PREECLAMPSIA-ECLAMPSIA IN INDONESIA: INCIDENCE, MATERNAL AND PERINATAL MORTALITY, PATHOGENESIS AND POSSIBILITY OF PREVENTION HM Sulchan Sofoewan

Division of Feto-Maternal Departement of Obstetrics and Gynecology Fakulty of Medicine Gadjah Mada University/DR Sardjito Hospital, Yogyakarta

INTRODUCTION PREECLAMPSIA-ECLAMPSIA Multisystem disorder, unknown etiology Management and prevention is limited Lack of knowledge regarding the cause Associated with the presence of placenta Pathogenic mechanisme is still unclear No specific Dx or Tx available as yet Endothelial dysfunction is final pathway Primary, secondary and tertiary prevention

INCIDENCE
Hospital Mangkuyudan DR Sardjito DR Sardjito Hasan Sadikin Hasan Sadikin Ciptmangunksm Dr. Kariadi Dr. Pirngadi UNSRI Year 74-75 82 95 73-75 95-98 93-94 82 72-79 86-90 Incidence 1.0 1.5 4.1 2.9 13.0 14.3 3.36 0.07 3.37

MATERNAL MORTALITY
Hospital Mangkuyudan DR Sardjito DR Sardjito Hasan Sadikin Hasan Sadikin 12 Teaching H Year 77-81 82 95 90-91 91-94 81 M.Mortality 8.3 2.3 9.8-25 33.0-34.5 41.6 30.0-40.0

PERINATAL MORTALITY

Hospital
DR Sardjito DR Sardjito Cipto Mksm Hasan Sadikin

Year
82 93-98 91 95-98

Per mortal
36.1 33.1 17.1 36.8

CAUSE OF MATERNAL MORTALITY DR Sardjito Hospital 1997-2001: Preeclmp-eclmp 34.89% Hemorrhage 27.27% Infection 11.36% Others 27.28% DR Hasan Sadikin 1995-1998: Preeclmp-eclamp 53.33 Post part hemorr 13.33 Heart failure 13.33 Others 20.01

CAUSE OF MATERNAL MORTALITY DR Wahidin S. Hospital 1996-1999: Preeclmp-eclmp 38.46% Hemorrhage 30.77% Infection 19.23% Others 11.55% Sri Ratu 1995-1999: Preclmp-eclmp 37.5% Hemorrhage 25.0%

ETIOLOGY
Endothelial cell dysfunction is central theme in the pathogenesis. Cause of endothelial changes is unknown. Four hypothesis: 1. Placental ischemia 2. VLDL vs toxicity-preventing activity 3. Immune maladaptation 4. Genetic imprinting

PATHOGENESIS Absence of normal stimulation of renin-angiotensin system TxA2/prostacyclin increase LPO/Antioxidant increase Vasoconstriction Platelet aggregation Uteroplacental blood flow decrease Increase level of: Factor VIII-related antigen Total cellular fibronectin Thrombomodulin Endothelin Growth factor activity Thrombin/fibrin formation Decrease level of: Prostacyclin and Nitric oxide

PATHOGENESIS
Endothelial cell dysfunction and platelet aggregation --- thrombin/fibrin formation Inadequqte production of antiaggregatory: prostacyclin and nitric oxide TxA2 and serotonin --- platelet aggregation and fibrin formation. Prostacyclin/TxA2 imbalance Impaired placental perfusion, immunological maladaptation oxygen free radical, LPO, cyclooxygenase and impaired endothlial prostacyclin synthetase --- decrease prostacyclin. LPO/Antioxidants imbalance

MANAGEMENT
PREVENTION: Aspirin: Led to decrease in thromboxane production, relatively change in prostacyclin synthesis. Large double-blind study found no significant reduction in the incidence PEE. Calsium: Potential hypotensive action of calsium. Meta analysis of RCT no benefit of calsium supplementation could be identified.

Garlic: Antithrombotic, antiplatelet aggregation, antioxidant, immunomedulator, vasodilator, and hypertensive effect, shows a promising result in preventing need to be further evaluated. Antioxidants: Antioxidants therapy significantly reduced endothelial cell activation, suggesting that such therapy might indeed be beneficial in the prevention of preeclampsia. Administration of N-acetylcystein, an antioxidant itself and a precursor of endogenous antioxidant glutathione , might stabilize or even partly recovery the process of endothelial damage and may lead to prolongation of pregnancy.

TREATMENT The management of severe preeclampsia will consist of (1) prevention of seizures, (2) control of hypertension, and (3) delivery. Prevention of seizures: MgSO4 Antihypertension: Nifedipin, Methyldopa Delivery: Decision relatively simple when the pregnancy is 36 weeks or older. The decision is more difficult the patient is less than 36 weeks, especially when less than 32 or 30 weeks. Balance the maternal risks associated with prolongation of pregnancy with the fetal risks associated with early delivery.

MANAGEMENT OF SEVERE PREECLAMPSIA 28-34 WEEKS OF GESTATION

Management UGM UNDIP UNHAS UI

Anticonvulsi Preventive Therapy Antihypert

Corticoster

SM/IM Diazepam/IV

SM/IM Diazepam/IV

SM/IM SM/IV

SM/Drip SM/IV

Nifedipin Methyl Dopa Yes

Methyl Dopa Nifedipin Yes

Catapres
No

Nifedipin
No Comp-Active No Complic-Conservative 28 w Select Conservative

Termination

Comp Active PEE Active Imp, fail, BS < 6 Mesop BS < 8 CSectn HELLP, BS > 6 Oxyt BS > 8 Vagina IUGR Act BS, % C Sect BS > 5 : Oxyt

CONCLUSIONS
The incidence of PEE is increasing during three decade. Maternal and perinatal mortality is not too much change. Preventing need to be further evaluated. Management principally the same among the teaching hospitals.