A nationwide cohort study published in December 2015 in the Annals of Rheumatic Diseases found that children of parents with rheumatoid arthritis (RA) are at increased risk for numerous morbidities, especially autoimmune diseases.

In the first investigation into long-term health outcomes of children exposed to parental RA, researchers followed a sample of approximately 1.9 million people, comprising all single-birth children born in Denmark between 1977 and 2008, for an average of 16 years starting at birth. In a previous study using the same sample, the researchers found that children born to mothers with RA had increased risk of preterm birth and lower birth weight, suggesting a potentially increased vulnerability to subsequent disease.

Information was obtained from The Danish National Hospital Registry, and the parent’s timing of initial diagnosis was used to determine in utero exposure to clinical RA or preclinical RA (RA diagnosed either before or after birth). The main outcome measures in the current study were adjusted hazard ratios (HRs) for child morbidity for 11 diagnostic groups and autoimmune diseases from the 8th and 10th versions of the International Classification of Diseases (ICD-8 and ICD-10).


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For the children who had been exposed to parental  RA (13,566 maternal cases and 6330 paternal cases), compared with unexposed children, results “indicate an excess morbidity for all diagnostic groups examined, except for circulatory system diseases among children exposed to paternal RA,” the authors wrote.  Among those exposed to maternal RA, morbidity was up to 26% higher in 8 of the 11 diagnostic groups examined. Similar results were observed in children exposed to paternal RA, with the exception of HRs for “infectious and parasitic diseases” and “mental and behavioral disorders,” which did not show a statistically significant increase among these children.

For children exposed to both maternal and paternal RA, the highest HRs were found for autoimmune diseases, including juvenile idiopathic arthritis (HRs 3.30 and 2.97; 95% confidence interval [CI], 2.71-4.03 and 2.20-4.01, respectively), type 1 diabetes mellitus (HRs 1.37 and 1.44; 95% CI, 1.12-1.66 and 1.09-1.90, respectively), and asthma (HRs 1.28 and 1.15; 95% CI, 1.20-1.36 and 1.04- 1.26, respectively). For the majority of diseases, the increased risk was found for children exposed to parents with both clinical and preclinical RA at the time of the child’s birth.

“Our findings indicate an important role of genetic factors, since we found increased child morbidity in children of both mothers with RA and fathers with RA,” lead study author Ane L. Rom, PhD, of Copenhagen University Hospital in Denmark, told Rheumatology Advisor. “The particularly increased risk of specific autoimmune diseases in children of parents with RA also indicates that genetic factors play a role, rather than fetal programming due to the disease,” which holds that intrauterine exposure influences susceptibility to long-term morbidities. The current findings are supported by previous studies demonstrating an aggregation of autoimmune diseases in families. “Because this is the first study to investigate long-term morbidity in children of parents with RA, we do not know if the associations are causal, especially regarding the increased risk of other nonautoimmune diseases,” says Dr Rom. Additionally, “even though we were able to adjust for relevant confounding factors, potential unknown confounding factors cannot be excluded in this type of study.” Further research is needed to replicate and expand on these findings before conclusions can be drawn.

Summary and Clinical Applicability

Children born to mothers and fathers with RA show an increased risk of childhood and long-term morbidity for multiple common disease categories in the ICD-8 and ICD-10, as well as for specific autoimmune diseases.  These findings support a genetic basis for the increased risk, rather than a fetal programming mechanism. “The clinical implications warrant increased knowledge and awareness among health professionals–including rheumatologists and primary care physicians–with the aim of early detection, especially of autoimmune diseases among the offspring,” says Dr Rom.

References

1.       Rom AL, Wu CS, Olsen J, et al. Parental rheumatoid arthritis and long-term child morbidity: a nationwide cohort study. Ann Rheum Dis. 2015; pii: annrheumdis-2015-208072.

2.       Rom AL, Wu CS, Olsen J, et al. Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis: a nationwide cohort study. Arthritis Rheumatol. 2014;66:3265-3273.