Background: Women with gestational diabetes mellitus are rarely treated with a sulfonylurea drug, because of concern about teratogenicity and neonatal hypoglycemia. There is little information about the efficacy of these drugs in this group of women. Methods: We studied 404 women with singleton pregnancies and gestational diabetes that required treatment. The women were randomly assigned be- tween 11 and 33 weeks of gestation to receive gly- buride or insulin according to an intensified treatment protocol. The primary endpoint was achievement of the desired level of glycemic control. Secondary endpoints included maternal and neonatal complications. Results: The mean (±SD) pretreatment blood glucose concentration as measured at home for one week was 114±19 mg per deciliter (6.4±1.1 mmol per liter) in the glyburide group and 116±22 mg per deciliter (6.5±1.2 mmol per liter) in the insulin group (P=0.33). The mean concentrations during treatment were 105± 16 mg per deciliter (5.9±0.9 mmol per liter) in the glyburide group and 105±18 mg per deciliter (5.9±1.0 mmol per liter) in the insulin group (P=0.99). Eight women in the glyburide group (4 percent) required insulin therapy. There were no significant differences between the glyburide and insulin groups in the percentage of infants who were large for gestational age (12 percent and 13 percent, respectively); who had macrosomia, defined as a birth weight of 4000 g or more (7 percent and 4 percent); who had lung complications (8 percent and 6 percent); who had hypoglycemia (9 percent and 6 percent); who were admitted to a neonatal intensive care unit (6 percent and 7 percent); or who had fetal anomalies (2 percent and 2 percent). The cord-serum insulin concentrations were similar in the two groups, and glyburide was not detected in the cord serum of any infant in the glyburide group. Conclusion : In women with gestational diabetes, glyburide is a clinically effective alternative to insulin therapy

ISSUE:Medical educators share the belief that fostering the development of lifelong learning skills is a fundamental task for teachers and learners in all stages of a physician's education: undergraduate medical education, graduate medical education, and continuing medical education. A significant challenge to developing and implementing best practices in lifelong learning is the varied interpretation and application of its related terminology, such as 'self-directed learning' in this context.EVIDENCE:This paper discusses the scholarly origins of key terms in lifelong learning ('self-directed learning' and 'self-regulated learning') and explores their commonalities and their common conflation.IMPLICATION:The authors propose a renewed attention to precision in use of lifelong learning terminology in medical education across the spectrum as a way to best design and deploy impactful educational experiences for learners at all levels.

Objective Delta-like homolog 1 (DLK1) is a growth factor that is reduced in maternal sera in pregnancies with small for gestational age neonates. We sought to determine if DLK1 is associated with stillbirth (SB), with and without placental insufficiency. Study Design A nested case-control study was performed using maternal sera from a multicenter case-control study of SB and live birth (LB). SB and LB were stratified as placental insufficiency cases (small for gestational age <5% or circulatory lesions on placental histopathology) or normal placenta controls (appropriate for gestational age and no circulatory lesions). Enzyme-linked immunosorbent assay (ELISA) was used to measure DLK1. The mean difference in DLK1 was compared on the log scale in an adjusted linear regression model with pairwise differences, stratified by term/preterm deliveries among DLK1 results in the quantifiable range. In exploratory analysis, geometric means were compared among all data and the proportion of “low DLK1” (less than the median value for gestational age) was compared between groups and modeled using linear and logistic regression, respectively. Results Overall, 234 SB and 234 LB were analyzed; 246 DLK1 values were quantifiable within the standard curve. Pairwise comparisons of case and control DLK1 geometric means showed no significant differences between groups. In exploratory analysis of all data, adjusted analysis revealed a significant difference for the LB comparison only (SB: 71.9 vs. 99.1 pg/mL, p = 0.097; LB: 37.6 vs. 98.1 pg/mL, p = 0.005). In exploratory analysis of “low DLK1,” there was a significant difference between the odds ratio of having “low DLK1” between preterm cases and controls for both SB and LB. There were no significant differences in geometric means nor “low DLK1” between SB and LB. Conclusion In exploratory analysis, more placental insufficiency cases in preterm SB and LB had “low DLK1.” However, low DLK1 levels were not associated with SB. Key Points

