Arch Gynecol Obstet (2011) 284:587–591 DOI 10.1007/s00404-010-1728-2
MATERNO-FETAL MEDICINE
Iron status parameters in preeclamptic women Imran A. Siddiqui • Anila Jaleel • Hanan M. F. Al Kadri Waleed Al Saeed • Waleed Tamimi
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Received: 2 August 2010 / Accepted: 14 October 2010 / Published online: 28 October 2010 Ó Springer-Verlag 2010
Abstract Background Evidence of increased oxidative stress due to endothelial dysfunction in preeclampsia has been well established. Increase in the oxidative stress is catalyzed in the presence of free transitional metals. Therefore, the relationship of iron status with preeclampsia was under investigation. Objective The objective of the study was to compare red blood cell (RBC) count, hemoglobin (Hb) concentration, hematocrit (Hct), RBC indices, and iron status parameters in preeclamptic and healthy pregnant women. Method Blood samples were collected from 40 pregnant females diagnosed as preeclampsia and 80 normal pregnant females at the Department of Obstetrics and Gynecology at King Abdulaziz Medical City, Riyadh, Saudi Arabia between February 2009 and January 2010. We recorded RBC count, Hb concentration, Hct, RBC indices, serum iron and ferritin levels in both the groups.
I. A. Siddiqui (&) W. Tamimi College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, PO Box 22490, MC: 3127, Riyadh 11426, Kingdom of Saudi Arabia e-mail:
[email protected] A. Jaleel Department of Biochemistry, Ziauddin Medical University, Karachi, Pakistan H. M. F. A. Kadri Department of OB/GYN, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia W. A. Saeed W. Tamimi Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia
Result Mean serum iron in preeclampsia group was 23.48 ± 9.05, while 12.2 ± 5.21 in normal group (p \0.05). Similarly, mean serum ferritin concentration in preeclamptic and normal pregnant women were 32.56 ± 11.72 and 19.89 ± 8.86, respectively (p \ 0.05). No significant differences were found among RBC count, Hb concentration, Hct, and RBC indices in both the groups. Conclusion We recommend that any pregnant female with higher serum iron and ferritin concentrations should be further investigated for preeclampsia. Keywords
Preeclampsia Serum iron Serum ferritin
Introduction Hypertensive disorders complicating pregnancy are common. They are responsible for a large number of maternal deaths [1, 2]. The development of hypertension and proteinuria and/or edema induced by pregnancy after 20th week of gestation is described as preeclampsia and if convulsion or coma is added it is named as eclampsia. It is one of the components of the deadly triad along with hemorrhage and thromboembolism during pregnancy and found in 3–7% of pregnancies [3]. It is associated with increased maternal and fetal mortality and 18% of maternal deaths are attributed to preeclampsia [4]. Other major complications of preeclampsia are premature delivery resulting in the need of intensive care admissions for neonates, intracranial hemorrhage, acute tubular or cortical necrosis, heart failure, pulmonary edema, rupture of the liver, disseminated intravascular coagulopathy (DIC), hemolysis, increased liver enzymes and about 10% of preeclampsia and eclampsia develop HELLP syndrome [5]. Some risk factors for development of preeclampsia are also
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documented like nulliparity, age more than 40, AfricanAmerican race, positive family history of preeclampsia, chronic hypertension, chronic renal failure, diabetes mellitus and multiple gestation [6]. Preeclampsia is best described as blood pressure C140/90 mmHg after 20th week of gestation and proteinuria C300 mg/24 h urine or C2? dipstick [7]. However, why pregnancy incites or aggravates hypertensive vascular disease remains unsolved. Despite decades of intensive research, these disorders remain among the most important unsolved problems in obstetrics but evidence points to the placenta as a key source of factors that lead to the maternal endothelial cell dysfunction in preeclampsia because the clinical signs and lesions of preeclampsia remit after delivery, implicating the placenta as a main culprit in the disease [8, 9]. The disease can occur in anembryonic pregnancy, suggesting that the presence of a fetus is not strictly necessary. In rare cases of extrauterine (abdominal) pregnancy, in which delivery of the fetus is not followed by delivery of the placenta, the signs of preeclampsia persist postpartum until the placenta is resorbed [10]. An initiating event in preeclampsia has been postulated to be the reduced placental perfusion that leads to widespread dysfunction of the maternal vascular endothelium by mechanisms that are not well defined [11]. With increasing gestational age, hypoxic environment of placenta changes into oxygen rich environment, leading to the production of reactive oxygen species (ROS). These ROS initiate the cellular damage including destruction of RBCs in the presence of transitional metals like iron [12, 13]. Disturbances in iron parameters and hematological abnormalities have been reported by some other investigators [14, 15]. Despite extensive literature on the pathogenesis of preeclampsia, only few studies have investigated the relationship of hematological and iron parameters in preeclampsia. We designed this study with the objective to compare RBC count, Hb concentration, Hct, RBC indices and iron status parameters in preeclamptic and healthy pregnant women.
