Prenatal Hazardous Substance Use And Adverse Infant Birth Outcomes

PRENATAL HAZARDOUS SUBSTANCE USE AND ADVERSE INFANT BIRTH OUTCOMES. Odayme Quesada, Nathan Gotman, Kimberly A. Yonkers (Sponsored by Doris Duke Charitable Foundation). Department of Psychiatry, Yale University, School of Medicine, New Haven, CT. This thesis is composed of two studies, which assessed the effect of prenatal substance use on infant birth outcomes. The first study systematically analyzed a full spectrum of hazardous substance and known risk factors to determine which has a greater effect on infant birth outcomes. We used data from two comprehensive, prospective cohort studies and recursive partitioning class analysis to characterize the effect of in utero hazardous substance exposure on preterm birth and delivering a small for gestational age infant. Compared to cocaine and opiate non-users, cocaine users were 3.53 times as likely (95% CI: 1.65-7.56; p=0.001) and opiate users 2.86 times as likely (95% CI: 1.11-7.36; p=0.03) to deliver preterm. The odds of delivering a small for gestational age infant for women who smoked more than two cigarettes daily was 3.74, (95% CI: 2.47-5.65; p\u3c0.0001) compared to women who smoked two or less cigarettes daily and had one previous child. Similarly, less educated, nulliparous women who smoked two or fewer cigarettes daily were 4.12 times as likely (95% CI: 2.04-8.34; p\u3c0.0001) to have a small for gestational age infant. In conclusion, among our covariates, prenatal cocaine and opiate use are the predominant risk factors for preterm birth; while tobacco use was the primary risk factor predicting small for gestational age at delivery. Multi-substance use did not substantially increase risk of adverse birth outcomes over these risk factors. Our second study focused on the effects of timing and amount of exposure on birth outcomes. Despite our desire to look at these effects for different substances individually our sample size only allowed us to do so for marijuana and tobacco. To explore effects, we used prospectively collected biological and self report data from participants enrolled in an integrated obstetrical/substance abuse treatment program. In our cohort prenatal marijuana use appeared to affect infant head circumference. There was no clear association between marijuana use and other growth parameters, gestational age, or ponderal index. Nor was there a clear association between cigarette use and any of the infant birth outcomes assessed. In conclusion, marijuana use appeared to affect growth parameters, thus implying some effect on growth retardation

Multidimensional Sleep Health Is Associated with Cardiovascular Disease Prevalence and Cardiometabolic Health in US Adults.

Individual sleep dimensions have been linked to cardiovascular disease (CVD) risk and cardiometabolic health (CMH), but sleep health is multifaceted. We investigated associations of a multidimensional sleep health (MDSH) score, enabling the assessment of sleep health gradients, with CVD and CMH. Participants were 4555 adults aged ≥20 years from the 2017-2018 National Health and Nutrition Examination Survey. A MDSH score, capturing poor, moderate, and ideal sleep was computed from self-reported sleep duration, sleep regularity, difficulty falling asleep, symptoms of sleep disorders, and daytime sleepiness. Survey-weighted multivariable linear and logistic models examined associations of MDSH with CVD and CMH. Ideal and moderate vs. poor MDSH were related to lower odds of hypertension (62% and 41%), obesity (73% and 56%), and central adiposity (68% and 55%), respectively; a statistically significant linear trend was observed across gradients of MDSH (p-trend < 0.001). Ideal vs. moderate/poor MDSH was associated with 32% and 40% lower odds of prevalent CVD and type 2 diabetes, respectively. More favorable MDSH was associated with lower blood pressure, BMI, waist circumference, and fasting glucose. In sex-stratified analyses, ideal vs. moderate/poor MDSH was associated with lower CVD odds and blood pressure in women only. The MDSH framework may be more than just the sum of its parts and could better capture information regarding CVD risk

Production, purification and preliminary X-ray crystallographic studies of adeno-associated virus serotype 7

Crystals of baculovirus-expressed adeno-associated virus serotype 7 capsids have been produced which diffract X-rays to ∼3.0 Å resolution

Cardiovascular Complications During Delivery Admissions Associated With Assisted Reproductive Technology (from a National Inpatient Sample Analysis 2008 to 2019)

