Search

We sought to determine if soluble levels of C5b-9, the terminal complement complex, correlate with end-organ injury in preeclampsia.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 χC5b-9 concentrations in plasma and urine, using enzyme linked immunosorbent assays.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)].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.

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.

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. 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. 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). 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. 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.

Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy which may be mistaken for hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. We sought to identify laboratory parameters that differentiate aHUS and HELLP syndrome in the postpartum period. PubMed was searched from inception to March 2018 to identify cases of aHUS in the postpartum period, while cases of HELLP syndrome were identified from a cohort of deliveries at our institution from January 2015 to December 2018. Postpartum laboratory data were abstracted as either peak values (AST [aspartate transaminase]; creatinine; LDH [lactate dehydrogenase]) or nadir values (hemoglobin; platelet count). Differences were compared using the t test, Wilcoxon Rank Sum, or χ 2 test, and receiver operating characteristic (ROC) curve analyses were performed. We identified 46 cases of aHUS and 45 cases of HELLP syndrome in the postpartum period. Women with HELLP syndrome were older, but rates of nulliparity and cesarean delivery, and gestational age at delivery, were similar between groups. Peak serum creatinine and LDH values after delivery were the most useful to diagnose aHUS with area under the curve 0.996 (95% CI, 0.99–1.0) and 0.91 (95% CI, 0.83–0.98) respectively. Serum creatinine ≥1.9 mg/dL, LDH ≥1832 U/L, or serum creatinine ≥1.9 mg/dL in combination with LDH ≥600 U/L were the optimal thresholds for diagnosing pregnancy-associated aHUS. We conclude that standard laboratory data, most specifically peak serum creatinine and LDH, may be used to differentiate aHUS and HELLP syndrome in the postpartum period.

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

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.

We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals.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.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.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.

Background Remdesivir is efficacious for severe coronavirus disease 2019 (COVID-19) in adults, but data in pregnant women are limited. We describe outcomes in the first 86 pregnant women with severe COVID-19 who were treated with remdesivir. Methods The reported data span 21 March to 16 June 2020 for hospitalized pregnant women with polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 infection and room air oxygen saturation ≤94% whose clinicians requested remdesivir through the compassionate use program. The intended remdesivir treatment course was 10 days (200 mg on day 1, followed by 100 mg for days 2–10, given intravenously). Results Nineteen of 86 women delivered before their first dose and were reclassified as immediate “postpartum” (median postpartum day 1 [range, 0–3]). At baseline, 40% of pregnant women (median gestational age, 28 weeks) required invasive ventilation, in contrast to 95% of postpartum women (median gestational age at delivery 30 weeks). By day 28 of follow-up, the level of oxygen requirement decreased in 96% and 89% of pregnant and postpartum women, respectively. Among pregnant women, 93% of those on mechanical ventilation were extubated, 93% recovered, and 90% were discharged. Among postpartum women, 89% were extubated, 89% recovered, and 84% were discharged. Remdesivir was well tolerated, with a low incidence of serious adverse events (AEs) (16%). Most AEs were related to pregnancy and underlying disease; most laboratory abnormalities were grade 1 or 2. There was 1 maternal death attributed to underlying disease and no neonatal deaths. Conclusions Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate-use remdesivir, recovery rates were high, with a low rate of serious AEs., Among 86 pregnant and postpartum women with severe coronavirus disease 2019 who received compassionate-use remdesivir, recovery rates from serious infection were high with a low rate of serious adverse events.

