Society for Maternal-Fetal Medicine Consult Series #67: Maternal sepsis.

Maternal sepsis is a significant cause of maternal morbidity and mortality, and is a potentially preventable cause of maternal death. This Consult aims to summarize what is known about sepsis and provide guidance for the management of sepsis during pregnancy and the postpartum period. Most studies cited are from the nonpregnant population, but where available, pregnancy data are included. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend that clinicians consider the diagnosis of sepsis in pregnant or postpartum patients with otherwise unexplained end-organ damage in the presence of a suspected or confirmed infectious process, regardless of the presence of fever (GRADE 1C); (2) we recommend that sepsis and septic shock in pregnancy be considered medical emergencies and that treatment and resuscitation begin immediately (Best Practice); (3) we recommend that hospitals and health systems use a performance improvement program for sepsis in pregnancy with sepsis screening tools and metrics (GRADE 1B); (4) we recommend that institutions develop their own procedures and protocols for the detection of maternal sepsis, avoiding the use of a single screening tool alone (GRADE 1B); (5) we recommend obtaining tests to evaluate for infectious and noninfectious causes of life-threatening organ dysfunction in pregnant and postpartum patients with possible sepsis (Best Practice); (6) we recommend that an evaluation for infectious causes in pregnant or postpartum patients in whom sepsis is suspected or identified includes appropriate microbiologic cultures, including blood, before starting antimicrobial therapy, as long as there are no substantial delays in timely administration of antibiotics (Best Practice); (7) we recommend obtaining a serum lactate level in pregnant or postpartum patients in whom sepsis is suspected or identified (GRADE 1B); (8) in pregnant or postpartum patients with septic shock or a high likelihood of sepsis, we recommend administration of empiric broad-spectrum antimicrobial therapy, ideally within 1 hour of recognition (GRADE 1C); (9) after a diagnosis of sepsis in pregnancy is made, we recommend rapid identification or exclusion of an anatomic source of infection and emergency source control when indicated (Best Practice); (10) we recommend early intravenous administration (within the first 3 hours) of 1 to 2 L of balanced crystalloid solutions in sepsis complicated by hypotension or suspected organ hypoperfusion (GRADE 1C); (11) we recommend the use of a balanced crystalloid solution as a first-line fluid for resuscitation in pregnant and postpartum patients with sepsis or septic shock (GRADE 1B); (12) we recommend against the use of starches or gelatin for resuscitation in pregnant and postpartum patients with sepsis or septic shock (GRADE 1A); (13) we recommend ongoing, detailed evaluation of the patient's response to fluid resuscitation guided by dynamic measures of preload (GRADE 1B); (14) we recommend the use of norepinephrine as the first-line vasopressor during pregnancy and the postpartum period with septic shock (GRADE 1C); (15) we suggest using intravenous corticosteroids in pregnant or postpartum patients with septic shock who continue to require vasopressor therapy (GRADE 2B); (16) because of an increased risk of venous thromboembolism in sepsis and septic shock, we recommend the use of pharmacologic venous thromboembolism prophylaxis in pregnant and postpartum patients in septic shock (GRADE 1B); (17) we suggest initiating insulin therapy at a glucose level >180 mg/dL in critically ill pregnant patients with sepsis (GRADE 2C); (18) if a uterine source for sepsis is suspected or confirmed, we recommend prompt delivery or evacuation of uterine contents to achieve source control, regardless of gestational age (GRADE 1C); and (19) because of an increased risk of physical, cognitive, and emotional problems in survivors of sepsis and septic shock, we recommend ongoing comprehensive support for pregnant and postpartum sepsis survivors and their families (Best Practice).

SMFM Consult Series #47: Sepsis during pregnancy and the puerperium.

