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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 20  |  Issue : 3  |  Page : 294-298

Fetal hemoglobin as a predictor in cases of pre-eclampsia


1 Abo El Mahmoudya Hospital, El Behaira, Egypt
2 Department of Obstetricsï Gynecology, Faculty of Medicine, Alazhar University, Cairo, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Alazhar University, Cairo, Egypt

Date of Submission17-Jul-2020
Date of Decision05-Sep-2020
Date of Acceptance15-Oct-2020
Date of Web Publication11-Oct-2022

Correspondence Address:
BSc Ahmed M.A. Elrefaei
Department of Obstetrics and Gynecology, El Mahmoudya General Hospital, Alexandria University, El Behaira
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/azmj.azmj_113_20

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  Abstract 


Background and Aim Fetal hemoglobin (Hb) has been described as a new predictive biomarker for pre-eclampsia and has also been hypothesized to be a causative factor. Interestingly, the heme scavenger and antioxidant α-microglobulin increases in parallel with fetal Hb.
The aim was to measure the level of fetal Hb in the serum of pregnant women with pre-eclampsia.
Patients and methods This a prospective study that was conducted on 100 pregnant women selected from the Obstetrics and Gynecology Department of Al-Hussein University Hospital.
Results There was a significant increase in fetal Hb in the patient group more than the control group. The fetal Hb shows a high sensitivity, specificity, and accuracy in prediction of pre-eclampsia and eclampsia.
Conclusion Fetal Hb was significantly higher in patients with eclampisa and pre-eclampsia. Moreover, it can be used as a predictive marker for both eclampisa and pre-eclampsia.

Keywords: eclampsia, fetal hemoglobin, pre-eclampsia


How to cite this article:
Elrefaei AM, Zakarya AM, Abdel Motaal AO, Assem AA. Fetal hemoglobin as a predictor in cases of pre-eclampsia. Al-Azhar Assiut Med J 2022;20:294-8

How to cite this URL:
Elrefaei AM, Zakarya AM, Abdel Motaal AO, Assem AA. Fetal hemoglobin as a predictor in cases of pre-eclampsia. Al-Azhar Assiut Med J [serial online] 2022 [cited 2023 Jan 27];20:294-8. Available from: http://www.azmj.eg.net/text.asp?2022/20/3/294/358033




  Introduction Top


Pre-eclampsia and eclampsia are hypertensive disorders of pregnancy, and they are major causes of perinatal and maternal morbidity and mortality. These diseases affect between 3 and 5% of all pregnancies and account for more than 60 000 maternal and 500 000 fetal deaths per year worldwide [1].

Eclampsia is defined as pre-eclampsia accompanied by development of new-onset grand mal seizures or coma during pregnancy or the postpartum period, not attributable to other causes. Eclampsia can occur before, during, or after labor [2].

Eclampsia represents the consequence of brain injuries caused by pre-eclampsia. It is defined as pre-eclampsia with the abrupt development of seizures or coma during the gestational period or postpartum, nonattributable to other neurologic diseases that can justify the convulsive state (namely epilepsy or cerebral stroke) [3]. Eclampsia is the rarest and most severe of all the hypertensive disorders of pregnancy, with a high maternal and fetal mortality [1].

Fetal hemoglobin (Hb) is a new predictive biomarker for pre-eclampsia and has also been hypothesized to be a causative factor [4]. Interestingly, the heme scavenger and antioxidant α1-microglobulin increases in parallel with fetal Hb [5].

Vasoconstriction is caused by free HbF of the fetoplacental vasculature by binding nitric oxide and disrupting placental endothelial morphology. HbF levels in fetal blood warrant further investigation in normal and pathological pregnancies [6].

In pre-eclampsia, fetal Hb from fetal sources enters the maternal bloodstream and can be noticed in maternal serum. Moreover, factors derived from the placenta damage maternal blood cells, leading to the release of fetal Hb from erythrocytes [5].

The redox potential of free HbF is the cause of oxidative stress and damage of the placenta barrier [4],[7]. As a consequence, leakage of HbF into the maternal circulation has been reported as early as the first trimester in pregnant women who later develop PE [8]. Furthermore, in term pregnancies, the level of HbF in the maternal plasma correlates with the severity of the disease [9].

The aim of this study was to measure the level of fetal Hb in the serum of pregnant women with pre-eclampsia.


  Patients and methods Top


This is a prospective study that was conducted on 100 pregnant women selected from the Obstetrics and Gynecology Department of Al-Hussein University Hospital during the period from May 2018 to December 2018. They were classified into two equal groups. The study was approved by Ethics Committee of Faculty of Medicine, Al-Azhar University and conducted in accordance of Helsinki standards 2013.