OBJECTIVE To assess whether mild thrombocytopenia (platelet count 100-149 k/microliter) is associated with an increased risk of postpartum hemorrhage. METHODS Nulliparous women with term, singleton, vertex pregnancies undergoing labor at our institution between August 2016 and September 2017 were included. The primary exposure was mild thrombocytopenia, defined as platelet count 100-149 k/microliter, and the comparator was normal platelet count (150 k/microliter or greater). Those with severe thrombocytopenia (platelet count less than 100 k/microliter) were excluded from analysis. The primary outcome was postpartum hemorrhage, determined by International Classification of Diseases, Tenth Revision codes and the hospital discharge problem list. Secondary outcomes included use of uterotonic agents (methylergonovine maleate or carboprost tromethamine), total blood loss 1,000 mL or greater, and blood transfusion. Data were analyzed by t test, χ or Fisher exact test, and multivariable logistic regression, with significance at α

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).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 includedOne thousand and eight hundred patients met study criteria. Patients with elevated BP during epidural window (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.

Objective To evaluate whether women with protracted active phase labor longer than 6 hours have an increased risk of adverse maternal and neonatal outcomes after the implementation of new labor management guidelines. Methods This was a retrospective study of nulliparous, term, singleton, vertex deliveries at Cedars Sinai Medical Center from August 2016 to September 2017. Women were included if they progressed to active phase labor, defined by cervical dilation of 6 cm or more. Women then were divided into three groups based on the time course of cervical change between 6 and 10 cm: 1) normal active phase: cervical change 1 cm or more within 4 hours throughout active labor; 2) mildly protracted active phase: cervical change 1 cm or less over 4-6 hours; and 3) very protracted active phase: cervical change 1 cm or less over 6 hours. Rate of change was assessed between cervical examinations. Primary outcome was a composite of maternal morbidity by study group. Secondary outcome was a composite of neonatal morbidity. We hypothesized that women with very protracted active phase had higher rates of adverse outcomes when compared with normal active phase. Regression analyses were performed to compare maternal and neonatal outcomes by study group. Results There were 2,559 deliveries, of which 2,378 (90.8%) were vaginal deliveries. Composite maternal and neonatal morbidity was higher with longer labor. Maternal morbidity-very protracted active phase (42.0%) compared with normal active phase (22.6%) adjusted odds ratio (aOR) 2.15 (95% CI 1.62-2.86); mildly protracted active phase (39.5%) compared with normal active phase (22.6%) aOR 2.18 (95% CI 1.67-2.84). Neonatal morbidity: very protracted active phase (19.8%) compared with normal active phase (13.8%) aOR 1.38 (95% CI 0.98-1.96); mildly protracted active phase (19.4%) compared with normal active phase (13.8%) aOR 1.44; (95% CI 1.04-1.99). Composite maternal and neonatal morbidity was not different between mildly protracted and very protracted groups. Conclusion Composite maternal morbidity was greater in women with cervical change consistent with mildly protracted (4-6 hours) and very protracted (more than 6 hours) labor compared with cervical change in the normal active phase (less than 4 hours) group. However, composite maternal and neonatal morbidity was not different between mildly protracted and very protracted groups.

Background Atypical hemolytic uremic syndrome is a rare group of disorders that have in common underlying complement amplifying conditions. These conditions can accelerate complement activation that results in a positive feedback cycle. The known triggers for complement activation can be diverse and include, infection, autoimmune disease, and malignancy. Recent reports suggest that certain autoimmune and rheumatological triggers of complement activation may result in atypical hemolytic uremic syndrome that does not resolve despite treating the underlying disorder. Specifically, patients with systemic lupus erythematosus and microangiopathic hemolysis may not respond to treatment of their underlying rheumatological trigger but responded to complement blockade. Case presentations We report two patients with inflammatory bowel disease complicated by development of atypical hemolytic uremic syndrome. In both cases, patients were on treatment for inflammatory bowel disease, that was not well controlled/flaring at the time. The first patient is a male who developed Crohn’s disease and microangiopathic hemolysis at age 5 and was treated with eculizumab successfully. Discontinuation of the medication led to multiple relapses, and the patient currently is being treated with eculizumab and has normal hematological and stable renal parameters. The second patient is a 49-year-old female with Ulcerative Colitis treated with 6-Mercaptopurine. She developed acute kidney injury and microangiopathic hemolysis. Prompt diagnosis and treatment with eculizumab resulted in the recovery of kidney injury along with a complete hematological response. Conclusions These two cases are the fifth and sixth patients to be published in the literature with atypical hemolytic uremic syndrome and inflammatory bowel disease treated with complement blockade. This confirms that C5 complement blockade is effective in treating complement mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome when it is triggered in patients with inflammatory bowel disease.

