RESUMEN
First-degree relatives of patients with bipolar disorder (BD), particularly their offspring, have a higher risk of developing BD and other mental illnesses than the general population. However, the biological mechanisms underlying this increased risk are still unknown, particularly because most of the studies so far have been conducted in chronically ill adults and not in unaffected youth at high risk. In this preliminary study we analyzed genome-wide expression and methylation levels in peripheral blood mononuclear cells from children and adolescents from three matched groups: BD patients, unaffected offspring of bipolar parents (high risk) and controls (low risk). By integrating gene expression and DNA methylation and comparing the lists of differentially expressed genes and differentially methylated probes between groups, we were able to identify 43 risk genes that discriminate patients and high-risk youth from controls. Pathway analysis showed an enrichment of the glucocorticoid receptor (GR) pathway with the genes MED1, HSPA1L, GTF2A1 and TAF15, which might underlie the previously reported role of stress response in the risk for BD in vulnerable populations. Cell-based assays indicate a GR hyporesponsiveness in cells from adult BD patients compared to controls and suggest that these GR-related genes can be modulated by DNA methylation, which poses the theoretical possibility of manipulating their expression as a means to counteract the familial risk presented by those subjects. Although preliminary, our results suggest the utility of peripheral measures in the identification of biomarkers of risk in high-risk populations and further emphasize the potential role of stress and DNA methylation in the risk for BD in youth.
Asunto(s)
Trastorno Bipolar/genética , Hijo de Padres Discapacitados , Metilación de ADN/genética , Perfilación de la Expresión Génica , ARN Mensajero/metabolismo , Adolescente , Estudios de Casos y Controles , Niño , Femenino , Proteínas HSP70 de Choque Térmico/genética , Humanos , Masculino , Subunidad 1 del Complejo Mediador/genética , Riesgo , Factores Asociados con la Proteína de Unión a TATA/genéticaRESUMEN
Coordinated efforts to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders are now underway. These studies have focused on recurrent, early-onset MDD (RE-MDD), the most heritable form of this disorder. The goal of this study was to characterize the burden of MDD and other mood disorders, comorbid mental disorders, and excess mortality in RE-MDD families. A total of 81 families were identified through probands over the age of 18, who met criteria for recurrent (> or = 2 episodes), early-onset (< or = 25 years), nonpsychotic, unipolar MDD (RE-MDD), and included 407 first-degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Approximately half of the first-degree relatives and a quarter of extended relatives of RE-MDD probands suffered from at least one mood disorder, typically MDD. As commonly observed for other oligogenic, multifactorial disorders, the severity of MDD reflected by age at onset and number of episodes attenuated with increasing familial/genetic distance from the proband. A substantial fraction of RE-MDD probands and their first-degree relatives met diagnostic criteria for additional psychiatric disorders that include prominent disturbances of mood. The deceased relatives of RE-MDD probands died at a median age that was 8 years earlier than for the local population; over 40% died before reaching age 65. These differences in mortality statistics resulted from a shift toward younger ages at death across the lifespan, including a fivefold increase in the proportion of individuals who died in the first year of life. Several-fold increases in the proportion of deaths by suicide, homicide, and liver disease were observed among the relatives of RE-MDD probands. However, the rank order of the three most common causes of death-heart disease, cancer, and stroke-remained unchanged and differences in the proportions of deaths from the remaining causes were small. RE-MDD is a strongly familial condition with a high rate of psychiatric comorbidity, whose malignant effects have a significant negative impact on the health and longevity of patients and their family members.
Asunto(s)
Trastorno Depresivo/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Trastorno Depresivo/mortalidad , Trastorno Depresivo/patología , Familia , Salud de la Familia , Femenino , Humanos , Masculino , Trastornos Mentales/genética , Trastornos Mentales/patología , Persona de Mediana Edad , Trastornos del Humor/genética , Trastornos del Humor/patología , Recurrencia , Índice de Severidad de la Enfermedad , Estadística como Asunto , Tasa de SupervivenciaRESUMEN
Lord (1992) published a brief report showing a trend for decreasing nonverbal IQ scores with increasing birth order in a sample of 16 autism multiplex families, and urged replication in a larger sample. In this report, analyses of nonverbal IQ scores for a sample of 144 autism multiplex families indicated that nonverbal IQ scores were significantly lower in secondborn compared with firstborn siblings with autism. This birth order effect was independent of gender as well as the age differences within sib pairs. No such birth order effects were found for social or communicative deficits as measured by the Autism Diagnostic Interview-Revised (ADI-R), but there was a modest tendency for increased scores for ritualistic behaviors for the firstborn sibs. Further, there were no gender differences on nonverbal IQ scores in this sample. Results are discussed in terms of implications for genetic studies of autism.
