Differences in Cardiometabolic Proteins in Pregnancy Prioritize Relevant Targets of Preeclampsia.

BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by widespread vascular inflammation. It occurs frequently in pregnancy, often without known risk factors, and has high rates of maternal and fetal morbidity and mortality. Identification of biomarkers that predict preeclampsia and its cardiovascular sequelae before clinical onset, or even before pregnancy, is a critical unmet need for the prevention of adverse pregnancy outcomes. METHODS: We explored differences in cardiovascular proteomics (Olink Explore 384) in 256 diverse pregnant persons across 2 centers (26% Hispanic, 21% Black). RESULTS: We identified significant differences in plasma abundance of markers associated with angiogenesis, blood pressure, cell adhesion, inflammation, and metabolism between individuals delivering with preeclampsia and controls, some of which have not been widely described previously and are not represented in the preeclampsia placental transcriptome. While we observed a broadly similar pattern in early (<34 weeks) versus late (≥34 weeks) preeclampsia, several proteins related to hemodynamic stress, hemostasis, and immune response appeared to be more highly dysregulated in early preeclampsia relative to late preeclampsia. CONCLUSIONS: These results demonstrate the value of performing targeted proteomics using a panel of cardiovascular biomarkers to identify biomarkers relevant to preeclampsia pathophysiology and highlight the need for larger multiomic studies to define modifiable pathways of surveillance and intervention upstream to preeclampsia diagnosis.

The impact of different strategies for modeling associations between medications at low doses and health outcomes: a simulation study and practical application to postpartum opioid use.

Pharmacoepidemiological studies commonly examine the association between drug dose and adverse health outcomes. In situations where no safe dose exists, the choice of modeling strategy can lead to identification of an apparent safe low dose range in the presence of a non-linear relationship or due to the modeling strategy forcing a linear relationship through a dose of 0. We conducted a simulation study to assess the performance of several regression approaches to model the drug dose-response curve at low doses in a setting where no safe range exists, including the use of a (1) linear dose term, (2) categorical dose term, and (3) natural cubic spline terms. Additionally, we introduce and apply an expansion of prior work related to modeling dose-response curves at low and infrequently used doses in the setting of no safe dose ("spike-at-zero" and "slab-and-spline"). Furthermore, we demonstrate and empirically assess the use of these regression strategies in a practical scenario examining the association between the dose of the initial postpartum opioid prescribed after vaginal delivery and the subsequent total dose of opioids prescribed in the entire postpartum period among a cohort of opioid-naïve women with a vaginal delivery enrolled in a State Medicaid program (2007-2014).

Decreased postpartum exercise capacity after a diagnosis of pre-eclampsia: Implications for CVD risk prediction.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs. preeclamptic pregnancies. METHODS: Preeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum. RESULTS: Recruited subjects (n=68) were grouped according to their blood pressure as: a) normotensive pregnancy n=15; b) PreE with normotensive postpartum (PreE-Resolved, n=36); c) PreE with persistent postpartum HTN (PreE-HTN, n=17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], p<0.001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, p<0.001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, p<0.001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, p = 0.001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e' (18.0 vs 18.0 vs 13.5, p=0.045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, p = 0.045). Exercise duration was negatively associated with gravidity (R=-0.27, p=0.029) and postpartum LV mass index (R=-0.45, p<0.001), resting average E/e' (R=-0.51, p<0.001), BMI (R=-0.6, p<0.001) and resting SBP (R=-0.51, p<0.001). CONCLUSIONS: Postpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.

Age-Stratified Sex Differences in Heart Failure With Preserved Ejection Fraction Among Adult Hospitalizations.