OBJECTIVE:Umbilical cord abnormalities are commonly cited as a cause of stillbirth, but details regarding these stillbirths are rare. Our objective was to characterize stillbirths associated with umbilical cord abnormalities using rigorous criteria and to examine associated risk factors.METHODS:The Stillbirth Collaborative Research Network conducted a case-control study of stillbirth and live births from 2006 to 2008. We analyzed stillbirths that underwent complete fetal and placental evaluations and cause of death analysis using the INCODE (Initial Causes of Fetal Death) classification system. Umbilical cord abnormality was defined as cord entrapment (defined as nuchal, body, shoulder cord accompanied by evidence of cord occlusion on pathologic examination); knots, torsions, or strictures with thrombi, or other obstruction by pathologic examination; cord prolapse; vasa previa; and compromised fetal microcirculation, which is defined as a histopathologic finding that represents objective evidence of vascular obstruction and can be used to indirectly confirm umbilical cord abnormalities when suspected as a cause for stillbirth. We compared demographic and clinical factors between women with stillbirths associated with umbilical cord abnormalities and those associated with other causes, as well as with live births. Secondarily, we analyzed the subset of pregnancies with a low umbilical cord index.RESULTS:Of 496 stillbirths with complete cause of death analysis by INCODE, 94 (19%, 95% CI 16-23%) were associated with umbilical cord abnormality. Forty-five (48%) had compromised fetal microcirculation, 27 (29%) had cord entrapment, 26 (27%) knots, torsions, or stricture, and five (5%) had cord prolapse. No cases of vasa previa occurred. With few exceptions, maternal characteristics were similar between umbilical cord abnormality stillbirths and non-umbilical cord abnormality stillbirths and between umbilical cord abnormality stillbirths and live births, including among a subanalysis of those with hypo-coiled umbilical cords.CONCLUSION:Umbilical cord abnormalities are an important risk factor for stillbirth, accounting for 19% of cases, even when using rigorous criteria. Few specific maternal and clinical characteristics were associated with risk.