Asunto(s)
Trastorno Autístico/psicología , Orden de Nacimiento/psicología , Familia/psicología , Inteligencia , Comunicación no Verbal , Niño , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Factores Sexuales , Conducta SocialRESUMEN
Chromosomal region 15q11-q13 has been implicated to harbor a susceptibility gene or genes underlying autism. Evidence has been derived from the existence of cytogenetic anomalies in this region associated with autism, and the report of linkage in a modest collection of multiplex families. Most recently, linkage disequilibrium with the marker GABRB3-155CA2 in the candidate locus GABRB3, located in this region, has been reported. We searched for linkage using eight microsatellite markers located in this region of chromosome 15 in 147 affected sib-pairs from 139 multiplex autism families. We also tested for linkage disequilibrium in the same set of families with the same markers. We found no evidence for excess allele sharing (linkage) for the markers in this region. Also, we found no evidence of linkage disequilibrium, including for the locus GABRB3-155CA2. Thus, it appears that the role of this region of chromosome 15 is minor, at best, in the majority of individuals with autism.
Asunto(s)
Trastorno Autístico/genética , Cromosomas Humanos Par 15 , Ligamiento Genético , Desequilibrio de Ligamiento , Repeticiones de Microsatélite , Adolescente , Adulto , Alelos , Niño , Preescolar , Familia , Femenino , Genotipo , Humanos , MasculinoRESUMEN
We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying =10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.
Asunto(s)
Trastorno Autístico/genética , Ligamiento Genético , Herencia Multifactorial , Adolescente , Adulto , Niño , Preescolar , Cromosomas Humanos/genética , Femenino , Genotipo , Humanos , Pruebas de Inteligencia , Desequilibrio de Ligamiento , Masculino , Análisis por Apareamiento , Repeticiones de Microsatélite , Modelos Genéticos , Datos de Secuencia Molecular , Núcleo Familiar , Factores Sexuales , Distribuciones EstadísticasRESUMEN
Several studies have suggested a role for the histocompatibility complex of loci (HLA) in the genetic susceptibility to autism. We have tested this hypothesis by linkage analysis using genetic marker loci in the HLA region on chromosome 6p in multiplex families with autism. We have examined sharing of alleles identical by descent in 97 affected sib pairs from 90 families. Results demonstrate no deviation from the null expectation of 50% sharing of alleles in this region; in fact, for most marker loci, the observed sharing was less than 50%. Thus, it is unlikely that loci in this region contribute to the genetic etiology of autism to any significant extent in our families.
Asunto(s)
Trastorno Autístico/genética , Ligamiento Genético/genética , Antígenos HLA/genética , Adolescente , Adulto , Alelos , Niño , Preescolar , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Cromosomas Humanos Par 6/genética , Femenino , Marcadores Genéticos/fisiología , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Análisis por Apareamiento , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Genetic factors undoubtedly play a major etiologic role in autism, but how it is inherited remains unanswered. The increased incidence in males suggests possible involvement of the X chromosome. METHODS: Using data from 38 multiplex families with autism (2 or more autistic siblings), we performed a multipoint sib-pair linkage analysis between autism and 35 microsatellite markers located on the X chromosome. The model included a single parameter, the risk ratio lambda xs (i.e., ratio of risk to siblings compared with the population prevalence), owing to an X-linked gene. Different lambda xs values were assumed and regions of exclusion were established. RESULTS: The entire X chromosome could be excluded for a lambda xs value of 4. The ability to exclude an X-linked gene decreased with smaller lambda xs values, and some positive evidence was obtained with smaller values. A maximum lod score of 1.24 was obtained at locus DXS424 with a lambda xs value of 1.5. CONCLUSIONS: We were able to exclude any moderate to strong gene effect causing autism on the X chromosome. Smaller gene effects (lambda xs < 4) could not be excluded, in particular, a gene of small effect located between DXS453 and DXS1001.
