Epigenetics and the Exposome: DNA Methylation as a Proxy for Health Impacts of Prenatal Environmental Exposures.

The accumulation of every day exposures can impact health across the life course, but our understanding of such exposures is impeded by our ability to delineate the relationship between an individual's early life exposome and later life health effects. Measuring the exposome is challenging. Exposure assessed at a given time point captures a snapshot of the exposome but does not represent the full spectrum of exposures across the life course. In addition, the assessment of early life exposures and their effects is often further challenged by lack of relevant samples and the time gap between exposures and related health outcomes in later life. Epigenetics, specifically DNA methylation, has the potential to overcome these barriers as environmental epigenetic perturbances can be retained through time. In this review, we describe how DNA methylation can be framed in the world of the exposome. We offer three compelling examples of common environmental exposures, including cigarette smoke, the endocrine active compound bisphenol A (BPA), and the metal lead (Pb), to illustrate the application of DNA methylation as a proxy to measure the exposome. We discuss areas for future explorations and current limitations of this approach. Epigenetic profiling is a promising and rapidly developing tool and field of study, offering us a unique and powerful way to assess the early life exposome and its effects across different life stages.

Emergency Department Utilization for Substance Use Disorder During Pregnancy and Postpartum in the United States (2006-2016).

OBJECTIVES: We aimed to better understand emergency department (ED) use, admission patterns, and demographics for substance use disorder in pregnancy and postpartum (SUDPP). METHODS: In this longitudinal study, the United States Nationwide Emergency Department Sample was queried for all ED visits by 15- to 50-year-old women with a primary diagnosis defined by International Classification of Diseases, 9th or 10th edition Clinical Modification, codes of SUDPP between 2006 and 2016. Patterns of ED visit counts, rates, admissions, and ED charges were analyzed. RESULTS: Annual national estimated ED visits for SUDPP increased from 2,919 to 9,497 between 2006 and 2016 (a 12.4% annual average percentage change), whereas admission rates decreased (from 41.9% to 32.0%). ED visits were more frequent among women who were 20-29 years old, using Medicaid insurance, in the lowest income quartile, living in the South, and in metropolitan areas. Compared with the proportion of ED visits, 15- to 19-year-olds had significantly lower admission rates, whereas women with Medicaid and in the lowest income quartile had higher admission rates (p < .001). Opioid use, tobacco use, and mental health disorders were most commonly associated with SUDPP. The ED average inflation-adjusted charges for SUDPP increased from $1,486 to $3,085 between 2006 and 2016 (7.1% annual average percentage change; p < .001), yielding total annual charges of $4.02 million and $28.53 million. CONCLUSIONS: Despite the decrease in admissions, the number and charges for ED visits for SUDPP increased substantially between 2006 and 2016. These increasing numbers suggest a continuous need to implement preventive public health measures and provide adequate outpatient care for this condition in this population specifically.

There is reduced immunohistochemical staining of placental aromatase in severe neonatal opioid withdrawal syndrome.

BACKGROUND: Placental cytochrome p450 (CYP450) enzymes and efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are critical for transfer of drugs from the placenta to maternal circulation. CYP19A1 (aromatase) is the enzyme responsible for metabolizing methadone and buprenorphine in the human placenta. OBJECTIVE: We sought to determine if differences exist in CYP19A1 and efflux transporter immunostaining intensity and density within the syncytiotrophoblast in opioid-exposed and unexposed pregnancies. Additionally, we sought to investigate whether CYP19A1 and efflux transporter expression was different in placentas of infants who developed severe neonatal opioid withdrawal syndrome (NOWS) and those who did not. STUDY DESIGN: This was a retrospective nested case control study from 2014 to 2019 at a single tertiary care center. The opioid-exposed cohort included pregnant women aged ≥18 years on maintenance methadone or buprenorphine with non-anomalous singleton fetuses and gestational age ≥33 weeks. Controls included pregnant women with no medication exposure delivering at ≥37 weeks. De-paraffinized placental sections, inclusive of the apical syncytiotrophoblast membrane, were labeled with monoclonal antibodies for aromatase, P-gp, and BCRP. Placentas were scored for the presence and intensity of staining using the Allred scoring schema. Data were analyzed using descriptive, parametric, and nonparametric statistics. p < .05 was considered significant. RESULTS: One hundred and ten opioid-exposed neonates were included in this analysis (51 opioid-exposed cases and 59 opioid-exposed controls), with 68/110 delivering at term. Ten unexposed controls delivering at term were also included. The median placental Allred scores for aromatase were significantly lower in the opioid-exposed cohort compared with the unexposed controls (exposed 6.8 ± 1.4 vs. unexposed 7.5 ± 0.7, p = .03). The median placental Allred scores for aromatase were significantly lower in opioid-exposed cases that developed severe NOWS compared to opioid-exposed controls (p = .03) that did not develop severe NOWS. There were no differences in P-gp and BCRP scores between groups. CONCLUSIONS: Syncytiotrophoblast aromatase immunostaining scores were reduced in opioid-exposed cases compared to unexposed controls. Additionally, infants who developed severe NOWS had significantly lower placental aromatase in the apical syncytiotrophoblast compared with those without severe NOWS.