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PubMed1995

Autistic behaviors in offspring of mothers abusing alcohol and other drugs: a series of case reports.

Although autistic-like behaviors were described even in the earliest reports of fetal alcohol syndrome, it was only recently that fetal alcohol syndrome and autism were reported as a dual diagnosis in six school-aged children. The purpose of the present series of case reports is to describe marked autistic characteristics in three much younger children (25-36 months) with histories of prenatal exposure to alcohol and other drugs. The behavioral characteristics of these children are described and compared with current diagnostic criteria for autistic disorder. In addition, longitudinal scores on the Bayley Scales of Infant Development are provided to underscore the marked developmental delays shown by each of the children. Limitations of these case reports are discussed with suggestions for future prospective research.

Autistic Disorder↗
PubMed2004

Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity.

Methylenetetrahydrofolate reductase (MTHFR) is the only route for the synthesis of 5-methyltetrahydrofolate, which is utilized to convert homocysteine to methionine. In this study, we measured the enzyme activity of a mutant MTHFR that was detected in a patient with hyperhomocysteinemia. The 428C>T mutation in exon 2 of the MTHFR gene is a novel mutation, while the [458G>T+459C>T] mutation in exon 2 is a previously reported mutation. The activity of mutant enzymes containing the 428C>T, [458G>T+459C>T] and 677C>T mutations was 12.7+/-4.7%, 48.1+/-18.8%, and 43.6+/-14.4%, respectively, of that of the wild type enzyme. Our results suggest that these two variants each result in a severe MTHFR deficiency, which causes a developmental delay and cerebral vascular disease.

Adolescent↗
PubMed2005

Neurodevelopmental implications of "deformational" plagiocephaly.

Over the past decade there has been a dramatic increase in referrals to specialty clinics, craniofacial centers, plastic surgeons, and neurosurgeons for assessment and treatment of deformational plagiocephaly (DP). Though considered a medically benign condition, preliminary reports suggest that DP may be associated with developmental problems. However, mechanisms to account for this association have not been hypothesized or empirically tested. Although treatment justifications often center on prevention of atypical appearance, little is known about the cosmetic outcomes of treated and untreated children. In this review we hypothesize different etiological pathways linking DP with neurodevelopment (e.g., environmental positioning limitations with and without underlying CNS pathology). We outline directions for research on incidence and prevalence, developmental outcomes, sex differences, determinants of treatment participation, and craniofacial appearance. Despite the paucity of existing research, preliminary findings suggest that children with this condition should be screened and monitored for developmental delays or deficits, as we await more conclusive information from future studies.

Cognition Disorders↗
PubMed2005

Causes of death in remote symptomatic epilepsy.

OBJECTIVE: To determine the causes of death of individuals with developmental disabilities that occur more frequently among those with remote symptomatic epilepsy (i.e., epilepsy occurring in persons with developmental delay or identified brain lesions) than for those without. METHODS: The authors compared causes of mortality in persons with (n = 10,030) and without (n = 96,163) history of epilepsy in a California population of persons with mild developmental disabilities, 1988 to 2002. Subjects had traumatic brain injury, cerebral palsy, Down syndrome, autism, or a developmental disability with other or unknown etiology. There were 721,759 person-years of data, with 2,397 deaths. Underlying causes of death were determined from the State of California's official mortality records. Cause-specific death rates and standardized mortality ratios (SMRs) were computed for those with and without epilepsy relative to subjects in the California general population. Comparisons were then made between SMRs of those with and without epilepsy, and CIs on the ratios of SMRs were determined. RESULTS: Death rates for persons with epilepsy were elevated for several causes. The greatest excess was due to seizures (International Classification of Diseases-9 [ICD-9] 345; SMR 53.1, 95% CI 28.0 to 101.0) and convulsions (ICD-9 780.3; SMR 25.2, 95% CI 11.7 to 54.2). Other causes occurring more frequently in those with epilepsy included brain cancer (SMR 5.2, 95% CI 2.2 to 12.1), respiratory diseases (SMR 1.7, 95% CI 1.2 to 2.5), circulatory diseases (SMR 1.3, 95% CI 1.0 to 1.7), and accidents (SMR 2.7, 95% CI 1.9 to 3.7), especially accidental drowning (SMR 12.8, 95% CI 7.0 to 23.2). CONCLUSIONS: Remote symptomatic epilepsy is associated with an increased risk of death. Seizures, aspiration pneumonia, and accidental drowning are among the leading contributors.

