Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

OBJECTIVE: To evaluate the association between maternal blood pressure (BP) below 130/80 mm Hg compared with 130-139/80-89 mm Hg and pregnancy outcomes. METHODS: We conducted a planned secondary analysis of CHAP (Chronic Hypertension and Pregnancy), an open label, multicenter, randomized controlled trial. Participants with mean BP below 140/90 mm Hg were grouped as below 130/80 mm Hg compared with 130-139/80-89 mm Hg by averaging postrandomization clinic BP throughout pregnancy. The primary composite outcome was preeclampsia with severe features, indicated preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The secondary outcome was small for gestational age (SGA). RESULTS: Of 2,408 patients in CHAP, 2,096 met study criteria; 1,328 had mean BP 130-139/80-89 mm Hg and 768 had mean BP below 130/80 mm Hg. Participants with mean BP below 130/80 mm Hg were more likely to be older, on antihypertensive medication, in the active treatment arm, and to have lower BP at enrollment. Mean clinic BP below 130/80 mm Hg was associated with lower frequency of the primary outcome (16.0% vs 35.8%, adjusted relative risk 0.45; 95% CI 0.38-0.54) as well as lower risk of severe preeclampsia and indicated birth before 35 weeks of gestation. There was no association with SGA. CONCLUSION: In pregnant patients with mild chronic hypertension, mean BP below 130/80 mm Hg was associated with improved pregnancy outcomes without increased risk of SGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Breastfeeding initiation and duration among people with mild chronic hypertension: a secondary analysis of the Chronic Hypertension and Pregnancy trial.

BACKGROUND: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown. OBJECTIVE: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg). STUDY DESIGN: We performed a secondary analysis of the Chronic Hypertension and Pregnancy trial. This was an open-label, multicenter, randomized trial where pregnant participants with mild chronic hypertension were randomized to receive antihypertensive medications with goal blood pressure <140/90 mm Hg (active treatment) or deferred treatment until blood pressure ≥160/105 mm Hg (control). The primary outcome was initiation and duration of breastfeeding, assessed at the postpartum clinic visit. We performed bivariate analyses and log-binomial and cumulative logit regression models, adjusting models for variables that were unbalanced in bivariate analyses. We performed additional analyses to explore the relationship between breastfeeding duration and blood pressure measurements at the postpartum visit. RESULTS: Of the 2408 participants from the Chronic Hypertension and Pregnancy trial, 1444 (60%) attended the postpartum study visit and provided breastfeeding information. Participants in the active treatment group had different body mass index class distribution and earlier gestational age at enrollment, and (by design) were more often discharged on antihypertensives. Breastfeeding outcomes did not differ significantly by treatment group. In the active and control treatment groups, 563 (77.5%) and 561 (78.1%) initiated breastfeeding, and mean durations of breastfeeding were 6.5±2.3 and 6.3±2.1 weeks, respectively. The probability of ever breastfeeding (adjusted relative risk, 0.99; 95% confidence interval, 0.93-1.05), current breastfeeding at postpartum visit (adjusted relative risk, 1.01; 95% confidence interval, 0.94-1.10), and weeks of breastfeeding (adjusted odds ratio, 0.87; 95% confidence interval, 0.68-1.12) did not differ by treatment group. Increased duration (≥2 vs <2 weeks) of breastfeeding was associated with slightly lower blood pressure measurements at the postpartum visit, but these differences were not significant in adjusted models. CONCLUSION: In a secondary analysis of the cohort of Chronic Hypertension and Pregnancy trial participants who attended the postpartum study visit and provided breastfeeding information (60% of original trial participants), breastfeeding outcomes did not differ significantly by treatment group. This suggests that maintaining goal blood pressure <140/90 mm Hg throughout the perinatal period is associated with neither harm nor benefit for short-term breastfeeding goals. Further study is needed to understand long-term breastfeeding outcomes among individuals with chronic hypertension and how to support this population in achieving their breastfeeding goals.

