The Association between Sickle Cell Disease and Postpartum Severe Maternal Morbidity.

OBJECTIVE: To compare the risk of severe maternal morbidity (SMM) from the delivery admission to 42 days' postdischarge among persons with sickle cell disease (SCD) to those without SCD. STUDY DESIGN: This retrospective cohort study included deliveries ≥20 weeks' gestation at an urban safety net hospital in Atlanta, GA from 2011 to 2019. The exposure was SCD diagnosis. The outcome was a composite of SMM from the delivery admission to 42 days' postdischarge. SMM indicators as defined by the Centers for Disease Control and Prevention were identified using the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes; transfusion of blood products and sickle cell crisis were excluded. RESULTS: Of N = 17,354 delivery admissions, n = 92 (0.53%) had SCD. Persons with SCD versus without SCD had an increased risk of composite SMM (15.22 vs. 2.29%, p < 0.001), acute renal failure (6.52 vs. 0.71%, p < 0.001), acute respiratory distress syndrome (4.35 vs. 0.17%, p < 0.001), puerperal cerebrovascular disorders (3.26 vs. 0.10%, p < 0.001), sepsis (4.35 vs. 0.42%, p < 0.01), air and thrombotic embolism (5.43 vs. 0.10%, p < 0.001), and ventilation (2.17 vs. 0.09%, p < 0.01). Ultimately, those with SCD had an approximately 6-fold higher incidence risk ratio of SMM, which remained after adjustment for confounders (adjusted incidence risk ratio [aIRR]: 5.96, 95% confidence interval [CI]: 3.4-9.19, p < 0.001). Persons with SCD in active vaso-occlusive crisis at the delivery admission had an approximately 9-fold higher risk of SMM up to 42 days' postdischarge compared with those with SCD not in crisis at the delivery admission (incidence: 25.71 vs. 8.77%, p < 0.05; aIRR: 8.92, 95% CI: 4.5-10.04, p < 0.05). Among those with SCD, SMM at the delivery admission was primarily related to renal and cerebrovascular events, whereas most postpartum SMM was related to respiratory events or sepsis. CONCLUSION: SCD is significantly associated with an increased risk of SMM during the delivery admission and through 42 days' postdischarge. Active crisis at delivery further increases the risk of SMM. KEY POINTS: · Sickle cell disease was associated with an approximately 6-fold increased risk of SMM.. · Active vaso-occlusive crisis at delivery was associated with an approximately 9-fold increased risk of SMM.. · 48% of SMM events in persons with SCD occurred postpartum and were respiratory- or sepsis-related..

Society for Maternal-Fetal Medicine Position Statement: Extending Medicaid coverage for 12 months postpartum.

Position: The Society for Maternal-Fetal Medicine supports federal and state policies that expand Medicaid eligibility and extend Medicaid coverage through 12 months postpartum to address the maternal morbidity and mortality crisis and improve health equity. Access to coverage is essential to optimize maternal health following pregnancy and childbirth and avoid preventable causes of maternal morbidity and mortality that extend throughout the first year postpartum. The Society opposes policies such as work requirements or limitations on coverage for undocumented individuals that unnecessarily impose restrictions on Medicaid eligibility.

Trauma and Posttraumatic Stress Disorder as Important Risk Factors for Gestational Metabolic Dysfunction.

Gestational metabolic diseases adversely impact the health of pregnant persons and their offspring. Pregnant persons of color are impacted disproportionately by gestational metabolic disease, highlighting the need to identify additional risk factors contributing to racial-ethnic pregnancy-related health disparities. Trauma exposure and posttraumatic stress disorder (PTSD) are associated with increased risk for cardiometabolic disorders in nonpregnant persons, making them important factors to consider when identifying contributors to gestational metabolic morbidity and mortality health disparities. Here, we review current literature investigating trauma exposure and posttraumatic stress disorder as psychosocial risk factors for gestational metabolic disorders, inclusive of gestational diabetes, low birth weight and fetal growth restriction, gestational hypertension, and preeclampsia. We also discuss the physiological mechanisms by which trauma and PTSD may contribute to gestational metabolic disorders. Ultimately, understanding the biological underpinnings of how trauma and PTSD, which disproportionately impact people of color, influence risk for gestational metabolic dysfunction is critical to developing therapeutic interventions that reduce complications arising from gestational metabolic disease. KEY POINTS: · Gestational metabolic diseases disproportionately impact the health of pregnant persons of color.. · Trauma and PTSD are associated with increased risk for cardiometabolic disorders in nonpregnant per.. · Trauma and PTSD impact physiological cardiometabolic mechanisms implicated in gestational metabolic..