Maternal sepsis is a significant cause of maternal morbidity and mortality and is a preventable cause of maternal death. The purpose of this guideline is to summarize what is known about sepsis and to provide guidance for the management of sepsis in pregnancy and the postpartum period. The following are SMFM recommendations: (1) we recommend that sepsis and septic shock be considered medical emergencies and that treatment and resuscitation begin immediately (GRADE 1B); (2) we recommend that providers consider the diagnosis of sepsis in pregnant patients with otherwise unexplained end-organ damage in the presence of an infectious process, regardless of the presence of fever (GRADE 1B); (3) we recommend that empiric broad-spectrum antibiotics be administered as soon as possible, ideally within 1 hour, in any pregnant woman in whom sepsis is suspected (GRADE 1B); (4) we recommend obtaining cultures (blood, urine, respiratory, and others as indicated) and serum lactate levels in pregnant or postpartum women in whom sepsis is suspected or identified, and early source control should be completed as soon as possible (GRADE 1C); (5) we recommend early administration of 1-2 L of crystalloid solutions in sepsis complicated by hypotension or suspected organ hypoperfusion (GRADE 1C); (6) we recommend the use of norepinephrine as the first-line vasopressor during pregnancy and the postpartum period in sepsis with persistent hypotension and/or hypoperfusion despite fluid resuscitation (GRADE 1C); (7) we recommend against immediate delivery for the sole indication of sepsis and that delivery should be dictated by obstetric indications (GRADE 1B).

Term cesarean delivery in the first pregnancy is not associated with an increased risk for preterm delivery in the subsequent pregnancy.

BACKGROUND: Prior studies have reported an increased risk for preterm delivery following a term cesarean delivery. However, these studies did not adjust for high-risk conditions related to the first cesarean delivery and are known to recur. OBJECTIVE: The objective of the study was to determine whether there is an association between term cesarean delivery in the first pregnancy and subsequent spontaneous or indicated preterm delivery. STUDY DESIGN: This was a retrospective cohort study of women with the first 2 consecutive singleton deliveries (2007-2014) identified through a linked pregnancy database at a single institution. Women with a first pregnancy that resulted in cesarean delivery at term were compared with women whose first pregnancy resulted in a vaginal delivery at term. Exclusion criteria were known to recur medical or obstetrical complications during the first pregnancy. A propensity score analysis was performed by matching women who underwent a cesarean delivery with those who underwent a vaginal delivery in the first pregnancy. The association between cesarean delivery in the first pregnancy and preterm delivery in the second pregnancy in this matched set was examined using conditional logistic regression. The primary outcome was overall preterm delivery <37 weeks in the second pregnancy. Secondary outcomes included type of preterm delivery (spontaneous vs indicated), late preterm delivery (34-36 6/7 weeks), early preterm delivery (<34 weeks), and small-for-gestational-age birth. RESULTS: Of a total of 6456 linked pregnancies, 2284 deliveries were matched; 1142 were preceded by cesarean delivery and 1142 were preceded by vaginal delivery. The main indications for cesarean delivery in the first pregnancy were dystocia in 703 (61.5%), nonreassuring fetal status in 222 (19.4%), breech presentation in 100 (8.8%), and other in 84 (7.4%). The mean (SD) gestational ages at delivery for the second pregnancy was 38.8 (1.8) and 38.9 (1.7) weeks, respectively, for prior cesarean delivery and vaginal delivery. The risks of preterm delivery in the second pregnancy among women with a previous cesarean and vaginal delivery were 6.0% and 5.2%, respectively (adjusted odds ratio, 1.46, 95% confidence interval, [CI] 0.77-2.76). In an analysis stratified by the type of preterm delivery in the second pregnancy, no associations were seen between cesarean delivery in the first pregnancy and spontaneous preterm delivery (4.6% vs 3.9%; adjusted odds ratio, 1.40, 95% confidence interval, 0.59-3.32) or indicated preterm delivery (1.6% vs 1.4%; adjusted odds ratio, 1.21, 95% confidence interval, 0.60-2.46). Similarly, no significant differences were found in late preterm delivery (4.6% vs 4.1%; adjusted odds ratio, 1.13, 95% confidence interval, 0.55-2.29), early preterm delivery (1.6% vs 1.2%; adjusted odds ratio, 1.25, 95% confidence interval, 0.59-2.67), or neonates with birthweight less than the fifth percentile for gestational age (3.6% vs 2.2%; adjusted odds ratio, 1.26, 95% confidence interval, 0.52-3.06). CONCLUSION: After robust adjustment for confounders through a propensity score analysis related to the indication for the first cesarean delivery at term, cesarean delivery is not associated with an increase in preterm delivery, spontaneous or indicated, in the subsequent pregnancy.

Obesity and the risk of stillbirth: a population-based cohort study.

