Summary:
ABSTRACT
Aim of the study: Preeclampsia is a systematic disease of pregnancy
characterized by hypertension and proteinouria developing after the 20th week
of pregnancy. Several new studies have shown that the blood serum levels of
circulating NGAL are seriously altered in preeclamptic pregnancies and their
measurement in maternal serum may be useful in screening and/or diagnosis of
patients at high risk of developing preeclampsia.
The purposes of our study were initially to explore the levels and the possible
pathophysiological role of NGAL, MMP-9, their complex (MMP-9/NGAL), PLGF and
sFLT-1 in normal and preeclamptic pregnancies and then to evaluate their
significance as specific diagnostic markers in the prediction of the disease.
Patients and Methods: In 95 pregnant women [69 normal, 12 pregnancies that
developed preeclampsia and 14 with SGA (small for gestational age) fetuses] we
determined the serum concentrations of NGAL, MMP-9, MMP-9/NGAL complex, PLGF
and sFLT-1 in the first (11+1 to 13+6 weeks), second (20+1 to 24+0 weeks) and
third (28+1 – 34+0 weeks) trimester of pregnancy. Serum concentrations of NGAL,
MMP-9 and MMP-9/NGAL complex were determined with commercially available kits:
Human Lipocalin-2/NGAL Quantikine ELISA Kit, Human Matrix
Metalloproteinase-9/MMP-9 Quantikine ELISA Kit and Human MMP-9/NGAL Complex
Quantikine ELISA Kit, R&D SYSTEMS.
Results: Median serum concentrations (ng/ml) and interquartile range (IQR) of
NGAL in normal pregnancies were: 12.8 (8 - 21.1); 25.9 (14.7 – 34.6) and 48
(22.7 – 78.6) ng/mL in the three trimesters of pregnancy respectively. NGAL
serum concentrations (ng/ml) in pregnancies that developed preeclampsia were
significantly different from normal in the 1st and 2nd trimester but not in the
3rd [30.9 (21 – 52.3)/p=0,006; 44.6 (35.7 – 71.8)/p=0,015; 87.6 (43.5 – 115.6)/
p=0,174 in the three trimesters respectively]. On the contrary, MMP-9 and
MMP-9/NGAL complex serum concentrations in pregnancies that developed
preeclampsia didn’t differ significantly between normal and preeclamptic
pregnancies in any trimester. Additionally, women with SGA fetuses had no
significantly different NGAL, MMP-9 and MMP-9/NGAL complex serum concentrations
in any trimester compared to normal or pre-eclamptic pregnancies. Finally, PLGF
serum concentrations (pg/ml) were statistically different between normal and
preeclamptic pregnancies in the 2nd and in the 3rd (p=0.019 and p<0.001
respectively) but not in the 1st trimester, while those of sFLT-1 (pg/ml) were
different only in the 3rd trimester (p=0.011).
Conclusion: According to our findings serum concentrations of NGAL, MMP-9,
MMP-9/NGAL and PLGF in normal pregnancies were significantly different between
the 1st and the 3rd, trimester increasing as the pregnancy develops. In
pregnancies that developed preeclampsia, statistically significant difference
in NGAL, MMP-9, MMP-9/NGAL complex, PLGF and sFLT-1 serum concentrations was
found between 1st and 3rd trimesters. The most important finding of our study
is the fact that NGAL levels in pregnancies with preeclampsia were
significantly different than those in normal pregnancies in the 1st and 2nd but
not in the 3rd trimester (p=0,006 for 1st trim; p=0,015 for 2nd trim; p=0,174
for 3rd trim). Finally NGAL, MMP-9, MMP-9/NGAL complex and PLGF serum
concentrations in pregnancies that developed preeclampsia didn’t differ
significantly from concentrations in normal or pregnancies with SGA fetuses in
any trimester.
Keywords:
Preeclampsia, NGAL, MMP-9, PLGF, sFLt-1
