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Health Care Utilization Among Children Diagnosed with
Developmental Delay

Margaret M. Gallaher, Dimitri A. Christakis, Frederick A. Connell Dept
of Pediatrics; School of Public Health and
Community Medicine, University of Washington, Seattle, WA

OBJECTIVE: To describe the demographic characteristics, clinical forms,
and health care utilization and
expenditures during the first five years of life of a cohort of Medicaid
children diagnosed with developmental delay.
BACKGROUND: Little is known about the population-based prevalence of
developmental delay, and how the
health care utilization of these children compares to that of others.
DESIGN/METHODS: We performed a retrospective cohort study using
Washington State Medicaid claims data. We
identified children born between 11/90 and 12/96, diagnosed with
developmental delay (ICD9-CM 315, 317, 318,
319) before the age of five years, who were enrolled in Medicaid within
one month of birth, remained continuously
enrolled for at least 12 months and had the diagnosis of developmental
delay prior to the first break in enrollment.
Four controls per case were matched within one month of birth and by the
duration of continuous enrollment in
Medicaid. We included claims data until the first break in enrollment or
until five years of age, whichever came first.
RESULTS: A total of 3,948 children had a diagnosis of developmental
delay. Children were continuously enrolled a
mean of 3.8 years. Sixty-two percent of the case children were males,
compared to 51% of the control children
(p<.001). Of those diagnosed with developmental delay 1.3% had mental
retardation, 64.9% had cognitive or mixed
developmental delay, 29.6% had an isolated speech/language delay and
4.2% had an isolated motor delay. Case
children averaged nearly twice as many physician visits/child/year (12.9
vs. 6.7, p<.001), 23 times as many
visits/child/year with ancillary providers (2.3 vs. 0.1, p<.001) and
three times the number of
hospitalizations/child/year (0.3 vs. 0.08, p<.001). The mean Medicaid
reimbursement/child/year for physician visits
was 3.4 times greater ($858 vs. $249, p<.001), for ancillary providers
was over 44 times greater ($178 vs. $4,
p<.001) and for hospitalizations was nearly 20 times greater among case
children ($4,223 vs. $215, p<.001).
CONCLUSIONS: Children diagnosed with developmental delay have
significantly increased health care utilization
and expenditures associated with that care. Careful profiling of the
clinical needs of this population must be
undertaken to assure that these children with developmental delay are
provided the care that they need to achieve
optimal outcomes.


The Contributory Role of Otitis Media in the Developmental Problems of Children at High
Social Risk

Roy Grant, Lourdes Lynch, Peter Sherman, Paul Kory, Irwin Redlener
Community Pediatrics, Children's Hospital
at Montefiore Medical Center, Albert Einstein College of Medicine, New
York, NY

OBJECTIVE: To determine whether otitis media is a significant
contributing factor in developmental, behavioral,
and school problems identified by primary pediatricians treating high
social risk children.
BACKGROUND: High social risk children and homeless children experience
more acute and chronic health
conditions, and worse health status, than other low income children
(Weinreb et al., 1998; Parker et al., 1991;
Wood et al., 1990). Homeless children frequently present speech-language
delay, hyperactivity, and school
problems (Bassuk et al., 1997; Zima et al., 1994; Grant 1990). These
developmental problems may be related to
chronic otitis media, especially among children who do not receive
adequate language stimulation (Gravel and
Wallace, 1998; Nittrouer, 1996; Wallace et al., 1996).
DESIGN/METHODS: Chart review of high social risk and homeless patients
of the New York Children's Health
Project (NYCHP) referred for psychological assessment during 1998,
noting diagnoses of otitis media, asthma,
anemia, high lead levels, and other potentially contributory conditions.
A total of 148 children from 4 months to
15.6 years (mean age, 62.5 months) were assessed by a clinical child
psychologist after referral from their primary
pediatrician.
RESULTS: Among these 148 patients, 77% were diagnosed with developmental
delay or learning disorder, among
whom there is a signficant correlation with diagnosed otitis media
(p=<0.05); 10.8% were diagnosed with failure to
thrive (FTT); and 25% with attention deficit disorder. For children 36
months or younger, excluding those with
FTT, 71.4% were diagnosed with otitis media (or impacted cerumen). By
comparison, there was a 27% rate of otitis
media among NYCHP patients during 1998 (Redlener and Johnson, 1999).
CONCLUSIONS: Otitis media is signficantly more prevalent among children
referred for developmental and
behavioral assessment. It may be a contributing factor to developmental
delays and school problems. Pediatricians
treating high social risk children with recurrent otitis media should
monitor development and refer for assessment
and intervention as early as possible to maximize their opportunities
for educational success.


The Role of Biliary Excretion in Carnitine Homeostasis
Chunli Yu, Hye-Ran Yoon, Giuseppe Giordano, Mark J. Magera, Piero
Rinaldo Genetics, Yale University, New
Haven, CT; Special Biochemistry, Seoul Medical Science Institute, Seoul,
Korea, Republic of; Pediatrics,
University of Padova, Padova, Italy; Laboratory Medicine & Pathology;
Pediatric & Adolescent Medicine, Mayo
Clinic, Rochester, MN

OBJECTIVE: To study the relevance of biliary excretion in carnitine
metabolism and bioavailability.
BACKGROUND: Patients affected with fatty acid oxidation (FAO) disorders
are at risk of sudden unexpected
death, usually triggered by hypoglycemia, accumulation of toxic
metabolites, and organ failure in response to
fasting. This notion has been supported by the application of
biochemical methods to the postmortem investigation
of sudden death cases, including the analysis of bile. Results obtained
in the mouse model of LCAD deficiency
[PNAS 95:15592,98] are supportive of the hypothesis that carnitine
conjugation and biliary excretion may represent
the predominant route to eliminate toxic acyl-CoA species accumulated in
the liver as consequence of FAO disorders
and possibly other conditions associated with secondary carnitine
deficiency in vivo, such as valproic acid (VPA)
therapy.
DESIGN/METHODS: Bile specimens are tested for total and free carnitine
(TC, FC) by radioenzymatic assay and
acylcarnitines (AC) by tandem mass spectrometry. To date, we have
analyzed postmortem bile samples of 11 cases:
MCAD deficiency (n=3), VLCAD deficiency (4), and LCHAD deficiency (4).
Using the isolated perfused rat liver
(IPRL) system, we investigated the effect of VPA perfusion (0.5-1.5 mM;
carnitine 50 mM) on biliary carnitine
excretion over a period of 90 min.
RESULTS: Postmortem bile samples: The AC fractions were elevated in all
cases (AC/FC ratios: 0.7-8.8; nl:
0.1-0.5), and the acylcarnitine profiles were typical of the underlying
disorder. In one case with MCAD deficiency,
the biliary excretion of total carnitine was markedly elevated (2.66
mmol/L; nl: 0.32-0.57) despite a concurrent
severe liver carnitine depletion (0.05 mmol/g wet wt; nl: 0.34-1.09).
IPRL experiments:VPA causes a dose-dependent increase of TC excretion
(controls at 90 min (n=3): 55±9
pmol/min/g liver wet wt; 1.5 mM VPA at 90 min (n=5): 389±123; p<0.001),
an effect not observed with 1.5 mM
octanoic acid (32±10) and 0.5 mM phenobarbital (79±10). Of note, the rat
bile AC profiles were remarkably similar
to those observed in plasma and bile of patients with MCAD deficiency.
Separation of C8-isomers by LC-MS/MS
confirmed that the C8 peak in the bile from VPA infused livers was
mostly octanoylcarnitine, not valproylcarnitine.
CONCLUSIONS: These results suggest that biliary excretion is an
important factor in determining carnitine
homeostasis in metabolic disorders and other conditions associated with
secondary carnitine deficiency.


