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Abstrak :
ABSTRAK
Adverse pregnancy outcome (APO) adalah kondisi patologis kehamilan yang berperan dalam morbiditas dan mortalitas maternal dan perinatal, antara lain preeklamsia (PE)/ eklamsia, keguguran berulang, kematian janin dalam kandungan, dan pertumbuhan janin terhambat (PJT). Penelitian ini bertujuan mengetahui peran resistensi arteri uterina, kadar Annexin-V, sTNF-R2, dan sFlt-1 pada serum wanita hamil trimester II sebagai prediktor PE dan PJT. Penelitian ini dilakukan menggunakan desain potong lintang, kohort dan nested case control di RS.Fatmawati dan Puskesmas Kecamatan Cilandak, Jakarta Selatan. Subjek penelitian adalah ibu hamil 22?24 minggu yang datang ke poliklinik antenatal care. Dilakukan pemeriksaan doppler velosimetri arteri uterina. Bila tinggi/takik dikategorikan sebagai kasus dan bila normal sebagai kontrol. Pada seluruh subjek penelitian dilakukan pemeriksaan Annexin-V, sTNF-R2 dan sFlt-1. Seluruh subjek diikuti secara prospektif sampai dengan timbul gejala PE atau PJT. Dari 96 subjek, 47 kasus dan 49 kontrol, lima subjek (5,2 %) dengan manifestasi APO, terdiri dari 3 subjek mengalami Preeklamsia (PE) dan Pertumbuhan Janin Terhambat (PJT), 2 subjek hanya mengalami Pertumbuhan Janin Terhambat (PJT). Seluruhnya terjadi pada kelompok kasus (10,6 %), dengan risiko relatif kejadian APO 11,46 (95 % IK: 0,65?201,66). Nilai titik potong kadar Annexin-V serum pada APO ≤ 0,84 ng/mL dengan nilai sensitivitas 80% dan spesifisitas 61,50%. Nilai titik potong kadar sTNF-R2 serum pada APO ≤ 236,93 ng/mL dengan nilai sensitivitas 60,00% dan spesifisitas 53,80%. Titik potong kadar sFlt-1 serum pada APO ≥ 1331,66 pg/mL dengan nilai sensitivitas 40,00% dan spesifisitas 75,80 %. Di buat model prediksi, menggunakan variabel paritas, usia maternal dan kadar annexin-V < 0,84 ng/mL. Resistensi arteri uterina yang tinggi di usia kehamilan 22?24 minggu meningkatkan peluang terjadinya APO 11,46 kali

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ABSTRACT
Adverse pregnancy outcomes (APO) is a group of pathological conditions of pregnancy which play a role in morbidity and/or mortality maternal/perinatal. Included in this complications are preeclampsia (PE)/eclampsia, recurrent miscarriage, fetal death in utero, and Fetal Growth Restriction (FGR). The objective of this study was to determine the role of resistance of the uterine artery by doppler velocymetry examination, the serum levels of annexin-V, sTNF-R2, and sFlt-1 in the 22?24 weeks of pregnancy as a predictor of PE and FGR. This study was conducted at Fatmawati Hospital and Cilandak Subdistrict Health Center, South of Jakarta. Subjects of the study was a 22?24 weeks pregnant women who came to the antenatal care clinic. Doppler velocymetry examination of uterine artery was conducted, subjects with high resistance categorized as cases, while when normal, categorized as a control. To all of the subjects, measurement of serum Annexin-V, sTNF-R2 and sFlt-1 was carry out. Out of 96 subjects, 47 were cases and 49 were controls. Five (5.2 % ) subjects with APO, consisting of three subjects had PE and FGR, two subjects experienced only FGR. All of APO found in the case