Medical Education Program Highlights The Long School of Medicine (Long SOM), a U.S. Department of Education Hispanic-Serving Institution, has a strong and supportive faculty and numerous opportunities for building clinical and research skills. Medical research institutes and nationally recognized cancer treatment programs combine education and research to provide some of the country’s most innovative care. The MD degree program offers several unique features: Degree distinction programs in research, medical education, and humanities Dual-degree program for MD–MPH, whereby a student can earn both degrees in 4 years Dual-degree program for MD–PhD, offered by an NIH-designated Medical Scientist Training Program The Center for Clinical Ultrasound Education, integrating bedside ultrasound curriculum throughout all 4 years of medical school Curriculum Curriculum description The medical education program is named the CIRCLE curriculum (Curricular Integration: Researchers, Clinicians, Leaders, Educators). The name represents the continuous cycle of learning for physicians, as well as the roles students and graduates are encouraged to embrace. The CIRCLE curriculum has been in place since 2012. The Long SOM class size has remained stable at approximately 220 students per year since 2010. The 20-month preclinical curriculum begins with 3 foundational modules (Molecules to Medicine, Attack and Defense, and Language of Medicine) in July of the first year. The foundational modules are followed by 8 sequential organ-system modules, concluding in February of the second year. Two longitudinal modules (Medicine, Behavior, and Society; Clinical Skills) thread throughout the entire preclinical curriculum. Within each module, there is an integration of knowledge in a systematic fashion as follows: normal structure and function; pathogenesis/pathophysiology; clinical manifestations; interpretation of diagnostic tests; therapeutic interventions (including pharmacotherapy); relevant clinical/translational research, evidence-based medicine, and value-based care; and epidemiology/prevention. Each module has a weekly theme, culminating in a team-based interactive patient case. In March of the second year, students have the option to begin their clerkships and electives, creating flexibility later in the third and fourth year for career preparation, research, licensing examinations, and service activities. The clinical curriculum comprises 8 required rotations: emergency medicine (4 weeks), family medicine (6 weeks), internal medicine (8 weeks), neurology (4 weeks), obstetrics–gynecology (6 weeks), pediatrics (6 weeks), psychiatry (6 weeks), and surgery (8 weeks). Students assume increasing patient care responsibilities commensurate with achievement of specific milestones and competencies derived from nationally recognized standards, such as the AAMC’s Core Entrustable Professional Activities (EPAs) and Physician Competency Reference Set (PCRS). The elective curriculum provides students flexibility to determine their own developmental needs as they transition to residency. The schedule includes 8 weeks of selectives (4 weeks of inpatient subinternship, 4 weeks of ambulatory care), 20 weeks of electives, and 4 weeks of mandatory didactics. See Supplemental Digital Appendix 1—Curriculum Overview—at https://links.lww.com/ACADMED/A900. The curriculum has changed substantially since 2010. Before the launch of the CIRCLE curriculum in 2012, it had a traditional “Flexnerian” format: basic science in the first 2 years followed by clinical science. Classroom sessions previously employed primarily lecture-dense, passive learning experiences. Preclinical modules are co-led by 2 module directors, a pairing of 1 scientist–educator and 1 clinician–educator. Discipline coordinators serve as subject matter experts who ensure vertical and horizontal integration of their area of expertise across the educational program. Learning objectives drive session design and delivery, student assessment, and course/program evaluation. There has been a net reduction of classroom hours, leveraging best practices in blended learning, an emphasis on application of knowledge over memorization, and team-based learning. Demonstration of accountability, collaboration, and diligence are emphasized as foundations of physician excellence. As such, each preclinical module has designated portions that require in-person student engagement to meet passing requirements. The clinical phase of the curriculum also represents an evolution in student experiences, assessment frameworks, and sequencing. All students now take 4-week core clerkships in emergency medicine and neurology during their third year. Unified clinical assessment tools are used across all 8 clerkships and are built on the concept and framework of Core EPAs. Clerkship students now take part in 2 new experiences that transcend any individual clerkship: the cross-clerkship clinical skills (CS) exam, a series of 3 sequentially more complex objective structured clinical examinations that replicate and prepare students for the format of USMLE Step 2 CS examination; and the TeamCare series, large- and small-group interactive half-day sessions where all clerkship students are brought together as a class to cover widely applicable clinical topics, such as patient safety/quality improvement, value-based care, physician resilience, and challenging patient encounters. Program objectives and assessment methods The Long SOM competencies and objectives were initially developed by a working group of the Curriculum Committee (CC) in 2008 in preparation for a comprehensive curriculum renewal. The Medical School Objectives Project served as the primary framework upon which we based our final product. They are the backbone of instructional design, student assessment, and program evaluation of the curriculum. All competencies and objectives are mapped to module, clerkship, and elective objectives; session objectives within modules; assessment tools; and the PCRS. See Supplemental Digital Appendix 2—Competencies, Program Objectives, and Assessment Methods—at https://links.lww.com/ACADMED/A900. In keeping with full integration of foundational science and clinical content in preclinical modules and reduction in classroom contact hours, approaches to assessment have changed since 2010. Daily opportunities for formative feedback on acquisition of key concepts and frequent quizzing have been incorporated into preclinical modules. Items on summative module examinations mimic USMLE Step 1 item format. Before students begin electives and clerkships, they must demonstrate readiness to pass USMLE Step 1 via performance on the NBME Comprehensive Basic Science Exam. In the clinical phase, assessment of clinical performance is captured using a common tool across clerkships. The domains map to Core EPAs and performance levels are descriptive in nature, permitting students to monitor their own progress within key domains and set developmental goals for ongoing improvement. Pedagogy The Long SOM uses a wide variety of pedagogical approaches to achieve program objectives and competencies. The appropriate approach is selected based on the topic, desired learning outcomes, level of the learner, and educational setting. A pillar of the curriculum renewal in 2012 was an emphasis on applied knowledge and engaged, often collaborative, learning. Students are provided guided preparation for each session, and face-to-face time targets higher levels of cognitive skills: applying, analyzing, evaluating, and creating. This is primarily accomplished through case-based learning, large- and small-group discussions, simulations, role play, standardized patient encounters, and team-based learning. Clinical experiences The CS longitudinal module runs for the duration of the preclinical phase of the medical education program, providing students with opportunities to learn medical history-taking and physical examination skills using standardized and real patients. Reinforcing the learning and development continuum of the module, CS core clinical faculty facilitators shepherd a small cohort of students at the CS simulation center from the first week of medical school through the end of the course, serving as role models and coaches in the development of key skills. Students have their first clinical experiences in the first semester as part of the CS module’s longitudinal preceptor component. Students meet periodically in clinical settings with their assigned preceptor, engaging in basic CS and patient encounters, through the end of the preclinical phase. Long SOM and its faculty practice plan own and run outpatient sites but currently do not own a teaching hospital. Thus, most clinical rotations for our students occur at community-based locations for both inpatient and outpatient experiences. Most of these clinical sites are within the San Antonio metro area. Inpatient experiences are conducted primarily at 2 locations: University Hospital, which is a Level 1 trauma center, a Level 4 NICU, and a Level 4 maternal care facility, and the Bexar County safety net hospital and a regional referral center for central and south Texas; and at the Audie L. Murphy Memorial Veterans’ Hospital. Students also have opportunities to work at several other local hospitals, including a large military hospital located at Brook Army Medical Center, as well as private hospital systems. Outpatient experiences occur primarily at University Health System (Bexar County) and UT Health/Long SOM faculty practice sites, as well as in private practice settings. As it is with many other medical schools, it can be a challenge to find and maintain enough quality placement sites to host medical students for clinical experiences. There is added competition locally and regionally pursuing placements for students in an already limited pool of potential sites. Curriculum Governance The Long SOM Faculty Assembly bylaws designates the CC as the faculty committee with ultimate authority and responsibility for central oversight of the medical education curriculum, including the overall design, management, integration, evaluation, and enhancement of a coherent and coordinated curriculum. The CC maintains 2 standing subcommittees to fully carry out its overarching charge: Evaluation Subcommittee and Design and Integration (D&I) Subcommittee. The Evaluation Subcommittee is charged with recurring review of all required modules, clerkships, didactics, and (s)electives within the medical school curriculum. The D&I Subcommittee is charged with monitoring and influencing design of the curriculum to ensure the opportunity for students to achieve the stated program competencies and objectives. See Figure 1—Curriculum design, implementation, and evaluation.Figure 1: Curriculum design, implementation, and evaluation.Education Staff Medical education leadership The Office for Undergraduate Medical Education (OUME), under the direction of the vice dean for UME, has primary responsibility for supporting the UME program. It is a comprehensive academic home comprising 3 administrative units: admissions and outreach, curriculum oversight, and student affairs. The curriculum oversight team, led by the associate dean for curriculum, works closely with the CC and course/module and clerkship directors to provide administrative, operational, and academic support for the development and maintenance of tools (i.e., Canvas LMS, one45 curriculum management software) to support curriculum delivery, monitoring, evaluation, and management. The student affairs team sponsors a wide variety of services, programs, and events for students in the Long SOM. Its mission is to help create a supportive and positive environment for students that enhances and supports learning to promote the personal and professional development of students as they progress through the curriculum. Department of Medical Education Separate from the OUME, the Department of Medical Education (DME) supports individuals interested in conducting medical education research and facilitates translation of research findings into educational practice across the continuum of medical education. Faculty with cross appointments in the DME also hold faculty appointments with their academic home department. See Figure 2—Dean leadership.Figure 2: Dean leadership.Faculty Development and Support in Education The OUME has an education development services (EDS) team dedicated to working with faculty members on development; implementation; and enhancement of existing and new courses, modules, initiatives, programs, and services in support of the teaching mission. The EDS staff meet with faculty on an individual basis as well as provide workshops on teaching and assessment of students. The OUME hosts the AAMC Medical Education Research Certification program locally in conjunction with a faculty development week when invited guests from other institutions and local education experts provide sessions on a variety of topics relevant to educational best practices, teaching, and educational research. Role of teaching in promotion and tenure In promotion and tenure decision, documented excellence (i.e., scholarly achievement) in teaching is considered a fundamental academic activity and is evaluated for advancement in rank based on performance in original or imaginative accomplishments in the conduct of academic responsibilities in teaching and research. Strength and leadership in education is demonstrated when a faculty member engages in sustained scholarly activities such as teaching in the curriculum, serving as a director of a training program, or serving as a module/course director or discipline coordinator. Initiatives in Progress Planned curriculum initiatives include a detailed analysis of the fourth year with resultant changes to its goals and structure (target implementation date 2022) and a coordinated, integrated interprofessional education plan that spans all 4 years of the curriculum (target implementation date 2020).

