Maternal serum C-reactive protein (CRP) and offspring attention deficit hyperactivity disorder (ADHD)

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.

Primate Models as a Translational Tool for Understanding Prenatal Origins of Neurodevelopmental Disorders Associated With Maternal Infection

“…Likewise, quantification of cytokines, chemokines, and other inflammatory markers obtained from archived maternal sera ( 52 , 53 ) and amniotic fluid ( 54 , 55 ) lends further support to the link between maternal infection and increased ASD risk, though not all studies have found positive associations ( 56 ). Recent efforts have focused on exploring disease-specific maternal inflammatory pathways associated with other NDDs, including ADHD, depression, bipolar disorder and other neuropsychiatric conditions ( 57 , 58 , 59 , 60 , 61 , 62 ). Collectively, the growing epidemiological literature provides compelling evidence linking the maternal immune response to offspring NDDs, though underlying mechanisms are difficult to ascertain due to constraints associated with human research, including differences in study design, timing of biospecimen collection, methods for determining maternal infection exposure, and long delays before clinical diagnosis of affected offspring.…”

Role of Oxidative Stress and Neuroinflammation in Attention-Deficit/Hyperactivity Disorder

“…Moreover, the risk of ADHD in offspring has been found to increase in mothers with inflammatory or immune diseases [ 38 ]. Furthermore, a maternal history of autoimmune disease could be associated with an increased risk of ADHD [ 127 ], but recently, the maternal C-reactive protein during early pregnancy showed no significant associations with ADHD in offspring [ 134 ].…”

“…The outcomes of neuroinflammation are summarized in Table 3. Maternal C-reactive protein during early pregnancy showed no significant association in offspring [134] The table summarizes the neuroinflammation and outcomes. More details in the text.…”

Mast cell‑mediated neuroinflammation may have a role in attention deficit hyperactivity disorder (Review)

“…In a study on depression and anxiety in from the Netherlands including 2,307 subjects indicated that there was no evidence that ADHD development was associated with dysregulation of inflammatory markers, and there was no interaction between ADHD symptoms and stress-associated affective disorders (155). Examination of the early gestational maternal C-reactive protein in maternal serum and the risk of ADHD in offspring suggests a lack of correlation (156). In addition to clinical studies, several animal studies have identified or confirmed the association between ADHD and inflammation.…”