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Serum concentrations of PlGF (Placental Growth Factor) Severe Preeclampsia

Patients in Dr. Mohammad Hoesin Palembang General Hospital

Rodiani, Kurdi S, Nuswil B, Erial B
Department of Obstetrics and Gynecology
Medical Faculty Sriwijaya University
Dr. Mohammad Hoesin Palembang General Hospital

Abstract
Objective: To analyze the relationship between maternal serum concentration of PlGF
with severe preeclampsia
Methods: A case study on the control of severe preeclampsia group as a group of cases
and normal pregnancies as a control group. Data obtained dientry using SPSS version
21.0 software Windows. Analysis conducted in the form of univariate, bivariate
analysis, ROC analysis and multivariate analysis
Results: Based on the results of ROC analysis showed that the cut-off point of PlGF in
preeclampsia is predictive 123.35 pg / ml (sensitivity 93.3%, specificity 70.0%). The
percentage of Severe Preeclampsia majority occur in low PlGF level group (38.3% of
the 60 samples). The existence of a significant relationship with the occurrence of low
levels of PlGF in Severe Preeclampsia (p = <0.001). Based analisismultivariat also
obtained the best groups in the determination of gestational age through examination
PlGF in Severe Preeclampsia is a group of gestation> 29 weeks (± 75%)
Conclusion: There is a significant correlation with the incidence of low levels of PlGF
in Severe Preeclampsia
Keywords: Placental Growth Factor, Severe Preeclampsia

Medical records at the Dr. The incidence of preeclampsia in RSHS (RS Hasan Sadikin) in 1998 amounted to 13. Jakarta reported that in 2002 there were the incidence of preeclampsia by 9.6 Etiology of preeclampsia is still unknown. At the age of 28-30 weeks gestation increased dramatically PlGF worth 180-200 pg / ml.2 In normal pregnancy PlGF worth 40-50 pg / ml at 7-15 weeks gestation. which cause bad perfusion trophoblast. VEGF-D and VEGF-E. theory Maladaptation immune. Serum PlGF at the end of the second trimester increased up to four times from the end of the first trimester.INTRODUCTION PlGF (Placental Growth Factor) and VEGF (Vascular Endothelial Growth Factor) is a factor proangiogenik best and most potent who work directly which increases vascular permeability. Mohamad Hoesin Palembang General Hospital.1. The imbalance between antiangiogenic form of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble soluble endoglin high with proangiogenik the . if an interruption occurs in the placenta of pregnancy with preeclampsia. PlGF is a member of the group other than VEGF VEGF-B. Furthermore. RSCM (Cipto Mangunkusumo Hospital). Adam Malik Hospital) in 2002 amounted to 7. while in RSHAM (H. Whereas. the concentration of PlGF would decreased. whereas the term gestational age between 39-41 weeks gestation serum concentrations of PlGF worth 55-65 pg / ml.05. it has spread toxins that cause dysfunction of endothelial cells and vascular endothelial function imbalance maternal vasodepresor. the incidence of preeclampsia in 2012 found 12% .17%.3-5 In some hospitals in Indonesia the incidence of preeclampsia was not much different.8-10 There is another theory says preeclampsia associated with an imbalance of circulating angiogenic factors. genetic theory and the theory of change in VLDL and activities antitoxin. There are several hypotheses to explain the pathogenesis of preeclampsia include placental ischemia theory.0%. VEGF-C.7 It is considered important in the development of preeclampsia theory is incomplete trophoblast invasion or with other terms be regarded as abnormal cytotrophoblast invasion of the maternal spiral arteries. 6. These molecules are secreted dimeric glycoproteins.

capillaries collapse and cause proteinuria. The process of angiogenesis and vaskulogenesis require several growth factor. trophoblast implantation less than perfect so that blood flow is reduced. and placental hypoxia and an increase in the production of sFlt1 that will bind VEGF angiogenic factors are independent and free P1GF so that the amount in circulation is reduced. 8 Grill expressed in severe preeclampsia will decrease from the first trimester of pregnancy until delivery. proteinuria and other systemic manifestations syndrome. causing edema.2. glomerular endothelial cells will swell. They showed concentrations of angiogenic and antiangiogenic factors from serum of pregnant women with preeclampsia at 34-36 weeks of gestation.form of a low PlGF and VEGF.11. This condition triggers vascular endothelial cell injury in the liver. liver and affect the function of capillary gromelurus. continued evaluation of this antiangiogenic protein.13-17 Petrozella et al. This will cause the endothelial dysfunction that would disrupt the blood brain barrier and cause intracranial hypertension.18 Chaiworapongsa et al. kidney.9. Thus the level of sFlt-1 increased maternal preeclampsia and vice versa levels of VEGF and free PlGF decreased. When VEGF on renal prodocyte decreased by 50%.11 The pathogenesis of preeclampsia is still being studied further. brain and placenta. observing the relationship between placental protein in patients with preeclampsia and protein-protein sFlt proangiogenic such as VEGF and PlGF concentrations. Endothelial dysfunction and injury causes a state of hypertension.12 Research shows that in pregnant women with preeclampsia. found increased levels of sFlt-1 and PlGF levels decrease compared to both normal mRNA concentrations in placenta and serum levels in preeclampsia. They showed that the combination of soluble endoglin levels and the ratio of sFlt-1 by PlGF increases the predictive value of . but allegedly associated with angiogenesis and vasculogenesis process that occurs in fetomaternal circulation. 7 Grill et al. The main growth factor in this process are VEGF and PIGF. Both of these processes is necessary to anticipate the threat of hypoxia on fetomaternal circulation along with the growth of the fetus.