Group A

Pregnant women with pre-eclampsia who were subjected to the determination of the level of fetal Hb in their sera.

Group B

Pregnant women with normal pregnancy as a control group who were subjected to the determination of the level of fetal Hb in their sera.

Inclusion criteria

Cases of pre-eclampsia (hypertension, proteinuria, and lower limb edema and fits) were included.

Exclusion criteria

Other causes of presence of fetal Hb in the mother’s sera were excluded from the study.

All patients was subjected to the following:

Complete medical history taking.

Clinical examinations

  1. Laboratory investigations:
  2. Complete blood picture.
  3. Urine analysis ‘for proteinuria’.


Kidney function tests including blood urea and serum creatinine.

Each woman in both groups was subjected to the determination of fetal Hb level in their sera by direct sampling from their veins once presented to the antenatal care clinic.


  Results Top


The age of group A ranged between 22 and 35 years, with a mean age of 29.38±3.26 years, whereas in group B, the age ranged between 20 and 34 years, with a mean age of 29.32±2.6 years. There was no statistical significant difference between both groups of the study regarding age. The BMI of group A ranged between 25.5 and 41.0 kg/m2, with a mean BMI of 28.68±2.68 kg/m2, whereas in group B, the BMI ranged between 26.1 and 38.9 kg/m2, with a mean value of 29.22±2.103 kg/m2. There was no statistically significant difference between the groups regarding BMI.

The liver function test showed that aspartate transaminase (AST) in group A ranged from 27 to 49 units/l, with a mean value of 37.42±5.296 units/l, and in group B ranged from 24 to 45 units/l, with a mean value of 33.94±5.297 units/l. Alanine aminotransferase (ALT) in group A ranged from 27 to 49 units/l, with a mean value of 39.56±4.900 units/l, and in group B ranged from 22 to 45 units/l, with a mean value of 34.02±6.659 units/l. There was no statistically significant difference between the two studied groups regarding AST and ALT.

The kidney function test showed that blood urea in group A ranged from 24 to 128 mmol/L, with a mean value of 55.34±15.427, and in group B ranged from 22 to 46, with a mean value 30±6.224.

Serum creatinine in group A ranged from 0.75 to 2.1 mg/dl, with a mean value of 1.2876±0.297 mg/dl, and in group B ranged from 0.325 to 1.1 mg/dl, with a mean value of 0.8025±0.213 mg/dl.

There was a statistically significant difference between the two studied groups regarding the maternal Hb level in group A, which ranged from 9.9 to 15, with a mean value of 12.05±1.215 g/dL, and in group B, which ranged from 10 to 15, with a mean value of 12.184±1.118. There was no statistically significant difference between the two studied groups regarding Hb concentration.

Elevated cases of fetal Hb were higher in group A (60%), whereas normal was higher in group B (70%). Fetal HB in group A ranged from 0.97 to 3.85, with a mean value of 2.09±0.71, whereas in group B, it ranged from 0.67 to 3.09, with a mean value of 1.57±0.727. There was a statistically significant difference between the two studied groups regarding fetal Hb (P<0.05).

Free cases were higher in group B, with 44 (88%), whereas pre-eclampsia cases were higher in group A, with 40 (80%). There was a statistically significant difference between the two studied groups regarding the net results of pregnancy women at end of follow-up (P<0.05). CS mode in group A was 41 (82%) and in group B was 34 (68%), whereas NVD mode was 9 (18%) and 16 (32%), respectively. There was no statistically significant difference between the two studied groups regarding the mode of delivery ([Table 1]).
Table 1 Comparison between the two studied groups regarding fetal hemoglobin level and the net results of pregnancy women at the end of follow-up

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There was a significant negative correlation between fetal Hb and AST, whereas there was a positive significant correlation between the fetal Hb and blood urea and serum creatinine. There was no significant relation between fetal Hb and ALT and maternal Hb concentration ([Table 2]).
Table 2 Correlation between fetal hemoglobin and different studied variables

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The cutoff value of fetal Hb to predict the pre-eclampsia was 2.00; the sensitivity at this point was 70.0%, specificity 65.0, total accuracy was 66.0, positive predictive value was 71.0%, and negative predictive value was 65.0%. The cutoff value of fetal Hb to predict the pre-eclampsia was 2.4.0; the sensitivity at this point was 88.0%, specificity 84.0, total accuracy 86.0, positive predictive value was 90.0%, and negative predictive value was 82.0% ([Table 3], [Figure 1]).
Table 3 Sensitivity, specificity, and accuracy of fetal hemoglobin in prediction of pre-eclampsia and eclampsia

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Figure 1 Receiver operating characteristic curve to predict the sensitivity, specificity, and accuracy of fetal hemoglobin in prediction of pre-eclampsia and eclampsia.

