Search

Background: The Early Markers for Autism (EMA) study is a population-based case–control study designed to learn more about early biologic processes involved in ASD. Methods: Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n = 629) and intellectual disability without ASD (ID, n = 230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n = 599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions. Results: EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels. Limitations: Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced. Conclusions: Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures. [ABSTRACT FROM AUTHOR]

Background: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. Methods: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. Results: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22). Conclusions: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation. [ABSTRACT FROM AUTHOR]