The development of young children with retinoblastoma.

OBJECTIVES: To assess the health and development of children with retinoblastoma (RB), or cancer of the retina, and to determine if they are at greater risk for developmental delays than normal children. Specific aims were to determine if type of RB (unilateral vs bilateral), family history, and number of treatment types affected mental and motor development. DESIGN: Descriptive study based on medical record review and pediatric, psychological, and visual evaluations. SETTING: Major referral center for patients with RB and early intervention program in a voluntary urban hospital. SUBJECTS AND METHODS: Fifty-four children younger than 41 months with RB who attend an ophthalmology oncology clinic were recruited for study. Measures included demographic variables such as social class and race/ethnicity, and medical factors such as age at diagnosis (<18 months vs >18 months), type of RB (unilateral or bilateral), family history of RB, and number and types of treatments. All children received a pediatric examination that assessed physical growth and health; a behavioral test of visual acuity using Teller acuity cards; and the Bayley Scales of Infant Development II, a standardized test of mental and motor development. Children found to have delays were referred to intervention services to treat their specific areas of weakness. RESULTS: Three quarters of the children had had 1 eye enucleated; 51 of 54 had normal vision in at least 1 eye, and the other 3 had partial vision in 1 eye. Except for the RB, 46 children were largely normal in growth and health, and 8 had medical diagnoses that were unrelated to RB or its treatment. The average mental and motor development scores were in the normal range (91.4 +/- 16.3, and 91.1 +/- 13.4) and not significantly lower than the normal population. Twenty-six children were referred for early intervention services, and 21 of 26 were referred for services to improve their visuomotor coordination. Demographic variables were not associated with medical variables or outcome. Children with bilateral RB, in which both eyes are affected, performed significantly less well in motor development, received many more types of treatments, and were more likely to be referred for visuomotor therapy than children with unilateral RB. CONCLUSIONS: Children with RB generally function normally in terms of physical health and mental and motor development. However, they are more likely to show delays in visuomotor integration. Early developmental evaluations may improve the visuomotor development of children with visual impairment due to RB.

Fragile X syndrome in two siblings with major congenital malformations.

We report on 2 brothers with both fragile X and VACTERL-H syndrome. The first sibling, age 5, had bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb. The second sibling, age 2 1/2, had a trachesophageal fistula, esophageal atresia, and vertebral abnormality. High-resolution chromosome analysis showed a 46, XY chromosome constitution in both siblings. By PCR and Southern blot analysis, the siblings were found to have large triplet repeat expansions in the fragile X gene (FMR 1) and both had methylation mosaicism. Enzyme kinetic studies of iduronate sulfatase demonstrated a two-fold increase in activity in the first sib as compared to the second. Possible mechanisms through which the fragile X mutation can cause down-regulation of adjacent loci are discussed.

Hand preference, prematurity and developmental outcome at school age.

Information was obtained on the hand preference of 88 premature and 80 matched full-term children at 7-8 years old. These children were also evaluated for neurologic status, IQ, attention-deficit hyperactivity disorder, and learning disabilities. Although the difference on hand preference was not significant, 12% more of the premature children than the full-term children were left- or mixed-handed. Results showed that, among premature children, there is an association between non-right-handedness and cognitive and behavioral deficits and that left-handed children show relative clumsiness with the non-preferred hand.

Educational status and school-related abilities of very low birth weight premature children.

Eighty-eight premature children with birth weights less than or equal to 1500 g were evaluated at ages between 7 and 8 years old to determine their academic status in comparison with those of a matched full-term group. Results showed that a much higher proportion of the premature children required special educational interventions (48%) than either the full-term children (15%) or the New York State public elementary school population (10%). More than half of the premature children who received educational intervention were neurologically impaired or had below normal intelligence. The entire group of premature children differed significantly from the matched full-term group on IQ score and on tests of verbal ability, school achievement, and auditory memory. Lower socioeconomic status children performed significantly less well on each type of these measures and on a measure of attention than children of the higher socioeconomic status group. There was an interaction of prematurity and social class on Full Scale IQ, verbal tests, academic achievement, and attention, with lower socioeconomic status premature children scoring lowest on these measures. The subset of premature children normal in both IQ and neurologic status did not differ significantly from a matched normal full-term group on any cognitive measures other than arithmetic ability, but they continued to have significantly lower academic achievement scores.

