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.