Sarah Rae Easter

Urinary tract infection during pregnancy, angiogenic factor profiles, and risk of preeclampsia

BACKGROUND Despite decades of research, and much progress in discernment of biomarkers in the maternal circulation, the pathogenesis of preeclampsia (PE) remains elusive. The pathophysiology of PE is believed to involve aberrant placentation and an associated increase in systemic inflammation. In this conceptualization, PE becomes more likely when the level of systemic inflammatory burden inherent in pregnancy itself exceeds the maternal capacity to compensate for this additional stress. If this is the case, then it is possible to hypothesize that conditions, such as infectious disease, that increase systemic inflammatory burden should also increase the risk of PE. As urinary tract infection (UTI) represents a common source of inflammation during pregnancy, we tested whether presence of UTI during pregnancy increased the odds of developing PE. Prior work has documented this association. However many of these studies were limited by small cohort sizes and insufficient control for covariates. OBJECTIVE The present study is a secondary analysis of a robust contemporary obstetrical cohort recruited to examine the ability of longitudinally sampled maternal angiogenic concentrations to predict PE. We hypothesize that the occurrence of UTI during a pregnancy is associated with the later occurrence of PE in that pregnancy. As PE is believed to be associated with aberrations in systemic angiogenic levels (placental growth factor and soluble isoform of VEGF receptor), we further hypothesize that there will be significant interactions between maternal angiogenic protein levels and the occurrence of UTI. STUDY DESIGN Women aged ≥18 years (n = 2607) were recruited and followed up prospectively from the initiation of prenatal care through delivery at 3 regional academic centers. PE was defined by American Congress of Obstetricians and Gynecologists criteria and was independently validated by a panel of physicians. UTI was defined by the presence of clinical symptoms necessitating treatment in addition to supportive laboratory evidence. Multivariate logistic regression models were used and controlled for maternal age, race, parity, body mass index, hypertension, diabetes, in vitro fertilization, and smoking status. RESULTS There were 129 women with diagnosed UTIs and 235 with PE. Patients with UTI in pregnancy had higher rates of PE (31.1% vs 7.8%, P < .001) compared to those without reported UTI. The mean gestational age (SD) for UTI diagnosis in PE cases and controls was 25.6 (10.4) and 21.9 (10.9) weeks, respectively (P = .08). The unadjusted odds ratio for PE in the setting of UTI was 5.29 (95% confidence interval, 3.54-7.89). After controlling for confounders, UTI was associated with an odds ratio for PE of 3.2 (95% confidence interval, 2.0-5.1). CONCLUSION Presence of UTI in pregnancy, particularly in the third trimester, is strongly associated with PE. This association supports the hypothesis that the risk of PE is enhanced by an increased maternal inflammatory burden. Prophylaxis against UTI represents a potentially low-cost global intervention to slow or halt the development of PE.

Complement Activation and Kidney Injury Molecule-1–Associated Proximal Tubule Injury in Severe Preeclampsia

Kidney injury with proteinuria is a characteristic feature of preeclampsia, yet the nature of injury in specific regions of the nephron is incompletely understood. Our study aimed to use existing urinary biomarkers to describe the pattern of kidney injury and proteinuria in pregnancies affected by severe preeclampsia. We performed a case–control study of pregnant women from Brigham and Women’s Hospital from 2012 to 2013. We matched cases of severe preeclampsia (n=25) 1:1 by parity and gestational age to 2 control groups with and without chronic hypertension. Urinary levels of kidney injury molecule-1 and complement components (C3a, C5a, and C5b-9) were measured by enzyme-linked immunosorbent assay, and other markers (albumin, &bgr;2 microglobulin, cystatin C, epithelial growth factor, neutrophil gelatinase–associated lipocalin, osteopontin, and uromodulin) were measured simultaneously with a multiplex electrochemiluminescence assay. Median values between groups were compared with the Wilcoxon signed-rank test and correlations with Spearman correlation coefficient. Analysis of urinary markers revealed higher excretion of albumin and kidney injury molecule-1 and lower excretion of neutrophil gelatinase–associated lipocalin and epithelial growth factor in severe preeclampsia compared with chronic hypertension and healthy controls. Among subjects with severe preeclampsia, urinary excretion of complement activation products correlated most closely with kidney injury molecule-1, a specific marker of proximal tubule injury (C5a: r=0.60; P=0.001; and C5b-9: r=0.75; P<0.0001). Taken together, we describe a pattern of kidney injury in severe preeclampsia that is characterized by glomerular impairment and complement-mediated inflammation and injury, possibly localized to the proximal tubule in association with kidney injury molecule-1.

