Association of Maternal Autoimmune Disease With Attention-Deficit/Hyperactivity Disorder in Children

Abstract

IMPORTANCEMaternal autoimmune disease has been associated with increased risk of neurodevelopmental disorders in offspring, but few studies have assessed the association with attention-deficit/hyperactivity disorder (ADHD).OBJECTIVE To examine the association between maternal autoimmune disease and ADHD within a population-based cohort and combine results in a subsequent systematic review and meta-analysis. DESIGN, SETTING, AND PARTICIPANTSA cohort study was conducted of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia, from July 1, 2000, to December 31, 2010, and followed up until the end of 2014; and a systematic review evaluated articles from the MEDLINE, Embase, and Web of Science databases to identify all studies published before November 20, 2019. A total of 12 610 children exposed to maternal autoimmune disease were propensity score matched (1:4) to 50 440 unexposed children, for a total cohort of 63 050. A child was considered to have ADHD if they had (1) an authorization or filled prescription for stimulant treatment for ADHD or (2) a hospital diagnosis of ADHD. Children linked to a first ADHD event before 3 years of age were excluded. Data were analyzed from January 13 to April 20, 2020.EXPOSURES One or more maternal autoimmune diagnoses in linked hospital admission records between July 1, 2000, and December 31, 2012. Thirty-five conditions were considered together and individually. MAIN OUTCOMES AND MEASURESThe main outcome was child ADHD identified from stimulant authorization or prescription data and diagnoses in linked hospital admission records. Multivariable Cox regression was used to assess the association between maternal autoimmune disease and ADHD adjusted for child sex. Pooled hazard ratios (HRs) were calculated using random-effects meta-analysis with inverse-variance weights for each exposure reported by 2 or more studies. RESULTSIn the population-based cohort analysis, 831 718 singleton, term infants born to 831 718 mothers (mean [SD] age, 29.8 [5.6] years) were assessed. Of 12 767 infants (1.5%) who were linked to a maternal autoimmune diagnosis, 12 610 were propensity score matched to 50 440 control infants, for a total study cohort of 63 050 infants. In this cohort, any autoimmune disease was associated with ADHD in offspring (HR, 1.30; 95% CI 1.15-1.46), as was type 1 diabetes (HR, 2.23; 95% CI, 1.66-3.00), psoriasis (HR, 1.66; 95% CI, 1.02-2.70), and rheumatic fever or rheumatic carditis (HR, 1.75; 95% CI, 1.06-2.89). Five studies (including the present study) were included in the meta-analysis. Any autoimmune disease (2 studies: HR,

Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

“…Maternal autoimmune diseases and asthma were significantly associated with ADHD [49][50][51] . Higher risk of ADHD was observed among offspring of mothers with asthma exacerbations and only exacerbations after delivery (HR 1.25 [1.08-1.44] 51 ), suggesting that a more severe asthma phenotype results in greater risk to the offspring 51 .…”

Association of Maternal Autoimmune Diseases With Risk of Mental Disorders in Offspring in Denmark

“… 29 A limited number of studies focused on ADHD, another common neurodevelopmental disorder in childhood. 9 , 14 , 30 , 31 Our study extended the finding of a recent hybrid study in which ADHD risk in offspring was the main outcome of interest and both original data from a cohort and meta-analyses of published studies were included. 14 Results from a Danish study suggested that mothers with an autoimmune disease were more likely to have a child with poorer school performance than their unexposed counterparts, 12 suggesting a potential association of maternal autoimmune activity with fetal brain development.…”

“…Empirical evidence has suggested an association between certain maternal autoimmune diseases (eg, type 1 diabetes, rheumatoid arthritis) and specific mental disorders (eg, autism spectrum disorder, attention-deficit/hyperactivity disorder [ADHD]) in offspring. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 However, most previous population-based studies were restricted to certain maternal autoimmune diseases and mental disorders in offspring during childhood and had small sample sizes. Using a Danish registry-based cohort of more than 2 million live-born singletons with up to 38 years of follow-up, we investigated the associations between a wide range of maternal autoimmune diseases diagnosed before childbirth and the risks of the full spectrum of mental disorders in offspring during childhood and early adulthood.…”

The Diagnostic Performance of Early Sjögren’s Syndrome Autoantibodies in Juvenile Sjögren’s Syndrome: The University of Florida Pediatric Cohort Study

“…Similarly, dental caries or dental-related issues were also more prevalent in JSS patients (p = 0.01). Interestingly, about 11% of our cohort patients reported attention-deficit/hyperactive disorder (ADHD) or autism spectrum disorders, suggesting a potential link between maternal autoimmune diseases/inflammation and those conditions (19,20).…”