group (10.6%), with relative risk was 11.46 (95% CI: 0.65?201.66), with p = 0.096. If the notch was seen, the relative risk of APO was 6.44 (95% CI: 0.78?53.20), with p = 0.04. The cut-off point of serum Annexin V in subject with APO was ≤ 0.84 ng / mL with a sensitivity of 80% and specificity of 61.50%. The cut-off point serum levels of TNF-R2 in subject with APO was ≤ 236.93 ng/mL, with a 60.00% sensitivity and specificity of 53.80%. The cut-off point serum levels of sFlt-1 in subject with APO was ≥1331.66 pg/mL with a 40.00% sensitivity and specificity of 75.80%. Prediction model has been made, using variabel maternal age, parity and the serum level of Annexin V. High uterine artery resistance at 22?24 weeks gestational age increases the chances of APO 11.46 times

Abstrak :
ABSTRAK
Preeklamsia merupakan masalah kesehatan maternal yang berdampak luas pada kesehatan manusia. Defek plasentasi merupakan faktor predisposisi utama preeklamsia yang mengakibatkan spektrum kematian sel apoptosis, aponekrosis dan autofagi. Autofagi juga berperan sebagai mekanisme ketahanan selular melalui nutrisi sebagai regulator utama. Penelitian ini bertujuan untuk mengetahui peran nutrisi dan autofagi sebagai ketahanan selular pada patomekanisme preeklamsia . Penelitian ini merupakan penelitian dengan desain potong lintang yang dilakukan terhadap 4 kelompok yakni; hamil normal, preeklamsia awitan lanjut, preeklamsia awitan dini dan PJT dengan jumlah sampel 10 pasien tiap kelompok. Dilakukan analisis nutrisi secara kualitatif dan kuantitatif untuk zat nutrisi vitamin D, kalsium dan seng serta zat nutrisi sebagai marka inflamasi yaitu vitamin A dan mineral besi. Dilakukan pemeriksaan marka kematian sel LDH dan pemeriksaan marka autofagi LC3, Beclin-1, kegagalan autofagi rasio LC3/Beclin-1 serta marka nutrisi plasenta VDR. Selama periode Agustus hingga Oktober 2015 terdapat 40 pasien yang mengikuti penelitian di RSUPN Cipto Mangunkusumo dan RS Budi Kemuliaan Jakarta. Terdapat perbedaan bermakna ekspresi LC3 dan Beclin-1 serta rasio LC3/Beclin-1 di antara kelompok penelitian. Kelompok preeklamsia awitan dini dan PJT memiliki ekspresi LC3 dan Beclin-1 tertinggi, sedangkan kelompok hamil normal dan preeklamsia awitan lanjut memiliki rasio LC3/Beclin-1 tertinggi. Terdapat korelasi antara kegagalan autofagi dengan LDH. Terdapat defisiensi vitamin D, kalsium dan seng serta terdapat peningkatan retinol dan ferrum sebagai marka inflamasi pada kelompok kehamilan patologis. Terdapat mekanisme up regulation ekspresi nutrisi plasenta reseptor vitamin D VDR pada kelompok preeklamsia awitan lanjut dan awitan dini , sementara ditemukan ekspresi VDR yang rendah pada kelompok PJT. Terdapat korelasi negatif antara rasio LC3/Beclin-1 dengan marka nutrisi maternal terutama kelompok preeklamsia awitan lanjut dan awitan dini. Terdapat korelasi bermakna antara rasio LC3/Beclin-1 dengan ekspresi VDR sebagai marka nutrisi plasenta pada kelompok preeklamsia awitan dini. Autofagi berperan dalam proses kematian sel dan ketahanan selular trofoblas. Terdapat peran nutrisi yang berkorelasi dengan proses autofagi pada patomekanisme preeklamsia. Kata kunci : Autofagi, kematian sel, ketahanan selular, nutrisi, preeklamsia.

