This is a revised application for a K23 award to support Dr. Alexander Butwick's proposed research and training focusing on clinically effective and cost-effective strategies for reducing hematologic-related maternal morbidities, specifically postpartum hemorrhage (PPH) and early postpartum anemia (EPA), in women undergoing cesarean delivery (CD). Severe PPH can cause major obstetric morbidity and is a leading cause of maternal death in the US;EPA is an underappreciated adverse outcome, which may lead to long-term deleterious psychological, physical, and cognitive effects among postpartum women. Currently, risk- stratification for severe PPH and EPA and therapeutic approaches for EPA lack consensus and are predominantly non-standardized. For women undergoing CD, innovative approaches are needed for: (1) preoperative risk stratification for PPH and, (2) postoperative screening and cost-effective treatment regimens for EPA. These approaches comprise the central aspects of the proposed research.
In Aim 1, Dr. Butwick will perform a nested case-control study, using hospitalization data at Stanford University School of Medicine (SUSM), to determine predictors and develop prediction models for severe PPH in patients undergoing prelabor CD and intrapartum CD.
In Aim 2, Dr. Butwick will assess the incidence of and risk factors for EPA in women post-CD using linked hospitalization databases from Kaiser Permanente Medical Care Program - Northern California (KPMCP-NC).
In Aim 3, Dr. Butwick will perform a cost-effectiveness analysis to assess the costs, benefits, and harms of oral versus intravenous iron therapy for the treatment of EPA. The candidate is an obstetric anesthesiologist at SUSM with additional training in Clinical Epidemiology, and is therefore uniquely qualified to address these aims. Furthermore, Dr. Butwick is supported by a multidisciplinary and collaborative team with expertise in Clinical Epidemiology, Obstetrics, Perinatology, Health Services Research, and Anesthesiology. The candidate's proposal will benefit from the diverse strength of resources at SUSM (the Department of Health Research and Policy, the Stanford Center for Clinical Informatics) and at Division of Research, KPMCP-NC. To accomplish his research goals and prepare him for a career as an independent investigator, Dr. Butwick has created a multi-disciplinary career development plan incorporating: (1) graduate level didactic training in health outcomes research with mentoring in cost-effectiveness analyses and analytic approaches for medical decision-making;(2) mentoring in advanced epidemiologic techniques, integrating electronic health information and linked hospitalization databases;(3) targeted education in obstetrical and perinatal medicine;and (4) mentoring in leadership in interdisciplinary research in obstetric anesthesiology and perinatology. Successful completion of this research will form the basis for future R01 applications to validate the clinical effectivenes and cost-effectiveness of computerized predictive rules for severe PPH and to investigate individualized therapeutic strategies for EPA and other major peripartum morbidities.

Public Health Relevance

Severe postpartum hemorrhage (PPH) is a leading cause of maternal death in the US, and postpartum anemia is an underappreciated complication that is associated with reduced quality-of-life and psychological impairment among women undergoing cesarean delivery (CD). Our proposed research aims to address these serious public health problems by: (i) using clinically rich data and advanced modeling techniques to identify predictors for severe PPH and postpartum anemia;(ii) will assess the costs, benefits and harms of intravenous iron vs. oral iron therapies for the treatment of postpartum anemia. Scientific knowledge gained from this research will be used to advance preventative and therapeutic strategies for reducing rates of PPH and postpartum anemia, thereby improving maternal health for increasing numbers of women who undergo CD each year in the US.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Reddy, Uma M
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Stanford University
Schools of Medicine
United States
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Guo, Nan; Robakis, Thalia; Miller, Claire et al. (2018) Prevalence of Depression Among Women of Reproductive Age in the United States. Obstet Gynecol 131:671-679
Butwick, Alexander J; Abreo, Anisha; Bateman, Brian T et al. (2018) Effect of Maternal Body Mass Index on Postpartum Hemorrhage. Anesthesiology 128:774-783
Butwick, Alexander J; Walsh, Eileen M; Kuzniewicz, Michael et al. (2018) Accuracy of international classification of diseases, ninth revision, codes for postpartum hemorrhage among women undergoing cesarean delivery. Transfusion 58:998-1005
Butwick, Alexander J; Wong, Cynthia A; Guo, Nan (2018) Maternal Body Mass Index and Use of Labor Neuraxial Analgesia: A Population-based Retrospective Cohort Study. Anesthesiology 129:448-458
Seligman, K; Ramachandran, B; Hegde, P et al. (2017) Obstetric interventions and maternal morbidity among women who experience severe postpartum hemorrhage during cesarean delivery. Int J Obstet Anesth 31:27-36
Duffield, Adrienne; McKenzie, Christine; Carvalho, Brendan et al. (2017) Effect of a High-Rate Versus a Low-Rate Oxytocin Infusion for Maintaining Uterine Contractility During Elective Cesarean Delivery: A Prospective Randomized Clinical Trial. Anesth Analg 124:857-862
Butwick, Alexander J; Walsh, Eileen M; Kuzniewicz, Michael et al. (2017) Patterns and predictors of severe postpartum anemia after Cesarean section. Transfusion 57:36-44
Butwick, Alexander J; Ramachandran, Bharathi; Hegde, Priya et al. (2017) Risk Factors for Severe Postpartum Hemorrhage After Cesarean Delivery: Case-Control Studies. Anesth Analg 125:523-532
Miller, C M; Cohn, S; Akdagli, S et al. (2017) Postpartum hemorrhage following vaginal delivery: risk factors and maternal outcomes. J Perinatol 37:243-248
Shaylor, Ruth; Weiniger, Carolyn F; Austin, Naola et al. (2017) National and International Guidelines for Patient Blood Management in Obstetrics: A Qualitative Review. Anesth Analg 124:216-232

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