Association of Early-Life Social and Digital Media Experiences With Development of Autism Spectrum Disorder-Like Symptoms.

Importance: Despite growing evidence that parent-child interactions and time viewing digital media affect child development, these factors have rarely been studied in association with autism spectrum disorder (ASD) symptoms. Objective: To determine the association of experiential factors, including social activities and screen viewing in the first 18 months of life, perinatal factors, and demographic factors, with ASD-like symptoms and risk on the Modified Checklist for Autism in Toddlers (M-CHAT) at 2 years. Design, Setting, and Participants: Data for this cohort study were derived from the National Children's Study, a US multicenter epidemiological study of environmental influences on child health and development. A total of 2152 children were enrolled at birth from October 1, 2010, to October 31, 2012. Data were analyzed from December 1, 2017, to December 3, 2019. Exposures: Caregivers reported whether the child viewed television and/or videos (yes or no) at 12 months of age, hours of viewing at 18 months of age, time spent by the caregiver reading to the child (number of days per week compared with daily) at 12 months of age, and frequency of playing with the child (daily or less than daily) at 12 months of age. Prematurity, maternal age at birth, child sex, household income, race/ethnicity, and caregiver English-language status were included in analysis. Main Outcomes and Measures: Significant association of exposures with ASD risk by M-CHAT and/or ASD-like symptoms assessed by revised M-CHAT (M-CHAT-R) total score in multiple regression models. Results: Among the 2152 children included in the analysis (1099 boys [51.1%]), television and/or video viewing (yes or no) at 12 months of age was significantly associated with greater ASD-like symptoms at 2 years of age (change, 4.2%; 95% CI, 0.1%-8.3%) but not with ASD risk (risk prevalence rates, 8.3% vs 4.4%; adjusted odds ratio [AOR], 1.40; 95% CI, 0.86-2.29). Similarly, parent-child play daily compared with less than daily was significantly associated with fewer ASD-like symptoms at 2 years of age (change, -8.9%; 95% CI, -16.5% to -0.9%) but not with ASD risk (risk prevalence rates, 6.4% vs 14.0%; AOR, 0.58; 95% CI, 0.31-1.08). However, high screen viewing at 18 months of age was not significantly associated with ASD-like symptoms (change, 10.7%; 95% CI, -2.0% to 23.0%) or ASD risk by M-CHAT (AOR, 1.18; 95% CI, 0.56-2.49) at 2 years of age. Conclusions and Relevance: This cohort study found greater screen exposure and less caregiver-child play early in life to be associated with later ASD-like symptoms. Further research is needed to evaluate experiential factors for potential risk or protective effects in ASD.

Metabolism of deoxypyrimidines and deoxypyrimidine antiviral analogs in isolated brain mitochondria.

The goal of this project was to characterize deoxypyrimidine salvage pathways used to maintain deoxynucleoside triphosphate pools in isolated brain mitochondria and to determine the extent that antiviral pyrimidine analogs utilize or affect these pathways. Mitochondria from rat brains were incubated in media with labeled and unlabeled deoxynucleosides and deoxynucleoside analogs. Products were analyzed by HPLC coupled to an inline UV monitor and liquid scintillation counter. Isolated mitochondria transported thymidine and deoxycytidine into the matrix, and readily phosphorylated both of these to mono-, di-, and tri-phosphate nucleotides. Rates of phosphorylation were much higher than rates observed in mitochondria from heart and liver. Deoxyuridine was phosphorylated much more slowly than thymidine and only to dUMP. 3'-azido-3'-deoxythymidine, zidovudine (AZT), an antiviral thymidine analog, was phosphorylated to AZT-MP as readily as thymidine was phosphorylated to TMP, but little if any AZT-DP or AZT-TP was observed. AZT at 5.5 ± 1.7 µM was shown to inhibit thymidine phosphorylation by 50%, but was not observed to inhibit deoxycytidine phosphorylation except at levels > 100 µM. Stavudine and lamivudine were inert when incubated with isolated brain mitochondria. The kinetics of phosphorylation of thymidine, dC, and AZT were significantly different in brain mitochondria compared to mitochondria from liver and heart.