DISCUSSION
To our current knowledge, this is the first study in the literature to
evaluate fetal well being with IMA. IMA was first used in 2000 as a
finding in early diagnosis of myocardial ischemia (MI) (6-8). In this
regard, albumin cobalt binding (ACB) assay has been approved by Food and
Drug Administration as an early marker of acute coronary syndrome (ACS)
among low-risk patient groups (9). In addition to cardiac pathologies,
usage of IMA has been expanded over time including the assessment of
mesenteric ischemia (10), muscle ischemia (11), and peripheral vascular
events. Extended clinical applications soon emerged to cover diagnostic
workup for conditions such as hypercholesterolemia, type 2 diabetes
mellitus (DM), and pulmonary thromboembolism. Furthermore, studies have
been conducted to investigate effect of surgical interventions on IMA
(12,13).
Obstetricians could not remain unresponsive to the spectacular
introduction of IMA utilization into literature. Ischemia modified
albumin levels are higher in pregnant women compared to nonpregnant
women. Two theories are thought about it; These are the relative
intrauterine hypoxic environment in the early placentation stage and
reactive oxygen species formed due to increased oxygenation after the
first trimester (14).
Elevated IMA levels were demonstrated in women with recurrent pregnancy
loss (RPL), gestational DM, intrauterine growth retardation (IUGR), and
preeclampsia (15-18).
Poor placental perfusion characterizes preeclampsia because of vasospasm
of uterine spiral arteries, which forms hypoxia and oxidative stress
(19,20). Yet, the etiology is still unknown. Some theories that are
under consideration are abnormal trophoblast invasion, coagulation
abnormalities, vascular endothelial damage, cardiovascular
maladaptation, immunologic factors and genetic predisposition (21).
Evidence is accumulating that lipid peroxides and free radicals may be
important in the pathogenesis of preeclampsia. Superoxide ions may be
cytotoxic to the cell by changing the characteristics of the cellular
membrane and producing membrane lipid peroxidation (20,21). It formed
serum IMA in response to hypoxia or free radical injury to N terminus
(asp-ala-his-lys) of albumin. IMA is a marker of cardiac ischemia, but
IMA levels may be elevated in other conditions such as scleroderma, end
stage renal disease, vascular disorders, and any event that is
associated with hypoxia (8,9,22,23). In literature, Kagan et al showed
it. (24) for the first time that in preeclamptic pregnant women albumin
binding to cobalt and copper is corrupted. With these data, our
hypothesis in this study was to predict preeclampsia and fetal wellbeing
with the measurement of the IMA levels which increases in conditions
related to hypoxia.
Gafsou et al. (25) evaluated the serum IMA levels of 22 non-pregnant
women, 19 healthy pregnant women and 20 preeclamptic women. Just like
our study data, they found IMA was significantly higher in preeclamptic
patients and the elevated levels continue even after delivery. The
authors claimed IMA can be used as a marker in first trimester to
predict the patients who will develop preeclampsia. We can say that poor
placental perfusion may cause hypoxia and oxidative stress, which may
lead to preeclampsia and elevation of IMA levels.
In another study, it was found that ischemia modified albumin levels
measured at the 12th gestational week were higher in small gestational
age babies compared to babies with normal birth weight, and the authors
emphasized that this may be because of defective placentation (25-29).
Papageoghiour et al. (26) declared that IMA can be an early marker of
preeclampsia. At 11-12 weeks of gestation they measured the IMA levels
and conducted the women who developed preeclampsia. They found a
positive correlation with elevated IMA levels and preeclampsia.
Papageoghiour et al. stated that poor placental perfusion caused
hypoxia, which lead to pregnancy induced hypertension. Ustun Y et
al.(21) in his study observed that IMA had 80% sensitivity and 77.8%
specificity for preeclampsia.
Previously, an imbalance between oxidative stress markers and
antioxidant capacity has been shown in fetuses with IUGR resulting in
increased oxidative stress index (27). IMA, as a marker of oxidative
stress, has also been evaluated in two studies in IUGR fetuses. In
another study IMA in cord blood of IUGR fetuses with abnormal Doppler
indices (a decrease of >2 SD in middle cerebral artery
pulsatility indices or an elevation of >2 SD umbilical
artery pulsatility indices) performed in the last six hours prior to
delivery at between 33 and 41 weeks’ gestation, were found to be
significantly elevated and needed intensive care unit submission
compared to SGA fetuses with normal Doppler measurements (n = 20).
Besides, antioxidant markers were found to be significantly lower in
IUGR group.
The outcomes of our study showed a correlation between increased
systolic/diastolic umbilical artery flow, brain sparing impact, and
maternal IMA (18).
IMA has been also evaluated in cord blood of neonates from complicated
deliveries (28). The cord blood IMA levels in neonates from complicated
deliveries (n = 14) was significantly higher (50%) than cord blood from
uncomplicated deliveries (n = 12) classified by normal or low Apgar
scores.
Our study results showed the elevated levels of maternal IMA in
preeclampsia when compared to normotensive pregnant women. Also, when we
observe the outcomes of the study, we can tell that IMA may be a
predictive value for evaluating the fetal well being. Non-stress test,
umbilical artery doppler flow and middle cerebral artery doppler flow
are the methods to assess the fetal well being. The outcomes of our
study showed a correlation between elevated maternal IMA results and
poor NST, increased systolic/diastolic umbilical artery flow, brain
sparing impact and poor Apgar scores. When the cut-off value for IMA is
taken 18 IU/ml, sensitivity is 85.3%, specificity is 91% for fetal
well-being while positive predictive value is 70% and negative
predictive value is 96% for fetal wellbeing. We can claim that IMA is a
good predictive value for estimating fetal hypoxia.
In conclusion, the detected elevations in serum concentrations of IMA
propose that measurements of this biomarker may be useful in assessing
fetal hypoxia and predicting pregnancies which preeclampsia may develop.