Serum Beclin-1 Levels in Patients With Preeclampsia: a Case Control Study

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Beclin-1 is a protein that regulates this process and is used as a marker of this process in tissues. We evaluated the serum beclin-1 levels in pregnancies complicated by preeclampsia. Methods 41 women with preeclampsia and 47 women with uncomplicated pregnancies were enrolled in the study. Maternal serum levels of beclin-1 were measured by using enzyme-linked immunosorbent assay kit (ELISA). Demographic data and several other parameters were also recorded and analyzed. Results Mean serum beclin-1 levels were lower in patients with preeclampsia and this difference was statistically significant (6.32±.65 vs 4.05±.67, p<0.05). Urea and creatinine levels were significantly higher in patients with preeclampsia (p<0.005). Beclin-1 levels were found as statistically different in early and late preeclampsia groups as well, again revealing lower mean beclin-1 levels in preeclamptic patients (p: 0.000, p: 0.000 respectively) Conclusions To the best of our knowledge, this study is the first to investigate the serum beclin-1 levels in patients with preeclampsia and demonstrated the altered serum beclin-1 levels in preeclamptic patients. This finding suggests that serum beclin-1 levels also reflect the altered autophagy process in preeclampsia and can be utilized as a clinical tool. Autophagy Creatinine Preeclampsia Serum Obstetrics INTRODUCTION Autophagy is an intracellular catabolic degradation process that involves the digestion of damaged or dysfunctional cellular components, aggregated proteins and cytoplasmic macromolecules through fusion with lysosomes 1 . This digestion process ultimately generates micro molecules to be recycled into the cytosol 2 . Also known as auto phagocytosis, autophagy has a crucial role in cellular physiology, including the maintenance of cellular homeostasis during proliferation, differentiation and cell death as well as cellular survival during nutrient starvation or the blockage of metabolism in the cell 3 . Autophagy is a catabolic mechanism and the abnormalities in autophagy processes are suggested to be involved in autoimmune and inflammatory diseases, as well as cancer 4 , 5 . Preeclampsia refers to the new onset of hypertension and proteinuria or the new onset of hypertension and significant end-organ dysfunction with or without proteinuria after 20 weeks of gestation or postpartum in a previously normotensive woman 6 , 7 . It is considered as one of the most important global maternal health problems and significantly affects maternal mortality and morbidity 8 . The pathogenesis of preeclampsia is still unclear. However, it is widely suggested that placentation is a major contributor to the development of the disease. 9 Although often accompanied by new-onset proteinuria, hypertension and other signs or symptoms of preeclampsia may present in the absence of proteinuria 10 . It has been reported that autophagy is impacted in placenta-related obstetrical diseases such as preeclampsia and intrauterine growth retardation, although the mechanisms are still unclear. It is suggested that autophagy protects the trophoblasts in placenta from apoptosis which is induced by hypoxia or nutritional deprivation 11 . In particular, abnormal autophagic mechanisms prevent trophoblast invasion and inhibit trophoblast functions 12 . Autophagy biomarkers, including Beclin-1 were observed in trophoblastic tissues and maternal decidual stroma cells in pregnancy 13 . The impairment of autophagic activity in villous trophoblasts from patients with preeclampsia and FGR has been shown with immunohistochemistry in previous studies 14 , 15 . 11 different proteins involved in autophagy processes in mammals have been identified so far. Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3) are the most studied autophagy proteins in mammals. Autophagosomes are structures that enable autophagic reactions to take place safely inside the cell by wrapping the cell debris that is the target of autophagy with a membrane. Beclin-1, together with the Bcl-2 protein family, is a protein that regulates autophagosome formation via phosphatidylinositol-3 phosphate. The pro-autophagic activity of beclin-1 is directly inhibited by its binding to Bcl-2, an anti-apoptotic protein. In stress exposure, beclin-1 and Bcl-2 connectivity is disrupted and autophagy is induced. However, there are cases where beclin-1 inhibits apoptosis by mitochondrial membrane stabilization 16 , 17 . Autophagy is a process that is mostly studied at tissue level. However, autophagy markers have also been studied in serum. Serum beclin-1 levels were investigated in patients with chronic obstructive pulmonary disease and diabetic nephropathy, and statistically significant correlations were found between the progression of the disease and serum levels 18 , 19 . Both studies revealed decreased serum levels with increased severity of the disease. In this study, we aimed to evaluate the serum beclin-1 levels in pregnancies complicated by preeclampsia. METHODS This cross-sectional study was conducted among pregnant women who received antenatal care and were delivered at a single tertiary center between January 2019 and January 2020. The ethics committee of our hospital approved the study. The informed consent was given to all participants before their enrollment into this study. Study group consisted of women with pregnancies complicated by preeclampsia. Diagnostic criteria for preeclampsia includes new onset of hypertension and proteinuria or the new onset of hypertension and significant end-organ dysfunction with or without proteinuria after 20 weeks of gestation or postpartum in a previously normotensive patient. Hypertension in pregnancy is defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg on at least 2 occasions at least 4 hours apart. 6 Diagnostic criteria for end-organ damage includes the following: Proteinuria ≥ 0.3 g in a 24-hour urine specimen or protein/creatinine ratio ≥ 0.3 (mg/mg) (30 mg/mmol) in a random urine specimen or dipstick ≥ 2 + if a quantitative measurement is unavailable, platelet count 1.1 mg/dL (97.2 micromol/L) or doubling of the creatinine concentration in the absence of other renal disease, liver transaminases at least twice the upper limit of the normal concentrations for the local laboratory, pulmonary edema, new-onset and persistent headache not accounted for by alternative diagnoses and not responding to usual doses of analgesics and visual symptoms (eg, blurred vision, flashing lights or sparks, scotomata). Preeclampsia with severe features is diagnosed based on systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 110 mmHg on 2 occasions at least 4 hours apart (unless antihypertensive therapy is initiated before this time) or with presence of criteria for end-organ damage. Chronic hypertension in pregnant women was defined as systolic BP above 140 mm Hg or diastolic BP above 90 mm Hg that was present prior to pregnancy or before 20 weeks’ gestation 6 . Patients with preeclampsia were further divided into two groups based on their time of diagnosis either before or after 34 gestational weeks, as having early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE). The normotensive control group consisted of singleton pregnancies without hypertension. Gestational age was based on the precise date of the last menstrual period and an ultrasound measurement of the crown-rump length (CRL) in the first trimester with appropriate adjustments 20 . Exclusion criteria were as follows: Multiple pregnancies, pregnancies with fetal anomalies, pregnancies with a known chronic disease, premature rupture of membranes, chorioamnionitis, diabetes mellitus, chronic hypertension and gestational diabetes. The venous blood samples were obtained from pre-eclamptic and normotensive women at admittance to the hospital before administration of any medication and the onset of labor. For beclin-1, blood samples were collected in tubes containing heparin. Serum samples were removed by centrifugation for 10 min at 3000 x rpm. The samples were maintained at -80°C before performing assays. Samples