Prepregnancy physiology and subsequent preterm preeclampsia.

BACKGROUND: Preeclampsia is a common pregnancy complication with debated etiology. OBJECTIVE: To evaluate the contribution of prepregnancy physiology, biochemistry, and anthropometrics to the subsequent development of preterm preeclampsia. STUDY DESIGN: One hundred twenty-four participants were recruited through open recruitment and targeted mailings. Participants included 81 nulliparous women and 43 with a history of preterm preeclampsia. We characterized cardiovascular function, metabolic profile, and body composition in 100 nonpregnant women who went on to subsequent pregnancy. Measures included plasma volume, baseline cardiovascular function and cardiovascular response to volume challenge, body composition, and circulating biochemical measures. Pregnancy outcome was obtained through chart review. Prepregnancy metrics for women who developed preterm preeclampsia were compared with measurements for those who did not, with adjustment for a history of prior preterm preeclampsia. Logistic regression modeling was used to identify the strongest prepregnancy factors associated with preterm preeclampsia. RESULTS: Pregnancy outcomes included 11 women with preterm preeclampsia, 7 women with term preeclampsia, 20 women with other hypertension affecting their pregnancy, and 62 with uncomplicated pregnancies. We observed no difference in maternal age, study cycle day, lean body mass, uterine hemodynamics, or flow-mediated dilation across groups. Women with preterm preeclampsia had greater android fat content 3215±1143 vs 1918±1510 g (P=.002), faster supine pulse, 77±7 vs 67±10 beats per minute (P=.001), higher supine diastolic blood pressure 82±6 vs 68±6 mmHg (P<.001), increased cardiac output 5.6±1.1 vs 4.6±1 L/min (P=.002), faster aortic-popliteal pulse wave velocity 4.5±0.7 vs 3.8±0.5 m/sec (P<.001), and exaggerated cardiac output response to volume challenge 20±9 vs 9±12 L/min (P=.002) compared to those with other pregnancy outcomes. Women who developed preterm preeclampsia also had reduced renal vascular resistance index 0.86±0.08 vs 0.97±0.12 (P=.005) compared with other pregnancy outcomes when assessed prior to pregnancy. Women with subsequent preterm preeclampsia had higher serum c-reactive protein 10.7±12.5 vs 4.1±5.8 mg/mL (P=.003) and greater insulin resistance, as assessed by Homeostatic Model Assessment for Insulin Resistance calculation 2.2±1.1 vs 1.2±0.9 (P<.001). CONCLUSION: Prepregnancy physiology is linked to subsequent preterm preeclampsia. The same factors associated with metabolic syndrome are more prominent in patients who develop preterm preeclampsia than those who do not, including increased vessel stiffness, low vascular compliance, high cardiac output, reduced renal vascular resistance index, insulin resistance, and increased android fat, all consistent with subclinical features of the metabolic syndrome.

Care plan for individuals at risk for preeclampsia: shared approach to education, strategies for prevention, surveillance, and follow-up.

Preeclampsia is a multisystemic disorder of pregnancy that affects 250,000 pregnant individuals in the United States and approximately 10 million worldwide per annum. Preeclampsia is associated with substantial immediate morbidity and mortality but also long-term morbidity for both mother and offspring. It is now clearly established that a low dose of aspirin given daily, beginning early in pregnancy modestly reduces the occurrence of preeclampsia. Low-dose aspirin seems safe, but because there is a paucity of information about long-term effects on the infant, it is not recommended for all pregnant individuals. Thus, several expert groups have identified clinical factors that indicate sufficient risk to recommend low-dose aspirin preventive therapy. These risk factors may be complemented by biochemical and/or biophysical tests that either indicate increased probability of preeclampsia in individuals with clinical risk factors, or more importantly, identify increased likelihood in those without other evident risk. In addition, the opportunity exists to provide this population with additional care that may prevent or mitigate the short- and long-term effects of preeclampsia. Patient and provider education, increased surveillance, behavioral modification, and other approaches to improve outcomes in these individuals can improve the chance of a healthy outcome. We assembled a group with diverse, relevant expertise (clinicians, investigators, advocates, and public and private stakeholders) to develop a care plan in which providers and pregnant individuals at risk can work together to reduce the risk of preeclampsia and associated morbidities. The plan is for care of individuals at moderate to high risk for developing preeclampsia, sufficient to receive low-dose aspirin therapy, as identified by clinical and/or laboratory findings. The recommendations are presented using the GRADE methodology with the quality of evidence upon which each is based. In addition, printable appendices with concise summaries of the care plan's recommendations for patients and healthcare providers are provided. We believe that this shared approach to care will facilitate prevention of preeclampsia and its attendant short- and long-term morbidity in patients identified as at risk for development of this disorder.