BACKGROUND: There is evidence that heart failure with preserved ejection fraction (HFpEF)-related hospitalizations are increasing in the United States. However, there is a lack of knowledge about HFpEF-related hospitalizations among younger adults. OBJECTIVE: The aims of this study were to perform a retrospective analysis using the Nationwide Inpatient Sample and to examine age-stratified sex differences in the prevalence, correlates, and outcomes of HFpEF-related hospitalization across the adult life span. METHOD: Using the Nationwide Inpatient Sample (2002-2014), patient and hospital characteristics were determined. Joinpoint regression was used to describe age-stratified sex differences in the annual average percent change of hospitalizations with HFpEF. Survey logistic regression was used to estimate adjusted odds ratios representing the association of sex with HFpEF-related hospitalization and in-hospital mortality. RESULTS: There were 8 599 717 HFpEF-related hospitalizations (2.43% of all hospitalizations). Women represented the majority (5 459 422 [63.48%]) of HFpEF-related adult hospitalizations, compared with men (3 140 295 [36.52%]). Compared with men younger than 50 years, women within the same age group were 6% to 28% less likely to experience HFpEF-related hospitalization. Comorbidities such as hypertensive heart disease, renal disease, hypertension, obstructive sleep apnea, atrial fibrillation, obesity, anemia, and pulmonary edema explained a greater proportion of the risk of HFpEF-related hospitalization in adults younger than 50 years than in adults 50 years or older. CONCLUSION: Before the age of 50 years, women exhibit lower HFpEF-related hospitalization than men, a pattern that reverses with advancing age. Understanding and addressing the factors contributing to these sex-specific differences can have several potential implications for improving women's cardiovascular health.

Pregnancy-associated takotsubo cardiomyopathy hospitalizations in the United States.

Takotsubo cardiomyopathy (TCM) is most common not only in postmenopausal women aged ≥50 yr but also in pregnant individuals. However, there are no national estimates on the prevalence, timing of occurrence, correlates, and outcomes of pregnancy-associated TCM. Using the Nationwide Inpatient Sample (NIS: 2016-2020), we describe rates of pregnancy-associated TCM hospitalizations among 13- to 49-yr-old pregnant individuals in the United States by selected demographic, behavioral, hospital, and clinical characteristics. Joinpoint regression was used to describe the annual average percent change of pregnancy-associated TCM hospitalizations. Survey logistic regression was used to measure the association of pregnancy-associated TCM hospitalizations with maternal outcomes. Of the 19,754,535 pregnancy-associated hospitalizations, 590 were TCM associated. The overall trend in pregnancy-associated TCM hospitalizations remained stable during the study period. The majority of TCM occurred during the postpartum, followed by antepartum and delivery-associated hospitalizations. When compared with pregnancy hospitalizations without TCM, those with TCM were more likely to be over the age of 35 yr and use tobacco and opioids. Comorbidities during TCM-associated pregnancy hospitalizations included heart failure, coronary artery disease, hemorrhagic stroke, and hypertension. After controlling for potential confounders, the odds of pregnancy-associated TCM hospitalizations were 98.7 times [adjusted odds ratio (aOR) = 98.66, 95% confidence interval (CI) 31.23-311.64] and 14.7 times (aOR = 14.75, 95% CI 9.99-21.76) higher for experiencing in-hospital mortality and a prolonged hospital stay, respectively, than those without TCM. Although rare, pregnancy-associated TCM hospitalization is more likely to occur during the postpartum period and is associated with in-hospital mortality and prolonged hospital stay.NEW & NOTEWORTHY Although rare, pregnancy-associated takotsubo cardiomyopathy hospitalizations are more likely to occur during the postpartum period and are associated with in-hospital mortality and prolonged hospital stay.

Impact of sedentary behavior and emotional support on prenatal psychological distress and birth outcomes during the COVID-19 pandemic.

Abstract. BACKGROUND: Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics. METHODS: Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report. RESULTS: After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed. CONCLUSIONS: There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.