Social competence and behavior problems in premature children at school age.

Social competence and behavior problems of 87 children born weighing less than 1501 g were measured using the Child Behavior Checklist when the children were 7 to 8 years old. Both premature boys and girls had significantly lower Social Competence scores than the normative samples of their respective sexes. Only premature boys had significantly higher Behavior Problems scores, with significantly higher scores on behaviors associated with conduct disorders. Premature children in each of three social class groups had significantly lower Social Competence scores and higher Behavior Problems scores than normative children. Furthermore, there was an interaction between prematurity and social class on Behavior Problems scores, with the greatest discrepancy in scores between premature and normative children in the lower-class group. Relative to other predictors, IQ score best explained Social Competence scores and family stability best explained Behavior Problems scores in the premature sample.

Survival and outcome of infants weighing less than 800 grams at birth.

This study reports on two aspects of outcome in a sample of infants whose birth weights ranged from 500 to 799 gm. First, maternal and early neonatal variables were analyzed by means of stepwise logistic regression. Five-minute Apgar score and initial pH were the only variables that predicted mortality at p less than or equal to 0.05. Second, the surviving infants were examined at ages ranging from 17 months to 7 years. The majority (72%) had neurologic and/or developmental examinations in the suspect or abnormal range and required rehabilitation or early intervention services.

Hand preference of four-year-old children: its relationship to premature birth and neurodevelopmental outcome.

Information was obtained at age four years on the hand preference of 98 children who had been born prematurely with a very low birthweight and of 54 children born at term with no birth complications. Data were also collected on the hand preference of their parents. The preterm children had been assessed at age three years for IQ, expressive language, speech articulation and neurological status. A significantly lower proportion of preterm than of term children used their right hand for unimanual activities. Furthermore, those preterm children who were not right-handed were significantly more likely to have lower IQs, expressive language delays and articulation problems. Among preterm children with IQs greater than or equal to 85, language and speech problems were no more likely to occur in those who preferred the left hand or who used both hands than in those who preferred the right. The findings of this study support the theory that birth complications lead to cerebral insult which may alter hand preference, and at the same time affect mental and motor development.

MRI of the central nervous system in neonates and young children.

Twelve normal neonates and young children, ages 32 weeks gestation to 20 months, and 22 abnormal children up to four years old had MRI scans using a 0.5 T superconducting scanner. A faint signal that was presumed to be myelin was detected in the thalami at 32 weeks; myelination of the occipital lobes was present at full term, and visible throughout the hemispheres by 8 weeks of age. Anatomical locations of congenital lesions were well demonstrated, especially in sagittal views. The signal changes of perinatal abnormalities, such as hemorrhage and hemiatrophy, were often specific. Abnormal position of the spinal cord, spinal lipomas, and other congenital lesions were also well visualized.

Early predictors of one-year outcome for infants asphyxiated at birth.

This study attempted to identify within the first 48 hours of life those infants sustaining hypoxic-ischemic insults and destined to have neurodevelopmental abnormalities at one year of age. Neurological examination and cranial CT scan were quantitated to provide a post-asphyxia score and CT low-density index for each of 34 fullterm infants. The post-asphyxia score and CT infarction index were used to predict infants with normal and abnormal outcomes at one year of age, and both were valuable predictors of neurodevelopmental sequelae.

Early predictors of neurodevelopmental outcome of very low-birthweight infants at three years.

Seventy-nine premature infants weighting less than 1501 g at birth but appropriate for gestational age underwent a neurodevelopmental examination at one, three, six, nine and 12 months post-term, and a standard neurological examination and the Stanford-Binet Intelligence Scale at three to four years of age. Children were classified as normal, suspect or abnormal on the three-year neurological examination, on the IQ test, and on composite neurodevelopmental outcome at age three years. Results showed that items from both the nine- and 12-month neurodevelopmental examinations correctly classified about 80 per cent of the children as to composite outcome at three years. In addition, the 12-month examination enabled correct prediction for 89 per cent of the children as to neurological outcome and for 82 per cent as to IQ. Neurodevelopmental examination of high-risk infants in the last quarter of the first year of life (post-term) should assist pediatricians in predicting which children will be normal and which will require early intervention.