Method This is a case–control study. The research protocol was first submitted to the King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia which reviewed the scientific aspects of the protocol and then sent to the Institutional Review Board (IRB) to review the ethical aspects of the protocol. Upon the recommendations of the Research Committee, the IRB granted the permission to conduct this study. The study population comprised of 120 pregnant females, selected from women attending the Obstetrics and Gynecology
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Department of King Saud Bin Abdulaziz University for health science at King Abdulaziz Medical City, Riyadh, Saudi Arabia between February 2009 and January 2010. Among 120 pregnant females, 40 were eligible cases who were singleton pregnancies in late second or third-trimester with the diagnosis of preeclampsia according to the criteria for the definition of preeclampsia given by the International Society for the Study of Hypertension in Pregnancy [16]. Preeclampsia was diagnosed in previously normotensive women with two repeat (at least 4 h apart) diastolic blood pressure measurements of 90 mmHg or greater after the 20th week of gestation, plus proteinuria of more than 300 mg in 24 h as measured quantitatively or C2? protein with dipstick and 80 were nonpreeclamptic and otherwise healthy pregnant females. Women in labor, multiple pregnancies, known hypertensive or any concurrent medical complications before or developing during pregnancy, such as diabetes mellitus or inflammatory diseases, were not considered eligible for the study. The control group comprised pregnant women matched by gestational age with the preeclamptic women, followed up at our setting exclusion criteria. No cases or controls received vitamin or iron supplements or aspirin in the month before enrollment. We explained about the study to those pregnant females who agreed to participate in the study and were asked to sign the informed consent form and then 10 ml of venous blood was drawn from the antecubital vein, after proper aseptic precautions. Hematological parameters including the RBC count, Hb concentration, hematocrit, red cell width, RBC indices [mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC)] were estimated using Abbot CELL-DYNE Sapphire. Iron parameters including serum iron and ferritin concentrations were recorded using Arhitect ci 8200-Abbott.
Statistical analysis Data was analyzed using SPSS for Windows (version 15.0, SPSS Inc., Chicago, IL, USA). The data is presented descriptively, providing number of women, mean values and standard deviations. The differences between preeclamptic cases and normal pregnant women were investigated using t test for continuous data.
Results All included cases and controls were Saudi nationals. The age of the studied pregnant females ranged between 16 and 42 years. The mean age of cases, i.e., preeclamptic and controls, i.e., normal pregnant women showed no statistical
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Table 1 Physical characteristics of the preeclampsia and normal pregnant groups Preeclampsia (n = 40) Mean ± SD Age (years) 2
29 ± 6.1
Normal (n = 80) Mean ± SD 29.5 ± 6.0
p value 0.95
BMI (kg/m )
32.11 ± 6.28
31.1 ± 5.20
0.38
SBP (mmHg) DBP (mmHg)
143.1 ± 7.8 94.3 ± 4.9
125.1 ± 19.6 78 ± 13.3
\0.05* \0.05*
SD standard deviation, BMI body mass index, SBP systolic blood pressure, DBP diastolic blood pressure * Significant difference at p \ 0.05 Table 2 Comparison of age, RBC count, hemoglobin, hematocrit, RBC indices, iron and ferritin between the preeclampsia and normal pregnant groups Preeclampsia (n = 40) Mean ± SD RBC count (1012/l) Hemoglobin (g/l)
Normal (n = 80) Mean ± SD
p value
4.20 ± 0.5
4.09 ± 0.4
0.26
117.52 ± 15.41
116.38 ± 17.42
0.71
Hematocrit (%)
34.14 ± 0.04
34.22 ± 0.04
0.96
MCV (fl)
81.85 ± 8.12
84.19 ± 12.03
0.21
MCH (pg)
serum ferritin and AST in the preeclamptic group (r = 0.39, p = 0.06).