Randomized Controlled Trial Examining the Efficacy of Adding Financial Incentives to Best practices for Smoking Cessation Among pregnant and Newly postpartum Women.

We report results from a single-blinded randomized controlled trial examining financial incentives for smoking cessation among 249 pregnant and newly postpartum women. Participants included 169 women assigned to best practices (BP) or BP plus financial incentives (BP + FI) for smoking cessation available through 12-weeks postpartum. A third condition included 80 never-smokers (NS) sociodemographically-matched to women who smoked. Trial setting was Burlington, Vermont, USA, January, 2014 through January, 2020. Outcomes included 7-day point-prevalence abstinence antepartum and postpartum, and birth and other infant outcomes during 1st year of life. Reliability and external validity of results were assessed using pooled results from the current and four prior controlled trials coupled with data on maternal-smoking status and birth outcomes for all 2019 singleton live births in Vermont. Compared to BP, BP + FI significantly increased abstinence early- (AOR = 9.97; 95%CI, 3.32-29.93) and late-pregnancy (primary outcome, AOR = 5.61; 95%CI, 2.37-13.28) and through 12-weeks postpartum (AOR = 2.46; CI,1.05-5.75) although not 24- (AOR = 1.31; CI,0.54-3.17) or 48-weeks postpartum (AOR = 1.33; CI,0.55-3.25). There was a significant effect of trial condition on small-for-gestational-age (SGA) deliveries (χ2 [2] = 9.01, P = .01), with percent SGA deliveries (+SEM) greatest in BP, intermediate in BP + FI, and lowest in NS (17.65 + 4.13, 10.81 + 3.61, and 2.53 + 1.77, respectively). Reliability analyses supported the efficacy of financial incentives for increasing abstinence antepartum and postpartum and decreasing SGA deliveries; external-validity analyses supported relationships between antepartum cessation and SGA risk. Adding financial incentives to Best Practice increases smoking cessation among antepartum and postpartum women and improves other maternal-infant outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02210832.

The Independent Contribution of Uterine Blood Flow to Birth Weight and Body Composition in Smoking Mothers.

OBJECTIVE: This study aims to evaluate the relationship of maternal smoking to uterine artery hemodynamics and examine independent contributions to birth weight and fetal body composition. STUDY DESIGN: Women were enrolled in a prospective randomized controlled study targeting smoking abstinence. Uterine artery Doppler ultrasound was performed and volumetric blood flow was calculated. Third trimester ultrasound estimates of fetal body composition were performed and birth weight was recorded. RESULTS: Uterine artery volumetric flow and resistance index (RI) were significantly correlated with birth weight adjusted for gestational age (R = 0.35, p = 0.002; R = - 0.27, p = 0.02). Volumetric flow was significantly associated with fetal fat mass (R = 0.30, p = 0.018). Smoking status did not have significant effects on lean body mass (t [61] = 0.60, p = 0.55), fat mass (t [61] = 1.67, p = 0.10), or volumetric flow (t = 0.86, df = 87, p = 0.39). Stepwise regression identified volumetric flow (ß = 0.81, 95% confidence interval [CI]: 0.35-1.27, p < 0.001), maternal prepregnancy body mass index (ß = 16.04, 95% CI: 2.57-29.50, p = 0.02), and fetal sex (ß = 346.28, 95% CI: -532.64 to 159.91, p < 0.001, where male = 0 and female = 1) as independent contributors to birth weight adjusted for gestational age. CONCLUSION: No direct relationship of smoking to uterine artery hemodynamics was demonstrated. Volumetric flow was an independent contributor to birth weight and was associated with fetal fat deposition, while smoking was not independently associated with either outcome.

