Background Prenatal exposure to organophosphate insecticides may be associated with autism spectrum disorders and related behaviors. This association may be modified by single nucleotide polymorphisms in the paraoxonase (PON1) enzyme. Objective We examined the relationship of prenatal organophosphate insecticide biomarkers with reciprocal social, repetitive, and stereotypic behaviors in 8-year old children, and modification of this relationship by child PON1 polymorphisms. Methods Among 224 pregnant women, we quantified concentrations of six nonspecific dialkyl phosphate (DAP) metabolites of organophosphate insecticides in two urine samples collected at ~16 and ~26 weeks gestation. When children were eight years old, we administered the Social Responsiveness Scale (SRS), a continuous measure of various dimensions of interpersonal behavior, communication, and repetitive/stereotypic behaviors. We estimated the association between a 10-fold increase in the sum of six DAP concentrations (ΣDAP) and SRS scores. We examined whether child PON1192 and PON1−108 genotypes modified this association. Results After covariate adjustment, ΣDAP concentrations were not associated with SRS scores [β = −1.2; 95% confidence interval (CI): −4.0, 1.6]. Among children with the PON1−108TT genotype, ΣDAP concentrations were associated with 2.5-point higher (95% CI: −4.9, 9.8) SRS scores; however, the association was not different from the 1.8-point decrease (95% CI: −5.8, 2.2) among children with PON1−108CT/CC genotypes (ΣDAP × PON1−108 p-value = 0.54). The association between ΣDAP concentrations and SRS scores was not modified by PON1192 (ΣDAP × PON1192 p-value = 0.89). Conclusions In this cohort, prenatal urinary DAP concentrations were not associated with children’s social behaviors; these associations were not modified by child PON1 genotype.

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Background: The arterial switch operation (ASO) is the gold standard operative correction of neonates with transposition of the great arteries and intact ventricular septum, with excellent operative survival. The associations between patient and surgeon characteristics and outcomes are well understood, but the associations between variation in preoperative care and outcomes are less well studied. Methods: A multicenter retrospective cohort study of infants undergoing neonatal ASO between 1/2010 and 9/2015 at hospitals contributing data to the Pediatric Health Information Systems Database was performed. The association between preoperative care (timing of ASO, preoperative use of balloon atrial septostomy, prostaglandin infusion, mechanical ventilation, and vasoactive agents) and operative outcomes (mortality, length of stay, and cost) was studied using multivariable mixed effects models. Results: Over the study period, 2,159 neonates at 40 hospitals were evaluated. Perioperative mortality was 2.8%. Between hospitals, the use of adjuvant therapies and timing of arterial switch operation varied broadly. At the subject-level, older age at ASO was associated with higher mortality risk (age >6 days OR: 1.90, 95% CI: 1.11–3.26, p=0.02), cost, and length of stay. Receipt of a balloon atrial septostomy was associated with lower mortality risk (OR: 0.32, 95% CI: 0.17–0.59, p<0.001), cost, and length of stay. Later hospital median age at ASO was associated with higher odds of mortality (OR: 1.15 per day, 95% CI: 1.02 to 1.29, p=0.03), longer length of stay (p<0.004), and higher cost (p<0.001). Other hospital factors were not independently associated with the outcomes of interest. Conclusion: There was significant variation in preoperative care between hospitals. Some potentially modifiable aspects of perioperative care (timing of ASO and septostomy) were significantly associated with mortality, length of stay, and cost. Further research on the perioperative care of neonates is necessary to determine if modifying practice based on the observed associations translates into improved outcomes.