They compared the levels of PlGF between early-onset preeclampsia group and slow in Dr Hasan Sadikin. Therefore. bivariate analysis and ROC analysis. M. They conclude that VEGF and PlGF decreased. and also the prediction of severe impact of this disease (fetal growth restriction and the HELLP syndrome) 10 weeks before emerging clinical manifestations. each with a different mechanism causes endothelial dysfunction and mediate the manifestation of preeclampsia. This makes the interest of researchers to examine further why PlGF decreased in patients with severe preeclampsia in.0 software Windows. Hoesin Palembang General Hospital. makes the size of the angiogenic protein as a potential test tool in predicting preeclampsia. Data obtained dientry using SPSS version 21.19 Mutter et al. and urinary PlGF about 5 weeks prior to the manifestation of preeclampsia. which is when the increase in the level of sFlt and lower levels of free VEGF. PlGF is free. both of which occur earlier or slower. RESULT Data taken in this study of primary data is to perform sampling of maternal blood were diagnosed with severe preeclampsia from June 2013 to February 2014. Routine blood tests.9. Dr. METHODS Case-control study in severe preeclampsia group as a group of cases and normal pregnancies as a control group.preeclampsia. this research needs to be done in the clinical management of severe preeclampsia in Department Obstetrics and Gynecology Dr. Hoesin Palembang General Hospital.19-22 Some researchers at the above also show that low serum levels of PlGF can be a useful marker in predicting and diagnosing severe preeclampsia. Research in Indonesia on PlGF in preeclampsia is still has inadequate data as reported by Ekapatria et al. Bandung. M.18. Researchers examined levels of PlGF in maternal blood serum of . soluble endoglin increased. routine urine and blood chemistry that has been done before in the diagnosis of severe preeclampsia. Analysis conducted in the form of univariate.

Characteristics of Research Subjects Characteristic Age (Years) < 20 20 – 35 > 35 Parity 1 2 >2 History of hypertension Hypertension (+) Hypertension (-) Gestational Age 13 – 28 weeks > 29 weeks PEB Normal % n Total % n % n 0 20 10 0 33. Subject recruitment carried out in accordance reference with full respect for the freedom of the subject.7 1 29 1.3 16. The following table below describes the characteristics of the study subjects which are risk factors for preeclampsia Table 3.3 11 19 18.3 31.7 30 14 5 11 23.7 48. CHARACTERISTICS OF RESEARCH This study is a case-control study with the aim to determine the prevalence of PlGF levels in the two groups and whether there is a connection with a reduction in the incidence of severe preeclampsia serum PlGF levels. The subjects were normotensive pregnant women and severe preeclampsia.3 18.3 5 25 8. The characteristics of the study sample are described as follows. Data collection is done in IRD (Emergency Room).7 0 30 0 50 11 49 18.7 6 54 10 90 .3 41.7 15 48. delivery room and outpatient clinic Obstetrics RSMH Palembang.3 22 9 29 36.7 2 23 5 3.3 8.3 6.3 81.30 people who suffer from severe preeclampsia and 30 normal pregnant women in the lab PRODIA Palembang.3 2 43 15 3.3 38.3 8. A.3 71.7 25 8 4 18 13.

7 > 35 Years 10 30 16.7 50 5 30 8.144 Descriptively shown that the percentage of SEVERE PREECLAMPSIA in majority occur in maternal age group> 35 years (66.1.001 Descriptively apparent that the percentage of the majority of events occurred in the group Severe Preeclampsia history of hypertension (+) (100% of 11 samples).5% of 43 samples). this can be caused by a number of samples 2.144). followed by maternal age group 20-35 years (46.7 100 P <0. Age Group Distribution of Severe Preeclampsia Age PEB (+) PEB (-) Total P n % n % < 20 Years 20 – 35 Years 0 20 0 33.7% of the 15 samples).3 N 2 43 % 3. This finding is consistent with the theory Dildy et al. Distribution History of Hypertension with Severe Preeclampsia History of Hypertension Hypertension (+) Hypertension (-) n 11 19 30 PEB (+) % 18.3 81. Maternal Age Relationship with Severe Preeclampsia Table 4.3 2 23 3. that maternal age above 40 years old have a risk of Severe Preeclampsia in pregnancy. However no significant relationship was found between the age group with the incidence of Severe Preeclampsia (p = 0. that women with a history of .3 50 15 60 25 100 0. This finding is consistent with the theory of English et al.3 71.7 50 PEB (-) n 0 30 30 Total % 0 50 50 N 11 49 60 % 18.3 31.3 38. Relationship between History of Hypertension with Severe Preeclampsia Table 5.