Auditory Attention Processing in 5-year-Old Preterm Children: Evidence from Event
Related Potentials (ERP)

Elie M. Saliba, Remy Dupin, Jean-Paul Laurent, Anne Henrot, Jean
Laugier, Leandre Pourcelot Neonatology,
INSERM 316; University Hospital Tours, Tours, France

OBJECTIVE: To test the assumption that preterm children have
difficulties in maintaining active attention
BACKGROUND: Studies on school-age outcome of premature children indicate
that they scored lower than control
children on tests of academic achievemnt. Learning disabilities in
children born prematurely might be the
consequence of attentional disorders
DESIGN/METHODS: Twenty 5-year-old premature children (PC) born between
26 and 32 weeks of gestation were
compared to twenty term children (TC), matched for age, socio-economic
status and IQ, using an auditory
paradigm. In the passive task subjects had to watch a cartoon presented
on videotape and to ignore auditory stimuli.
In the active task they had to detect a rare tone (10% target) among
frequent tones (90% standard). Accuracy and
reaction time (RT) were analysed and ERP were recorded at
F3,Fz,F4,T4,Cz,T5,Pz,Oz sites. Behavioral and
electrophysiological data were analysed in repeated measure ANOVAs.
RESULTS: There was a group difference for percentage of correct hits but
not for RTs.The TC group achieved
better scores (p=0.025). There was no significant group effect on
amplitudes or latenties (p=0.71) in the passive
attention task. N1 amplitude was larger in the active task in the PC
group compared to the TC group for target
stimuli (mean±SD;-14.44±7.6 vs.-8.5±5.3; p=0.047). Inversely, P3a
amplitude was greater in the TC group than
the PC group for target stmuli (7.21±4.8 vs.-0.37±0.52; p=0.011).
Moreover P3b amplitude was larger in the TC
group compared the PC group(p=0.045).
CONCLUSIONS: The preterm children scored fewer correct hits and were
less efficient in their attentional strategy
as assessed by ERP components. Active auditory discrimination, which
requires effort and is task demanding, was
defective in the 5-year-old preterm children.


How the History of Children with Disabilities Affects Current Policy and Practice
Jeffrey P. Brosco Pediatrics, University of Miami, Miami, FL

OBJECTIVE: To uncover recurrent problems in public policy and medical
practice through analysis of the medical,
social, and political history of children with disabilities.
BACKGROUND: There are 50 federal programs that provide services to two
million American children with
physical and mental disabilities. Although our nation spends 40 billion
dollars per year on research, education,
supplemental income, and health care benefits, families commonly report
frustration in obtaining services, and much
debate remains regarding the appropriate use of resources.
DESIGN/METHODS: Traditional historical methods were used to investigate
the history of children with
developmental disabilities in the U.S. over last 75 years. The previous
scholarship was reviewed; data was
abstracted from primary documents; key themes were identified from the
historical record.
RESULTS: Over the last 75 years, medical research and practice in the US
has become increasingly focused on
preventing mental and physical disabilities. This has led to enormous
advances, such as the eradication of polio and
near elimination of the two most common causes of mental retardation in
the early 20th century -- hypothyroidism
and congenital syphilis. In the meantime, social attitudes have changed
just as dramatically: children with
development disabilities were once considered merely a burden on society
and often allowed to die shortly after
birth; ethical standards today protect the disabled child's inherent
value as a person and his right to full participation
in society.
Despite the benefits of medicine, however, there remain frequent
conflicts in day-to-day medical encounters and in
public policy. Many of these conflicts are partly explained by the
divergent paths of the medical and disability rights
communities. While physicians and researchers focus on the potential of
science to cure or prevent disability, people
with disabilities struggle with a legacy of discrimination that has not
disappeared from their everyday lives. These
historical differences often frustrate communication between providers
and consumers, and lead to disagreements in
policy questions such as how to focus research efforts. For example,
most physicians and researchers do not
question the value of prenatal testing for various conditions, but many
families and activists view this approach as an
attempt to eliminate people with disabilities.
CONCLUSIONS: Problems in current disability policy and practice are
partially explained by the historically
divergent aims of the medical community and the disability rights
community.


Functional Changes in Self Care, Mobility, and Cognitive Skills and Rehabilitation
Resources in Children with Neurodevelopmental Disabilities
Michael E. Msall, James Roistacher, Brain T. Rogers, Michelle R.
Tremont, Nancy Lyon, Mary Fournier, Kathleen
Schlenz, Darryl Ernst Brown University, Providence, RI; SUNY-AB,
Buffalo, NY