Adolescent↗
PubMed1996

The developmental outcome of children born to heroin-dependent mothers, raised at home or adopted.

In the present investigation we were interested to study the possible role of in-utero exposure to heroin and of the home environmental in the etiology of long-term developmental problems in children born to heroin-dependent parents in comparison to matched controls. The children were examined at .5-6 years of age by a developmental pediatrician and a developmental psychologist using, for the children up to 2.5 years of age, the Bayley Developmental Scales, and for children aged 3-6 years the McCarthy Scales for Children's Abilities. We examined 83 children born to heroin-dependent mothers, and compared the results to those of 76 children born to heroin-dependent fathers and to three control groups; 50 children with environmental deprivation, 50 normal children from families of moderate or high socioeconomic class, without environmental deprivation, and 80 healthy children from kindergartens in Jerusalem. There were five children (6.0%) with significant neurological damage among the children born to heroin-dependent mothers and six (7.9%) children among those born to heroin-dependent fathers. The children born to heroin-dependent mothers had a lower birth weight and a lower head circumference at examination when compared to controls. The children born to heroin-dependent parents also had a high incidence of hyperactivity, inattention, and behavioral problems. The lowest DQ or IQ among the children with cognitive levels above 70 was found in the children with environmental deprivation, next was the DQ or IQ of children born to heroin-dependent fathers, then the DQ or IQ of the children born to heroin-dependent mothers. When the children born to heroin-dependent mothers were divided to those that were adopted at a very young age and to those raised at home, the adopted children were found to function similarly to the controls while those not adopted functioned significantly lower. Our results show that the developmental delay and behavioral disorders observed among children born to drug-dependent parents raised at home may primarily result from severe environmental deprivation and the fact that one or both parents are addicted. The specific role of the in-utero heroin exposure in the determination of the developmental outcome of these children (if they do not have significant neurological damage), seems to be less important in comparison to the home environment.

Abnormalities, Drug-Induced↗
PubMed2004

Common antiepileptic drugs in pregnancy in women with epilepsy.

BACKGROUND: The potential adverse effects of antiepileptic drug (AED) exposure in pregnancy have been well recognised but the relative risks of specific antiepileptic drug exposures remain poorly understood. OBJECTIVES: To assess the adverse effects of commonly used antiepileptic drugs on maternal and fetal outcomes in pregnancy in women with epilepsy. Comparison of outcomes following specific antiepileptic drug exposures in utero to unexposed pregnancies in the general population or women with epilepsy are described. The current manuscript reports the first phase of this review which focuses upon neurodevelopmental outcomes in children exposed to antiepileptic drugs in utero. SEARCH STRATEGY: We searched MEDLINE, Pharmline, EMBASE, Reprotox and TERIS from 1966 to December 2003. Review articles and conference abstracts were also hand searched. SELECTION CRITERIA: All randomized controlled trials, prospective cohorts of children of pregnant women with and without epilepsy and case control studies (cases: developmental delay or impaired cognitive outcome, control: normal development) were included. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed using an adapted version of the Newcastle-Ottawa Scale. The wide variety of outcome measures and methodological approaches made meta-analysis difficult and a descriptive analysis of the results is presented. MAIN RESULTS: PART A 1b - DEVELOPMENTAL OUTCOMES: The majority of studies were of limited quality. There was little evidence about which specific drugs carry more risk than others to the development of children exposed in utero. The results between studies are conflicting and while most failed to find a significant detrimental outcome with in utero exposure to monotherapy with carbamazepine, phenytoin or phenobarbitone, this should be interpreted cautiously. There were very few studies of exposure to sodium valproate. Polytherapy exposure in utero was more commonly associated with poorer outcomes, as was exposure to any AEDs when analysis did not take into account type of AED. The latter may reflect the large proportion of children included in these studies who were in fact exposed to polytherapy. REVIEWERS' CONCLUSIONS: PART A 1b - DEVELOPMENTAL OUTCOMES: Based on the best current available evidence it would seem advisable for women to continue medication during pregnancy using monotherapy at the lowest dose required to achieve seizure control. Polytherapy would seem best avoided where possible. More population based studies adequately powered to examine the effects of in utero exposure to specific monotherapies which are used in everyday practice are required.