Twin vaginal delivery: innovate or abdicate

Neonatal safety data along with national guidelines have prompted renewed interest in vaginal delivery of twins, particularly in the case of the noncephalic second twin. Yet, the rising rate of twin cesarean deliveries, coupled with the national decline in operative obstetrics, raises concerns about the availability of providers who are skilled in twin vaginal birth. Providers are key stakeholders for increasing rates of twin vaginal delivery. We surveyed a group of practicing obstetricians to explore potential barriers to the vaginal birth of twins with a focus on delivery of the noncephalic second twin. Among 107 responding providers, only 57% would deliver a noncephalic second twin by breech extraction. Providers who preferred breech extraction had a higher rate of maternal-fetal medicine subspecialty training (26.2% vs 4.3%; P<.01) and were more likely to be in an academic practice environment (36.1% vs 10.9%; P<.01) and to practice in high-volume centers that deliver >30 sets of twins annually (57.4% vs 34.8%; P=.02). Most providers (54.2%) were familiar with the findings from the recent randomized trial that demonstrated the safety of twin vaginal birth. However, knowledge of the trial was not associated statistically with a preference for breech extraction (62.3% vs 43.5%; P=.05). Providers who preferred breech extraction were more likely to agree with recent society guidelines that encourage the vaginal birth of twins (86.9% vs 63.0%; P<.01). In an adjusted analysis, the 46% of providers with a perceived need for more training were far less likely to prefer breech extraction for delivery of a noncephalic second twin (adjusted odds ratio, 0.38; 95% confidence interval, 0.16-0.95). Furthermore, 57% of providers who would not offer their patient breech extraction would be willing to consult a colleague for support with a noncephalic twin delivery. These results suggest that scientific evidence and society opinion are likely insufficient to reverse the national trends that favor cesarean delivery for twins. Instead, implementation of provider training and support programs is critical for increasing the rates of twin vaginal birth. Changing our national landscape of vaginal twin delivery may require innovation. Without novel provider-focused strategies, we may relinquish passively the requisite skills for not only our patients but also for future generations of obstetricians.

Simulation to Improve Trainee Knowledge and Comfort About Twin Vaginal Birth

OBJECTIVE: To describe a simulation-based curriculum on twin vaginal delivery and evaluate its effects on trainee knowledge and comfort about twin vaginal birth. METHODS: Trainees participated in a three-part simulation consisting of a patient counseling session, a twin delivery scenario, and a breech extraction skills station. Consenting trainees completed a 21-item presimulation survey and a 22-item postsimulation survey assessing knowledge, experience, attitudes, and comfort surrounding twin vaginal birth. Presimulation and postsimulation results were compared using univariate analysis. Our primary outcomes were change in knowledge and comfort before and after the simulation. RESULTS: Twenty-four obstetrics and gynecology residents consented to participation with 18 postsimulation surveys available for comparison (75%). Trainees estimated their participation in 445 twin deliveries (median 19, range 0–52) with only 20.4% of these as vaginal births. Participants reported a need for more didactic or simulated training on this topic (64% and 88%, respectively). Knowledge about twin delivery improved after the simulation (33.3% compared with 58.3% questions correct, P<.01). Before training, 33.3% of participants reported they would strongly counsel a patient to attempt vaginal birth instead of elective cesarean delivery for twins compared with 50% after training (P=.52). Personal comfort with performing a breech extraction of a nonvertex second twin improved from 5.5% to 66.7% after the simulation (P<.01). CONCLUSION: Resident exposure to twin vaginal birth is infrequent and variable with a demonstrable need for more training. Our contemporary obstetric climate is prioritizing vaginal birth despite less frequent operative obstetric interventions. We describe a reproducible twin delivery simulation associated with a favorable effect on resident knowledge and comfort levels.