In utero exposure to maternal diabetes or hypertension and childhood hypothalamic gliosis.

Exposure to maternal diabetes (DM) or hypertension (HTN) during pregnancy impacts offspring metabolic health in childhood and beyond. Animal models suggest that induction of hypothalamic inflammation and gliosis in the offspring's hypothalamus is a possible mechanism mediating this effect. We tested, in children, whether in utero exposures to maternal DM or HTN were associated with mediobasal hypothalamic (MBH) gliosis as assessed by brain magnetic resonance imaging (MRI). The study included a subsample of 306 children aged 9-11 years enrolled in the ABCD Study®; 49 were DM-exposed, 53 were HTN-exposed, and 204 (2:1 ratio) were age- and sex-matched children unexposed to DM and/or HTN in utero. We found a significant overall effect of group for the primary outcome of MBH/amygdala (AMY) T2 signal ratio (F(2,300):3.51, p = 0.03). Compared to unexposed children, MBH/AMY T2 signal ratios were significantly higher in the DM-exposed (ß:0.05, p = 0.02), but not the HTN-exposed children (ß:0.03, p = 0.13), findings that were limited to the MBH and independent of adiposity. We concluded that children exposed to maternal DM in utero display evidence of hypothalamic gliosis, suggesting that gestational DM may have a distinct influence on offspring's brain development and, by extension, children's long-term metabolic health.

Chronic hypertension diagnosed by the American Heart Association and American College of Cardiology criteria is associated with increased risk of developing hypertensive disorders of pregnancy.

BACKGROUND: ACOG uses a systolic blood pressure (SBP) ≥140 or diastolic blood pressure (DBP) ≥90 documented at <20 weeks of gestation to define chronic hypertension. In the nonpregnant state, the American Heart Association (AHA) and the American College of Cardiology (ACC) define chronic hypertension using lower diagnostic thresholds of SBP ≥130 or DBP ≥80. It remains unclear whether using more conservative guidelines in pregnancy improves identification of those at risk for gestational hypertension (GHTN) or preeclampsia (PRE). OBJECTIVE: We sought to investigate whether subjects with chronic hypertension based on the American Heart Association and American College of Cardiology criteria had an increased risk for gestational hypertension and preeclampsia than those without chronic hypertension. STUDY DESIGN: We conducted a retrospective cohort study utilizing a clinical database at a diverse, large urban, safety-net hospital. Subjects aged 18 to 40 years with singleton gestations and first trimester prenatal care were included. We defined subjects that met the criteria for stage 1 chronic hypertension based on first trimester systolic blood pressure and diastolic blood pressure cutoffs satisfying the American Heart Association and American College of Cardiology criteria (systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg). Those who did not meet these criteria had a systolic blood pressure <130 mm Hg and a diastolic blood pressure <90 mm Hg. We did not include those with chronic hypertension based on the American College of Obstetricians and Gynecologists criteria in this cohort (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg at <20 weeks); therefore, those who met the American Heart Association and American College of Cardiology criteria solely consisted of subjects with systolic blood pressure of 130 to 139 mm Hg and diastolic blood pressure of 80 of 89 mm Hg. By doing this, we were able to specifically investigate the increased risk for this specific population, which remains unclear. Diagnoses of gestational hypertension and preeclampsia were based on the established American College of Obstetricians and Gynecologists criteria. Preeclampsia included those with and without severe features. Tests for normality were performed. Student t-tests or rank sum tests were performed as appropriate for continuous variables; chi-square or Fisher's exact tests were performed for categorical variables. Generalized linear models were performed to calculate risk ratios while controlling for appropriate confounders. RESULTS: Of N=3354 subjects, 18% (n=629) were diagnosed with stage 1 chronic hypertension based on American Heart Association and American College of Cardiology criteria. Those with American Heart Association and American College of Cardiology stage 1 chronic hypertension had increased rates of gestational hypertension (35.4% vs 20%; P<.001) and preeclampsia (22.3% vs 10%; P<.001) than those without Stage 1 chronic hypertension based on these criteria. When controlling for maternal age, race, first trimester body mass index, pregestational diabetes, and substance use, those with the American Heart Association and American College of Cardiology stage 1 chronic hypertension had an almost 1.5-fold higher adjusted risk ratio of experiencing gestational hypertension (adjusted risk ratio, 1.49±0.10; P<.001) and almost 2-fold increased adjusted risk ratio of experiencing preeclampsia (adjusted risk ratio, 1.98±0.19; P<.001). CONCLUSION: Our data suggest an increased risk for developing gestational hypertension and preeclampsia for subjects satisfying the American Heart Association and American College of Cardiology cutoff for stage 1 chronic hypertension. Future studies need to consider whether diagnosis of chronic hypertension in pregnancy should conform with American Heart Association and American College of Cardiology criteria, and if those with stage 1 chronic hypertension based on American Heart Association and American College of Cardiology criteria require the same preventative measures and interventions utilized by those diagnosed by American College of Obstetricians and Gynecologists criteria.

