Concurrent progestogen and cerclage to reduce preterm birth: a multicenter international retrospective cohort.

BACKGROUND: Both progestogens and cerclage are individually effective in preterm birth prevention in high risk pregnancies. However, national and international guidelines cite a lack of data available to comment on the potential benefit of concurrent progestogen therapy after cerclage has been placed. Studies to date have been small with mixed results regarding benefit of concurrent progestogen with cerclage leaving uncertainty regarding best clinical practice. OBJECTIVE: This study aimed to evaluate whether cerclage with progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth in singleton pregnancies. METHODS: This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016 to June 2020. Exclusion criteria were lack of documentation regarding whether progestogen was prescribed, unavailable delivery outcome, and pregnancy termination (spontaneous or induced) before 16 weeks' gestation. The exposure of interest was progestogen use with cerclage placement, which included those who continued to use progestogen or who started progestogen after cerclage. The comparison group consisted of those without progestogen use after cerclage placement, which included those who had no progestogen use during the entire pregnancy or who initiated progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. The primary outcome was spontaneous preterm birth at <37 weeks. The secondary outcomes were spontaneous preterm birth at <34 weeks, gestational age at delivery, and a composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, and bronchopulmonary dysplasia. There were planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate), preterm birth history, and site. Continuous variables were compared in adjusted analyses with analysis of covariance, and categorical variables were compared with multivariable logistic regression, adjusting for potential confounders with adjusted odds ratio. A Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks. RESULTS: During the study period, a total of 699 singletons met the inclusion criteria: 561 in the progestogen with cerclage group and 138 with cerclage alone. Baseline characteristics were similar, except the higher likelihood of previous spontaneous preterm birth in the progestogen group (61% vs 41%; P<.001). Within the progestogen group, 52% were on 17-hydroxyprogesterone caproate weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of spontaneous preterm birth <37 weeks (31% vs 39%; adjusted odds ratio, 0.59 [0.39-0.89]; P=.01) and <34 weeks (19% vs 27%; adjusted odds ratio, 0.55 [0.35-0.87]; P=.01), increased latency to spontaneous delivery (hazard ratio for spontaneous preterm birth <37 weeks, 0.66 [0.49-0.90]; P=.009), and lower frequency of perinatal death (7% vs 16%; adjusted odds ratio, 0.37 [0.20-0.67]; P=.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a previous preterm birth, those with ultrasound- or examination-indicated cerclage, those who started progestogen therapy before cerclage, and in sites restricted to the United States. CONCLUSION: Use of progestogen with cerclage was associated with reduced rates of spontaneous preterm birth and early spontaneous preterm birth compared with cerclage alone. Although this study was not sufficiently powered for subgroup analysis, the strength of evidence for benefit appeared greatest for those with ultrasound- or examination-indicated cerclage, and with vaginal progesterone.

Angiogenic Biomarkers in Preeclampsia.

Preeclampsia contributes disproportionately to maternal and neonatal morbidity and mortality throughout the world. A critical driver of preeclampsia is angiogenic imbalance, which is often present weeks to months before overt disease. Two placenta-derived angiogenic biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), have proved useful as diagnostic and prognostic tests for preeclampsia. Recently, the U.S. Food and Drug Administration approved the sFlt-1/PlGF assay to aid in the prediction of preeclampsia with severe features among women with hypertensive disorders of pregnancy at 24-34 weeks of gestation. In this narrative review, we summarize the body of work leading to this approval and describe how the sFlt-1/PlGF ratio may be implemented in clinical practice as an adjunctive measure to help optimize care and to reduce adverse outcomes in preeclampsia.

The association between maternal insurance status on maternal and neonatal outcomes in women with hypertensive disorders of pregnancy.