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.To evaluate if the use of PP-Abx decreases postpartum infection after emergent CD with "splash" PI skin preparation.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 byIn 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 (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.

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.

Female carriers are more common than males with hemophilia and unrecognized factor VIII or IX deficiency is associated with intrauterine growth retardation, epidural hematomas, blood transfusion, and peripartum hemorrhage. A review was conducted to assess the evidence for professional society recommendations for > 50% factor levels during labor. Two searches of Pubmed, CINAHL, Cochrane, and Google Scholar were completed in October 2019. The first for case reports and series described neuraxial techniques in patients with hemophilia—regardless of sex, age, or pregnant status. The second for case reports and series described bleeding outcomes of parturients with hemophilia. Primary outcomes were diagnosis of neuraxial hematoma (first search) and postpartum bleeding complications (second search). Thirteen articles (n = 134) described neuraxial techniques in patients with hemophilia. Neuraxial hematoma with paraplegia occurred in 3/134 patients—all had a factor level of 1%. Nineteen articles (2712 deliveries in 2657 women) described bleeding outcomes. Postpartum hemorrhage occurred in 7.1% (193/2712) of deliveries, of which 60% necessitated blood transfusion. Postpartum bleeding complications were twice as likely (51.0% [25/49] vs. 25.6% [52/203], P

Dysregulation of CD59 may lead to increased complement-mediated end-organ injury in preeclampsia. We sought to determine if soluble CD59 concentrations are altered in preeclampsia with severe features.Observational case-control study, which enrolled subjects prospectively from six centers in Colombia from 2015 to 2016. Cases had preeclampsia with severe features and controls were either healthy or had chronic hypertension, gestational hypertension, or preeclampsia without severe features. Trained coordinators collected clinical data, blood and urine. Analyses were by test of medians and Spearman's correlation.Soluble CD59 concentration in plasma and urine, using enzyme linked immunosorbent assays.In total, 352 subjects were enrolled (104 cases; 248 controls). Compared to healthy women or those with other hypertensive disorders of pregnancy, women with preeclampsia with severe features had increased concentration of CD59 in plasma (P 0.001) and decreased CD59 in urine (P = 0.01). In sub-group analyses, plasma CD59 concentrations were increased in preeclampsia with severe features compared to healthy controls (P 0.001) or controls with either chronic hypertension (P = 0.002) or gestational hypertension (P = 0.02). Increased plasma CD59 concentrations correlated with decreased platelet count and increased lactate dehydrogenase, creatinine, aspartate transaminase, urine protein/creatinine ratio, systolic blood pressure and diastolic blood pressure (P 0.01, all correlations).In women with preeclampsia with severe features, soluble CD59 concentrations were increased in plasma and decreased in urine, and plasma levels correlated with increased blood pressure and end-organ injury. Soluble CD59 concentrations may help identify a subset of women with preeclampsia that have altered regulation of terminal complement proteins.

BACKGROUND: There are limited data regarding treatment options for pregnant women with severe coronavirus disease 2019 (COVID-19). CASE: A 35-year-old primigravid patient at 22 weeks of gestation presented with 7 days of fever, cough, anosmia, and dyspnea. Nasopharyngeal swab was positive for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a chest X-ray demonstrated bilateral patchy infiltrates. Laboratory evaluation was notable for marked elevation of interleukin-6 and C-reactive protein concentrations. On hospital day 3, owing to increased dyspnea and oxygen requirement, the patient was treated with tocilizumab followed by 5 days of remdesivir. She responded well, recovered to room air, and was discharged home after a 9-day hospitalization. CONCLUSION: Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.