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ABSTRACT
Preeclampsia is a maternal health problem which largely affects human well being. Placentation defects is the main predisposition factor of preeclampsia which cause cell death spectrum of apoptotic, aponecrosis, and autophagy. Autophagy also has a role as cellular survival mechanism as well through nutrition as main regulator. This research aims to understand the roles of nutrition and autophagy as cellular survival in pathomechanism of preeclampsia. The research has cross sectional study design which was conducted to four groups of pregnancy normal pregnancy, late onset preeclampsia, early onset preeclampsia, and intrauterine growth restriction IUGR with 10 samples for each group. Qualitative and quantitative nutrition analysis was done for vitamin D, calcium and zinc. The same methods was done to nutrients as inflammatory markers which is vitamin A and iron. Assessment was done for cell death marker LDH, autophagy markers LC3, Beclin 1, autophagy failure ratio of LC3 Beclin 1, and placenta nutrition marker VDR. During the period of August to October 2015 there were 40 patients participated in research which was conducted in RSUPN Cipto Mangunkusumo and RS Budi Kemuliaan Jakarta. Analysis shows statistically significant difference between groups of the expression of LC3 and Beclin 1 and ratio of LC3 Beclin 1 as well. Early onset preeclampsia and IUGR group showed the highest LC3 and Beclin 1 expression, while normal pregnancy and late onset preeclampsia group showed the highest ratio of LC3 Beclin 1. There was a correlation between autophagy failure and LDH. There were deficiencies of vitamin D, calcium and zinc and the increase of retinol and iron as inflammatory markers in pathological pregnancy. There was up regulation of vitamin D receptor VDR expression in early and late onset preeclampsia, while low expression of VDR in placenta of IUGR group. There was negative correlation between ratio of LC3 Beclin 1 and maternal nutrition markers particularly in preeclampsia group. There was significant correlation between the ratio of LC3 Beclin 1 and expression of placenta VDR as nutrition marker in early onset preeclampsia group. Autophagy plays a role in the spectrum of cell death and cellular survival in trophoblast. There is role of nutrition in correlation with autophagy process in pathomechanism of preeclampsia Keywords Autophagy, cell death, cellular survival, nutrition, preeclampsia

Abstrak :
Latar belakang: Rekomendasi Centers for Disease Control and Prevention (CDC) 2010 (revisi 2002) tidak spesifik memberi panduan dalam pencegahan sekunder sepsis awitan dini (SAD) pada neonatus cukup bulan (NCB), asimtomatik lahir dari ibu yang mengalami KPD < 18 jam. Tujuan: Didapatnya model determinan SAD pada NCB sesuai masa kehamilan (SMK), asimtomatik lahir dari ibu yang mengalami KPD lebih dari 12 jam. Metodologi: penelitian observasional potong lintang untuk mendapatkan model determinan sepsis neonatorum awitan dini (SNAD) yang dilakukan dari Februari 2013 sampai bulan Mei 2014 di RSAB Harapan Kita, RSUD Tarakan, RSIA Budi Kemuliaan. Determinan yang diteliti adalah jenis persalinan, petanda infeksi saluran kemih (ISK) pada ibu, petanda infeksi intra amnion (IIA) seperti demam intrapartum, ibu takikardia, janin takikardia, adanya perubahan warna dan bau cairan ketuban, leukosit darah ibu, dan petanda infeksi darah tali pusat (peningkatan jumlah total leukosit, neutrofil, peningkatan rasio I/T, hs-CRP dan IL-6). Diagnosis sepsis ditegakkan berdasarkan catatan medis bayi yang dipastikan berdasarkan hasil positif biakan darah tali pusat. Model determinan SNAD yang dihasilkan adalah suatu persamaan regresi logistik yang digunakan untuk menentukan probabilitas terjadinya SNAD sebagai acuan terapi antibiotik. Hasil: model determinan SAD pada NCB SMK, asimtomatik lahir dari ibu KPD > 12 jam berupa kalkulator dan sistem skor yang dibentuk dari determinan persalinan per vaginam, perubahan warna dan bau cairan ketuban, leukosit darah ibu, leukosit darah tali pusat, kadar hs-CRP darah tali pusat dan kadar IL-6 darah tali pusat. Model determinan SNAD memiliki dua varian, varian lengkap digunakan untuk fasilitas pelayanan neonatus subspesialistik dan varian alternatif digunakan untuk fasilitas pelayanan spesialistik. Titik potong ideal penentuan probabilitas terjadinya SNAD memiliki sensitivitas di antara 24,2 – 40,3 % dan spesifisitas 87,1 - 94,5 %. Nilai diskriminasi dengan nilai AUC berkisar di antara 0,743 – 