were thawed and commercially available elisa kits for Human beclin-1 (MyBiosource Inc., Catalog No MBS732891, SanDiego, USA) were used for the quantitative measurement in serum samples. In summary, samples and standards were introduced into wells pre-coated with Anti-Human monoclonal antibody before undergoing incubation. Subsequently, Biotin was applied to all wells, followed by another incubation. The removal of uncombined enzyme was achieved through washing steps. Chromogen Solution A and B were then added, causing the liquid to change color to blue. Finally, under the influence of acid, the color transformed into yellow. The optical density was measured at 450 nm using a standard automated plate reader (Thermo Scientific Microplate Reader, USA). The detection range of beclin-1 was between 0.1–10 ng/ml. Analyses were performed using the statistical package for the social sciences (SPSS) software version 20.0 (Chicago, IL, USA). The Kolmogorov–Smirnov test was used to assess the normality of the distribution of variables. Using the independent samples t-test, we compared the variables with normal distributions and data was presented as mean ± standard deviation. Continuous variables in more than two groups were analyzed by using either the Kruskal–Wallis test or ANOVA and were represented as median and interquartile range (IQR) or mean ± standard deviation, respectively. Spearman’s rank correlation coefficient was performed to calculate correlations between continuous variables. A two-tailed p-value of less than .05 was considered statistically significant. RESULTS A total number of 88 pregnant women, 47 with normal pregnancy and 41 with preeclampsia were included in this study. The demographic data and the biochemical parameters are summarized in Table 1. There were no significant differences in terms of maternal age, gravidity and parity between the preeclamptic patients and the control group. Mean gestational age at delivery was significantly lower in the preeclampsia group (p:0.003). Mean BMI was also significantly different between the groups, as the patients with preeclampsia had an higher average value of BMI (p:0.032). Mean serum beclin-1 levels were lower in patients with preeclampsia and this difference was statistically significant ( 6.32±.65 vs 4.05±.67, p<0.05) . Among other serum parameters, urea and creatinine levels were significantly higher in patients with preeclampsia (p<0.005). Correlation analysis revealed that serum beclin-1 levels were negatively correlated with mean gestational week and serum urea levels. Preeclamptic patients were grouped as diagnosed with early or late preeclampsia. Comparison of these groups did not reveal a significant difference in mean beclin-1 levels. When the control group was compared to early and late preeclampsia patients separately, mean Bbeclin-1 levels were found as statistically different in both groups, again revealing lower mean beclin-1 levels in preeclamptic patients (p: 0.000, p: 0.000 respectively) (Table 2). DISCUSSION To the best of our knowledge, this study is the first to investigate the serum beclin-1 levels in patients with preeclampsia. Our results demonstrated significantly lower mean serum beclin-1 levels in preeclamptic pregnant patients compared to patients with uncomplicated pregnancies. In addition, serum beclin-1 levels were negatively correlated with mean gestational week at delivery. Preeclampsia patients were grouped as diagnosed with early onset and late onset preeclampsia and comparison of both groups to control group also revealed significantly lower beclin-1 levels. Mean beclin-1 levels between early onset and late onset preeclamptic patients did not yield any statistically significant difference. This finding supports the association of lower serum beclin-1 levels with preeclampsia diagnosis and excludes the significance of gestational week on beclin-1 levels in preeclamptic patients. Autophagy and its involvement in placentation has been an area of interest in research in the recent years. It is demonstrated that autophagy is essential in early placentation 21 . Beclin-1’s possible role in preeclampsia was evaluated in previous studies which investigated the autophagy process in placenta. Most of the studies point out an altered process in autophagy which can be related to development of preeclampsia. Akcora Yildiz et al. demonstrated significant increase in protein levels of both beclin-1 and SQSTM1/p62 in preeclamptic placentas 22 . Similarly, Gao et al. revealed that the expression of beclin-1 was significantly increased in placentas from pregnancies complicated by early-onset preeclampsia 15 . Another study of Oh et al. showed an elevated protein expression of LC3-II in the placentas from patients with severe preeclampsia, suggesting an altered response in autophagy pathway. However, the expression of beclin 1 protein was found to be unchanged 23 . In contrary, Zhang et al. demonstrated that autophagy proteins including beclin 1 and LC3II/LC3I were decreased in preeclamptic placentas 24 . Beclin-1 was studied as a serum marker in numerous studies focused on a variety of diseases. Schlemmer et al. investigated serum beclin-1 level and its association with chronic obstructive pulmonary disease (COPD). Results of this study demonstrated a significant decrease in serum Beclin-1 protein level, in smokers and even more in COPD patients compared to healthy controls which supported the theoretical association of altered autophagy pathways in pathogenesis of COPD 19 . Naguib et al. investigated serum level of beclin-1 in diabetic kidney disease (DKD). Results were significant with lower beclin-1 levels in DKD patients compared to controls 18 . Another recent study by Kubicka-Trazaska et al. evaluated the serum autophagy markers including Beclin-1 and mTOR in patients with exudative age-related macular degeneration AMD and the results demonstrated significantly decreased serum beclin-1 levels in patients with AMD 25 . In addition, Lu et al. demonstrated that mean serum beclin-1 levels were significantly lower in patients with borderline ovarian tumors and ovarian cancer, compared to healthy individuals, suggesting the altered autophagy response in ovarian tumors 26 . Our study demonstrated the altered serum beclin-1 levels in preeclamptic patients. With the previous data suggesting the altered mechanism of autophagy in preeclamptic patients, this finding suggests that serum beclin-1 levels also reflect the impact on autophagy and can be utilized as a clinical tool. As we mentioned above, histopathologic studies reveal conflicting results in levels expression of beclin-1 in placental tissues when compared to healthy individuals. But it is important to emphasize that all studies demonstrate significantly different levels of expressions in preeclamptic patients. We believe further studies should focus on the predictive value of serum beclin-1 levels for preeclampsia diagnosis in a bigger patient population. Declarations Ethics approval and consent to participate Informed consent of the participants were obtained. This study was approved by the Ege University School of Medicine Ethics Committee. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analysed during the current study are not publicly available due to absence of resources to provide a publicly available link on a server but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests Funding Not applicable Authors' contributions M.I. developed the hypothesis, wrote the main text H.E. assisted in data collection F.O. assisted in data analysis I.H. assisted in sample collection A.O.Y. assisted in data analysis and reviewed the manuscript Acknowledgements None References Lieberthal W. Macroautophagy: a mechanism for mediating cell death or for promoting cell survival? Kidney Int . Sep 2008;74(5):555-7. doi:10.1038/ki.2008.325 Rogov V, Dotsch V, Johansen T, Kirkin V. Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol Cell . Jan 23 2014;53(2):167-78. doi:10.1016/j.molcel.2013.12.014 He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet . 2009;43:67-93. doi:10.1146/annurev-genet-102808-114910 Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature . Jan 20 2011;469(7330):323-35. doi:10.1038/nature09782 Mathew R, Karantza-Wadsworth V, White E. Role of autophagy in cancer. Nat Rev Cancer . Dec 2007;7(12):961-7. doi:10.1038/nrc2254 Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol . Jun 2020;135(6):e237-e260. doi:10.1097/AOG.0000000000003891 Payne B, Magee LA, von Dadelszen P. Assessment, surveillance and prognosis in pre-eclampsia. Best Pract Res Clin Obstet Gynaecol . Aug 2011;25(4):449-62. doi:10.1016/j.bpobgyn.2011.02.003 Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet . Aug 21 2010;376(9741):631-44. doi:10.1016/S0140-6736(10)60279-6 Pennington KA, Schlitt JM, Jackson DL, Schulz LC, Schust DJ. Preeclampsia: multiple approaches for a multifactorial disease. Dis Model Mech . Jan 2012;5(1):9-18. doi:10.1242/dmm.008516 Homer CS, Brown MA, Mangos G, Davis GK. Non-proteinuric pre-eclampsia: a novel risk indicator in women with gestational hypertension. J Hypertens . Feb 2008;26(2):295-302. doi:10.1097/HJH.0b013e3282f1a953 Hung TH, Hsieh TT, Chen SF, Li MJ, Yeh YL. Autophagy in the human placenta throughout gestation. PLoS One . 2013;8(12):e83475. doi:10.1371/journal.pone.0083475 Gong JS, Kim GJ. The role of autophagy in the placenta as a regulator of cell death. Clin Exp Reprod Med . Sep 2014;41(3):97-107. doi:10.5653/cerm.2014.41.3.97 Chifenti B, Locci MT, Lazzeri G, et al. Autophagy-related protein LC3 and Beclin-1 in the first trimester of pregnancy. Clin Exp Reprod Med . Mar 2013;40(1):33-7. doi:10.5653/cerm.2013.40.1.33 Hung TH, Chen SF, Lo LM, Li MJ, Yeh YL, Hsieh TT. Increased autophagy in placentas of intrauterine growth-restricted pregnancies. PLoS One . 2012;7(7):e40957. doi:10.1371/journal.pone.0040957 Gao L, Qi HB, Kamana KC, Zhang XM, Zhang H, Baker PN. Excessive autophagy induces the failure of trophoblast invasion and vasculature: possible relevance to the pathogenesis of preeclampsia. J Hypertens . Jan 2015;33(1):106-17. doi:10.1097/HJH.0000000000000366 Marino G, Niso-Santano M, Baehrecke EH, Kroemer G. Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol . Feb 2014;15(2):81-94. doi:10.1038/nrm3735 Mukhopadhyay S, Panda PK, Sinha N, Das DN, Bhutia SK. Autophagy and apoptosis: where do they meet? Apoptosis . Apr 2014;19(4):555-66. doi:10.1007/s10495-014-0967-2 Naguib M, Rashed LA. Serum level of the autophagy biomarker Beclin-1 in patients with diabetic kidney disease. Diabetes Res Clin Pract . Sep 2018;143:56-61. doi:10.1016/j.diabres.2018.06.022 Schlemmer F, Boyer L, Soumagne T, et al. Beclin1 circulating levels and accelerated aging markers in COPD. Cell Death Dis . Feb 5 2018;9(2):156. doi:10.1038/s41419-017-0178-1 Committee on Practice B-O, the American Institute of Ultrasound in M. Practice Bulletin No. 175: Ultrasound in Pregnancy. Obstet Gynecol . Dec 2016;128(6):e241-e256. doi:10.1097/AOG.0000000000001815 Nakashima A, Yamanaka-Tatematsu M, Fujita N, et al. Impaired autophagy by soluble endoglin, under physiological hypoxia in early pregnant period, is involved in poor placentation in preeclampsia. Autophagy . Mar 2013;9(3):303-16. doi:10.4161/auto.22927 Akcora Yildiz D, Irtegun Kandemir S, Agacayak E, Deveci E. Evaluation of protein levels of autophagy markers (Beclin 1 and SQSTM1/p62) and phosphorylation of cyclin E in the placenta of women with preeclampsia. Cell Mol Biol (Noisy-le-grand) . Dec 30 2017;63(12):51-55. doi:10.14715/cmb/2017.63.12.12 Oh SY, Choi SJ, Kim KH, Cho EY, Kim JH, Roh CR. Autophagy-related proteins, LC3 and Beclin-1, in placentas from pregnancies complicated by preeclampsia. Reprod Sci . Nov 2008;15(9):912-20. doi:10.1177/1933719108319159 Zhang Y, Hu X, Gao G, Wang Y, Chen P, Ye Y. Autophagy protects against oxidized low density lipoprotein-mediated inflammation associated with preeclampsia. Placenta . Dec 2016;48:136-143. doi:10.1016/j.placenta.2016.09.015 Kubicka-Trzaska A, Zuber-Laskawiec K, Plutecka H, Romanowska-Dixon B, Sanak M, Karska-Basta I. Altered serum levels of autophagy proteins Beclin-1 and mTOR in patients with exudative age-related macular degeneration. J Physiol Pharmacol . Feb 2021;72(1)doi:10.26402/jpp.2021.1.09 Lu H, Hu H, Li S. Diagnostic value of beclin-1 and mTOR in ovarian cancer. Int J Clin Exp Pathol . 2021;14(2):238-246. Tables Table I . The demographic data and biochemical parameters of the study groups. Control (n:47 ) Preeclampsia(n:41 ) P value Maternal Age (years) 27.02±5.99 28.61±5.22 .201 BMI † (kg/m 2 ) 30.96±4.86 33.83±6.08 .032 Gravidity 2.30 1.536 2.33±1.493 .927 Parity 0.81± 1.09 1.13± 1.28 .235 Gestational Age at Delivery 37.61±3.27 35.21±3.77 .003 Infant weight (g) 3102.61± 653.33 2527.89±894.99 .001 APGAR 1 st min 7.63±1.12 7.61±1.09 .996 APGAR 5 th min 8.97±0.99 8.78±0.87 .502 Systolic BP (mmHg) 109.25±9.43 156.34±21.83 .002 Diastolic BP (mmHg) 66.35±7.73 99.12±15.56 .002 Beclin (ng/ml) 6.32± .65 4.05±.67 .000 Platelet (/mcl) 218.785±67.64 218.179±65.57 .967 WBC ‡ (/mm3) 9754.69±2607.36 10729.23±2856.03 .112 Urea (mg/dl) 14.04±4.41 19.89±8.92 .000 Creatinine (mg/dl) 0.51±0.11 0.58±0.15 . 034 ALT (IU/L) 12.54±8.07 13.00±7.49 .795 AST (IU/L) 18.04±10.52 20.94±8.6 .181 † Body Mass Index, ‡ White Blood Cells, § Alanine Amino Transferase, ¶ Aspartate Amino Transferase Table 2 The demographic data and biochemical parameters of the control group and patients with early and late preeclampsia Control (n:47 ) Early-Onset Preeclampsia (EOPE † ) (n:14 ) Late -Onset Preeclampsia (LOPE‡) (n:27 ) p Control vs EOPE † p Control vs LOPE ‡ p EOPE † vs LOPE ‡ Maternal Age (years) 27.0222±5.99048 30.25±5.08 27.88±5.21 .088 .535 .197 BMI § (kg/m 2 ) 30.9669±4.86398 32.66±4.62 34.34±6.51 . 268 .027 .454 Gravidity 2.30 1.536 2.50±1.38 2.26±1.55 .490 .910 .648 Parity 0.81± 1.09 1.25± 1.42 1.07± 1.23 .255 .361 .698 Gestational Age at Delivery 37.61±3.27 30.72±4.02 37.03±1.42 . 000 .387 . 000 Infant weight (g) 3102.61± 653.33 1477.27± 691.73 2955.92± 546.46 . 000 .336 .000 APGAR 1 st min 7.63±1.12 6 7.71±1.04 .122 .808 .428 APGAR 5 th min 8.97±0.99 7 8.88±0.78 .088 .759 .032 Systolic BP (mmHg) 109.25±9.43 157.05±16.58 155.76±25.2 .002 .002 .427 Diastolic BP (mmHg) 66.35±7.73 98.22±12.46 100.12±19.23 .002 .002 .572 Beclin (ng/ml) 6.32± .65 4.05± .65 4.05±.67 .000 .000 .975 Platelet (/mcl) 218.785±67.64 218.666±51.87 227.29±69.74 .236 .616 .454 WBC ¶ (/mm3) 9754.69±2607.36 111168.33± 3765.79 10534.23± 2406.94 .293 .216 .332 Urea (mg/dl) 14.04±4.41 24.91±13.01 17.66±5.29 .002 .003 .017 Creatinine (mg/dl) 0.51±0.11 0.62±0.24 0.56±0.09 .045 .049 .266 ALT †† (IU/L) 12.54±8.07 16.33±8.41 11.51±6.69 .583 .583 .063 AST ‡‡ (IU/L) 18.04±10.52 21.41±7.12 20.74±9.35 .283 .283 .825 † Early Onset Preeclampsia; ‡ Late Onset Preeclampsia; § Body Mass Index, ¶ : White Blood Cells, †† Alanine Amino Transferase, ‡‡ Aspartate Amino Transferase Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3870756","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":269736713,"identity":"5f2aa937-f2e9-486a-b217-3a2f253b8b1a","order_by":0,"name":"Metehan Imamoglu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYDCCAzCSvQFIG1gQqeUAiOQBsQwkSNEikQDiEqGF7/bpxMcfKu7Im0s+v7rhR4EEA397dwJeLZLncjcbHDjzzHDn7Jyymz1Ah0mcObsBrxaDM7zbJA62HWbccDsn7QYPUIuBRC5BLdt/HPx32H7DzTNpN/8QqWUbw8GGw4kbbrAfu02ULZJneDdLnDl2OHnDmRy22zIGEjwE/cJ3hnfjh4qaw7Ybjh9/dvPNHxs5/vZe/FqQAI8BmCRWOQiwPyBF9SgYBaNgFIwgAADrJ1Qp97kFYQAAAABJRU5ErkJggg==","orcid":"","institution":"Bridgeport Hospital / Yale New Haven Health","correspondingAuthor":true,"prefix":"","firstName":"Metehan","middleName":"","lastName":"Imamoglu","suffix":""},{"id":269736714,"identity":"9d807651-ba77-4a2d-a16a-ebfc67e67ccb","order_by":1,"name":"Huseyin Ekici","email":"","orcid":"","institution":"Ondokuz Mayıs University","correspondingAuthor":false,"prefix":"","firstName":"Huseyin","middleName":"","lastName":"Ekici","suffix":""},{"id":269736715,"identity":"cdf88321-8666-4e54-a0cf-179d232ba4c8","order_by":2,"name":"Firat Okmen","email":"","orcid":"","institution":"Buca State Hospital","correspondingAuthor":false,"prefix":"","firstName":"Firat","middleName":"","lastName":"Okmen","suffix":""},{"id":269736716,"identity":"da009223-09b7-4a67-a57f-3385f0707298","order_by":3,"name":"Ismet Hortu","email":"","orcid":"","institution":"Ege