|Year : 2020 | Volume
| Issue : 4 | Page : 325-330
CA125 levels in pregnancy: A case-control study amongst pregnant women in Aminu Kano teaching hospital, North-West Nigeria
Badia Maje Sayyadi1, Idris Usman Takai2, Saidu Adamu Ibrahim2, Kabiru Abdulsalam3, Usman Muhammad Ibrahim4
1 Department of Obstetrics and Gynaecology, Muhammad Abdullahi Wase Teaching Hospital, Kano, Nigeria
2 Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, College of Health Sciences, Bayero University, Kano, Nigeria
3 Department of Chemical Pathology and Immunology, Faculty of Clinical Sciences, College of Health Sciences, Bayero University, Kano, Nigeria
4 Department of Community Medicine, Aminu Kano Teaching Hospital, Kano, Nigeria
|Date of Submission||29-Jul-2020|
|Date of Decision||29-Aug-2020|
|Date of Acceptance||11-Sep-2020|
|Date of Web Publication||04-Nov-2020|
Dr. Idris Usman Takai
Department of Obstetrics and Gynaecology, Aminu Kano Teaching Hospital, Bayero University, Kano
Source of Support: None, Conflict of Interest: None
Background: Induction of inflammatory response within the placenta in patients with pre-eclampsia triggers the expression of CA125, thus making CA125 a potential marker reflecting the severity of preeclampsia. Objective: The study was aimed to assess and compare CA125 levels in pre-eclamptics and normotensives. Subjects and Methods: A case–control design was used to study 83 each of the selected pre-eclamptics and normotensives women using a systematic sampling technique. Data were collected using interviewer-administered questionnaire; blood and urine samples were also collected and analysed in the laboratory. Data were summarised using frequencies, percentages, mean ± standard deviation (SD) or median, and range as appropriate. Inferential statistical measures were used to determine the relationship between the outcome and independent variables with a P value set to be statistically significant at ≤0.05. Results: The ages of the pre-eclamptics and normotensives women were found to have a mean ± SD of 29.46 ± 6.92 and 29.70 ± 6.90 years, respectively. More than half 58 (69.9%) of the cases had proteinuria of 3+ (300 mg/dL). Significant difference was statistically (P < 0.01) found in mean serum CA125 levels between women with mild and severe pre-eclampsia with CA125 being more likely to be higher (>50 IU/mL) in severe pre-eclampsia than in mild pre-eclampsia. Conclusion: The study has shown that serum CA125 is elevated in pre-eclamptic pregnancies compared to normotensive pregnancies and the possibility of CA125 being a biomarker of severity and hence may provide information to make an informed choice in early-onset pre-eclampsia to consider conservative management and thus improve perinatal outcome.
Keywords: CA125, Kano, normotensive pregnancy, pre-eclampsia
|How to cite this article:|
Sayyadi BM, Takai IU, Ibrahim SA, Abdulsalam K, Ibrahim UM. CA125 levels in pregnancy: A case-control study amongst pregnant women in Aminu Kano teaching hospital, North-West Nigeria. Niger Postgrad Med J 2020;27:325-30
|How to cite this URL:|
Sayyadi BM, Takai IU, Ibrahim SA, Abdulsalam K, Ibrahim UM. CA125 levels in pregnancy: A case-control study amongst pregnant women in Aminu Kano teaching hospital, North-West Nigeria. Niger Postgrad Med J [serial online] 2020 [cited 2020 Nov 24];27:325-30. Available from: https://www.npmj.org/text.asp?2020/27/4/325/299912
| Introduction|| |
Pre-eclampsia being a multi-systemic disorder, contributes significantly to feto-maternal morbidity and mortality globally. The likelihood of having pre-eclampsia was reported to be 4.1% among primigravida with an increased likelihood of 7.1% in the subsequent pregnancies., Similarly, the likelihood was reported to increase to 14.7% in the subsequent pregnancy among women who had a history of pre-eclampsia in the first pregnancy, and many folds increase among women who had pre-eclampsia in the first and second pregnancies, respectively., The new reported cases of pre-eclampsia associated with childbirth before 34 weeks was 0.42% in the first delivery, 0.11% among women who have had previous childbirth with no history of pre-eclampsia, and 6.8% and 12.5% among women who were affected in one or two past pregnancies, respectively. The incidence of pre-eclampsia ranges from 3% to 7% for nullipara and 1%–3% for multipara. Mild pre-eclampsia occurs in approximately 15% of pregnancies and severe pre-eclampsia in about 1%–2%. In Nigeria, pre-eclampsia/eclampsia was found to contribute up to 54.4% of maternal mortality in Kano and 28.5% in another study, while a study in Ilorin recorded a mortality of 27.8%. Although maternal mortality is low in the United Kingdom, pre-eclampsia-eclampsia accounts for 10%–15% of maternal mortality.