OBJECTIVE: To characterize stillbirths associated with pregestational diabetes and gestational diabetes mellitus (GDM) in a large, prospective, U.S. case-control study. METHODS: A secondary analysis of stillbirths among patients enrolled in a prospective; multisite; geographically, racially, and ethnically diverse casecontrol study in the United States was performed. Singleton gestations with complete information regarding diabetes status and with a complete postmortem evaluation were included. A standard evaluation protocol for stillbirth cases included postmortem evaluation, placental pathology, clinical testing as performed at the discretion of the health care professional, and a recommended panel of tests. A potential cause of death was assigned to stillbirth cases using a standardized classification tool. Demographic and delivery characteristics among women with pregestational diabetes and GDM were compared with characteristics of women with no diabetes in pairwise comparisons using chi(2) or two-sample t tests as appropriate. Sensitivity analysis was performed excluding pregnancies with genetic conditions or major fetal malformations. RESULTS: Of 455 stillbirth cases included in the primary analysis, women with stillbirth and diabetes were more likely to be older than 35 years and have a higher body mass index. They were also more likely to have a gestational hypertensive disorder than women without diabetes (28% vs 9.1%; P<.001). Women with pregestational diabetes had more large-forgestational-age (LGA) neonates (26% vs 3.4%; P<.001). Stillbirths occurred more often at term in women with pregestational diabetes (36%) and those with GDM (52%). Maternal medical complications, including pregestational diabetes and others, were more often identified as a probable or possible cause of death among stillbirths with maternal diabetes (43% vs 4%, P<.001) as compared with stillbirths without diabetes. CONCLUSION: Compared with stillbirths in women with no diabetes, stillbirths among women with pregestational diabetes and GDM occur later in pregnancy and are associated with hypertensive disorders of pregnancy, maternal medical complications, and LGA.

OBJECTIVE To better characterize infection-related stillbirth in terms of pathogenesis and microbiology. METHODS We conducted a secondary analysis of 512 stillbirths in a prospective, multisite, geographically, racially and ethnically diverse, population-based study of stillbirth in the United States. Cases underwent evaluation that included maternal interview, chart abstraction, biospecimen collection, fetal autopsy, and placental pathology. Recommended evaluations included syphilis and parvovirus serology. Each case was assigned probable and possible causes of death using the INCODE Stillbirth Classification System. Cases where infection was assigned as a probable or possible cause of death were reviewed. For these cases, clinical scenario, autopsy, maternal serology, culture results, and placental pathology were evaluated. RESULTS For 66 (12.9%) cases of stillbirth, infection was identified as a probable or possible cause of death. Of these, 36% (95% CI 35-38%) were categorized as a probable and 64% (95% CI 62-65%) as a possible cause of death. Infection-related stillbirth occurred earlier than non-infection-related stillbirth (median gestational age 22 vs 28 weeks, P=.001). Fetal bacterial culture results were available in 47 cases (71%), of which 35 (53%) grew identifiable organisms. The predominant species were Escherichia coli (19, 29%), group B streptococcus (GBS) (8, 12%), and enterococcus species (8, 12%). Placental pathology revealed chorioamnionitis in 50 (76%), funisitis in 27 (41%), villitis in 11 (17%), deciduitis in 35 (53%), necrosis in 27 (41%), and viral staining in seven (11%) cases. Placental pathology found inflammation or evidence of infection in 65 (99%) cases and fetal autopsy in 26 (39%) cases. In infection-related stillbirth cases, the likely causative nonbacterial organisms identified were parvovirus in two (3%) cases, syphilis in one (2%) case, cytomegalovirus (CMV) in five (8%) cases, and herpes in one (2%) case. CONCLUSION Of infection-related stillbirth cases in a large U.S. cohort, E coli, GBS, and enterococcus species were the most common bacterial pathogens and CMV the most common viral pathogen.

