EVALUATION OF HEPATIC, RENAL AND CEREBRAL FUNCTION TEST IN PREECLAMPSIA-ECLAMPSIA SYNDROME AND ITS CORRELATION TO MATERNAL AND FETAL OUTCOME

study was a prospecve cohort study comparing the maternal and fetal outcomes of preeclampsia and eclampsia paents with abnormal parameters (cases; n=50) and preeclampsia and eclampsia paents with normal parameters (controls; n=50). Both case and control were examined clinically apart from biophysical and biochemical invesgaon. Deranged LFT was present in approximately 56% -70% of cases. Serum albumin was decreased in 80% of cases. Prothrombin me (PT) was raised in 48% of cases. Abnormal GFR, urea, creanine and uric acid level were present in 44%, 10%, 10% and 64% of cases. Among all the pregnancy outcomes in preeclampsia and eclampsia cases with abnormal LFT, preterm labour, PPH, IUFD, meconium stained liquor and neonatal death had signiﬁcant “p” value <.05. There were 16% preterm labours, 60% IUGR, 36% ARF, 18% Neonatal death, in cases with abnormal RFT. It was found from the study that CVA, Cerebral hemorrhage, fetal distress, and sll birth were present in 16%, 24%, 36% and 8% of cases with abnormal cerebral funcon. Deranged liver funcon test was associated with increased incidence of postpartum hemorrhage (P value=0.0001) and postpartum eclampsia (P value <0.0001). Deranged Renal Funcon Test is associated with increased incidence of IUGR (P value=0.0002) and ABSTRACT


INTRODUCTION
Hypertensive disorders complicates 5-10% of pregnancies all over the world and its incidence in India was found to be 10.08% as per data of Na onal Eclampsia Registry (NEP). Prevalence of eclampsia is 1.9% among registry pa ents. Considering a global scenario, according to World Health Organiza on (WHO) mul country survey, incidence of hypertensive disorders in pregnancy is 2.73%, incidence of 1 preeclampsia is 2.16% and eclampsia is 0.28%. They form one of the deadly triad along with hemorrhage and infec on 2 contribu ng to maternal and fetal morbidity and mortality. The World Health Organiza on systema cally reviews maternal mortality worldwide and in developed countries 16% of maternal death were reported to be due to 3 hypertensive disorders. The complica ons of preeclampsia includes eclampsia, cerebral hemorrhage, cardiovascular complica ons, hepa c failure, acute renal failure (ARF) , pulmonary edema, Acute Respiratory Distress Syndrome (ARDS), Disseminated Intravascular Coagula on (DIC), Hemolysis, Elevated Liver Enzymes, Low Platelet Count (HELLP) Syndrome, re nal detachment, cor cal blindness, hypoxic cerebral damage and even maternal chronic 3 hypertension and death. ACOG 2013 Bulle n has classified hypertensive disorders in pregnancy into four categorieschronic hypertension of any e ology, Gesta onal hypertension, Preeclampsia-eclampsia syndrome and preeclampsia 4 superimposed on chronic hypertension. In United Kingdom, among 38% eclamp c cases, seizure occurred without any prior documenta on of either hypertension or proteinuria in the hospital se ng. De novo seizure in the absence of preeclampsia suggest that pregnancy alone may be a state of increased seizure suscep bility due to decreased expression of gamma amino butyric acid receptors (GABA R ) and A S and/or neuro-inflamma on that acts to lower seizure 5 threshold. In the pathogenesis of preeclampsia, placenta is the central organ, since the removal of placenta abolishes the disease. In preeclampsia the invasion of the cytotropho blast into the spiral arteries is incomplete, i.e. only in 6 the superficial layer of the decidua. The typical histopathological changes characteris cs of preeclampsia is glomerular endotheliosis i.e. fibrin deposi on, endothelial swelling and loss of capillary spaces. It resolves at variable rates postpartum. Lately, podocy c altera on, podocyturia, enhanced apoptosis, downregula on of nephron and other key proteins of slit diaphragm may explain proteinuria in 6 preeclampsia. Disturbance in the vascular development of placenta resul ng in a placental hypoperfusion and ischemia. The damaged placenta secretes a wide range of an angiogenic factors into the maternal circula on causing systemic endothelial cell dysfunc on and microangiopathy. The endothelial damage in liver can produce periportal hemorrhagic necrosis with the release of hepatocellular enzymes into the circula ons. Alanine Aminotransferase (ALT) is considered more liver specific than Aspartate Amino 7 Transferase AST. On the basis of observed total oxidant status (TOS) and total an oxidant status (TAS) it has been inferred that increased oxida ve stress and an oxida ve defense mechanism may contribute to the diseases process in preeclampsia. Increased forma on of reac ve oxygen species (ROS) may contribute to renal dysfunc on apart from renal dysfunc on. Uric acid, crea nine and urea may possess water soluble/hydrophilic an oxidant property, which inhibit or delay cellular damage through the free radical scavenging property and it also prevents strong an oxidant ac vi es towards ROS in aqueous phase. Elevated blood uric acid together with urea and crea nine level may predict and correlate with the severity of 8 preeclampsia. Women with preeclampsia have a 3-4 fold increased risk of developing chronic hypertension and a 2 fold increased risk of developing ischemic heart diseases, 10 stroke and venous thromboembolism later in life. Our aims and objec ves were to determine the incidence of abnormal liver, renal and cerebral func on test in preeclampsia and eclampsia cases and to study the effect of abnormal liver func on, renal func on and cerebral func on on maternal and fetal outcome in preeclampsia and eclampsia cases.

