Jacob Larkin, MD
Assistant Professor, University of Pittsburgh, Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal-Fetal Medicine
Research in Brief
I am a practicing Maternal-Fetal Medicine physician, and my research is directed towards answering challenges encountered at the bedside. In particular, work in our lab focuses on the mechanistic and clinical determinants of fetal growth abnormalities, particularly fetal growth restriction. Fetal growth restriction confers risk for stillbirth, neonatal death and morbidity, as well as long-term health problems throughout an individual’s lifetime. Despite these broad public health implications, early delivery remains the only therapy to treat, prevent, or ameliorate fetal growth restriction. Moreover, there is limited consensus on the appropriate diagnostic criteria or management strategies for fetal growth restriction, leaving broad gaps in our understanding of the optimal ways to define and manage this common clinical problem.
We employ parallel strategies to approach this problem from different perspectives. Our first line of investigation is translational in nature, probing mechanisms of placental injury and dysfunction. Recent work has focused on the effect of hypoxia and oxidative stress, two common placental insults germane to fetal growth restriction, on placental function. Specifically, we are investigating the impact of cholesterol oxidation and cholesterol oxidation products (oxysterols) on the transcription factors LXRα, LXRβ, and SREBP2, and gene expression pathways that regulate trophoblast viability, differentiation, steroid hormone synthesis, and lipid trafficking.
Our second line of investigation focuses on the diagnostic criteria and prognostic implications of fetal growth restriction. Fetal growth restriction is currently defined as a fetal weight below the 10th percentile in a population distribution, irrespective of the risk of morbid outcomes associated with this weight threshold. Moreover, the appropriate methodology to determine the 10th percentile as well as the appropriate reference population remains undefined. We are actively engaged in uncovering the underlying relationship between perinatal mortality and fetal growth through the analysis of large data sets. This analysis will facilitate the determination of diagnostic criteria for fetal growth restriction that will reflect relevant clinical risk thresholds.
- Larkin JC, Speer PD, Simhan HN. A customized standard of large size for gestational age to predict intrapartum morbidity. Am J Obstet Gynecol 2011;204(6):499.e1-10.
- Larkin JC, Hill LM, Speer PD, Simhan HN. Risk of morbid perinatal outcomes in small-for-gestational-age pregnancies: customized compared with conventional standards of fetal growth. Obstet Gynecol 2012;119(1):21-7.
- Shi XH, Larkin JC, Chen B, Sadovsky Y. The expression and localization of N-myc downstream-regulated gene 1 in human trophoblasts. PLoS One 2013;8(9):e75473.
- Larkin JC, Sears SB, Sadovsky Y. The influence of ligand-activated LXR on primary human trophoblasts. Placenta 2014;35(11):919-24.
- Stacy SL, Brink LL, Larkin JC, Sadovsky Y, Goldstein BD, Pitt BR, Talbott EO. Perinatal outcomes and unconventional natural gas operations in Southwest Pennsylvania. PLoS One 2015;10(6):e0126425.
- Froehlich R, Simhan HN, Larkin JC. An Evidence-Based Approach to Defining Fetal Macrosomia. Am J Perinatol 2015, Epub ahead of print, DOI: 10.1055/s-0035-1565998
For additional publications, visit Pubmed.