To evaluate the association between prenatal vitamin use and stillbirth (SB). The SCRN was a case-control study conducted between 2003-2008 to determine the risk factors and causes of SB. A total of 2595 women (663 SB, 1932 live births) were enrolled. Over the counter (OTC) vitamin usage was reported via questionnaires, while vitamin prescription was assed via medical record review. Individuals were considered to have taken vitamins if they used prenatal multivitamin, iron, folic acid, or other. Any vitamin usage was categorized if the mother took prescription vitamins, OTC vitamins, or both. Causes of stillbirth were previously categorized and reported using the INCODE system. Within each category, reasons for stillbirth were identified as either probable, possible, present, or absent. Chi-square and univariate logistic regression were used for statistical analyses. SB was found to be correlated with prescribed vitamin use (p=0.000), OTC vitamin (p=0.001) and any vitamin (p=0.000) consumption, with higher proportions of all vitamin usage among Live Births. Prescription, OTC, or any vitamin usage was show to have lower odds of SB (see table, p<.001). There was no significant relationship between OTC and prescription vitamin use and identified causes of stillbirth, such as placental disease (p=0.42, p=0.37), infection (p=0.36, p=0.79), fetal genetic or structural abnormalities (p=0.89, p=0.46), maternal medical complications (p=0.77, p=0.17), hypertensive disorders (p=0.35, p=0.78), umbilical cord abnormalities (p=0.96, p=0.77), obstetric complications (p=0.31, p=0.18) or other unspecified causes (p=0.73, p=0.86). Those who consumed two types of OTC vitamins had lower odds of SB than singular consumption (OR=0.68, p=0.001), but there were no protective effects for consumption of higher volumes of vitamins. Both OTC and prescribed vitamin usage decreased the odds of SB. However, we did not identify a relationship between causes of stillbirth and prescription nor OTC vitamin usage.

Background Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation. Objective This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth. Study Design White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived. Results A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m2) categorized as normal (18.5–24.9), overweight (25.0–29.9), or obese (30.0 + ). Overweight (COR, 1.48; 95% confidence interval [CI]: 1.14–1.94) and obese women (COR, 1.60; 95% CI: 1.23–2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p < 0.0001) and C-reactive protein levels lower (geometric mean: 2.9 mg/dL vs. 3.3, p = 0.0279), among women with stillbirth compared with live birth. Elevated white blood cell count (15.0 uL × 103 or greater) was associated with stillbirth (21.2% SB vs. 10.0% live birth, p < 0.0001). Histologic chorioamnionitis was more common (33.2% vs. 15.7%, p < 0.0001) among women with stillbirth compared with those with live birth. Serum ferritin, C-reactive protein, and chorioamnionitis had little impact on the ORs associating stillbirth with overweight or obesity. Adjustment for elevated white blood cell count did not meaningfully change the OR for stillbirth in overweight versus normal weight women. However, the stillbirth OR for obese versus normal BMI changed by more than 10% when adjusting for histologic chorioamnionitis (AOR, 1.38; 95% CI: 1.02–1.88), indicating confounding. BMI by inflammatory marker interaction terms were not significant. The association of serum ferritin levels with stillbirth was stronger among preterm births (p = 0.0066). Conclusion Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths.

OBJECTIVE:To estimate the proportion of potentially preventable stillbirths in the United States.METHODS:We conducted a secondary analysis of 512 stillbirths with complete evaluation enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based case-control study of stillbirth in the United States. Cases of stillbirth underwent standard evaluation that included maternal interview, medical record abstraction, biospecimen collection, postmortem examination, placental pathology, and clinically recommended evaluation. Each stillbirth was assigned probable and possible causes of death using the Initial Causes of Fetal Death algorithm system. For this analysis, we defined potentially preventable stillbirths as those occurring in nonanomalous fetuses, 24 weeks of gestation or greater, and weighing 500 g or greater that were 1) intrapartum, 2) the result of medical complications, 3) the result of placental insufficiency, 4) multiple gestation (excluding twin-twin transfusion), 5) the result of spontaneous preterm birth, or 6) the result of hypertensive disorders of pregnancy.RESULTS:Of the 512 stillbirths included in our cohort, causes of potentially preventable stillbirth included placental insufficiency (65 [12.7%]), medical complications of pregnancy (31 [6.1%]), hypertensive disorders of pregnancy (20 [3.9%]), preterm labor (16 [3.1%]), intrapartum (nine [1.8%]), and multiple gestations (four [0.8%]). Twenty-seven stillbirths fit two or more categories, leaving 114 (22.3%) potentially preventable stillbirths.CONCLUSION:Based on our definition, almost one fourth of stillbirths are potentially preventable. Given the predominance of placental insufficiency among stillbirths, identification and management of placental insufficiency may have the most immediate effect on stillbirth reduction.