The association between parental SARS-CoV-2 infection in pregnancy and fetal growth restriction.

OBJECTIVES: Although the relationship between maternal viral infections and fetal growth restriction (FGR) is well established, the association between SARS-CoV-2 infection in pregnancy and FGR remains unclear. We investigated the association between SARS-CoV-2 infection in pregnancy and FGR at a single county hospital. METHODS: We performed a prospective cohort study with cohorts matched by gestational age and month of SARS-CoV-2 PCR testing between April 2020 and July 2022. Individuals were included if they had a SARS-CoV-2 PCR testing up to 32 weeks of gestation and had a third trimester ultrasound. Primary outcome was a diagnosis of FGR, while secondary outcomes were rates of preeclampsia, small for gestational age (SGA) and birthweight. Univariate analyses, chi-square test and logistic regression were used for analysis. RESULTS: Our cohorts constituted of 102 pregnant individuals with a positive SARS-CoV-2 PCR test result and 103 pregnant individuals with a negative SARS-CoV-2 PCR test result in pregnancy. FGR rates were 17.8 % and 19.42 % among positive and negative SARS-CoV-2 cohorts respectively. While a statistical difference in preeclampsia rates was noted (34.31 % vs. 21.36 %, p=0.038) between cohorts, odds of getting preeclampsia based on SARS-CoV-2 test result was not significant (aOR 1.01, CI=0.97-1.01, p=0.75). No statistical difference was noted in demographics, FGR and SGA rates, and birthweight. CONCLUSIONS: Our findings suggest no association between SARS-CoV-2 infection in pregnancy and FGR at a single institution. Our results validate emerging data that additional fetal growth ultrasonographic assessment is not indicated solely based on SARS-CoV-2 infection status.

The Significance of Hypothalamic Inflammation and Gliosis for the Pathogenesis of Obesity in Humans.

Accumulated preclinical literature demonstrates that hypothalamic inflammation and gliosis are underlying causal components of diet-induced obesity in rodent models. This review summarizes and synthesizes available translational data to better understand the applicability of preclinical findings to human obesity and its comorbidities. The published literature in humans includes histopathologic analyses performed postmortem and in vivo neuroimaging studies measuring indirect markers of hypothalamic tissue microstructure. Both support the presence of hypothalamic inflammation and gliosis in children and adults with obesity. Findings predominantly point to tissue changes in the region of the arcuate nucleus of the hypothalamus, although findings of altered tissue characteristics in whole hypothalamus or other hypothalamic regions also emerged. Moreover, the severity of hypothalamic inflammation and gliosis has been related to comorbid conditions, including glucose intolerance, insulin resistance, type 2 diabetes, and low testosterone levels in men, independent of elevated body adiposity. Cross-sectional findings are augmented by a small number of prospective studies suggesting that a greater degree of hypothalamic inflammation and gliosis may predict adiposity gain and worsening insulin sensitivity in susceptible individuals. In conclusion, existing human studies corroborate a large preclinical literature demonstrating that hypothalamic neuroinflammatory responses play a role in obesity pathogenesis. Extensive or permanent hypothalamic tissue remodeling may negatively affect the function of neuroendocrine regulatory circuits and promote the development and maintenance of elevated body weight in obesity and/or comorbid endocrine disorders.

Exposure to Gestational Diabetes Mellitus Prior to 26 Weeks Is Related to the Presence of Mediobasal Hypothalamic Gliosis in Children.

