Opioid Use Among HIV-Positive Pregnant Women and the Risk for Maternal-Fetal Complications.

OBJECTIVE: To assess patient- and hospital-level characteristics associated with opioid use in human immunodeficiency virus (HIV)-positive pregnant women and fetal health outcomes. METHODS: Using the 2002-2014 Nationwide Inpatient Sample database, we analyzed discharge records to describe the rates of opioid use among HIV-positive pregnant women. Logistic regression was used to quantify the magnitude of the association between exposure status and maternal-fetal outcomes. RESULTS: Opioid use was fourfold greater among HIV-positive pregnant women compared with their HIV-negative counterparts (odds ratio 4.0; 95% confidence interval 3.15-5.12). Relatively smaller but significant increases in the early onset of delivery, poor fetal growth, abortive pregnancy, and spontaneous abortion also were observed in association with HIV-positive status and opioid drug use during pregnancy. CONCLUSIONS: An increased risk of negative maternal-fetal complications persists among HIV-positive women who use opioids during pregnancy. Focusing on predisposing factors and monitoring opioid dispensing may mitigate overuse or abuse in this vulnerable population.

Arginase 1 Insufficiency Precipitates Amyloid-ß Deposition and Hastens Behavioral Impairment in a Mouse Model of Amyloidosis.

Alzheimer's disease (AD) includes several hallmarks comprised of amyloid-ß (Aß) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1fl/fl and LysMcreTg/+ mice crossed with APP Tg2576 mice. Our data indicated that Arg1 haploinsufficiency promoted Aß deposition, exacerbated some behavioral impairment, and decreased components of Ragulator-Rag complex involved in mechanistic target of rapamycin complex 1 (mTORC1) signaling and autophagy. Additionally, Arg1 repression and arginine supplementation both impaired microglial phagocytosis in vitro. These data suggest that proper function of Arg1 and arginine metabolism in myeloid cells remains essential to restrict amyloidosis.

Effects of Maternal Carbohydrate and Fat Intake on Fetal Telomere Length.

OBJECTIVES: Telomere length can be affected by dietary factors in adults. We investigated the association between maternal carbohydrate and fat intake during pregnancy and telomere length in neonatal cord blood leukocytes. We hypothesized that high fat consumption and high carbohydrate consumption would be associated with shortened fetal telomere length. METHODS: We collected umbilical cord blood at delivery from women admitted for labor and delivery in a university hospital (N = 62) and extracted genomic DNA using quantitative polymerase chain reaction. We quantified telomere length using the telomere-to-single copy gene ratio method (T:S ratio). High carbohydrate intake was defined as consumption of >175 g/day and high fat intake as >35 g/day. We performed generalized linear regression modeling and bootstrap statistical analyses to derive precise estimates of association. RESULTS: Of the 62 maternal-fetal dyads included in this study, 79% were classified as high carbohydrate consumers and 37% were classified as high fat consumers. High fat consumption had a significant negative effect on T:S ratio (P < 0.05). Although high carbohydrate consumption was associated with a decreased T:S ratio, this relation did not attain statistical significance. CONCLUSIONS: To our knowledge, this study is the first evidence of an association between maternal high fat consumption and shortened fetal telomere length. These findings could enhance our understanding of the role of maternal diet in fetal programming.

Association Between Maternal-Perceived Psychological Stress and Fetal Telomere Length.

OBJECTIVE: Our study aimed to investigate the association between maternal-perceived psychological stress and fetal telomere length. METHODS: We recruited women in labor upon hospital delivery admission. Based on responses to the Perceived Stress Scale, we categorized participants as having "high," "normal," or "low" perceived stress. We collected umbilical cord blood samples (N = 71) and isolated genomic DNA from cord blood leukocytes using quantitative polymerase chain reaction. We used a ratio of relative telomere length derived by telomere-to-single-copy gene ratio (T/S ratio). We applied analysis of variance and bootstrapping statistical procedures. RESULTS: Sixteen (22.5%) women were classified as having low perceived stress, 42 (59.2%) were classified as having normal perceived stress, and 13 (18.3%) were classified as having high perceived stress. Fetal telomere length differed significantly across the three stress groups in a dose-response pattern (T/S ratio of those with low perceived stress was greater than those with normal perceived stress, which was greater than those with high perceived stress [P < 0.05]). CONCLUSIONS: Our findings support our hypothesis that maternal-perceived psychological stress during pregnancy is associated with shorter fetal telomere length and suggest maternal stress as a possible marker for early intrauterine programming for accelerated chromosomal aging.