March 16, 2012 (Prague, Czech Republic) — Immune dysfunction during pregnancy and after birth may play a role in the development of autism spectrum disorder (ASD).
In a presentation here at EPA 2012: 20th European Congress of Psychiatry, Morsi Abdallah, MD, MPH, of the Department of Psychiatry and Psychotherapy at Rostock University Hospital in Rostock, Germany, presented evidence of differences in cytokine levels in amniotic fluid and in neonatal blood of children later diagnosed with ASD compared with control participants.
Although the neurobiological basis of ASD is complex and involves genetic and environmental factors, many studies have implicated immune processes in the pathophysiology of ASD. Fetal, maternal, and placental cytokines mediate pro- and anti-inflammatory effects and are thought to affect the neurodevelopment of the fetus, Dr. Abdallah explained.
Comprehensive Data
Using the Danish Historic Birth Cohort of more than 100,000 pregnant women who underwent screening or diagnostic amniocentesis and/or phlebotomy, he compared cytokine and chemokine levels in amniotic fluid and neonatal blood using neonatal dried blood spot samples from the same individuals to investigate the possible contributory role of immune dysfunction during pregnancy and after birth in the development of ASD.
The Danish Historic Birth Cohort is a collection of biological samples obtained from the late 1970s through 2004, with residual samples after screening or diagnostic tests preserved at -20˚ C at the Danish State Serum Institute.
In addition, the Danish Newborn Screening Biobank contains neonatal dried blood spot samples that were collected since 1982 for screening newborns for certain genetic and metabolic diseases and conditions. Population coverage has been almost universal, and the biobank now contains about 2 million samples.
The Danish National Birth Register contains birth data (eg, height, weight, Apgar score) on all live births and stillbirths in the country since 1968, with computer records going to back 1973.
Initiated in 1977, the birth register contains information on all hospital admissions and discharges in the country, including outpatient and emergency room visits since 1995.
The Danish Psychiatric Central Register is part of the hospital register, with controlled access for researchers. Only specialists in child and adolescent psychiatry are authorized to code the diagnosis of ASD in this register.
Concatenating these various databases allowed the researchers to address the questions of interest. On the basis of availability of all required information and biological samples, among singleton births the researchers identified 414 ASD patients and 820 control participants who were matched by year of birth and sex for the birth years 1982 to 2000. Cytokines were measured in amniotic fluid and neonatal blood for each individual.
The investigators performed a primary analysis comparing ASD patients to non-ASD control participants and a supplementary analysis of typical autism patients vs control participants with no psychiatric comorbidities.
The ASD and control participants were similar demographically except that 44.7% of mothers of ASD participants were older than 35 years vs 37.9% of control mothers; the ASD participant was a first child in 37.7% of cases vs 31.5% for control participants; 2.7% of ASD children had an Apgar score <7 at 5 minutes after birth vs 1.1% of control participants; and 20.1% of ASD participants had a congenital malformation vs 8.3% of control participants.
Novel Finding
Variations in several cytokines and chemokines in amniotic fluid and neonatal blood were observed between the ASD children and their control counterparts. Dr. Abdallah noted that some markers that were elevated in amniotic fluid of ASD participants (eg, interleukin-4 and interleukin-10) were present in lower levels in neonatal blood compared with normal control participants.
"Different studies have shown similar patterns to the ones that we have in amniotic fluid, for example...but [in] the neonatal samples, we haven't seen it before," he said. "And maybe that's because most of the studies that were performed up to date are mainly on children later in life [and] older than the population we have here."
Table. Cytokine/chemokine Levels: Children Later Diagnosed With ASD Compared With Control Levels
| Increased Levels |
Decreased Levels |
|
| Amniotic fluid |
IL-4, IL-10, MCP-1, TNF |
— |
| Neonatal blood |
IL-8, sIL-6rα |
IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IFN-γ, GM-CSF, RANTES |
IL: interleukin; sIL-6rα: soluble IL-6 receptor-α; MCP-1: monocyte chemotactic protein-1; TNF: tumor necrosis factor; IFN: interferon; GM-CSF: granulocyte-macrophage colony-stimulating factor; RANTES: Regulated upon Activation, Normal T-cell Expressed, and Secreted (a chemotactic cytokine)
On the basis of the pattern of cytokines and chemokines that he observed, Dr. Abdallah concluded that his findings suggest a proinflammatory intrauterine state during pregnancy in children diagnosed later in life with ASD, compensated for by an anti-inflammatory response. The lower level of neonatal cytokines may indicate postnatal hypoactivity of immune cells, associated with ASD.
On the basis of the pattern of cytokines and chemokines that he observed, Dr. Abdallah concluded that his findings suggest a proinflammatory intrauterine state during pregnancy in children diagnosed later in life with ASD, compensated for by an anti-inflammatory response. The lower level of neonatal cytokines may indicate postnatal hypoactivity of immune cells, associated with ASD.
A strength of the study is the ability to link nationwide health registry data with large-scale biobanks, likely allowing generalization of the results. But reliance on retrospective registry data is also a limitation of the study, along with lack of access to clinical symptomatology data and the long storage periods of the samples.
Session moderator David Ben-Dor, MD, a child and adolescent psychiatrist and deputy head of the Psychiatric Ward at Geha Mental Health Center in Petah Tikva, Israel, told Medscape Medical News that the relationship of the immune system to autism is a popular research area, but, he said, "I don't think there's anything really right now that is specific enough for autism." He noted that Dr. Abdallah mentioned that some of the findings also have to do with psychiatric disorders other than ASD.
Dr. Abdallah and Dr. Ben-Dor have disclosed no relevant financial relationships.
EPA 2012: 20th European Congress of Psychiatry. Abstract O-01. Presented Monday, March 5, 2012.
Medscape Medical News © 2012 WebMD, LLC
Send comments and news tips to news@medscape.net.
Cite this: Pre- and Postnatal Immune Dysfunction May Influence Autism Risk - Medscape - Mar 16, 2012.
Comments