OBJECTIVE: Our purpose was to examine the relationship between
functional limitation severity, functional change
over time and rehabilitation resources in children with cerebral palsy
(CP), spina bifida (SB), developmental
disabilities (DD)and technology dependent-medically complex (MC).
BACKGROUND: 103 children with CP, 330 children with DD, 39 children with
SB, and 42 children with MC
were assessed using the Functional Independence Measure for Children
(WeeFIM). Children were part of the
WeeFIM Application Network between January 1, 1999 and June 30, 1999.
DESIGN/METHODS: Evaluators were credentialled to criterion standards in
functional assessment using the
WeeFIM. Medical impairments included CP, SB, DD and MC. Functional
quotients were calculated for the total
WeeFIM score, as well as for self-care, motor, and
cognitive-communicative domains. Functional quotients were
used to classify limitations as mild (>75%), moderate (50-75%), and
severe (<50%). Rehabilitation resources
included physical, occupational, and speech therapy quantified by 15
minute units of treatment time.
RESULTS: 212 children had 2 or more assessments over a 6 month period
among children with CP and DD.
Functional gains in mobility were greatest for children with CP, DD, and
MC with mild and moderate limitations
and in children with SB with mild and severe limitations. Self-care
functional gains occurred the most in children
with CP or DD mild limitations. Children with mild functional
limitations demonstrated the most
communicative/cognitive functional gains. Examination of rehabilitation
resources for children with CP revealed that
children with moderate functional limitations received twice as much
physical therapy than children with mild
limitations. Despite significant self-care challenges among children
with SB and moderate and severe functional
limitations, few received occupational therapy (OT) services. Children
with CP, DD, and MC received increased OT
and speech therapy services if they had more severe functional
limitations.
CONCLUSIONS: In this pilot project, functional quotients in mobility,
self-care, and communication/cognition can
profile disability status across centers and begin the process of
understanding the relationship between functional
changes, rehabilitation inputs, and family supports.


Medical Impairments, Functional Limitations, and Disability Status in 41,300 School Age
Children

Michael E. Msall, Roger C. Avery, Dennis P. Hogan, Julie C. Lima,
Michelle L. Rogers, Michelle R. Tremont

OBJECTIVE: To examine the relationship between medical impairments,
functional limitations in essential activities
and disability status in school age children.
BACKGROUND: The National Center for Medical Rehabilitation Research
(NCMRR) Model of Disability provides
a framework for analyzing the complexity of disability. Categories in
the NCMRR model include impairment,
functional limitations, disability, and societal limitations. The 1994
and 1995 National Health Interview Survey
Disability Interview Supplement (NHIS-D) is a representative national
sample.
DESIGN/METHODS: ICD-9 impairment codes were categorized as life
threatening (n=167), chronic (n=269),
medical (n=263), episodic (n=820), injury (n=98), asthma (n=1186),
neurosensory (n=1,094), genetic (n=245),
mental retardation/autism (n=465), attention deficit/learning disorder
(AD/LD)(n=792), and behavior disorders
(n=161). Categories from the Pediatric Functional Independence Measure
(WeeFIM) were used to categorize
functional limitations in self-care/continency, mobility, communication,
and learning skills. Activity limitations
included impact on play and school. Disability status was classified as
none, minor (mild limitations in one area),
major (moderate limitations in one area), and multiple (moderate/severe
limitations in 2 or more areas).
RESULTS: Of the 41,300 children, functional limitations were distributed
as follows: mobility 12/1000, self care
9/1000, communication 54/1000, and learning 104/1000. Disability status
by most severe condition included 88%
none, 4.1%minor, 5.9% major, and 1.9% multiple. Neurosensory impairments
accounted for 38% of mobility,
33% of self-care, 33% of communicative and 15.4% of learning functional
limitations of severe degree. Mental
retardation/autism accounted for 15.6% of severe and 7.6% of moderate
communicative limiations. AD/LD
accounted for 24% of severe, and 15.9% of moderate learning limitations.
Severe activity limitations occurred in
3.2%. Asthma accounted for 46% and neurosensory impairments accounted
for 15% of school activity limitations.
CONCLUSIONS: Health impairments, developmental disabilities, and
functional limitations status in essential
activities are required to assess disability in school age children.


Special Education Administrator Perceptions of Hospital-Based Assessments of Children
with Learning Problems

Ludwig von Hahn, Caroline Linse, Janet Hafler Department of Psychiatry,
Harvard Medical School, Boston, MA;
Faculty of Education, University of North Carolina-Charlotte, Charlotte,
NC; Department of Pediatrics, Harvard
Medical School, Boston, MA

OBJECTIVE: To provide an assessment of the consultation process between
hospital-based clinicians and schools.
BACKGROUND: One of the roles of the pediatrician is to consult to
schools and other agencies concerned with the
welfare of children. Little is known about their success with this
process. In one study, Forness et al. (1983)
assessed the interagency status of University Affiliated Programs and
schools through use of a questionnaire.
However, no study to our knowledge discusses each system's perceptions
about the consultative activity which
occurs between the two.
DESIGN/METHODS: Semi-structured audiotaped interviews were conducted
with five focus groups (Special
Education Administrators [1], and medically-based clinicians involved in
the evaluation of children with learning
problems [4]). Interviews were transcribed and themes counted for
frequency.
A questionnaire was used to corroborate the findings of the Special
Education Administrator focus group. 193
questionnaires were distributed to all attendees of a meeting of the
Association of Special Education Administrators
of Massachusetts. Respondents were asked to rate a series of 40 items on
5-point Likert scales. 117 questionnaires
were returned. Response rate=60.3%
RESULTS: Special Education Administrators are "often or almost always
frustrated" (77%) or "angry" (61%) about
their relationship with hospital-based evaluators. Most (75.9%) stated
that the school's perspective is "rarely" or
"never" included in hospital-based reports. Almost all (98%) were
concerned that hospital reports make
recommendations without regard for how they should be implemented in the
school setting. Almost all (96%) stated
that hospitals and schools work together more than they do.
Three of the themes highlighted in the medical focus groups were:
1. The receptivity of hospital reports, and their concern that hospital
reports are not read or considered.
2. Contentious interactions with schools
3. The need for greater communication with schools.
CONCLUSIONS: The consultative process for children with special needs is
characterized by significant degrees of
frustration. School personnel may disagree with the conclusions and
recommendations in hospital-based reports.
They seek a greater degree of collaboration with hospital-based
personnel.
Hospital-based evaluators acknowledge the frustration experienced by
school personnel, and recognize how
increased communication improves the consultation process. Lack of trust
and a shortage of time make
communication difficult.


Ketogenic Diet-Induced Bruising and Changes in Platelet Function
Elizabeth Berry-Kravis, Gayle Booth, Leonard Valentino

OBJECTIVE: To determine the frequency and mechanism of bruising/bleeding
side effects in patients treated with
the ketogenic diet.
BACKGROUND: The ketogenic diet has recently experienced a surge in
popularity as a treatment for
difficult-to-control epilepsy. Bruising has been identified as a side
effect of ketogenic diet treatment by families and
patients, but this symptom is not reported in the existing literature.
DESIGN/METHODS: We evaluated our cohort of diet-treated patients for
symptoms of bruising or bleeding via
chart review and screening at follow-up visits.
RESULTS: A significant increase in bruising or other minor bleeding was
noted in 16/51 total patients (31.4%).
There were no differences in sex distribution or numbers of
anticonvulsants between the bruising/bleeding and
non-bruising/bleeding groups, although the bruising/bleeding group was
significantly younger. No specific
anticonvulsant was associated with bruising/bleeding. Five patients with
diet-induced bruising/bleeding had
prolonged bleeding times and diminished responsiveness to various
platelet-aggregating agents, with no evidence of
a release defect. These abnormalities all normalized in the one patient
tested after coming off the diet. No patients
had serious hemorrhage. Some patients were Stimate-responsive,
suggesting a treatment for more severe symptoms.