28.35 ± 3.12
28.48 ± 4.39
0.78
MCHC (g/l)
344.93 ± 11.23
340.65 ± 26.69
0.22
Iron (lmol/l)
23.48 ± 9.05
12.2 ± 5.21
\0.05*
Ferritin ( g/l)
32.56 ± 11.72
19.89 ± 8.86
\0.05*
SD standard deviation, MCV mean corpuscular volume, MCH mean corpuscular hemoglobin, MCHC mean corpuscular hemoglobin concentration * Significant difference at p \ 0.05
difference (p = 0.95). Similarly, body mass index (BMI) of preeclamptic and normal pregnant group also showed no statistical difference (p = 0.38). There were significant statistical differences (p \ 0.05) in the mean values of systolic blood pressure (SBP) and diastolic blood pressure between two groups (Table 1). Mean serum iron concentrations in preeclamptic and control normal pregnant women were 23.48 ± 9.05 and 12.2 ± 5.21, respectively. Similarly, mean serum ferritin concentration in preeclamptic and normal pregnant women were 32.56 ± 11.72 and 19.89 ± 8.86, respectively. There were significantly high serum iron (p \ 0.05) and serum ferritin concentration (p \ 0.05) in the preeclamptic group than in the normal pregnant women. No significant differences were observed in other hematological parameters including hematocrit, MCV, mean corpuscular hemoglobin (MCH), and MCHC (Table 2). No significant correlation was found between serum iron and AST (r = 0.27, p = 0.23) in the preeclamptic group. Similarly, no significant correlation was found between
Discussion Some evidences suggest that the RBC count, hematocrit and hemoglobin concentrations are higher in preeclamptic women than the normal pregnant women [17]. In our study we did not find any significant differences in RBC count, hemoglobin, and hematocrit concentrations when we compared these parameters among preeclamptic and normal pregnant women. These findings were also reported by Makuyana et al. [18] who also did not observed significant differences in the hematological parameters including RBC count, hemoglobin, and hematocrit concentration in 38 preeclamptic patients and 72 normal pregnant women. Hershkovitz et al. [19] also reported same observations among 21 preeclamptic and 19 normotensive pregnant females. In the same study they also measured serum erythropoietin concentrations in both groups. Though they noted the presence of higher serum erythropoietin levels in preeclamptic women, but did not reach to the statistically significant level when compared with that of normotensive pregnant women. Gamzu et al. [20] also reported the similar findings when they studied 25 preeclamptic and 25 normal pregnant women. Although there are some evidences which on the contrary suggest that complete blood count parameters are higher in preeclamptic women [21, 22]. They are advocating their results on the basis of the increased maternal blood levels of erythropoietin in preeclampsia due to decreased perfusion to the kidneys and/or hemolysis during this condition [23]. On the other hand findings of Conrad and Benyo [24] for the presence of erythropoietin receptors in placental tissue suggest that increased maternal erythropoietin levels in women with preeclampsia is a result of placental function and not of decreased renal perfusion and/or hemolysis. In addition, we did not find any significant differences in the RBC indices including MCV, MCH, and MCHC among two studied groups. In this study, serum iron levels were found to be significantly higher in preeclamptic women than in the normal pregnant women. This finding on serum iron is in agreement of previous studies [12, 25–27]. Furthermore, we find no significant correlation between serum iron levels with AST levels which reflect that the raised iron levels cannot be explained by liver damage which was also reported by some previous authors [25, 27]. Previous studies have come to different conclusions about raise in serum ferritin levels in preeclampsia [25, 27]. In our study, we found significant higher serum ferritin levels in preeclamptic women than those in the normal
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pregnant females. Rayman et al. [28] reported similar findings when they compared 40 preeclamptic women with matched pregnant control subjects. Taheripanah and Farkush [29] studied 33 preeclamptic women and 33 normal pregnant females to compare iron status parameters including serum ferritin levels. Our findings are also in agreement with the results of their study. Serum ferritin is also considered as an acute phase reactant [30, 31]. We analyzed the serum ferritin levels against the AST levels of preeclamptic group and we found no significant correlation between these two parameters. This suggests that acute phase response is not the principal cause of the raised ferritin levels in preeclamptic group, reinforcing previous findings [28, 32]. The results of this study should be viewed while considering its limitations. One limitation is the smaller number of recruited pregnant females with preeclampsia which might affect the power of the study, although we recruited normal pregnant females as a control twice than the cases in order to minimize this effect. The other limitation is the absence of the information on other parameters of body iron status like total iron binding capacity (TIBC), transferring saturation and apotransferrin which might be more helpful in corroborating our findings.
Conclusion In conclusion, our results indicate that higher serum iron and ferritin are associated with the preeclampsia than those of uncomplicated normal pregnancy. Whether serum iron and ferritin levels can serve as useful markers or play an important role in the pathogenesis in preeclampsia awaits further investigation. Acknowledgments This study was supported by the grant from the King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. We are thankful for Dr. Amir Omair for his helpful discussion of this manuscript. Conflict of interest
We declare that we have no conflict of interest.
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