Potential screening strategies for early prediction of pre-eclampsia

Hymavathi K., Sandhya Rani Davuluru, Sameera Shaik, Sahithi Kaviti


Background: This study was conducted to evaluate the efficacy of different biochemical and biophysical markers in the early weeks of gestation as screening tools for early prediction of preeclampsia.

Methods: This hospital-based prospective observational study conducted on 52 pregnant women, at less than 13 weeks of gestation were recruited. Maternal serum inhibin A and USG uterine artery PI levels were analyzed among the pregnant women who subsequently developed PE and compare with those who did not develop PE. Methods used for the detection of markers were: chemiluminescence immunoassay (CLIA) for serum inhibin A levels, and uterine artery Doppler velocimetry was done by PHILIPS HD11XE transabdominal ultrasound machine using a 4-6 MHz probe with the same sonographer.

Results: The present study revealed a significant rise of inhibin A in preeclamptic women when compared to normotensive women (p<0.0001). The mean levels of 1st and 2nd trimester uterine artery PI significantly high in women who subsequently developed PE when compared to those who did not develop preeclampsia (p<0.0001). Study results showed a strong association between gestational age at delivery and neonatal outcome (neonatal birth weight and APGAR) with preeclampsia. The maternal serum inhibin A, and uterine artery PI found to have good sensitivity and specificity for early prediction of PE.

Conclusions: Study concluded that the women who are prone to develop PE subsequently, had high levels of MAP, UAPI, inhibin A. In our setting, MAP, UAPI, inhibin A, appeared to be better screening modalities. Combination of the biochemical markers with the biophysical markers, demographic characteristics, and other novel markers will establish the effective screening models for early prediction of PE. Early identification of high-risk cases will offer an opportunity for prophylactic therapy, such as Low- dose Aspirin in selected groups of high-risk women screened in the first trimester, thus improving the maternal and perinatal outcome.


Antioxidants, Colour Doppler ultrasonography, Pregnancy induced hypertension

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Callen PW. The role of Doppler ultrasound in obstetrics. In: Ultrasonography in Obstetrics and Gynaecology. 5th edn. Elsevier Saunders publication; 2008:794-807.

Guzman ER, Kontopoulos E, Zalud I. Doppler velocimetry of the utero placental circulation. In: Doppler Ultrasound in Obstetrics and Gynecology. 2nd edn. Springer publication; 2005:227-254.

Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130-7.

Sharma K, Singh R, Kumar M, Gupta U, Rohil V, Bhattacharjee J. First-trimester inflammatory markers for risk evaluation of pregnancy hypertension. J Obstet Gynecol India. 2018;68(1):27-32.

Spencer-Jones J. Make every mother and child count. S Afr Med. 2005;95:382.

Bowyer L. The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving Mothers’ Lives: reviewing maternal deaths to make motherhood safer 2003–2005. The Seventh Report of the Confidential Enquiries into Maternal Deaths in the UK. Obstetric Medicine. 2008 Sep;1(1):54.

Thilaganathan B, Wormald B, Zanardini C, Sheldon J, Ralph E, Papageorghiou AT. Early-pregnancy multiple serum markers and second-trimester uterine artery Doppler in predicting pre-eclampsia. Obstet Gynecol. 2010;115:1233-8.

Akolekar R, Syngelaki A, Beta J, Kocylowski R, Nicolaides KH. Maternal serum placental protein 13 at 11-13 weeks of gestation in pre-eclampsia. Prenat Diagn. 2009;29:1103-8.

Cuckle HS. Screening for pre-eclampsia- lessons from aneuploidy screening. Placenta. 2011;32(Suppl.1):S42-8.

Nicolaides KH, Bindra R, Turan OM, Chefetz I, Sammar M, Meiri H, et al. A novel approach to first-trimester screening for early pre-eclampsia combining serum PP-13 and Doppler ultrasound. Ultrasound Obstet Gynecol. 2006;27:13-7.