Abnormalities, Drug-Induced↗
PubMed1984

Recurrent seizures after diphtheria, tetanus, and pertussis vaccine immunization. Onset less than 24 hours after vaccination.

Twenty-two patients with recurrent seizures that started less than 24 hours after immunization with diphtheria, tetanus, and pertussis (DTP) vaccine were retrospectively studied. The initial seizure generally occurred after one of the first three DTP vaccine immunizations, and followed that immunization by less than 12 hours. Two of the 22 patients were siblings. Eight patients had additional immunizations with DTP vaccine and four had immediate worsening of their seizures. Of the 22 patients, only one was seizure free and stopped taking anticonvulsants. Three patients exhibited normal development, and 11 had severe developmental delays. Based on these observations, we reviewed current contraindications for immunization with pertussis vaccine.

Child↗
PubMed1984

Familial autism and the fragile-X chromosome.

This report presents two male siblings in whom the diagnosis of infantile autism was found in association with a fragile site on the X chromosome. In addition to their marked autistic characteristics, formal examinations indicated that both boys were severely mentally retarded and had several physical features commonly observed in association with the fragile-X syndrome. The mother of these two siblings also gave birth to identical twin boys, who were developmentally delayed and showed several autistic features prior to their untimely death in a house fire. The possible role of the fragile-X chromosome as an etiological factor in families where there is a clustering of autism and related developmental disturbances is discussed.

Autistic Disorder↗
PubMed2006

Speech perception and short-term memory deficits in persistent developmental speech disorder.

Children with developmental speech disorders may have additional deficits in speech perception and/or short-term memory. To determine whether these are only transient developmental delays that can accompany the disorder in childhood or persist as part of the speech disorder, adults with a persistent familial speech disorder were tested on speech perception and short-term memory. Nine adults with a persistent familial developmental speech disorder without language impairment were compared with 20 controls on tasks requiring the discrimination of fine acoustic cues for word identification and on measures of verbal and nonverbal short-term memory. Significant group differences were found in the slopes of the discrimination curves for first formant transitions for word identification with stop gaps of 40 and 20 ms with effect sizes of 1.60 and 1.56. Significant group differences also occurred on tests of nonverbal rhythm and tonal memory, and verbal short-term memory with effect sizes of 2.38, 1.56, and 1.73. No group differences occurred in the use of stop gap durations for word identification. Because frequency-based speech perception and short-term verbal and nonverbal memory deficits both persisted into adulthood in the speech-impaired adults, these deficits may be involved in the persistence of speech disorders without language impairment.

Adolescent↗
PubMed2006

Munchausen Syndrome by Proxy/Fabricated and Induced Illness: does the diagnosis serve economic vested interests, rather than the interests of children?

The discourse of Munchausen Syndrome by Proxy/Fabricated and Induced Illness posits the widespread incidence of a highly dangerous form of child abuse in which illness and developmental delay in children, is caused by their parents or carers. The discourse has been linked to false allegations of child abuse, hostile adoptions and miscarriages of justice. It has also stimulated concerns that the children's real medical and developmental needs are neglected when their conditions are misdiagnosed as child abuse. This study examines the critical claims that have been levelled against the Munchausen discourse. They provide explanations of the children's problems that compete with the discourse. The claim of the discourse to scientific validity is thereby shown to be questionable. The explanations have been distilled into specific hypotheses, to stimulate further research. The literature from which the hypotheses were derived, identifies problems in the MSbP/FII discourse in five broad areas of science, regarding: the test validity of techniques; construct validity; statistical methods; evidentiary standards and adverse impacts. The main conclusion is that the detailed critical hypotheses, cohere around the central claim that the discourse of Munchausen Syndrome by Proxy/Fabricated and Induced Illness serves economic vested interests, rather than the interests of children. The hypotheses predict adverse health and social outcomes, as a result of the discourse. Consequently, the continued deployment of the discourse would probably be "unsafe and therefore unwise".

Child↗
PubMed2002

Validity and reliability of the communication and symbolic behavior scales developmental profile with very young children.