Placental surface area is often estimated using diameter measurements. However, as many placentas are not elliptical, we were interested in the validity of these estimates. We compared placental surface area from images for 491 singletons from the Stillbirth Collaborative Research Network (SCRN) Study (416 live births, 75 stillbirths) to estimates obtained using diameter measurements. Placental images and diameters were obtained from pathologic assessments conducted for the SCRN Study and images were analyzed using ImageJ software. On average, diameter-based measures underestimated surface area by -5.58% (95% confidence interval: -30.23, 19.07); results were consistent for normal and abnormal shapes. The association between surface area and birthweight was similar for both measures. Thus, diameter-based surface area can be used to estimate placental surface area.

OBJECTIVE: To estimate the usefulness of each diagnostic test in the work-up for potential causes of stillbirth. METHODS: A secondary analysis of 512 stillbirths enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008 was performed. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based study of stillbirth in the United States. Participants underwent standardized evaluations that included maternal interview, medical record abstraction, biospecimen collection, fetal autopsy, and placental pathology. Also, most participants had a clinical work-up that included karyotype, toxicology screen, syphilis serology, antibody screen, fetal–maternal hemorrhage testing, and testing for antiphospholipid antibodies as well as testing performed on biospecimens for research purposes. Previously, each participant had been assigned probable and possible causes of death using the Initial Causes of Fetal Death classification system. In this analysis, tests were considered useful if a positive result established (or helped to establish) this cause of death or a negative result excluded a cause of death that was suspected based on the clinical history or other results. RESULTS: The usefulness of each test was as follows: placental pathology 64.6% (95% confidence interval [CI] 57.9–72.0), fetal autopsy 42.4% (95% CI 36.9–48.4), genetic testing 11.9% (95% CI 9.1–15.3), testing for antiphospholipid antibodies 11.1% (95% CI 8.4–14.4), fetal–maternal hemorrhage 6.4% (95% CI 4.4–9.1), glucose screen 1.6% (95% CI 0.7–3.1), parvovirus 0.4% (95% CI 0.0–1.4), and syphilis 0.2% (95% CI 0.0–1.1). The utility of the tests varied by clinical presentation, suggesting a customized approach for each patient. CONCLUSION: The most useful tests were placental pathology and fetal autopsy followed by genetic testing and testing for antiphospholipid antibodies.

Purpose: To determine the association between maternal exposure to childhood maltreatment (CM) and risk of stillbirth (fetal death at or after 20 weeks' gestation). Methods: Population-based case-control study from the Stillbirth Collaborative Research Network (SCRN) conducted in 2006-2008, and the follow-up study, SCRN-Outcomes after Study Index Stillbirth (SCRN-OASIS), conducted in 2009 in the United States. Cases (n = 133) included women who experienced a stillbirth, excluding stillbirths attributed to genetic/structural or umbilical cord abnormalities and intrapartum stillbirths. Controls (n = 500) included women delivering a healthy term live birth (excluding births less than 37 weeks gestation, neonatal intensive care unit admission, or death). CM exposure was measured using the Childhood Trauma Questionnaire, administered during the SCRN-OASIS study. Dichotomized scores for five subscales of CM (physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse) and an overall measure of CM exposure were analyzed using logistic regression. Results: Generally, there was no association between CM and stillbirth, except for the emotional neglect subscale (OR: 1.93; 95% CI: 1.17, 3.19). Conclusions: Childhood neglect is understudied in comparison to abuse and should be included in the future studies of associations between CM and pregnancy outcomes, including stillbirth. (C) 2017 Elsevier Inc. All rights reserved.

OBJECTIVE: To describe delivery management of singleton stillbirths in a population-based, multicenter case series.METHODS: We conducted a retrospective chart review of 611 women with singleton stillbirths at 20 weeks of gestation or greater from March 2006 to September 2008. Medical and delivery information was abstracted from medical records. Both antepartum and intrapartum stillbirths were included; these were analyzed both together and separately. The primary outcome was mode of delivery. Secondary outcomes included induction of labor and indications for cesarean delivery. Indications for cesarean delivery were classified as obstetric (abnormal fetal heart tracing before intrapartum demise, abruption, coagulopathy, uterine rupture, placenta previa, or labor dystocia) or nonobstetric (patient request, repeat cesarean delivery, or not documented).RESULTS: Of the 611 total cases of stillbirth, 93 (15.2%) underwent cesarean delivery, including 43.0% (46/107) of women with prior cesarean delivery and 9.3% (47/ 504) of women without prior cesarean delivery. No documented obstetric indication was evident for 38.3% (18/47) of primary and 78.3% (36/46) of repeat cesarean deliveries. Labor induction resulted in vaginal delivery for 98.5% (321/326) of women without prior cesarean delivery and 91.1% (41/45) of women with a history of prior cesarean delivery, including two women who had uterine rupture. Among women with a history of prior cesarean delivery who had spontaneous labor, 74.1% (20/27) delivered vaginally, with no cases of uterine rupture.CONCLUSION: Women with stillbirth usually delivered vaginally regardless of whether labor was spontaneous or induced or whether they had a prior cesarean delivery. However, 15% underwent cesarean delivery, often without a documented obstetric indication.