Pregnancy induces persistent changes in vascular compliance in primiparous women.

OBJECTIVE: Pregnancy induces rapid, progressive, and substantial changes to the cardiovascular system. The low recurrence risk of preeclampsia, despite familial predisposition, suggests an adaptation associated with pregnancy that attenuates the risk for subsequent preeclampsia. We aimed to evaluate the persistent effect of pregnancy on maternal cardiovascular physiology. STUDY DESIGN: Forty-five healthy nulliparous women underwent baseline cardiovascular assessment before conception and repeated an average of 30 months later. After baseline evaluation, 17 women conceived singleton pregnancies and all delivered at term. The remaining 28 women comprised the nonpregnant control group. We measured mean arterial blood pressure, cardiac output, plasma volume, pulse wave velocity, uterine blood flow, and flow-mediated vasodilation at each visit. RESULTS: There was a significant decrease in mean arterial pressure from the prepregnancy visit to postpartum in women with an interval pregnancy (prepregnancy, 85.3±1.8; postpartum, 80.5±1.8 mm Hg), with no change in nonpregnant control subjects (visit 1, 80.3±1.4; visit 2, 82.8±1.4 mm Hg) (P=.002). Pulse wave velocity was significantly decreased in women with an interval pregnancy (prepregnancy, 2.73±0.05; postpartum, 2.49±0.05 m/s), as compared with those without an interval pregnancy (visit 1, 2.56±0.04; visit 2, 2.50±0.04 m/s) (P=.005). We did not observe a residual effect of pregnancy on cardiac output, plasma volume, uterine blood flow, or flow-mediated vasodilation. CONCLUSION: Our observations of decreased mean arterial pressure and reduced arterial stiffness following pregnancy suggest a significant favorable effect of pregnancy on maternal cardiovascular remodeling. These findings may represent a mechanism by which preeclampsia risk is reduced in subsequent pregnancies.

Increased oxidized low-density lipoprotein causes blood-brain barrier disruption in early-onset preeclampsia through LOX-1.

Early-onset preeclampsia (EPE) is a severe form of preeclampsia that involves life-threatening neurological complications. However, the underlying mechanism by which EPE affects the maternal brain is not known. We hypothesized that plasma from women with EPE increases blood-brain barrier (BBB) permeability vs. plasma from women with late-onset preeclampsia (LPE) or normal pregnancy (NP) and investigated its underlying mechanism by perfusing cerebral veins from nonpregnant rats (n=6-7/group) with human plasma from women with EPE, LPE, or NP and measuring permeability. We show that plasma from women with EPE significantly increased BBB permeability vs. plasma from women with LPE or NP (P<0.001). BBB disruption in response to EPE plasma was due to a 260% increase of circulating oxidized LDL (oxLDL) binding to its receptor, LOX-1, and subsequent generation of peroxynitrite (P<0.001). A rat model with pathologically high lipid levels in pregnancy showed symptoms of preeclampsia, including elevated blood pressure, growth-restricted fetuses, and LOX-1-dependent BBB disruption, similar to EPE (P<0.05). Thus, we have identified LOX-1 activation by oxLDL and subsequent peroxynitrite generation as a novel mechanism by which disruption of the BBB occurs in EPE. As increased BBB permeability is a primary means by which seizure and other neurological symptoms ensue, our findings highlight oxLDL, LOX-1, and peroxynitrite as important therapeutic targets in EPE.

Examining the timing of changes in cigarette smoking upon learning of pregnancy.

