-examination 6 months later. The original findings were confirmed in only 6 of these children (5 with no enamel defects and 1 with an enamel defect). Discrepancies noticed between the 2 examinations in the other 8 children could be explained on the basis of biological processes that occurred during the 6-month interim, namely, attrition, abrasion, crown fracture, caries, and possibly remineralization of a hypomineralized defect. These findings suggest that the optimum time for studying such defects is as soon as possible after the teeth erupt.

Cerebral Palsy↗
PubMed1988

Cluster of perinatal events identifying infants at high risk for death or disability.

To determine the prognostic import of neonatal seizures according to the presence or absence of certain other postnatal characteristics, we studied a population of 39,000 infants with birth weight greater than 2500 gm. Children with clinically recognized neonatal seizures and 5-minute Apgar scores less than or equal to 5 and who had at least one of five signs compatible with neonatal encephalopathy had a risk for first-year death of 33%. Survivors of this cluster of events (low Apgar score-abnormal signs-seizures) had a risk for motor disability of 55%. In contrast, survivors of neonatal seizures who did not have poor Apgar scores or other abnormal signs had a risk for motor disability of only 0.13%. Thus, among infants with neonatal seizures the risk for cerebral palsy was 420 times greater if there had been a low 5-minute Apgar score and other neonatal signs. Low Apgar score-abnormal signs-seizures constituted a cluster of events that served to identify, within the first days of life, a tiny subgroup of term newborn infants in whom risk for chronic motor disability was 55%, and for death or disability was 70%.

Apgar Score↗
PubMed1988

Intrapartum asphyxia and cerebral palsy.

Signs of presumed hypoxia/asphyxia of the fetus are not uncommon and can be detected during labor, in the delivery room, and during the early neonatal period. Virtually no single sign or symptom has sufficient correlation to enable prediction of later cerebral palsy with a reasonable degree of medical certainty. To attribute cerebral palsy to prior asphyxia with reasonable certainty, there must be evidence that a substantial hypoxic injury occurred and that a sequence of events ensued which would prove the clinical impact of that hypoxic insult. Few cases of cerebral palsy meet these criteria.

Acidosis↗
PubMed1987

The asymptomatic newborn and risk of cerebral palsy.

We investigated whether infants weighing over 2500 g who had experienced one or more of 14 late pregnancy or birth complications, but who were free of certain signs in the nursery period were at increased risk of cerebral palsy (CP). The signs evaluated were decreased activity after the first day of life, need for incubator care for three or more days, feeding problems, poor suck, respiratory difficulty, or neonatal seizures. More than 90% of the infants weighing over 2500 g had none of these signs. In asymptomatic infants with one or more birth complications, the rate of CP by 7 years of age was 2.3/1000; among asymptomatic infants whose births were uncomplicated, the rate of CP was 2.4/1000. The risk for CP rose with number of abnormal neonatal signs, and children with sustained neonatal abnormalities were at higher risk than those whose abnormalities were transient. Most children with CP did not derive from groups at increased risk. The full-term infant whose birth was complicated but who was free of certain abnormal signs in the newborn period was not at increased risk of CP.

Apgar Score↗
PubMed1987

Predisposing and causative factors in childhood epilepsy.

We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one nonfebrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.

Brain Ischemia↗
PubMed1986

Antecedents of cerebral palsy. Multivariate analysis of risk.

We examined prenatal and perinatal factors predicting cerebral palsy, using multivariate analysis to investigate which factors were most important and the proportion of cases for which they accounted. Maternal mental retardation, birth weight below 2001 g, and fetal malformation were among the leading predictors. Breech presentation was also a predictor, but breech delivery was not. A third of the children with cerebral palsy who had breech presentations had a major noncerebral malformation. Among 189 children with cerebral palsy, 40 (21 percent) had at least one of three clinical markers suggestive of asphyxia; only 17 of these 40 children (9 percent of all cases) lacked major congenital malformation or other intrinsic defects that might have contributed to an unfavorable outcome. When all the principal risk factors present by the time labor began were considered, the 5 percent of the population at highest estimated risk was seen to have contributed 34 percent of the cases. When all the risk factors present during the period beginning before pregnancy and extending through the nursery stay were included, the 5 percent at highest risk was seen to have contributed 37 percent of the cases. Thus, the inclusion of information about the events of birth and the neonatal period accounted for a proportion of cerebral palsy only slightly higher than that accounted for when consideration was limited to characteristics identified before labor began.

Analysis of Variance↗