University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ismet","middleName":"","lastName":"Hortu","suffix":""},{"id":269736717,"identity":"1fb71f77-9946-4045-b16c-3017bc84ec1f","order_by":4,"name":"Ahmet Ozgur Yeniel","email":"","orcid":"","institution":"Ege University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"Ozgur","lastName":"Yeniel","suffix":""}],"badges":[],"createdAt":"2024-01-16 19:14:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3870756/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3870756/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51351418,"identity":"e9771046-286c-4257-aa69-90239304e1e2","added_by":"auto","created_at":"2024-02-20 05:25:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":284972,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3870756/v1/52300548-785c-4d87-bfb6-910a23ce62e3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eSerum Beclin-1 Levels in Patients With Preeclampsia: a Case Control Study\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAutophagy is an intracellular catabolic degradation process that involves the digestion of damaged or dysfunctional cellular components, aggregated proteins and cytoplasmic macromolecules through fusion with lysosomes \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. This digestion process ultimately generates micro molecules to be recycled into the cytosol \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Also known as auto phagocytosis, autophagy has a crucial role in cellular physiology, including the maintenance of cellular homeostasis during proliferation, differentiation and cell death as well as cellular survival during nutrient starvation or the blockage of metabolism in the cell \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Autophagy is a catabolic mechanism and the abnormalities in autophagy processes are suggested to be involved in autoimmune and inflammatory diseases, as well as cancer\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePreeclampsia refers to the new onset of hypertension and proteinuria \u003cb\u003eor\u003c/b\u003e the new onset of hypertension and significant end-organ dysfunction with or without proteinuria after 20 weeks of gestation or postpartum in a previously normotensive woman \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. It is considered as one of the most important global maternal health problems and significantly affects maternal mortality and morbidity \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. The pathogenesis of preeclampsia is still unclear. However, it is widely suggested that placentation is a major contributor to the development of the disease.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Although often accompanied by new-onset proteinuria, hypertension and other signs or symptoms of preeclampsia may present in the absence of proteinuria\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt has been reported that autophagy is impacted in placenta-related obstetrical diseases such as preeclampsia and intrauterine growth retardation, although the mechanisms are still unclear. It is suggested that autophagy protects the trophoblasts in placenta from apoptosis which is induced by hypoxia or nutritional deprivation \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. In particular, abnormal autophagic mechanisms prevent trophoblast invasion and inhibit trophoblast functions \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Autophagy biomarkers, including Beclin-1 were observed in trophoblastic tissues and maternal decidual stroma cells in pregnancy \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. The impairment of autophagic activity in villous trophoblasts from patients with preeclampsia and FGR has been shown with immunohistochemistry in previous studies \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e .\u003c/p\u003e \u003cp\u003e11 different proteins involved in autophagy processes in mammals have been identified so far. Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3) are the most studied autophagy proteins in mammals. Autophagosomes are structures that enable autophagic reactions to take place safely inside the cell by wrapping the cell debris that is the target of autophagy with a membrane. Beclin-1, together with the Bcl-2 protein family, is a protein that regulates autophagosome formation via phosphatidylinositol-3 phosphate. The pro-autophagic activity of beclin-1 is directly inhibited by its binding to Bcl-2, an anti-apoptotic protein. In stress exposure, beclin-1 and Bcl-2 connectivity is disrupted and autophagy is induced. However, there are cases where beclin-1 inhibits apoptosis by mitochondrial membrane stabilization \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAutophagy is a process that is mostly studied at tissue level. However, autophagy markers have also been studied in serum. Serum beclin-1 levels were investigated in patients with chronic obstructive pulmonary disease and diabetic nephropathy, and statistically significant correlations were found between the progression of the disease and serum levels \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Both studies revealed decreased serum levels with increased severity of the disease.\u003c/p\u003e \u003cp\u003eIn this study, we aimed to evaluate the serum beclin-1 levels in pregnancies complicated by preeclampsia.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e This cross-sectional study was conducted among pregnant women who received antenatal care and were delivered at a single tertiary center between January 2019 and January 2020. The ethics committee of our hospital approved the study. The informed consent was given to all participants before their enrollment into this study. Study group consisted of women with pregnancies complicated by preeclampsia. Diagnostic criteria for preeclampsia includes new onset of hypertension and proteinuria or the new onset of hypertension and significant end-organ dysfunction with or without proteinuria after 20 weeks of gestation or postpartum in a previously normotensive patient. Hypertension in pregnancy is defined as systolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;140 mmHg or diastolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;90 mmHg on at least 2 occasions at least 4 hours apart.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Diagnostic criteria for end-organ damage includes the following: Proteinuria\u0026thinsp;\u0026ge;\u0026thinsp;0.3 g in a 24-hour urine specimen or protein/creatinine ratio\u0026thinsp;\u0026ge;\u0026thinsp;0.3 (mg/mg) (30 mg/mmol) in a random urine specimen or dipstick\u0026thinsp;\u0026ge;\u0026thinsp;2\u0026thinsp;+\u0026thinsp;if a quantitative measurement is unavailable, platelet count\u0026thinsp;\u0026lt;\u0026thinsp;100,000/microL, serum creatinine\u0026thinsp;\u0026gt;\u0026thinsp;1.1 mg/dL (97.2 micromol/L) or doubling of the creatinine concentration in the absence of other renal disease, liver transaminases at least twice the upper limit of the normal concentrations for the local laboratory, pulmonary edema, new-onset and persistent headache not accounted for by alternative diagnoses and not responding to usual doses of analgesics and visual symptoms (eg, blurred vision, flashing lights or sparks, scotomata). Preeclampsia with severe features is diagnosed based on systolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;160 mmHg or diastolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;110 mmHg on 2 occasions at least 4 hours apart (unless antihypertensive therapy is initiated before this time) or with presence of criteria for end-organ damage. Chronic hypertension in pregnant women was defined as systolic BP above 140 mm Hg or diastolic BP above 90 mm Hg that was present prior to pregnancy or before 20 weeks\u0026rsquo; gestation\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Patients with preeclampsia were further divided into two groups based on their time of diagnosis either before or after 34 gestational weeks, as having early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE).\u003c/p\u003e \u003cp\u003eThe normotensive control group consisted of singleton pregnancies without hypertension. Gestational age was based on the precise date of the last menstrual period and an ultrasound measurement of the crown-rump length (CRL) in the first trimester with appropriate adjustments\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Exclusion criteria were as follows: Multiple pregnancies, pregnancies with fetal anomalies, pregnancies with a known chronic disease, premature rupture of membranes, chorioamnionitis, diabetes mellitus, chronic hypertension and gestational diabetes. The venous blood samples were obtained from pre-eclamptic and normotensive women at admittance to the hospital before administration of any medication and the onset of labor.\u003c/p\u003e \u003cp\u003eFor beclin-1, blood samples were collected in tubes containing heparin. Serum samples were removed by centrifugation for 10 min at 3000 x rpm. The samples were maintained at -80\u0026deg;C before performing assays. Samples were thawed and commercially available elisa kits for Human beclin-1 (MyBiosource Inc., Catalog No MBS732891, SanDiego, USA) were used for the quantitative measurement in serum samples.\u003c/p\u003e \u003cp\u003eIn summary, samples and standards were introduced into wells pre-coated with Anti-Human monoclonal antibody before undergoing incubation. Subsequently, Biotin was applied to all wells, followed by another incubation. The removal of uncombined enzyme was achieved through washing steps. Chromogen Solution A and B were then added, causing the liquid to change color to blue. Finally, under the influence of acid, the color transformed into yellow. The optical density was measured at 450 nm using a standard automated plate reader (Thermo Scientific Microplate Reader, USA). The detection range of beclin-1 was between 0.1\u0026ndash;10 ng/ml.\u003c/p\u003e \u003cp\u003eAnalyses were performed using the statistical package for the social sciences (SPSS) software version 20.0 (Chicago, IL, USA). The Kolmogorov\u0026ndash;Smirnov test was used to assess the normality of the distribution of variables. Using the independent samples t-test, we compared the variables with normal distributions and data was presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Continuous variables in more than two groups were analyzed by using either the Kruskal\u0026ndash;Wallis test or ANOVA and were represented as median and interquartile range (IQR) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, respectively. Spearman\u0026rsquo;s rank correlation coefficient was performed to calculate correlations between continuous variables. A two-tailed p-value of less than .05 was considered statistically significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total number of 88 pregnant women, 47 with normal pregnancy and 41 with preeclampsia were included in this study. The demographic data and the biochemical parameters are summarized in Table 1. There were no significant differences in terms of maternal age, gravidity and parity between the preeclamptic patients and the control group. Mean gestational age at delivery was significantly lower in the preeclampsia group (p:0.003). Mean BMI was also significantly different between the groups, as the patients with preeclampsia had an higher average value of BMI (p:0.032). \u0026nbsp; Mean serum beclin-1 levels were lower in patients with preeclampsia and this difference was statistically significant ( 6.32\u0026plusmn;.65 vs 4.05\u0026plusmn;.67, p\u0026lt;0.05) . Among other serum parameters, urea and creatinine levels were significantly higher in patients with preeclampsia (p\u0026lt;0.005). \u0026nbsp;Correlation analysis revealed that serum beclin-1 levels were negatively correlated with mean gestational week and serum urea levels.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePreeclamptic patients were grouped as diagnosed with early or late preeclampsia. Comparison of these groups did not reveal a significant difference in mean beclin-1 levels. When the control group was compared to early and late preeclampsia patients separately, mean Bbeclin-1 levels were found as statistically different in both groups, again revealing lower mean beclin-1 levels in preeclamptic patients (p: 0.000, p: 0.000 respectively) (Table 2).\u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eTo the best of our knowledge, this study is the first to investigate the serum beclin-1 levels in patients with preeclampsia. Our results demonstrated significantly lower mean serum beclin-1 levels in preeclamptic pregnant patients compared to patients with uncomplicated pregnancies. In addition, serum beclin-1 levels were negatively correlated with mean gestational week at delivery. Preeclampsia patients were grouped as diagnosed with early onset and late onset preeclampsia and comparison of both groups to control group also revealed significantly lower beclin-1 levels. Mean beclin-1 levels between early onset and late onset preeclamptic patients did not yield any statistically significant difference. This finding supports the association of lower serum beclin-1 levels with preeclampsia diagnosis and excludes the significance of gestational week on beclin-1 levels in preeclamptic patients.\u003c/p\u003e \u003cp\u003eAutophagy and its involvement in placentation has been an area of interest in research in the recent years. It is demonstrated that autophagy is essential in early placentation \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Beclin-1\u0026rsquo;s possible role in preeclampsia was evaluated in previous studies which investigated the autophagy process in placenta. Most of the studies point out an altered process in autophagy which can be related to development of preeclampsia. Akcora Yildiz et al. demonstrated significant increase in protein levels of both beclin-1 and SQSTM1/p62 in preeclamptic placentas\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Similarly, Gao et al. revealed that the expression of beclin-1 was significantly increased in placentas from pregnancies complicated by early-onset preeclampsia \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAnother study of Oh et al. showed an elevated protein expression of LC3-II in the placentas from patients with severe preeclampsia, suggesting an altered response in autophagy pathway. However, the expression of beclin 1 protein was found to be unchanged \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. In contrary, Zhang et al. demonstrated that autophagy proteins including beclin 1 and LC3II/LC3I were decreased in preeclamptic placentas \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBeclin-1 was studied as a serum marker in numerous studies focused on a variety of diseases. Schlemmer et al. investigated serum beclin-1 level and its association with chronic obstructive pulmonary disease (COPD). Results of this study demonstrated a significant decrease in serum Beclin-1 protein level, in smokers and even more in COPD patients compared to healthy controls which supported the theoretical association of altered autophagy pathways in pathogenesis of COPD \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Naguib et al. investigated serum level of beclin-1 in diabetic kidney disease (DKD). Results were significant with lower beclin-1 levels in DKD patients compared to controls \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Another recent study by Kubicka-Trazaska et al. evaluated the serum autophagy markers including Beclin-1 and mTOR in patients with exudative age-related macular degeneration AMD and the results demonstrated significantly decreased serum beclin-1 levels in patients with AMD \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. In addition, Lu et al. demonstrated that mean serum beclin-1 levels were significantly lower in patients with borderline ovarian tumors and ovarian cancer, compared to healthy individuals, suggesting the altered autophagy response in ovarian tumors\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur study demonstrated the altered serum beclin-1 levels in preeclamptic patients. With the previous data suggesting the altered mechanism of autophagy in preeclamptic patients, this finding suggests that serum beclin-1 levels also reflect the impact on autophagy and can be utilized as a clinical tool. As we mentioned above, histopathologic studies reveal conflicting results in levels expression of beclin-1 in placental tissues when compared to healthy individuals. But it is important to emphasize that all studies demonstrate significantly different levels of expressions in preeclamptic patients. We believe further studies should focus on the predictive value of serum beclin-1 levels for preeclampsia diagnosis in a bigger patient population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent of the participants were obtained. This study was approved by the Ege University School of Medicine Ethics Committee.