OBJECTIVE AND METHOD: Timeline Follow-back interviews were conducted with 107 pregnant women enrolling in smoking cessation and relapse prevention clinical trials in the Burlington, VT area between 2006 and 2009 to examine the time course of changes in smoking between learning of pregnancy and the first prenatal care visit. We know of no systematic studies of this topic. RESULTS: Women reported learning of pregnancy at 5.1±2.2 weeks gestation and attending a first prenatal care visit at 10.1±3.6 weeks gestation. In the intervening five weeks, 22% of women became abstainers, 62% reduced their smoking, and 16% maintained or increased their smoking. Women who made changes typically reported doing so within the first 2 days after learning of pregnancy, with few changes occurring beyond the first week after learning of pregnancy. CONCLUSION: In this first effort to systematically characterize the time course of changes in smoking upon learning of pregnancy, the majority of pregnant smokers who quit or made reductions reported doing so soon after receiving the news. Further research is needed to assess the reliability of these results and to examine whether devising strategies to provide early interventions for women who continue smoking after learning of pregnancy is warranted.

Examining two different schedules of financial incentives for smoking cessation among pregnant women.

OBJECTIVE: To examine whether an efficacious voucher-based incentives intervention for decreasing smoking during pregnancy and increasing fetal growth could be improved without increasing costs. The strategy was to redistribute the usual incentives so that higher values were available early in the quit attempt. METHOD: 118 pregnant smokers in greater Burlington, Vermont (studied December, 2006-June, 2012) were randomly assigned to the revised contingent voucher (RCV) or usual contingent voucher (CV) schedule of abstinence-contingent vouchers, or to a non-contingent voucher (NCV) control condition wherein vouchers were provided independent of smoking status. Smoking status was biochemically verified; serial sonographic estimates of fetal growth were obtained at gestational weeks 30-34. RESULTS: RCV and CV conditions increased point-prevalence abstinence above NCV levels at early (RCV: 40%, CV: 46%, NCV: 13%, p=.007) and late-pregnancy (RCV: 45%; CV: 36%; NCV, 18%; p=.04) assessments, but abstinence levels did not differ between the RCV and CV conditions. The RCV intervention did not increase fetal growth above control levels while the CV condition did so (p<.05). CONCLUSION: This trial further supports the efficacy of CV for increasing antepartum abstinence and fetal growth, but other strategies (e.g., increasing overall incentive values) will be necessary to improve outcomes further.

Maternal body mass index moderates the influence of smoking cessation on breast feeding.

INTRODUCTION: Smoking cessation is associated with greater breast feeding in newly postpartum women, while being overweight or obese is associated with lower rates of breast feeding. The purpose of this study is to examine whether the increases in breast feeding associated with smoking cessation are moderated by maternal body mass index (BMI). To our knowledge, the interaction of maternal smoking status and overweight/obesity on breast feeding has not been previously reported. METHODS: Participants (N = 370) were current or recent smokers at the start of prenatal care who participated in controlled trials on smoking cessation or relapse prevention during/after pregnancy. Study participants were followed from the start of prenatal care through 24 weeks postpartum. Smoking status was biochemically verified, and maternal reports of breast feeding were collected at 2-, 4-, 8-, 12-, and 24-week postpartum assessments. RESULTS: Women who reported postpartum smoking abstinence or had a normal/underweight prepregnancy BMI (<25) were more likely to be breast feeding at the time that smoking status was ascertained (odds ratio [OR] = 3.02, confidence interval [CI] = 2.09-4.36, and OR = 2.07, CI = 1.37-3.12, respectively). However, smoking status and BMI interacted such that (a) normal/underweight women showed a stronger association between smoking abstinence and breast feeding (OR = 4.58, CI = 2.73-7.66) than overweight/obese women (OR = 1.89, CI = 1.11-3.23), and (b) abstainers showed an association between normal/underweight BMI and breast feeding (OR = 3.53, CI = 1.96-6.37), but smokers did not (OR = 1.46, CI = 0.88-2.44). CONCLUSIONS: Overweight/obesity attenuates the positive relationship between smoking abstinence and greater breast feeding among newly postpartum women.