CONCLUSIONS: A mild ketogenic diet-induced bleeding tendency occurs in
about 1/3 of treated patients, due to
diminished platelet responsiveness probably related to changes in
platelet membrane lipid composition and resultant
changes in function of membrane-embedded proteins. Patients on the diet
undergoing anticoagulation or surgery
should be evaluated carefully for symptoms of bleeding tendency.


Cerebral GABA in Pediatric Epilepsy
Edward J. Novotny, Fahmeed Hyder, Graeme F. Mason, Douglas L. Rothman
Pediatrics; Diagnostic Imaging,
Yale University, New Haven, CT; Psychiatry

OBJECTIVE: We measured brain GABA levels in a group of children with
generalized and localization related
epilepsy to investigate whether abnormalities of GABA physiology may
play a role in the pathogenesis of this group
of disorders.
BACKGROUND: Many forms of epilepsy in childhood have no known cause and
normal anatomical
neuroimaging. The etiology of generalized epilepsies is unknown in
greater than 80% of cases. Subjects with
generalized epilepsies have onset in childhood and likely have a genetic
basis. The generalized epilepsies are divided
into idiopathic where subjects have a normal neurological exam and
cryptogenic where they have abnormalities
on neurological and psychological studies. Many types of localization
related epilepsies in children also have normal
anatomy on MRI. Alterations in GABA physiology may play an important
role in these types of epilepsies.
DESIGN/METHODS: A group of 20 children with generalized and focal
epilepsies were studied using the NMRS
protocol. Two subjects were studied on two occasions at six and twelve
months following the first NMRS exam.
GABA measurements of the occipital lobe were obtained on all subjects.
The subjects all had normal clinical MRI
exams. Eight subjects had cryptogenic generalized epilepsy. Seven had
idiopathic generalized epilepsies. Four
adolescents had juvenile myoclonic epilepsy and two had childhood
absence epilepsy. Five subjects with focal
epilepsy had benign rolandic epilepsy. Thirteen age-matched control
subjects were also studied.
RESULTS: Studies on control subjects demonstrated an age-dependent
decrease in occipital lobe GABA
concentrations (R = 0.81; n = 28). The subjects with idiopathic
generalized epilepsy did not have significantly lower
cortical GABA levels than controls [1.5 + 0.1, n = 13 (controls) vs. 1.1
+ 0.4, n = 15; p = 0.2]. The subjects with
focal epilepsy were also not different from controls. However, the
subjects with cryptogenic generalized epilepsy
had significantly lower cortical GABA levels than controls (0.8 + 0.3, n
= 8; p < 0.001).
CONCLUSIONS: These results are the first to identify changes in
steady-state concentrations of cerebral GABA in
human generalized epilepsies. Further in vivo NMRS studies measuring the
turnover of GABA and glutamate can
be performed to elucidate the mechanisms by which these changes take
place. These NMRS studies can be
combined with molecular genetic techniques to help identify the
molecular basis of generalized epilepsies and guide
pharmacological therapy.


Indomethacin Protects Language Systems in Developing Brain
Laura R. Ment, Betty Vohr, Walter Allan, Michael Westerveld, Sara
Sparrow, Karen C. Schneider, Karol H. Katz,
Robert W. Makuch Pediatrics, Neurology, Neurosurgery, Child Study
Center, EPH, Yale University School of
Medicine, New Haven, CT; Pediatrics, Brown University School of
Medicine, Providence, RI; Pediatrics, Maine
Medical Center, Portland, ME

OBJECTIVE: To test the hypothesis that those preterm infants randomized
to receive early low-dose indomethacin
for the prevention of neonatal intraventricular hemorrhage (IVH) would
perform significantly better on measures of
cognitive testing at school age than placebo subjects.
BACKGROUND: Preterm birth results in significant disability, and IVH
represents one of several conditions which
have been associated with adverse neurodevelopmental outcome. Although
previous studies have demonstrated that
indomethacin both lowers the incidence and decreases the severity of IVH
in preterm infants of 600 - 1250 g birth
weight, indomethacin has been shown to decrease cerebral blood flow in
preterm infants and thus concern remains
about the longterm sequelae of this neonatal prevention strategy.
DESIGN/METHODS: We provided follow-up for the 384 surviving preterm
subjects of the Multicenter
Randomized Indomethacin IVH Prevention Trial. Cognitive testing and
neurologic examinations were performed;
demographic data were collected from caregivers.
RESULTS: Three hundred thirty six (88%) of the study children were seen
at 6 yrs corrected age (CA).
Indomethacin children were of lower gestational age (p=0.02), and had
less IVH and low pressure ventriculomegaly
(p=0.03 and 0.05, respectively) than placebo subjects. There were no
differences in the incidences of CP, seizures,
low vision or hearing loss between study groups.
Children randomized to indomethacin had significantly fewer verbal IQ
scores < 70 (5% vs 12%, p=0.06), Peabody
Picture Vocabulary scores < 70 (4% vs 12%, p=0.01), and higher Peabody
Individual Achievement Test Reading
Recognition Scores (p=0.04). In addition, indomethacin children had
better Vineland Adaptive Behavior Scale
Communication Scores (p=0.01) and were less withdrawn on the Child
Behavior Checklist (p < 0.001). These
effects were independent of the effect of IVH in this study population
(p=0.06).
When the need for special services within the school setting was
assessed for the children at 8 yrs CA, the
indomethacin dhildren required significantly less special services
overall (31% vs 58%, p=0.02). Almost three times
the number of placebo children required speech and language therapy when
compared to the indomethacin subjects.
CONCLUSIONS: These data suggest that early low dose indomethacin
protects language systems in developing
brain; these effects are independent of IVH. (supported by NS 27116)


Laboratory Analysis of Blood Serum Obtained from Children on the Ketogenic Diet:
Elevated b-OH-Butyrate and Hexacosanoic Acid (C26:0)

Douglas D. Fraser, Sharon Whiting, Athen MacDonald Paediatrics, Queen's
University, Kingston, ON, Canada;
Anatomy and Cell Biology, Queen's University, Kingston, ON, Canada;
Paediatrics, CHEO, Ottawa, ON, Canada