The objective of this study was to examine the association between maternal insurance status and maternal and neonatal adverse outcomes in women who had hypertensive disorders in pregnancy. A population-based retrospective cohort study was undertaken using the US Vital Statistics dataset on Period Linked Birth-Infant Data from 2016-2020. The study population was restricted to non-anomalous births from women whose pregnancies were complicated by hypertensive disorders. Insurance status was categorized as private, Medicaid, self-pay and other. The primary outcome was a composite of maternal adverse outcomes, which included admission to the intensive care unit, unplanned hysterectomy, maternal blood transfusion or uterine rupture. We examined the role of prenatal care in these relationships using a mediation analysis with Kotelchuck's Adequacy of Prenatal Care Utilization Index. Multivariable logistic regression models were used to estimate the association between maternal insurance status and adverse outcomes (using adjusted odds ratios [aOR] and 99% confidence interval [CI]). Of the 18,999,865 live births in the five-year study, 1,642,654 (8.6%) met the inclusion criteria. The frequency of the composite maternal adverse outcome was 1.3%. The maternal composite occurred more frequently in women with Medicaid (aOR = 1.11, 99% CI: 1.06, 1.16) or self-pay (aOR = 1.40, 99% CI: 1.25, 1.55) when compared to private insurance. Adjusting for prenatal care slightly attenuated this association, but remained significant. Among women with hypertensive disorders in pregnancy, women with Medicaid insurance or self-pay were more likely to experience maternal and neonatal adverse outcomes than women with private insurance.

Identification of complement factor H variants that predispose to pre-eclampsia: A genetic and functional study.

OBJECTIVE: The objective of the study was to investigate the role of genetic variants in complement proteins in pre-eclampsia. DESIGN: In a case-control study involving 609 cases and 2092 controls, five rare variants in complement factor H (CFH) were identified in women with severe and complicated pre-eclampsia. No variants were identified in controls. SETTING: Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Immune maladaptation, in particular, complement activation that disrupts maternal-fetal tolerance leading to placental dysfunction and endothelial injury, has been proposed as a pathogenetic mechanism, but this remains unproven. POPULATION: We genotyped 609 pre-eclampsia cases and 2092 controls from FINNPEC and the national FINRISK cohorts. METHODS: Complement-based functional and structural assays were conducted in vitro to define the significance of these five missense variants and each compared with wild type. MAIN OUTCOME MEASURES: Secretion, expression and ability to regulate complement activation were assessed for factor H proteins harbouring the mutations. RESULTS: We identified five heterozygous rare variants in complement factor H (L3V, R127H, R166Q, C1077S and N1176K) in seven women with severe pre-eclampsia. These variants were not identified in controls. Variants C1077S and N1176K were novel. Antigenic, functional and structural analyses established that four (R127H, R166Q, C1077S and N1176K) were deleterious. Variants R127H and C1077S were synthesised, but not secreted. Variants R166Q and N1176K were secreted normally but showed reduced binding to C3b and consequently defective complement regulatory activity. No defect was identified for L3V. CONCLUSIONS: These results suggest that complement dysregulation due to mutations in complement factor H is among the pathophysiological mechanisms underlying severe pre-eclampsia.

Elevated liver enzymes and adverse outcomes among patients with preeclampsia with severe features.

OBJECTIVE: The rate of preeclampsia with severe features has increased. Previous studies have shown elevated liver enzymes are an indicator of worsening hypertensive disease of pregnancy and adverse outcomes, therefore leading to their inclusion as a diagnostic criterion for severe features of preeclampsia. Despite this, there are limited data to support an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration ≥ two times the upper limit of normal as the critical point at which maternal harm from ongoing pregnancy exceeds neonatal harm from delivery. The objective of this study is to evaluate the association between elevated liver enzymes and maternal and neonatal outcomes among patients with preeclampsia with severe features. METHODS: Retrospective cohort study among hypertensive patients who delivered ≥23 weeks' gestation at Oregon Health & Science University (October 2013-September 2018). Those with preeclampsia with severe features (including chronic hypertension with superimposed preeclampsia meeting criteria for severe features) were included after a screening of ICD-9 and ICD-10 codes and chart validation. The primary exposure was elevated liver enzymes prior to delivery, according to the American College of Obstetricians and Gynecologists' criteria for severe features of preeclampsia: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2x the upper limit of normal (above threshold liver function tests [LFTs]). Primary outcomes included adverse maternal and neonatal outcomes. Differences were analyzed by Chi-squared, Fisher's exact, t-test, and logistic regression, with α = 0.05. RESULTS: Of 11,825 deliveries, 319 (2.7%) met inclusion criteria and had preeclampsia with severe features. Of these, 44 (13.8%) had above threshold LFTs. Adverse maternal outcomes were no different in those with above threshold LFTs compared to those with below threshold LFTs. The unadjusted odds of an adverse neonatal outcome were 2.08 times greater in patients with above threshold LFTs (95% CI: 1.04-4.14), and 2.43 times greater when adjusting for maternal characteristics (95% CI: 1.17-5.04) compared to those with below threshold LFTs. However, the association between above threshold LFTs and adverse neonatal outcomes became non-significant after adjustment for gestational age at delivery (OR: 1.54, 95% CI: 0.63-3.76). CONCLUSION: Among patients with preeclampsia with severe features, above threshold LFTs are not independently associated with an increased risk of adverse maternal or neonatal outcomes. Adverse neonatal outcomes in patients with preeclampsia with severe features and above threshold LFTs are driven by earlier gestational age at delivery. Prospective studies are needed to guide delivery timing in patients with preeclampsia and elevated liver enzymes. BRIEF RATIONALE: The criteria for elevated liver function tests (greater than two times the upper limit of normal) are widely accepted among obstetricians to diagnose a severe feature of preeclampsia. However, these criteria are based on expert opinion and extrapolated from data on patients with HELLP syndrome. Since preterm delivery of the neonate is recommended for preeclampsia with severe features, the threshold used to define severe liver enzyme elevation has a direct impact on neonatal outcomes. Therefore, the goal of our study was to determine if patients with preeclampsia with severe features and a pre-delivery AST or ALT level ≥ two times the upper limit of normal have worse maternal and neonatal outcomes compared to those with an AST and ALT below this level.