Asunto(s)
Trastorno Autístico/genética , Cromosoma X/genética , Adolescente , Adulto , Trastorno Autístico/etiología , Mapeo Cromosómico , Familia , Femenino , Marcadores Genéticos , Genotipo , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite , Oportunidad RelativaRESUMEN
Videotaped play interactions of 182 low birth weight, premature toddlers and their mothers were used to investigate whether a model including maternal responsiveness together with level of maternal education was a better predictor of play maturity scores of the children than a model consisting of education level alone. The videotapes were coded using the responsiveness subscale of the Maternal Behavior Rating Scale. Regression analyses revealed that maternal education alone significantly predicted play scores, accounting for 9% of the variance. However, the model that included both maternal responsiveness and maternal education together also significantly predicted play scores and accounted for 20% of the variance. Including responsiveness together with maternal education significantly increased the proportion of variance accounted for by maternal education alone. Implications of these findings are discussed.
Asunto(s)
Escolaridad , Recién Nacido de Bajo Peso/psicología , Recien Nacido Prematuro/psicología , Conducta Materna , Relaciones Madre-Hijo , Madres/educación , Juego e Implementos de Juego , Conducta Infantil , Preescolar , Intervención Educativa Precoz , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Determinación de la PersonalidadRESUMEN
Despite strong genetic influences in autism, the true mode of inheritance remains unknown. Sex differences in autism have been described in both singleton and multiplex families [Lord et al., 1982; Volkmar et al., 1993; McLennan et al., 1993; Lord, 1992]: Boys outnumber girls by 3 or 4 to 1, and so a sex-linked mode of transmission must also be considered. The key characteristic of X-linkage is that all sons of affected men are unaffected (no male-to-male transmission). In the present study, which is part of an ongoing linkage project in autism, we describe 77 multiplex autism families, 11 of who are affected cousin or half-sibling families. By using these families, it is possible to trace the path of genetic transmission and observe whether the hypothesis of X-linkage is tenable. Of 11 extended pedigrees from 77 multiplex families, six show male-to-male transmission; in these families, X-linkage can be excluded as the genetic basis for their autism. The data from the other five families are compatible with either an autosomal or an X-linked mode of transmission. The key point to emerge, then, is that autism cannot be exclusively an X-linked disorder; there must be an autosomal mode of transmission at least in some families. Thus we must consider the alternative hypotheses that autism is either entirely autosomal, or it is genetically heterogeneous, involving at least one autosomal locus with genderspecific expression, as well as a possible locus on the X-chromosome.
Asunto(s)
Trastorno Autístico/genética , Ligamiento Genético , Cromosoma X , Niño , Femenino , Genes Dominantes , Humanos , Masculino , LinajeRESUMEN
Approximately 2%-5% of autistic children show cytogenetic evidence of the fragile X syndrome. This report tests whether infantile autism in multiplex autism families arises from an unusual manifestion of the fragile X syndrome. This could arise either by expansion of the (CGG)n trinucleotide repeat in FMR-1 or from a mutation elsewhere in the gene. We studied 35 families that met stringent criteria for multiplex autism. Amplification of the trinucleotide repeat and analysis of methylation status were performed in 79 autistic children and in 31 of their unaffected siblings, by Southern blot analysis. No examples of amplified repeats were seen in the autistic or control children or in their parents or grandparents. We next examined the hypothesis that there was a mutation elsewhere in the FMR-1 gene, by linkage analysis in 32 of these families. We tested four different dominant models and a recessive model. Linkage to FMR-1 could be excluded (lod score between -24 and -62) in all models by using probes DXS548, FRAXAC1, and FRAXAC2 and the CGG repeat itself. Tests for heterogeneity in this sample were negative, and the occurrence of positive lod scores in this data set could be attributed to chance. Analysis of the data by the affected-sib method also did not show evidence for linkage of any marker to autism. These results enable us to reject the hypothesis that multiplex autism arises from expansion of the (CGG)n trinucleotide repeat in FMR-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Trastorno Autístico/genética , Ligamiento Genético , Proteínas del Tejido Nervioso/genética , Proteínas de Unión al ARN , Adolescente , Adulto , Secuencia de Bases , Niño , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil/genética , Haplotipos , Humanos , Escala de Lod , Masculino , Datos de Secuencia Molecular , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