OBJECTIVE: Obesity is a known risk factor for stillbirth. However, this relationship has not been characterized fully. We attempted to further examine this relationship with a focus on delivery near and at term. STUDY DESIGN: We designed a retrospective cohort study of singleton nonanomalous live births and stillbirths in the states of Washington and Texas to examine the associations of maternal prepregnancy body mass index (BMI) and risk of stillbirth. Confounder-adjusted hazard ratio of stillbirth in relation to BMI was estimated through Cox proportional hazards regression model. The hazard ratio was used to estimate the population-attributable risk. We also estimated the fetuses who were at risk for stillbirth based on gestational age. RESULTS: Among 2,868,482 singleton births, the overall stillbirth risk was 3.1 per 1000 births (n = 9030). Compared with normal-weight women, the hazard ratio for stillbirth was 1.36 for overweight women, 1.71 for class I obese women, 2.00 for class II obese women, 2.48 for class III obese women, and 3.16 for women with a BMI of ≥50 kg/m(2). The fetuses who are at risk for stillbirth increased after 39 weeks' gestation for each obesity class; however, the risk increased more rapidly with increasing BMI. Women with a BMI of ≥50 kg/m(2) were at 5.7 times greater risk than normal weight women at 39 weeks' gestation and 13.6 times greater at 41 weeks' gestation. Obesity was associated with nearly 25% of stillbirth that occurred between 37 and 42 weeks' gestation. CONCLUSION: There is a pronounced increase in the risk of stillbirth with increasing BMI; the association is strongest at early- and late-term gestation periods. Extreme maternal obesity is a significant risk factor for stillbirth.

Vaginorectal Streptococcus porcinus in pregnancy: an emerging pathogen?

OBJECTIVE: Streptococcus porcinus has previously been isolated from the genitourinary tract of reproductive-aged women. However, very little is known about the pathogenicity of this microorganism in pregnancy. The study aimed to report pregnancies complicated by vaginorectal S. porcinus and associated adverse outcomes. MATERIALS AND METHODS: We present 2 patients with 3 pregnancies complicated by vaginorectal S. porcinus and preterm cervical change. RESULTS: The first patient lost a twin pregnancy to previable preterm rupture of membranes. During her subsequent pregnancy, again positive for S. porcinus, cervical shortening prompted antibiotic treatment and cerclage. The second patient delivered preterm despite cerclage placed for sonographic indications. CONCLUSIONS: Our cases suggest that S. porcinus may contribute to the pathogenesis of preterm rupture of membranes and cervical insufficiency.

Improving Asthma Symptoms Among Inner-City Women During Pregnancy: A Prospective Cohort Intervention.

BACKGROUND: It is unknown how active asthma management influences symptom control among inner-city pregnant women who have unique exposures and socioeconomic limitations affecting their care. OBJECTIVE: To assess the impact of an integrated subspecialty intervention composed of education and monitoring on asthma control among underserved women in an antenatal clinic setting. METHODS: We conducted a prospective cohort study of pregnant asthmatic patients participating in a subspecialty clinic integrated into routine prenatal care. We compared baseline characteristics and objective measurements of asthma control between women at an initial visit and those who were evaluated in at least one follow-up. For follow-up, we measured symptom control at successive visits and the incidence of asthma-related complications. RESULTS: Among 85 women enrolled, 53 (62.4%) returned for at least one follow-up visit. Mean baseline Asthma Control Test scores were similarly low (≤19) between groups (one or more follow-up and no follow-up), as were self-administered Asthma Quality of Life Questionnaire scores (<4.7). A total of 72 women had inadequate asthma control resulting in step-up therapy after the initial visit (84.7%). There was a significant increase in ACT scores between the initial and first follow-up visits. For those with an intervening self-administered Asthma Quality of Life Questionnaire, there was also a significant increase by 1.39 ± 0.67 (P = .0003). CONCLUSIONS: We found that uncontrolled asthma is common among urban women seeking routine obstetric care. Our results suggest that even one interventional visit can result in significant improvement in asthma control. Further investigation into mechanisms for optimizing treatment strategies may improve the quality of asthma care during pregnancy in this underserved population.

Airway pressure-release ventilation in pregnant patients with acute respiratory distress syndrome: a novel strategy.

