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Background: Children with developmental delay (DD) have a
variety of problems in developmental functions. The purposes
of this study were to analyze the underlying diseases and
risk factors in children with different functional delays.
Methods: We collected data on 1048 children who underwent
assessments of developmental function, related diseases, and
risk factors. All children were classified into 6 functional
delay groups: cognitive, speech, motor, pervasive, global,
and non-specific DDs. Differences in related diseases and
risk factors of the 6 functional delay groups were determined.
Results: Most children had global (51.2%), speech (21.9%),
and motor (13.9%) delays. Approximately 62.8% of children
were associated with biological factors (19% with genetic
defects or congenital anomalies, 16.5% with central nervous
system lesions, 13.9% with prematurity/low birth body weight,
and 13.4% with neonatal insult). We could not identify the
risk factors in 36.6% of the children. Most children with
motor delay had brain/neuromuscular diseases and were associated
with risks of prematurity or low birth body weight; while
most children with global delay had brain neuromuscular diseases
or psychological/mental disorders and were associated with
risks of genetic defects or congenital anomalies.
Conclusion: Our findings suggest that there are heterogeneous
risk factors and related diseases in children with different
kinds of functional delay.
(Chang Gung Med J 2002;25:743-50)
Key words: developmental delay, developmental function, risk
factor, related disease.
Developmental delay (DD) is simply a chief complaint referring
to a condition whereby infants or children do not achieve
developmental milestones in 1 or more major streams including
motor, perceptual, speech, cognition, and behavior.(1) Children
with DD have a variety of developmental dysfunctions; thus,
different related diseases may exist. It should be stressed
that identifying the underlying diseases as early as possible
can provide these children with appropriate service and ongoing
surveillance.(2) But few studies have determined the related
diseases across the spectrum of early childhood DD subtypes.(3-5)
Early intervention indicates early detection, diagnosis, and
rehabilitation training for children with DD. Early intervention
not only expands children's developmental capacity but also
reduces the social and economic costs and impacts. Thus, it
is important to survey the risk factors to be able to identify
children who are suspected of having DD at an early stage
and subsequently monitor their developmental function. It
would be advantageous if it could be determined at an early
time whether children suspected of having DD really do have
developmental problems and to clarify the range of associated
deficits; then clinicians could offer a complete service system
for early intervention.(6) A series of steps are included:
a thorough evaluation such as medical assessment and psychological
testing, a rehabilitation program with physical, occupational,
and speech therapy for positioning, handling, feeding, language,
and cognitive stimulation, and an educational plan to instruct
families in proper functioning.(7) Tirosh et al. suggested
that children with fine motor deficits possessed risk factors
associated with early antepartum, possibly of genetic origins,
while there were few clinical studies to follow up the developmental
functions for children with different risk factors.(8-11)
The purposes of this study were to investigate the underlying
diseases according to the developmental function and early
detection of children with risk factors. We attempted to classify
children with DD into functional delay groups based on their
developmental dysfunction. Then, we analyzed the related underlying
diseases and risk factors in children of different functional
delay groups.
METHODS
From October 1998 to September 2000, infants or young children
with DD, who were either referred from the Pediatric Department
or sent to our clinics for first aid, were recruited into
this study. In total, data on 1048 patients were collected
in this study. The children underwent an assessment of functional
development, related diseases, and risk factors. To assess
the functional development, we used the Chinese Children Developmental
Inventory (CCDI) to assess 8 functional domains: gross motor,
fine motor, expressive language, concept comprehension, social
comprehension, self help, personal social, and general development.(12)
Based on the clinical assessment combined with the results
of the CCDI and other evaluation tests including the Peabody
Developmental Motor Scale, Peabody Picture Vocabulary Test,
Gross Motor Functional Measure, Wechsler Preschool and Primary
Scale of Intelligence, etc, all children were classified into
6 functional delay groups: cognitive, speech, motor, pervasive,
global, and non-specific DD. "Significant" was defined
as 2 or more standard deviations below the mean of normal
references of developmental screening or assessment tests.