Subclinical Metabolic and Cardiovascular Factors and Brain White Matter Microstructural Integrity in Young Women.

Women who have experienced pregnancy complications, specifically preeclampsia and gestational diabetes, have well documented increased risks of cardiovascular, metabolic, and neurological disease later in life. This study examined how specific cardiovascular and metabolic risk factors for preeclampsia assessed in a non-pregnant state were associated with brain white matter microstructural integrity. This study examined sixty-two healthy women (mean age 31 ± 5 years) who received metabolic and cardiovascular assessments as well as multiple modality MRI imaging. Participants were either nulliparous (n = 31) or had a history of preterm preeclampsia (n = 31). Imaging included acquisition Diffusion Tensor Imaging (DTI) to assess white matter integrity within the brain. We hypothesized that healthy, young, non-pregnant women with cardiovascular and metabolic profiles suggesting elevated risk would have decreased white matter integrity, represented by lower Fractional Anisotropy (FA) and increased Mean Diffusivity (MD) estimates in the posterior cortical areas of the brain. We observed increased white matter degradation (lower FA and increased MD) in posterior and occipital tracts, commissural fibers, and subcortical structures in women with increased adiposity, worse measures of cardiovascular and metabolic function, including greater insulin resistance (HOMA-IR), hyperlipidemia, elevated blood pressure, and increased arterial stiffness. The relationships detected between subclinical cardiovascular and metabolic phenotypes and increased white matter disruption at a young age, outside of pregnancy, are indicative that adverse changes are detectable long before cognitive clinical presentation. This may suggest that many of the long-term cardiovascular and metabolic risks of aging are influenced by physiologic aging trajectories rather than damage caused by pregnancy complications.

Dilation of Pregnant Rat Uterine Arteries with Phenols from Extra Virgin Olive Oil Is Endothelium-Dependent and Involves Calcium and Potassium Channels.

During pregnancy, uterine vasculature undergoes significant circumferential growth to increase uterine blood flow, vital for the growing feto-placental unit. However, this process is often compromised in conditions like maternal high blood pressure, particularly in preeclampsia (PE), leading to fetal growth impairment. Currently, there is no cure for PE, partly due to the adverse effects of anti-hypertensive drugs on maternal and fetal health. This study aimed to investigate the vasodilator effect of extra virgin olive oil (EVOO) phenols on the reproductive vasculature, potentially benefiting both mother and fetus. Isolated uterine arteries (UAs) from pregnant rats were tested with EVOO phenols in a pressurized myograph. To elucidate the underlying mechanisms, additional experiments were conducted with specific inhibitors: L-NAME/L-NNA (10-4 M) for nitric oxide synthases, ODQ (10-5 M) for guanylate cyclase, Verapamil (10-5 M) for the L-type calcium channel, Ryanodine (10-5 M) + 2-APB (3 × 10-5 M) for ryanodine and the inositol triphosphate receptors, respectively, and Paxilline (10-5 M) for the large-conductance calcium-activated potassium channel. The results indicated that EVOO-phenols activate Ca2+ signaling pathways, generating nitric oxide, inducing vasodilation via cGMP and BKCa2+ signals in smooth muscle cells. This study suggests the potential use of EVOO phenols to prevent utero-placental blood flow restriction, offering a promising avenue for managing PE.

Illicit drug use among pregnant women enrolled in treatment for cigarette smoking cessation.