BACKGROUND: Airway pressure-release ventilation (APRV) is a novel mode of positive-pressure ventilation that has several advantages over low-tidal-volume, assist-control ventilation in patients with acute respiratory distress syndrome, specifically, lower airway pressures, lower minute ventilation, minimal effects on cardio-circulatory function, ability to spontaneously breathe throughout the entire ventilatory cycle, and decreased sedation requirements. APRV is consistent with lung-protective strategies that aim to limit lung injury associated with mechanical ventilation. APRV utilization in obstetrical patients has not previously been reported. CASES: We present 2 cases of pregnant women with severe life-threatening ARDS who were successfully managed with APRV. CONCLUSIONS: APRV may have particular utility in pregnant patients with ARDS. We believe APRV was life-saving in our cases. APRV ventilation should be considered in pregnant patients with ARDS.

Patient-choice vaginal delivery?

Patient-choice cesarean delivery is increasing in the United States. The American College of Obstetricians and Gynecologists supports this option, citing ethical premises of autonomy and informed consent, despite a lack of evidence for its safety. This increase in patient-choice cesarean delivery occurs during a time when women with a breech-presenting fetus or a previous cesarean section have fewer choices as to vaginal birth. Patient-choice cesarean delivery may become widely disseminated before the potential risks to women and their children have been well analyzed. The growing pressure for cesarean delivery in the absence of a medical indication may ultimately result in a decrease of women's childbirth options. Advocacy of patient-choice requires preserving vaginal birth options as well as cesarean delivery.

Public health implications of cesarean on demand.

Cesarean rates have been rising in the United States. Recently, there has been an upsurge of interest in "cesarean on maternal request" in the absence of any medical indication, a phenomenon that will further increase the cesarean rate. This trend may not be benign on a population basis, and reliable data are lacking. This article reviews reasons for the increasing cesarean rate, describes maternal and neonatal consequences likely to accrue with a policy of cesarean on demand, and explores larger implications for public health.

Management of Sepsis and Septic Shock for the Obstetrician-Gynecologist.

The incidence of sepsis is increasing in the United States, both in the general adult population and among pregnant and postpartum women. Neither infection nor bacteremia are synonymous with sepsis: it is a dysregulated host response to a pathogen in which organ dysfunction is key. New clinical criteria have been released. Cornerstones of management are early suspicion and recognition, effective fluid resuscitation, and appropriate antimicrobial therapy.

RGS2 squelches vascular Gi/o and Gq signaling to modulate myogenic tone and promote uterine blood flow.

Uterine artery blood flow (UABF) is critical to maintaining uterine perfusion in nonpregnant states and for uteroplacental delivery of nutrients and oxygen to the fetus during pregnancy. Impaired UABF is implicated in infertility and several pregnancy complications including fetal growth restriction, small for gestational age, and preeclampsia. The etiology of abnormal UABF is not known. Here, we determined whether deficiency or loss of RGS2, a GTPase-activating protein for Gq/11 and Gi/o class G proteins, affects UABF in nonpregnant mice. We used Doppler ultrasonography to assess UABF in wild type (WT), Rgs2 heterozygous (Rgs2+/-), and homozygous knockout (Rgs2-/-) mice. Video microscopy was used for ex vivo examination of uterine artery myogenic tone and fura-2 imaging for in vitro assessment of internal stores Ca(2+) release. We found that baseline UABF velocity was markedly decreased while impedance measured as resistive index (WT = 0.58 ± 0.04 vs. Rgs2-/- = 0.71 ± 0.03, P < 0.01) and pulsatile index (WT = 0.90 ± 0.06 vs. Rgs2-/- = 1.25 ± 0.11, P < 0.01) was increased in Rgs2-/- mice. Uterine artery tone was augmented in Rgs2+/- and Rgs2-/- mice, which was normalized to WT levels following Gi/o and Gq inactivation. Conversely, blockade of ryanodine receptors increased WT myogenic tone to RGS2 mutant levels. The data together indicate that RGS2 deficiency decreases UABF by increasing myogenic tone at least partly through prolonged G protein activation. Mutations that decrease vascular RGS2 expression may be a predisposition to decreased uterine blood flow. Targeting G protein signaling therefore might improve uterine and uteroplacental underperfusion disorders.

Circulating Cell-Free DNA to Determine the Fetal RHD Status in All Three Trimesters of Pregnancy.