Recent estimates reported that >63,000 women lose their lives yearly due to pre-eclampsia and its sequelae, and up to 98% were found to occur in developing countries., The pathological changes produces endothelial dysfunction which results in the clinical presentation among pre-eclamptics. CA -125 is a chemical marker, expressed by patients with ovarian cancers and benign pelvic conditions. Foetal contribution in the release of serum CA-125 during the first trimester of pregnancy, and other factors after delivery period is still unknown. Meta-analysis of nine studies which involved 977 women revealed significant differences among patients having pre-eclampsia compared with control (MD 15.86 IU/mL, 95% CI, 9.03-22.69). The study participants with severe pre-eclampsia were found to have significantly elevated levels of CA-125 in comparison with patients who had mild pre-eclampsia (MD 13.21 IU/mL, 95% confidence interval, 1.94–24.49) and meta-regression analysis found that gestational age of <34 weeks could affect the association positively. CA125 has been found to be a potential biomarker that can be used for diagnosis and follow-up in pre-eclampsia and correlates significantly with the degree of pre-eclampsia.
Simple, sensitive and specific investigations are needed that can be easily done in resources limited settings like ours to determine the need for early delivery as a result of high-risk pre-eclampsia, especially with the reported associated link between the serum levels of the biomarker and severity of pre-eclampsia. In this regard, serum levels of CA125 turn out to be a valuable parameter to evaluate those pregnancies that can be safely prolonged. This study, the first of its kind in northern Nigeria, was, therefore, conducted to assess and compare the levels of CA-125 among pregnant women with pre-eclampsia and normal pregnant women and also determine the relationship between pre-eclampsia and levels of CA-125.
| Subjects and Methods|| |
Case–control study was conducted at a tertiary hospital, Aminu Kano Teaching Hospital (AKTH) in Kano State, situated in Northern Nigeria that lies between latitude 12.000 N North and longitude 8.590 E East, to study all the normotensive and pre-eclamptic pregnant women attending antenatal clinic of the hospital at gestational age of >20 weeks. However, Pregnant women with history of chronic hypertension, multiple gestation, renal disease, chorioamnionitis, known history of ovarian disease, uterine fibroids coexisting with pregnancy, those with non-viable orin vitro fertilisation pregnancy and normotensive patients at recruitment who become hypertensives later were excluded from this study.
The Health and Research Ethics Committee of the study hospital (AKTH) provided ethical approval for conducting the study. The ethical clearance was obtained on 22nd December 2016, with ethical approval number NHREC/21/08/2008/AKTH/EC/1844. We obtained written informed consent from the study participants, and maintained the privacy of their laboratory results and responses, adhering to all the principles of research ethics. Data were collected from January 2017 to January 2018.
The sample size was determined using 99% confidence level, 1% precision and the values of Zα standing for the standard normal deviate equivalent to 1% level of significance = 2.58 (calculated using normal distribution table), Z1−β representing standard normal deviate which is equals to the power of 80% = 0.84 (calculated also using normal distribution table), ð1 and ð2 = standard deviation (SD) of CA125 level among patients with pre-eclampsia and normotensive women = 8.4 and 8.1 obtained from a previous study,, μ1andμ2 = The mean of CA125 among pre-eclamptic and normotensive women = 18.8 and 17.2 obtained from a previous study, and attrition rate of 10%. The minimum sample size of 75.4 was calculated. The sample size was increased to 83 in each of the two arms (cases and control) when the anticipated attrition rate of 8 was added to the calculated sample size of (75).
