Abstract

Exposure to infection and inflammation during the fetal period are associated with offspring neuropsychiatric disorders. Few previous studies have examined this association with ADHD with mixed findings. This study aims to examine the association between early gestational maternal C-reactive protein (CRP), prospectively assayed in stored maternal sera and the risk of ADHD in offspring. This study is based on the Finnish Prenatal studies of ADHD (FIPS-ADHD) with a nested case–control design. It includes all singleton-born children in Finland between January 1, 1998 and December 31, 1999 and diagnosed with ADHD. A total of 1079 cases and equal number of controls were matched on date of birth, sex and place of birth. Maternal CRP levels were assessed using a latex immunoassay from archived maternal serum specimens, collected during the first and early second trimester of pregnancy. Elevated maternal CRP when analyzed as a continuous variable was not associated with offspring ADHD (OR 1.05, 95% CI 0.96–1.15). No significant associations were seen in the highest quintile of CRP (OR 1.18, 95% CI 0.88–1.58). The results were similar in both sexes as well as among ADHD cases with or without comorbid ASD or conduct disorder. In this first study examining CRP, a biomarker for inflammation, during early pregnancy in relation to offspring ADHD, we report no significant associations. The lack of any association, when considered with positive findings seen in ASD and schizophrenia, and negative findings in bipolar disorder suggests different pathways linking maternal immune activation and development of various neuropsychiatric disorders.

Highlights

  • Attention deficit hyperactivity disorder (ADHD) is defined as impairment due to behavioral symptoms of inattention, hyperactivity and impulsivity and has an estimated worldwide prevalence of around 5% [1]

  • The aim of this study is to examine the association between early gestational maternal C-reactive protein (CRP), prospectively assayed in stored maternal sera and the risk of ADHD in offspring

  • There was no association seen between maternal CRP levels and offspring ADHD

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Summary

Introduction

Attention deficit hyperactivity disorder (ADHD) is defined as impairment due to behavioral symptoms of inattention, hyperactivity and impulsivity and has an estimated worldwide prevalence of around 5% [1]. Despite having a strong genetic component, several environmental factors contribute to the development of ADHD [2]. An exaggerated central nervous system inflammatory response to a pre-/perinatal insult in the developing fetus has been hypothesized as a potential cause of ADHD [3]. Studies showing an association between maternal diseases with an immune component and offspring ADHD provide support to the role of maternal immune activation during pregnancy in development of ADHD [4,5,6]. In a Norwegian nationwide case–control study, maternal diagnoses of multiple sclerosis, rheumatoid arthritis, asthma, hypothyroidism, and type 1 diabetes were associated with an increased risk of ADHD in. Diabetes mellitus among mothers [6] as well as in both parents [5] was associated with offspring ADHD

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