OBJECTIVE: To estimate the accuracy of a new assay to determine the fetal RHD status using circulating cell-free DNA. METHODS: This was a prospective, observational study. Maternal blood samples were collected in each trimester of pregnancy in 520 nonalloimmunized RhD-negative patients. Plasma samples were analyzed for circulating cell-free DNA using the SensiGENE RHD test, which used primers for exons 4 and 7 as previously described and incorporated a new primer design for exon 5 of the RHD gene. Neonatal serology for RhD typing using cord blood at birth was undertaken and results were stored in a separate clinical database. After unblinding the data, results of the DNA analysis were compared with the neonatal serology. RESULTS: Inconclusive results secondary to the presence of the RHD pseudogene or an RHD variant were noted in 5.6%, 5.7%, and 6.1% of the first-, second-, and third-trimester samples, respectively. The incidence of false-positive rates for RhD (an RhD-negative fetus with an RHD-positive result) was 1.54% (95% confidence interval [CI] 0.42-5.44%), 1.53% (CI 0.42-5.40%), and 0.82% (CI 0.04-4.50%), respectively. There was only one false-negative diagnosis (an RhD-positive fetus with an RHD-negative result), which occurred in the first trimester (0.32%; 95% CI 0.08-1.78%). Genotyping for mismatches across repeated samples revealed that this error was related to mislabeling of samples from two patients collected on the same day at one of the collection sites. Overall test results were in agreement across all three trimesters (P>.99). CONCLUSION: Circulating cell-free DNA can accurately predict the fetal RhD status in all three trimesters of pregnancy.

Cystic fibrosis and hemolytic uremic syndrome coexisting during pregnancy.

BACKGROUND: As more women with cystic fibrosis are living into their reproductive years, this disease can complicate pregnancy and coexist with other entities. We report a case of cystic fibrosis with hemolytic uremic syndrome. CASE: An 18-year-old primigravida with cystic fibrosis was admitted at term with pulmonary symptoms, hypertension, and thrombocytopenia. She was delivered with the admitting diagnosis of severe preeclampsia. Postpartum, thrombocytopenia, and microangiopathic hemolytic anemia worsened. She developed renal failure and acute respiratory distress syndrome, requiring plasmapheresis, mechanical ventilation, and hemodialysis. Renal biopsy was consistent with the diagnosis of hemolytic uremic syndrome. CONCLUSION: Cystic fibrosis, a disease once managed predominantly by pediatric subspecialists, will be seen increasingly by physicians caring for adults, including obstetrician-gynecologists. We may also expect to see it coexisting with other disorders. The management of such patients may prove challenging.

Misoprostol vaginal insert and time to vaginal delivery: a randomized controlled trial.

OBJECTIVE: To compare the efficacy and safety of a 200-microgram misoprostol vaginal insert with a 10-mg dinoprostone vaginal insert for reducing the time to vaginal delivery. METHODS: In a phase III, double-blind, multicenter study, women being induced with a modified Bishop score of 4 or less were randomly assigned to receive either a 200-microgram misoprostol vaginal insert or a 10-mg dinoprostone vaginal insert. Coprimary end points were time to vaginal delivery and rate of cesarean delivery. Secondary end points included time to any delivery mode, time to onset of active labor, and oxytocin use. RESULTS: A total of 1,358 women were randomized to receive the 200-microgram misoprostol vaginal insert (n=678) or dinoprostone vaginal insert (n=680). Women receiving the misoprostol vaginal insert had a significantly shorter median time to vaginal delivery compared with patients receiving the dinoprostone vaginal insert (21.5 hours compared with 32.8 hours, P<.001). Cesarean delivery occurred in 26.0% and 27.1% of women receiving the misoprostol vaginal insert and dinoprostone vaginal insert, respectively. A significant reduction in time to any delivery (18.3 hours compared with 27.3 hours), time to onset of active labor (12.1 hours compared with 18.6 hours), and proportion of women requiring predelivery oxytocin (48.1% compared with 74.1%) was observed with the misoprostol vaginal insert compared with dinoprostone vaginal insert (P<.001 for each). Uterine tachysystole requiring intervention occurred in 13.3% and 4.0% of participants receiving the misoprostol vaginal insert and dinoprostone vaginal insert, respectively (P<.001). CONCLUSION: Use of a 200-microgram misoprostol vaginal inset significantly reduced times to vaginal delivery and active labor with reduced need for oxytocin compared with the dinoprostone vaginal insert. Cesarean delivery rates were similar with both treatments. Tachysystole was more common in women receiving the 200-microgram misoprostol vaginal insert. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01127581. LEVEL OF EVIDENCE: I.