The average weekly number of pre-eclamptic and normotensive pregnant women seen in AKTH obtained from the hospital records unit were (100) and (400), respectively, making the sampling frame of the two groups of pregnant women. Systematic sampling technique was used to study eligible pregnant women. The sampling interval of normotensive pregnant women was obtained as the sampling frame divided by the sample size of normotensive pregnant women (400/83 = 5), which was found to be equals to 5. The first normotensive pregnant woman to be studied was obtained by balloting using number within the ranges of 1–5. Similarly, Sampling interval of pre-eclamptic pregnant women was obtained as the sampling frame divided by the sample size (100/83 = 1). The first respondent was obtained by simple balloting using numbers from 1 to 5 from which 4 was randomly selected for normotensive pregnant women. Therefore, the fourth pregnant woman was the first to be studied. Subsequent pregnant women were obtained by adding the sampling interval until the calculated sample size was obtained. Similarly, consecutive pre-eclamptics were studied until the calculated sample size was obtained.
Pre-eclamptics clients (cases) were selected based on inclusion criteria as they presented to the antenatal clinic until the required sample size was obtained. The other arm of the study consisting normotensive patients, were also recruited. Pre-eclamptics and normotensives were recruited based on two measurements of blood pressure at different times using appropriately sized cuffs for each patient's arm by the trained research assistants with an average of the two readings used for data analysis. The study objectives were explained to the study participants using simple language, and were asked to provide evidence of acceptance to participate based on the information given in writing.
Pre-eclampsia was defined as the onset at the age of pregnancy ≥20 weeks with 24-h proteinuria of ≥300 mg/day or, if not available, a protein concentration ranging from ≥30 mg (≥1 + on dipstick) in at least two random urine samples collected within 4–6 h but no more than 1 week apart, a systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg, measured two times, using a proper sized cuff, within 4–6 h but not up to 1 week apart, and resolution of all these conditions before 6th week after delivery., Severe pre-eclampsia was considered in a situation of uncontrolled elevated blood pressure greater than (160/110 mmHg) and any severe maternal or foetal complications. Early-onset PE occurs before 34 weeks of gestation and late-onset PE after 34 weeks of gestation.
An interviewer-administered pro forma consisting of four sections was used to obtain information. Section A elicited information on sociodemographic characteristics of the pregnant women, Section B found out the clinical characteristics, Section C was for laboratory results documentation while Section D for information regarding delivery. Patients found to have severe pre-eclampsia were appropriately managed according to the guideline of the department and adequately prepared for delivery. Intravenous access was secured and blood was drawn for estimation of serum CA125 and a urine samples was taken to assess for proteinuria.
Samples were taken by the researchers or by the research assistants at presentation before initiation of treatment. The venous blood samples were collected aseptically using a sterile disposable 5 ml syringe from a suitable vein on the patients' forearm or antecubital fossa. The puncture site was cleaned with ethanol and allowed to air dry and about 4 ml of blood withdrawn. Blood samples were taken similarly from the control group. The blood sample was then put into a labelled specimen bottle and kept to clot at room temperature. Samples drawn at night were kept at room temperature for analysis in the morning. The samples were run at 4000 revolutions every minute for a period of 10 min and then separated into a new container that was appropriately labelled, and the recommended 2010 instruments were used to quantify CA-125 levels.
The patient was also asked to void about 10–20 ml of urine into a clean wide bore well labelled container for urinalysis to detect proteinuria. Readings were reported in terms of negative, trace and 1+, 2+, 3+, and 4+ each corresponding to 30, 100, 300, or >2000 mg/dL, respectively, with values >1+ considered to be significant. Trace values were considered to be <30 mg/dL.
