Maternal heart examination in pregnancy affected by low PAPP-A MoM in the first trimester

Introduction
Pregnancy-associated plasma protein A (PAPP-A) protease is known for its role as a key regulator of insulin-like growth factors and hence of foetal development. With the present study we intend to investigate its role in the maternal haemodynamic adaptation to the state of pregnancy.

Material and methods
We selected 18 patients referred to our unit between February 2017 and July 2017, of whom 10 showed low PAPP-A values at the first trimester screening for chromosomal anomalies. Each patient had 3 serial echocardiographic evaluations at the 13th, 24th, and 33rd week of pregnancy. On the basis of the plasma values of PAPP-A, the patients were divided into cases (n = 10) and controls (n = 8), where cases had a mean PAPP-A concentration of 0.345 with a standard deviation of 0.086, while the controls were characterised by a mean PAPP-A concentration of 1.380 with a standard deviation of 0.613. The main outcome measures were peripheral vascular resistance (PVR), cardiac output (CO), systolic excursion of the tricuspid ring (TAPSE), and E/E’ ratio. Systolic and diastolic arterial blood pressure and heart rate (HR) were measured at each visit. Mono- and bidimensional, Doppler, and TDI images were acquired and analysed blindly by a single sonographer.

Results
A slight increase in heart rate (HR, + 12%, p < 0.05) was observed in the control group at the 33rd week visit, while there was no change in the group with low levels of PAPP-A. Cardiac output and PVR also changed in the high-value PAPP-A group (ANOVA for repeated measures, p < 0.05), while they remained unchanged in the group with low PAPP-A values. It was observed that in the case group, the lower the PAPP-A values, the lower the extent of the haemodynamic adjustment in terms of PVR drop and increase in CO. A lack of physiological adaptation to pregnancy was also observed in the systolic function of the right ventricle. Women with normal PAPP-A showed a slight reduction (t test, p < 0.05) of TAPSE, while in women with low PAPP-A no change was observed. The E/E’ ratio was significantly increased in the control group at the last two visits (p < 0.005 and p < 0.05, respectively).

Conclusions
This study shows that the physiological haemodynamic adaptation and the morphofunctional changes in the heart are incomplete in women with low PAPP-A levels, creating a favourable substrate for the development of preeclampsia. The assay of PAPP-A in the first trimester can therefore be used as a screening method to select at-risk pregnancies, with the aim of creating a specific path and a closer follow-up.