Women who conceive through assisted reproductive technology (ART) have a known increased risk of obstetric complications. However, whether ART is also associated with higher risk of developing cardiovascular complications during delivery admissions has not been well established. We used data from the National Inpatient Sample (2008 to 2019) and used the International Classification of Diseases codes to identify delivery hospitalizations and ART procedures. A total of 45,867,086 weighted delivery cases were identified, of which 0.24% were among women who conceived through ART (n = 108,542). Women with an ART history were older at the time of delivery (median 35 vs 28 years, p \u3c 0.01) and had a higher prevalence of hypertension, gestational diabetes, and dyslipidemia (all, p \u3c 0.01). After adjustment for age, race/ethnicity, co-morbidities, multiple gestation, insurance, and income, ART remained an independent predictor of peripartum cardiovascular complications, including pre-eclampsia/eclampsia (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.45 to 1.51), heart failure (aOR 1.94, 95% CI 1.10 to 3.40), and cardiac arrhythmias (aOR 1.39, 95% CI 1.30 to 1.48), compared with natural conception. Likewise, the risk of acute kidney injury (aOR 2.57, 95% CI 2.25 to 2.92), ischemic stroke (aOR 1.73, 95% CI 1.24 to 2.43), hemorrhagic stroke (aOR 1.63, 95% CI 1.27 to 2.11), pulmonary edema (aOR 2.29, 95% CI 2.02 to 2.61), and venous thromboembolism (aOR 1.92, 95% CI 1.63 to 2.25) were higher with ART. However, odds of developing peripartum cardiomyopathy or acute coronary syndrome were not associated with ART. Length of stay (3 vs 2 days, p \u3c 0.01) and cost of hospitalization ($5,903 vs$3,922, p \u3c 0.01) were higher for deliveries among women with a history of ART. In conclusion, women who conceived with ART had higher risk of pre-eclampsia, heart failure, arrhythmias, stroke, and other complications during their delivery hospitalizations. This may, in part, contribute to their increased resource utilization seen

Use of Ballistocardiography to Monitor Cardiovascular Hemodynamics in Preeclampsia.

Objective: Pregnancy requires a complex physiological adaptation of the maternal cardiovascular system, which is disrupted in women with pregnancies complicated by preeclampsia, putting them at higher risk of future cardiovascular events. The measurement of body movements in response to cardiac ejection via ballistocardiogram (BCG) can be used to assess cardiovascular hemodynamics noninvasively in women with preeclampsia. Methods: Using a previously validated, modified weighing scale for assessment of cardiovascular hemodynamics through measurement of BCG and electrocardiogram (ECG) signals, we collected serial measurements throughout pregnancy and postpartum and analyzed data in 30 women with preeclampsia and 23 normotensive controls. Using BCG and ECG signals, we extracted measures of cardiac output, J-wave amplitude × heart rate (J-amp × HR). Mixed-effect models with repeated measures were used to compare J-amp × HRs between groups at different time points in pregnancy and postpartum. Results: In normotensive controls, the J-amp × HR was significantly lower early postpartum (E-PP) compared with the second trimester (T2; p = 0.016) and third trimester (T3; p = 0.001). Women with preeclampsia had a significantly lower J-amp × HR compared with normotensive controls during the first trimester (T1; p = 0.026). In the preeclampsia group, there was a trend toward an increase in J-amp × HR from T1 to T2 and then a drop in J-amp × HR at T3 and further drop at E-PP. Conclusions: We observe cardiac hemodynamic changes consistent with those reported using well-validated tools. In pregnancies complicated by preeclampsia, the maximal force of contraction is lower, suggesting lower cardiac output and a trend in hemodynamics consistent with the hyperdynamic disease model of preeclampsia

Use of Ballistocardiography to Monitor Cardiovascular Hemodynamics in Preeclampsia.

Objective: Pregnancy requires a complex physiological adaptation of the maternal cardiovascular system, which is disrupted in women with pregnancies complicated by preeclampsia, putting them at higher risk of future cardiovascular events. The measurement of body movements in response to cardiac ejection via ballistocardiogram (BCG) can be used to assess cardiovascular hemodynamics noninvasively in women with preeclampsia. Methods: Using a previously validated, modified weighing scale for assessment of cardiovascular hemodynamics through measurement of BCG and electrocardiogram (ECG) signals, we collected serial measurements throughout pregnancy and postpartum and analyzed data in 30 women with preeclampsia and 23 normotensive controls. Using BCG and ECG signals, we extracted measures of cardiac output, J-wave amplitude × heart rate (J-amp × HR). Mixed-effect models with repeated measures were used to compare J-amp × HRs between groups at different time points in pregnancy and postpartum. Results: In normotensive controls, the J-amp × HR was significantly lower early postpartum (E-PP) compared with the second trimester (T2; p = 0.016) and third trimester (T3; p = 0.001). Women with preeclampsia had a significantly lower J-amp × HR compared with normotensive controls during the first trimester (T1; p = 0.026). In the preeclampsia group, there was a trend toward an increase in J-amp × HR from T1 to T2 and then a drop in J-amp × HR at T3 and further drop at E-PP. Conclusions: We observe cardiac hemodynamic changes consistent with those reported using well-validated tools. In pregnancies complicated by preeclampsia, the maximal force of contraction is lower, suggesting lower cardiac output and a trend in hemodynamics consistent with the hyperdynamic disease model of preeclampsia

