PAPER Neurocognitive abnormalities in offspring of mothers with systemic lupus erythematosus MB Urowitz 1 , DD Gladman 1 , A MacKinnon 1 , D Ibañez 1 , V Bruto 2 , J Rovet 3 and E Silverman 3 1 Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital, University of Toronto Lupus Clinic, Toronto, Ontario, Canada; 2 Hamilton Health Sciences Centre, Hamilton, Ontario, Canada; and 3 Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada Offspring of systemic lupus erythematosus (SLE) patients delivered during follow-up in the lupus clinic from 1973 to 1998 were assessed for SLE and by age-appropriate neurocognitive tests. Nine domains were evaluated. Controls, matched for age, sex, race and socio-economic status, under- went the same neurodevelopmental/neuropsychological evaluation. A domain was considered ‘abnormal’ if at least one of the tests in the domain yielded abnormal results. The number of off- spring with normal/abnormal results was compared in each of the nine domains using McNemar test for matched analysis. In addition, an unmatched analysis using chi-square tests was performed. Logistic regression was run on both the matched pairs and unmatched groups to adjust for possible gender differences. A total of 106 children, 49 pairs of SLE offspring and matched controls (20 male and 29 female) and an extra eight offspring (three male and five female) of SLE patients without a control match were included. Of the 57 SLE offspring, none were diagnosed with SLE. The matched analyses of the neuropsychological domains revealed impairment in SLE children compared with matched controls in two of the nine domains: learning and memory and behav- iour. Lupus (2008) 17, 555–560. Key words: SLE; offspring; neuropsychological abnormalities Systemic lupus erythematosus (SLE) is a chronic auto- immune disease that predominantly affects women in the childbearing years. 1 Recent studies indicate a prev- alence of approximately 1:1000 women, making SLE more common than leukaemia, multiple sclerosis and muscular dystrophy. Because SLE is no longer consid- ered a contraindication to pregnancy, 2 it is likely that an increasing number of children will be born to women with SLE. Although the majority of lupus pregnancies result in apparently healthy babies, these pregnancies are associated with a higher risk of foetal loss, premature birth, intrauterine growth retardation, neonatal lupus and congenital heart block. 3 Minor physical anomalies were not found to be increased in offspring of mothers with lupus. 4 Exposure to mater- nal autoantibodies (e.g. anti-phospholipid and anti-Ro antibodies) and/or pathophysiological factors of maternal disease (e.g. active kidney disease) has been linked to poor foetal development and neonatal lupus. 5 Although controversial, the observation that autoimmune factors have been implicated in SLE- related brain dysfunction in children and adults with SLE raises the possibility that maternal autoantibodies may also represent a potential insult to the developing brain. Some studies have suggested that exposure to anti-Ro is associated with a higher prevalence of devel- opmental dyslexia. 6–8 Surveys of parental reports sug- gest that the sons of mothers with SLE may be at increased risk for the development of verbal learning disabilities. 9 However, these studies were retrospective in nature and are marked by methodological limita- tions (e.g. self-report rather than formal examination, limited focus). More recent studies used standardized psychological tests to evaluate neuropsychological function in offspring of mothers with SLE and also report learning disabilities in sons. 8,10 These latter studies did not include matched controls. The objective of this study was to determine the prevalence of neuropsychological abnormalities in offspring born to mothers with SLE during their follow-up in the lupus clinic from 1973 to 1998 com- pared with a control population matched for age, sex, race and socio-economic status. Lupus (2008) 17, 555–560 http://lup.sagepub.com © 2008 SAGE Publications Los Angeles, London, New Delhi and Singapore 10.1177/0961203308089326 Correspondence to: Dr. Murray Urowitz, Toronto Western Hospital, 1E- 410B, 399 Bathurst Street, Toronto, Ontario, Canada, M5T 2S8. Email: m.urowitz@utoronto.ca Received 9 October 2007; accepted 18 December 2007