Three studies were conducted to evaluate the validity and reliability of the three measures of the Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP): (1) a one-page parent-report checklist; (2) a four-page follow-up caregiver questionnaire (CQ); and (3) a behavior sample (BS), which is a face-to-face evaluation of the child. Participants for these studies were drawn from a pool of 603 children for the checklist and CQ (ages 6-24 months) and 364 children for the BS (ages 12-24 months). Study 1 examined the concurrent relationship of standard scores for the checklist, CQ, and BS. Large correlations were found between the checklist and CQ and moderate to large correlations were found between each of the parent report tools and the BS. Study 2 examined test-retest stability by comparing the raw and standard scores over a 4-month retest interval. The results indicated significantly greater retest raw scores but no significant differences between standard scores from test to retest for the checklist, CQ and BS, providing evidence that the three measures detect growth over short periods but produce relatively stable rankings of children. Study 3 examined the concurrent and predictive relationship of the three CSBS DP measures and children's outcomes on standardized tests of receptive and expressive language at 2 years of age. Moderate to large correlations were found between all of the CSBS DP measures and language outcomes at 2 years of age. Multiple regression analyses indicated that the three composites were a significant predictor of receptive and expressive language outcomes. The findings from these three studies support the use of the CSBS DP as a screening and evaluation tool for identifying children with developmental delays at 12 to 24 months of age.

Child Behavior↗
PubMed1988

Unisensory and bisensory processing skills of children having misarticulations and normally speaking peers.

The purpose of this investigation was to test the developmental delay hypothesis as a possible explanation for the existence of misarticulations in 7- and 8-year-old children. To accomplish this, 10 normally speaking children, 10 having mild misarticulations, and 10 children with severe misarticulations were administered unisensory and bisensory processing tasks. Unisensory tasks consisted of oral and manual form discrimination and auditory recall of word strings. Bisensory tasks were combinations of the unisensory ones and were of major interest, because this form of processing has been considered a test of children's CNS maturity. Results showed that children having misarticulations obtained lower scores than children with normal articulation on all bisensory tasks and had larger decrements from unisensory to bisensory tasks than control subjects. On unisensory tasks involving recall of word strings and manual form discrimination, differences were also found in favor of the control subjects. The results supported the hypothesis that delayed CNS development may coexist with misarticulations of 7- and 8-year-old children.

Articulation Disorders↗
PubMed1988

Developmental outcome of 519 small-for-gestational age children at the age of two years.

At the age of two years developmental outcome of 519 small-for-gestational age (SGA) children and 3375 control children was studied in southwestern Finland. A modification of the Denver Developmental Screening Test was used for follow-up. A significantly higher number of developmental abnormalities was found in SGA children than in the control children at the age of two years. Significant differences were found in walking, manual performance and comprehension between SGA and control children. Asphyxia was the only perinatal complication associated with later developmental abnormalities in SGA infants. Term SGA infants had a significantly higher frequency of developmental delays than term appropriate-for-gestational age (AGA) infants. In preterm infants no difference was found between SGA and AGA infants. Poor head growth during the first two years of life was an important risk factor for later developmental abnormality in SGA infants.

Child Development↗
PubMed2005

Maternal methylenetetrahydrofolate reductase deficiency and low dietary folate lead to adverse reproductive outcomes and congenital heart defects in mice.

BACKGROUND: Genetic or nutritional disturbances in folate metabolism may affect embryonic development because of the critical role of folate in nucleotide synthesis and methylation reactions. The possible role of a mild deficiency in methylenetetrahydrofolate reductase (MTHFR) and low dietary folate in pregnancy outcomes and heart morphogenesis requires further investigation. OBJECTIVE: We investigated the effect of mild MTHFR deficiency, low dietary folate, or both on resorption rates, on length and weight, and on the incidence of heart malformations in murine embryos. DESIGN: Female Mthfr +/+ and +/- mice were fed a control diet (CD) or a folic acid-deficient diet (FADD) before mating with male Mthfr +/- mice. On gestational day 14.5, implantation and resorption sites were recorded and viable embryos were examined for gross malformations, growth delay, and congenital heart defects. RESULTS: Plasma homocysteine in Mthfr +/- dams and in FADD-treated dams was significantly higher than that in Mthfr +/+ dams and CD-treated dams, respectively. A significantly higher rate of resorption and greater developmental delay were observed in hyperhomocysteinemic mice than in CD-treated +/+ dams. Heart defects were identified in 4 of 11, 5 of 10, and 4 of 10 litters from CD-treated +/-, FADD-treated +/+, and FADD-treated +/- dams, respectively, but not in any of those from CD-treated +/+ dams (0/11 litters). CONCLUSION: Our findings suggest that mild MTHFR deficiency, low dietary folate, or both in the dams increase the incidence of fetal loss, intrauterine growth retardation, and heart defects. These data support the benefit of folic acid supplementation in pregnant women, particularly in those with MTHFR deficiency.