Cognition involves the high-integrated processes of attention,
perception, memory, and functional task performance. Neuropsychological
and intelligence tests are helpful in identifying children
with cognitive DD. Speech DD indicates a deficit in articulation
function, verbal expression, comprehension, or mixtures of
the above conditions. Motor DD was defined as a delay in gross
motor or fine motor skills with presentation of age-appropriate
performances in other developmental domains. Children with
core features of observed qualitative deficits in social skills,
communication, and repetitive/restrictive patterns of behavior
were placed in the pervasive DD group, and those children
with visual, hearing, or sensory integration (SI) dysfunction
were placed in the non-specific DD group. SI dysfunction results
from a disturbance in the integrating process of the subcortical
multisensory system. Children whose developmental quotients
were less than 80% in 2 or more domains were placed in the
global DD group.
To determine the related diseases, children with DD received
detailed clinical and laboratory investigations across specialized
departments such as neurological (echography, magnetic resonance
imaging, computed tomography, electroencephalography, brain
auditory evoked potential, etc.), genetic (chromosome, DNA,
etc.), metabolic, hearing, or visual studies depending on
individual indications. Based on the related diseases ultimately
determined by various experts (neurologists, psychiatrists,
geneticist, otologists, ophthalmologists, etc), the children
with DD were classified into 5 major categories: brain/neuromuscular,
psychological/mental, genetic or congenital, visual, hearing,
and other diseases. Children with brain lesions (cerebral
palsy (CP), hypoxic encephalopathy, microcephaly, central
nervous system (CNS) infection, traumatic brain injury, epilepsy,
hydrocephalus, tumor, etc.), and neuromuscular diseases (motor
neuron disease, peripheral neuropathy, myopathy, etc.) were
categorized as having brain/neuromuscular diseases. Children
with mental retardation (MR), speech delay, articulation disorder,
attention-deficit/hyperactive disorder, SI dysfunction, autism,
and non-specific psychomotor retardation were categorized
as having psychological/mental disorders. Children with chromosomal
or genetic abnormalities, congenital syndromes, metabolic
or endocrine diseases, and inborn-error metabolic diseases
were categorized as having genetic/congenital diseases. Children
with other systemic diseases, such as orthopedic, cardiovascular,
digestive, or urinary pathologies, were categorized as having
other diseases.
To survey the related risk factors in children with DD, all
children underwent detailed birth history taking, chart review,
and prospective clinical investigations. The risk factors
contributing to DD were categorized into 6 factors: prematurity
or low birth body weight (BBW), genetic defects or congenital
anomalies, neonatal insult, CNS lesions caused by disease
or trauma, environmentally related factors, and unknown causes.
A gestational age (GA) below 32 weeks was defined as prematurity,
and a BBW of < 2000 g was defined as low BBW. Those who
had chromosome or genetic abnormalities, craniofacial anomalies,
spinal bifida, congenital heart disease, and limb deformities/deficiencies
were categorized into the genetic defect or congenital anomaly
group. Neonatal insults included the related factors which
had occurred before, during, or after pregnancy, such as low
Apgar scores (a score of < 5 at 5 min), infantile spasms,
and severe hyperbilirubinemia post-exchange transfusion. CNS
lesions consisted of hydrocephalus, intracranial hemorrhage,
hypoxic encephalopathy, infection, and seizure disorders.
However, we only included parent's mental and psychological
disorders as categorized as environmentally related factors
in this study. Risk factors not clearly determined were categorized
as unknown factors. In addition, the age, body weight (BW),
body height (BH), gender, GA, BBW, and delivery modes for
the pregnancy were also recorded.