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).

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

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.

The effect of breastfeeding on postpartum fructosamine and HbA1c values after normal pregnancy.

INTRODUCTION: Breastfeeding can lower postpartum oral glucose tolerance test results by 5%. Similar data do not exist regarding fructosamine and HbA1c. The primary outcome was to determine if breastfeeding would lower fructosamine values by 5%. METHODS: At the 4-8 week postpartum visit, women with uncomplicated pregnancies were given a questionnaire and had blood drawn for fructosamine and HbA1c. RESULTS: Breastfeeding (n = 22) and non-breastfeeding women (n = 28) were demographically similar, including postpartum weight loss. The respective values among breastfeeding and non-breastfeeding women were: fructosamine 2.20 versus 2.21 mmol/L; HbA1c 5.2% versus 5.2%. Only two of the seven women with an HbA1c of 5.7% or more had an abnormal fructosamine. CONCLUSION: After uncomplicated pregnancies, breastfeeding was not associated with lower levels of postpartum fructosamine or HbA1c. Future research to improve screening for persistent postpartum dysglycemia in high-risk populations can utilize these tests without concern that results will be confounded by breastfeeding.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancyassessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). We conducted a systematic review of evidence relating to contraception, ART, fertility preservation,HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process todetermine final recommendations and grade their strength (conditional or strong). Good practice statements wereagreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.. This American College of Rheumatology guideline provides 12 ungraded good practice statements and131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended toguide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSBantibodies. Recommendations and good practice statements support several guiding principles: use of safe andeffective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physicianpatient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to the recommendations within this guideline to be voluntary, with the ultimate determination regarding their application to be made by the clinician in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes, but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision, as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions. These recommendations cannot adequately convey all uncertainties and nuances of patient care. The American College of Rheumatology is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service. This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

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.

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).

Obstetric Disorders in the ICU.

Pregnant and postpartum patients represent a challenge to critical care physicians, as two patients in one have to be cared for and because specific obstetric disorders, not universally covered in formal critical care training, need to be managed. Pregnancy also alters physiologic norms, so that the critical care physician may either fail to recognize a value as abnormal in pregnancy or mistakenly identify as abnormal a value within the normal range for a pregnant woman. In this article, we will review the most frequent obstetric causes of admission of pregnant/postpartum patients to the intensive care unit (hypertensive disease of pregnancy, obstetric hemorrhage, and obstetric sepsis) along with their diagnostic criteria, clinical presentation, and recommended treatment. We will also cover some specific, although less frequent, obstetric disorders, such as acute fatty liver of pregnancy, peripartum cardiomyopathy, and amniotic fluid embolism. Our primary aim is to improve quality of care for these types of patients.

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.

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.

Antenatal testing in uncomplicated pregnancies: should testing be initiated after 40 or 41 weeks?

OBJECTIVE: This study aims to compare outcomes of antenatal testing in women who received testing between 40 weeks and 40+6 weeks versus those who received testing at ≥41 weeks. MATERIALS AND METHODS: This retrospective study included women without maternal comorbidities, who were referred for outpatient antenatal testing for gestational age ≥40 weeks. We compared women who received antenatal testing between 40 and 40+6 weeks (Group 1), to those who were only tested at ≥41 weeks (Group 2). RESULTS: A total of 827 Group 1 and 244 Group 2 pregnancies were evaluated. One-hundred and eighty-nine (18%) were sent to labor and delivery (L&D) for further evaluation. There were no significant differences between groups in terms of being sent or admitted to labor and delivery, the reason for which women were sent, induction of labor, mode of delivery, neonatal length of stay, or admission to intensive care. CONCLUSION: Pregnancies tested at 40 weeks were identified as abnormal and sent to L&D at the same rate as those tested at 41 weeks. Therefore, it may be reasonable to initiate fetal surveillance at the estimated date of delivery.

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.