Society for Maternal-Fetal Medicine Consult Series #64: Systemic lupus erythematosus in pregnancy.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, inflammatory autoimmune disease characterized by relapses (commonly called "flares") and remission. Many organs may be involved, and although the manifestations are highly variable, the kidneys, joints, and skin are commonly affected. Immunologic abnormalities, including the production of antinuclear antibodies, are also characteristic of the disease. Maternal morbidity and mortality are substantially increased in patients with systemic lupus erythematosus, and an initial diagnosis of systemic lupus erythematosus during pregnancy is associated with increased morbidity. Common complications of systemic lupus erythematosus include nephritis, hematologic complications such as thrombocytopenia, and a variety of neurologic abnormalities. The purpose of this document is to examine potential pregnancy complications and to provide recommendations on treatment and management of systemic lupus erythematosus during pregnancy. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend low-dose aspirin beginning at 12 weeks of gestation until delivery in patients with systemic lupus erythematosus to decrease the occurrence of preeclampsia (GRADE 1B); (2) we recommend that all patients with systemic lupus erythematosus, other than those with quiescent disease, either continue or initiate hydroxychloroquine (HCQ) in pregnancy (GRADE 1B); (3) we suggest that for all other patients with quiescent disease activity who are not taking HCQ or other medications, it is reasonable to engage in shared decision-making regarding whether to initiate new therapy with this medication in consultation with the patient's rheumatologist (GRADE 2B); (4) we recommend that prolonged use (>48 hours) of nonsteroidal antiinflammatory drugs (NSAIDs) generally be avoided during pregnancy (GRADE 1A); (5) we recommend that COX-2 inhibitors and full-dose aspirin be avoided during pregnancy (GRADE 1B); (6) we recommend discontinuing methotrexate 1-3 months and mycophenolate mofetil/mycophenolic acid at least 6 weeks before attempting pregnancy (GRADE 1A); (7) we suggest the decision to initiate, continue, or discontinue biologics in pregnancy be made in collaboration with a rheumatologist and be individualized to the patient (GRADE 2C); (8) we suggest treatment with a combination of prophylactic unfractionated or low-molecular-weight heparin and low-dose aspirin for patients without a previous thrombotic event who meet obstetrical criteria for antiphospholipid syndrome (APS) (GRADE 2B); (9) we recommend therapeutic unfractionated or low-molecular-weight heparin for patients with a history of thrombosis and antiphospholipid (aPL) antibodies (GRADE 1B); (10) we suggest treatment with low-dose aspirin alone in patients with systemic lupus erythematosus and antiphospholipid antibodies without clinical events meeting criteria for antiphospholipid syndrome (GRADE 2C); (11) we recommend that steroids not be routinely used for the treatment of fetal heart block due to anti-Sjögren's-syndrome-related antigen A or B (anti-SSA/SSB) antibodies given their unproven benefit and the known risks for both the pregnant patient and fetus (GRADE 1C); (12) we recommend that serial fetal echocardiograms for assessment of the PR interval not be routinely performed in patients with anti-SSA/SSB antibodies outside of a clinical trial setting (GRADE 1B); (13) we recommend that patients with systemic lupus erythematosus undergo prepregnancy counseling with both maternal-fetal medicine and rheumatology specialists that includes a discussion regarding maternal and fetal risks (GRADE 1C); (14) we recommend that pregnancy be generally discouraged in patients with severe maternal risk, including patients with active nephritis; severe pulmonary, cardiac, renal, or neurologic disease; recent stroke; or pulmonary hypertension (GRADE 1C); (15) we recommend antenatal testing and serial growth scans in pregnant patients with systemic lupus erythematosus because of the increased risk of fetal growth restriction (FGR) and stillbirth (GRADE 1B); and (16) we recommend adherence to the Centers for Disease Control and Prevention medical eligibility criteria for contraceptive use in patients with systemic lupus erythematosus (GRADE 1B).

Associations between area-level arsenic exposure and adverse birth outcomes: An Echo-wide cohort analysis.

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

A Systematic Scoping Review of Peridelivery Pain Management for Pregnant People With Opioid Use Disorder: From the Society for Obstetric Anesthesia and Perinatology and Society for Maternal Fetal Medicine.