METHODOLOGY
The Prospec ve Cohort study was conducted at the Department of Obstetrics and Gynecology, Medical College Hospital, Kolkata-73, from 01.02.19 to 31.01.2020. This is a prospec ve cohort study. All preeclampsia and eclampsia mothers with normal (control) and abnormal (case) liver func on, renal func on and cerebral func on were included in our study. Pregnancy with chronic hypertension and /with superimposed preeclampsia-eclampsia, pregnancy with epilepsy, pregnancy with cerebrovascular accident, chronic hypertension, mul ple gesta on, molar pregnancy, intrahepa c cholestasis, viral hepa s, portal hypertension with esophageal varices, Wilsons diseases, autoimmune hepa s, hepa c adenomas, hepatocellular carcinoma, nonalcoholic fa y liver diseases and any systemic illness were excluded from our study. The Ins tute of Ethics Commi ee of Medical College and Hospital Kolkata approved our study. Informed consent of the pa ents were taken before including them into the study. The criteria for the diagnosis of preeclampsia and eclampsia were in accordance with the guidelines of the American College of Obstetricians and Gynecologists, January 2019. There were 50 pa ents of preeclampsia and eclampsia with abnormal liver func on, renal func on and cerebral func on (Cases) and 50 pa ents of preeclampsia and eclampsia with normal liver func on, renal func on and cerebral func on (Controls). We calculated the sample size by using formula for cohort study 2 2 i.e. (p 0 q 0 + p 1 q 1 ) (z1 -a/2 + z1 -) / (p1 -p 0 We put the data about the study pa ents over preplanned proforma. Then data were entered in MS Excel according to parameters. They were analyzed by calcula ng frequency and percentages. The tables and graph charts were prepared based over frequency and percentage calcula ons. "Con ngency table" were obtained and "Fisher's Exact Test" is done to obtain', p value and rela ve risk with 95% confidence interval. It had been found that 16% of cases having increased total bilirubin level. Out of 50 cases, there were 30 pa ents with eclampsia and 20 pa ents with pre-eclampsia. Among them, 16% had increased total bilirubin level. Liver enzymes were also raised i.e. increased level of AST and ALT were observed in 70% and 56% of cases respec vely. Be er not to comment on ALP as it is nonspecific in pregnancy. Liver enzymes were also raised i.e. increased level of AST , ALT and Alkaline Phosphatase were observed in 70%, 56% and 60% of cases respec vely. Serum albumin was decreased in 80% of cases. . 48% of the cases presented with raised Prothrombin Time (PT). There was significant ("p" value) difference in LFT parameters derangement like total bilirubin, ALT , serum albumin and P-me (PT) between preeclampsia and eclampsia cases. Abnormal Glomerular Filtra on Rate (GFR), urea, crea nine and uric acid level were present in 44%, 10%,10% and 64% of cases of preeclampsia and eclampsia. Abnormal GCS (4/5) was found in 54% of cases. Plantar extensor, cerebral edema and re nal hemorrhage were present in 24%, 24% and 10% of cases. There was significant ("p" value) difference in cerebral func on test parameters derangement like abnormal Glasgow coma scale and plantar extensor reflex between  There were 16% preterm labour, 60% IUGR , 36% ARF, 18% Neonatal death, in preeclampsia eclampsia cases. The most common complica on was IUGR (RR 2.159; 95%CI 1.444-3.226 ; p value 0.0002). The least common complica on was preterm labour and neonatal death with a non significant "p" value 0.0916 and 0.3881 respec vely Fetomaternal complica ons were more in severe renal disease. Our study also revealed same type of outcome like preterm labour (16%), IUGR (60%), ARF (36%) and neonatal death (18%) in preeclampsia and eclampsia mother with abnormal renal func on. Marilyn J. Cipolla 14 Marilyn JC had established in his study that cerebral autoregula on mechanism is totally lost in preeclampsia and eclampsia leading to cerebral edema forma on 14 responsible for different neurological sequel. Paul Nkemtendong Tolefac et al Paul NTet al. presented a case report of spontaneous hemorrhagic stroke complica ng 15 severe preeclampsia). Our study showed different pregnancy outcome in preeclampsia and eclampsia with abnormal cerebral func on tests, like CVA (16%), cerebral hemorrhage (24%), fetal distress (36%) and s ll birth (8%).

CONCLUSION
Preeclampsia and eclampsia are the significant causes of maternal and fetal morbidity and mortality in our country. Deranged liver, renal and cerebral func on tests parameters are associated with poor maternal and fetal outcome in preeclampsia and eclampsia. It is very essen al to recognize early warning symptoms and signs to avert the life threatening complica ons in the cases where preven on is not totally possible.

RECOMMENDATIONS
Provision of quality antenatal health care services, inves ga ons, mely delivery, intensive monitoring in the intrapartum and postpartum period, essen al educa on to the women and accessible health care services to the socioeconomically deprived and rural popula on are required.

LIMITATIONS OF THE STUDY
Single study centre, referral bias, reason for NICU admission would not be sought for as neonates in NICU would not be followed up ll discharge.