Evaluation of Low-Dose Aspirin to Prevent Preeclampsia in Pregnant People with Chronic Hypertension.

OBJECTIVE: Our objective was to evaluate if the use of low-dose aspirin (LDA) among pregnant individuals with chronic hypertension (CHTN) reduces the rate of superimposed preeclampsia or other adverse maternal and neonatal outcomes. STUDY DESIGN: Our study included single-center cohort of pregnant individuals with CHTN who had a live birth after 23 weeks' gestation, between 2013 and 2018. The primary exposure was the use of LDA in pregnancy and the primary outcome was superimposed preeclampsia. LDA use was also evaluated by the timing of initiation, before or after 16 weeks' gestation. Secondary outcomes included preeclampsia subtypes (e.g., preeclampsia with severe features, early-onset disease), as well as adverse maternal and neonatal outcomes. Differences were analyzed by χ 2, Fisher's exact, or t tests, with logistic regression to adjust for confounders. RESULTS: Of 11,825 deliveries during the study period, 494 (4.2%) occurred in women with CHTN. Among those with CHTN, 174 (35%) were prescribed LDA, most often 81 mg daily (173 out of 174, 99%). Baseline characteristics were similar between groups, but the history of preeclampsia was more common in those prescribed LDA. The rate of superimposed preeclampsia was no different among those with CHTN-prescribed LDA compared with those who were not (36% vs. 30%, p = 0.2), even when restricting the analysis to those prescribed LDA before 16 weeks' gestation (33 vs. 30%, p = 0.2). In addition, LDA did not lead to a reduction in the rate of preeclampsia with severe features, early-onset preeclampsia, or other adverse maternal outcomes. However, the composite rate of adverse neonatal outcomes was lower in LDA users versus nonusers (4.0 vs. 13%, p = 0.002), which persisted after multivariable adjustment (adjusted odds ratio: 0.28, 95% confidence interval: 0.12-0.67). CONCLUSION: Among pregnant individuals with CHTN, LDA did not decrease the rate of superimposed preeclampsia. Further studies are warranted to validate our observed reduction in adverse neonatal outcomes and to determine if aspirin is more beneficial at dosages greater than 81 mg daily. KEY POINTS: · Superimposed preeclampsia rates are the same regardless of LDA.. · Decreased rate of adverse neonatal outcomes is seen with LDA.. · No decrease in adverse maternal outcomes is seen with LDA..

Maternal and fetal outcomes of pregnancy occurring after a diagnosis of immune-mediated thrombotic thrombocytopenic purpura.