The prevalence of pregnant people with opioid use disorder (OUD), including those receiving medications for opioid use disorder (MOUD), is increasing. Challenges associated with pain management in people with OUD include tolerance, opioid-induced hyperalgesia, and risk for return to use. Yet, there are few evidence-based recommendations for pain management in the setting of pregnancy and the postpartum period, and many peripartum pain management studies exclude people with OUD. This scoping review summarized the available literature on peridelivery pain management in people with OUD, methodologies used, and identified specific areas of knowledge gaps. PubMed and Embase were comprehensively searched for publications in all languages on peripartum pain management among people with OUD, both treated with MOUD and untreated. Potential articles were screened by title, abstract, and full text. Data abstracted were descriptively analyzed to map available evidence and identify areas of limited or no evidence. A total of 994 publications were imported for screening on title, abstracts, and full text, yielding 84 publications identified for full review: 32 (38.1%) review articles, 14 (16.7%) retrospective studies, and 8 (9.5%) case reports. There were 5 randomized controlled trials. Most studies (64%) were published in perinatology (32; 38.1%) journals or anesthesiology (22; 26.2%) journals. Specific areas lacking trial or systematic review evidence include: (1) methods to optimize psychological and psychosocial comorbidities relevant to acute pain management around delivery; (2) alternative nonopioid and nonpharmacologic analgesia methods; (3) whether or not to use opioids for severe breakthrough pain and how best to prescribe and monitor its use after discharge; (4) monitoring for respiratory depression and sedation with coadministration of other analgesics; (5) optimal neuraxial analgesia dosing and adjuncts; and (6) benefits of abdominal wall blocks after cesarean delivery. No publications discussed naloxone coprescribing in the labor and delivery setting. We observed an increasing number of publications on peripartum pain management in pregnant people with OUD. However, existing published works are low on the pyramid of evidence (reviews, opinions, and retrospective studies), with a paucity of original research articles (<6%). Opinions are conflicting on the utility and disutility of various analgesic interventions. Studies generating high-quality evidence on this topic are needed to inform care for pregnant people with OUD. Specific research areas are identified, including utility and disutility of short-term opioid use for postpartum pain management, role of continuous wound infiltration and truncal nerve blocks, nonpharmacologic analgesia options, and the best methods to support psychosocial aspects of pain management.

Skin Incision Selection in Superobese Women Undergoing Cesarean Birth.

OBJECTIVE: The aim of this study was to examine whether vertical versus transverse skin incision is associated with increased wound complications in superobese women undergoing cesarean. STUDY DESIGN: This is a secondary analysis of a retrospective cohort study that included women with a body mass index (BMI) ≥ 50 kg/m2 and a cesarean birth with documented skin incision type from 1/1/2008 to 12/31/2015 at a single academic medical center. The primary outcome was a composite of wound complications: infection requiring antibiotics including superficial cellulitis, deep and organ space infections requiring packing, vacuum placement or exploration and debridement in the operating room. Secondary outcomes included estimated blood loss (EBL), time from skin incision to delivery, need for classical or T-hysterotomy, prolonged hospital admission (>4 days), and a composite of adverse neonatal outcomes. The primary exposure was skin incision type, transverse or vertical. Modified Poisson regression variance was used to adjust for differences in baseline characteristics. RESULTS: During the study period, 298 women underwent a cesarean with a known skin incision type. Vertical skin incision occurred in 25.8%. Women with a vertical skin incision were younger, had a higher BMI at delivery, had less weight gain in pregnancy, and were less likely to have labored prior to cesarean. Wound complications were not significantly more common in women with a vertical skin incision after adjusting for covariates (vertical 48.1 vs. transverse 29.4%, adjusted relative risk (aRR): 1.31, 95% confidence interval [CI]: 0.92-1.86). Compared with a transverse skin incision, vertical skin incision was associated with an increased risk for classical hysterotomy (67 vs. 17%, aRR: 2.96, 95% CI: 2.12-4.14), higher EBL, prolonged hospital stay, and composite neonatal morbidity. There were no statistically significant differences in the time from skin incision to delivery. CONCLUSION: In superobese women, vertical skin incision was not associated with increased wound complications, but was associated with increased risk for classical hysterotomy. KEY POINTS: · Vertical skin incision was not associated with a higher risk for composite wound morbidity after adjusting for covariates.. · Vertical skin incision was significantly associated with classical hysterotomy without associated decrease in incision to delivery time or neonatal morbidity.. · When selecting a skin incision approach in superobese women, clinicians should consider whether potential benefits outweigh known risks..

Risk of Death at 1 Year Following Postpartum Opioid Exposure.