Association of Intended Route of Delivery and Maternal Morbidity in Twin Pregnancy.

OBJECTIVE To evaluate maternal morbidity in twin pregnancies according to intended mode of delivery. METHODS We assembled a 7-year retrospective cohort (2007-2014) of women delivering viable, vertex-presenting twins at or beyond 32 weeks of gestation without contraindication to labor or uterine scar. We classified women as undergoing a trial of labor to attempt vaginal birth or choosing an elective cesarean delivery. Our primary outcome was a measure of composite maternal morbidity including death, postpartum hemorrhage, infection, major procedure, readmission for infection or reoperation, need for dilation and evacuation for hemorrhage or infection, venous thromboembolism, small bowel obstruction or ileus, or intensive care unit admission. Postpartum hemorrhage was defined as estimated blood loss greater than or equal to 1,500 mL or need for transfusion. The rate of lacerations in each group was also determined. Using logistic regression to control for confounders, we examined the odds of maternal morbidity according to intended mode of delivery. RESULTS Of 2,272 twin pregnancies at or beyond 32 weeks of gestation, 1,140 (50%) met inclusion criteria with 571 (50%) electing cesarean delivery and 569 (50%) undergoing a trial of labor to attempt vaginal birth. Vaginal delivery of both twins was achieved in 74% (n=418) of women choosing a trial of labor. The rate of maternal morbidity was 12.3% in the trial of labor group compared with 9.1% in the elective cesarean delivery group (P=.08, adjusted odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.4). Postpartum hemorrhage was more common among women who attempted vaginal delivery (n=52) compared with those electing cesarean delivery (n=28) with rates of 9.1% compared with 4.9%, respectively (P<.01, adjusted OR 2.2, 95% CI 1.4-3.6) and was responsible for the difference in the composite morbidity rate between groups. CONCLUSION When adjustment is made for potential confounders, women undergoing a trial of labor with twins experience a higher odds of maternal morbidity than those electing cesarean delivery, primarily as a result of hemorrhage. In pragmatic terms, the tradeoff for a 74% chance of vaginal delivery is a 4% absolute increase in the rate of serious postpartum hemorrhage.

Defining Physiological Predictors of Peripartum Maternal Bacteremia.

OBJECTIVE This study aims to examine physiological and laboratory parameters associated with peripartum maternal bacteremia. STUDY DESIGN This case-control study matched 115 cases (women with fever and bacteremia during the peripartum period) to 285 controls (defined as the next two febrile women with negative blood cultures at the same institution) from two academic medical centers from 2009 to 2013. Conditional logistic regression models were used to evaluate the association of physiological and laboratory parameters with maternal bacteremia at the time of initial and maximum fever. RESULTS At the time of initial fever, temperature > 103°F (adjusted odds ratio [aOR]: 5.58, 95% confidence interval [CI]: 2.05-15.19) and respiratory rate (RR) > 20 respirations per minute (aOR: 5.27, 95% CI: 2.32-11.96) were associated with bacteremia. At the time of maximum fever, temperature (> 102°F, aOR: 3.37, 95% CI: 1.61-7.06; > 103°F, aOR: 7.96, 95% CI: 3.56-17.82), heart rate > 110 beats per minute (aOR: 2.20, 95% CI: 1.21-3.99), and RR > 20 (aOR: 3.65, 95% CI: 1.65-8.08) were associated with bacteremia. Bandemia > 10% (aOR: 2.44, 95% CI: 1.07-5.54) was associated with bacteremia. CONCLUSION Physiological and laboratory parameters associated with maternal bacteremia differed from those reported with sepsis in the adult critical care population. Further studies of objective markers are needed to improve detection and treatment of peripartum bacteremia.