Consistency and change in the development of premature infants weighing less than 1,501 grams at birth.

Ninety-four infants with birth weights less than 1,501 g were evaluated on neurologic functioning and mental abilities at 1 year and, again, at 3 to 4 years of age. Results of the examination showed high correspondence in neurologic status and in mental ability between infancy and the preschool period, particularly for children who were diagnosed as clearly normal or abnormal at 1 year. In addition, poorer performance in a test of infant mental ability (which relies primarily on sensorimotor skills), in motor skills, and in neurologic functioning, respectively, were linked to lower IQ, difficulties in expressive language, and articulation deficits at the preschool age. Socioeconomic status predicted 3-year IQ scores and changes in mental ability scores but was not a factor in determining either preschool age neurologic status or changes in neurologic status in the children studied. Socioeconomic status of the children was less predictive of preschool outcome than results of the 1-year examinations.

Occlusive vascular disease in asphyxiated newborn infants.

Six full-term severely asphyxiated newborn infants underwent evaluation with digital intravenous angiography. All infants were comatose and flaccid and had seizures, depressed brainstem function, and signs of intracranial hypertension. An initial brain CT scan revealed diffuse hypodensities and compressed ventricles. Follow-up noncontrast CT scans showed areas of increased attenuation. Digital intravenous angiography demonstrated venous sinus thrombosis in five infants, two of whom also had arterial thrombosis, and hypervascularity in the sixth infant. Our data document that occlusive vascular disease is a prominent feature of severe perinatal asphyxia.

Digital intravenous cerebral angiography in neonates.

Digital intravenous cerebral angiography was performed in 13 neonates. Injections were made either centrally into the right atrium or peripherally into a distal vein. Seven infants suffered from anoxia, one infant had clinical brain death, another had focal infarcts, and two had intracranial hemorrhage. One infant had an intracranial tumor and another had a neck tumor. Venous sinus thrombosis was seen in five of the seven anoxic infants. A total absence of intracranial arterial circulation was demonstrated in the clinically brain-dead infant. Vascularity and venous involvement by neoplasm were excellently delineated by this technique.

Early contact, social support, and mother-infant bonding.

A study was designed to explore further the hypothesis that a period of close contact between mother and infant immediately after birth facilitates the establishment of a close bond. The study investigated whether the effects of extra contact interact with other variables present in the labor and delivery situation and with the extent of social support available to the mother. Two sets of procedures for the immediate postpartum period were established and mothers were randomly assigned to one of these conditions. Twenty-nine mothers experienced extracontact procedures in which the baby was placed on the mother's abdomen for 1 hour. Thirty mothers received routine care procedures in which the baby was shown to the mother and then taken to the nursery. Observations of maternal behavior during a feeding were made two days after birth by an observer blind to the randomization status of the mother. The mothers who received extra contact exhibited significantly more affectionate behavior toward their infants than did the mothers who received routine care. The extracontact treatment produced more affectionate behaviors in the mothers who had less social support than in those who had more social support. The extra contact was equally effective for multiparous and primiparous mothers. Mothers of female infants exhibited more affectionate behavior to their infants regardless of which postpartum procedures the mothers had experienced.

Determinants of neurobehavioral outcome in low-birth-weights infants.

The relative importance of (1) birth weight, gestational age, and head circumference at birth, and (2) appropriateness of birth weight and head circumference to gestational age in the predictability of neurobehavioral outcome was evaluated in 127 low-birth-weight infants at 7 months of age. Lower absolute birth weights, shorter gestational ages, and smaller head circumferences at birth correlated with poorer outcome (Bayley Scales of Infant Development and abnormal neurologic examination) at the corrected chronologic age of 7 months (r = .28 to .42, all P less than .005). The incidence of low scores on the Mental Development Index and of severe neurologic deficit was significantly higher in small head circumference for gestational age infants than in appropriate head circumference for gestational age infants (both, P less than .05). In the absence of small head circumference, small for gestational age infants had similar incidences of low Bayley scores and abnormal neurologic examinations as did appropriate for gestational age infants. These observations suggest that head circumference at birth may be the single most important variable for subsequent neurobehavioral outcome, and that both birth weight and gestational age may simply be markers of fetal head growth in their relationship to later outcome.