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.

Objective To investigate the impact of gestational exposure to selective serotonin reuptake inhibitors (SSRIs) on offspring neurodevelopment. Method This is a cohort study using national register data in Finland between the years 1996-2010. Pregnant women and their offspring were categorized into four groups: SSRI exposed (n=15,729); exposed to psychiatric disorder, no antidepressants (n=9,651); exposed to SSRIs only before pregnancy (n=7,980); and unexposed to antidepressants and psychiatric disorders (n=31,394). We investigated the cumulative incidence of offspring diagnoses of depression, anxiety, autism spectrum disorders (ASDs), and attention-deficit/hyperactivity disorders (ADHD) for the four groups from birth to 14 years, adjusting for confounders. Results The cumulative incidence of depression among offspring exposed prenatally to SSRIs was 8.2% (95% CI, 3.1-13.3%) by age 14.9, compared to 1.9% (95% CI, 0.9-2.9%) in the psychiatric disorder, no medication group (adjusted hazard ratio [HR], 1.78; 95% CI, 1.12-2.82; p=.02) and to 2.8% (95% CI, 1.4-4.3%) in the SSRI discontinued group (HR 1.84; 95% CI, 1.14-2.97; p=.01). Rates of anxiety, ASD, and ADHD diagnoses were comparable to rates in offspring of mothers with a psychiatric disorder but no medication during pregnancy. Comparing SSRI exposed to unexposed, the HRs were significantly elevated for each outcome. Conclusion Prenatal SSRI exposure was associated with increased rates of depression diagnoses in early adolescence but not with ASD or ADHD. Until confirmed, these findings must be balanced against the substantial adverse consequences of untreated maternal depression.

Objective The goal of the present study was to investigate an association between early gestational C-reactive protein (CRP), an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large national birth cohort with an extensive serum biobank. Methods This study utilized a nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort. 777 schizophrenia cases (630 with schizophrenia, 147 with schizoaffective disorder) that had maternal sera available for CRP testing were identified and matched to 777 controls in the analysis. Maternal CRP levels were assessed using a latex immunoassay from archived maternal serum specimens. Results Increasing maternal CRP levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio (OR)=1.31, 95% confidence interval (CI)=1.10-1.56, p=0.003). This finding remained significant after adjusting for potential confounders including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status. Conclusion This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders.

IMPORTANCE There is a large gap worldwide in the provision of evidence-based early treatment of children with disruptive behavioral problems. OBJECTIVE To determine whether an Internet-assisted intervention using whole-population screening that targets the most symptomatic 4-year-old children is effective at 6 and 12 months after the start of treatment. DESIGN, SETTING, AND PARTICIPANTS This 2-parallel-group randomized clinical trial was performed from October 1, 2011, through November 30, 2013, at a primary health care clinic in Southwest Finland. Data analysis was performed from August 6, 2015, to December 11, 2015. Of a screened population of 4656 children, 730 met the screening criteria indicating a high level of disruptive behavioral problems. A total of 464 parents of 4-year-old children were randomized into the Strongest Families Smart Website (SFSW) intervention group (n = 232) or an education control (EC) group (n = 232). INTERVENTIONS The SFSW intervention, an 11-session Internet-assisted parent training program that included weekly telephone coaching. MAIN OUTCOMES AND MEASURES Child Behavior Checklist version for preschool children (CBCL/1.5-5) externalizing scale (primary outcome), other CBCL/1.5-5 scales and subscores, Parenting Scale, Inventory of Callous-Unemotional Traits, and the 21-item Depression, Anxiety, and Stress Scale. All data were analyzed by intention to treat and per protocol. The assessments were made before randomization and 6 and 12 months after randomization. RESULTS Of the children randomized, 287 (61.9%) were male and 79 (17.1%) lived in other than a family with 2 biological parents. At 12-month follow-up, improvement in the SFSW intervention group was significantly greater compared with the control group on the following measures: CBCL/1.