The risk of perinatal and cardiometabolic complications in pregnancies conceived by medically assisted reproduction.

PURPOSE: To examine the impact of medically assisted fertility treatments on the risk of developing perinatal and cardiometabolic complications during pregnancy and in-hospital deliveries. METHODS: We conducted a retrospective cohort study using medical health records of deliveries occurring in 2016-2022 at a women's specialty hospital in a southern state of the Unites States (US). Pregnancies achieved using medically assisted reproductive (MAR) techniques were compared with unassisted pregnancies using propensity score matching (PSM), based on demographic, preexisting health, and reproductive factors. Study outcomes included cesarean delivery, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), delivery complications, and postpartum readmission. We used Poisson regression with robust standard errors to generate risk ratios (RRs) and 95% confidence intervals (CIs) for all study outcomes. RESULTS: Among 57,354 deliveries, 586 (1.02%) pregnancies were achieved using MAR and 56,768 (98.98%) were unassisted ("non-MAR"). Compared to the non-MAR group, MAR pregnancies had significantly higher prevalence of all study outcomes, including GDM (15.9% vs. 11.2%, p < 0.001), HDP (28.2% vs. 21.1%, p < 0.001), cesarean delivery (56.1% vs. 34.6%, p < 0.001), delivery complications (10.9% vs. 6.8%, p = 0.03), and postpartum readmission (4.3% vs. 2.7%, p = 0.02). In a PSM sample of 584 MAR and 1,727 unassisted pregnancies, MAR was associated with an increased risk of cesarean delivery (RR = 1.11, 95% CI = 1.01-1.22); whereas IVF was associated with an increased risk of cesarean delivery (RR = 1.15, 95% CI = 1.03-1.28) and delivery complications (RR = 1.44, 95% CI = 1.04-2.01). CONCLUSIONS: Women who conceived with MAR were at increased risk of cesarean deliveries, and those who conceived with IVF were additionally at risk of delivery complications.

Attitudes and barriers to breastfeeding among women at high-risk for not breastfeeding: a prospective observational study.

BACKGROUND: Rates of breastfeeding are lower among minority and underserved populations in the United States. Our study objective was to assess pregnant persons attitudes and barriers to breastfeeding among a cohort at high risk for not breastfeeding. METHODS: We disseminated the Iowa Infant Feeding Attitude Scale (IIFAS) to 100 pregnant persons at least 18 years of age attending a prenatal visit in a low-resource, academic practice in south-central Louisiana (Woman's Hospital). The IIFAS, as well as questions collecting information on breastfeeding experience and sociodemographic characteristics, were administered via interview. Medical records were reviewed to investigate associations between attitudes about breastfeeding in pregnancy and patient's feeding choices during the delivery hospital stay. Fisher exact tests and Wilcoxon rank-sum tests were used to assess associations between categorical and continuous variables respectively. RESULTS: Of the 98 participants who completed the study, 8% were Hispanic, 63% were Black, 95% were Medicaid eligible, and 50% were unemployed. 59% (n = 58) went on to breastfeed/combination breast-formula feed (called "Any-Breastfeeding Group") during the delivery stay. Total IIFAS score during pregnancy was significantly higher among those who went on to breastfeed during delivery hospital stay (Any-Breastfeeding Group vs. Formula-Feeding-Only Group: 58.9 ± 5.5 vs. 53.7 ± 6.2 respectively, p < 0.001). In the group that went on to only formula feed (Formula-Feeding-Only Group), only 4% agreed breastfeeding was more convenient when surveyed during pregnancy, compared to 45% of the Any-Breastfeeding Group. 60% of Formula-Feeding-Only Group agreed formula is as healthy as breast milk. CONCLUSION: The three major themes that coincided with favorability toward breastfeeding in the study, and can be addressed during prenatal counseling, are: mother-infant bonding, convenience, and health benefits. By identifying attitudes and barriers to breastfeeding for patients during pregnancy who went on to not breastfeed, directed educational opportunities can be developed to address these specific attitudes to ultimately increase breastfeeding initiation and continuation.

Implementation of and Barriers to Optimizing Postpartum Care by Resident and Attending Physicians.