Perspectives on global health amongst obstetrician gynecologists: A national survey

Objective To characterize contemporary attitudes toward global health amongst board-certified obstetricians-gynecologists (Ob-Gyns) in the US. Methods A questionnaire was mailed to members of the American College of Obstetricians and Gynecologists. Respondents were stratified by interest and experience in global health and group differences were reported. Results A total of 202 of 400 (50.5%) surveys were completed; and 67.3% (n = 136) of respondents expressed an interest in global health while 25.2% (n = 51) had experience providing healthcare abroad. Personal safety was the primary concern of respondents (88 of 185, 47.6%), with 44.5% (57 of 128) identifying 2 weeks as an optimal period of time to spend abroad. The majority (113 of 186, 60.8%) cited hosting of local physicians in the US as the most valuable service to developing a nation’s healthcare provision. Conclusion Despite high interest in global health, willingness to spend significant time abroad was limited. Concerns surrounding personal safety dovetailed with the belief that training local physicians in the US provides the most valuable service to international efforts. These attitudes and concerns suggest novel solutions will be required to increase involvement of Ob-Gyns in global women’s health.

The impact of health insurance status on the stage of cervical cancer diagnosis at a tertiary care center in Massachusetts

OBJECTIVE To evaluate the impact of insurance status on the stage of cervical cancer diagnosed and treated at a tertiary care center in Massachusetts and review the preceding screening history. METHODS An IRB approved retrospective cohort study was conducted of patients with a diagnosis of cervical cancer treated at Brigham and Womens Hospital (BWH) between January 2011 and June 2016. Clinical and demographic data was extracted from the longitudinal medical record. Statistical analysis was performed using SAS. RESULTS 117 cases of cervical cancer met the inclusion criteria during the study period. Most patients (76%) were diagnosed with stage I disease. On univariate analysis, compared to patients with private insurance, patients with public insurance or no documented insurance presented at older ages, were more likely to be non-white races, and present with advanced stage disease. In an adjusted model, the risk of being diagnosed with advanced stage disease persisted among women with public or no documented insurance, adjusted odds ratio (aOR) 4.13 (1.37-12.45). There was no difference in screening history among women with private vs. public insurance, p = 0.30. CONCLUSIONS Despite access to insurance, patients with public issued insurance had an increased risk of presenting with advanced stage cervical cancer in this cohort. These data suggest that additional barriers to screening and prevention may exist and are important for future investigation.

Obstetric History and Likelihood of Preterm Birth of Twins

Objective The objective of this study was to investigate the relationship between preterm birth in a prior pregnancy and preterm birth in a twin pregnancy. Study Design We performed a secondary analysis of a randomized controlled trial evaluating 17‐&agr;‐hydroxyprogesterone caproate in twins. Women were classified as nulliparous, multiparous with a prior term birth, or multiparous with a prior preterm birth. We used logistic regression to examine the odds of spontaneous preterm birth of twins before 35 weeks according to past obstetric history. Results Of the 653 women analyzed, 294 were nulliparas, 310 had a prior term birth, and 49 had a prior preterm birth. Prior preterm birth increased the likelihood of spontaneous delivery before 35 weeks (adjusted odds ratio [aOR]: 2.44, 95% confidence interval [CI]: 1.28‐4.66), whereas prior term delivery decreased these odds (aOR: 0.55, 95% CI: 0.38‐0.78) in the current twin pregnancy compared with the nulliparous reference group. This translated into a lower odds of composite neonatal morbidity (aOR: 0.38, 95% CI: 0.27‐0.53) for women with a prior term delivery. Conclusion For women carrying twins, a history of preterm birth increases the odds of spontaneous preterm birth, whereas a prior term birth decreases odds of spontaneous preterm birth and neonatal morbidity for the current twin pregnancy. These results offer risk stratification and reassurance for clinicians.

Fetal growth restriction: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data

http://dx.doi.org/10.1016/j.vaccine.2017.01.042 0264-410X/ 2017 Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). ⇑ Corresponding author. E-mail address: contact@brightoncollaboration.org (T. McElrath). 1 Brighton Collaboration homepage: http://www.brightoncollaboration.org. 2 Present address: University of Washington, Seattle USA. Sarah Rae Easter , Linda O. Eckert , Nansi Boghossian , Rebecca Spencer , Eugene Oteng-Ntim , Christos Ioannou , Manasi Patwardhan , Margo S. Harrison , Asma Khalil , Michael Gravett , Robert Goldenberg , Alastair McKelvey , Manish Gupta , Vitali Pool , Stephen C. Robson, Jyoti Joshi , Sonali Kochhar , Tom McElrath a,⇑, The Brighton Collaboration Fetal Growth Restriction Working Group 1