Screening for Hypertensive Pregnancy Complications through Maternal Serum PAPP-A 5 and 10 Percentiles during the 11-14 Weeks Gestational Age Interval

VOICU DASCAU*, GHEORGHE FURAU, LUMINITA PILAT, CRISTINA ONEL, MARIA PUSCHITA Vasile Goldis Western University, Department of Obstetrics and Gynecology, 94 Revoluţiei 310025, Arad, Romania Vasile Goldis Western University, Department of Biochemistry, 94 Revolutiei Blvd., 310025 Arad, Romania Vasile Goldis Western University, Department of Internal Medicine, 94 Revoluţiei Blvd., 310025 Arad, Romania

Pregnancy-associated plasma protein-A (PAPP-A) is the largest of the pregnancy associated proteins produced by the syncytiocytotrophoblast [1]. This protein has several different functions, including preventing recognition of the fetus by the maternal immune system, matrix mineralization and angiogenesis1. The serum levels of PAPP-A rise from first detection in the first trimester until term [1].
Maternal serum concentrations are related to subsequent fetal growth and it can be used as a diagnostic test for adverse pregnancy outcomes, including intrauterine growth restriction, premature birth, preeclampsia, and stillbirth [1].
The plasmatic concentrations of PAPP-A are altered in pregnant patients who will develop preeclampsia (PE), the predictive value being high especially for the preterm type 2,3. The accuracy of PAPP-A is low for term PE, most probably because this type of PE is due to maternal cardiovascular disease and/or placental insufficiency at term4-6.
The value of MoM PAPP-A was statistically significantly decreased in the 224 pateients who developed PE in a study comprising 47994 pregnant women with the gestational age between 11 and 13 weeks7.
Another study on 3663 pregnant patients demonstrated that the ones with MoM PAPP-A below the 10th percentile had a relative risk for PE and preterm PE of 3.27 and 9.26, respectively, with the frequency thereof statistically significantly increased compared to the other patients in the study group8.
PAPP-A used separately or combined with uterine artery PI revealed higher AUC for preterm PE than for term PE9.

Materials and methods
The study included 128 pregnant patients with gestational ages between 11 weeks and 13 weeks+6 days, who were examined by ultrasound, including uterine artery Doppler, and who had the plasmatic concentration of PAPP-A determined. Plasmatic PAPP-A was determined with the ELISA Sunrise device, Tecan, Switzerland, and Pregnancy Associated Plasma Protein A reactant, MBS026323, MyBioSource, Inc., USA.

Results and discussions
The 128 in our study had a total of 16 pregnancies with different types of hypertensive complications (12.5%), the number and frequency thereof being detailed in table 1.  The demographics of the paients (total, with complications and with normal outcome) are shown in table 2; Student's t-test was used to compare mean values and standard deviations, while the statistical significance for differences in frequencies was assessed with the Chi-square test.
The 5 th and the 10 th percentile for MoM PAPP-A were 0.27 and 0.33, respectively.    Table 5 shows the detection rate of these complications for a false positive rate of 5% and 10%.   The prevalence of preeclampsia was 11.15% and PIH appeared in 2.34%. The detection rate for PE was 7.69% for all PE cases for both 5% and 10% FPR, with 0% for severe and 9.09% for mild PE for both FPR rates. The sensitivity and PPV were low, while the specificity and NPV were high.
The detection rate for PE, mild PE and severe PE was the same for MoM PAPP-A below the 5 th and the 10 th percentile, while PIH and all hypertensive complications had a higher detection rate for MoM PAPP-A below the 10 th percentile.
The only statistical significant differences between the patients with and without hypertensive complications were for the values of blood pressure, BMI, and for the personal history of chronic hypertension and any type of hypertension.
The prevalence of PE, the detection rate and the OR for PAPP-A below the 5 th percentile in several studies were: -prevalence 1.9%. detection rate 9.6%, with an OR of 2.0 10 -prevalence 1.5%. detection rate 23.1%, with an OR of 4.6 11 -prevalence 2.6%. detection rate 11.1%, with an OR of 2.1 12 -prevalence 3.7%. detection rate 10.6%, with an OR of 2.3 13 -prevalence 1.5%. detection rate 14.1%, with an OR of 2.8 14 -prevalence 0.5%. detection rate 14.6%, with an OR of 3.7 15 The values of MoM PAPP-A were 0,903 for PE and 0,837 for PIH in another study 16 .

Conclusions
Although the size of the population in our study was small, the results, including prevalence, OR and detection rate, are very similar to those in literature.
The detection rate for PIH and for all hypertensive complications of pregnancy is higher for values of MoM PAPP-A below the 10 th percentile compared to values thereof below the 5 th percentile, but the FPR is higher (10% versus 5%).