OBJECTIVE: To estimate the usefulness of each diagnostic test in the work-up for potential causes of stillbirth.METHODS: A secondary analysis of 512 stillbirths enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008 was performed. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based study of stillbirth in the United States. Participants underwent standardized evaluations that included maternal interview, medical record abstraction, biospecimen collection, fetal autopsy, and placental pathology. Also, most participants had a clinical work-up that included karyotype, toxicology screen, syphilis serology, antibody screen, fetal-maternal hemorrhage testing, and testing for antiphospholipid antibodies as well as testing performed on biospecimens for research purposes. Previously, each participant had been assigned probable and possible causes of death using the Initial Causes of Fetal Death classification system. In this analysis, tests were considered useful if a positive result established (or helped to establish) this cause of death or a negative result excluded a cause of death that was suspected based on the clinical history or other results.RESULTS: The usefulness of each test was as follows: placental pathology 64.6% (95% confidence interval [CI] 57.9-72.0), fetal autopsy 42.4% (95% CI 36.9-48.4), genetic testing 11.9% (95% CI 9.1-15.3), testing for anti-phospholipid antibodies 11.1% (95% CI 8.4-14.4), fetal-maternal hemorrhage 6.4% (95% CI 4.4-9.1), glucose screen 1.6% (95% CI 0.7-3.1), parvovirus 0.4% (95% CI 0.0-1.4), and syphilis 0.2% (95% CI 0.0-1.1). The utility of the tests varied by clinical presentation, suggesting a customized approach for each patient.CONCLUSION: The most useful tests were placental pathology and fetal autopsy followed by genetic testing and testing for antiphospholipid antibodies.

OBJECTIVE: To describe delivery management of singleton stillbirths in a population-based, multicenter case series. METHODS: We conducted a retrospective chart review of 611 women with singleton stillbirths at 20 weeks of gestation or greater from March 2006 to September 2008. Medical and delivery information was abstracted from medical records. Both antepartum and intrapartum stillbirths were included; these were analyzed both together and separately. The primary outcome was mode of delivery. Secondary outcomes included induction of labor and indications for cesarean delivery. Indications for cesarean delivery were classified as obstetric (abnormal fetal heart tracing before intrapartum demise, abruption, coagulopathy, uterine rupture, placenta previa, or labor dystocia) or nonobstetric (patient request, repeat cesarean delivery, or not documented). RESULTS: Of the 611 total cases of stillbirth, 93 (15.2%) underwent cesarean delivery, including 43.0% (46/107) of women with prior cesarean delivery and 9.3% (47/504) of women without prior cesarean delivery. No documented obstetric indication was evident for 38.3% (18/47) of primary and 78.3% (36/46) of repeat cesarean deliveries. Labor induction resulted in vaginal delivery for 98.5% (321/326) of women without prior cesarean delivery and 91.1% (41/45) of women with a history of prior cesarean delivery, including two women who had uterine rupture. Among women with a history of prior cesarean delivery who had spontaneous labor, 74.1% (20/27) delivered vaginally, with no cases of uterine rupture. CONCLUSION: Women with stillbirth usually delivered vaginally regardless of whether labor was spontaneous or induced or whether they had a prior cesarean delivery. However, 15% underwent cesarean delivery, often without a documented obstetric indication.