OBJECTIVE: Opioids are commonly prescribed to women for acute pain following childbirth. Postpartum prescription opioid exposure is associated with adverse opioid-related morbidities but the association with all-cause mortality is not well studied. This study aimed to examine the association between postpartum opioid prescription fills and the 1-year risk of all-cause mortality among women with live births. METHODS: In a retrospective cohort study of live births among women enrolled in Tennessee Medicaid (TennCare) between 2007 and 2015, we compared women who filled two or more postpartum outpatient opioid prescriptions (up to 41 days of postdelivery discharge) to women who filled one or fewer opioid prescription. Women were followed from day 42 postdelivery discharge through 365 days of follow-up or date of death. Deaths were identified using linked death certificates (2007-2016). We used Cox's proportional hazard regression and inverse probability of treatment weights to compare time to death between exposure groups while adjusting for relevant confounders. We also examined effect modification by delivery route, race, opioid use disorder, use of benzodiazepines, and mental health condition diagnosis. RESULTS: Among 264,135 eligible births, 216,762 (82.1%) had one or fewer maternal postpartum opioid fills and 47,373 (17.9%) had two or more fills. There were 182 deaths during follow-up. The mortality rate was higher in women with two or more fills (120.5 per 100,000 person-years) than in those with one or fewer (57.7 per 100,000 person-years). The risk of maternal death remained higher in participants exposed to two or more opioid fills after accounting for relevant covariates using inverse probability of treatment weighting (adjusted hazard ratio: 1.46 [95% confidence interval: 1.01, 2.09]). Findings from stratified analyses were consistent with main findings. CONCLUSION: Filling two or more opioid prescriptions during the postpartum period was associated with a significant increase in 1-year risk of death among new mothers. KEY POINTS: · Opioid prescribing in the postpartum period is common.. · Prior studies show that >1 postnatal opioid fill is associated with adverse opioid-related events.. · > 1 opioid fill within 42 days of delivery was associated with an increase in 1-year risk of death..

Society for Maternal-Fetal Medicine Consult Series #58: Use of antenatal corticosteroids for individuals at risk for late preterm delivery: Replaces SMFM Statement #4, Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery, August 2016.

The administration of antenatal corticosteroids has been widely adopted as the standard of care in the management of pregnancies at risk for preterm delivery before 37 weeks of gestation, with the primary goal of reducing neonatal morbidity. However, the long-term risks associated with antenatal corticosteroid use remain uncertain. The purpose of this Consult is to review the current literature on the benefits and risks of antenatal corticosteroid use in the late preterm period and to provide recommendations based on the available evidence. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we recommend offering a single course of antenatal corticosteroids (2 doses of 12 mg of intramuscular betamethasone 24 hours apart) to patients who meet the inclusion criteria of the Antenatal Late Preterm Steroids trial, ie, those with a singleton pregnancy between 34 0/7 and 36 6/7 weeks of gestation who are at high risk of preterm birth within the next 7 days and before 37 weeks of gestation (GRADE 1A); (2) we suggest consideration for the use of antenatal corticosteroids in select populations not included in the original Antenatal Late Preterm Steroids trial, such as patients with multiple gestations reduced to a singleton gestation on or after 14 0/7 weeks of gestation, patients with fetal anomalies, or those who are expected to deliver in <12 hours (GRADE 2C); (3) we recommend against the use of antenatal corticosteroids for fetal lung maturity in pregnant patients with a low likelihood of delivery before 37 weeks of gestation (GRADE 1B); (4) we recommend against the use of late preterm corticosteroids in pregnant patients with pregestational diabetes mellitus, given the risk of worsening neonatal hypoglycemia (GRADE 1C); (5) we recommend that patients at risk for late preterm delivery be thoroughly counseled regarding the potential risks and benefits of antenatal corticosteroid administration and be advised that the long-term risks remain uncertain (GRADE 1C).

Society for Maternal-Fetal Medicine Consult Series #50: The role of activity restriction in obstetric management: (Replaces Consult Number 33, August 2014).