Intrauterine exposure to metabolic dysfunction leads to offspring metabolic dysfunction in human and rodent models, but underlying mechanisms are unclear. The mediobasal hypothalamus (MBH) is involved in energy homeostasis and weight regulation, and MBH gliosis is associated with obesity and insulin resistance. We tested the hypothesis that offspring exposed to gestational diabetes mellitus (GDM) in utero versus those unexposed would show evidence of MBH gliosis. Participants in the BrainChild Study (age 7-11 years with confirmed GDM exposure or no GDM exposure) underwent brain MRI to acquire T2-weighted images. By using the amygdala (AMY) and white matter (WM) as reference regions, MBH:AMY and MBH:WM T2 signal ratios were calculated as a radiologic measure of MBH gliosis. Linear regressions were used to examine associations between GDM exposure (GDM overall) and by timing of GDM exposure (≤26 weeks or >26 weeks) and MBH gliosis. Associations between prepregnancy BMI and child MBH gliosis were examined in secondary analyses. There were no differences in T2 signal ratios in children exposed versus not exposed to GDM overall, but children exposed to early GDM (≤26 weeks of gestation) had higher MBH:WM signal ratios than those not exposed (ß = 0.147; SE 0.06; P = 0.03), adjusting for child's age, sex, and BMI z score and maternal prepregnancy BMI, whereas no associations were seen for the control ratio (AMY:WM). Prepregnancy BMI was not associated with evidence of MBH gliosis. Early exposure to GDM was associated with radiologic evidence of MBH gliosis in children. These data provide mechanistic insight into brain pathways by which exposure to GDM may increase risk for metabolic dysfunction.

American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.

OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS: This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS: This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

Association of fetal fraction with hypertensive disorders of pregnancy incidence and disease severity.

BACKGROUND: Hypertensive disorders of pregnancy contribute to maternal and offspring morbidity and mortality. Studies suggest that a lower early pregnancy fetal fraction is associated with an increased risk of hypertensive disorders of pregnancy. However, maternal obesity significantly affects fetal fraction and is a risk factor for hypertensive disorders of pregnancy. OBJECTIVE: We determined the association between fetal fraction (using a standardized single-institution platform, including male and female fetuses) and hypertensive disorders of pregnancy, stratified by obesity status. Second, we evaluated differences in total cell-free DNA concentration and correlation of fetal fraction with clinical markers of hypertensive disorders of pregnancy severity. STUDY DESIGN: This was a retrospective, single-institution study of a previously validated cell-free DNA-based noninvasive prenatal screening assay of 1058 samples. Maternal body mass index at the time of noninvasive prenatal screening was assessed, and hypertensive disorders of pregnancy were confirmed by a detailed medical record review. Differences in fetal fraction and total cell-free DNA concentration between the groups were assessed with univariate analyses. Multivariable regression was used to evaluate the association between fetal fraction and hypertensive disorders of pregnancy, adjusted for body mass index, maternal age, gestational age at noninvasive prenatal screening, and fetal sex. The association between fetal fraction and hypertensive disorders of pregnancy among individuals with obesity (body mass index, ≥30 kg/m2) and individuals without obesity (body mass index, <30 kg/m2) was investigated while controlling for the aforementioned covariates. Lastly, multivariable linear regression was used to evaluate the association between fetal fraction and clinical markers of hypertensive disorders of pregnancy severity. RESULTS: We identified individuals with (n=117) and without (n=941) hypertensive disorders of pregnancy with noninvasive prenatal screening drawn before 20 weeks of gestation and with fetal fraction and body mass index data available. Those with hypertensive disorders of pregnancy had a lower fetal fraction (10.2%±4.2% vs 11.6%±4.7%; P<.01), without differences in total cell-free DNA concentration (P=.14). When groups were stratified by obesity status, this relationship was only valid for individuals without obesity (P=.02). Only when logistic regression analysis was restricted to individuals without obesity did the likelihood of hypertensive disorders of pregnancy rise with decreasing fetal fraction (odds ratio, 0.93; 95% confidence interval, 0.88-0.99; P=.02). In addition, fetal fraction was inversely associated with maximum systolic blood pressure at the time of hypertensive disorders of pregnancy only in the population without obesity (ß, -0.08; 95% confidence interval, -0.147 to -0.01; P=.02). CONCLUSION: Although a lower fetal fraction is associated with the development of hypertensive disorders of pregnancy, the use of this parameter for the prediction may be problematic in individuals with obesity, as obesity has such a profound effect on fetal fraction. However, we uniquely noted that among individuals without obesity, fetal fraction is lower for those that develop hypertensive disorders of pregnancy and lower fetal fraction increases the odds of hypertensive disorders of pregnancy development. Lastly, low fetal fraction in the population without obesity that developed hypertensive disorders of pregnancy was associated with higher systolic blood pressure at the time of hypertensive disorders of pregnancy, an important clinical marker of hypertensive disorders of pregnancy severity. As analytical approaches of cell-free DNA interrogation advance, the prediction of placental-mediated disorders with first-trimester sampling is likely to improve, although this may remain challenging in gravidas with obesity, a cohort at high risk of developing hypertensive disorders of pregnancy.

