Clinical Importance of Low Level of PAPP-A in First Trimester of Pregnancy - An Obstetrical Dilemma in Chromosomally Normal Fetus

Background: A variety of recent evidence exists about the clinical implication of low level of Pregnancy-associated plasma protein A (PAPP-A) in pregnancy. This glycoprotein is a protease, which releases the Insulin-like growth factor from IGFBP 4. Its role is a trophoblastic invasion of decidua, stimulation of cell mitosis and differentiation. It has an immunosuppressive effect in the placenta, inhibition of coagulation and complex role for integration of all these processes in the placenta. Level of PAPP-A (under 0.4 MoM-Multiple of Medians) in first-trimester screening in chromosomally and morphologically normal fetuses, could influence fetal weight, preeclampsia, premature birth and stillbirth. As a result of the complications mentioned above, there is implication on timing, mode of delivery and condition of the newborn.

Aim: The study aims to evaluate the influence of low PAPP-A, measured in the first trimester on the outcome of pregnancy, with accent disorders which are the result of placental insufficiency. Also, gestational week, mode of delivery and condition of newborn secondary underlying conditions will be evaluated.

Material and methods: After given information and consultation about the expectation from the screening, pregnant women with a singleton pregnancy were tested for First Trimester Screening to estimate the risk for Trisomy 21, 13, 18- the most frequent chromosomopathies. After exclusion of chromosomopathies and congenital malformations, one hundred and fourteen patients enrolled in the study. The target group (n = 64) with PAPP-A below 0.4 MoM and control group (n = 50) with PAPP-A equal and above 0.4 MoM. An assessment of mode and time of delivery and presence of small for gestational age newborns, preeclampsia, premature birth and newborn condition at delivery was made.

Results: The percentage of the patients delivered in term was similar between the target group (n = 64) and the control group (n = 50), 82.81% vs 82.0% respectively. The rate of cesarean section was 29.7 % in the target group vs 32% in the control group. A significant difference was found about elective vs urgent cesarean section in favour of the target group. The difference was present about the complication in pregnancy before delivery, 56% vs 22%, p = 0.023, which were the main indication for cesarean section. The difference in newborn outcome was not significant.

Conclusion: There is a difference in frequency of complications, in the cases with PAPP-A under 0.4 MoM, such as premature birth, preeclampsia compound with SGA fetuses versus the control group. The difference for SGA newborn and premature birth among the groups has statistical significance. The patients delivered with cesarean section were with the main indications SGA or elevated blood pressure, often occurred combined with prematurity. Apgar score and birth weight were similar in target and control group, but the newborns with a birth weight under 2500 g. were more frequent in the target group. Because these results did not show another significance among two groups, probably lower cut-off is needed, combining with another test (Doppler of uterine arteries in the first trimester, biochemical test). Presence of other diseases which could hurt placental function should be emphasised.