The data were analysed using Minitab 17 Computer Statistical Software (2010). State College, PA. Quantitative variables were summarised using appropriate measures of central tendencies and dispersion.
Accuracy of the CA125 screening test was defined as: Positive predictive value (the ratio of true positives to the sum of true positives and false positives), negative predictive value (The ratio of true negatives to the sum of true negatives to the false negatives), sensitivity (the ratio of true positives to the sum of true positives and false negatives) and specificity (the ratio of true negatives to the sum of true negatives to false positives).
CA125 levels of 50 IU/mL, the outcome variable was considered the cut-off point in screening for pre-eclampsia, while the independent variables were severity of pre-eclampsia, time of onset, study group among others. Student's t-test was used for quantitative variables where appropriate and normality was determined by plotting a histogram of the data and comparing it with that of normal probability curve and was found to have bell shape. The Chi-squared test or Fisher's exact test where appropriate were used for categorical data. Relationship between two quantitative variables was estimated using the Pearson's coefficient r, with a statistically significant relationship considered at P < 0.01.
| Results|| |
[Table 1] shows the sociodemographic and other characteristics of the study population. The age range of the study population is 17–42 years. The mean age of the pre-eclamptics and normotensives were 29.46 ± 6.92 and 29.65 ± 6.90 years, respectively. More than one quarter (34.9%) were >35 years compared to 36.1% of the controls. All of them were married. More than half 58 (69.9%) of the pre-eclamptics had proteinuria of 3+ (300 mg/dL) while none of the normotensives had proteinuria.
|Table 1: Sociodemographic, reproductive and clinical characteristics of study population|
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Higher levels were noted in the pre-eclamptics, with the mean serum CA125 level in the pre-eclamptics and normotensives was 41.23 ± 16.83 IU/mL and 13.02 ± 9.40 IU/mL, respectively. Statistically, significant difference was found (P < 0.01) between serum CA125 levels of pre-eclamptics and normotensives. More so, a significant difference (P < 0.01) with CA125 being more likely to be higher (>50 IU/mL) in severe pre-eclampsia than in mild pre-eclampsia as shown in [Table 2].
Thirty-two (38.6%) mothers had vaginal delivery and 51 (61.4%) had caesarean section among the pre-eclamptics. While in the normotensive group, 81 (97.6%) had vaginal delivery and 2 (2.4%) had Caesarean section, and there were 76 (91.6) live births and 7 (8.4%) stillbirths among the pre-eclamptics, with no stillbirths among the normotensives. In addition, statistically significant difference was found (P < 0.01) between the pre-eclamptics and normotensives with also a positive and significant correlation between CA125 and systolic blood pressure with systolic blood pressure increasing as CA125 levels increase and a negative and significant correlation between CA125 and birth weight; birth weight decreasing as CA125 levels increases as depicted in [Table 3]. Screening for CA125 has a specificity of 95.2%, as shown in [Table 4].
| Discussion|| |
The study investigated the possible presence of a relationship between CA125 levels and pre-eclampsia that would allow CA125 to be used to monitor pre-eclampsia and identify those patients at risk of progression and those of lower-risk, especially in early-onset pre-eclampsia that may benefit from expectant management to improve neonatal outcomes.
Significantly elevated levels of CA-125 was found among pre-eclamptics compared to their normotensive counterparts by our study, similar to the study conducted by Cebosay et al. in which pre-eclamptic/eclamptic women were identified to have significantly higher CA125 and C-reactive protein (CRP) than healthy pregnant women, with authors hypothesizing that CRP and CA125 were significant markers in pre-eclampsia. Other studies by Bhattacharya and Saha and Karaman E et al. also found a significant higher levels of serum CA125 among patients with mild, severe pre-eclamptics and eclamptics as compared to normal pregnancies.