Cancer and Pregnancy: National Trends.

OBJECTIVE: Cancer and pregnancy are likely increasing; however, updated estimates are needed to optimally address the unique needs of this patient population. The study aims to estimate the prevalence of cancer and cancer survivorship at delivery, to test the change in odds of cancer and cancer survivorship at delivery over the 10-year period, and to compare medical conditions, serious events, and obstetric complications between pregnancies with and without cancer at delivery. STUDY DESIGN: We conducted a retrospective analysis of the National Inpatient Sample (NIS), the largest all-payer inpatient health database in the United States. We identified delivery admissions from 2004 to 2013 with a concurrent diagnosis of cancer using International Classification of Disease, ninth revision (ICD-9) codes. Multivariable logistic regression was used to test the change in prevalence of concurrent cancer, cancer survivorship, and pregnancy and to compare outcomes between deliveries with and without cancer. All analyses were adjusted for NIS-provided population weights and strata. RESULTS: During the study period, the NIS represented a national estimate of 40,855,208 deliveries. The odds of cancer increased from 3.41/10,000 deliveries in 2004 to 4.33/10,000 in 2013. This trend was statistically significant, including after adjustment for maternal age (adjusted odds ratio [aOR] = 1.03 [95% confidence interval (CI): 1.01-1.04]). Cancer survivorship at delivery increased significantly (aOR = 1.07 [95% CI: 1.06-1.08]). Women with cancer more often experienced one or more of the following: death, ventilation, cardiac arrest, sepsis, or acute respiratory or renal failure during delivery (aOR for composite outcome 10.7 [95% CI: 6.6-17.2]), even after adjustment in a multivariable logistic regression model. CONCLUSION: The odds of cancer and cancer survivorship at delivery increased from 2004 to 2013, independent of maternal age. Women with cancer were more likely to experience medical or obstetric complications during their delivery compared with women without cancer. These findings highlight the importance of obstetric and oncologic clinical and research collaboration to improve patient care. KEY POINTS: · The odds of cancer at delivery increased.. · Women with cancer may have delivery complications.. · Cancer survivorship at delivery increased..

Low fetal fraction in obese women at first trimester cell-free DNA based prenatal screening is not accompanied by differences in total cell-free DNA.

OBJECTIVE: Reasons for first trimester noninvasive prenatal screening (NIPS) test failure in obese women remain elusive. As dilution from maternal sources may be explanatory, we determined the relationship between obesity, fetal fraction (FF), and total cell-free DNA (cfDNA) using our NIPS platform. METHODS: We assessed differences in first trimester (≤14 weeks) FF, indeterminate rate, and total cfDNA between obese (n = 518) and normal-weight women (n = 237) after exclusion of confounders (anticoagulation, autoimmunity, aneuploidy) and controlling for covariates. RESULTS: Fetal fraction was lower, and the indeterminate rate higher, in obese compared to controls (9.2% ± 4.4 vs. 12.5% ± 4.5, p < 0.001 and 8.4 vs. 1.7%, p < 0.001, respectively), but total cfDNA was not different (92.0 vs. 82.1 pg/µl, p = 0.10). For each week, the FF remained lower in obese women (all p < 0.01) but did not increase across the first trimester for either group. Obesity increased the likelihood of indeterminate result (OR 6.1, 95% CI 2.5, 14.8; p < 0.001) and maternal body mass index correlated with FF (ß -0.27, 95% CI -0.3, -0.22; p < 0.001), but not with total cfDNA (ß 0.49, 95% CI -0.55, 1.53; p = 0.3). CONCLUSIONS: First trimester obese women have persistently low FF and higher indeterminate rates, without differences in total cfDNA, suggesting placental-specific mechanisms versus dilution from maternal sources as a potential etiology.

Institutional prevalence of class III obesity modifies risk of adverse obstetrical outcomes.

