Maternal ankylosing spondylitis linked to twofold higher Kawasaki disease risk in children
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Maternal ankylosing spondylitis is associated with a 2.02-times higher likelihood of Kawasaki disease in the offspring, according to a research letter published in JAMA Network Open.
“Increased [Kawasaki disease (KD)] incidence among East Asian children, a high risk among siblings and twins, and familial occurrence suggest a genetic predisposition,” Chaw-Liang Chang, MD, of National Chiao Tung University, in Taiwan, and colleagues wrote. “However, genetic factors alone cannot explain seasonal variations, periodic outbreaks, or the continued increase in KD incidence.”
“Many other factors, including exposure to infectious agents, pollution, and elevated atmospheric biological particle concentrations, are associated with KD,” they added. “Several studies have suggested that maternal and perinatal factors might be associated with KD development.”
To analyze the role of perinatal factors and maternal autoimmune disease in the development of Kawasaki disease, Chang and colleagues conducted a case-control study. The researchers examined data from patients aged younger than 5 years with Kawasaki disease who were born between 2004 and 2010, using the Taiwan National Health Insurance Research Database. According to the researchers, this database was established in 1995 and covered 99.9% of the population by 2003. Kawasaki disease diagnoses were confirmed based on the patient receiving intravenous immunoglobulins and hospitalization.
Meanwhile, Chang and colleagues included age- and index-date-matched individuals from the general population as a control group. To link parents and children, researchers used the Taiwan Maternal and Child Health Database, which contains national identification numbers of both groups. In all, the researchers included 4,197 patients with Kawasaki disease — 1,717 aged younger than 1 year and 1,261 aged 1 year — and 16,788 matched individuals without Kawasaki disease.
According to the researchers, male sex (OR = 1.47; 95% CI, 1.37-1.57), a maternal age of 35 years or older (OR = 1.18; 95% CI, 1.07-1.30), maternal Sjögren syndrome (OR = 1.75; 95% CI, 1.03-2.95), and maternal ankylosing spondylitis (OR = 2.01; 95% CI, 1.17-3.43) were associated with an increased risk for Kawasaki disease in children. Meanwhile, low birth weight, preterm delivery, other maternal autoimmune diseases and maternal comorbidities demonstrated no associations with Kawasaki disease risk.
In the multivariable analysis, maternal ankylosing spondylitis was associated with a 2.02 times higher likelihood of developing Kawasaki disease in children (95% CI, 1.18-3.47).
“In this study, we found that advanced maternal age was significantly associated with KD development in the offspring,” Chang and colleagues wrote. “This association may partly explain the increasing KD incidence in developed countries because ages at marriage and childbearing are increasing. The advanced parental age may be associated with more germline de novo variants, which may lead to KD in the offspring.”
“Furthermore, we demonstrated that maternal ankylosing spondylitis and Sjögren syndrome may be perinatal factors associated with increased risk of KD,” they added. “This suggests that a maternal autoimmune disease or its associated medical treatment might induce an epigenetic predisposition to developing KD in the offspring.”
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