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  Discussion Top


Our results revealed no significant difference between both groups regarding age and BMI. Anderson et al. [8] and Abdelrahman et al. [10] found that there was no significant difference between both groups of their study regarding age and BMI.

There was no significant difference in AST and ALT liver enzymes in pre-eclampsia than in normal pregnancy. Peralta et al. [11] found no difference in levels of AST, ALT, and total bilirubin between women with pre-eclampsia and normal controls.

Ekun et al. [12], in contrast to our results, stated that there was a significant increase in the serum level of liver enzymes (AST and ALT) in cases of pre-eclampsia, which was in agreement with our results.

The difference in results between the study of Ekun et al. [12] and our own may be owing to differences in sample size and study patient populations.

Our results revealed that renal functions tests ‘serum urea and creatinine’ did not show significant difference between pre-eclampsia group and normal pregnant women. In addition to that, there was no significant difference between both groups regarding maternal Hb concentration.

Ekun et al. [12] found in their study that there was a significant increase in the serum blood urea and serum creatinine in cases of pre-eclampsia, which may be owing to decreased urinary clearance secondary to reduced glomerular filtration rate and increased reabsorption, and these findings were conflicting with our results.

Our study revealed that elevated fetal Hb was more in women with pre-eclampsia than in women with normal pregnancy significantly, and in addition to that, the development of complications in preeclamptic women was more than women with normal pregnancy in a significant manner.

Masoumi et al. [9] found in their study that fetal Hb was more in pre-eclampsia than in normal pregnant women, but there was no significant difference between both groups regarding the level of fetal Hb in sera of both groups, and this runs in line with our results.

Vijaya et al. [13] found in their study a significant relation between fetal Hb and development of pre-eclampsia, with a cut-off level 1.92 ng/ml, above which the pregnant women develop PE, which run in line with our results. Moreover, fetal Hb can be a causative factor for development of eclampsia in preeclamptic women, which was in agreement with our results.

Ali et al. [14] revealed in their study that fetal Hb was correlated with the severity of pre-eclampsia in preeclamptic women, which runs in line with our study.

In our results, on examining the correlation between fetal Hb and different studied variables, it was found that there was a significant negative correlation between fetal Hb and AST, whereas there was a positive significant correlation between the fetal Hb and blood urea and serum creatinine. There was no significant relation between fetal Hb and ALT and maternal Hb concentration.

In agreement with our study, Anderson et al. [15] found a significant correlation between fetal Hb and kidney function parameters, whereas there was no significant relation with maternal Hb.

In this study, the sensitivity, specificity, and accuracy of fetal Hb in the prediction of pre-eclampsia were assessed. The cutoff value of fetal Hb to predict the pre-eclampsia was 2.00, and the sensitivity at this point was 70.0%, specificity 65.0, total accuracy 66.0, positive predictive value was 71.0%, and negative predictive value was 65.0%.

In agreement with our study, Ali et al. [14] found that the fetal Hb level was higher in patients with pre-eclampsia. Severe pre-eclampsia cases showed higher level of fetal Hb when compared with mild pre-eclampsia cases. The mean value was 0.6, 1.7, and 2.7 gg/ml in the control, mild PE, and severe PE groups, with sensitivity of 82.5% and specificity of 85%. Fetal Hb level in the serum of maternal blood increased threefolds in patients with mild pre-eclampsia and more than fourfolds in patients with severe pre-eclampsia. So, HBF in our study was well correlated with the severity of PE.Our study was in line with Anderson et al. [16], who found that the mean value of fetal Hb was 5.6 g/ml in the control group and 10.1 g/ml in the pre-eclampsia group (twofold increase), with sensitivity of 65%. They also found that HBF level in early pregnancy in women who subsequently developed pre-eclampsia was elevated, so it can be used in prediction and early diagnosis of pre-eclampsia.

Results found by Inversetti et al. [17] were in agreement with this study. The concentration of fetal Hb in early pregnancy was significantly elevated in women who subsequently developed pre-eclampsia, with sensitivity of 69%.

In agreement with the present study, Anderson et al. [15] found that sensitivity of HBF in diagnosis of pre-eclampsia was 70%. They also reported that fetal Hb plays a central role in the pathophysiology of pre-eclampsia.

Olsson et al. [18] reported that the fetal Hb level in pre-eclampsia group (mean value 1.09 gg/ml) increased nine-folds compared with control group (mean value 0.126 gg/ml).

These variations in sensitivity may be owing to small size of sample in our study. Moreover, the gestational age at sampling was above 28 weeks (pre-eclampsia signs become well established and fetal Hb level increased). However, in the other studies, gestational age at sampling was early in the first trimester.


