Neonatal Morbidity and Risk of Autism Spectrum Disorder (ASD)

Background: While there is substantial evidence for a genetic influence upon the risk of Autism Spectrum Disorder (ASD), including infants diagnosed with Childhood Autism, Pervasive Developmental Disorder (PDD),PDD Not Otherwise Specified (NOS), and Asperger’s Syndrome, recent research also demonstrates the association between perinatal and prenatal factors and ASD. It has been suggested that those infants most impacted by adverse prenatal and perinatal events exhibit neonatal morbidity. Thus, the aim of this study is to investigate the hypothesis that neonatal disorders mediate the association between perinatal and prenatal factors and ASD. 

Objectives: The primary objective of this study is to systematically examine the relation between each neonatal disorder (as specified in the International Classification of Diseases (ICD)-10), and risk of ASD, as well as each ASD subtype, after accounting for factors strongly associated with prenatal and perinatal adversity, such as low birth weight, and other environmental or demographic characteristics previously shown in some studies to be related to ASD (e.g. maternal age, socioeconomic status).

Methods: A nested case-control study design was utilized.  All ASD cases born in 1990-2005 were identified from the Finnish Hospital Discharge Register (FHDR). Information concerning controls (1:4), as well as data on neonatal morbidity, was obtained from the Finnish Medical Birth Registry (FMBR). Neonatal disorders: 1. Birth Trauma, (ICD-10, P10-P15); 2. Respiratory and Cardiovascular Disorder of the Newborn, (ICD-10,P20-P29); 3. Newborn Infection (ICD-10,P36-P39); 4. Hemorrhagic and Haematological disorders of the newborn, (ICD-10, P50-P61); 5. Transitory Disorders of Carbohydrate Metabolism Specific to Newborn (ICD-10, P70-P74); 6. Conditions Involving the Integument and Temperature Regulation of the Newborn, (ICD-10, P80-P83); and 7. Other Neonatal Conditions (ICD-10, P90-P96), were analyzed as grouped/categorized in the ICD-10. Covariate data was collected from the FMBR.  Data were analyzed using conditional logistic regression, and associations between neonatal conditions and ASD were estimated using odds ratios (ORs) with 95% confidence intervals (CIs). 

Results:  Odds ratios from unadjusted univariate analyses revealed newborns diagnosed with “Respiratory and Cardiovascular Disorders” (ICD-10, P20-29) were more likely to be diagnosed with Childhood Autism  [OR=1.6 (95% CI: 1.04-2.49)], (p=.03) and PDD [OR=2.3 (1.65-3.21)], (p<.001).  "Newborn Infection"  (ICD-10, P36-P39) and  “Haemorrhagic and Haematological Disorders” (ICD-10, P50-P61), were more likely to be diagnosed with PDD/PDD NOS [OR=1.6 (95% CI:1.02-2.51)], (p=.04), and [OR= 1.6 (95% CI: 1.1-2.4)], (p=.01), respectively.  Further exploration of the Haemorrhagic and Haematological Disorders category revealed that neonatal jaundice (ICD-10, P58) was associated with PDD/PDD NOS [OR=1.95, 95% CI: 1.26-3.02], (p=.00) . Additionally, “Transitory Disorders of Carbohydrate Metabolism Specific to Newborns” was associated with ASD (p=.05), [OR=1.4, 95% CI: 1.00-2.01], and PDD/PDD NOS, [OR=2.06, (95% CI: 1.25-3.42)], (p=.00). “Birth Trauma”, and “Conditions Involving the Integument and Temperature Regulation of the Newborn”, (ICD-10, P80-P83), were unrelated to diagnosis of ASD, (p=.95) and (p=.86), respectively.

Conclusions: It is necessary to further explore each of the neonatal disorders that are included in each of these broad ICD-10 categories of neonatal morbidity, and their relation to ASD.  Further understanding of the role of neonatal disorders in the development of ASD may inform treatment and prevention of the disorder.