\u003c/p\u003e\n\u003ch4\u003eConsent for publication\u003c/h4\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch4\u003eAvailability of data and materials\u003c/h4\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due\u0026nbsp;to absence of resources to provide a publicly available link on a server\u0026nbsp;but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch4\u003eCompeting interests\u003c/h4\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003ch4\u003eFunding\u003c/h4\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch4\u003eAuthors' contributions\u003c/h4\u003e\n\u003ch4\u003eM.I. developed the hypothesis, wrote the main text\u003c/h4\u003e\n\u003ch4\u003eH.E. assisted in data collection\u003c/h4\u003e\n\u003ch4\u003eF.O. assisted in data analysis\u003c/h4\u003e\n\u003ch4\u003eI.H. assisted in sample collection\u003c/h4\u003e\n\u003ch4\u003eA.O.Y. assisted in data analysis and reviewed the manuscript\u003c/h4\u003e\n\u003ch4\u003eAcknowledgements\u003c/h4\u003e\n\u003cp\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLieberthal W. Macroautophagy: a mechanism for mediating cell death or for promoting cell survival? \u003cem\u003eKidney Int\u003c/em\u003e. Sep 2008;74(5):555-7. doi:10.1038/ki.2008.325\u003c/li\u003e\n\u003cli\u003eRogov V, Dotsch V, Johansen T, Kirkin V. Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. \u003cem\u003eMol Cell\u003c/em\u003e. Jan 23 2014;53(2):167-78. doi:10.1016/j.molcel.2013.12.014\u003c/li\u003e\n\u003cli\u003eHe C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. \u003cem\u003eAnnu Rev Genet\u003c/em\u003e. 2009;43:67-93. doi:10.1146/annurev-genet-102808-114910\u003c/li\u003e\n\u003cli\u003eLevine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. \u003cem\u003eNature\u003c/em\u003e. Jan 20 2011;469(7330):323-35. doi:10.1038/nature09782\u003c/li\u003e\n\u003cli\u003eMathew R, Karantza-Wadsworth V, White E. Role of autophagy in cancer. \u003cem\u003eNat Rev Cancer\u003c/em\u003e. Dec 2007;7(12):961-7. doi:10.1038/nrc2254\u003c/li\u003e\n\u003cli\u003eGestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. \u003cem\u003eObstet Gynecol\u003c/em\u003e. Jun 2020;135(6):e237-e260. doi:10.1097/AOG.0000000000003891\u003c/li\u003e\n\u003cli\u003ePayne B, Magee LA, von Dadelszen P. Assessment, surveillance and prognosis in pre-eclampsia. \u003cem\u003eBest Pract Res Clin Obstet Gynaecol\u003c/em\u003e. Aug 2011;25(4):449-62. doi:10.1016/j.bpobgyn.2011.02.003\u003c/li\u003e\n\u003cli\u003eSteegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. \u003cem\u003eLancet\u003c/em\u003e. Aug 21 2010;376(9741):631-44. doi:10.1016/S0140-6736(10)60279-6\u003c/li\u003e\n\u003cli\u003ePennington KA, Schlitt JM, Jackson DL, Schulz LC, Schust DJ. Preeclampsia: multiple approaches for a multifactorial disease. \u003cem\u003eDis Model Mech\u003c/em\u003e. Jan 2012;5(1):9-18. doi:10.1242/dmm.008516\u003c/li\u003e\n\u003cli\u003eHomer CS, Brown MA, Mangos G, Davis GK. Non-proteinuric pre-eclampsia: a novel risk indicator in women with gestational hypertension. \u003cem\u003eJ Hypertens\u003c/em\u003e. Feb 2008;26(2):295-302. doi:10.1097/HJH.0b013e3282f1a953\u003c/li\u003e\n\u003cli\u003eHung TH, Hsieh TT, Chen SF, Li MJ, Yeh YL. Autophagy in the human placenta throughout gestation. \u003cem\u003ePLoS One\u003c/em\u003e. 2013;8(12):e83475. doi:10.1371/journal.pone.0083475\u003c/li\u003e\n\u003cli\u003eGong JS, Kim GJ. The role of autophagy in the placenta as a regulator of cell death. \u003cem\u003eClin Exp Reprod Med\u003c/em\u003e. Sep 2014;41(3):97-107. doi:10.5653/cerm.2014.41.3.97\u003c/li\u003e\n\u003cli\u003eChifenti B, Locci MT, Lazzeri G, et al. Autophagy-related protein LC3 and Beclin-1 in the first trimester of pregnancy. \u003cem\u003eClin Exp Reprod Med\u003c/em\u003e. Mar 2013;40(1):33-7. doi:10.5653/cerm.2013.40.1.33\u003c/li\u003e\n\u003cli\u003eHung TH, Chen SF, Lo LM, Li MJ, Yeh YL, Hsieh TT. Increased autophagy in placentas of intrauterine growth-restricted pregnancies. \u003cem\u003ePLoS One\u003c/em\u003e. 2012;7(7):e40957. doi:10.1371/journal.pone.0040957\u003c/li\u003e\n\u003cli\u003eGao L, Qi HB, Kamana KC, Zhang XM, Zhang H, Baker PN. Excessive autophagy induces the failure of trophoblast invasion and vasculature: possible relevance to the pathogenesis of preeclampsia. \u003cem\u003eJ Hypertens\u003c/em\u003e. Jan 2015;33(1):106-17. doi:10.1097/HJH.0000000000000366\u003c/li\u003e\n\u003cli\u003eMarino G, Niso-Santano M, Baehrecke EH, Kroemer G. Self-consumption: the interplay of autophagy and apoptosis. \u003cem\u003eNat Rev Mol Cell Biol\u003c/em\u003e. Feb 2014;15(2):81-94. doi:10.1038/nrm3735\u003c/li\u003e\n\u003cli\u003eMukhopadhyay S, Panda PK, Sinha N, Das DN, Bhutia SK. Autophagy and apoptosis: where do they meet? \u003cem\u003eApoptosis\u003c/em\u003e. Apr 2014;19(4):555-66. doi:10.1007/s10495-014-0967-2\u003c/li\u003e\n\u003cli\u003eNaguib M, Rashed LA. Serum level of the autophagy biomarker Beclin-1 in patients with diabetic kidney disease. \u003cem\u003eDiabetes Res Clin Pract\u003c/em\u003e. Sep 2018;143:56-61. doi:10.1016/j.diabres.2018.06.022\u003c/li\u003e\n\u003cli\u003eSchlemmer F, Boyer L, Soumagne T, et al. Beclin1 circulating levels and accelerated aging markers in COPD. \u003cem\u003eCell Death Dis\u003c/em\u003e. Feb 5 2018;9(2):156. doi:10.1038/s41419-017-0178-1\u003c/li\u003e\n\u003cli\u003eCommittee on Practice B-O, the American Institute of Ultrasound in M. Practice Bulletin No. 175: Ultrasound in Pregnancy. \u003cem\u003eObstet Gynecol\u003c/em\u003e. Dec 2016;128(6):e241-e256. doi:10.1097/AOG.0000000000001815\u003c/li\u003e\n\u003cli\u003eNakashima A, Yamanaka-Tatematsu M, Fujita N, et al. Impaired autophagy by soluble endoglin, under physiological hypoxia in early pregnant period, is involved in poor placentation in preeclampsia. \u003cem\u003eAutophagy\u003c/em\u003e. Mar 2013;9(3):303-16. doi:10.4161/auto.22927\u003c/li\u003e\n\u003cli\u003eAkcora Yildiz D, Irtegun Kandemir S, Agacayak E, Deveci E. Evaluation of protein levels of autophagy markers (Beclin 1 and SQSTM1/p62) and phosphorylation of cyclin E in the placenta of women with preeclampsia. \u003cem\u003eCell Mol Biol (Noisy-le-grand)\u003c/em\u003e. Dec 30 2017;63(12):51-55. doi:10.14715/cmb/2017.63.12.12\u003c/li\u003e\n\u003cli\u003eOh SY, Choi SJ, Kim KH, Cho EY, Kim JH, Roh CR. Autophagy-related proteins, LC3 and Beclin-1, in placentas from pregnancies complicated by preeclampsia. \u003cem\u003eReprod Sci\u003c/em\u003e. Nov 2008;15(9):912-20. doi:10.1177/1933719108319159\u003c/li\u003e\n\u003cli\u003eZhang Y, Hu X, Gao G, Wang Y, Chen P, Ye Y. Autophagy protects against oxidized low density lipoprotein-mediated inflammation associated with preeclampsia. \u003cem\u003ePlacenta\u003c/em\u003e. Dec 2016;48:136-143. doi:10.1016/j.placenta.2016.09.015\u003c/li\u003e\n\u003cli\u003eKubicka-Trzaska A, Zuber-Laskawiec K, Plutecka H, Romanowska-Dixon B, Sanak M, Karska-Basta I. Altered serum levels of autophagy proteins Beclin-1 and mTOR in patients with exudative age-related macular degeneration. \u003cem\u003eJ Physiol Pharmacol\u003c/em\u003e. Feb 2021;72(1)doi:10.26402/jpp.2021.1.09\u003c/li\u003e\n\u003cli\u003eLu H, Hu H, Li S. Diagnostic value of beclin-1 and mTOR in ovarian cancer. \u003cem\u003eInt J Clin Exp Pathol\u003c/em\u003e. 2021;14(2):238-246.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eI\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e The demographic data and biochemical parameters of the study groups.