Gram M, Anderson UD, Johansson ME, Edström-Hägerwall A, Larsson I, Jälmby M, et al. The human endogenous protection system against cell-free hemoglobin and heme is overwhelmed in preeclampsia and provides potential biomarkers and clinical indicators. PLoS One. 2015;10(9):e0138111.

Anderson UD, Gram M, Thilaganathan B, Åkerström B, Hansson SR. [97-POS]: Free fetal hemoglobin and hemoglobin-scavenging proteins are predictive first and second trimester biochemical markers for preeclampsia. Pregnanc Hypertens. 2015;5(1):53.

Fatema K, Khatun M, Akter S, Ali L. Role of urinary albumin in the prediction of preeclampsia. Faridpur Med Coll J. 2011;6(1):14-8.

Narang S, Agarwal A, Das V, Pandey A, Agrawal S, Ali w, et al. Prediction of pre-eclampsia at 11-14 weeks of pregnancy using mean arterial pressure, uterine artery Doppler and pregnancy-associated plasma protein-A. Int J Reprod Contracept Obstet Gynecol. 2016;5(11):3948-53.

Ritukamra HD, Gupta KD, Natu SM. Role of Urinary calcium/creatinine ratio prediction of PIH. J Obset Gynecol India. 1997;47(4).

Rodriguez MH, Masaki DI, Mestman J, Kumar D, Rude R. Calcium/creatinine ratio and microalbuminuria in the prediction of pre-eclampsia. Am J Obstet Gynecol. 1988;159:1452-5.

El-Gharib MN, Morad. M Maternal serum inhibin-A for predicting preeclampsia. J Matern Fet Neonat Med. 2011;24(4):595-9.

Moslemi Zadeh N, Naghshvar F, Peyvandi S, Gheshlaghi P, Ehetshami S. PP13 and PAPP-A in the first and second trimesters: predictive factors for preeclampsia?. Int Schol Res Notice. 2012;2012.

Yu N, Cui H, Chen X, Chang Y. First trimester maternal serum analytes and second trimester uterine artery Doppler in the prediction of preeclampsia and fetal growth restriction. Taiwan J Obstet Gynecol. 2017;56(3):358-61.

Poon L, Kametas N, Bonino S, Vercellotti E, Nicolaides K. Urine albumin concentration and albumin-to-creatinine ratio at 11+0 to 13+6 weeks in the prediction of pre-eclampsia. BJOG. 2008;115:866-73.

Akolekar R, Syngelaki A, Sarquis R, Zvanca M, Nicolaides KH. Prediction of early, intermediate and late pre‐eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks. Prenat Diagn. 2011;31(1):66-74.

Sharma K, Singh R, Kumar M, Gupta U, Rohil V, Bhattacharjee J. First-trimester inflammatory markers for risk evaluation of pregnancy hypertension. J Obstet Gynecol India. 2018;68(1):27-32.

Salomon LJ, Benattar C, Audibert F, Fernandez H, Duyme M, Taieb J, et al. Severe preeclampsia is associated with high inhibin A levels and normal leptin levels at 7 to 13 weeks into pregnancy. Am J Obstet Gynecol. 2003;189:1517-22.

Gallo D, Poon LC, Fernandez M, Wright D, Nicolaides KH. Prediction of preeclampsia by mean arterial pressure at 11-13 and 20-24 weeks’ gestation. Fet Diagn Therap. 2014;36(1):28-37.

Jadli A, Ghosh K, Damania K, Satoskar P, Bansal V, Shetty S. Prediction of preeclampsia using combination of biomarkers at 18–23 weeks of gestation: A nested case-control study. Pregnanc Hypertens. 2019;17:20-7.

Gupta N, Gupta T, Asthana D. Prediction of preeclampsia in early pregnancy by estimating the spot urinary albumin/creatinine ratio. J Obstet Gynecol India. 2017;67(4):258-62.