Pregnancy is a well-established trigger for a first episode or relapse of immune thrombotic thrombocytopenic purpura (iTTP). Other outcomes of subsequent pregnancy after a diagnosis of iTTP are less well described. We conducted this retrospective cohort study to evaluate maternal and fetal outcomes of pregnancy in women with prior iTTP from the Johns Hopkins Thrombotic Microangiopathy Cohort. Of 168 women in the cohort, 102 were of reproductive age at diagnosis. Fourteen pregnancies (in 9 women) that occurred after the initial iTTP episode were included in the analysis. iTTP relapse occurred in 9 (64%) pregnancies. Out of the 9 instances of relapse, 5 relapses occurred in 2 women. Seven pregnancies (50%) ended in fetal death or miscarriage in the setting of iTTP relapse and three were electively terminated due to fear of relapse. Four pregnancies (50% of the 8 that progressed beyond 20 weeks) were complicated by preeclampsia or HELLP syndrome, which is over ten-fold higher than that of the general population. No maternal deaths occurred. Only 4 pregnancies resulted in live births, of which, 2 were pre-term. Pregnancy in women with prior iTTP is associated with a substantial risk of iTTP relapse and fetal loss. Preeclampsia and HELLP syndrome is also more common than that in the general population. ADAMTS13 monitoring and preemptive therapy may improve pregnancy outcomes, which needs to be evaluated prospectively.

Soluble concentrations of the terminal complement complex C5b-9 correlate with end-organ injury in preeclampsia.

OBJECTIVE: We sought to determine if soluble levels of C5b-9, the terminal complement complex, correlate with end-organ injury in preeclampsia. STUDY DESIGN: Project COPA (Complement and Preeclampsia in the Americas), a multi-center observational study in Colombia from 2015 to 2016, enrolled hypertensive pregnant women into four groups: chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia with severe features. Trained coordinators collected clinical data, blood and urine. End-organ injury was defined by serum creatinine ≥ 1.0 mg/dl, aspartate transaminase ≥ 70U/L, platelet count < 150,000/µl, or lactate dehydrogenase ≥ 500 U/L. Data were analyzed by χ2 or Fisher's exact test with significance at P < 0.05. MAIN OUTCOME MEASURE: C5b-9 concentrations in plasma and urine, using enzyme linked immunosorbent assays. RESULTS: In total, 298 hypertensive participants were enrolled. Plasma and urine C5b-9 levels were measured in all participants and stratified by quartile (Q1-4), from lowest to highest C5b-9 concentration. Participants with low plasma C5b-9 levels (Q1) were more likely to have end-organ injury compared to those with higher levels (Q2-Q4) [platelet count < 150,000/µl (20.8% vs. 8.4%, P = 0.01); elevated serum creatinine ≥ 1.0 mg/dl (14.9% vs. 4.5%, P = 0.009)]. In contrast, participants with high urinary C5b-9 levels (Q4) were more likely to have end-organ injury compared to those with lower levels (Q1-Q3) [platelet count < 150,000/µl (19.7% vs. 7.4%, P = 0.003); elevated serum creatinine ≥ 1.0 mg/dl (12.3% vs. 4.4%, P = 0.025)]. CONCLUSION: We identified a pattern of increased urine and low plasma C5b-9 levels in patients with preeclampsia and end-organ injury. Soluble C5b-9 levels may be used to identify complement-mediated end-organ injury in preeclampsia.

Thrombotic Microangiopathy Syndromes-Common Ground and Distinct Frontiers.

Thrombotic microangiopathies (TMAs) have in common a terminal phenotype of microangiopathic hemolytic anemia with end-organ dysfunction. Thrombotic thrombocytopenic purpura results from von Willebrand factor multimerization, Shiga toxin-mediated hemolytic uremic syndrome causes toxin-induced endothelial dysfunction, while atypical hemolytic uremic syndrome results from complement system dysregulation. Drug-induced TMA, rheumatological disease-induced TMA, and renal-limited TMA exist in an intermediate space that represents secondary complement activation and may overlap with atypical hemolytic uremic syndrome clinically. The existence of TMA without microangiopathic hemolytic features, renal-limited TMA, represents an undiscovered syndrome that responds incompletely and inconsistently to complement blockade. Hematopoietic stem cell transplant-TMA represents another more resistant form of TMA with different therapeutic needs and clinical course. It has become apparent that TMA syndromes are an emerging field in nephrology, rheumatology, and hematology. Much work remains in genetics, molecular biology, and therapeutics to unravel the puzzle of the relationships and distinctions apparent between the different subclasses of TMA syndromes.