0,816 dengan kalibrasi baik berdasarkan uji Hosmer-Lemeshow. Simpulan: Hasil penelitian ini adalah model determinan SAD pada NCB SMK asimtomatik lahir dari ibu yang mengalami KPD > 12 jam, berbentuk kalkulator dan sistem skor yang memiliki varian lengkap dan alternatif untuk menentukan probabilitas terjadinya SNAD sebagai dasar pemberian terapi antibiotik empiris secara rasional. ......Background: Centers for Disease Control and Prevention (CDC) 2010 (revised 2002) recommendations does not specifically provide guidance in secondary prevention of asymptomatic early-onset sepsis (EOS) on term infant born to mother experiencing PROM < 18 hours. Objective: to develop early-onset neonatal sepsis (EONS) determinant model as a rational basis for determining the empirical antibiotic therapy in asymptomatic, term infant born to mother with PROM > 12 hours. Method: A cross-sectional observational study to obtain an EONS determinant model which was conducted from February 2013 to May 2014 in RSAB Harapan Kita, Tarakan Hospital, RSIA Budi Kemuliaan. The determinant factor is the type of delivery, marker of maternal urinary tract infection (UTI), intra-amniotic infection markers (intrapartum fever, maternal tachycardia, fetal tachycardia, change in the color and odor of amniotic fluid, maternal blood leukocytes), and umbilical cord blood infection marker (increased the total number of leukocytes, neutrophils, an increase in the ratio of I / T, hs-CRP and IL-6). Early-onset neonatal sepsis was diagnosed base on infant medical record on 72 hours afeter birth and confirmed by the positive results of umbilical cord blood cultures. The resulting of EONS determinants model is a logistic regression equation used to determine the probability of the occurrence of EONS as reference rational basis empirical antibiotic therapy. Results: The EOS determinants model on asymptomatic term infant born to mothers with PROM> 12 hours is a calculator and scoring system that is formed from the determinant of vaginal delivery, change the color and odor of amniotic fluid, maternal blood leukocytes, cord blood leukocytes, the levels of hs-CRP and IL-6 umbilical cord blood level. Early-onset neonatal sepsis determinant model has two variants, the full variant used for subspecialty neonatal care facilities and alternative variant is used for specialty neonatal care facilities. Ideal cutoff point probability of occurrence SNAD has sensitivity range of 24.2 to 40.3% and specificity of 87.1 to 94.5%. The model performe is good based on Hosmer-Lemeshow test anda discrimination value AUC in in range of 0.743 to 0.816. Conclusion: The EOS determinant model of asymptomatic term infant born to mothers with PROM > 12 hours is a calculator and scoring system that is used to determine the probability of EONS occurrence as the basis of determining the rational empirical antibiotic therapy.

Abstrak :
Preeklamsia dibagi menjadi preeklamsia awitan dini (PEAD) jika terjadi pada usia kehamilan < 34 minggu dan preeklamsia awitan lanjut (PEAL) pada kehamilan > 34 minggu. Intoleransi imun diduga menyebabkan penolakan imun terhadap fetus di plasenta. Dendritic cell 10 (DC-10) dan sel T regulator CD4+CD25+FoxP3 (Treg) di desidua berperan penting dalam menciptakan lingkungan yang tolerogenik selama kehamilan. Namun, peran spesifik dalam patomekanisme PEAD dan PEAL serta faktor-faktor nutrisi yang berperan dalam regulasi DC-10 dan Treg, yaitu seng, vitamin A, dan vitamin D belum diteliti secara jelas. Penelitian ini bertujuan untuk memahami patomekanisme penolakan imun pada preeklamsia melalui jumlah DC-10 dan sel Treg desidua serta hubungannya dengan vitamin A, vitamin D, dan seng. Desain penelitian ini adalah studi potong lintang komparatif antara kehamilan dengan PEAD, PEAL, dan NT antara Oktober 2019 dan Desember 2021. Subjek penelitian direkrut dari RSUP Fatmawati (Jakarta), RSUPN Cipto Mangunkusumo (Jakarta), dan RSUD Karawang (Jawa Barat). Kriteria penerimaan adalah semua ibu hamil 20–40 minggu yang menjalani persalinan dengan seksio sesaria dan setuju untuk dilibatkan dalam penelitian. Kriteria penolakan meliputi pasien dengan penyulit obstetrik, plasenta previa, memiliki riwayat penyakit kronik, hipertensi sebelum kehamilan 20 minggu, terdiagnosis COVID-19, demam dan leukosit >15.000 /mL pada saat pemeriksaan dan kematian janin dalam rahim. Spesimen desidua diperoleh dengan kuretase tajam setelah seksio sesaria. Jumlah DC-10 dan sel Treg dihitung dengan flow cytometry. Konsentrasi faktor nutrisi diperiksa dengan metode