Background: The American College of Obstetricians and Gynecologists released Committee Opinion No. 736: Optimizing Postpartum Care (CO No. 736) to address severe maternal morbidity and mortality in the United States by outlining recommendations for care in the critical time following birth. This study aimed to evaluate implementation of and barriers to the recommendations of CO No. 736 among obstetricians in south Louisiana. Methods: A survey to general obstetric providers assessed opinions on the CO No. 736 recommendations, implementation of these recommendations, and barriers to implementation. Fisher exact test was used to compare distributions between resident and attending groups. Qualitative, free-text responses about barriers to implementation were organized by common themes and categorized into systemic and patient factors. Results: Of 124 survey responses, 59.7% of respondents reported that they had read CO No. 736. Of the respondents who had read the document, 86.5% believed it was important to implement these recommendations, but only 50.0% had established the recommendations in their practices. Overall, fewer than half (46.8%) of respondents reported actively implementing the recommendation to make contact with postpartum patients at 3 weeks or sooner, but 86.3% reported having comprehensive clinic visits within 12 weeks of delivery. Commonly identified systemic barriers to implementation included the 3-week contact not being common practice, overbooked schedules, and unclear provider expectations. Commonly identified patient factor barriers to implementation included childcare or transportation and no-shows at postpartum appointments. Conclusion: Both resident and attending obstetricians in South Louisiana believe that the CO No. 736 recommendations are important but reported lacking the ability to implement them into clinical practice.

Trends in Gestational Weight Gain in Louisiana, March 2019 to March 2022.

Importance: Average gestational weight gain (GWG) increased during the COVID-19 pandemic, but it is not known whether this trend has continued. Objective: To examine patterns of GWG during the COVID-19 pandemic by delivery and conception timing through the second year of the pandemic. Design, Setting, and Participants: This cohort study is a retrospective review of birth certificate and delivery records from 2019 to 2022. Electronic health records were from the largest delivery hospital in Louisiana. Participants included all individuals giving birth from March 2019 to March 2022. Data analysis was performed from October 2022 to July 2023. Exposure: Delivery date (cross-sectionally) and conception before the pandemic (March 2019 to March 2020) and during the peak pandemic (March 2020 to March 2021) and late pandemic (March 2021 to March 2022). Main Outcomes and Measures: The primary outcome was GWG (total GWG and adherence to the 2009 Institute of Medicine recommendations) analyzed using linear and log-linear regression with control for covariates. Results: Among 23 012 total deliveries (8763 Black individuals [38.1%]; 11 774 White individuals [51.2%]; mean [SD] maternal age, 28.9 [5.6] years), 3182 individuals (42.0%) exceeded the recommended weight gain in the year proceeding the pandemic, 3400 (45.4%) exceeded recommendations during the peak pandemic, and 3273 (44.0%) exceeded recommendations in the late pandemic. Compared with those who delivered before the pandemic (reference), participants had higher total GWG if they delivered peak or late pandemic (adjusted ß [SE], 0.38 [0.12] kg vs 0.19 [0.12] kg; P = .007). When cohorts were defined by conception date, participants who conceived before the pandemic but delivered after the pandemic started had higher GWG compared with those whose entire pregnancy occurred before the pandemic (adjusted ß [SE], 0.51 [0.16] kg). GWG was lower in the pregnancies conceived after the pandemic started and the late pandemic (adjusted ß [SE], 0.29 [0.12] kg vs 0.003 [0.14] kg; P = .003) but these participants began pregnancy at a slightly higher weight. Examining mean GWG month by month suggested a small decrease for March 2020, followed by increased mean GWG for the following year. Individuals with 2 pregnancies (1289 individuals) were less likely to gain weight above the recommended guidelines compared with their prepandemic pregnancy, but this association was attenuated after adjustment. Conclusions and Relevance: In this cohort, individuals with critical time points of their pregnancy during the COVID-19 pandemic gained more weight compared with the previous year. The increased GWG leveled off as the pandemic progressed but individuals were slightly heavier beginning pregnancy.

Co-occurrence of depression, anxiety, and perinatal posttraumatic stress in postpartum persons.