Similarly, another study, in which the plasma CA125 levels of 50 pregnant women with pregnancy-related hypertensive diseases were compared with those of 50 controls with singleton pregnancies at term and 50 healthy controls that were not pregnant, CA125 levels where higher in the pregnant women compared to the non-pregnant controls showing a statistically significant difference, but showed no significant association between the hypertensive and normal pregnant women. This could be due to the fact that all hypertensive disorders were considered in their study and not only pre-eclampsia which shows a higher elevation of CA125 than hypertension without proteinuria. Even though Bon et al. also showed that though serum CA125 levels were higher during the first and last trimester of pregnancy, it showed no relationship with the pregnancy outcome, but in this study, relationship was found between the serum CA-125 levels and the outcome. In another study conducted in Lagos, in which 70 women who were diagnosed with pre-eclampsia and 70 controls matched for some characteristics at enrolment found elevated serum CA-125 in pre-eclamptics to be significantly higher than those with normal pregnancy, this is in keeping with the finding of our study. Though women in Lagos are presumably having different socio-cultural practices in pregnancy and possibly varying level of health seeking behaviour, this may however be explained by similar genetic makeup, with risk of pre-eclampsia being relatively similar in both Northern and Southern Nigeria.
The discrepancies between present findings and other available results may not be unconnected to the different methods of estimation of CA125, sample size and the differences that may be attributed to biological and other characteristics of the study participants. Another study also hypothesised that the elevation of CA125 in pre-eclampsia to be associated with the presence of ascites among pre-eclamptics that was linked to hypoalbuminaemia, as also agreed by other studies., CA125 levels were linked with severity of pre-eclampsia, and our findings agreed with the study by Karaman et al., where the CA125 levels among mild pre-eclampsia and severe pre-eclampsia were found to be higher. It was proposed that pre-eclampsia is related to decrease in trophoblastic movement into the maternal decidua, which results in chronic inflammation within the placenta, the process may therefore results in increased expression of CA125, thus, it can be proposed that, maternal serum CA125 levels may be higher in patients with severe pre-eclampsia.
Birth weights of babies whose mothers were pre-eclamptics were lower than those whose mothers were normotensives in our study, similar finding related to the birth weight and presence of pre-eclampsia was also observed by Karaman et al. Comparable to the findings in this study, there was also a poorer perinatal outcome in terms of special care baby unit admission and incidence of stillbirths among the cases in the study by Karaman et al., similarly, they reported the cesarean deliveries to be lower among the control group than the pre-eclamptics, this observation is similar to what was obtained in this study. No statistically significant difference (P = 1.000) in Apgar score was observed between the cases and controls in the current study, however this outcome has not been analysed in all the studies cited.
In this study, serum CA125 levels were found to have a positive correlation with systolic blood pressure, this is in keeping with what was reported by another study. This study found out that birth weight was negatively correlated with CA125 levels, which were similar to the correlation findings by Karaman et al. A significant relationship was also observed in the study by Bhattacharya and Saha with a positive correlation between systolic blood pressure and urine concentrations of protein and negative correlation with birth weight. Ozat et al. also found a positive correlation between CA125, systolic blood pressure and urine protein concentrations and negative correlation with birth weight. Therefore this study, similar to other studies, observed that CA125 level reflects the degree of the underlying pathological processes in pre-eclamptics, and CA-125 levels to correlates positively with systolic blood pressure and negatively with birth weight.
This study is limited by the fact that CA125 was measured at different gestational age; however, it is among the first research in Northern Nigeria that tried to assess the effect of CA125 in the pathogenesis of pre-eclampsia and can therefore serve as a foundation for future research.
| Conclusion and Recommendations|| |
The study has shown that serum CA125 is elevated in pre-eclamptic pregnancies compared to normotensive pregnancies, especially in cases of severe pre-eclampsia. It also highlights the possibility of CA125 as a biomarker of severity and hence may provide information to make an informed choice in early-onset pre-eclampsia to consider conservative management and thus improve perinatal outcome. Further studies in a larger population are therefore required to clarify the exact pathogenesis of elevation of CA125 levels and its relationship to prediction and severity of pre-eclampsia and possibly determine a cut-off value acceptable for conservative management in low resource settings that will also create a threshold to develop management guidelines.
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Conflicts of interest
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[Table 1], [Table 2], [Table 3], [Table 4]