ICP-MS dan LC-MS. Perbandingan median dianalisis dengan uji Kruskal-Wallis, sedangkan koefisien korelasi diperoleh dengan uji korelasi Spearman. Subjek penelitian adalah 14 ibu hamil untuk setiap kelompok (total 42 kasus). Jumlah DC-10 lebih rendah secara bermakna pada PEAD dibandingkan NT (p < 0,001) dan lebih rendah secara bermakna pada PEAL dibandingkan NT (p = 0,015). Sebaliknya, sel Treg FoxP3+CD25+ lebih tinggi secara bermakna pada PEAD dibandingkan NT (p = 0,015). Tidak terdapat korelasi antara faktor nutrisi dan jumlah faktor tolerogenik pada kelompok preeklamsia (PE). Namun, terdapat korelasi sedang antara konsentrasi seng desidua dan DC-10 di kelompok NT (r = 0,656; p = 0,011) dan korelasi kuat antara konsentrasi retinol desidua dan DC-10 juga di kelompok NT (r = 0,746; p = 0,002). Korelasi sedang didapatkan antara konsentrasi vitamin D dan jumlah sel Treg FoxP3+CD25+ di kelompok NT (r = 0,590; p = 0,026). Disimpulkan bahwa jumlah DC-10 pada PEAD lebih rendah dibandingkan dengan kehamilan NT, sedangkan jumlah sel Treg pada PEAD secara bermakna lebih tinggi dibandingkan dengan kehamilan NT. Konsentrasi faktor nutrisi desidua tidak berkorelasi dengan jumlah DC-10 atau Treg desidua pada preeklamsia (PEAD dan PEAL). Namun, pada kelompok NT terdapat korelasi positif antara seng dan DC-10, retinol dan DC-10, serta vitamin D dan jumlah sel Treg desidua. ......Preeclampsia is categorized as early-onset preeclampsia (EOPE) at < 34 week of gestation and late-onset preeclampsia (LOPE) at > 34 week of gestation. Immune intolerance is thought to be the underlying cause of immune rejection to the fetus in the placenta. Decidual dendritic cell-10 (DC-10) and T regulator cell CD4+CD25+FoxP3 (Treg) play important role to create a tolerogenic environment during pregnancy. However, the specific role in the pathomechanism of EOPE or LOPE and nutritional factors that play role in the regulation of DC-10 and Treg, i.e. zinc, vitamin A, and vitamin D have not been widely studied. This study was aimed to know the pathomechanism of immune rejection in preeclampsia through the number of decidual DC-10 and Treg cell and their correlations with vitamin A, vitamin D, and zinc. The study design was cross-sectional comparative among EOPE, LOPE, and NT pregnancies between October 2019 and December 2021. Study subjects were recruited from Fatmawati General Hospital (Jakarta), Cipto Mangukusumo National General Hospital (Jakarta), and Karawang Regional Public Hospital (West Java). Inclusion criteria were all pregnant women between 20–40 weeks of gestation who underwent cesarean delivery and gave their written consent to be included in the study. Exclusion critera were patients with obstetric complications, placenta previa, history of chronic disease, hypertension before 20 weeks of gestation, was diagnosed with COVID-19, fever and leukocyte count of >15.000 /mL at the time of examination and presence of intrauterine fetal death. Decidual specimens were obtained by curettage after the cesarian section. The number of DC-10 and Treg cells were counted using flow cytometry. Concentrations of nutritional factors were assayed using ICP-MS and LC-MS method. Median comparison among groups was analyzed using Kruskal-Wallis test, while correlation coefficient was obtained by using the Spearman correlation test. Study subjects were 14 pregnant women for each group (42 cases in total). The DC-10 was significantly lower in EOPE compared to NT (p < 0.001) and significantly lower in LOPE compared to NT (p = 0.015). On the other hand, Treg FoxP3+CD25+ cells were significantly higher in EOPE compare to NT (p = 0.015). No correlation between nutritional factors and the number of tolerogenic factors in the preeclampsia group. However, there was a moderate correlation between decidual zinc concentration and DC-10 in the NT group (r = 0.656; p = 0.011) and a strong correlation between decidual retinol concentration and DC-10 also in NT group (r = 0.746; p= 0.002). A moderate correlation was found between vitamin D concentration and Treg FoxP3+CD25+ cells in the NT group (r = 0.590; p = 0.026). To conclude, the number of DC-10 in EOPE is lower than NT pregnancy, whereas the number of Treg cells in EOPE is higher than NT pregnancy. Concentrations of dedicual nutritional factors do not correlate with the number of decidual DC-10 or Treg cells in preeclampsia (EOPE and LOPE). However, in NT group, there is positive correlation between decidual zinc and DC-10, retinol and DC-10, and vitamin D and Treg cells.