BACKGROUND: Women with prepregnancy class III obesity (body mass index ≥40 kg/m2) are at an increased risk of perinatal complications and adverse obstetrical outcomes. Estimates of the magnitude of risk that these women face vary widely, which may reflect differences in institutional experience caring for women with obesity. OBJECTIVE: We sought to characterize the relationship between institutional prevalence of prepregnancy class III obesity and the risk of adverse perinatal outcomes among these women, hypothesizing that higher-prevalence institutions would have lower rates of adverse maternal and perinatal outcomes among this population. STUDY DESIGN: We conducted a retrospective cohort study using chart-abstracted data on births in Washington state from Jan. 1, 2012, to Dec. 31, 2017. The analysis was restricted to hospitals that delivered at least 1 patient per month with prepregnancy class III obesity. Institutional prevalence of prepregnancy class III obesity was calculated, and hospitals were classified as either high or low prevalence. We included nulliparous women with vertex-presenting singleton pregnancies at ≥37 weeks of gestation. We excluded births with missing initial body mass index. The primary outcome was the incidence of cesarean delivery. Secondary outcomes were induction of labor, postpartum complications, postpartum readmission, and neonatal intensive care unit admissions. We compared outcomes between women with prepregnancy class III and all obesity at high- and low-prevalence hospitals using the χ2 test or the Fishers exact test as appropriate. Binary logistic regression was performed to compare outcomes at high- and low-prevalence hospitals. A hospital-adjusted multivariable regression model that controlled for baseline institutional rates of each outcome and compared outcomes between high- and low-prevalence hospitals was developed. A final multivariable logistic regression that controlled for both baseline institutional variation as well as potential clinical confounders was performed. RESULTS: A total of 20,556 women at 6 hospitals were eligible for inclusion; the prevalence of prepregnancy class III obesity was 6.2% and 2.1% in high- and low-prevalence hospitals, respectively. Obese women, including those with class III obesity in a high-prevalence hospital, were more likely to be Latina and less likely to be of advanced maternal age and carry private insurance. After adjusting for the institutional cesarean delivery rate, women with prepregnancy class III obesity had significantly increased odds of cesarean delivery (odds ratio, 1.53, 95% confidence interval, 1.12-2.10); however, after adjusting for significant covariates, the association no longer achieved significance (odds ratio, 1.68, 95% confidence interval, 0.97-2.94). The hospital-adjusted odds of postpartum readmission were significantly increased for women with prepregnancy class III obesity when delivering in low-prevalence institutions (odds ratio, 6.61, 95% confidence interval, 1.93-22.56), and the association was further strengthened after controlling for significant covariates (odds ratio, 15.20, 95% confidence interval, 2.32-99.53). None of the models demonstrated significantly different odds of induction of labor, postpartum complications, or neonatal intensive care unit admission by institutional prevalence of prepregnancy class III obesity. CONCLUSION: Even after controlling for underlying hospital and subject characteristics, women with prepregnancy class III obesity had significantly increased odds of postpartum readmission, and a trend toward increased odds of cesarean delivery, when delivering in institutions with less experience caring for women with obesity.

Adipokine profiles in preeclampsia.

Objectives: Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE), are associated with short- and long-term maternal health complications, and obesity is a leading attributable risk factor for HDP. Yet, most women identified as obese [by body mass index (BMI) ≥ 30 kg/m2] do not develop HDP, indicating limited predictability of BMI alone. In nonpregnant populations, increased visceral fat mass (VFM) is an obesity-associated phenotype increasing the risk of developing hypertension. We sought to assess whether, in pregnancy, obese women with PE would have higher circulating levels of adipokines preferential to VFM compared to obese women without PE.Study Design: We performed a case-control study of women with and without PE, including obese (n = 65; BMI ≥ 30 kg/m2) and normal weight (n = 52; BMI 18.4-24.9 kg/m2) women. Plasma concentrations of adipokines preferential to VFM (visfatin, resistin), adipokines reflecting overall adiposity (leptin, adiponectin), and inflammatory cytokines were compared.Results: We found that among obese women, cases had significantly higher levels of VFM-associated adipokines and cytokines compared to controls [visfatin (p < .01, t = -3.8), resistin (p = .002, t = 1.12), IFN gamma (p = .04, t = -2.0), IL-6 (p < .01, t = -2.65), IL1-beta (p < .01, t = -4.1), IL-2 (p < .01, t = -3.9)]. Interestingly, however, obese and normal weight cases had similar VFM-adipokine and cytokine levels [visfatin (p = .34, t = -0.35), resistin (p = .55, t = -0.25)], and inflammatory marker concentrations [IFN gamma (p = .86, t = -0.76), IL-6 (p = .91, t = -0.53), IL-1beta (p = .67, t = 1.18), and IL-2 (p = .45, t = -1.16)]. These data possibly suggest an association between VFM and PE that is present independent of BMI.Conclusion: In summary, we demonstrated that, in normal-weight and obese women, PE was associated with higher concentrations of VFM-preferential adipokines compared to normal-weight and obese controls without PE.