47 .1%). found that 29% multigravida who suffer Severe Preeclampsia make the turn pairs.7 15 48.3 100 P 0. and decreased in line with the addition of parity (based theory extends exposure to the antigen husband).579) 3. Jasovic et al.3 18.179 Descriptively shown that the percentage of Severe Preeclampsia increases with the addition of parity. and highest in parity> 2 (62. are other possible causes are multiparas common in women older age where old age itself is a risk factor for the development of Severe Preeclampsia. Parity Relationship with Severe Preeclampsia Table 6. Distribution of Parity against Severe Preeclampsia Parity 1 2 >2 PEB (+) n 8 4 18 30 % 13. as determined Trupin et al.3 8. expressed in much of the literature mentions the phenomenon binominal highest probability which is owned by the Severe Preeclampsia risk nulliparous mothers and mothers of young age multiparous old age.37 And analytically also found a significant association between a history of hypertension with Severe Preeclampsia events (p <0.. This is contrary to the theory Dildy et al.4%).4%).579 times greater in mothers history of hypertension (+) than maternal history of hypertension (-) (OR 2.hypertension (+) have a higher risk of occurrence of Severe Preeclampsia in pregnancy.3 6. Occurrence of the phenomenon of increased risk of Severe Preeclampsia in multiparas can be caused in part by the alternation of the couple.001) with Severe Preeclampsia risk 2. the lowest on the parity 1 (36.3 50 Total N 22 9 29 60 % 36. an increase in parity 2 (44. the risk factors Severe Preeclampsia where the highest risks are owned by nulliparity.7 30 50 PEB (-) n 14 5 11 30 % 23.37.

3 1.49 B.0 97 Descriptively shown that the percentage of the majority Severe Preeclampsia incident occurred in the age group of gestation> 29 weeks / trimester III (53. However no significant relationship was found between gestational age at Severe Preeclampsia events (p = 0. 4. this can be caused by a number of samples that are too small. Samples required a larger and more diverse number of parity to find a relationship maternal age and incidence of Severe Preeclampsia.Nevertheless. which for early onset <34 gestational weeks.3 50 Total N 54 6 60 % 90 10 100 P 0.48.7 8. The division of early onset and late onset severe preeclampsia follow the basic research of Ghosh et al.7% of 54 samples).097). Gestational Age Relationship with Severe Preeclampsia Table 7.7 50 PEB (-) N 25 5 30 % 41. PlGF RELATIONSHIP WITH SEVERE PREECLAMPSIA 1. Gestational Age Distribution of Severe Preeclampsia Gestational Category > 29 weeks 13–28 weeks PEB (+) N 29 1 30 % 48. Of the 30 patients Severe Preeclampsia is known that the majority of patients with late onset Severe Preeclampsia (83.179). analytically not found a significant relationship between parity with Severe Preeclampsia events (p = 0. Cut off point PlGF .3%).

b .Area Under the Curve Asymptotic 95% Confidence Interval Asymptotic Sig. it can be concluded that: .000 Lower Bound Upper Bound .952 From the calculation of ROC and AUC (Area Under the Curve) PlGF levels.754 .

PlGF Relationship with Severe Preeclampsia Table 9.35 PEB (+) N 21 9 30 PEB (-) % 35 15 50 N 2 28 30 % 3.3 61.05) was excellent / good (AUC = 0.7 100 <0. Distribution Category PIGF levels with Severe Preeclampsia PIGF Category < 123. This finding is consistent with the theory that low levels of PlGF is closely related to the high incidence of Severe Preeclampsia. specificity = 70.754 to 0.7 50 Total N 23 37 60 P % 38.3%.35 pg / ml (sensitivity = 93. It is also strengthened by the statistical analysis showed a significant association PIGF levels (cut off point = 123.35 pg / ml) with Severe Preeclampsia events with OR = 21.35 pg / ml) 21 times greater risk of experiencing Severe Preeclampsia than patients with higher levels of PIGF. which showed that patients with low levels of PIGF (PIGF <123.0%) 2.952) b. 95% CI 0. MULTIVARIATE ANALYSIS From the logistic regression analysis found the best group in the determination of gestational age through examination Severe Preeclampsia PlGF is a group of gestation> . PlGF degree of sensitivity and specificity in determining the incidence of preeclampsia was significantly (P <0.3% of the 60 samples).001 Descriptively shown that the percentage of Severe Preeclampsia majority occur in low PlGF level group (38. PlGF cut-off point in the determination preeklampisa with the best sensitivity and specificity were in the value of PlGF 123.3 46.35 > 123.a.853.

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