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eControl (n:47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003ePreeclampsia(n:41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eMaternal\u0026nbsp;Age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e27.02\u0026plusmn;5.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e28.61\u0026plusmn;5.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.201\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eBMI\u003csup\u003e\u0026dagger;\u003c/sup\u003e (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e30.96\u0026plusmn;4.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e33.83\u0026plusmn;6.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.032\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eGravidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e2.30 1.536\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e2.33\u0026plusmn;1.493\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.927\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eParity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e0.81\u0026plusmn;\u0026nbsp;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e1.13\u0026plusmn;\u0026nbsp;1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.235\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eGestational Age at Delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e37.61\u0026plusmn;3.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e35.21\u0026plusmn;3.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eInfant weight (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e3102.61\u0026plusmn;\u0026nbsp;653.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e2527.89\u0026plusmn;894.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eAPGAR 1\u003csup\u003est\u003c/sup\u003e min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e7.63\u0026plusmn;1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e7.61\u0026plusmn;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.996\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eAPGAR 5\u003csup\u003eth\u003c/sup\u003e min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e8.97\u0026plusmn;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e8.78\u0026plusmn;0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.502\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eSystolic BP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e109.25\u0026plusmn;9.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e156.34\u0026plusmn;21.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eDiastolic\u0026nbsp;BP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e66.35\u0026plusmn;7.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e99.12\u0026plusmn;15.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eBeclin (ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e6.32\u0026plusmn;\u0026nbsp;.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e4.05\u0026plusmn;.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003ePlatelet (/mcl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e218.785\u0026plusmn;67.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e218.179\u0026plusmn;65.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.967\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eWBC\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e (/mm3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e9754.69\u0026plusmn;2607.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e10729.23\u0026plusmn;2856.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.112\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eUrea (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e14.04\u0026plusmn;4.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e19.89\u0026plusmn;8.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eCreatinine (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e0.51\u0026plusmn;0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e0.58\u0026plusmn;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.\u003cstrong\u003e034\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eALT (IU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e12.54\u0026plusmn;8.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e13.00\u0026plusmn;7.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.795\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003eAST (IU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e18.04\u0026plusmn;10.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.040128410914928%\" valign=\"top\"\u003e\n \u003cp\u003e20.94\u0026plusmn;8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.879614767255216%\" valign=\"top\"\u003e\n \u003cp\u003e.181\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eBody Mass Index, \u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003eWhite Blood Cells, \u003csup\u003e\u0026sect;\u003c/sup\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAlanine Amino Transferase, \u003csup\u003e\u0026para;\u003c/sup\u003eAspartate Amino Transferase\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e The demographic data and biochemical parameters of the control group and patients with early and late preeclampsia\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003eControl (n:47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003eEarly-Onset\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePreeclampsia (EOPE \u003csup\u003e\u0026dagger;\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(n:14 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003eLate -Onset\u003c/p\u003e\n \u003cp\u003ePreeclampsia (LOPE\u0026Dagger;)\u003c/p\u003e\n \u003cp\u003e(n:27 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;p Control vs EOPE\u003c/em\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eControl vs LOPE\u003c/em\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep EOPE\u003c/em\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003cem\u003e\u0026nbsp;vs LOPE\u003c/em\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eMaternal Age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e27.0222\u0026plusmn;5.99048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e30.25\u0026plusmn;5.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e27.88\u0026plusmn;5.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.535\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.197\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eBMI\u003csup\u003e\u0026sect;\u003c/sup\u003e\u0026nbsp; (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e30.9669\u0026plusmn;4.86398\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e32.66\u0026plusmn;4.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e34.34\u0026plusmn;6.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.\u003c/strong\u003e268\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.454\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eGravidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e2.30 1.536\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e2.50\u0026plusmn;1.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e2.26\u0026plusmn;1.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.490\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.910\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.648\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eParity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e0.81\u0026plusmn;\u0026nbsp;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e1.25\u0026plusmn;\u0026nbsp;1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e1.07\u0026plusmn;\u0026nbsp;1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.361\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.698\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eGestational Age at Delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e37.61\u0026plusmn;3.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e30.72\u0026plusmn;4.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e37.03\u0026plusmn;1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.