INTRODUCTION: Smoking during pregnancy is the leading preventable cause of poor pregnancy outcomes in the United States. In population studies and nationwide surveys, pregnant smokers report more illicit drug use than pregnant nonsmokers. The purpose of this study was to examine the prevalence of illicit drug use among pregnant women enrolled in clinical trials for smoking cessation. METHODS: Urine specimens from 115 pregnant women were tested for illicit drug use during a study intake visit (~10th week of pregnancy) and during the final antepartum (FAP) smoking-status assessment (~28th week of pregnancy). Participants smoked about 18 cigarettes/day prepregnancy, were generally young (<25 years), Caucasian, with a high school education and without private insurance. RESULTS: About 34% of specimens from the intake visit and 25% of those from the FAP assessment tested positive for an illicit drug. The most common drug detected was marijuana (90% of positive specimens), followed by opioids (18%), cocaine (5%), benzodiazepines (3%), and methadone (3%). None tested positive for amphetamines. The majority of women (53%) who tested positive for an illicit substance at intake also tested positive at the FAP assessment. CONCLUSIONS: Approximately a quarter to a third of pregnant women enrolled in these smoking-cessation trials were determined to be using illicit drugs, with marijuana use being the most prevalent. Those providing smoking-cessation services to pregnant women may want to be prepared to assist with obtaining services for other drug use as well.

Tissue factor-dependent thrombin generation across pregnancy.

OBJECTIVE: Normal pregnancy results in a prothrombotic state. Studies that have investigated the capacity of pregnant women to generate thrombin are limited. Our aim was to evaluate thrombin generation longitudinally from the preconception period, through pregnancy, and after pregnancy. STUDY DESIGN: We evaluated young, healthy nulligravid women (n = 20) at 4 time points and compared the data with 10 control women at 2 time points. Coagulation was initiated with tissue factor in contact pathway inhibited plasma, and thrombin generation was determined in the presence of a fluorogenic substrate. RESULTS: The maximum level and rate of thrombin generation increased during pregnancy; the highest level and rate occurred in late pregnancy compared with prepregnancy (P < .001). Subsequently, thrombin generation decreased in the postpregnancy samples that included maximum level, rate, and area under the curve (P < .001). CONCLUSION: Our data provide evidence for an increase in tissue factor-dependent thrombin generation with pregnancy progression, followed by a return to prepregnancy thrombin levels.

Financial incentives for smoking cessation among pregnant and newly postpartum women.

OBJECTIVE: Smoking during pregnancy is the leading preventable cause of poor pregnancy outcomes in the U.S., causing serious immediate and longer-term adverse effects for mothers and offspring. In this report we provide a narrative review of research on the use of financial incentives to promote abstinence from cigarette smoking during pregnancy, an intervention wherein women earn vouchers exchangeable for retail items contingent on biochemically-verified abstinence from recent smoking. METHODS: Published reports based on controlled trials are reviewed. All of the reviewed research was conducted by one of two research groups who have investigated this treatment approach. RESULTS: Results from six controlled trials with economically disadvantaged pregnant smokers support the efficacy of financial incentives for increasing smoking abstinence rates antepartum and early postpartum. Results from three trials provide evidence that the intervention improves sonographically estimated fetal growth, mean birth weight, percent of low-birth-weight deliveries, and breastfeeding duration. CONCLUSIONS: The systematic use of financial incentives has promise as an efficacious intervention for promoting smoking cessation among economically disadvantaged pregnant and recently postpartum women and improving birth outcomes. Additional trials in larger and more diverse samples are warranted to further evaluate the merits of this treatment approach.

Corrigendum: Preeclampsia and its relationship to pathological brain aging.

[This corrects the article DOI: 10.3389/fphys.2022.979547.].

Preeclampsia and its relationship to pathological brain aging.

The development of preeclampsia during pregnancy may have long-term effects on brain aging in women. Associations between preeclampsia and vascular dementia have been established, however the connection between preeclampsia and Alzheimer's disease has not been as thoroughly explored. Both preeclampsia and Alzheimer's disease have been associated with misfolded amyloid beta proteins and inflammation; due to these similarities, in this minireview, we examined the potential links between a history of preeclampsia and the development of dementia. We also discussed how hypertensive disorders of pregnancy may relate to both normal brain aging and dementia to highlight the need for additional research regarding the long-term cognitive effects of preeclampsia on the brain.

Cardiovascular profiles associated with white matter hyperintensities in healthy young women.