Despite current recommendations against its use, activity restriction remains a common intervention used to prevent preterm birth in multiple clinical settings. Hypertensive disorders of pregnancy, preterm premature rupture of membranes, multiple gestations, vaginal bleeding, short cervical length, placenta previa, and fetal growth restriction are also common reasons for antepartum hospital admission and frequently lead to a recommendation for activity restriction. However, numerous reports have shown that activity restriction does not prevent adverse obstetrical outcomes but does confer significant physical and psychosocial risks. This consult reviews the current literature on activity restriction and examines the evidence regarding its use in obstetrical management. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we recommend against the routine use of any type of activity restriction in pregnant women at risk of preterm birth based on preterm labor symptoms, arrested preterm labor, or shortened cervix (GRADE 1B); (2) we recommend against the use of routine inpatient hospitalization and activity restriction for the prevention of preterm birth in women with multiple gestations (GRADE 1A); and (3) given the lack of data definitively demonstrating that activity restriction improves perinatal outcome in pregnancies complicated by fetal growth restriction, preterm premature rupture of membranes, or hypertensive diseases of pregnancy, coupled with evidence of adverse effects of activity restriction, we suggest that activity restriction not be prescribed for the treatment of pregnancies complicated by fetal growth restriction, preterm premature rupture of membranes, or hypertensive disease (GRADE 2B).

Low-grade Appendiceal Mucinous Neoplasm and Endometriosis: Incidental Coincident Pathologies at Cesarean Section.

Incidental pathologic findings at the time of Cesarean section are exceedingly uncommon. Similarly, occult low-grade appendiceal mucinous neoplasms and other noninflammatory, non-neoplastic appendiceal pathologies are rare, although appendiceal neoplasia, most commonly well-differentiated neuroendocrine tumors, may be found during evaluation of acute appendicitis. Here we report the first case of incidental coincident low-grade appendiceal mucinous tumor and endometriosis involving the appendix at the time of Cesarean section. We highlight pitfalls in the histopathologic evaluation of these processes, particularly given the setting of decidualization of ectopic endometrial stroma, as well as the prognostic implications of low-grade appendiceal mucinous tumors to emphasize the importance of clinicopathologic correlation and careful intraoperative examination of the appendix and other visible structures during Cesarean section.

Effect of Trial of Labor before Cesarean and Risk of Subsequent Placenta Accreta Spectrum Disorders.

OBJECTIVE: This study aimed to examine whether labor before cesarean affects the risk of placenta accreta spectrum (PAS) disorders in a subsequent pregnancy. STUDY DESIGN: This is a secondary analysis of the Cesarean Registry, a prospective cohort study of women undergoing cesarean between 1999 and 2002. Women with one prior cesarean with known indications, which were categorized as likely associated with labor (labored cesarean) versus likely not associated with labor (unlabored cesarean), were included. Primary outcome was PAS disorder. RESULTS: Of 34,224 women, 60% had a "labored cesarean" and 40% had an "unlabored cesarean." Women with prior unlabored cesarean were more likely to have subsequent PAS disorder compared with women with a prior labored cesarean after adjusting for confounders (0.28 vs. 0.13%; adjusted odds ratio: 2.03; 95% confidence interval: 1.22-3.38). CONCLUSION: Prior unlabored cesarean is associated with an increased risk of PAS disorders in a subsequent pregnancy. This association may aid in risk stratification in women with suspected PAS disorders and help counsel about risks associated with cesarean on maternal request.

Deep learning predicts extreme preterm birth from electronic health records.

OBJECTIVE: Models for predicting preterm birth generally have focused on very preterm (28-32 weeks) and moderate to late preterm (32-37 weeks) settings. However, extreme preterm birth (EPB), before the 28th week of gestational age, accounts for the majority of newborn deaths. We investigated the extent to which deep learning models that consider temporal relations documented in electronic health records (EHRs) can predict EPB. STUDY DESIGN: EHR data were subject to word embedding and a temporal deep learning model, in the form of recurrent neural networks (RNNs) to predict EPB. Due to the low prevalence of EPB, the models were trained on datasets where controls were undersampled to balance the case-control ratio. We then applied an ensemble approach to group the trained models to predict EPB in an evaluation setting with a nature EPB ratio. We evaluated the RNN ensemble models with 10 years of EHR data from 25,689 deliveries at Vanderbilt University Medical Center. We compared their performance with traditional machine learning models (logistical regression, support vector machine, gradient boosting) trained on the datasets with balanced and natural EPB ratio. Risk factors associated with EPB were identified using an adjusted odds ratio. RESULTS: The RNN ensemble models trained on artificially balanced data achieved a higher AUC (0.827 vs. 0.744) and sensitivity (0.965 vs. 0.682) than those RNN models trained on the datasets with naturally imbalanced EPB ratio. In addition, the AUC (0.827) and sensitivity (0.965) of the RNN ensemble models were better than the AUC (0.777) and sensitivity (0.819) of the best baseline models trained on balanced data. Also, risk factors, including twin pregnancy, short cervical length, hypertensive disorder, systemic lupus erythematosus, and hydroxychloroquine sulfate, were found to be associated with EPB at a significant level. CONCLUSION: Temporal deep learning can predict EPB up to 8 weeks earlier than its occurrence. Accurate prediction of EPB may allow healthcare organizations to allocate resources effectively and ensure patients receive appropriate care.