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.

Hemolysis predisposes to adverse pregnancy outcomes. Yet, there are limited data on hemolysis in hypertensive disorders of pregnancy other than hemolysis, elevated liver enzymes, and low platelet count syndrome. To evaluate the prevalence and impact of hemolysis in hypertensive disorders of pregnancy, we performed a retrospective cohort study at a single center (October 2013–May 2017), among women screened for hemolysis using lactate dehydrogenase (LDH) levels. We compared LDH levels by hypertensive disorder (chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia with severe features) and evaluated impact on adverse pregnancy outcomes. Data were analyzed by χ 2 or t test, ANOVA, test of medians, and logistic regression. Among 8645 deliveries, 1188 (13.7%) had a hypertensive disorder. Of these, 812 (68.4%) had LDH measurement before delivery: chronic hypertension (n=152); gestational hypertension (n=209); preeclampsia (n=216); and preeclampsia with severe features (n=235). LDH ≥400 U/L (≥1.6× normal) was more common in preeclampsia with severe features compared with other hypertensive disorders of pregnancy (9.8% versus 2.3%; P P P P =0.006), and adverse neonatal outcomes (eg, preterm birth 59.4% versus 22.5%; P

Background Use of intraperitoneal local anesthetic to treat intraoperative pain during cesarean delivery has not been described previously. The aim of this study was to determine if intraperitoneal chloroprocaine may be useful as an adjunct to neuraxial block in reducing the proportion of patients with severe intraoperative pain that requires conversion to general anesthesia. Intraperitoneal chloroprocaine was administered during cesarean delivery as a potential alternative, when the anesthesiologist considered performing a general anesthetic due to severe intraoperative pain. Methods A keyword search for “chloroprocaine” was performed for patients on labor and delivery between November 2013 and March 2017. Patients were included if cesarean delivery was initiated with neuraxial anesthesia and there was documented intraoperative intraperitoneal instillation of chloroprocaine. Results Among 2479 patients who had cesarean delivery with neuraxial anesthesia, 32 received intraperitoneal chloroprocaine (mean dose 11.8 mg/kg). No patients exhibited signs of local anesthetic systemic toxicity or required conversion to general anesthesia. Among the 32 patients who received chloroprocaine, 17 had improved pain scores documented after instillation. Conclusion Intraperitoneal chloroprocaine may be useful as part of a multimodal approach to managing intraoperative pain during cesarean delivery.

To assess the incidence and severity of preeclampsia in pregnancies complicated by fetal hydrops.We performed a retrospective cohort study of singleton gestations from 2005 to 2008 in California. The primary predictor was fetal hydrops and the primary outcome was preeclampsia. Selected adverse maternal and neonatal events were assessed as secondary outcomes. Potential confounders examined included fetal anomalies, polyhydramnios, race/ethnicity, nulliparity, chronic hypertension, and gestational or pregestational diabetes mellitus.We identified 337 pregnancies complicated by fetal hydrops, 70.0% had a concomitant fetal anomaly and 39.8% had polyhydramnios. Compared to the general population, hydrops was associated with an increased risk for severe preeclampsia (5.26 versus 0.91%, p .001) but not mild preeclampsia (2.86 versus 2.02%, p = .29). In multivariable analysis, fetal hydrops remained an independent risk factor for severe preeclampsia (as adjusted odds ratios (aOR) 3.13, 1.91-5.14). Hydrops was also associated with increased rates of eclampsia, acute renal failure, pulmonary edema, postpartum hemorrhage, blood transfusion, preterm birth, and neonatal death.We find that fetal hydrops is an independent risk factor for severe preeclampsia. In light of serious concerns for maternal and neonatal health, heightened surveillance for signs and symptoms of severe preeclampsia is warranted in all pregnancies complicated by fetal hydrops.

