From biomarker to bedside? A critical commentary on ischemia-modified albumin in preeclampsiaDear Editor,
We read with interest the article by Zuhal et al.,(1) which compared serum ischemia-modified albumin (IMA) levels between preeclamptic and healthy pregnant women. The authors deserve credit for addressing a potential biomarker that may elucidate oxidative stress mechanisms in preeclampsia (PE). The observed increase in IMA levels among preeclamptic patients is consistent with established knowledge of oxidative imbalance in PE. However, the diagnostic performance reported (AUC: 0.690) was only moderate, and the lack of serum albumin measurements precluded calculation of the IMA/albumin ratio (IMAR), which prior studies suggest could improve diagnostic precision.(2,3)
Several investigations have demonstrated progressive rises in IMA from normal pregnancies to more severe forms of PE.(4-10) Elevated IMA has also been associated with hypertension, deranged hepatic enzymes, and adverse neonatal outcomes such as fetal growth restriction (FGR).(5,6) Teselkin et al. reported correlations between IMA and antioxidant status, reinforcing the oxidative stress link in PE.(4) Similarly, higher serum IMA levels were documented in preeclamptic women versus controls.(7-9) Further, D’Souza et al.(3) provided early evidence for salivary IMA and IMAR as useful in identifying PE severity. Notably, salivary IMAR distinguished controls from mild PE and correlated inversely with birthweight, raising the possibility of future non-invasive screening. Mokhtar et al.(5) showed significantly higher IMA levels in severe PE compared to mild cases and reported strong diagnostic accuracy (sensitivity 82.5%, specificity 77.5%, AUC 0.889). Conversely, Karaşin et al. (11) and Zuhal et al.(1) did not find significant differences between mild and severe PE, though both confirmed higher IMA in PE than in normotensive pregnancies. Karaşin et al. reported significant differences (p = 0.003 and 0.001) between PE groups and controls, but not between mild and severe PE (p = 0.191).(11)
Beyond diagnostic comparisons, other studies have highlighted IMA's broader clinical implications. Parasher et al.(12) demonstrated elevations of both IMA and neutrophil gelatinase–associated lipocalin (NGAL) in PE, implicating renal stress and endothelial dysfunction. Gupta et al.(13) reported positive correlations of IMA with creatinine, uric acid, and proteinuria, and negative correlations with bilirubin and albumin, supporting its role as an integrative marker of systemic stress. Jaiswar et al.(6) linked increased IMA with placental pathology and poor neonatal outcomes. Schoots et al.(7) found higher IMA in PE-related FGR compared to isolated FGR and controls, along with an inverse association with free thiols, suggesting IMA may differentiate oxidative pathways in FGR subtypes. Complementing maternal data, Ozmert et al.(10) reported elevated cord blood IMA in preterm infants of preeclamptic mothers, associated with inflammation and increased risk of small-for-gestational-age births.
Together, these findings underscore IMA's potential as a clinically relevant biomarker in PE. Nevertheless, variability in assay methods, study designs, and patient populations complicates interpretation. While most studies confirm elevated IMA in PE, discrepancies remain regarding its capacity to stratify disease severity. Correcting IMA for albumin (IMAR) appears promising, especially given links to fetal outcomes and its feasibility in saliva or cord blood. Future research should: (i) routinely assess IMAR alongside IMA; (ii) stratify findings by mild versus severe PE; (iii) investigate associations with maternal, fetal, and neonatal outcomes; (iv) incorporate longitudinal sampling across gestation; and (v) explore salivary and cord blood IMAR as non-invasive maternal and neonatal markers.(3,10)
To conclude, IMA is a promising yet complex biomarker of PE. Consistent elevations across studies highlight its link to oxidative stress, but its diagnostic accuracy varies. Incorporating IMAR, integrating IMA with angiogenic and inflammatory markers, and focusing on longitudinal outcome-linked analyses may enhance its value. Establishing standardized methodologies and robust clinical validation will determine whether IMA can be reliably implemented in obstetric practice.
References
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1 Zuhal D, Erbil Ç, Pınar K, Özcan E, Salim N, Nilüfer C, Gizem B. Comparison of serum ischemia modified albumin levels between preeclamptic and healthy pregnant women. Rev Bras Ginecol Obstet. 2025;46:e-rbgo97. doi: 10.61622/rbgo/2024rbgo97.