BACKGROUND: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network previously demonstrated an association between stillbirth and maternal marijuana use as defined by the presence of 11-nor-delta-9-tetrahydrocannabinol- 9-carboxylic acid in the umbilical cord homogenate. However, the relationship between marijuana use and perinatal complications in live births is uncertain. OBJECTIVE: Our aim was to examine if maternal marijuana use is associated with increased odds of adverse pregnancy outcomes and neonatal morbidity among live-born controls in the Stillbirth Collaborative Research Network cohort. STUDY DESIGN: We conducted a secondary analysis of singleton, live-born controls in the Stillbirth Collaborative Research Network data set. Marijuana use was measured by self-report and/or the presence of 11nor- delta-9-tetrahydrocannabinol-9-carboxylic acid in umbilical cord homogenate. Tobacco use was measured by self-report and/or presence of any cotinine in maternal serum. Adverse pregnancy outcome was a composite of small for gestational age, spontaneous preterm birth resulting from preterm labor with or without intact membranes, and hypertensive disorders of pregnancy. Neonatal morbidity included neonatal intensive care unit admission and composite neonatal morbidity (pulmonary morbidity, necrotizing enterocolitis, seizures, retinopathy of prematurity, infection morbidity, anemia requiring blood transfusion, neonatal surgery, hyperbilirubinemia, neurological morbidity, or death prior to hospital discharge). Effect of maternal marijuana use on the probability of an adverse outcome was estimated using weighted methodology to account for oversampling in the original study. 11-nor-delta-9-tetrahydrocannabinol- 9-carboxylic acid cord homogenate analysis was performed in the subset of women for whom biospecimens were available. Comparisons using logistic modeling, x(2), and t tests were weighted to account for oversampling of preterm births and non-Hispanic blacks. Results are reported as weighted percent and unweighted frequencies. RESULTS: Maternal marijuana use was identified in 2.7% (unweighted frequency 48/1610) of live births. Use was self-reported by 1.6% (34/1610) and detected by 11-nor-delta-9-tetrahydrocannabinol-9carboxylic acid in cord homogenate for 1.9% (17/897), n = 3 overlapping. Rate of tobacco use was 12.9% (217/1610), with 10.7% (167/1607) by self-report and 9.5% (141/1313) by serum cotinine. The composite adverse pregnancy outcome was not significantly increased in women with marijuana use compared to nonusers (31.2% vs 21.2%; P = .14). After adjustment for tobacco, clinical, and socioeconomic factors, marijuana use was not associated with the composite adverse pregnancy outcome (adjusted odds ratio, 1.29; 95% confidence interval, 0.56-2.96). Similarly, among women with umbilical cord homogenate and serum cotinine data (n = 765), marijuana use was not associated with adverse pregnancy outcomes (adjusted odds ratio, 1.02; 95% confidence interval, 0.18-5.66). Neonatal intensive care unit admission rates were not statistically different between groups (16.9% users vs 9.5% nonusers, P = .12). Composite neonatal morbidity or death was more frequent among neonates of mothers with marijuana use compared to nonusers (14.1% vs 4.5%; P = .002). In univariate comparisons, the components of the composite outcome that were more frequent in neonates of marijuana users were infection morbidity (9.8% vs 2.4%; P < .001) and neurologic morbidity (1.4% vs 0.3%; P = .002). After adjustment for tobacco, race, and other illicit drug use, marijuana use was still associated with composite neonatal morbidity or death (adjusted odds ratio, 3.11; 95% confidence interval, 1.40-06.91). CONCLUSION: Maternal marijuana use was not associated with a composite of small for gestational age, spontaneous preterm birth, or hypertensive disorders of pregnancy. However, it was associated with an increased risk of neonatal morbidity.

BACKGROUND:Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. METHODS AND FINDINGS:Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (<10th percentile) and large (>90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner; (5) a different pattern of fetal growth abnormalities in stillbirths and live births. CONCLUSIONS:The patterns of association between placental abnormalities, fetal growth, and stillbirth provide insights into the mechanism of impaired placental function and stillbirth. They also suggest implications for clinical care, especially for placental findings amenable to prenatal diagnosis using ultrasound that may be associated with term stillbirths.

BACKGROUND: An evaluation for heritable thrombophilias is recommended in the evaluation of stillbirth. However, the association between thrombophilias and stillbirth remains uncertain.OBJECTIVE: We sought to assess the association between maternal and fetal/placental heritable thrombophilias and stillbirth in a population-based, case-control study in a geographically, racially, and ethnically diverse population.STUDY DESIGN: We conducted secondary analysis of data from the Stillbirth Collaborative Research Network, a population-based case-control study of stillbirth. Testing for factor V Leiden, prothrombin G20210A, methylene tetrahydrofolate reductase C677T and A1298C, and plasminogen activating inhibitor (PAI)-1 4G/5G mutations was done on maternal and fetal (or placental) DNA from singleton pregnancies. Data analyses were weighted for oversampling and other aspects of the design. Odds ratios (OR) were generated from univariate models regressing stillbirth/live birth status on each thrombophilia marker.RESULTS: Results were available for >= 1 marker in 488 stillbirths and 1342 live birth mothers and 405 stillbirths and 990 live birth fetuses. There was an increased odds of stillbirth for maternal homozygous factor V Leiden mutation (2/488; 0.4% vs 1/1380; 0.0046%; OR, 87.44; 95% confidence interval, 7.88-970.92). However, there were no significant differences in the odds of stillbirth for any other maternal thrombophilia, even after stratified analyses. Fetal 4G/4G PAI-1 (OR, 0.63; 95% confidence interval, 0.43-0.91) was associated with decreased odds of stillbirth. Other fetal thrombophilias were similar among groups.CONCLUSION: Most maternal and fetal thrombophilias were not associated with stillbirth. Maternal factor V Leiden was weakly associated with stillbirth, and the fetal PAI-1 4G/4G polymorphism was associated with live birth. Our data do not support routine testing for heritable thrombophilias as part of an evaluation for possible causes of stillbirth.