Adverse neonatal outcomes associated with maternal severe mental health diagnoses and opioid use.

OBJECTIVE: Determine odds ratios for neonatal abstinence syndrome (NAS) and neonatal intensive care unit (NICU) admissions for babies born to women associated with severe mental illness (SMI) and gestational opioid use. STUDY DESIGN: A retrospective pharmacoepidemiologic study using Medicaid data included 17,130 mothers with and 170,430 mothers without SMI, and their babies. Odds ratios for NAS and NICU admissions among babies born to mothers associated with SMI diagnoses and associated with varying degrees of gestational opioid use were determined using logistic regression. RESULTS: The adjusted odds ratio for a baby in the methadone or buprenorphine group having NAS was 168.93 [95% confidence interval (CI) 148.78-191.71, P < 0.001] and was 9.64 (95% CI 8.74-10.65, P < 0.001) for NICU admissions compared to babies with no opioid exposure. CONCLUSIONS: Chronicity of prescription maternal opioid use was the strongest factor associated with NAS and NICU admissions.

Ethanol alters proliferation and differentiation of normal and chromosomally abnormal human embryonic stem cell-derived neurospheres.

Ethanol is a powerful substance and, when consumed during pregnancy, has significant psychoactive and developmental effects on the developing fetus. These abnormalities include growth retardation, neurological deficits, and behavioral and cognitive deficiencies, commonly referred to as fetal alcohol spectrum disorder. The effect of ethanol has been reported to affect cellular development on the embryonic level, however, not much is known about mutations contributing to the influence of ethanol. The purpose of our study was to determine if mutation contribute to changes in differentiation patterning, cell-cycle regulatory gene expression, and DNA methylation in human embryonic stem cells after ethanol exposure. We exposed human embryonic stem cells (with and without know DNA mutations) to a low concentration (20 mM) of ethanol and measured neurosphere proliferation and differentiation, glial protein levels, expression of various cell-cycle genes, and DNA methylation. Ethanol altered cell-cycle gene expression between the two cell lines; however, gene methylation was not affected in ether lines.

Physiologic estrogen receptor alpha signaling in non-tumorigenic human mammary epithelial cells.

Currently, a number of breast cancer cell lines exist that serve as models for both estrogen receptor alpha (ERalpha) positive and ERalpha negative disease. Models are also available for pre-neoplastic breast epithelial cells that do not express ERalpha; however, there are no ideal systems for studying pre-neoplastic cells that are ERalpha positive. This has been largely due to the inability to establish an estrogen growth stimulated, non-tumorigenic breast epithelial cell line, as most human breast epithelial cells engineered to overexpress ERalpha have been found to be growth inhibited by estrogens. We have developed independently derived clones from the non-cancerous MCF-10A human breast cell line that express ERalpha and are growth stimulated by 17-beta-estradiol (E2) in the absence of epidermal growth factor (EGF), a cytokine normally required for MCF-10A cell proliferation. This effect is blocked by the selective estrogen receptor modulator (SERM), Tamoxifen and the selective estrogen receptor downregulator, ICI 182,780 (Faslodex, Fulvestrant). Exposure of these cells to EGF and E2 results in a growth inhibitory phenotype similar to previous reports. These data present a reconciling explanation for the previously described paradoxical effects of ERalpha overexpression, and provide a model for examining the carcinogenic effects of estrogens in non-tumorigenic human breast epithelial cells.