Abstrak Objective: To determine the relationship between serum levels of TNF- with the occurrence of preeclampsia.

Methods: In normotensive and preeclamptic pregnant women with gestational age> 28 weeks who met the inclusion criteria examined serum levels of TNF-. Results: From January to April 2013 has been examined serum levels of TNF- in pregnant women with preeclampsia and normotensive 26 people 26 people found the age group of 20-30 years with preeclampsia most 12 cases (46.15%), and the gestational age> 37 with preeclampsia found 18 cases (69.24%) and primipara with preeclampsia found 14 cases (53.84%). In this study obtained a cut off point of the levels of TNF- was 3.618 pg / ml with a sensitivity value of 100% and the specificity 100%. Conclusions: Serum levels of TNF- in the preeclampsia group higher at 3.733 to 31.870 pg / ml compared to normotensive pregnant women is 1.188 to 3.504 pg / ml. In this study also found a cut off point of serum levels of TNF- was 3.618 pg / ml with a sensitivity of 100% and the value of the specificity 100%, higher serum levels of TNF- the higher the chances of occurrence of preeclampsia. Keywords: TNF-, normotensive, preeclampsia Pendahuluan Preeclampsia is a pregnancy specific disorder complicating approximately 3-5% of all kehamilan.1, 2 Preeclampsia is a major cause of maternal and neonatal mortality in the entire world.3 effect on pregnant women varies from mild hypertension, severe hypertension / hypertensive crisis , eclampsia until the syndrome hemolysis, elevated liver enzymes, low platelet count (HELLP), whereas the impact of these abnormalities in the fetus also varies from premature birth, intrauterine growth (IUGR) until death janin.1, 4 According to the study, the incidence of preeclampsia in nulliparous population of the world at about 3-10% .5 In the United States, preeclampsia complications occurred about 5% of all kehamilan.4 The incidence of preeclampsia in RSCM Jakarta in 2002 gained 9.17% .6 In Manado General Hospital in 2007 was the incidence of preeclampsia 9.4% of the total 3350 patients. According to the Working Group of the National High Blood Pressure Education Program (NHBPEP), preeclampsia diagnosis is made based on an increase in blood pressure 140/90 mmHg after 20 weeks of pregnancy, accompanied by proteinuria 300 mg/24 h or 1 + dipstick examination .5 -7

The initial cause of preeclampsia is still unknown, recent developments explain the background of the molecular mechanisms and especially the development of abnormal manifestations, placental hypoxia, endothelial dysfunction. Cytokines are proteins released by intermediaries immune cells that regulates the function of other immune cells. Cytokines secreted by inflammatory cells and immune cells as well as growth factors, oncogenes, chemokines and other soluble factors that influence the growth and differentiation of cell viability. Cytokines were divided into 6 groups: interleukins, colony-stimulating factor, interferon, tumor necrosis factor, growth factors and chemokines. Several types of cytokines proven increased in preeclampsia and may be used as a marker of a preeklampsia.5, 8 Several studies have reported a rise in proinflammatory cytokines such as TNF- and IL-6 in preeclampsia compared with gestational normal.8, 9 TNF- and IL6 in mediating the cardiovascular and renal dysfunction in response to placental ischemia during pregnancy can not be explained by lengkap.8 , 10 These findings suggest that TNF- and IL-6 may play an important role in mediating hypertension and decreased renal hemodynamics were observed during reduction of uterine perfusion pressure in rats hamil.11 The results showed the role of TNF- in preeclampsia where TNF- serum levels obtained were higher in preeclampsia than normal pregnancy. 12-15 However, there are conflicting reports, which increased serum levels of TNF- was not significantly associated with preeklampsia.16, 17 The role of TNF- interesting to study as a risk factor for preeclampsia, which this study has not been done in the Department of Obstetrics and Gynaecology Dr Prof. Dr.. RD Kandou Manado / FK UNSRAT Manado, because it was interesting research done to determine differences in serum levels of TNF- in preeclampsia and normal pregnancy. RESEARCH OBJECTIVES The purpose of this study was to determine the relationship between serum levels of TNF- with the occurrence of preeclampsia.

METHODS This study is observational form correlative analysis with cross-sectional design.

PLACE AND TIME RESEARCH

The research was conducted at the Department of Obstetrics and Gynecology, Faculty of Medicine, University of Sam Ratulangi / Prof Dr. Dr.. RD Kandou Manado in January to April 2013.

MATERIALS AND PROCEDURES 1. This research was conducted at the research subjects who met the inclusion criteria and provided an explanation of the research procedures to be performed and benefits. 2. For prospective research subjects who are willing to follow the study were asked to complete and sign a consent form (informed consent) you have available. 3. Subjects research conducted anamnesis, physical examination, and then recorded in the general status of the research. Then the pregnant women> 28 weeks with preeclampsia and normal pregnancies> 28 weeks a blood sample, and then blood samples were immediately taken to the laboratory. 4. Examination in the laboratory with the method Prodia Quantikine Human TNF- Immunassay.