Evidence from twin and family studies strongly suggests that genetic factors play a prominent role in the etiology of some cases of infantile autism. Genetic factors would be expected to be especially strong in families with multiple autistic members (multiplex families). This report describes the identification and evaluation of 44 families with two or more autistic children collected as part of a genetic linkage study in autism. Families were referred with a presumptive classification of multiplex autism. Children referred as autistic, as well as their presumptively normal siblings, were assessed using the Autism Diagnostic Interview (ADI) and the Autism Diagnostic Observation Scale (ADOS). Thirty-seven of the 44 families (87%) had at least two children who met diagnostic criteria for autism on the ADI. Of the total group of 117 children evaluated in those families, 83 (71%) met all ADI criteria and could be unambiguously classified as autistic (affected), 26 (22%) met none of the ADI criteria and were classified as not autistic (unaffected), and 8 (7%) were classified as uncertain because they met one or more but not all of the ADI cutpoints. Autistic siblings were not significantly concordant for most autism characteristics, for IQ, or for verbal ability. Significant concordances were found, however, for behaviors related to rituals and repetitive play, and for social impairments in the expression and understanding of facial expressions of emotion.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Trastorno Autístico/genética , Adolescente , Adulto , Trastorno Autístico/diagnóstico , Niño , Preescolar , Salud de la Familia , Femenino , Humanos , Pruebas de Inteligencia , Masculino , Variaciones Dependientes del Observador , Linaje , Fenotipo , Escalas de Valoración Psiquiátrica , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Método Simple Ciego , Conducta VerbalAsunto(s)
Trastorno Autístico/inducido químicamente , Aberraciones Cromosómicas/genética , Contaminantes Ambientales/efectos adversos , Plásticos/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Trastorno Autístico/genética , Niño , Trastornos Generalizados del Desarrollo Infantil/inducido químicamente , Trastornos Generalizados del Desarrollo Infantil/genética , Preescolar , Trastornos de los Cromosomas , Citogenética , Femenino , Humanos , Masculino , Embarazo , Factores de RiesgoRESUMEN
This study examines whether clinical assessments of mother-infant interactions collected at 8-month health supervision visits are associated with standardized measures of the home environment and mother-child interaction collected at later dates in other settings, and whether these clinical assessments are associated with the child's future developmental and behavioral status. The observation component of the Pediatric Review of Children's Environmental Support and Stimulation (PROCESS) was collected on 46 consecutive mother-infant pairs during an 8-month health supervision visit. The Home Observation Measurement of Environment (HOME) Inventory was collected on these infants' families at 12 and 36 months of age, and mother-child interaction was assessed in a laboratory setting at 30 months. The Bayley Scales of Infant Development were collected at 12 and 24 months, and the Stanford Binet Intelligence Test and the Achenbach Child Behavior Checklist were collected at 36 months of age. The 8-month clinical ratings were strongly associated with the measures of the home environment and mother-child interaction and with child developmental and behavioral problem status at 36 months. These findings attest to the power and usefulness of systematic observations of maternal behavior by the clinician during health supervision visits.
Asunto(s)
Relaciones Madre-Hijo , Madres/psicología , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Conducta Materna , Pruebas Psicológicas , Grabación de Cinta de VideoRESUMEN
Effects of a comprehensive early intervention program for low birth weight, premature infants--the Infant Health and Development Program--on mother-child interaction were examined at 30 months (N = 683). Small significant positive effects were found: Intervention mothers had higher ratings on quality of assistance; intervention children had higher ratings on persistence and enthusiasm and on an overall child rating of competence and involvement and lower ratings on percentage of time off-task; intervention dyads were rated as more synchronous. Of a set of initial status variables indexing biological and environmental risk, only 2 treatment interactions were found. Intervention group black children had higher ratings on enthusiasm and lower percentage of time off-task. Independent of treatment, maternal ethnicity and education were significant predictors of maternal and dyadic ratings, while ethnicity and birth weight predicted child ratings. Implications for early intervention and center-based care are discussed.
Asunto(s)
Recién Nacido de Bajo Peso , Recien Nacido Prematuro , Conducta Materna , Relaciones Madre-Hijo , Madres/psicología , Adulto , Conducta Infantil , Desarrollo Infantil , Preescolar , Escolaridad , Etnicidad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Reproducibilidad de los Resultados , Grabación de Cinta de VideoRESUMEN
The Infant Health and Development Program is a randomized clinical trial to test the efficacy of educational and family support services and pediatric follow-up offered in the first 3 years of life on reducing the incidence of developmental delay in low-birthweight (LBW), preterm infants in 8 clinical sites (N = 985). Effects of the intervention on cognitive and behavior problem scores over the 3 years are examined. Significant intervention effects were seen on cognitive scores at 24 and 36 but not 12 months of age; effect sizes were similar at both ages. These effects persist when controlling for earlier cognitive scores. At 24 and 36 months, behavior problem scores for the intervention group were significantly lower than for the follow-up group; the intervention was more efficacious for children with higher initial behavior problem scores. Results are discussed in terms of timing and targeting of services for LBW and disadvantaged children.
