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Predictive Role of First-Trimester ELABELA Levels for Late-Onset

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Predictive Role of First-Trimester ELABELA Levels for Late-Onset ORIGINAL ARTICLE Predictive Role of First-trimester ELABELA Levels for Late-onset Preeclampsia Gulten Ozgen1, Gultekin Adanas Aydin1 and Habibe Ayvaci2 1Department of Obstetrics and Gynecology, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey 2Department of Obstetrics and Gynecology, Zeynep Kamil Women and Children Disease Training and Research Hospital, Istanbul, Turkey ABSTRACT Objective: To determine the predictive role of first trimester maternal serum ELABELA (ELA) levels in late-onset preeclampsia (PE). Study Design: Comparative descriptive study. Place and Duration of Study: Department of Obstetrics and Gynecology, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey between January and September 2019. Methodology: A total of 600 pregnant women, whose maternal serum samples were collected through the first trimester screening test, were recruited. Twenty-three patients with late-onset PE group and 47 without PE group were included. All parti- cipants in whom maternal serum samples were collected between 11th and 14th weeks of pregnancy were followed until delivery. Results: Median ELA level was 654.53 [217.67-870.20] pg/mL in the PE group and 645.80 [367.25-1833.17] pg/mL in the control group, indicating no significant difference between the groups (p=0.408). There was a statistically significant difference between the two groups in terms of frequency of history of hypertension, intrauterine growth restriction (IUGR) and acute fetal distress (AFD), (p=0.003, p=0.016, and p=0.005, respectively). Three patients had preterm delivery in the PE group which was non-significant, while seven patients had gestational diabetes mellitus in PE group that was significantly higher compared to controls (p<0.001). Conclusion: Only ELA level in the first trimester of pregnancy may not be of much value in predicting late-onset PE. Key Words: ELABELA, Preeclampsia, Late-onset, Predictive marker. How to cite this article: Ozgen G, Aydin GA, Ayvaci H. Predictive Role of First-trimester ELABELA Levels for Late-onset Preeclampsia. J Coll Physicians Surg Pak 2021; 31(08):916-920. INTRODUCTION The placental hypoxia contributes to the formation of inade- quate syncytiotrophoblasts and results in downregulation of A successful pregnancy is defined as a healthy embryonic devel- syncytin-1 found in early-onset preeclampsia (PE) and intrau- opment and viable pregnancy with favourable maternal and terine growth restriction (IUGR). 2,3 fetal outcomes; and appropriate placental development is essential for a successful pregnancy.1 Placental perfusion is Preeclampsia is a pregnancy condition which accounts for 5-8% achieved by adequate remodelling of the spiral arteries of of all pregnancies and is associated with increased fetal and 4 uterus in early pregnancy, resulting in invasion of the extra-vil- maternal morbidity and mortality, if left untreated. Its aeti- loustrophoblasts.1 ology is multifactorial and environmental factors, health and disease status, maternal or fetal malnutrition, have been Reperfusion accompanied by placental hypoperfusion and mostly blamed.5 ischemic injury leads to the release of circulating antiangio- genic factors, which are associated with maternal vascular ELABELA (ELA) is a novel peptide which encodes an endogenous dysfunction. ligand for the apelin/AJP receptor, a member of Class A G-pro- tein coupled receptor family, which shares common features Correspondence to: Gulten Ozgen, Department of Obstet- with angiotensin receptor type 1 including regulation of blood rics and Gynecology, Bursa Yüksek Ihtisas Training and pressure, electrolyte balance, energy metabolism, inflamma- Research Hospital, Bursa, Turkey tory process, oxidative stress, vasodilation, vasoconstriction, E-mail: [email protected] cardiac contractility, and angiogenesis.6 It is expressed in ..................................................... human embryonic stem cells and has involvement in self-re- Received: December 23, 2021; Revised: April 07, 2021; newal and embryonic cell apoptosis.7 Although early studies Accepted: June 28, 2021 showed that ELA was involved in the placenta, kidney and pros- DOI: https://doi.org/10.29271/jcpsp.2021.08.916 tate tissue; however, recent studies have demonstrated that it 916 Journal of the College of Physicians and Surgeons Pakistan 2021, Vol. 31(08): 916-920 Gulten Ozgen, Gultekin Adanas Aydin and Habibe Ayvaci is additionally released in lungs and endothelia of the common uteroplacental dysfunction (IUGR and impaired Doppler velocit- vessels.8-10 ometry).4 Late-onset PE was defined as the presence of PE after 34 weeks of gestation. 14,15 Furthermore, apelin and ELA peptides have been recently investigated as predictors of PE in placenta and maternal circula- Maternal venous blood samples were obtained between 11th tion samples of PE patients and healthy controls. 