Elevated maternal C-reactive protein and autism in a national birth cohort

Abstract

Autism is a complex neuropsychiatric syndrome with a largely unknown etiology. Inflammation during pregnancy may represent a common pathway by which infections and other insults increase risk for the disorder. Hence, we investigated the association between early gestational C-reactive protein (CRP), an established inflammatory biomarker, prospectively assayed in maternal sera, and childhood autism in a large national birth cohort with an extensive serum biobank. Other strengths of the cohort included nearly complete ascertainment of pregnancies in Finland (N=1.2 million) over the study period and national psychiatric registries consisting of virtually all treated autism cases in the population. Increasing maternal CRP levels, classified as a continuous variable, were significantly associated with autism in offspring. For maternal CRP levels in the highest quintile, compared to the lowest quintile, there was a significant, 43% elevated risk. This finding suggests that maternal inflammation may play a significant role in autism, with possible implications for identifying preventive strategies and pathogenic mechanisms in autism and other neurodevelopmental disorders.

Maternal Depressive Symptoms During and After Pregnancy and Psychiatric Problems in Children

“…37 Also, higher maternal prenatal pro-inflammatory marker levels have been associated with both maternal depressive symptoms during pregnancy 6,7 and offspring autism risk. 38 However, the sociobiological pathways underlying the development of maternal depression and child psychopathology are beyond the scope of this study. Further studies unraveling these underlying mechanisms and studies focusing on the underlying genetic and epigenetic mechanisms are warranted.…”

Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies

“…Maternal infectious or inflammatory insults during pregnancy have been repeatedly implicated in the etiology of developmental neuropsychiatric disorders, including schizophrenia (Brown and Derkits, 2010;Canetta et al, 2014b), autism (Atladóttir et al, 2010;Brown et al, 2014), and bipolar disorder (Canetta et al, 2014a;Parboosing et al, 2013). Preclinical support for these epidemiological associations has been obtained by various translational rodent models demonstrating multiple brain and behavioral abnormalities following prenatal exposure to infection and/or immune activation (reviewed in Boksa, 2010;Harvey and Boksa, 2012;Meyer, 2014;.…”

Prenatal Inflammation, Infections and Mental Disorders

“…Some studies [26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41] additionally collected exposure data by interviewing mothers during or shortly after pregnancy or using their medical records. Thereafter, several studies [42,43,44,45,46,47,48,49] used a more rigorous way of estimating maternal exposure by investigating prospectively collected maternal sera of offspring with psychiatric disorders. To explore mechanisms and the site of action of the infectious agents, researchers have also used animal models.…”