BACKGROUND: The study aim was to describe the incidence of depression, anxiety, perinatal-post-traumatic stress disorder (PTSD), and their co-occurrences in the early postpartum period in a low-resource OB/GYN clinic serving majority Medicaid-eligible persons. We hypothesized that postpartum persons screening positive for depression will have an increased risk of a positive screen for anxiety and perinatal PTSD. METHODS: A retrospective study of postpartum persons receiving care in Baton Rouge, Louisiana was conducted using responses abstracted from the electronic medical record (EMR) of the Patient Health Questionnaire-9 (PHQ9), Generalized Anxiety Disorder-7 (GAD7), and Perinatal Post Traumatic Stress Disorder Questionnaire-II (PPQII). Categorical distributions were compared using Fisher exact tests, while t-tests were used to compare continuous covariates. Multivariable logistic regression was used to predict anxiety (GAD7) and perinatal PTSD (PPQII) scores while adjusting for potential confounders, as well as to predict continuous PPQII and GAD7 based on continuous PHQ9 scores. RESULTS: There were 613 birthing persons 4-12 weeks postpartum that completed mental health screening (PHQ9, GAD7, and PPQII) between November 2020 and June 2022 as part of routine postpartum care in the clinic. The incidence of screening positive for symptoms of depression (PHQ9 > 4) was 25.4% (n = 156), while the incidence of positive screening for symptoms of anxiety (GAD7 > 4) and perinatal PTSD (PPQII [Formula: see text] 19) were 23.0% (n = 141) and 5.1% (n = 31) respectively. Postpartum patients with mild anxiety or more (i.e. GAD7 > 4) had 26 times higher odds of screening positive for symptoms of depression (PHQ9 > 4) (adjusted odds ratio [aOR] 26.3; 95% confidence interval [CI] 15.29-46.92; p < 0.001). Postpartum persons with a PPQII score indicating symptoms of perinatal PTSD (PPQII [Formula: see text] 19) had 44 times higher odds of screening positive for symptoms of depression (PHQ > 4) (aOR 44.14; 95%CI 5.07-5856.17; p < 0.001). CONCLUSIONS: Depression, anxiety, and perinatal PTSD are each independent risk factors for each other. To comply with the American College of Obstetricians and Gynecologists (ACOG) recommendations, providers should universally screen postpartum persons with validated screening tools for mood disturbances. However, if a complete full mood assessment is not feasible, this study provides evidence to support screening patients for depression, and if the patient screens positive, prompt additional screening for anxiety and perinatal PTSD.

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.

Social distancing and mental health among pregnant women during the coronavirus pandemic.

BACKGROUND: The effect of social distancing due to the COVID-19 pandemic on the mental health of pregnant women is of particular concern, given potential effects on physical health, family functioning, and child development. METHODS: Pregnant women were recruited for the "Implications of and Experiences Surrounding being Pregnant during the COVID-19 Pandemic" study at Woman's Hospital in Baton Rouge, Louisiana. Participants enrolled at any point during their pregnancy and surveys were delivered weekly until the participant indicated that she had delivered her baby; a postpartum survey followed four weeks after delivery. This analysis includes 1037 participants with baseline, 596 with follow-up, and 302 with postpartum surveys. Questions on social distancing behaviors were asked at baseline and grouped based on whether they involved social distancing from work, friends and family, or public places. Symptoms of anxiety, stress, depression, and pregnancy-related anxiety were measured. Each type of social distancing was examined as a predictor of mental health using linear model with control for confounders. RESULTS: The study population was largely white (84.1%), married (81.8%), and educated (76.2% with a bachelor's or higher degree). Women who were younger, Black, unmarried, or had less education or income reported fewer social distancing behaviors. Mean anxiety score in the highest quartile of overall social distancing was 8.3 (SD 5.6), while in the lowest quartile it was 6.0 (SD 5.0) (p < 0.01), while perceived stress postpartum and pregnancy-related stress were not associated with social distancing. Associations were substantially diminished when controlled for baseline levels of anxiety symptoms. CONCLUSIONS: Greater social distancing was associated with more anxiety symptoms, but worse mental health, particularly anxiety, may also have contributed to greater social distancing behaviors.

Safe Newborn Sleep Practices on a Large Volume Maternity Service.