\u003cstrong\u003e000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.387\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.\u003cstrong\u003e000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eInfant weight (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e3102.61\u0026plusmn;\u0026nbsp;653.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e1477.27\u0026plusmn;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e691.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e2955.92\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e546.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.\u003cstrong\u003e000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eAPGAR\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;1\u003csup\u003est\u003c/sup\u003e min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e7.63\u0026plusmn;1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e7.71\u0026plusmn;1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.428\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eAPGAR 5\u003csup\u003eth\u003c/sup\u003e min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e8.97\u0026plusmn;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e8.88\u0026plusmn;0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.759\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.032\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eSystolic BP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e109.25\u0026plusmn;9.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e157.05\u0026plusmn;16.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e155.76\u0026plusmn;25.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.427\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eDiastolic BP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e66.35\u0026plusmn;7.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e98.22\u0026plusmn;12.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e100.12\u0026plusmn;19.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.572\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eBeclin (ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e6.32\u0026plusmn;\u0026nbsp;.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e4.05\u0026plusmn;\u0026nbsp;.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e4.05\u0026plusmn;.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.975\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003ePlatelet (/mcl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e218.785\u0026plusmn;67.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e218.666\u0026plusmn;51.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e227.29\u0026plusmn;69.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.454\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eWBC\u003csup\u003e\u0026para;\u003c/sup\u003e (/mm3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e9754.69\u0026plusmn;2607.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e111168.33\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e3765.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e10534.23\u0026plusmn;\u003c/p\u003e\n \u003cp\u003e2406.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.293\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.332\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eUrea (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e14.04\u0026plusmn;4.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e24.91\u0026plusmn;13.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e17.66\u0026plusmn;5.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eCreatinine (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e0.51\u0026plusmn;0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e0.62\u0026plusmn;0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e0.56\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.045\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.266\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eALT\u003csup\u003e\u0026dagger;\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(IU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e12.54\u0026plusmn;8.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e16.33\u0026plusmn;8.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e11.51\u0026plusmn;6.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.583 \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.583\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.063\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.530326594090202%\" valign=\"top\"\u003e\n \u003cp\u003eAST\u003csup\u003e\u0026Dagger;\u0026Dagger;\u003c/sup\u003e (IU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.61741835147745%\" valign=\"top\"\u003e\n \u003cp\u003e18.04\u0026plusmn;10.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.818040435458787%\" valign=\"top\"\u003e\n \u003cp\u003e21.41\u0026plusmn;7.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.573872472783826%\" valign=\"top\"\u003e\n \u003cp\u003e20.74\u0026plusmn;9.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.864696734059098%\" valign=\"top\"\u003e\n \u003cp\u003e.283\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.687402799377916%\" valign=\"top\"\u003e\n \u003cp\u003e.283\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.908242612752721%\" valign=\"top\"\u003e\n \u003cp\u003e.825\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e Early Onset Preeclampsia; \u003csup\u003e\u0026Dagger;\u003c/sup\u003e Late Onset Preeclampsia; \u003csup\u003e\u0026sect;\u003c/sup\u003e Body Mass Index, \u003csup\u003e\u0026para;\u003c/sup\u003e: White Blood Cells, \u003csup\u003e\u0026dagger;\u0026dagger;\u003c/sup\u003e Alanine Amino Transferase, \u003csup\u003e\u0026Dagger;\u0026Dagger;\u003c/sup\u003e Aspartate Amino Transferase\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Autophagy, Creatinine, Preeclampsia, Serum, Obstetrics","lastPublishedDoi":"10.21203/rs.3.rs-3870756/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3870756/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAutophagy is an intracellular catabolic degradation process in cellular physiology. Beclin-1 is a protein that regulates this process and is used as a marker of this process in tissues. We evaluated the serum beclin-1 levels in pregnancies complicated by preeclampsia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e41 women with preeclampsia and 47 women with uncomplicated pregnancies were enrolled in the study. Maternal serum levels of beclin-1 were measured by using enzyme-linked immunosorbent assay kit (ELISA). Demographic data and several other parameters were also recorded and analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMean serum beclin-1 levels were lower in patients with preeclampsia and this difference was statistically significant (6.32±.65 vs 4.05±.67, p\u0026lt;0.05). Urea and creatinine levels were significantly higher in patients with preeclampsia (p\u0026lt;0.005). Beclin-1 levels were found as statistically different in early and late preeclampsia groups as well, again revealing lower mean beclin-1 levels in preeclamptic patients (p: 0.000, p: 0.000 respectively)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge, this study is the first to investigate the serum beclin-1 levels in patients with preeclampsia and demonstrated the altered serum beclin-1 levels in preeclamptic patients. This finding suggests that serum beclin-1 levels also reflect the altered autophagy process in preeclampsia and can be utilized as a clinical tool.\u003c/p\u003e","manuscriptTitle":"Serum Beclin-1 Levels in Patients With Preeclampsia: a Case Control Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-29 16:32:18","doi":"10.21203/rs.3.rs-3870756/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"905eff0c-dff5-48eb-9870-f6ce336230a4","owner":[],"postedDate":"January 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-20T05:24:37+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-29 16:32:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3870756","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3870756","identity":"rs-3870756","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}