Animals↗
PubMed1981

Polymorphism in chromosome 4.

Chromosomal analyses were performed on 302 individuals, using QFQ banding techniques to determine the occurrence of heteromorphism of chromosome 4. Two type of heteromorphism were observed, one showing an intensely fluorescent band in the centromere region and the other an intensely fluorescent band in the proximal area of the short arm. No one individual possessed both type of heteromorphism. A higher frequency of chromosome 4 heteromorphism was found in patients with schizophrenia, mental retardation, hyperactivity, developmental delay and speech impediments than in normal individuals.

Adolescent↗
PubMed2004

Assessing psychopathology in individuals with developmental disabilities.

Individuals with developmental disabilities are at high risk for developing mental health problems. The prevalence of psychopathology is approximately 4 times higher than that found in the general population. Yet there is a tendency to underdiagnose psychiatric disorders in the developmentally delayed population because of diagnostic overshadowing, the lack of appropriate diagnostic criteria, and the paucity of appropriate assessment measures. Over the past decade, there has been an emergence of scales developed specifically to screen for psychopathology in individuals with developmental disabilities. In addition, advancements have been made in observation techniques, thus facilitating the ability to objectively observe behaviors often described as internal events. A description of a multimethod approach to assessing psychopathology in individuals with developmental disabilities is provided incorporating the recent advancements in the field, as well as suggestions for future research.

Adolescent↗
PubMed2001

Gross motor development of a toddler with barth syndrome, an x-linked recessive disorder: a case report.

PURPOSE: The purpose of this case report is to describe the gross motor development of a toddler with Barth Syndrome, an X-linked genetic disorder. SUMMARY OF KEY POINTS: Barth Syndrome is an unusual pediatric cardiovascular and neuromuscular disorder with a combination of features, including dilated cardiomyopathy, persistent aciduria, skeletal myopathy, severe neutropenia, and growth retardation. The child described in this report has a complicated medical history, including the diagnosis of Barth syndrome at 38 months of age. He began receiving early intervention services, including physical therapy, because of developmental delays at 13 months. This report was written when the child was 45 months old. Implications for working with a child with a cardiomyopathy and neutropenia are presented. Cardiovascular changes following transcatheterization for an atrial septal defect are described. Developmental changes secondary to an early intervention program that included physical therapy are discussed. RECOMMENDATIONS: Multiple aspects of care need to be considered when working with a child with a genetic syndrome that involves a cardiac defect and cardiomyopathy. When working with a child with a known cardiomyopathy, the physical therapist must watch for signs of cardiores-piratory distress. In addition, neutropenia is often associated with Barth syndrome, so the therapist must be cognizant of exposing the child to any illnesses.

Journal Article↗
PubMed1992

Counting knowledge and skill in cognitive addition: a comparison of normal and mathematically disabled children.

The relationship between counting knowledge and computational skills (i.e., skill at counting to solve addition problems) was assessed for groups of first-grade normal and mathematically disabled (MD) children. Twenty-four normal and 13 MD children were administered a series of counting tasks and solved 40 computer-administered addition problems. For the addition task, problem-solving strategies were recorded on a trial-by-trial basis. Performance on the counting tasks suggested that the MD children were developmentally delayed in the understanding of essential and unessential features of counting and were relatively unskilled in the detection of certain forms of counting error. On the addition task, the MD children committed many more computational errors and tended to use developmentally immature counting procedures. The immature counting knowledge of the MD children, combined with their relatively poor skills at detecting counting errors, appeared to underlie their poor computational skills on the addition task. Suggestions for future research are presented.

Child↗