PURPOSE: Reinforcing safe infant sleep conditions in the hospital setting supports continuation of safe sleep practices after hospital discharge and should be considered the first line of defense for reducing risk for sudden unexpected infant death (SUID) and sudden infant death syndrome (SIDS) at home. The purpose of this study is to determine knowledge of perinatal nurses, nursing assistants, physicians, and ancillary personnel about safe sleep recommendations and implementation of safe sleep practices on the mother-baby unit. STUDY DESIGN AND METHODS: Nurses and other members of the perinatal health care team in a level III maternity service were invited to participate in a survey about safe sleep knowledge and practices. An audit for safe sleep adherence was conducted on the mother-baby unit for 120 mother-baby couplets over 1 year as a process improvement project. RESULTS: N = 144 surveys were completed; most participants (86%) were nurses. They had high levels of knowledge about safe sleep recommendations and 74% reported making at least one safe sleep adjustment during one shift per week. The most common modifications at least once per week were removing baby from a sleeping caregiver (30%) and removing items from baby's bassinet (26%). Safe sleep audit findings revealed 32 out of 120 couplets were not fully following safe sleep recommendations, with most common unsafe sleep practice metrics being items in the baby's bassinet (18%) and bassinets propped up (8%). CLINICAL IMPLICATIONS: During the hospitalization for childbirth, new parents can learn about safe sleep practices from the perinatal health care team. Sharing information and role modeling safe sleep practices can promote continuation of safe sleep practices for the newborn at home after hospital discharge.

Factors Attributed to Breastfeeding Success in a Tertiary Obstetric Hospital.

Introduction: Increasing breastfeeding rates is a national health objective, however substantial barriers and disparities continue to exist in breastfeeding initiation and continuation. Our study aim is to identify factors associated with birthing persons' breastfeeding "success" (patients admitted to Labor & Delivery desiring to breastfeed and discharged breastfeeding) and breastfeeding "failure" (patients admitted to Labor & Delivery desiring to breastfeed and discharged exclusively formula feeding). Materials and Methods: We conducted a retrospective cohort study between July 2015 and June 2016. Patients were asked infant feeding plan intentions (breast, formula, combination) upon admission for delivery. Feeding plan was reassessed at discharge from delivery stay and validated to serve as proxy for feeding status at discharge. Logistic regression was used to identify the population(s) most likely to voice intent to breastfeed and to identify predictors of altered breastfeeding intent at discharge. Results: Between July 2015 and June 2016, 6690 patients met criteria for analysis. Patients reporting intent to breastfeed before delivery were more likely Caucasian (p < 0.0001), married (p < 0.001), nulliparous (p < 0.01), privately insured (p < 0.0001), educated (p < 0.0001), and older (p < 0.01) compared with patients not intending to breastfeed. These characteristics were similar in those who were "successful breastfeeders," that is, breastfeeding at discharge. The strongest predictor of breastfeeding at discharge was intent to breastfeed before delivery (p < 0.0001). African American race was the strongest predictor of nonbreastfeeding intent at admission (p < 0.0001) and conversion to formula feeding by hospital discharge (p < 0.001). Conclusion: Intent to breastfeed before delivery was the strongest predictor of breastfeeding at discharge; thus, prenatal breastfeeding education within the at-risk population is crucial to increasing breastfeeding rates.

Systematic Review and Meta-Analysis of Perioperative Administration of Acetazolamide for Management of Postoperative Pain after Laparoscopy.

Background and Objective: To perform a systematic review and meta-analysis to evaluate the efficacy of perioperative acetazolamide (ACTZ) administration with laparoscopy for reducing postoperative referred pain. Methods: The following databases were searched from inception to March 1, 2020: Cochrane, PubMed, PubMed Central, Ovid, and Embase. Electronic search used: Acetazolamide AND (laparoscopy OR laparoscopic OR Celioscopy OR Celioscopies OR Peritoneoscopy OR Peritoneoscopies). No limits or filters were used. We included only studies of patients who underwent abdominal laparoscopy (LSC), had a pain assessment at approximately 24 hours postoperatively, and included a treatment with ACTZ group and a no-treatment or minimal-treatment comparison group. Results: Five studies met inclusion criteria, with a combined total of 253 participants, 116 in the ACTZ group and 137 in the control group. A Bayesian hierarchical model was assumed for the study specific treatment effects. Posterior sampling was conducted via Markov Chain Monte Carlo methods, and posterior inference carried out on the hierarchical treatment effect. ACTZ significantly decreased average pain scores compared to control group by -0.726 points (95% confidence interval -1.175-0.264). The posterior probability that ACTZ decreases mean pain scores by ≥ 0.5 was 0.846. Conclusion: Current available evidence demonstrates that perioperative ACTZ may provide a modest improvement in postoperative referred pain following LSC.

l-Citrulline supplementation during pregnancy improves perinatal and postpartum maternal vascular function in a mouse model of preeclampsia.