Evaluating Relationships between Visceral Fat Measures and Adipokines Concentrations among Women with a History of Preeclampsia.

OBJECTIVE: We sought to evaluate associations between postpartum plasma adipokine concentrations among women with a history of preeclampsia (PE) without severe features (MPE), PE with severe features (SPE), and no PE (NPE). We also investigated relationships between adipokines and computed tomography (CT)-quantified measures of visceral fat (VF) area (VFA) and subcutaneous fat area (SCFA). STUDY DESIGN: We performed a secondary analysis of data collected as part of a previously performed cross-sectional study at our institution. Women with and without a history of PE were recruited in 10 years after delivery. VFA and SCFA measures were performed by CT scan. Anthropometric data and peripheral blood samples from subjects were collected concurrently. RESULTS: Plasma adiponectin concentrations (µg/mL) were significantly lower among MPE (18.5 ± 7.1) compared with NPE (27.3 ± 13.8) and SPE (25.7 ± 9.6). Leptin (p = 0.32) and resistin (p = 0.93) concentrations were similar among the groups. Adiponectin concentrations more closely aligned with VFA (ß = -0.001, p = 0.03), while resistin concentrations trended toward correlating with SCFA (ß = 0.02, p = 0.05). Leptin was not preferential to VFA or SCFA. CONCLUSION: VF distribution may contribute to the variation in PE phenotype. Adiponectin specifically may be a promising marker representing VFA.

Hepatic Complications in Preeclampsia.

In cases of preeclampsia with severe features and hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome, hepatic complications portend significant short-term and long-term maternal health implications. In this section, we will discuss the physiology of normal hepatic function in pregnancy, the pathophysiology of the abnormalities noted in hepatic function during the process of preeclampsia development, the diagnosis and management of preeclampsia, imitators of HELLP syndrome, the utility of various biomarkers in the diagnosis and prognosis of the preeclampsia disease spectrum, possible underlying genetic factors predisposing women to developing hepatic abnormalities with preeclampsia, and finally prognosis and management of a subcapsular hematoma.

Is Foley Catheter Use during a Trial of Labor after Cesarean Associated with Uterine Rupture?

OBJECTIVE: We sought to assess the safety of transcervical Foley catheter (TCF) placement for cervical ripening in women undergoing induction of labor (IOL) after prior cesarean by evaluating the risk of uterine rupture. STUDY DESIGN: We performed a secondary analysis of the Maternal-Fetal Medicine Unit's Cesarean Section Registry, a prospective observational cohort study. We included women with a history of ≤2 low-transverse cesarean deliveries who underwent IOL at ≥24 weeks of gestational age with a live singleton fetus without major anomalies. We excluded those who received prostaglandins or laminaria. We performed multinomial logistic regression to calculate adjusted odds ratios (aORs) for uterine rupture and dehiscence. Relevant confounders included prior vaginal delivery, pregnancy-induced hypertension, chorioamnionitis, and cervical effacement and dilation on admission. RESULTS: A total of 2,564 women were eligible. Unadjusted analysis demonstrated no increased risk of uterine rupture with TCF (1.9 vs. 0.9%; p = 0.10) but an increased risk of uterine dehiscence (1.9 vs. 0.6%; p = 0.02). After adjustment, TCF was not associated with an increased risk of uterine rupture (aOR: 2.02; 95% confidence interval [CI]: 0.71-5.78) or uterine scar dehiscence (aOR: 1.32; 95% CI: 0.37-4.72). CONCLUSION: Foley catheter is a safe tool for mechanical dilation in women undergoing IOL after prior cesarean.

Maternal urinary phthalate metabolites in relation to gestational diabetes and glucose intolerance during pregnancy.