Differences in the continuous data (age, BH, BW, BBW, and
GA) among the 6 functional delay groups (cognitive, speech,
motor, pervasive, global, and non-specific DD) were compared
using ANOVA with Tukey's HSD multiple comparison. Differences
in the categorical data (gender, delivery mode, risk factors,
and related diseases) among the 6 functional delay groups
were determined using Chi-square test. A value of p<0.05
was considered statistically significant.
RESULTS
Based on the geographic distribution, approximately 87% of
children came from the Taoyuan area (35.7%) and Taipei area
(Taipei County: 29.9%, Taipei City: 21%). The other 13% of
children came from other areas (Hsinchu area: 7.4%, Miaoli
area: 2.6%, Taichung: 2.1%, and eastern Taiwan: 1.3% including
the Keelung, Ilan, and Taitung areas).
According to the assessment of functional development, most
children had global (51.2%), speech (21.9%), and motor (13.9%)
delays (Fig. 1). The average age of all children with DD at
the first visit was 37.8 months, with males dominant (60%
vs. 40% (Table 1). The age range of children with speech,
pervasive, and non-specific DDs was 45-57 months, while that
of children with cognitive, motor, and global delay was approximately
32-33 months. Male dominance (71%-83%) was observed in children
with speech, pervasive, and non-specific DDs, but a female
dominance (62%) was observed in those with cognitive DD. Tracing
the birth history, the average GA of all subjects was 37 weeks,
and the BBW was 2834 g. However, the average GA and BBW were
lower in children with motor and global delays (motor: 35
weeks, 2546 g; global: 37 weeks, 2701 g). There were no significant
differences in the delivery modes (natural spontaneous delivery:
55%, cesarean section: 45%) (Table 1).
When risk factors were analyzed, it was found 62.8% of all
children had associated biological factors (20% with genetic
defects or congenital anomalies, 16.3% with CNS lesions, 14.2%
with prematurity or low BBW, and 13.5% with neonatal insults),
and 0.8% of all children were associated with environmental
factors (Table 2). However, we could not identify the related
risk factors in 35.2% of the children, especially in 48%-72%
of children with speech, pervasive, and non-specific DDs.
Children with cognitive and global delays were associated
with 28%-48% of risks of genetic defects or congenital anomalies,
while those with motor delay were associated with 32.4% of
risks of prematurity or low BBW (Table 2).
Based on the related diseases in the 6 major categories, our
results show that 53.8% of all cases were diagnosed with psychological/mental
disorders, 34.4% were diagnosed with brain/neuromuscular diseases,
and 7.7% were diagnosed with genetic diseases (Table 3). Approximately
83% of children with motor delay were associated with brain/neuromuscular
diseases, while 80% of children with global delay were associated
with brain/neuromuscular or psychological/mental disorders
(Table 3).
DISCUSSION
Some studies have suggested that the categories of cerebral
dysgenesis, hypoxic-ischemic encephalopathy (HIE), antenatal
toxin exposure, and chromosomal disorders provided 77% of
the diagnoses of children with global DD; 69% of children
with motor DD had HIE, cerebral dysgenesis, or benign congenital
hypotonia.(3-5) We found that most children (83%) with motor
delay were associated with brain/neuromuscular diseases, while
most children (80%) with global delay were associated with
brain/neuromuscular diseases or psychological/mental disorders.
These findings could provide clinicians with clues to investigate
the related underlying diseases according to the developmental
functions of children. For example, when approaching a child
presenting delays in many functional domains, brain or psychological/mental
disorders should be considered and evaluated.
We found that children with motor delay were associated with
32.4% of the risks of prematurity or low BBW, even if prematurity
or low BBW contributed only 14.2% of the risk to all children
with DD. Although prematurity or low BBW is a commonly mentioned
risk factor related to DD, the previous literature indicated
that it by itself is a relatively weak factor. Approximately
80%-95% of preterm infants are free of severe disabilities.(13-17)
The causes and complications of prematurity have been found
to be more predictive of developmental outcome than only prematurity.(18)
Lindahl et al.(9) found that a small GA, low BBW, and signs
of cerebral depression all increased the risk of poor motor
performance by about 2-3 fold. Prematurity is well known as
a strong risk factor for CP with spastic diplegia.(19,20)
Thus, clinicians should closely monitor functional outcomes,
especially the motor domain for children with a history of
prematurity and low BBW.