Association Between Low-Dose Aspirin and Development of Gestational Diabetes: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the association between the use of low-dose aspirin for preeclampsia prophylaxis and risks of gestational diabetes (primary outcome), neonatal hypoglycemia, macrosomia, large for gestational age, birth trauma, and shoulder dystocia (secondary outcomes). DATA SOURCES: We searched Ovid MEDLINE, Embase, CINAHL, and Cochrane/CENTRAL for studies published between January 1, 1989, and April 24, 2021. STUDY SELECTION: Randomized controlled trials (RCTs) or cohort studies of any size conducted in any setting were included. DATA EXTRACTION AND SYNTHESIS: We assessed risk of bias using the Cochrane Risk of Bias tool 2.0 (for RCTs) and the Newcastle-Ottawa Scale (for cohort studies). We meta-analyzed relative risks (RRs) using random-effects models. CONCLUSIONS: Our search retrieved 4441 records, of which 9 studies (6 RCTs with 1932 patients and 3 cohort studies with 313 837 patients) met inclusion criteria. We rated only 4 of the 6 RCTs and 1 of the 3 cohort studies at low risk of bias. Low-dose aspirin in pregnancy for preeclampsia prophylaxis was not associated with a greater risk of gestational diabetes (RR 1.18; 95% confidence interval 0.80-1.74). No studies reported data for the secondary outcomes. In summary, the use of low-dose aspirin does not appear associated with risk of gestational diabetes. The poor quality and small number of studies limit the interpretation of these results.

Complement blockade with eculizumab for treatment of severe Coronavirus Disease 2019 in pregnancy: A case series.

PROBLEM: We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals. METHOD OF STUDY: Protocol ECU-COV-401 (clinicaltrials.gov NCT04355494) is an open label, multicenter, Expanded Access Program (EAP), evaluating eculizumab for treatment of severe COVID-19. Participants enrolled at our center from August 2020 to February 2021. Hospitalized patients were eligible if they had severe COVID-19 with bilateral pulmonary infiltrates and oxygen requirement. Eculizumab was administered on day 1 (1200 mg IV) with additional doses if still hospitalized (1200 mg IV on Days 4 and 8; 900 mg IV on Days 15 and 22; optional doses on Days 12 and 18). The primary outcome was survival at Day 15. Secondary outcomes included survival at Day 29, need for mechanical ventilation, and duration of hospital stay. We evaluated pharmacokinetic and pharmacodynamic data, safety, and adverse outcomes. RESULTS: Eight participants were enrolled at the Cedars-Sinai Medical Center, six during pregnancy (mean 30 ± 4.0 weeks) and two in the postpartum period. Baseline oxygen requirement ranged from 2 L/min nasal cannula to 12 L/min by non-rebreather mask. The median number of doses of eculizumab was 2 (range 1-3); the median time to hospital discharge was 5.5 days (range 3-12). All participants met the primary outcome of survival at Day 15, and all were alive and free of mechanical ventilation at Day 29. In three participants we demonstrated that free C5 and soluble C5b-9 levels decreased following treatment. There were no serious adverse maternal or neonatal events attributed to eculizumab at 3 months. CONCLUSION: We describe use of eculizumab to treat severe COVID-19 in a small series of pregnant and postpartum adults. A larger, controlled study in pregnancy is indicated.

Elevated blood pressures during epidural placement are associated with increased risk of hypertensive disorders of pregnancy.

BACKGROUND: Many providers ignore hypertensive blood pressures (BPs) during epidural placement, attributing them to patient pain or malposition. We aimed to determine if an elevated BP during epidural placement was associated with increased risk for developing a hypertensive disorder of pregnancy (HDP). METHODS: Cohort study of previously normotensive nulliparous, singleton, term patients who received neuraxial analgesia and delivered at our institution in 2016. Primary exposure was BP during epidural window (one hour before and after epidural procedure start time). Primary outcome was HDP (gestational hypertension, preeclampsia, eclampsia, or HELLP syndrome) prior to discharge. Statistics included χ2, t-test, and multivariable logistic regression; α = 0.05. RESULTS: One thousand and eight hundred patients met study criteria. Patients with elevated BP during epidural window (n = 566, 31.4%) were more likely to develop HDP than patients who remained normotensive during epidural window (20.1% vs. 6.4%, adjusted OR 3.57 [95% CI 2.61-4.89]). The incidence of HDP increased in association with BP severity during epidural window: 7.3% for maximum systolic blood pressure (SBP) <140 mmHg; 18.4% for maximum SBP 140-159 mmHg (OR 2.9, 95% CI 2.0-4.0); and 29.9% for maximum SBP ≥160 mmHg (OR 5.4, 95% CI 2.9-9.8). The trend was similar for maximum diastolic BP. The magnitude of increased odds for HDP was highest for Black patients with elevated BP during epidural window (40.9% vs. 10.1%, OR 6.1, 95% CI 2.4-16). CONCLUSIONS: Previously normotensive patients with an elevated BP during labor epidural placement are significantly more likely to develop HDP than patients who remain normotensive. Elevated BP during epidural placement should not be disregarded to ensure timely diagnosis and treatment.