BACKGROUND: Phthalates are common plasticizer chemicals that have been linked to glucose intolerance in the general population, but there is only limited research on their association with gestational diabetes (GDM). OBJECTIVE: We evaluated the association between 11 urinary phthalate metabolites and GDM, impaired glucose tolerance (IGT), and continuous blood glucose concentration during pregnancy in The Infant Development and Environment Study (TIDES). Based on prior study results, our primary analyses focused on monoethyl phthalate (MEP) in relation to our outcomes of interest. STUDY DESIGN: We used multi-variable logistic regression to examine the odds of GDM and IGT in relation to an interquartile-range (IQR) increase in natural log (ln)-transformed, specific gravity (SG)-adjusted first trimester (T1) and average of T1 and third trimester (T3) ("T1T3avg") phthalate metabolite concentrations. We fit linear regression models to examine the percent change in blood glucose per IQR increase in ln-transformed, SG-adjusted T1 and T1T3avg phthalates. In sensitivity analyses, we examined interactions between exposure and race. We adjusted for maternal age, maternal body mass index, study center, race/ethnicity, parity, and gestational age at glucose testing. RESULTS: In our sample of 705 pregnant women, we observed 60 cases of GDM, 90 cases of IGT, and an average GLT blood glucose of 113.6 ±â€¯27.7 mg/dL. In our primary analysis, T1T3avg MEP was positively associated with GDM ([OR (95% CI) per IQR increase] T1T3avg MEP: 1.61 (1.10, 2.36)). In secondary analyses, most other phthalates were not found to be related to study outcomes, though some associations were noted. Sensitivity analyses indicated possible strong race-specific associations in Asians, though these results are based on a small sample size (n = 35). CONCLUSION: In alignment with our a priori selection, we documented an association between T1T3avg MEP and GDM. Additional phthalate metabolites were also found to be linked to glucose intolerance, with possible stronger associations in certain racial/ethnic subgroups. Given the prevalence of phthalate exposures and the growing evidence of associations with metabolic outcomes, future studies should continue to examine this question in diverse cohorts of pregnant women, particularly in those who may be at higher risk for GDM and IGT.

Short interpregnancy interval increases the risk of preterm premature rupture of membranes and early delivery.

OBJECTIVES: Preterm premature rupture of membranes (PPROM) is a major contributor to overall preterm birth (PTB) rates. A short interpregnancy interval (IPI) is a well-known risk factor for PTB. It is unknown if a short IPI specifically affects the risk of developing PPROM in a subsequent pregnancy. We sought to determine the association between IPI and the risk of PPROM in a subsequent pregnancy. METHODS: A retrospective cohort study using the Missouri birth certificate database of singleton births from 2003 to 2013 was conducted. A short IPI (delivery of the prior pregnancy to conception of the index pregnancy) was defined as ≤6 months. IPI >6 months was categorized into two groups: IPI 7-23 months and IPI ≥24 months. PPROM was defined as premature rupture of membranes between 160 and 366 weeks. Multivariable logistic regression was conducted to determine the association between IPI and PPROM while controlling for maternal age, race, body mass index (BMI), education level, use of social services (Medicaid insurance, food stamps, or participation in the WIC [Women, Infants, and Children] program), tobacco use, and history of PTB. Secondary outcome included the gestational age at delivery, categorized into five subgroups (≤240, 241-280, 281-320, 321-340, and 341-366 weeks). RESULTS: 474,957 subjects with singleton gestations had data available to calculate the IPI. Of these, 1.4% (n = 6797) experienced PPROM. IPI ≤6 months was significantly associated with an increased risk of developing PPROM compared with patients with IPI ≥24 months (odds ratio (OR) 1.80, 95% CI 1.70-1.90, p < .001). A higher proportion of women with IPI ≤6 months delivered between 281 and 320 weeks compared to the other two IPI groups (27.0 versus 15.0 and 16.4%, p < .001). Individual maternal factors associated with an increased risk of PPROM included advanced maternal age, African American race, BMI <18.5 kg/m2, BMI ≥30 kg/m2, use of social services, tobacco use, and a prior PTB. CONCLUSION: Our data demonstrate that an IPI of ≤6 months is significantly associated with an increased risk of developing PPROM in the subsequent pregnancy. Of greater clinical relevance is that these women were more likely to deliver between 281 and 320 weeks as compared with women with a longer IPI. Novel to this study is the establishment of a specific link between a short IPI and PPROM with subsequent early delivery. Several maternal demographic factors known to be associated with PTB risk were also found to be associated with an increased risk of PPROM. Further studies are necessary to elucidate plausible biologic mechanisms ultimately leading to the development and implementation of preventive and therapeutic strategies for this high-risk cohort.