Funded Projects

Development of a Mid-trimester Screening Algorithm for Early-onset Preeclampsia

Grantee: Sequoia Foundation
Principal Investigator: Juan Yang
Project Number: R40MC21525
Project Date: 2/1/2011

Age group(s)

• Women/Maternal
• Prenatal

Targeted/Underserved Population

• African American
• Hispanic/Latino

Abstract

Preeclampsia is a dangerous pregnancy disorder and a leading cause of maternal and infant illness and death. Currently no population screening tool is available for the detection of preeclampsia. It has been proposed that mid-gestation is an optimal timing to screen for preeclampsia and that screening tests focus on early-onset preeclampsia (<34 weeks gestation). Three markers in maternal circulation may be ideal candidates for preeclampsia screening: placental growth factor (PlGF), soluble vascular endothelial growth factor receptor 1 (sVEGFR-1), and soluble endoglin (sEng). Dramatically reduced levels of PlGF and increased levels of sVEGFR-1 and sEng have been observed in preeclamptic pregnancies before clinical onset, especially in early-onset preeclampsia. These factors satisfy other favorable criteria for population screening such as low risk and minimal discomfort to patients, low cost, and tests readily adaptable to existing prenatal screening protocols. Two recent prospective cohort studies showed that PIGF/sEng ratio and sum of sVEGFR-1 and sEng had sensitivity as high as 100%, specificity around 95% and positive predictive value of 24% in identifying early-onset preeclampsia. However, these promising results are too preliminary to apply in clinical practice due to small sample sizes (<40 cases) and variations in study design. A large-scale study is now needed to evaluate these three markers in terms of their suitability for routine prenatal screening and to solidify statistics for cost estimation, service planning, follow-up protocol development, and final policy making. This study will use a large population-based nested case-control design to develop a screening algorithm for early-onset preeclampsia, defined as hypertension and proteinuria criteria with onset prior to 32 weeks gestation in non-Hispanic Whites and Mexican Hispanic Whites and prior to 34 weeks in African Americans. It will include 258 cases based on hospital records identified from a seven-year cohort of 137,716 singleton live births born in five southern California counties during January 2000 - April 2007. A sample of 2,580 controls will be randomly selected from the same cohort for lab testing to develop expected analyte distributions. Existing maternal serum specimens collected at 15-20 weeks gestation for routine testing by the California Prenatal Screening Program and banked at -20�C will be used for lab testing. Lab results will be linked to hospital records, prenatal screening and birth certificate data for analysis. Odds ratios and 95% confidence intervals will be derived from Logistic regression models to measure effect strength in African Americans. Effects and distributions of the screening factors separated for cases and controls will be compared across the three racial-ethnic groups. Sensitivity, specificity, and positive/negative predictive values for PlGF, sVEGFR-1, and sEng, will be computed individually and in combination. Receiver Operating Characteristics curves will be generated to identify the optimal cut-off values where both sensitivity and specificity are maximized. Screening algorithms will be developed using multiple analytes and adjustment. This is the first study to investigate PlGF, sVEGFR-1, and sEng in prediction of early-onset preeclampsia in African Americans and to compare racial-ethnic differences in these factors. More importantly, it is also the first study to develop a feasible screening algorithm for prenatal screening programs and clinics/hospitals. This study addresses the current MCHB Strategic Research Issues #II of MCH Services and Systems of Care Effort to Eliminate Health Disparities and MCHB Strategic Research Issues #III of Services and Systems to Assure Quality of Care for MCH Populations. Results from this study could improve obstetrical care practices and may help reduce preeclampsia-induced mortality and morbidity for women and infants.

Publications

Listed is descending order by year published.

Yang J, Pearl M, DeLorenze GN, et al. Racial-ethnic differences in midtrimester maternal serum levels of angiogenic and antiangiogenic factors. Am J Obstet Gynecol. 2016;215(3):359.e1-9.