Abstrak :
Preeklamsia merupakan salah satu penyebab kematian utama ibu dan perinatal di dunia. Inflamasi disertai tingginya indeks apoptosis di syncytiotrophoblast dan ekspresi Cyclophilin A diduga berperan pada preeklamsia. Faktor tersebut diasumsikan menyebabkan jejas jantung/pembuluh darah yang meningkatkan risiko morbiditas dan mortalitas ibu dan perinatal. Tujuan penelitan ini adalah menganalisis peran inflamasi, indeks apoptosis dan Cyclophilin A terhadap jejas jantung/pembuluh darah pada preeklamsia awitan dini, lanjut dan kehamilan normal. Sebanyak 47 wanita hamil yang terpilih dilakukan pemeriksaan hematologi, ekokardiografi dan ultrasonografi Doppler. Plasenta diperiksa secara histopatologis untuk mengukur ekspresi NF-KB dan PARP-1, indeks apoptosis berdasarkan pemeriksan TUNEL, ekspresi Cyclophilin A dan pemeriksaan ultrastruktur mikroskopik pada syncytiotrophoblast. Analisis Anova digunakan untuk mengidentifikasi perbedaan antara ketiga kelompok, sedangkan regresi linier digunakan untuk mengetahui korelasi faktor yang diduga terhadap jejas jantung/pembuluh darah menggunakan SPSS 20. Usia ibu, indeks massa tubuh (IMT), hitung trombosit, NF- KB dan indeks apoptosis lebih tinggi disertai Cyclophilin A lebih rendah pada preeklamsia awitan dini dibandingkan preeklamsia awitan lanjut dan kehamilan normal. Hitung leukosit lebih tinggi pada preeklamsia awitan lanjut dibandingkan awitan dini dan normal. Total peripheral resistance (TPR) paling tinggi pada kelompok awitan dini dibandingkan awitan lanjut dan kehamilan normal, sedangkan cardiac index (CI) tidak berbeda bermakna pada ketiga kelompok. Resistensi indeks (RI) lebih tinggi pada preeklamsia awitan dini dibandingkan awitan lanjut dan kehamilan normal. Berdasarkan analisis regresi linier multivariat, membuktikan indeks apoptosis dan Cyclophilin A memiliki hubungan dengan jejas jantung/pembuluh darah. Hal tersebut menunjukkan inflamasi, indeks apoptosis, Cyclophilin A disertai pemeriksan ekokardiografi dan ultrasonografi Doppler merupakan metode yang cepat, tepat dan noninvasif faktor risiko terhadap jejas jantung/pembuluh darah pada preeklamsia. Penelitian yang dianjurkan di masa datang adalah menilai geometri jantung dengan ekokardiografi dan volumetri plasenta dengan ultrasonografi. ...... Preeclampsia is one of the leading cause of maternal and perinatal death in the world. Inflammation accompanied by a high apototic index of syncytiotrophoblast and Cyclophilin A were speculated to play a role in preeclampsia. Those response were assumed to cause cardiovascular injury which lead to the risk of maternal and perinatal morbidity and mortality in preeclampsia. The objective of the study was to investigate the role of inflammation, apoptotic index and Cyclophilin A in cardiovascular injury in early and late onset preeclampsia compared to normal pregnancy. A total of 47 pregnant women were selected, consisting almost the same size of each group (30%) and assessed for maternal hematology, echocardiography and Doppler ultrasound. Placentae were assessed histopathologically by measuring nuclear factor kappa-light-chain-enhancer of activated B cells (NF- KB) and Poly (ADP-ribose) polymerase 1 (PARP-1) expression for inflammation marker, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptotic index and Cyclophilin A. Confirmation by transmission electron microscopy (TEM) was done. Anova analysis