Maternal pregnancy associated plasma protein-A (PAPP-A) and uterine artery Doppler changes as predictors of pre-eclampsia: a prospective observational study from a teaching hospital in Mysore, Karnataka, India

Sharanya Satish, K. B. Suma, Madhu B., Sujatha M. S.


Background: Hypertensive disorder affects 10-12% of pregnancies. Identifying women, who are at risk is conducive to prompt gestational management. PAPP-A is a protein complex produced by the developing trophoblasts. Low levels of PAPP-A at 10–14 weeks is a marker of impaired placentation and a smaller placental mass. Doppler imaging permits non-invasive evaluation of the uteroplacental circulation and is invaluable in the management of high-risk pregnancies. The uterine artery Doppler screening identifies patients at risk for developing preeclampsia. To study the association of PAPP-A and the uterine artery Doppler changes as predictor of pre-eclampsia in pregnant women at 11-14 weeks of gestation.

Methods: This was a prospective study of 150 pregnant women presenting at 11-14 weeks of gestation for a prenatal check-up. After considering the inclusion and exclusion criteria, serum samples for PAPP-A were assayed. Ultrasound Doppler was used to obtain uterine artery flow velocity waveforms and mean pulsatility index and resistance index of uterine arteries were calculated. Cases were followed up till term and observed for development of pre-eclampsia.

Results: 48.6% had low serum PAPP-A levels, in which 77% developed PE. The Mean PI and RI is 2.34±1.16 and 0.58±0.1 respectively. 30% women with abnormal PI values and 24% of women with abnormal RI values developed PE.

Conclusions: The combination of maternal history with low serum PAPP-A levels and abnormal uterine artery Doppler at 11-14 weeks can be used as predictor of pre-eclampsia.


High risk pregnancy, Uterine artery Doppler, Uteroplacental circulation

Full Text:



Ales KL, Clarson ME. In search of the true inception cohort. J Chronic Dis. 1987;40(9):815-81.

Lehmann DK, Mabie WC, Miller JJ, Pernoll ML. The epidemiology and pathology of maternal mortality: Charity Hospital of Louisiana in New Orleans, 1965-1984. Obstet Gynecol. 1987;69(6):833-40.

Ales KL, Frayer W, Hawks G, Auld PM, Druzin ML. Development and validation of a multivariate predictor of mortality in very low birth weight. J Clinic Epidemiol. 1988;41(11):1095-103.

ACOG Committee on Obstetric Practice. Practice bulletin 33: diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol. 2002 ;99(1):159-67.

Alicia M, Lapidus MD. Effects of preeclampsia on mother, fetus and child. Obgyn Net. 2011:1-3.

Maternal mortality in 2005: estimates developed by WHO, UNICEF, UNIFPA and the World Bank, Geneva, World Health Organization, 2007.

Poon LC, Staboulidou I, Maiz N, Plasencia W, Nicolaides KH. Hypertensive disorders in pregnancy: screening by uterine artery Doppler at 11-13 weeks. Ultrasound Obstet Gynecol.2009;34(2):142-8.

Baker DW. Pulsed ultrasonic Doppler blood flow sensing IEEE Transsonic Ultrasonics. 1970;17(3):170-85.

Benifla JL, Tchobroutsky C, Uzan M, Sultan Y, Weill BJ, Laumond-Barny S. Predictive value of uterine artery velocity waveforms in pregnancies complicated by systemic lupus erythematosus and the antiphospholipid syndrome. Fetal Diagnos Therapy. 1992;7(3-4):195-202.

Guzman E, Schulman H, Bracero L, Rochelson B, Farmakides G, Coury A. Uterine‐umbilical artery Doppler velocimetry in pregnant women with systemic lupus erythematosus. J Ultrasound Med. 1992;11(6):275-81.

Ong CY, Liao AW, Spencer K, Munim S, Nicolaides KH. First trimester maternal serum free β human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications. BJOG: Int J Obstet Gynaecol. 2000;107(10):1265-70.

Campbell S, Griffin DR, Pearce JM, Diaz-Recasens J, Cohen-Overbeek TE, Willson K, Teague MJ. New Doppler technique for assessing uteroplacental blood flow. The Lancet. 1983;321(8326):675-7.

Kniss DA, Shubert PJ, Zimmerman PD, Landon MB, Gabbe SG. Insulinlike growth factors. Their regulation of glucose and amino acid transport in placental trophoblasts isolated from first-trimester chorionic villi. J Reproduct Med. 1994;39(4):249-56.

Clemmons DR. Role of insulin-like growth factor binding proteins in controlling IGF actions. Molecular Cellular Endocrinol. 1998;140(1-2):19-24.

Irwin JC, Suen LF, Martina NA, Mark SP, Giudice LC. Role of the IGF system in trophoblast invasion and pre-eclampsia. Human reproduction. 1999;14(2):90-8.

Balcı S. Predictive values of maternal serum PAPP-A level, uterine artery Doppler velocimetry, and fetal biometric measurements for poor pregnancy and poor neonatal outcomes in pregnant women. J Turkish German Gynecolo Assoc. 2016;17(3):143.

Asiltas B, Surmen-Gur E, Uncu G. Prediction of first-trimester preeclampsia: Relevance of the oxidative stress marker MDA in a combination model with PP-13, PAPP-A and beta-HCG. Pathophysiol. 2018;25(2):131-5.

Goetzinger KR, Singla A, Gerkowicz S, Dicke JM, Gray DL, Odibo AO. Predicting the risk of pre‐eclampsia between 11- and 13-weeks’ gestation by combining maternal characteristics and serum analytes, PAPP‐A and free β‐hCG. Prenatal Diagnosis. 2010;30(12‐13):1138-42.

Martin AM, Bindra R, Curcio P, Cicero S, Nicolaides KH. Screening for pre‐eclampsia and fetal growth restriction by uterine artery Doppler at 11–14 weeks of gestation. Ultrasound in Obstetrics and Gynecology: The Official J Int Society Ultrasound Obstet Gynecol. 2001;18(6):583-6.

Spencer K, Christina KH, Cowans NJ, Otigbah C, Nicolaides KH. Prediction of pregnancy complications by first‐trimester maternal serum PAPP‐A and free β‐hCG and with second‐trimester uterine artery Doppler. Prenatal diagnosis. 2005 Oct 1;25(10):949-53.