» https://doi.org/10.61622/rbgo/2024rbgo97 -
2 Afrose D, Chen H, Ranashinghe A, Liu CC, Henessy A, Hansbro PM, McClements L. The diagnostic potential of oxidative stress biomarkers for preeclampsia: systematic review and meta-analysis. Biol Sex Differ. 2022;13(1):26. doi: 10.1186/s13293-022-00436-0.
» https://doi.org/10.1186/s13293-022-00436-0 -
3 D'souza JM, Pai VR, Harish S, Shriyan C, D'souza N. IMA and IMAR in serum and saliva of preeclampsia--a preliminary study. Hypertens Pregnancy. 2014 Nov;33(4):440-8. doi: 10.3109/10641955.2014.931418.
» https://doi.org/10.3109/10641955.2014.931418 -
4 Teselkin YO, Babenkova IV, Lebedeva SY, Vykhristyuk YV, Shalina RI, Titov VY, et al. Ischemia-Modified Albumin and Antioxidant Capacity of Blood Serum in Normal Pregnancy and Preeclampsia. Bull Exp Biol Med. 2024 Nov;178(1):49-53. doi: 10.1007/s10517-024-06280-z.
» https://doi.org/10.1007/s10517-024-06280-z - 5 Mokhtar ER, Abd El-Hakam FA, Ebriheem EE, El Attar S, Hassan MM, Al Anany MG. Maternal serum perlecan and ischemia modified albumin levels as biomarkers of preeclampsia severity. Egypt J Immunol. 2022;29(3):64-79. PMID: 35758970.
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6 Jaiswar SP, Verma S, Agrawal M, Deo S, Goel M, Mahdi AA. Association of Maternal Serum Ischemia Modified Albumin (IMA) with placental histopathological changes and fetomaternal outcome: a prospective case control study in normotensive and pre-eclamptic women. J Obstet Gynaecol India. 2022;72(Suppl 1):166-73. doi: 10.1007/s13224-021-01614-7.
» https://doi.org/10.1007/s13224-021-01614-7 -
7 Schoots MH, Bourgonje MF, Bourgonje AR, Prins JR, van Hoorn EG, Abdulle AE, et al. Oxidative stress biomarkers in fetal growth restriction with and without preeclampsia. Placenta. 2021;115:87-96. doi: 10.1016/j.placenta.2021.09.013.
» https://doi.org/10.1016/j.placenta.2021.09.013 -
8 Dinc G, Karahan SC, Guven S. Maternal serum SCUBE-1: a novel ischemic marker in preeclampsia. J Pers Med. 2024;14(11):1102. doi: 10.3390/jpm14111102.
» https://doi.org/10.3390/jpm14111102 -
9 Taseer M, Shakeel N, Taseer M, Fawad, Rehman F; Durrira. Comparison of oxidative stress levels during the third Trimester in normal pregnancy and preeclampsia. J Ayub Med Coll Abbottabad. 2023;35(4):616-18. https://doi.org/10.55519/JAMC-04-12325
» https://doi.org/10.55519/JAMC-04-12325 -
10 Özdemir ÖM, Özdemir E, Enli Y, Öztekin Ö, Ergin H. Ischemia-modified albumin in preterm infants born to mothers with pre-eclampsia. Pediatr Int. 2018;60(6):553-59. doi: 10.1111/ped.13563.
» https://doi.org/10.1111/ped.13563 -
11 Karaşin SS, Çift T. The Role of ischemia-modified albumin as a biomarker in preeclampsia. Rev Bras Ginecol Obstet. 2020;42(3):133-39. doi: 10.1055/s-0040-1709662.
» https://doi.org/10.1055/s-0040-1709662 -
12 Parasher N, Kaushik P, Singh NK, Sweta, Yadav L, Bhurer Yadav B, Suri A. Association of neutrophil gelatinase associated lipocalin, ischemia modified albumin with uric acid in the etiopathogenesis of preeclampsia. Horm Mol Biol Clin Investig. 2022;44(1):39-43. doi: 10.1515/hmbci-2022-0012.
» https://doi.org/10.1515/hmbci-2022-0012 -
13 Gupta A, Jha PK, Aggarwal R, Ahirwar AK, Almeida EA, Kar R. Evaluation of diagnostic potential of maternal serum ischemia modified albumin in cases of pre-eclampsia. Horm Mol Biol Clin Investig. 2024;45(4):149-55. doi: 10.1515/hmbci-2024-0010.
» https://doi.org/10.1515/hmbci-2024-0010