was used to identify the differences between the three groups while linier regression was employed to assess the correlation between factors on cardiovascular injury using SPSS 20. Maternal age, body mass index (BMI), platelet count, NF- KB and apoptotic index, resistance index (RI) were higher supported by low Cyclophilin A in early onset preeclampsia (EOP) than in late onset preeclampsia (LOP) and normal pregnancy. Leukocyte count was higher in late onset preeeclampsia than in early and normal pregnancy. Total peripheral resistance (TPR) was highest in the EOP compared to LOP and normal pregnancy, while the cardiac index (CI) was not significantly different in all groups. Based on multivariate linear regression analysis, the apoptotic index and Cyclophilin A correlated to cardiovascular injury. Assesing inflammation, apoptotic index, Cyclophilin A, echocardiography examination and Doppler ultrasound examination might indicated timely and non-invasive detection as an alarm entry point for cardiovascular injury in both early and late onset preeclampsia. Cardiac geometry by echocardiography and placental volumetry by Doppler ultrasound should be performed in future research.

Abstrak :
Preeklamsia merupakan kondisi spesifik pada kehamilan yang menjadi penyebab utama morbiditas dan mortalitas maternal-perinatal. Plasentasi abnormal menyebabkan hipoksia plasenta dan gangguan regulasi responss imun sehingga mengakibatkan perubahan mikroskopik struktur plasenta berupa penurunan syncytial bridge. Penelitian ini bertujuan mengetahui toleransi imun dan nekrosis pada preeklamsia berdasarkan gambaran syncytial bridge, jumlah sel Treg, konsentrasi LDH serta profil vitamin 1,25(OH)2D3, dan seng. Penelitian potong lintang ini dilakukan pada bulan Februari–Agustus 2019 di RS Budi Kemuliaan dan RSUD Koja, Jakarta. Subjek penelitian adalah ibu hamil normotensi dan preeklamsia yang memenuhi kriteria penerimaan dan tidak memenuhi kriteria penolakan. Subjek dibagi tiga kelompok yaitu: normotensi/NT (n = 20), preeklamsia tanpa komplikasi/PE (n = 21), dan preeklamsia dengan komplikasi/PEK (n = 20). Semua subjek dilakukan pengukuran. jumlah syncytial bridge plasenta (HE), jumlah sel Treg (flowcytometric dan IHK), konsentrasi LDH (enzymatic colorimetric dan ELISA), vitamin 1,25(OH)2D3 (LC-MS/MS) dan seng (ICP-MS) darah maternal dan plasenta. Data diolah menggunakan SPSS versi 2 dan dianalisis dengan uji test-tidak berpasangan dan Mann-Whitney. Jumlah syncytial bridge pada kelompok PE (10,52/LPB) dan PEK (6,33/LPB) lebih rendah bermakna dibanding NT (14,71/LPB). Syncytial bridge PEK lebih rendah bermakna dibanding PE. Jumlah Treg plasenta kelompok PE (2,89/LPB) dan PEK (2,94/LPB) lebih rendah bermakna dibanding NT (4,11/LPB). Konsentrasi LDH maternal pada PEK (418U/L) lebih tinggi dibanding NT (167,5 U/L), dan PEK lebih tinggi dibanding PE (204 U/L) secara bermakna. Kkonsentrasi 1,25(OH)2D3 maternal kelompok PE (55 pg/mL) dan PEK (41,3 pg/mL) lebih rendah dibanding NT (63,5 pg/mL). Konsentrasi 1,25(OH)2D3 maternal PEK lebih rendah bermakna dibanding PE. Tidak ada perbedaan bermakna konsentrasi seng maternal dan plasenta pada ketiga kelompok. Sel Treg plasenta kelompok syncytial bridge sangat rendah (SSR) 2,86/LPB dan syncytial bridge rendah (SR) 3,09/LPB lebih rendah secara bermakna dibanding syncytial bridge normal (SN) 3,87/LPB. Konsentrasi LDH maternal SSR (318 