In this study, children with cognitive and global delays were
associated with 28%-43% of the risks of genetic defects or
congenital anomalies, although all children with DD were only
associated with 19% of those risks. Previous studies also
pointed out that infants with major congenital anomalies had
an increased incidence of developmental problems whether there
were any associated chromosomal disorders or dysmorphic syndrome.(21,22)
Thus, further surveys such as chromosomal, genetic, and metabolic
studies are indicated with this clinical approach for infants
or children with DD, especially those with cognitive and global
delays.
We found the neonatal insults and CNS lesions contributed
about 30% of the risk factors in all children with DD. Thus,
we should longitudinally follow-up developmental outcomes
of children with a history of pre-, peri-, and postnatal insults
and investigate CNS dysfunction. Prenatal maternal factors
such as drug abuse during pregnancy have been studied and
were proven to be associated with intrauterine growth retardation,
neonatal withdrawal syndrome, subtle neurological abnormalities,
fetal distress, congenital anomalies, and developmental sequelae.(23-25)
It is also well known that perinatal asphyxia results in marked
symptoms like seizures, coma, lethargy, or muscle tone abnormalities.
In studies of severely asphyxiated full-term newborns, 30%-50%
died; of those who survived, 12%-30% developed CP or MR.(26-28)
Kernicterus appeared to be a low risk factor for DD; our data
showed only a 0.5% incidence, but it is still suggested that
monitoring be carried out on the developmental outcome of
infants whose bilirubin rises to 20-25 or those who have received
an exchange transfusion.(7) The data imply that CNS lesions
like diffuse encephalomalacia, intraventricular hemorrhage,
and intraparenchymal hemorrhage all carry a high risk (70%-90%)
of a major handicap in full-term infants.(29) Sepsis complicated
with meningitis increased the risk of DD including hearing
impairment and congenital infections resulting in CNS injury
and long-term developmental sequelae.(30)
We found a relatively low incidence of environment factors
in our children, although cognitive delay was associated with
14.3% of environmental factors. While previous studies conducted
before 1989 reported that cognitive and speech/language disorders
were prevalent among children of parents with a low educational
level or low social class,(9-11,31) this discrepancy may possibly
have been caused by the patient classification, definitions
of environment factors, Chinese culture, risk factor categorization,
and genetic technology improvements among studies. In this
study, all children with pervasive delays were autistic, and
most children with speech delays had articulation disorders.
Environmental factors only included the parental MR or psychological
disorders and child abuse, and did not include low educational
level or low social class. In Chinese culture, people usually
do not mention any family history of MR, psychological disorders,
or child abuse. Thus, it is possible that the environmental
factors were underestimated in this study. Only 1 major risk
factor was selected for statistical analysis, and there may
have been several risk factors coexisting simultaneously.
The risk factors were categorized into biological factors
such as genetic defects, congenital anomalies, neonatal insults,
and CNS lesions if combined with environmental factors. Environment
factors categorized before 1990 might have been re-categorized
into genetic defects or congenital anomalies due to rapid
improvements in molecular biology and genetic technology in
recent years. Thus, the determined risk of genetic defects
or congenital anomalies was relatively increased, and that
of environmental factor was relatively decreased in this study.
This study shows there are heterogeneous risk factors and
related diseases in children with different functional delays.
These findings provide clues from which to investigate underlying
diseases according to developmental function and a comprehensive
assessment and to follow up the specific functional outcomes
in children with different risk factors. It is worthwhile
and beneficial to identify and provide therapeutic intervention
as early as possible to decrease disabilities and family stress
in children with DD. Further efforts should stress the development
of a referral organization which integrate aspects of medical,
educational, and social affairs units.
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