Preeclampsia is a spontaneously occurring pregnancy complication diagnosed by new-onset hypertension and end-organ dysfunction with or without proteinuria. This pregnancy-specific syndrome contributes to maternal morbidity and mortality and can have detrimental effects on fetal outcomes. Preeclampsia is also linked to increased risk of maternal cardiovascular disease throughout life. Despite intense investigation of this disorder, few treatment options are available. The aim of this study was to investigate the potential therapeutic effects of maternal l-citrulline supplementation on pregnancy-specific vascular dysfunction in the male C57BL/6J × female C57BL/6J C1q-/- preeclampsia-like mouse model. l-Citrulline is a nonessential amino acid that is converted to l-arginine to promote smooth muscle and blood vessel relaxation and improve nitric oxide (NO)-mediated vascular function. To model a preeclampsia-like pregnancy, female C57BL/6J mice were mated to C1q-/- male mice, and a subset of dams was supplemented with l-citrulline throughout pregnancy. Blood pressure, systemic vascular glycocalyx, and ex vivo vascular function were investigated in late pregnancy, and postpartum at 6 and 10 mo of age. Main findings show that l-citrulline reduced blood pressure, increased vascular glycocalyx volume, and rescued ex-vivo vascular function at gestation day 17.5 in this preeclampsia-like model. The vascular benefit of l-citrulline also extended postpartum, with improved vascular function and glycocalyx measures at 6 and 10 mo of age. l-Citrulline-mediated vascular improvements appear, in part, attributable to NO pathway signaling. Taken together, l-citrulline supplementation during pregnancy appears to have beneficial effects on maternal vascular health, which may have translational implications for improved maternal cardiovascular health.

Surgical site infection risk in cesarean delivery patients with obesity after negative pressure wound therapy: A retrospective cohort study.

BACKGROUND: There are conflicting reports of postoperative efficacy of negative pressure wound therapy in patients with obesity after cesarean delivery. METHODS: Retrospective cohort study for patients with obesity and negative pressure wound therapy or abdominal dressing after cesarean delivery between April 1, 2014 and January 31, 2018. Postoperative surgical site infection was defined from medical record charting or positive wound culture and confirmed by the hospital's Infection Prevention team. Multivariable logistic regression model for surgical site infection was conducted including additional potential confounding variables. Mantel-Haenszel tests were conducted to stratify by body mass index class and operative time, and we performed quasi-Poisson regression to determine which factors were associated with an increased operative time. RESULTS: We included 4,391 Black or White patients with obesity, 696 (15.9%) underwent negative pressure wound therapy and 3,695 (84.1%) abdominal dressing after cesarean delivery. Incidence of surgical site infection after negative pressure wound therapy and abdominal dressing were 6.1% and 3.4%, respectively (2-sample test of proportions P < .001). The multivariable logistic regression (covariates: race, diabetes, body mass index category, insurance, scheduled/emergency, artificial rupture, previous c-section, operative time, age, closure type) found negative pressure wound therapy dressing was associated with an increased risk of surgical site infection (adjusted odds ratio 1.54; 95% confidence interval, 1.01-2.34), as did a Mantel-Haenszel test which was stratified by body mass index (odds ratio 1.62; 95% confidence interval, 1.08-2.43) and a Mantel-Haenszel test stratified by operative time (odds ratio 1.85; 95% confidence interval, 1.28-2.65). Negative pressure wound therapy dressing also led to an increase in operative time in the Quasi-Poisson regression, which was the primary predictor of infection. CONCLUSION: Negative pressure wound therapy was associated with an increased the risk of postoperative surgical site infection after cesarean delivery in our obstetric patients with obesity. Future prospective studies are needed to determine a dressing type and other intervention to decrease postoperative cesarean surgical site infection in women with obesity.

Early Pregnancy Blood Pressure Elevations and Risk for Maternal and Neonatal Morbidity.