Asunto(s)
Conducta Infantil , Desarrollo Infantil , Cognición , Recién Nacido de Bajo Peso , Recien Nacido Prematuro , Preescolar , Trastornos del Conocimiento/diagnóstico , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/terapia , Etnicidad , Femenino , Humanos , Lactante , Recién Nacido , Pruebas de Inteligencia , MasculinoRESUMEN
A new neonatal medical index (NMI) was used to predict the mental and motor development of low birth weight, preterm infants up to 3-years-old. The NMI is a summary score of only a few clinically salient items that are readily available on brief chart review. The sample consisted of 512 of 608 infants randomly assigned to the control group of the eight-site Infant Health and Development Program and on whom the complete set of developmental outcome measures was available. The developmental tests administered were the Bayley Scales at 12 and 24 months and the Stanford-Binet at 3 years. The findings indicated the NMI was predictive of later cognitive and motor development, and in infants born weighing less than 1500 g, the effects of neonatal medical complications continued to adversely influence these children's development to at least 3 years of age. In the heavier babies the developmental effects of sociodemographic factors predominated by 24 months and beyond.
Asunto(s)
Desarrollo Infantil , Recién Nacido de Bajo Peso , Preescolar , Cognición , Escolaridad , Etnicidad , Femenino , Humanos , Recién Nacido , Masculino , Madres , Destreza Motora , Neonatología , Pronóstico , Factores SocioeconómicosRESUMEN
We report on recruiting and retaining a sample of low birth weight, premature infants for a clinical trial as well as results of tests evaluating sampling and retention biases. A total of 4551 infants were screened, and 1302 were found eligible. Consent was obtained for 1028 infants. After randomization and the presentation of group assignment, the number of infants enrolled was 985 (75.7% of those eligible). Of these, 92.7% completed the 3-year study. Tests to evaluate recruitment bias revealed significant relationships between nonenrollment and site, maternal race, and infant birth weight. Tests to evaluate retention bias revealed a significant relationship between dropout and maternal education. Additionally, infant birth weight and maternal age interacted with treatment in predicting dropout. Despite these statistically significant recruitment and retention biases, there was no evidence of problems with sample representativeness to the population of interest or of treatment group differences on study-relevant background variables.
Asunto(s)
Daño Encefálico Crónico/prevención & control , Ensayos Clínicos como Asunto/métodos , Discapacidades del Desarrollo/prevención & control , Recién Nacido de Bajo Peso , Enfermedades del Prematuro/prevención & control , Pacientes Desistentes del Tratamiento , Sesgo , Peso al Nacer , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Mothers, teachers, and assistant teachers completed the Richman Behavior Checklist (BCL) at ages 2 and 3 years and the Achenbach Child Behavior Checklist for Ages 2-3 (CBCL 2-3) at 3 years for a large sample of low birth weight, premature children. Interinstrument correlations for total scores were moderate, higher for teachers and assistant teachers than for mothers, with moderate temporal stability for BCL scores. Interrater agreement for either total scores or classifications of clinically significant scores was moderately high between teachers and assistant teachers only, and children identified as disturbed by mothers versus teachers represent almost nonoverlapping groups. Furthermore, many more children were identified as disturbed using the BCL. The most powerful predictors of mothers' total CBCL 2-3 scores were HOME Inventory scores and self-reported depression. The use of these scales in clinical and research contexts is discussed.
Asunto(s)
Trastornos de la Conducta Infantil/psicología , Desarrollo Infantil/fisiología , Preescolar , Ambiente , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Masculino , Psicología Infantil , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
The Infant Health and Development Program is a national collaborative study to test the efficacy of combining early child development and family support services with pediatric follow-up to reduce the incidence of health and developmental problems among low birth weight, preterm infants in eight medical school sites. Its efficacy in enhancing intellectual outcomes at age 3 in more and less environmentally vulnerable, low birth weight, preterm children, as defined by maternal education (high school completion or less vs some college) and race (black vs white/other), is explored. Children whose mothers had a high school education or less benefited from the intervention. This was true for both the black and white samples. Children whose mothers had attended college did not exhibit significant enhancement in IQ scores at 3 years. Birth weight affected the response to treatment for one of the four subgroups: Among white mothers with some college, the lighter (less than 2000 g) low birth weight, preterm children were less influenced by the intervention than were the corresponding heavier children. Implications for targeting certain subgroups of low birth weight, preterm children for services are considered.