Lack of association between birth order and juvenile idiopathic arthritis

Abstract

Lack of association between birth order and juvenile idiopathic arthritisAlthough the cause of juvenile idiopathic arthritis (JIA) is still not well elucidated, evidence suggests that a complex interplay of genetic and environmental factors underlies its pathogenesis. JIA includes phenotypically and genetically distinct subtypes, with different ages at onset. It has been hypothesized that intrauterine or early childhood environmental factors might influence susceptibility to autoimmune diseases. It is conceivable that reproductive factors, such as maternal age or birth order, could influence susceptibility to JIA and other autoimmune diseases. An association between ankylosing spondylitis (AS) and low birth order has been reported (1), although other investigators have been unable to confirm this association (2,3). To our knowledge, associations between JIA and birth order have not been reported. In this analysis, we address the question of a possible association between birth order and JIA.Information on JIA patients seen at the pediatric rheumatology clinics at the University of Utah was entered into a clinical database; clinical and demographic data were collected by chart review and questionnaire. Most of the patients had been cared for by one of the authors (JFB). Charts were reviewed by a second pediatric rheumatologist (SP) and the diagnosis confirmed. Patients who did not meet the International League of Associations for Rheumatology criteria for JIA (4) were not included. Subjects were linked with records in the Utah Population Database (UPDB), a computerized database of more than 7 million records that includes genealogies, birth certificates, death certificates, and other records. A program called Integrity was used to perform probabilistic linking of records in these 2 databases. Weights were calculated to measure the contribution of each field to the probability of matching 2 records. A link was accepted if the composite weight was above a specified threshold. For each linked case, ϳ10 controls matched by sex and birth year were selected. Information on birth order, sibship size, and maternal age at delivery was obtained primarily from 1.7 million birth certificates in the UPDB. The cases and matched controls were born between 1976 and 1999. Chi-square tests were used to compare the birth order distributions among cases and controls and t-tests were used to compare maternal age at delivery. The study was approved by the Institutional Review Board and the Utah Resource of Genetic and Epidemiology Research, which administers access to the UPDB.A total of 333 cases and 3,295 controls were analyzed. There were 206 female and 127 male patients with JIA.

Sibling Exposure and Risk of Juvenile Idiopathic Arthritis

“…Our data are consistent with this finding, showing that risk of JIA in only children is 2.2 times higher than that in children with at least one sibling. Prahalad et al showed no association between birth order and JIA (15). Again, our data are consistent with this work.…”

“…One study showed that an only child had a risk of developing “juvenile chronic arthritis” that was 1.6 times that of a child with at least one sibling . Another study revealed no relationship between juvenile arthritis and either birth order or sibship size (total number of children in the family) by comparison of 333 cases of “juvenile rheumatoid arthritis” and more than 3,000 controls matched to cases by age and sex . More recently, an analysis of more than 3,000 Swedish JIA cases and 13,000 controls did not find an association of JIA with number of older siblings .…”

Juvenile idiopathic arthritis in relation to perinatal and maternal characteristics: a case control study

“…In contrast, no risk reduction was observed in relation to having increased numbers of older siblings in a Swedish registry-based study [5]. Birth order was not found to be associated with JIA in two previous studies [6, 20]. …”

Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

“…This was also supported by a Norwegian study, which reported that singleton children had 1.6‐fold higher risk of JIA as compared to children with siblings. However, not all studies have observed the protective effect of contact with siblings …”

“…However, not all studies have observed the protective effect of contact with siblings. 15,64 A final factor which is linked to microbial alteration is prematurity. In a Northern American study that included fecal samples obtained from 30 premature and 176 term infants at 6 weeks of age 65 reduced alpha diversity was found in preterm vs term infants even after adjusting for exposures.…”