BACKGROUND Cardiovascular risk factors are associated with left ventricular hypertrophy (LVH), but little is known regarding related impact of longitudinal measures of childhood adiposity and left ventricular (LV) hemodynamics. OBJECTIVES The aim of this study is to examine the cumulative long-term burden and trends of excessive adiposity and elevated blood pressure (BP) during childhood on adult LVH and LV geometric remodeling patterns. Methods This longitudinal study consisted of 1,061 adults, aged 24 to 46 years, who had been examined 4 or more times for body mass index (BMI) and BP starting in childhood with an average follow-up of 28.0 years. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and BP from childhood to adulthood. Four LV geometric types were defined as normal, concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH), all based on LV mass indexed for body height (m2.7) and relative wall thickness. Results Higher values of BMI and systolic and diastolic BP of childhood and adulthood, as well as total AUC and incremental AUC were all significantly associated with higher LV mass index and LVH, adjusted for race, sex, and age. In addition, higher values of BMI and BP of childhood and adulthood, total AUC, and incremental AUC were significantly associated with EH and CH but not CR. Importantly, all these measures of BMI had a consistently and significantly greater influence on EH than measures of BP. Conclusions These findings indicate that the adverse influence of excessive adiposity and elevated BP levels on LVH begins in childhood.

Importance Electronic cigarette (e-cigarette) use in pregnancy has been steadily increasing and has been hyped as being a safe alternative to cigarette smoking during pregnancy. This review discloses what is currently known about e-cigarette use in pregnancy and the effects of its use on pregnancy outcomes. Objective To determine what is currently known about the prevalence of e-cigarette use in pregnancy and the effects of e-cigarette use on pregnancy and perinatal/neonatal outcomes. Evidence Acquisition A PubMed, CINAHL, and EMBASE search was undertaken using the search terms “pregnancy” OR “pregnancy complications” OR “pregnancy outcome” OR “newborn” OR “neonate” OR “birth” AND “electronic cigarettes” OR “e-cigarettes” OR “ecigarettes” OR “vaping” OR “vape.” The search was limited to the English language and between 2007 and October 12, 2017. Results The search identified 91 articles, 40 of which are the basis for this review. The prevalence of e-cigarette use is 0.6% to 15%. The amount of nicotine consumed by e-cigarette users is comparable to that consumed by cigarette smokers. Most of the animal model studies suggest a potential danger to the developing fetus primarily because of the nicotine consumed and that consumption has multiple effects on the immune system, neural development, lung function, and cardiac function. There is a widespread flawed perception that e-cigarettes are safe to use during pregnancy. Conclusions The marketing of e-cigarette use as a safer alternative to cigarette smoking has led to an increasing use even in pregnancy. The nicotine consumed by e-cigarettes is similar to that consumed by cigarette smoking. Animal studies confirm the dangers of nicotine to the developing fetus. More research needs to be done specifically assessing e-cigarette use, pregnancy, and pregnancy outcomes. Relevance The amount of nicotine consumed in cigarette smoking is similar to the amount of nicotine consumed with e-cigarettes. The effects of nicotine exposure during fetal development are well known and include effects on multiple organ systems. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to determine the prevalence of e-cigarette use in pregnancy, analyze and compare the nicotine consumed with cigarette smoking versus the nicotine consumed with e-cigarette smoking, and evaluate the risk in animal studies of the consumption of nicotine on the developing fetus.

