Increased Risk of Ankylosing Spondylitis with Older Siblings

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Observational Study Finds an Increased Risk of Ankylosing Spondylitis with Older Siblings

Observational Study Finds an Increased Risk of Ankylosing Spondylitis with Older Siblings

A recent study has revealed a potential link between having older siblings and childhood tonsillectomy and the development of ankylosing spondylitis (AS), a chronic inflammatory arthritis.

Researchers examined health registry data in Sweden and found that the presence of older siblings increased the risk by 12-15%, while the risk after childhood tonsillectomy increased by 30-36%.

This study, while observational and unable to establish causation, controlled for common family factors and supports the theory that early infections may contribute to the development of AS.

These findings strengthen the idea that childhood infections may impact the development of ankylosing spondylitis.

Observational Study Finds an Increased Risk of Ankylosing Spondylitis with Older Siblings

A large-scale study published in the open-access journal “RMD Open” demonstrates that having older siblings and undergoing tonsillectomy during childhood are associated with an increased risk of ankylosing spondylitis (AS), a chronic inflammatory joint disease causing pain, stiffness, and fatigue.

Although genetic susceptibility is a primary cause of ankylosing spondylitis, early environmental factors are believed to influence its onset.

To explore this further, researchers used health and family unit data from the Swedish national population registry to compare cases and non-cases of ankylosing spondylitis in adults exposed to various early-life risk factors.

To meet the requirements of a case-control analysis, cases had to have at least one hospitalization or outpatient specialist clinic visit record between January 2001 and December 2022 and be diagnosed with ankylosing spondylitis.

Each case’s gender, birth year, and residential area were matched with an average of four non-case members of the general public.

Early-life risk factors included maternal age at childbirth, early pregnancy body weight (BMI), smoking status, gestational duration, infant birth weight, multiple births, cesarean section, pregnancy infections, and season of birth.

Other considerations included the number of siblings, severe childhood infections from birth to age 15, and tonsillectomy and/or appendectomy before age 16.

Risk Factors and Sibling Analysis Results

Between 2001 and 2022, a total of 6,771 individuals born after 1973 were diagnosed with ankylosing spondylitis. Of these, 5,612 were born in Sweden and were selected as cases.

Several factors were associated with an increased risk of ankylosing spondylitis, including having one or more older siblings (an increased risk of 12-15%), especially if no siblings were present.

After adjusting for potential influencing factors, the risk increased by 13% for childhood severe infections and 30% for tonsillectomy before age 16.

Compared to single births, multiple births were associated with a 23% increased risk, while individuals born in summer or autumn had a significantly lower risk compared to those born in winter.

Subsequently, researchers conducted a sibling comparison analysis, including 1,965 affected siblings and 6,070 unaffected siblings to account for potential shared environmental factors within families.

This analysis indicated that, after adjusting for gender, maternal age, and birth year, having one older sibling increased the risk by 18%, and having two or more older siblings raised the risk to 34%.

Researchers explained, “Our data cannot determine the mechanisms behind this increased risk, but studies have suggested that infants with siblings may be more susceptible to early-life infections.”

While the risk related to childhood severe infections observed in the case-control analysis decreased to 4%, the risk associated with tonsillectomy increased to 36% after adjusting for potential influencing factors.

Limitations and Conclusion

This is an observational study, and causation cannot be determined. Researchers did not have access to family physician data, so they could only ascertain severe infections from hospital records and tonsillectomy history. Only individuals born after 1973 were included in the study.

Nonetheless, the researchers concluded that even after adjusting for shared family factors in sibling comparison analysis, “having older siblings and a history of childhood tonsillectomy are independently associated with [ankylosing spondylitis]. This strengthens the hypothesis that childhood infections play a role in the etiology of [ankylosing spondylitis].”