Women who experience hypertension in pregnancy have increased risk of both chronic hypertension and dementia. High blood pressure is associated with increased evidence of white matter hyperintensities (WMH) in brain imaging. WMH are disruptions of the white matter of the brain that occur with demyelination and axonal degeneration, are associated with vascular disease, occur more frequently in people with hypertension, and are associated with cognitive impairment. We evaluated the relationship between WMH and subclinical cardiovascular function in healthy young nulliparous women and women with a history of early-onset preeclampsia. Sixty-two reproductive-aged women were assessed during the follicular phase of the menstrual cycle after a 3-day sodium/potassium-controlled diet. Half of participants had a history of early-onset preeclampsia, and half were nulliparous. Blood was drawn to assess inflammatory markers. Cardiovascular assessments included tonometric blood pressure monitoring, volume loading to assess vascular compliance, echocardiography to assess cardiac ejection time, brachial pulse wave velocity of the brachial artery, assessing cardiovascular stiffness, and brachial artery flow mediated vasodilation to assess endothelial mediated dilatory response. T2 fluid-attenuated inversion recovery (FLAIR) MRI imaging was obtained. Two raters, blinded to cardiovascular assessments and pregnancy history, reviewed MRI scans for evidence of WMH using the Fazekas rating scale. WMHs were detected in 17 women; 45 had normal white matter structure. Participants with Fazekas score>0 had exaggerated response to volume loading compared to women with a Fazekas score of 0 and longer cardiac ejection times. Fazekas scores >0 had lower brachial flow-mediated vasodilation and increased white blood count compared to those with no evidence of WMH. Women with WMH had reduced cardiovascular compliance, and a trend towards decreased endothelial responsiveness compared to those without WMH. These data demonstrated that the relationship between cardiovascular and brain health was detectable in young, healthy, reproductive-aged women, and may play a role in later development of clinical disease. These findings may help identify women who are at risk for cognitive decline and pathological aging.

Placental Maternal Vascular Malperfusion is Associated with Prepregnancy and Early Pregnancy Maternal Cardiovascular and Thrombotic Profiles.

Characteristics of maternal vascular malperfusion (MVM) are frequently observed in placentas from pregnancies impacted by preeclampsia, intrauterine growth restriction, preterm labor, and intrauterine fetal demise. We sought to evaluate the associations of features of MVM with subclinical measures of cardiovascular health and coagulation potential in healthy young women. Sixty-three healthy young women were recruited and assessed prior to pregnancy on cycle day 9 ± 4, at gestational age 90 ± 6 of early pregnancy, and gestational age 216 ± 5 of late pregnancy. Women were assessed for plasma volume, blood pressure, response to volume loading, cardiac output, and uterine hemodynamics. Platelet-poor plasma was collected to assess thrombin generation on a subset of 33 women at all time points. Following delivery, placentas were collected and analyzed for evidence of MVM. Thrombin generation (TG) was evaluated in the presence of tissue factor (TF) with and without recombinant soluble thrombomodulin (TM). For each, we compared TG lagtime, peak level, and endogenous thrombin potential (ETP). Comparisons were made between dichotomized presence and absence of each individual feature of MVM and cardiovascular and coagulation features. Mean ± standard deviation are presented. Women were 31 ± 4 years of age, body mass index of 24 ± 5 kg/m2, 86% white race, and 80% nulliparous. MVM occurred in 70% of placentas, with infarcts and agglutination (44%), decidual arteriopathy (40%), accelerated villous maturation (32%), placental hypoplasia (29%), and distal villous hypoplasia (17%) documented. Decidual arteriopathy and distal villous hypoplasia were associated with prepregnancy maternal physiology, including decreased plasma volume and subclinical cardiovascular variations. All assessed MVM characteristics had identifiable early pregnancy physiologic characteristics consistent with altered cardiovascular function and decreased uterine response to pregnancy when compared with women who did and did not develop MVM. Accelerated villous maturation was the only MVM feature to differ by thrombin generation parameters in early pregnancy. Thrombin generation potential and blood pressure were elevated in late pregnancy in women who developed decidual arteriopathy. Prepregnancy health status and adaptation to pregnancy play important roles in pregnancy outcomes. Both cardiovascular health and thrombin generation potential may influence early placentation. Longitudinal assessment of subclinical maternal factors may allow for better understanding of the etiologies of MVM lesions, as well as allow for identification of a timeline of the origins of placental pathologies.

