This is the first report of the behavioral outcomes of extremely low birth weight (ELBW) children at school-age born in the United States since 1990. Results reveal that ELBW children continue to have significantly more behavioral problems than normal birth weight (NBW) children as evidenced by a higher number of symptoms pertaining to the attention, hyperactive, and combined subtypes of attention-deficit hyperactivity disorder (ADHD), to General Anxiety Disorder and to the Autistic and Asperger’s disorders. ELBW children also had twice as many symptom counts meeting DSM-IV criteria than their NBW counterparts, particularly for the inattentive and combined types of ADHD and specific phobias.
Our findings of an increase in behavioral disorders among ELBW children relative to NBW children are similar to those reported for other preterm populations born since 1990 in Australia, Sweden, and the United Kingdom.4–6
Follow-up of children born before 1990s revealed that the most common problems pertained to weaknesses in attention and hyperactivity,26–37
anxiety and depression,27,29,30,35,36,38,39
and poor social skills.28,30–32,35,40,41
With the exception of an increase in symptomatology suggestive of Autistic and Asperger’s disorders, the type of behavioral problems reported for preterm children born in the 1990s are thus similar to those of children born in the 1980s. However, geographic and cultural differences between study cohorts,31
as well as variation in the behavioral questionnaires used, make it difficult to assess whether the prevalence of the various problems has changed. Of note also is the fact that with the exception of 2 studies, diagnostic psychiatric evaluations have not been performed.29,37
Inattentive ADHD was the most common type of ADHD seen in our ELBW population. Furthermore fewer of our ELBW than NBW children presented with comorbid diagnoses of ADHD and conduct/oppositional disorders. These findings confirm those of Szatmari et al27,30,34
suggesting that the type of ADHD typically reported for preterm children pertains to attention difficulties rather than hyperactivity per se with no increase in comorbid conduct disorders. It has been suggested that the fewer comorbid disruptive behavioral disorders seen in pre-term children suggest a “purer” or more biological determined type of ADHD.34,42,43
We did not, however, find a relationship between cerebral ultrasound abnormalities or other neonatal risk factors and ADHD. The literature has been mixed in this regard with some reporting an association between ADHD and cerebral ultrasound31,37,44
or magnetic resonance imaging abnormality45
and others no relation to neonatal risk factors.27,30,32
The increased incidence of Autistic Spectrum Disorders (ASD), otherwise termed pervasive developmental disorder (PDD), reported nationally since the 1990s is considered to be mainly due to increased awareness and improved and earlier ascertainment following the introduction of ICD-10 and DSM-IV diagnostic criteria for ASD in the early 1990s.46,47
Recent estimates by the Center for Disease Control note that 6.6 of 1000 children who were 8 years old in 2000 had ASD.48
Our finding of one child or 0.6% of our NBW population so affected is in agreement with the Center for Disease Control estimates.
Studies of preterm children at school age have previously reported that they have poor social skills. Preterm children tend to be socially isolated, to play by themselves, are less likely to initiate social behaviors and have poorly developed adaptive skills.35,40,49
The majority of previous studies administered questionnaires that did not include symptoms of the Autistic or Asperger’s disorder. This, rather than a current increase in prevalence, could possibly explain the paucity of previous reports pertaining to these conditions. In addition to Johnson et al.’s study,8
2 school-age studies have previously screened for ASD, both in Norway. Indredavik et al29,50
reported a significantly higher mean sum score on the Autism Spectrum Screening Questionnaire among adolescents with birth weights <1.5 kg compared with controls. Four of 56 children were above the 75th criteria for Asperger’s with 1 (2%) at the diagnostic level.29
All 4 children had white matter reduction and ventricular dilatation on magnetic resonance imaging.45
Elgen et al30,51
administered the Asperger’s Syndrome Diagnostic Interview to parents of 130 11-year-old <2 kg birth weight children and found 1 child (1%) to have Asperger’s compared with none of the controls. In addition, Moster et al52
recently reported on Norwegian national outcomes for adults born 1967 to 1983 and found a higher risk for disability payments for autism at less than 30 weeks gestation compared with term born adults. None of the studies reported to date have administered confirmatory diagnostic tests for Autism. Older studies of preterm children, many involving samples with high rates of severe mental retardation and cerebral palsy, noted a relationship between autism and blindness due to retinopathy of prematurity,53
and infantile hydrocephalus.54
Ours is the first detailed clinical description of school-age preterm children who present with symptoms suggestive of the Autistic or Asperger’s disorders. The only neonatal risk factor that we found to be significantly associated with both Autistic Symptom Severity Scores and Autistic disorder based on DSM-IV Symptom Counts criteria was bronchopulmonary dysplasia defined as oxygen dependence at 36 weeks corrected age.
Epidemiologic studies have previously suggested an association between autism and preterm birth and/or low birth weight (<2.5 kg).55–58
Additional factors identified have included hypertension of pregnancy, intra-uterine bleeding, fetal distress, cesarean section, Apgar score of <7, oxygen requirement at birth, small size for gestational age, and congenital malformations.55,56,59,60
ELBW children, in addition to being born preterm, experience many of these pregnancy, delivery, and neonatal risk factors which may be associated with hypoxia. The association of autism with perinatal hypoxia is also consistent with its reported association with neonatal encephalopathy61
and our finding of higher rates of chronic lung disease which usually results from severe respiratory distress syndrome and may be associated with recurrent episodes of oxygen desaturation. Recent reports of genetic abnormalities in children with Autism62
have led to the hypothesis that it may result from a genetic predisposition to the condition, together with obstetric and perinatal complications which may adversely affect perinatal development.63
Strengths of this study include our high follow-up return rates of 90%, the detailed description of children with symptoms suggestive of Autistic and Asperger’s disorders and the use of the Child Symptom Inventory-4 which allows for Symptom Severity Scores that may be more sensitive to deviations in behavior than cutoff scores used to provide diagnoses. Weaknesses of the study include the lack of a clinical psychiatric assessment, which is needed to make definitive diagnoses. Our results are based on parent report only. The questions in the Child Symptom Inventory-4 provide only a limited screen for Autistic and Asperger’s disorders and we lack a formal structured diagnostic interview such as the Autism Diagnostic Interview-Revised.64
Magnetic resonance imaging studies during the neonatal period or later at school age may have provided a more sensitive measure of brain injury than neonatal cerebral ultrasound.65
Although the sensitivity scores for the Autistic and Asperger’s disorders among the ELBW children were significantly higher than those of NBW children, we may have underestimated the DSM-IV criteria rates of these disorders. The parent Child Symptom Inventory has however been shown to have a specificity of 0.99 for Autism and 3 of 4 of our children with Autism had previously been identified with this condition.
In conclusion, ELBW children born in the 1990s continue to suffer from higher rates of ADHD and anxiety disorders than NBW children. Furthermore our results, together with those reported in the literature, suggest an increase in symptoms suggestive of PDD/ASD in ELBW children which was not previously recognized. Future long-term studies of preterm children will need to include larger populations of children and to administer formal diagnostic measures of PDD/ASD at school age to confirm the diagnosis. Structural and functional magnetic resonance imaging studies of ELBW children may also in the future help identify specific abnormalities associated with ADHD and/or ASD/PDD.