U/L) lebih tinggi bermakna dibanding SR (213 U/L) dan SN (168 U/L). Konsentrasi vitamin 1,25(OH)2D3 maternal pada SSR (39 pg/mL) lebih rendah dibandingkan SR (53,85 pg/mL) dan SN (58,10 pg/mL). Peningkatan konsentrasi LDH maternal, penurunan konsentrasi 1,25(OH)2D3 maternal dan sel Treg plasenta merupakan faktor risiko berkurangnya jumlah syncytial bridge. Disimpulkan berkurangnya jumlah syncytial bridge menggambarkan beratnya proses nekrosis yang berhubungan dengan penurunan toleransi imun dan konsentrasi 1,25(OH)2D3 maternal. ......Preeclampsia is a specific condition in pregnancy as the main cause of maternal-perinatal morbidity and mortality. Abnormal placentation causes placental hypoxia and disturbances in the regulation of the immune response, thereby resulting in the microscopic structure of the placenta in the form of syncytial bridges. The present study aimed to determine the immune tolerance and necrosis in preeclampsia, on the basis of the syncytial bridge characteristic, Treg cell count, LDH concentration and vitamin 1,25(OH)2D3, and zinc profiles. This cross-sectional study was carried out from February to August 2019 at RS Budi Kemuliaan and RSUD Koja, Jakarta. The subjects were pregnant women who met the inclusion criteria and did not meet the exclusion criteria. The subjects were divided into three groups, namely the normotensive (NT) group (n = 20), the uncomplicated preeclampsia (PE) group (n = 21), and the complicated preeclampsia (PEC) group (n = 20). All subjects underwent the following examinations: placental syncytial bridge count (HE), Treg cell count (flowcytometric and IHC), LDH (enzymatic colorimetric and ELISA), 1,25(OH)2D3 (LC-MS/MS) and zinc (ICP-MS) concentration in maternal blood and placenta. The data were processed using SPSS version 20 and analyzed by means of the unpaired t and Mann-Whitney tests. The syncytial bridge count in groups PE (10.52/HPF) and PEC (6.33/HPF) was significantly lower compared with NT (14.71/HPF). PEC syncytial bridge count was significantly lower than PE. Placental Treg count in groups PE (2.89/HPF) and PEC (2.94/HPF) were significantly lower than that of the NT (4.11/HPF). Maternal LDH concentration in PEC (418U/L) was significantly higher than in NT (167.5 U/L), and PE (204 U/L). Maternal 1,25(OH)2D3 concentration in groups PE (55 pg/mL) and PEC (41.3 pg/mL) was lower compared with NT (63.5 pg/mL). Maternal 1,25(OH)2D3 concentration in group PEC was significantly lower than in PE. There were no significant differences in maternal blood and placental zinc concentration in the three groups. Placental Treg cell counts in the very low syncytial bridge count (VLSB) group (2.86/HPF) and the low syncytial bridge count (LSB) (3.09/HPF) were significantly lower than in the normal syncytial bridge count (NSB) (3.87/HPF). Maternal blood LDH in group VLSB (318 U/L) was higher than those in LSB (213 U/L) and NSB (168 U/L). Maternal 1,25(OH)2D3 concentration in group VLSB (39 pg/mL) was lower compared with LSB (53.85 pg/mL) and NSB (58.10 pg/mL). Increased maternal LDH concentration, decreased maternal 1,25(OH)2D3 concentration and placental Treg cell count were risk factors for decreased syncytial bridge count. It was concluded that the decrease in syncytial bridge count depicts the severity of the necrotic process that is associated with decreased immune tolerance and maternal 1,25(OH)2D3 concentration.