Complement activation and regulation in preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome.

The complement system is critical to human health owing to its central role in host defense and innate immunity. During pregnancy, the complement system must be appropriately regulated to allow for immunologic tolerance to the developing fetus and placenta. Although some degree of complement activation can be seen in normal pregnancy, the fetus seems to be protected in part through the placental expression of complement regulatory proteins, which inhibit complement activation at different steps along the complement activation cascade. In women who develop preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, there is a shift toward increased complement activation and decreased complement regulation. There is an increase in placental deposition of C5b-9, which is the terminal effector of classical, lectin, and alternative complement pathways. C5b-9 deposition stimulates trophoblasts to secrete soluble fms-like tyrosine kinase-1, which sequesters vascular endothelial growth factor and placental growth factor. Pathogenic mutations or deletions in complement regulatory genes, which predispose to increased complement activation, have been detected in women with preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Before the disease, biomarkers of alternative complement pathway activation are increased; during active disease, biomarkers of terminal complement pathway activation are increased. Urinary excretion of C5b-9 is associated with preeclampsia with severe features and distinguishes it from other hypertensive disorders of pregnancy. Taken together, existing data link preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome with increased activation of the terminal complement pathway that, in some cases, may be influenced by genetic alterations in complement regulators. These findings suggest that the inhibition of the terminal complement pathway, possibly through C5 blockade, may be an effective strategy to treat preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, but this strategy warrants further evaluation in clinical trials.

Marijuana use and pregnancy outcomes among women with hypertension in pregnancy.

BACKGROUND: Marijuana has vasoconstrictive properties and its use has been associated with increased blood pressure in the general population. Yet, there are limited data on marijuana use and adverse outcomes among women with hypertension in pregnancy, even though these disorders are associated with severe maternal and fetal morbidity and mortality. Since marijuana is currently the most commonly used illicit drug in pregnancy, there is an urgent need to better understand the potential association between marijuana use and hypertension in pregnancy. OBJECTIVE: To determine the adverse prenatal effects of marijuana use in women with hypertension in pregnancy. STUDY DESIGN: We conducted a retrospective cohort study among individuals with hypertension in pregnancy that delivered ≥23 weeks' gestation at Oregon Health & Science University (October 2013-September 2018). The primary exposure assessed was marijuana use, identified by chart review of documented patient self-report or positive urine toxicology screen. Individuals were stratified into two groups by marijuana use: use during pregnancy versus never used. Primary outcomes included composite adverse maternal and neonatal outcomes. Secondary outcomes included individual maternal outcomes, rarer neonatal outcomes and severe features of preeclampsia. Differences were analyzed by Fisher's exact, t-test, and logistic regression. Significance was determined by alpha = 0.05 for primary outcomes and alpha = 0.01 for secondary outcomes. RESULTS: From 11,825 deliveries, 1,613 (13.6%) were classified with hypertension in pregnancy. A total of 117 individuals (7.3%) used marijuana during pregnancy, 1,110 (68.2%) had never used marijuana and 396 (24.6%) had unknown marijuana use and were excluded, leaving 1,217 individuals in this analysis. Women using marijuana in pregnancy were more likely to be younger, non-Hispanic White, publicly insured and using other substances compared to women who did not use marijuana. There were no differences in the overall distribution of hypertensive disorders, including preeclampsia with severe features, in women who used marijuana versus those who did not (p = .80). In multivariable analyses, after adjusting for maternal factors and other substance use, marijuana use was not associated with adverse maternal (aOR 1.23, 95% CI 0.43-3.50, p = .69) or neonatal (aOR 0.90, 95% CI 0.28-2.89, p = .86) outcomes. CONCLUSIONS: Marijuana use in pregnancy was not associated with maternal or neonatal outcomes or worsened hypertensive disease among women with hypertension in pregnancy after adjusting for maternal characteristics, including use of other substances. Our data highlight the need to consider use of other substances when evaluating the association between marijuana use in pregnancy and adverse pregnancy outcomes.