OBJECTIVE: The objective of this study was to collect and analyse blood
serum obtained from children, (1) before
induction of the ketogenic diet and (2) three weeks after initiation of
the diet. More specifically, we measured
potential changes in pH, electrolytes, osmolality, b-OH-butyrate and
very long-chain fatty acids (VLCFA).
BACKGROUND: The ketogenic diet has been used for years as a treatment
for intractable childhood seizures.
Seizure control improves substantially in 2/3 of children on the high
fat, low carbohydrate diet. Despite the clinical
efficacy of the ketogenic diet for seizure control, the anticonvulsant
mechanism of action remains unknown. Clinical
observations have identified at least four possible biochemical
perturbations following initiation of the diet: acidosis,
cellular/extracellular dehydration, ketosis and alterations in energy
metabolism (e.g. VLCFA). Further analysis of
these biochemical changes, together with electrophysiological studies,
may elucidate the circulating anticonvulsant
compound(s) in ketogenic blood serum and the corresponding cellular
mechanism(s) of action.
DESIGN/METHODS: Blood was collected from children in standard tubes via
venipuncture, and serum separated
by centrifugation. Serum obtained before induction of the ketogenic diet
served as a 'control' to serum collected
three weeks after initiation of the diet ('ketogenic'). Serum was
analyzed for pH, electrolytes, osmolality,
b-OH-butyrate and VLCFA.
RESULTS: Laboratory analysis of serum from 6 children demonstrated
statistically significant elevations in
b-OH-butyrate (mmol/L; control, 0.649±0.230 vs ketogenic, 5.973±1.080)
and C26:0 (mmol/L; control
0.772±0.095 vs ketogenic, 1.208±0.240). No significant differences were
observed in pH, electrolytes, osmolality
or other VLCFA (C26:1, C24:0 or C22:0).
CONCLUSIONS: Our data suggests that changes in pH, electrolytes and
osmolality do not play a significant
anticonvulsant role in the ketogenic diet. The specific elevation of
C26:0, together with elevated b-OH-butyrate, may
contribute to the anticonvulsant mechanism of action of the ketogenic
diet. Electrophysiological analysis of both
ketogenic blood serum and exogenous compounds (e.g. C26:0) on cultured
neurons is in progress to substantiate
these findings.
Financial support to D.D.F.: Queen's University, Savoy Foundation for
Epilepsy Research and Physicians'
Services Incorporated Foundation. We thank Ms. J. Champagne, Dr. N.
Lapage and Dr. J. Raymond for
assistance.


Presentation and Follow-Up of Pediatric Patients with Positive Anti-Nuclear Antibodies in
the Absence of Disease

Holly Rothermel, Laurie O. Beitz, Jane G. Schaller, Laurie C. Miller
Pediatric Rheumatology, Floating Hospital for
Children, Boston, MA


BACKGROUND: A positive anti-nuclear antibody (ANA)is a frequent reason
for referral to pediatric rheumatology
clinics. While many patients are identified as having a rheumatic
disease during their initial evaluation, some persist
with only abnormal serology.
DESIGN/METHODS: We reviewed charts of patients referred to our clinic
for a positive ANA test. Patients in
whom a diagnosis was made in the first few visits were excluded, as were
patients with borderline ANAs (titer
1:40).
RESULTS: We identified 19 patients (17F:2M) with positive ANAs and no
diagnosis who have been followed for
an average of 31 months(9 mos-10 yrs). The average age at referral was
13 years. ANA titers ranged from 1:80 to
1:10,216. Symptoms that led to ANA testing included arthralgia (6),
arthralgia with Raynaud's (3), fatigue (2),
Raynaud's (2), parotitis (2), ITP(1), alopecia (1), urticaria (1) and
tremors (1). Other findings at first visit included
hypothyroidism (2), dry eyes(1), dry mouth (1), and lichen sclerosis(1).
No patient had arthritis, malar rash, oral
ulcers, photosensitivity, serositis, nephritis, seizures or psychosis.
Other auto-antibodies at presentation included
thyroid antibodies(Abs)(4), rheumatoid factor(4), anti-cardiolipin
antibodies(aCL Abs)(3), anti-Ro and/or anti-La
Abs(6), anti-histone Abs (3), dsDNA Ab with aCL Ab(1), and anti-Smith Ab
(1). Nine patients had low C3 and/or
C4 (9), three had lymphopenia or leukopenia, and two had polyclonal
cryoglobulins (2). CH50 levels were normal
in all patients. 8 patients had chest X-ray, echocardiogram, PFT and
abdominal ultrasound screens; none had
evidence of heart, lung, or organ involvement. The ANA has persisted in a
ll patients during the follow-up period. At
6 months one patient developed persistent polyarthritis requiring
treatment with steroids and methotrexate. Of the
remaining 18 patients 2 have developed transient arthritis, 3 developed
occasional oral ulcers, and 2 developed
anti-phospholipid antibodies. None of these patients have required
medication, and none have developed SLE or
other rheumatologic diseases.
CONCLUSIONS: Pediatricians often check an ANA titer in patients with
symptoms that might suggest rheumatic
disease. Persistent titers of ANA did not signify rheumatic disease in
the majority of patients who remained
undiagnosed after initial rheumatologic evaluation. Longer follow-up is
needed to further evaluate this group.


Seizures Associated with Rotavirus Gastroenteritis
Douglas S. Swanson, Michele M. Rooney, Dixie D. Griffin Infectious
Diseases, Children's Mercy Hospital,
Kansas City, MO; Viral Gastroenteritis Section, Centers for Disease
Control and Prevention, Atlanta, GA

