DNA methylation in children with prenatal methamphetamine exposure and environmental adversity.

BACKGROUND: Methamphetamine (MA) use during pregnancy is a significant public health concern in the United States and affects long-term brain and behavioral development in children. We hypothesized that prenatal MA exposure would be related to greater DNA methylation of HSD11B2 and postnatal environmental stress. METHODS: The Infant Development, Environment, and Lifestyle Study (IDEAL), a longitudinal study of prenatal MA exposure enrolled mother-infant dyads in California, Hawaii, Iowa, and Oklahoma. Prenatal exposure was defined by maternal self-report and/or meconium toxicology screening. At ages 10-11 years, 100 children were assessed for drug exposure and DNA methylation of HSD11B2. Hierarchical linear models were used to determine the association between prenatal MA exposure and methylation of HSD11B2 at four CpG sites. RESULTS: Prenatal MA exposure (1.4% vs 0.31%, P < 0.01) and early childhood adversity (3.0 vs 2.0, P < 0.01) were associated with greater DNA methylation of HSD11B2 at the CpG2 site. The statistically significant effects of early childhood adversity (B = 0.11, P < 0.01) and prenatal MA exposure (B = 0.32, P = 0.03) on DNA methylation remained after adjusting for covariates. CONCLUSIONS: Prenatal MA exposure is related to postnatal childhood adversity and epigenetic alterations in HSD11B2, an important gene along the stress response pathway suggesting prenatal and postnatal programming effects. IMPACT: Prenatal methamphetamine exposure has been associated with developmental issues in newborns, yet little is known about the stress pathophysiology of methamphetamine on neurobehavior. This is the first evidence that prenatal methamphetamine exposure acts as a stressor, confirming the third pathophysiology of methamphetamine exposure.

Knowledge and willingness to use pre-exposure prophylaxis among men who have sex with men in Northeastern Brazil.

Few studies evaluate knowledge and willingness to use pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in middle-income countries. Brazil added PrEP to public drug formularies in December 2017, but little is known about local knowledge and attitudes about PrEP among MSM outside metropolitan areas in Southern Brazil. The cross-sectional HIV Surveillance Survey Project in Brazil estimates HIV and STD prevalence among MSM in 12 state capitals. Among 32 participants at the Salvador, Bahia study site, we used qualitative interviews to assess knowledge, willingness, and barriers to PrEP use among MSM; few MSM had previous knowledge of PrEP and were willing to use PrEP. Clinical, behavioural, social, and structural factors influencing participants' knowledge and willingness to take PrEP included concerns about efficacy and side effects, access to culturally congruent services for MSM, and stigma. Some participants reported that learning about PrEP online positively influenced their willingness to use PrEP. Participants' opinions about PrEP's contribution to risk compensation varied. Interventions to provide culturally congruent care and destigmatise PrEP for MSM at high risk for HIV acquisition, particularly those conducted collaboratively with Brazil's civil society movement, may enhance the public health effort to expand access to PrEP in Brazil.