INTRODUCTION The 2016 US Surgeon General’s Report suggests that the use of electronic nicotine delivery systems (ENDS) is a fetal risk factor. However, no previous study has estimated their effect on adverse pregnancy outcomes. We assessed the prevalence of current ENDS use in pregnant women and explored the effect on birth weight and smallness-for-gestational-age (SGA), correcting for misclassification from nondisclosure of smoking status. METHODS We conducted a cohort study with 248 pregnant women using questionnaire data and biomarkers (salivary cotinine, exhaled carbon monoxide, and hair nicotine). We evaluated the association between birth weight and the risk of SGA by applying multivariate linear and log-binomial regression to reproductive outcome data for 232 participants. Participants who did not disclose their smoking status were excluded from the referent group. Sensitivity analysis corrected for misclassification of smoking/ENDS use status. RESULTS The prevalence of current ENDS use among pregnant women was 6.8% (95% CI: 4.4–10.2%); most of these (75%) were concurrent smokers. Using self-reports, the estimated risk ratio of SGA for ENDS users was nearly two times the risk in the unexposed (RR=1.9, 95% CI: 0.6–5.5), and over three times that for ENDS-only users versus the unexposed (RR=3.1, 95% CI: 0.8–11.7). Excluding from the referent group smokers who did not disclose their smoking status, the risk of SGA for ENDS-only use was 5 times the risk in the unexposed (RR=5.1, 95% CI: 1.1– 22.2), and almost four times for all types of ENDS users (RR=3.8, 95% CI: 1.3–11.2). SGA risk ratios for ENDS users, corrected for misclassification due to self-report, were 6.5–8.5 times that of the unexposed. CONCLUSIONS Our data suggest that ENDS use is associated with an increased risk of SGA.

INTRODUCTION Public awareness of electronic nicotine delivery systems (ENDS) has increased over time, and the perception that ENDS offer a safer alternative to cigarettes may lead some pregnant women to use them to reduce cigarette smoking during pregnancy. No previous studies have used metabolite levels in hair to measure nicotine exposure for ENDS users during pregnancy. We aimed to measure and compare levels of nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) in hair samples from pregnant women who were current ENDS users, current smokers, and current non-smokers. We also aimed to estimate the association between ENDS use/smoking and smallness for gestational age (SGA). METHODS We used hair specimens from pregnant women who were dual users (ENDS and cigarettes), smokers, and non-smokers from a prospective cohort study to estimate exposure to nicotine, cotinine, and TSNAs. The exposure biomarkers and self-reports of smoking and ENDS use were used in log-binomial regression models to estimate risk ratios (RRs) for SGA among offspring. RESULTS Nicotine concentrations for pregnant dual users were not significantly different from those for smokers (11.0 and 10.6 ng/mg hair, respectively; p=0.58). Similarly, levels of cotinine, and TSNAs for pregnant dual users were not lower than those for smokers. The RR for SGA was similar for dual users and smokers relative to nonsmokers, (RR=3.5, 95% CI: 0.8–14.8) and (RR=3.3, 95% CI: 0.9–11.6), respectively. Using self-reports confirmed by hair nicotine, the RR values for dual ENDS users and smokers were 8.3 (95% CI: 1.0–69.1) and 7.3 (95% CI:1.0–59.0), respectively. CONCLUSIONS We did not observe lower levels of nicotine, cotinine, and TSNAs for current dual users compared to smokers during pregnancy. The risk of SGA for offspring of pregnant dual users was similar to that for offspring of pregnant smokers. Future studies are needed to further estimate the magnitude of the association between ENDS use and smallness for gestational age.

There is no standard policy regarding the regulatory or institutional approval of N-of-1 trials in the United States. The objective of this study was to examine whether institutional review boards (IRBs) accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP) consider N-of-1 trials as meeting the definition of human subjects research (45CFR46.102) and requiring IRB approval. A questionnaire was distributed via email to 170 AAHRPP-accredited IRBs in the United States. Responses were analyzed using statistical and qualitative methods. Nineteen of 59 respondents reported viewing N-of-1 trials as research. Twelve respondents reported having a policy regarding N-of-1 trials, and in all cases, such policies did not consider N-of-1 trials as meeting the definition of research. This topic deserves wider examination in the IRB literature and community to inform policies and guidance as N-of-1 trials become more common in the pursuit of personalized, precision medicine.