OBJECTIVE: The purpose of this study is to 1) identify the prevalence of
seizures in a large group of children with
documented rotavirus gastroenteritis and 2) describe the clinical
features of these children.
BACKGROUND: Rotavirus is a common cause of acute gastroenteritis in
young children. In addition, reports from
Asia and Europe suggest a possible association between rotavirus
gastroenteritis and central nervous system (CNS)
disorders, especially seizures. Furthermore, rotavirus genomic RNA has
been detected in the cerebrospinal fluid
(CSF) of children with seizures and gastroenteritis.
DESIGN/METHODS: A three-year (Jan. 1997 - Nov. 1999) retrospective
survey was conducted at Children's
Mercy Hospital in Kansas City, MO. The case records of all patients with
documented rotavirus gastroenteritis were
reviewed for evidence of seizures. Patients with a known CNS disorder or
a coexisting CNS infection or metabolic
disorder were excluded.
RESULTS: Six of 486 (1.2%) children with rotavirus gastroenteritis had
an associated afebrile seizure.
Surprisingly, four of the six cases occurred within a seven-day period
in March 1998. The seizures were mostly
brief, although one patient had a generalized tonic-clonic seizure
lasting approximately one hour. Five children had
more than one seizure. Most of the patients had mild dehydration and
none had evidence of hypoglycemia or an
electrolyte abnormality to account for their seizure. Five children had
lumbar punctures performed and the CSF
results were unremarkable. A computed tomography (CT) head scan was
obtained in all six children, and one was
abnormal. The abnormal CT scan revealed multiple cerebral infarcts in a
previously healthy infant with possible
positional asphyxiation related to his seizure. Electroencephalograms
(EEGs) were performed in five patients and the
only abnormal EEG was from the infant with possible positional
asphyxiation. No patients had seizure recurrences
during follow-up and no long-term anticonvulsant therapy had been
prescribed. Two rotavirus isolates had strain
typing performed and were identified as serotypes G1P8 and G2P4.
CONCLUSIONS: In our case series, approximately 1% of children with
rotavirus gastroenteritis had benign afebrile
seizures with no apparent long-term sequelae. A cluster of four cases
that occurred within a seven-day period is
being further investigated.


Efficacy Of Vagal Nerve Stimulation In Children With Intractable Seizures
John J. Jakimczyk, Paula M. Abate, John P. Weaver, Paul C. Marshall,
Sanjeev V. Kothare Pediatrics, University
of Massachusetts Medical Center, Worcester, MA; Division of Pediatric
Neurology, Department of Pediatrics,
University of Massachusetts Medical Center, Worcester, MA; Division of
Neurosurgery, Department of Surgery,
University of Massachusetts Medical Center, Worcester, MA

OBJECTIVE: To evaluate the safety and efficacy of vagal nerve
stimulation (VNS) as adjunctive therapy in patients
< 18 years old with intractable seizures.
BACKGROUND: Since July 1997, the FDA has approved VNS as a
non-pharmacological adjunctive therapy for
patients > 12 years old with intractable seizures.
DESIGN/METHODS: Of the 11 patients implanted with the device, 36% were
female. The average age at
implantation was 8.7 years (range 3.4-17.3 years). Follow-up evaluation
ranged from 3 months to 1.1 year. Both
generalized and partial seizure types were represented. The etiology of
seizures included symptomatic generalized
(Lennox-Gestaut syndrome)(6/11), primary generalized (1/11),
Landau-Kleffner syndrome (1/11), tuberous
sclerosis (1/11), and unknown (2/11). Patients were taking an average of
2.3 anti-epileptic drugs (AEDs).
Activation of the device took place in the operating room at the time of
implantation (7/11), the next day (2/11), or
two weeks post-implantation (2/11). Current was increased to a maximum
of 2.5 mA in 36% of patients or as
tolerated in the others. 64% of the patients had their generators
eventually set at rapid cycling 7 sec on/12 sec off.
45% of the patients also had simultaneous dosage modification of their
AEDs.
RESULTS: 18% of patients became seizure free, while 18% had a >90%
seizure reduction; 18% had a > 75% but <
90% seizure reduction; 28% had seizure reduction > 25% but <50%, while
18% of patients had <25% decline in
seizure frequency. 100% of the patients had a >50% improvement in
quality of life and alerting response. The
magnet was useful in aborting or reducing the intensity or clustering of
seizures in 45% of patients. Adverse events
in our population included staphylococcal infection at the site of
implant in one patient necessitating removal of the
device (9%), hoarseness (18%), cough (27%), hiccups (9%), screaming
spells (9%), and aggressive behavior
responsive to risperidol (9%).
CONCLUSIONS: Using VNS, we were able to reduce seizure frequency in 80%
of patients and improve quality of
life in 100% of patients within six months of implantation. Rapid
cycling at higher intensities was well tolerated.
Possible reasons for good outcome in our series may be higher VNS
parameters including maximum rapid cycling
time, simultaneous modification of AEDs, and a high proportion of
patients with Lennox-Gestaut syndrome. VNS
is, thus, a safe and effective method of reducing seizures in patients <
18 years old with intractable seizures.


Growth and Development at 5 Years of Age of Infants Born Between 22 and 25 Weeks of
Gestation

Genevieve Piuze, Claudette L. Bardin, Apostolos Papageorgiou
Neonatology, McGill University, SMBD Jewish
General Hospital, Montreal, QC, Canada

OBJECTIVE: Outcome at 5 years of age of infants born between 22 and 25
weeks of gestation.
DESIGN/METHODS: Longitudinal follow-up of infants born between 22 and 25
weeks of gestation previously
reported at two years of age. Of the 58 children, 15 were lost to the
follow-up clinic. Their perinatal data, neonatal
outcome and evolution up to 2 years of age were similar to those of the
study cohort (43 children).
RESULTS: The percentage of infants with growth parameters <5th tile at 3
months, 2 years and 5 years varied as
follows: WT = 30, 13, 21; HT = 68, 14, 21; HC = 11, 38, 26. One child
has quadriplegia and 4 have spastic
diplegia. Fourteen (32%) children have visual impairment, 3 of them are
considered legally blind. Three need
hearing aids and 16 (37%) experience speech delay. The number of
children requiring hospitalization after the
second year of life decreased significantly, from 57 during the first
two years to 12% between 2 and 5 years.
Twenty three children have shown a normal psychological development. One
child was not testable and 19 (45%)
experienced difficulties on psychological evaluation. Ten were diagnosed
with borderline to mild intellectual deficit
and 4 with severe deficit. Features of attention deficit disorder were
detected in 14 children and autism in 3.
Furthermore, 16 children had difficulties in fine motor skills and
coordination. A higher incidence of deficits was
observed in children born SGA (67% vs 37% for those born AGA).
CONCLUSIONS: Severe global developmental delay changed marginally
between 2 years and 5 years of age, from
16 to 19%. Based on psychological evaluation, we anticipate that around
50% of the cohort may experience school
difficulties. Finally, children born SGA are at substantially higher
risk for complications.