OBJECTIVE: To investigate whether women with early pregnancy elevated blood pressure (BP) or stage 1 hypertension exhibit increased risk of preeclampsia and maternal or neonatal morbidity. METHODS: We conducted a clinical cohort study of 18,162 women who delivered a singleton neonate from 2015 to 2018 and attended at least two prenatal appointments before 20 weeks of gestation. Data were collected within the Magee Obstetric Maternal and Infant database, an aggregate of prenatal and delivery health records. Early pregnancy BP was defined as average BP before 20 weeks of gestation, and women were classified with normal, elevated BP, stage 1 or 2 hypertension according to current guidelines. The primary outcome was preeclampsia. Secondary outcomes were severe maternal morbidity, placental abruption, gestational diabetes, and composite neonatal morbidity. RESULTS: Overall, 75.2% of the women were categorized with normal BP, 13.9% with elevated BP, 5.4% with stage 1 hypertension, and 5.5% with stage 2 hypertension. Risk of preeclampsia increased in a stepwise fashion with increasing BP category, adjusted for covariates (normal BP, 4.7%, referent; elevated BP, 7.3%, adjusted odds ratio [aOR] 1.29, 95% CI 1.07-1.56; stage 1, 12.3%, aOR 2.35, 95% CI 1.86-2.96), and stage 2, 30.2%, aOR 6.49, 95% CI 5.34-7.89). Results were similar among black and white women. Gestational diabetes was more prevalent among women with stage 1 (11.4%; aOR 1.50, 95% CI 1.18-1.91] and stage 2 hypertension (14.2%; aOR 1.65, 95% CI 1.30-2.10). Severe maternal morbidity and neonatal morbidity were increased only among women with stage 2 hypertension (aOR 2.99, 95% CI 2.26-3.99, and aOR 2.67, 95% CI 2.28-3.12, respectively). CONCLUSION: Women with elevated BP, and stage 1 and 2 hypertension in early pregnancy are at increased risk for preeclampsia. These findings emphasize the importance of applying the 2017 BP guidelines to reproductive-aged women. Strategies to incorporate these guidelines into obstetric care may also be warranted.

Paternal deficiency of complement component C1q leads to a preeclampsia-like pregnancy in wild-type female mice and vascular adaptations postpartum.

Preeclampsia is a spontaneously occurring, pregnancy-specific syndrome that is clinically diagnosed by new onset hypertension and proteinuria. Epidemiological evidence describes an association between a history of preeclampsia and increased risk for cardiovascular disease in later life; however, the mechanism(s) driving this relationship are unclear. Our study aims to leverage a novel preeclampsia-like mouse model, the C1q-/- model, to help elucidate the acute and persistent vascular changes during and following a preeclampsia-like pregnancy. Female C57BL/6J mice were mated to C1q-/- male mice to model a preeclampsia-like pregnancy ("PE-like"), and the maternal cardiovascular phenotype (blood pressure, renal function, systemic glycocalyx, and ex vivo vascular function) was assessed in late pregnancy and postpartum at 6 and 10 mo of age. Uncomplicated, normotensive pregnancies (female C57BL/6J bred to male C57BL/6J mice) served as age-matched controls. In pregnancy, PE-like dams exhibited increased systolic and diastolic pressure during mid- and late gestation, renal dysfunction, fetal growth restriction, and reduced placental efficiency. Ex vivo wire myography studies of mesenteric arteries revealed severe pregnancy-specific endothelial-dependent and -independent vascular dysfunction. At 3 and 7 mo postpartum (6 and 10 mo old, respectively), hypertension resolved in PE-like dams, whereas mild vascular dysfunction persisted at 3 mo postpartum. In conclusion, the female C57BL/6J-by-male C57BL/6J C1q-/- model recapitulates many aspects of the human preeclampsia syndrome in a low-risk, wild-type female mouse. The pregnancy-specific phenotype results in systemic maternal endothelial-dependent and -independent vascular dysfunction that persists postpartum.

Nitric oxide signaling in pregnancy and preeclampsia.