11 In an animal and 14 thweeks of gestation and centrifuged at 4,000 rpm for 10 model, Ho et al. reported that decreased placental ELA level was minutes. Then, they were stored at °C-80 until analysis. a predictor of PE and maternal systemic vascular injury.12 The serum levels of ELA in duplicate were analysed using the However, Pritchardet al. measured placental messenger human ELA (ELA32 isoform) ELISA kit (Sunred Biological Tech- ribonucleic acid (mRNA) and circulating ELA in PE patients and nology, Shanghai, China). The serum ELA concentration of this healthy controls and found no significant correlation between assay ranges between 0.01 to 100 ng/mL. PE and ELA levels. 13 Statistical analysis was performed using the SPSS version 22.0 There are controversial results regarding the role of ELA, apelin (IBM Corp., Armonk, NY, USA). Shapiro-wilk test was used to or APJ in the literature. The aim of the present study was to determine the normality of distribution of variables. Descriptive investigate the predictive value of the first trimester maternal data were presented as mean ± standard deviation for normally th th serum ELA levels in late-onset PE. distributed variables and as median [IQR]: (25 -75 percentile)] for non-normally distributed ones. Categorical variables were METHODOLOGY shown in number and percentage. Student’s t-test was used for This prospective, case-control study was approved by the local variables showing normal distribution between the two groups Ethics Committee vide decision No. 2011-KAEK-25-2019/12-10 and the Mann-Whitney U-test was performed to compare non- and performed between January and September 2019. Anormally distributed variables between the two groups. Cate- written informed consent was obtained from each patient. The gorical variables were compared between the groups using the study was conducted in accordance with the principles of the Pearson Chi-square and Fisher’s Exact test. A p value of <0.05 Declaration of Helsinki. was considered statistically significant. A total of 600 singleton pregnant women with an age range of 18 RESULTS to 40 years, whose serum samples were collected for the first Late-onset PE developed in 23 (3.8%) of 600 patients. A total of th th trimester screening test (11 to 14 weeks), were screened.- 70 participants including 23 (32.9%) late-onset PE patients Women with multiple pregnancy, morbid obesity, malignancy, and 47 (67.1%) healthy pregnancy were included in this study. active labour, chorioamnionitis, systemic inflammatory condi- The mean age was 31.4 ± 6.6years in the PE group and 28.1 ± tions and non-steroidal anti-inflammatory drug use, severe 4.4 years in the control group. The median BMI was 30.12 liver and kidney failure were excluded from the study. Among [27.34-35.11] kg/m2 in the PE group and 28.51 [27.18-31.4] the patients with PE, only those with late-onset PE werekg/m2. A statistically significant difference was found between included. The control group consisted of healthy age- and body the two groups in terms of age (p=0.037). There was no statisti- mass index (BMI)-matched individuals. Finally, 23 patients with cally significant difference in the BMI values between the late-onset PE (PE group) and 47 without PE (control group) were groups (p=0.277). Demographic characteristics of the study included in the study. population are shown in Table I. Demographic and clinical characteristics of the participants The mean birth weight was 2910 [2680-3360] g in the PE group and perinatal and postnatal outcomes including age, height, and 3395 [3012.5-3600] g in the control group (p=0.002). The BMI, gravidity and parity, maternal height and weight, gesta- median ELA level was 654.53 [217.67-870.20] pg/mL in the PE tional age, birth weight, delivery mode, APGAR (Appearance, group and 645.80 [367.25-1833.17] pg/mL in control group, pulse, grimace, activity and respiration) score, adverse indicating no significant difference between the groups obstetric outcomes such as PE, gestational diabetes mellitus (p=0.408). Clinical characteristics of the study population are (GDM), preterm premature rupture of membranes (PPROM), also presented in Table I. There was a statistically significant IUGR, and preterm birth obtained using electronic medical difference between the two groups in terms of the frequency of records. hypertension, IUGR, and acute fetal distress (AFD), (p=0.003, The PE was diagnosed with the presence of the above, accom- p=0.016, and p=0.005, respectively). Three patients had panied by one of the followings; (1) new onset hypertension [at preterm delivery in the PE group, which was non-significant, least two high systolic (≥140mmHg) or diastolic (≥90 mmHg) while seven patients had GDM in the PE group that was signifi- blood pressure measurements at 4-hour intervals], (2) protein- cantly higher compared to the controls (p<0.001). A total of uria (≥300 mg/24 h, ≥30 mg/moL protein: creatinine ratio; or 87% cases in the PE group and 50% cases in the control group adipstick-test result ≥ 2+); (3) other maternal organ dysfunc- underwent caesarean-section delivery, indicating a statisti- tion (neurological complications such as eclampsia, stroke, cally significant difference between the groups (p=0.003, headaches, blindness, kidney or liver impairments); and (4) Table II).
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