  Conclusion Top


Fetal Hb was significantly higher in eclampisa and preeclampsia patients. It can be used as a predictive marker of both eclampisa and pre-eclampsia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Roberts JM, Bell MJ. If we know so much about pre-eclampsia, why haven’t we cured the disease?. J Reprod Immunol 2013; 99:1–9.  Back to cited text no. 2
    
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Moussa HN, Arian SE, Sibai BM. Management of hypertensive disorders in pregnancy. Womens Health 2014; 10:385–404.  Back to cited text no. 3
    
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Hansson SR, Gram M, Akerstrom B. Fetal hemoglobin in preeclampsia: a new causative factor, a tool for prediction/diagnosis and a potential target for therapy. Curr Opin Obstet Gynecol 2013; 25:448–455.  Back to cited text no. 4
    
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Huppertz B. Maternal-fetal interactions, predictive markers for preeclampsia, and programming. J Reprod Immunol 2015; 108:26–32.  Back to cited text no. 5
    
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Brook A, Hansson S, Åkerström B, Schneider H, Lang I, Desoye G, et al. Free fetal hemoglobin elevates vascular tone in the fetoplacental circulation. J Placenta 2013; 6:121.  Back to cited text no. 6
    
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May K, Rosenlof L, Olsson MG, Centlow M, Morgelin M, Larsson I, et al. Perfusion of human placenta with hemoglobin introduces preeclampsia-like injuries that are prevented by alpha1-microglobulin. Placenta 2011; 32:323–332.  Back to cited text no. 7
    
8.
Anderson UD, Olsson M, Rutardóttir S, Centlow M, Kristensen KH, Isberg PE, et al. Fetal hemoglobin and a 1-microglobulin as first-and early second-trimester predictive biomarkers for preeclampsia. Am J Obstet Gynecol 2011; 204:520.  Back to cited text no. 8
    
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Masoumi Z, Familari M, Källén K, Ranstam J, Olofsson P, Hansson SR. Fetal hemoglobin in umbilical cord blood in preeclamptic and normotensive pregnancies: a cross-sectional comparative study. PLoS One 2017; 12: e0176697.  Back to cited text no. 9
    
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Abdelrahman TN, Youssry MA, Radwan AM, Ahmed A. Impact of intravenous infusion of labetalol combined with magnesium sulfate versus hydralazine combined with magnesium sulfate on fetomaternal hemodynamics in severe preeclampsia. Ain-Shams J Anesthesiol 2019; 11:5–13.  Back to cited text no. 10
    
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Peralta Pedro ML, Basavilvazo RM, Cruz Avalar A, Sanchez Ambroz S, Guzman A, Martinez G. Clinical significance of the laboratory determinations of preeclamptic patients. Ginecol Obstet Mex 2014; 72:57–62.  Back to cited text no. 11
    
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Ekun OA, Olawumi OM, Makwe CC, Ogidi NO. Biochemical assessment of renal and liver function among preeclamptics in Lagos Metropolis. Intl J Reprod Med 2018; 2018:1594182.  Back to cited text no. 12
    
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Vijaya S, Mahalakshmi M, Inbapriyanka I. Fetal haemoglobin and alpha 1 microglobulin as biochemical markers in predicting preeclampsia in late first trimester and early second trimester of pregnancy. Int J Reprod Contracept Obstet Gynecol 2018; 7:3226–3231.  Back to cited text no. 13
    
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Ali F, Gharieb A, El-hamamy N. The role of fetal hemoglobin in maternal blood in determining the severity of pre-eclampsia. Med J Cairo Univ 2018; 86:1883–1889.  Back to cited text no. 14
    
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Anderson UD, Olsson MG, Kristensen KH, Åkerström B, Hansson SR. Biochemical markers to predict preeclampsia. Placenta 2012; 33:S42–S47.  Back to cited text no. 15
    
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Anderson UD, Gram M, Ranstam J, Thilaganathan B, Kerström B, Hansson SR. Fetal hemoglobin, a 1-microglobulin and hemopexin are specific predictive first and second trimester biomarkers of preeclampsia. Placenta 2015; 6:103–109.  Back to cited text no. 16
    
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Inversetti A, Smid M, Candiani M, Ferrari M, Galbiati S. Predictive biomarkers of pre-eclampsia and effectiveness of preventative interventions for the disease. Expert Opin Biol Ther 2014; 14:1161–1173.  Back to cited text no. 17
    
18.
Olsson MG, Centlow M, Rutardóttir S, Stenfors I, Larsson J, Hosseini-Maaf B, et al. Increased levels of cell-free hemoglobin, oxidation markers, and the antioxidativeheme scavenger a 1-microglobulin in preeclampsia. Free Radic Biol Med 2010; 48:284–291.  Back to cited text no. 18
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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