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Hypertension, Diabetes, Prematurity, Physiology

Poster Session II

287 Cathepsin D activity is associated with severity of preeclampsia
Christy Pearce1, Samantha Mast2, Rebecca Pollack3, John O’Brien2, Wendy Hansen2, Thomas Curry2
1 Vanderbilt University, Maternal Fetal Medicine, Nashville, TN, 2University of Kentucky, Obstetrics and Gynecology, Lexington, KY, 3Carolinas Healthcare, Maternal Fetal Medicine, Charlotte, NC

OBJECTIVE: Cathepsin D is associated with the pathophysiology of preeclampsia through an inflammatory, anti-angiogenic pathway. We sought to examine the relationship of cathepsin D with clinical and laboratory markers of preeclampsia. STUDY DESIGN: Women aged 18-43 diagnosed with preeclampsia were recruited for this IRB approved study. Demographics and clinical data and outcomes were recorded throughout the antepartum and postpartum course. PlGF (pg/ml) was determined using ELISA. Cathepsin D activity (mM) was determined using a fluorimetric SensolyteÒ 520 Immunoassay. Statistical analyses included ttest, ANOVA, Wilcoxon rank sum, and pairwise correlations. RESULTS: We recruited 23 women with mild (n¼10) and severe preeclampsia (n¼13). Mean age was 28.7 Æ 5.6 years. Most were Caucasian (n¼21) and primigravida (n¼14). Average gestational age at enrollment was 32.0 Æ 4.8 weeks. Mean cathepsin D activity in mild preeclampsia was 13.8 Æ 8.2 versus 18.0 Æ 21.3 in severe preeclampsia (p¼0.99). A ratio of cathepsin D activity to PlGF was higher in severe preeclampsia as opposed to mild preeclampsia (0.474 Æ 0.89 vs 0.095 Æ 0.05, p¼0.07). Increased cathepsin D: PlGF ratio was associated with worsening creatinine and uric acid (r¼0.5, p¼0.02 for both). CONCLUSION: A ratio of cathepsin D activity to PlGF as a marker of anti-angiogenic factors to pro-angiogenic balance better indicates severity in preeclampsia than cathepsin D activity alone. Future work with larger sample sizes is planned to further examine the relationship of cathepsin D with the severity of preeclampsia.

RESULTS: The early-onset preeclampsia group included 38% Filipinos, 29% Caucasians, 18% Pacific Islanders, and 13% Asians. Racial composition of the cohort did not differ significantly from that of the non-preeclamptic group (p ¼ 0.817). A total of 88 SNPs were significantly associated with early-onset preeclampsia in 53 chromosomal regions. Table 1 represents a portion of these regions, which were selected based on level of statistical significance or association with a gene of interest. The majority of these SNPs and their related genes have not been associated with preeclampsia in previous studies [1]. CONCLUSION: Multiple metabolically-related SNPs demonstrate associations with early-onset preeclampsia in a predominantly Asian population. These findings unfold new areas of research regarding the genetic determinants of early-onset preeclampsia. 1.Tuteja G, Cheng E, Papadakis H, Bejerano G. PESNPdb: A comprehensive database for SNPs studied in association with preeclampsia. Placenta 2012;22:1055-57.

Single-nucleotide polymorphisms significantly associated with early-onset preeclampsia

288 Evaluation of a maternal metabolic gene array in early-onset preeclampsia in a predominantly Asian cohort
Dena Towner , Kelly Yamasato , Marla Berry , Dongmei Li
1 1 2 3
1 John A Burns School of Medicine, University of Hawaii at Manoa, Department of Obstetrics, Gynecology, and Women’s Health, Honolulu, HI, 2 John A Burns School of Medicine, University of Hawaii at Manoa, Department of Cell and Molecular Biology, Honolulu, HI, 3John A Burns School of Medicine, University of Hawaii at Manoa, Department of Public Health Sciences. Office of Public Health Studies, Honolulu, HI

1

GRCh37.p10 assembly.

289 Collateral benefits of perinatal safety and risk reduction initiatives
Larry Shields2, Herman Hedriana3, Suzanne Wiesner1, Janet Fulton1, Barbara Pelletreau1
1 Dignity Health, Patient Safety and Quality, San Francisco, CA, 2Marian Regional Medical Center, Maternal Fetal Medicine, Santa Maria, CA, 3 Sacramento Maternal Fetal Medicine, Sacramento, CA

OBJECTIVE: To identify metabolic related single-nucleotide polymorphisms (SNPs) associated with early-onset preeclampsia in a predominantly Asian cohort in Hawaii. STUDY DESIGN: We compared DNA from 55 women with early-onset preeclampsia (< 35 weeks and 0 days gestation) with that from 54 non-preeclamptic women who delivered a full term infant with normal birthweight. Women with multiple gestations and/or known medical disorders associated with preeclampsia (diabetes, chronic hypertension, renal disease, hyperthyroidism, and lupus) were excluded. The MetaboChip (Illumina, San Diego, CA) genotyping array with approximately 200,000 SNP markers associated with metabolic and cardiovascular traits was used. Statistical analysis was performed using the R SNPassoc package. The Benjamini and Hochberg procedure was used to control the false discovery rate at the level of 0.001 to minimize false positives in identified statistically significant SNPs. The best inheritance model was determined for each SNP.

OBJECTIVE: To evaluate key perinatal outcome measures from a

continuous quality improvement project designed to improve patient care and reduce risk in a large hospital system with a diverse maternity services. STUDY DESIGN: In 2011, we rolled-out 5 programs designed to improve patient care and documentation. These included: 1) reduce Elective Early Deliveries (EED) at 37 0/7-38 6/7 weeks; 2) a planned vaginal delivery communication tool; 3) oxytocin Pre- and In-Use checklists; 4) standardized nurse and physician Shoulder Dystocia (SD) delivery record; and 5) a pre-elective Operative Vaginal Delivery (OVD) checklist. To determine the effect of these programs on perinatal outcomes, data was prospectively collected by a dedicated perinatal safety nurse at each site and entered into a proprietary administrative database. Data from each site were reported and summarized monthly. Outcome measures were evaluated for change during the 30-month time frame, which includes a 9-month

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