Fitness attenuates long-term cardiovascular outcomes in women with ischemic heart disease and metabolic syndrome

Background: The prevalence of metabolic syndrome continues to increase steadily while fitness remains relatively low. The contribution of fitness on longer-term cardiovascular outcomes and mortality in individuals with cardiovascular disease and metabolic syndrome remains unknown. Design: Women's Ischemia Syndrome Evaluation (WISE) prospective cohort (enrolled 1996–2001) of women undergoing invasive coronary angiography with signs/symptoms of ischemic heart disease. Methods: Investigated the association of fitness, defined as >7METs measured by self-reported Duke Activity Status Index (DASI), and both metabolic syndrome (ATPIII criteria) and dysmetabolism (ATPIII criteria and/or treated diabetes) with long-term cardiovascular outcomes and all-cause mortality risk. Results: Among the 492 women followed for a median of 8.6 years (range 0–11 years), 19.5% were fit-metabolically healthy (reference), 14.4% fit-metabolic syndrome, 29.9% unfit-metabolically healthy, and 36.2% unfit-metabolic syndrome. Compared to reference, MACE risk was 1.52-fold higher in fit-metabolic syndrome women (HR 1.52, 95% CI 1.03–2.26) and 2.42-fold higher in unfit-metabolic syndrome women (HR 2.42, 95% CI 1.30–4.48). Compared to reference, mortality risk was 1.96-fold higher in fit-dysmetabolism (HR 1.96, 95% CI 1.29–3.00) and 3-fold higher in unfit-dysmetabolism women (HR 3.0, 95% CI 1.66–5.43). Conclusions: In a high risk cohort of women with signs/symptoms of ischemic heart disease, unfit-metabolically healthy and fit-metabolically unhealthy women were at higher risk of long-term MACE and mortality compared to fit-metabolically healthy women; and women who were unfit and metabolically unhealthy were at the highest risk. Our study demonstrates that metabolic health and fitness play an important role in long term outcomes that warrants further investigation. Registration: https://www.clinicaltrials.gov/ct2/show/NCT00000554 (NCT00000554

Chronic rheumatologic disorders and cardiovascular disease risk in women

Cardiovascular disease (CVD) is a major health threat to women worldwide. In addition to traditional CVD risk factors, autoimmune conditions are increasingly being recognized as contributors to adverse CVD consequences in women. Chronic systemic autoimmune and inflammatory disorders can trigger premature and accelerated atherosclerosis, microvascular dysfunction, and thrombosis. The presence of comorbid conditions, duration of the autoimmune condition, disease severity, and treatment of underlying inflammation are all factors that impact CVD risk and progression. Early identification and screening of CVD risk factors in those with underlying autoimmune conditions may attenuate CVD in this population. Treatment with non-steroidal anti-inflammatory drugs, corticosteroids, disease modifying agents and biologics may influence CVD risk factors and overall risk. Multi-disciplinary and team-based care, clinical trials, and collaborative team-science studies focusing on systemic autoimmune conditions will be beneficial to advance care for women

Reduced myocardial perfusion is common among subjects with ischemia and no obstructive coronary artery disease and heart failure with preserved ejection fraction: a report from the WISE-CVD continuation study

Aim: Women with evidence of ischemia and no obstructive coronary artery disease (INOCA) have an increased risk of major adverse cardiac events, including heart failure with preserved ejection fraction (HFpEF). To investigate potential links between INOCA and HFpEF, we examined pathophysiological findings present in both INOCA and HFpEF.Methods: We performed adenosine stress cardiac magnetic resonance imaging (CMRI) in 56 participants, including 35 women with suspected INOCA, 13 women with HFpEF, and 8 reference control women. Myocardial perfusion imaging was performed at rest and with vasodilator stress with intravenous adenosine. Myocardial perfusion reserve index was quantified as the ratio of the upslope of increase in myocardial contrast at stress vs. rest. All CMRI measures were quantified using CVI42 software (Circle Cardiovascular Imaging Inc). Statistical analysis was performed using linear regression models, Fisher’s exact tests, ANOVA, or Kruskal-Wallis tests.Results: Age (P = 0.007), Body surface area (0.05) were higher in the HFpEF group. Left ventricular ejection fraction (P = 0.02) was lower among the INOCA and HFpEF groups than reference controls after age adjustment. In addition, there was a graded reduction in myocardial perfusion reserve index in HFpEF vs. INOCA vs. reference controls (1.5 ± 0.3, 1.8 ± 0.3, 1.9 ± 0.3, P = 0.02), which was attenuated with age-adjustment.Conclusion: Reduced myocardial perfusion reserve appears to be a common pathophysiologic feature in INOCA and HFpEF patients