Medical Impairments, Functional Limitations, and Disability Status in 41,300 School Age
Children

Michael E. Msall, Roger C. Avery, Dennis P. Hogan, Julie C. Lima,
Michelle L. Rogers, Michelle R. Tremont

OBJECTIVE: To examine the relationship between medical impairments,
functional limitations in essential activities
and disability status in school age children.
BACKGROUND: The National Center for Medical Rehabilitation Research
(NCMRR) Model of Disability provides
a framework for analyzing the complexity of disability. Categories in
the NCMRR model include impairment,
functional limitations, disability, and societal limitations. The 1994
and 1995 National Health Interview Survey
Disability Interview Supplement (NHIS-D) is a representative national
sample.
DESIGN/METHODS: ICD-9 impairment codes were categorized as life
threatening (n=167), chronic (n=269),
medical (n=263), episodic (n=820), injury (n=98), asthma (n=1186),
neurosensory (n=1,094), genetic (n=245),
mental retardation/autism (n=465), attention deficit/learning disorder
(AD/LD)(n=792), and behavior disorders
(n=161). Categories from the Pediatric Functional Independence Measure
(WeeFIM) were used to categorize
functional limitations in self-care/continency, mobility, communication,
and learning skills. Activity limitations
included impact on play and school. Disability status was classified as
none, minor (mild limitations in one area),
major (moderate limitations in one area), and multiple (moderate/severe
limitations in 2 or more areas).
RESULTS: Of the 41,300 children, functional limitations were distributed
as follows: mobility 12/1000, self care
9/1000, communication 54/1000, and learning 104/1000. Disability status
by most severe condition included 88%
none, 4.1%minor, 5.9% major, and 1.9% multiple. Neurosensory impairments
accounted for 38% of mobility,
33% of self-care, 33% of communicative and 15.4% of learning functional
limitations of severe degree. Mental
retardation/autism accounted for 15.6% of severe and 7.6% of moderate
communicative limiations. AD/LD
accounted for 24% of severe, and 15.9% of moderate learning limitations.
Severe activity limitations occurred in
3.2%. Asthma accounted for 46% and neurosensory impairments accounted
for 15% of school activity limitations.
CONCLUSIONS: Health impairments, developmental disabilities, and
functional limitations status in essential
activities are required to assess disability in school age children.


Analysis of Formal Language Testing Following an Open-Label Trial of Secretin in
Children with Autism

J. R. Lightdale, C. Hayer, A. Duer, C. Lind-White, B. Siegel, G. R.
Elliott, M. B. Heyman Gastroenterology and
Nutrition, Children's Hospital, Boston, MA; Pediatrics, University of
California; Psychiatry, University of
California, San Francisco, CA

OBJECTIVE: To determine the reproducibility of reported effects of
intravenous secretin on the language skills of
autistic children in a prospective clinical trial using objective and
subjective measures.
BACKGROUND: Autism is a severe developmental syndrome involving deficits
in communication skills, with no
known etiology or treatment. One recent retrospective report describes 3
autistic children (ages 3, 4 & 5) who
demonstrated improved language skills over a 5-week period following
endoscopy and pancreatic stimulation with
IV secretin.
DESIGN/METHODS: We performed a prospective open-label clinical trial and
conducted formal language testing
both before and repeatedly after a secretin infusion. Parents were also
surveyed about their impressions of the
effects of secretin. Following administration of the Preschool Language
Scale-3 (PLS-3), 20 (18 male) autistic
children were admitted to the Clinical Research Center at UCSF.
Inclusion criteria for our study were based on
profiles of those described in the published report, and included age
(3-6 years), confirmed diagnosis of autism, and
reported gastrointestinal symptoms. A 3 CU/Kg dose of secretin
(Secretin-Ferring) was administered IV. (EGD was
not performed.) Subjects returned for follow-up and repeated testing
with the PLS-3 at 1, 2, 3 and 5 weeks
post-infusion.
RESULTS: Single sample, within-subjects, repeated measures ANOVA of
subscale and total scores of the PLS-3
revealed no significant differences in either receptive or expressive
language over the course of five test
administrations, including the administration prior to the infusion
(p.>05). However, only 17% (3/18) parents
reported no change in their child's language skills. 83% (15/18)parents
reported moderate to significant
improvement following the secretin infusion.
CONCLUSIONS: Our findings do not support a previous report of
improvement in language skills of autistic
children following secretin infusion. Unlike the prior retrospective
case-series, our clinical trial utilized formal
language testing both before and after administration of secretin.
Nevertheless, parental observations differ
significantly from our test results, as parents both in the prior report
and in our study describe improvement in
language. Clearly, carefully conducted prospective randomized
placebo-controlled trials are necessary to fully
elucidate any therapeutic use for secretin in children with autism.
Supported in part by NIH Grants M01RR01271 and 2-T32-HD07397.


Infant Exposure to Thimerosal-containing Vaccines and Risk for Subsequent Neurologic
and Renal Disease

Robert L. Davis, Thomas Verstraeten, David Gu, Frank DeStefano, Robert
S. Thompson, Robert T. Chen, Vaccine
Safety Datalink Team Immunization Studies Program, Group Health
Cooperative, Seattle, WA; National
Immunization Program, Centers for Disease Control, Atlanta, GA

OBJECTIVE: We assessed the risk for neurologic and renal disease
associated with past exposure to
thimerosal-containing vaccines in the Vaccine Safety Datalink (VSD).
BACKGROUND: Hepatitis B vaccine recommendations were recently revised
due to safety concerns over the
(ethylmercury-containing) preservative thimerosal.
DESIGN/METHODS: The VSD links automated immunizations data with medical
diagnoses on over 400,000
children in four health maintenance organizations. We categorized
cumulative ethylmercury exposure levels
according to Environmental Protection Agency (EPA) safety limit for
methylmercury at one and three months of life.
Using proportional hazard models, we assessed the subsequent risk for
degenerative and developmental neurologic
disorders, and renal disorders diagnosed before 6 years of age. We also
looked at diagnostic codes specific for
autism, attention deficit disorder (ADD) and developmental delay.
RESULTS: Over half of all children exceeded the EPA limit at 1 and 3
months of age. There were 286 children with
degenerative disorders, 3702 with developmental disorders, and 310 with
renal disease. In addition, there were 153
children with autism, 346 with ADD, and 2568 with developmental delay.
Among children with ethylmercury
exposure exceeding EPA limits at one or three months of age, there were
no increased risks for degenerative,
developmental or renal disorders, nor were risks elevated for the
development of autism, attention deficit disorder or
developmental delay.
CONCLUSIONS: Among children followed up to 6 years of age, ethylmercury
exposure at one and three months of
age is not associated with adverse neurodevelopmental or renal outcomes.