While the etiology of preeclampsia continues to be elucidated, it is clear that preeclampsia is a complex obstetrical syndrome associated with maternal vascular dysfunction within which impairments in nitric oxide (NO) signaling likely play a key role in driving disease progression and severity. The goal of this review is to present the available evidence for maladaptations in NO and NO signaling in pregnancies complicated by preeclampsia. After a brief overview of preeclampsia, a review of the available evidence for NO and NO signaling adaptations in normal, uncomplicated pregnancy is given to lay a foundation for changes driven by preeclampsia. Next, current evidence for maladaptations of NO and NO signaling in preeclampsia is reviewed. Finally, a brief summary of NO-focused treatments for preeclampsia prevention is discussed. Considering preeclampsia is a syndrome solely occurring among pregnant women, this review focuses on NO signaling in clinical studies, with supplementary evidence from animal studies added when necessary.

Mood and quality of life changes in pregnancy and postpartum and the effect of a behavioral intervention targeting excess gestational weight gain in women with overweight and obesity: a parallel-arm randomized controlled pilot trial.

BACKGROUND: Intensive lifestyle interventions in pregnancy have shown success in limiting gestational weight gain, but the effects on mood and quality of life in pregnancy and postpartum are less known. The purpose was to quantify changes in mental and physical quality of life and depressive symptoms across pregnancy and the postpartum period, to determine the association between gestational weight gain and change in mood and quality of life, and to assess the effect of a behavioral intervention targeting excess gestational weight gain on these outcomes. METHODS: A three group parallel-arm randomized controlled pilot trial of 54 pregnant women who were overweight or obese was conducted to test whether the SmartMoms® intervention decreased the proportion of women with excess gestational weight gain. Individuals randomized to Usual Care (n = 17) did not receive any weight management services from interventionists. Individuals randomized to the SmartMoms® intervention (n = 37) were provided with behavioral weight management counseling by interventionists either in clinic (In-Person, n = 18) or remotely through a smartphone application (Phone, n = 19). In a subset of 43 women, mood and mental and physical quality of life were assessed with the Beck Depression Inventory-II and the Rand 12-Item short form, respectively, in early pregnancy, late pregnancy, 1-2 months postpartum, and 12 months postpartum. RESULTS: The SmartMoms® intervention and Usual Care groups had higher depressive symptoms (p < 0.03 for SmartMoms® intervention, p < 0.01 for Usual Care) and decreased physical health (p < 0.01) from early to late pregnancy. Both groups returned to early pregnancy mood and physical quality of life postpartum. Mental health did not change from early to late pregnancy (p = 0.8), from early pregnancy to 1-2 months (p = 0.5), or from early pregnancy to 12 months postpartum (p = 0.9), respectively. There were no significant intervention effects. Higher gestational weight gain was associated with worsened mood and lower physical quality of life across pregnancy. CONCLUSION: High depressive symptoms and poor quality of life may be interrelated with the incidence of excess gestational weight gain. The behavioral gestational weight gain intervention did not significantly impact these outcomes, but mood and quality of life should be considered within future interventions and clinical practice to effectively limit excess gestational weight gain. TRIAL REGISTRATION: NCT01610752 , Expecting Success, Registered 31 May 2012.

Deep Brain Stimulation of the Hypothalamus Leads to Increased Metabolic Rate in Refractory Obesity.

OBJECTIVE: Obesity has become a worldwide epidemic, with very few long-term successful treatment options for refractory disease. Deep brain stimulation (DBS) of the bilateral lateral hypothalamus (LH) in refractory obesity has been performed safely. However, questions remain regarding the optimal settings and its effects on metabolic rate. The goals of our experiment were to determine the optimal DBS settings and the actual effect of optimal stimulation on energy expenditure. METHODS: After bilateral LH DBS implantation, 2 subjects with treatment refractory obesity underwent 4 days of metabolic testing. The subjects slept overnight in a respiratory chamber to measure their baseline sleep energy expenditure, followed by 4 consecutive days of resting metabolic rate (RMR) testing at different stimulation settings. On day 4, the optimized DBS settings were used, and sleep energy expenditure was measured again overnight in the room calorimeter. RESULTS: During daily testing, the RMR fluctuated acutely with changes in stimulation settings and returned to baseline immediately after turning off the stimulation. Optimal stimulation settings selected for participants showed a 20% and 16% increase in RMR for the 2 participants. Overnight sleep energy expenditure measurements at these optimized settings on day 4 yielded a 10.4% and 4.8% increase over the baseline measurements for the 2 participants. CONCLUSIONS: These findings have demonstrated the efficacy of optimized DBS of the LH on increasing the RMR acutely and maintaining this increase during overnight sleep. These promising preliminary findings have laid the groundwork for the possible treatment of refractory obesity with DBS.