Prophylactic postoperative antibiotics after emergent cesarean delivery and risk of postpartum infection or wound complication.

BACKGROUND: Emergent cesarean delivery (CD) carries a high risk for postpartum infection. In cases with a "splash" povidone-iodine (PI) skin preparation, prophylactic postoperative antibiotics (PP-Abx) are sometimes utilized, but the benefit is unclear. OBJECTIVE: To evaluate if the use of PP-Abx decreases postpartum infection after emergent CD with "splash" PI skin preparation. STUDY DESIGN: Cohort study of patients undergoing emergent CD with PI skin preparation from July 2012 to April 2020 at a single institution. Cases were identified using a natural language search engine, DEEP-6, with key terms "emergent" and "cesarean delivery." Patients with chorioamnionitis or non-PI skin preparation (e.g. chlorhexidine) were excluded. The primary exposure was use of PP-Abx. The primary outcome was postpartum infection or wound complication, defined as a composite: endometritis, wound infection, cellulitis, seroma, hematoma, or intra-abdominal abscess. Rates of postpartum infection or wound complication were stratified by use of PP-Abx. Demographic and labor characteristics were evaluated as confounders. Statistics by χ2, t-test, and logistic regression (α = 0.05). RESULTS: In total, 481 patients underwent emergent CD; of those, 370 had PI skin preparation and were included. PP-Abx were given in 43% (160/370) of cases, including: cefazolin (n = 137), gentamicin/clindamycin (n = 18), azithromycin (n = 3), and vancomycin (n = 2). Those receiving PP-Abx were similar to those who did not, except the PP-Abx group was younger with longer CD duration. The rate of postpartum infection or wound complication was no different in patients who received PP-Abx compared to those who did not (12.6% vs. 9.5%, p = .34). This finding remained unchanged after multivariable adjustment (aOR 1.2, CI 0.61-2.4, p = .60). Moreover, the rate of postpartum infection or wound complication did not vary by antibiotic choice. CONCLUSIONS: After emergent CD with PI skin preparation, routine use of prophylactic postoperative antibiotics does not appear to reduce the rate of postpartum infection or wound complication, which is important as we consider antibiotic stewardship. More studies are needed to identify treatments that decrease infectious morbidity with emergent CD.

Monoclonal Antibodies Casirivimab and Imdevimab in Pregnancy for Coronavirus Disease 2019 (COVID-19).

BACKGROUND: For unvaccinated individuals with mild-to-moderate coronavirus disease 2019 (COVID-19), monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decrease the risk of severe disease and hospitalization. We describe the use of the monoclonal antibodies casirivimab and imdevimab for COVID-19 in pregnancy. CASE: Two unvaccinated pregnant individuals presented with moderate COVID-19, one in the second trimester and one in third trimester; both met criteria for outpatient management. To decrease the risk for severe disease, they were treated with casirivimab and imdevimab. Neither experienced an adverse drug reaction, and neither progressed to severe disease. CONCLUSION: Monoclonal antibodies such as casirivimab and imdevimab, approved under an emergency use authorization, should be considered in unvaccinated pregnant individuals with mild-to-moderate COVID-19 to decrease the risk of severe disease.

Differentiating Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome and Atypical Hemolytic Uremic Syndrome in the Postpartum Period.

[Figure: see text].

Complement-Mediated Thrombotic Microangiopathy Associated with Lupus Nephritis Treated with Eculizumab: A Case Report.

Thrombotic microangiopathies (TMAs) involve multiple organ systems due to the presence of microangiopathic hemolysis. One such condition, atypical hemolytic uremic syndrome (aHUS), is a complement-mediated process that is part of a spectrum of disorders that have underlying complement dysfunction of the alternative pathway due to overactivity or decreased self-nonself discrimination by innate immunity. Complement-amplifying conditions such as pregnancy may unmask a diagnosis of aHUS. We present an important case of a pregnant 23-year-old Hispanic female who presented in mid-gestation (21 weeks) with an initial diagnosis of systemic lupus erythematosus (SLE) complicated by aHUS. She met clinical criteria for aHUS on presentation and was found to have a pathogenic CFHR1-3 homozygous deletion. She has been treated with intravenous and oral steroids, cyclophosphamide, subsequently also with plasma exchange, and finally with eculizumab with partial improvement in renal function. This case adds to the emerging literature showing that SLE and aHUS (or complement-mediated TMA) can be successfully treated with C5 blockade.