Association of pre-pregnancy subclinical insulin resistance with cardiac dysfunction in healthy nulliparous women.

OBJECTIVES: To investigate the association between pre-pregnancy subclinical insulin resistance and cardiovascular dysfunction in healthy nulliparous women, and with hypertension in subsequent pregnancy. STUDY DESIGN: Secondary analysis of a single center prospective observational study conducted November 2011-June 2014. Healthy nulliparous women underwent detailed cardiovascular and metabolic assessment. Insulin resistance was determined by homeostasis model assessment (HOMA-IR). Associations of HOMA-IR with metabolic and cardiovascular measurements were assessed with Spearman correlations. Charts were reviewed in women who conceived singleton pregnancies. MAIN OUTCOME MEASURES: Metabolic measurements included serum glucose, insulin, creatinine, CRP, and lipids. HOMA-IR was calculated using fasting serum insulin and glucose. Indices of cardiovascular stiffness were determined from pulse wave velocity and response to volume challenge. Pregnancy outcomes included delivery mode and gestational age, birthweight, and hypertension. RESULTS: HOMA-IR was positively associated with BMI (r = 0.462, p < 0.001), body fat percentile (r = 0.463, p < 0.001), CRP (r = 0.364, p = 0.003), and negatively associated with serum HDL (r = -0.38, p = 0.002) and creatinine (r = -0.242, p = 0.049). HOMA-IR was positively associated with blood pressure (r = 0.347, p = 0.004), resting heart rate (r = 0.433, p = <0.001), response to volume challenge (r = 0.325, p < 0.01). Increased HOMA-IR was associated with a faster cardiac ejection time in response to volume challenge (r = -0.415, p < 0.001), which is a marker of decreased cardiac compliance to volume increase, or cardiac stiffness. CONCLUSION: HOMA-IR is associated with pre-pregnancy cardiac stiffness. Cholesterol was not associated with cardiovascular dysfunction. A non-significant trend was observed between HOMA-IR and hypertension in subsequent pregnancy.

Effects of cigarette smoking cessation on breastfeeding duration.

INTRODUCTION: The purpose of this study was to use data from controlled trials to examine whether smoking cessation increases breastfeeding duration. Correlational studies have confirmed associations between smoking status and breastfeeding duration, but whether smoking cessation increases breastfeeding duration has not been established. METHODS: Participants (N = 158) were smokers at the start of prenatal care who participated in controlled trials on smoking cessation. Women were assigned to either an incentive-based intervention wherein they earned vouchers exchangeable for retail items by abstaining from smoking or a control condition where they received comparable vouchers independent of smoking status. Treatments were provided antepartum through 12-week postpartum. Maternal reports of breastfeeding collected at 2-, 4-, 8-, 12-, and 24-week postpartum were compared between treatment conditions. Whether women were exclusively breastfeeding was not investigated. RESULTS: The incentive-based treatment significantly increased breastfeeding duration compared with rates observed among women receiving the control treatment, with significant differences between treatment conditions observed at 8-week (41% vs. 26%; odds ratio [OR] = 2.7, 95% CI = 1.3-5.6, p = .01) and 12-week (35% vs. 17%; OR = 3.4, 95% CI = 1.5-7.6, p = .002) postpartum. No significant treatment effects on breastfeeding were observed at other assessments. Changes in smoking status mediated the effects of treatment condition on breastfeeding duration. CONCLUSIONS: These results provide evidence from controlled studies that smoking cessation increases breastfeeding duration, which, to our knowledge, has not been previously reported.