Objective Traditionally, physiological variation in fetal weight is believed to emerge during the latter half of pregnancy. Although recent evidence suggests that crown-rump length (CRL) and nuchal translucency (NT) measured at 11–14 weeks correlate with abnormal fetal growth, findings have been limited by dating accuracy in spontaneous gestations. Therefore, we sought to determine whether CRL or NT measurements correlated with term birth weight (BW) or BW ratio in a cohort of IVF pregnancies, in which the date of conception is precisely known. Methods This retrospective cohort study included 227 term, singleton IVF pregnancies. Subjects were included if they had an early first-trimester ultrasound examination and subsequent nuchal translucency (NT) screening. The difference between the measured and the expected CRL and the biparietal diameter (BPD) and NT measurement were calculated and correlated with the actual term BW or BW ratio. The BW ratio was calculated using the actual BW and the expected BW for GA. Results The difference between measured and expected mid–first-trimester CRL, and the BPD at NT assessment, correlated with BW ratio at delivery ( r Spearman = 0.15, P = 0.023 and r Spearman = 0.27, P r Spearman = 0.18, r = 0.14, and P = 0.005 and 0.038, respectively). Conclusion In this well-dated IVF population, we report a significant correlation between BW ratio and first-trimester CRL, BPD, and NT measurements. These findings support the hypothesis that physiological variation in BW can be reflected by variation in first-trimester fetal measurements.

Pregnant women with chronic myeloid leukemia (CML) can be treated effectively with the tyrosine-kinase inhibitor imatinib, but data regarding fetal and neonatal exposure and safety are limited.We present a patient with newly diagnosed CML in early pregnancy. Leukapheresis and interferon-α were initiated in the second trimester with limited benefit. Imatinib was subsequently started at 28 weeks of gestation with complete hematologic response within 4 weeks. No significant maternal or neonatal adverse effects were noted, but imatinib and its primary active metabolite concentrated in maternal breast milk and neonatal urine.Imatinib is effective for CML in pregnancy, but caution is warranted in light of potentially unrecognized fetal and neonatal effects.

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease induced by many triggers, all of which produce a common end phenotype of microangiopathic hemolysis and thrombotic microangiopathy. We herein describe a 63-year-old woman with ongoing protein-losing enteropathy and frequent transudates caused by hypoalbuminemia. The patient was treated with eculizumab with a full hematologic and partial renal response. Protein-losing enteropathy is an inflammatory condition that has been linked with increased complement activation, which can trigger aHUS in patients with loss of CD55 expression. The patient in the present case had an increased estimated glomerular filtration rate but stage IV to V chronic kidney disease. One year later, she remains off dialysis with a stable estimated glomerular filtration rate. We herein report an unusual trigger of complement activation that in turn triggered aHUS in this patient.

Atypical hemolytic uremic syndrome (aHUS) is a diagnosis that has captured the interest of specialists across multiple fields. The hallmark features of aHUS are microangiopathic hemolysis and thrombocytopenia, which creates a diagnostic dilemma because of the occurrence of these findings in a wide variety of clinical disorders.In most of the instances, aHUS is a diagnosis of exclusion after ruling out causes such as Shigella toxin, acquired or genetic a disintegrin and metalloproteinase thrombospondin motif 13 deficiency (thrombotic thrombocytopenic purpura), and vitamin B12 deficiency. In the purest sense, aHUS is a genetic condition that is activated (or unmasked) by an environmental exposure. However, it is now evident that complement activation is a feature of many diseases. Variants in complement regulatory genes predispose to microangiopathic hemolysis in many rheumatologic, oncologic, and drug-induced vascular, obstetric, peritransplant, and infectious syndromes.Many 'hemolysis syndromes' overlap clinically with aHUS, and we review the literature on the treatment of these conditions with complement inhibition. New reports on the treatment of C3 glomerulopathy, Shiga toxin-related classic hemolytic uremic syndrome, and medication-related thrombotic microangiopathy will be reviewed as well.