Metabolic inflexibility in women with PCOS is similar to women with type 2 diabetes.

BACKGROUND: An ability to switch between primarily oxidizing fat in the fasted state to carbohydrate in the fed state, termed metabolic flexibility, is associated with insulin sensitivity. Metabolic flexibility has been explored previously in women with polycystic ovary syndrome (PCOS), yet the independent or synergistic contributions of androgen excess and/or insulin resistance is not yet known. Therefore, the purpose of this article was to characterize metabolic flexibility in women with PCOS compared to women of normal BMI, obesity, or type 2 diabetes (T2DM). METHODS: Eighty-six weight-stable women; thirty with either PCOS (n = 30), or fifty-six with obesity (n = 12), T2DM (n = 27), or normal BMI (n = 17) underwent a hyperinsulinemic euglycemic clamp and indirect calorimetry to measure insulin sensitivity and substrate oxidation via indirect calorimetry, respectively. RESULTS: All analyses were adjusted for differences in age, ethnicity, and BMI between groups. Women with PCOS were less metabolically flexible compared to healthy women with obesity (p < 0.0001), normal BMI (p < 0.0001), but after controlling for glucose disposal rate, were similar to women with T2DM (p = 0.99). When dividing women with PCOS above and below the mean cutoff for insulin resistance, the insulin resistant women with PCOS had lower rates of non-oxidative glucose metabolism (p = 0.0001), higher levels of percent free testosterone (p = 0.04), a higher free androgen index (p = 0.006), more visceral adipose tissue (p = 0.02), and were less metabolically flexible (p = 0.007). CONCLUSIONS: Women with T2DM were as metabolically inflexible as women with PCOS. When stratifying women with PCOS into those who are metabolically flexible and inflexible, the women who are inflexible display greater amounts of visceral fat and androgen excess. The inability to alter substrate use given the physiological stimulus may lead to subsequent increases in adiposity in women with PCOS thereby further worsening the insulin resistance. TRIAL REGISTRATION NUMBER: Clinical Trials.gov, NCT01482286. Registered 30 November 2011.

Maternal Outcomes Associated With Lower Range Stage 1 Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes in healthy, nulliparous women classified with stage 1 hypertension under the revised American College of Cardiology and American Heart Association Guidelines and to evaluate the effects of low-dose aspirin on maternal and neonatal outcomes in this population. METHODS: We conducted a secondary analysis of data from a multicenter randomized, double-blind, placebo-controlled trial of low-dose aspirin for prevention of preeclampsia in nulliparous, low-risk women recruited between 13 and 25 weeks of gestation. Of the 3,134 nulliparous women enrolled in the original study, 2,947 women with singleton pregnancies and without missing data were included in this analysis. Blood pressure was measured at enrollment between 13 and 25 weeks of gestation and outcomes were adjudicated from the medical record. RESULTS: One hundred sixty-four participants were identified with lower range stage 1 hypertension (5.6%), systolic blood pressure 130-135 mm Hg, diastolic blood pressure 80-85 mm Hg, or both by the new American College of Cardiology-American Heart Association guidelines. Within the placebo group (n=1,482), women with stage 1 hypertension had a significantly increased incidence of preeclampsia compared with normotensive women, 15.3% (15/98) vs 5.4% (75/1,384) (relative risk 2.66, 95% CI 1.56-4.54, P<.001). Moreover, women with stage 1 hypertension had an increased incidence of gestational diabetes mellitus (6.1% vs 2.5%, P=.03) and more indicated preterm deliveries (4.2% vs 1.1%, P=.01). Comparing women with stage 1 hypertension and normotensive women receiving low-dose aspirin during pregnancy (n=1,465), no differences in rates of preeclampsia (7.6% vs 4.4%, respectively, P=.2), gestational diabetes mellitus, or indicated preterm deliveries were observed. Rates of placenta abruption, small for gestational age, and spontaneous preterm birth did not differ significantly between groups. CONCLUSION: Application of the new American College of Cardiology-American Heart Association guidelines in a pregnant population identifies a cohort of women who are at increased risk for preeclampsia, gestational diabetes mellitus, and preterm birth.