Opioid prescribing after childbirth: overprescribing and chronic use.

PURPOSE OF REVIEW: Overprescribing opioids contributes to the epidemic of drug overdoses and deaths in the United States. Opioids are commonly prescribed after childbirth especially after caesarean, the most common major surgery. This review summarizes recent literature on patterns of opioid overprescribing and consumption after childbirth, the relationship between opioid prescribing and chronic opioid use, and interventions that can help reduce overprescribing. RECENT FINDINGS: It is estimated that more than 80% of women fill opioid prescriptions after caesarean birth and about 54% of women after vaginal birth, although these figures vary greatly by geographical location and setting. After opioid prescriptions are filled, the median number of tablets used after caesarean is roughly 10 tablets and the majority of opioids dispensed (median 30 tablets) go unused. The quantity of opioid prescribed influences the quantity of opioid used. The risk of chronic opioid use related to opioid prescribing after birth may seem not high (annual risk: 0.12-0.65%), but the absolute number of women who are exposed to opioids after childbirth and become chronic opioid users every year is very large. Tobacco use, public insurance and depression are associated with chronic opioid use after childbirth. The risk of chronic opioid use among women who underwent caesarean and received opioids after birth is not different from the risk of women who received opioids after vaginal delivery. SUMMARY: Women are commonly exposed to opioids after birth. This exposure leads to an increased risk of chronic opioid use. Physician and providers should judiciously reduce the amount of opioids prescribed after childbirth, although more research is needed to identify the optimal method to reduce opioid exposure without adversely affecting pain management.

Management of peripartum intra-abdominal hypertension and abdominal compartment syndrome.

Normal pregnancy leads to a state of chronically increased intra-abdominal pressure. Obstetric and non-obstetric conditions may increase intra-abdominal pressure further, causing intra-abdominal hypertension and abdominal compartment syndrome, which leads to maternal organ dysfunction and a compromised fetal state. Limited medical literature exists to guide treatment of pregnant women with these conditions. In this state-of-the-art review, we propose a diagnostic and treatment algorithm for the management of peripartum intra-abdominal hypertension and abdominal compartment syndrome, informed by newly available studies.

Early Pregnancy Hemoglobin A1C and Pregnancy Outcomes: A Population-Based Study.

OBJECTIVE: Women with prediabetes are identified from screening for overt diabetes in early pregnancy, but the clinical significance of prediabetes in pregnancy is unclear. We examined whether prediabetes in early pregnancy was associated with risks of adverse outcomes. STUDY DESIGN: We conducted a retrospective cohort study of pregnant women enrolled in Kaiser Permanente Washington from 2011 to 2014. Early pregnancy hemoglobin A1C (A1C) values, covariates, and outcomes were ascertained from electronic medical records and state birth certificates. Women with prediabetes (A1C of 5.7-6.4%) were compared with those with normal A1C levels (<5.7%) for risk of gestational diabetes mellitus (GDM) and other outcomes including preeclampsia, primary cesarean delivery, induction of labor, large/small for gestational age, preterm birth, and macrosomia. We used modified Poisson's regression to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Of 7,020 women, 239 (3.4%) had prediabetes. GDM developed in 48% of prediabetic women compared with 11% of women with normal A1C levels (adjusted RR: 2.8, 95% CI: 2.4-3.3). Prediabetes was not associated with all other adverse maternal and neonatal outcomes. CONCLUSION: Prediabetes in early pregnancy is a risk factor for GDM. Future research is needed to elucidate whether early intervention may reduce this risk.