RESULTS Basic characteristics of the study sample included age, parity and gestational age, with a sample size of 52 and divided into 2 groups: the group with normotensive pregnancy and preeclampsia group. The results obtained are described in tabular form below: 1. characteristics of studies

Table 1. Characteristics of the study by Age

In the table above, of the 52 people who follow the research, the vast majority were in the age group 20-30 years preeclampsia by as many as 12 cases (46.15%)

Table 2. Characteristics of Research by Age Pregnancy

Based on table 4 large value creation opportunities derived preeclampsia best cut off point value of the rate of TNF- was 3,618 pg / ml, 100% sensitivity and 100% specificity. .

DISCUSSION Underlying characteristics of the study sample includes age, parity and gestational age, with a total sample of 52 and divided namely cluster with 2 cluster with normotensi pregnancy and preeclampsia group. From the study sample characteristics found in most pregnant women 20-30 years of age that is 25 cases (48.07%) and the cluster characteristics recovered primipara most parity in preeclampsia 14 cases (53.84%) and the characteristics of gestational age group, the highest found in the preeclampsia group with gestational age> 37 weeks ie 18 cases (52.94%). In this study it was found that increased incidence of preeclampsia in the productive age, primipara and full-term gestation. Preeclampsia often occurs at a young age and nullipara, it was presumed that the existence of an immunological mechanism. During the first pregnancy occurs the formation of "blocking antibodies" against antigens not be more perfect and flawless in subsequent pregnancies, first pregnancy occurred in the formation of "Human leukocyte antigen G protein" (HLAG), which plays a role in modulating the immune response, so that the mother does not reject the results conception (placenta), with the HLA-G is also able to protect the fetus from lysis trofoblast can be done by "natural killer" (NK) or intolerance occurred and the mother to the placenta until further will result in the occurrence of preeclampsia. 17.26 In this study obtained serum TNF- in preeclampsia recovered 3733 pg / ml up to 31 870 pg / ml with the mean of 17 222 pg / ml are at normotensi TNF- results obtained from 1,188 pg / ml up to 3504 pg / ml with the mean of 2.533 This case is similar to the analysis conducted by I Gusti Ngurah Anom, namely et al obtained the level of serum TNF- in pregnancies with normotensi low (2.42 +1.77) dibandingankan with preeclampsia patients (6.64 +7.64), this is proved by using

independent t-test p = 0.006 obtained a statistically significant association was found (p <0.001) Based on their independent t-test analysis performed in this study obtained a very significant relationship between the serum level of TNF- in preeclampsia incidence (p = 0.000 <0.001). This means that the higher level of TNF- in the serum of pregnant women the greater the chance for terjanya preeclampsia. It is well suited to the analysis conducted by I Gusti Ngurah Anom, et al (2010) and Adi Indra, et al (2006) that there is a meaningful relationship between the serum level of TNF- with preeklampsia.31 incident, 32 In this study raised the cut off point 3.618 pg / ml, the result is slightly different from the research I Gusti Ngurah Anom, et al (2010) obtained a cut off point where the lower ie 2.42 pg / ml with a sensitivity of 75% and specificity 68% based on the research of a sample of 28 cases normotensi and preeclampsia samples of 28 kasus.31 According to the cytokine hypothesis, reduced perfusion pressure uteroplasenta and presence of ischemic / hypoxic placenta is thought to increase the release of cytokines into the maternal circulation and increased plasma cytokines would then cause vascular changes are common and hipertensi.33, 35 At the end of the trimester abnormal apoptosis occurs first release in which there was proliferation and differentiation sitotropoblast, mergers and sinsitiotrofoblast sitotrofoblast, lanjut sinsitiotrofoblast differentiation and apoptosis sinsitium tuft formation forming korpuskular structure, this structure will not release induced inflammatory response maternal.37 In normal apoptotic mechanisms of preeclampsia did not occur until necrosis occurs sinsitiotrofoblast (aponekrosis) giving rise to damage in the placenta, which will give rise to the release of various cytokines (TNF-) into the maternal circulation, which in turn will give rise to endothelial damage, with clinical manifestations of preeclampsia. Cytokines (TNF-) increased in patients with preeclampsia who stimulate the occurrence of activation and dysfunction endotel.34 netrofil, 36.38 from this research obtained the level of serum TNF- was significantly increased in patients with preeclampsia. There are several studies that support the hypothesis of a rise in the serum level of TNF- in patients with preeclampsia: Mihu, et al (2008) prove the hypothesis of an increase in significant serum level of TNF- in patients with preeclampsia compared with pregnant women normotensi.12 Afshari (2005) reported the rate of IL-6 and TNF- serum is immune activation markers and endothelial dysfunction in patients with preeclampsia. They get the average level of serum TNF- is higher in patients with preeclampsia compared to women with normal values of p> 0.1 which means that statistik.29

CONCLUSION 1. In this study, obtained the level of serum TNF- in preeclampsia group 3733 reached 31 870 pg / ml and in group normotensi pregnancy rate obtained values of serum TNF- 1,188 pg / ml up to 3504 pg / ml, were found statistically increased rates of serum TNF- significantly in preeclampsia group with the cut off point 3.618 pg / ml. 2. Results of the analysis of the relationship between the serum level of TNF- in preeclampsia and pregnancy normotensi with Lavene test t test and earned value = 100% sensitivity and specificity = 100% value.