Screening for Inborn Errors of Purine Metabolism in Children with Autistic Spectrum
Disorders

R. G. Voigt, D. Babovic-Vuksanovic, J. A. Gruetzmacher, D. Matern, P.
Rinaldo, P. S. Karnes Departments of
Pediatrics; Medical Genetics; Laboratory Medicine, Mayo Clinic,
Rochester, MN

OBJECTIVE: To review results of screening for inborn errors of purine
metabolism in children with autistic
spectrum disorders.
BACKGROUND: Estimates of the proportion of all cases of autism
associated with or attributable to defined
medical disorders range from 10 to 30%, with higher rates among those
with severe mental retardation. Although
inborn errors of metabolism, such as phenylketonuria, have been
associated with autism, metabolic screening is not
routinely performed in these children. A deficiency of adenylosuccinate
lyase, an enzyme essential for de novo
purine biosynthesis, has been associated with severe mental retardation,
profound hypotonia, and autistic features.
How often adenylosuccinate lyase deficiency (ASLD) is associated with
milder autistic phenotypes is uncertain.
DESIGN/METHODS: Retrospective chart review of patients diagnosed with
autistic spectrum disorders by a single
developmental pediatrician over a recent 18 month period.
RESULTS: 28 of 31 patients diagnosed with autistic spectrum disorders
consented to participate as subjects in this
record review. Urine purine and pyrimidine screening was ordered on 22
(79%) and completed on 18 subjects
(64%). Two subjects had abnormal screens. In both, two compounds similar
in retention time and UV absorption to
succinyl-adenosine and succinylaminoimidazole carboxamide ribotide
(SAICAR) were detected by HPLC,
consistent with a possible diagnosis of ASLD. The first subject was a 50
month old male with mild hypotonia, mild
mental retardation, and a score on the Childhood Autism Rating Scale
(CARS) of 34, placing him in the mildly to
moderately autistic range. The second subject was a 70 month old female
with mild hypotonia, moderate mental
retardation, and a score on the CARS of 36, placing her in the mildly to
moderately autistic range. The residual
adenylosuccinate lyase activity of the male subject was 25% of control
in skin fibroblasts; molecular characterization
is in progress.
CONCLUSIONS: Our review identified two cases of ASLD presenting with
milder phenotypes, including mild to
moderate mental retardation, mild hypotonia, and mild to moderate
autistic symptoms. As at least 7% of children in
our cohort had abnormal results, urine screening tests for inborn errors
of purine metabolism should be considered
in children presenting with milder autistic phenotypes.


Autistic Features in Preschool Children with Significant Cognitive Impairment
S. Vig, E. Jedrysek CERC/Pediatrics, Rose F. Kennedy Ctr, Albert
Einstein College of Medicine, Bronx, NY

OBJECTIVE: The purpose of this study was to explore autistic features of
preschool children with significant
cognitive impairment.
BACKGROUND: Differentiating autism and mental retardation in young
children who have autistic features as well
as significant degrees of cognitive impairment is a challenge for both
diagnosis and subsequent intervention
planning. The current study investigated autistic features and their
relevance to the differentiation of autism and
mental retardation in young children with severe to profound cognitive
impairment.
DESIGN/METHODS: The study was based on retrospective chart review for 65
young children, aged 2 to 6 years,
who were seen for developmental evaluation and found to function
cognitively within the ranges of severe to
profound mental retardation. The sample included all children under age
6 seen during a 10-year period who scored
four or more standard deviations below intelligence test means and did
not have physical or sensory impairments.
All of the children were ambulatory and were fully testable by
standardized psychological tests. Prior to initiation of
the study, a multidisciplinary team of clinicians, utilizing multiple
sources of information, had formulated primary
diagnoses of autism for 33 of the children and mental retardation for 32
children. Mean chronological ages of the
autism and mental retardation groups were 44 and 43 months, and mean
mental ages were 14 and 15 months,
respectively. Psychological reports of the 65 children were
retrospectively reviewed for behavioral descriptions and
mention of autistic features by independent raters blind to primary
diagnoses.
RESULTS: Results of the review revealed differences in autistic features
for the two diagnostic groups. Frequencies
of features were higher for children in the autism group. Types of
features also differentiated the diagnostic groups.
Prevalence differed between groups for eight specific features:
relatedness, imitation, hand flapping, repetitive
movement of objects, eye contact, sniffing objects, self-stimulatory
vocalization, and self absorption. Some autistic
features were found in both diagnostic groups; other features were
rarely observed in either group.
CONCLUSIONS: Deficits in socialization were thought to be particularly
relevant to the autistic features observed in
children functioning at very early developmental levels. Results of the
investigation suggested the need to consider
typical and atypical behaviors from a developmental perspective in
prioritizing their diagnostic significance for
young children.


The Use of Secretin to Treat Autism: a Pilot Study
Bruce Roseman, Elaine Schneider, Daniel Crimmins, Howard Bostwick, Paul
Visintainer, Stella Dong, Pasquale
Accardo Neurology, New York Medical College, Valhalla, NY; Pediatrics,
New York Medical College, Valhalla,
NY; Public Health, New York Medical College, Valhalla, NY

OBJECTIVE: To investigate the impact of a secretin infusion on the
neurobehavioral profile of children with
autism/PDD.
BACKGROUND: In 1999 Horvath et al reported three anecdotal cases of
significant functional improvement in
children with autism who were administered the secretin test as part of
a gastrointestinal assessment. Since that time
secretin has been used to treat children with autism without further
evidence to support its use.
DESIGN/METHODS: Ten children with autism/PDD with a mean age of 5.6
years [8 boys] were entered into a
double-blind crossover study of the impact of a secretin infusion on
their neurobehavioral profile over a 12 week
period. Weekly behavioral rating scales as well as formal testing and
videotapes [scored for pragmatic language and
MLU] were used to monitor change.
RESULTS: The therapist who performed the blinded evaluations was able to
correctly identify the secretin infusion
in 90% of cases, while parents were accurate only 50% of the time. Group
analyses along a number of dimensions
(i.e., Childhood Autism Rating Scales, parent ratings of behavior)
showed no significant differences between the
secretin and placebo conditions, and both were significantly different
from baseline. Thus, drug effects could not be
determined against the background of the placebo effect. Further
analyses are being conducted on videotape samples
of children's language and behavior to allow for a more fine-grained
assessment.
CONCLUSIONS: These results will be discussed in light of three issues:
1) placebo effects in a clinical context of
subject heterogeneity, 2) parental beliefs that individual children
clearly benefited (with some experimental support
for individual children), and 3) measurement issues for clinical effects
that may vary in their degree of expression in
different children. If there is a subgroup of children with autism who
do exhibit behavioral improvement with
secretin, the degree of their response does not appear to be strong
enough to warrant this invasive treatment.