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\begin{document}

             \author[1]{Dr.  Sampada}

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\date{\small \em Received: 7 December 2019 Accepted: 2 January 2020 Published: 15 January 2020}

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\begin{abstract}
        


Background: HEV infection, a major public health concern, is known to cause largescale epidemic and sporadic cases of acute viral hepatitis in developing countries. The infection occurs primarily in young adults and is generally mild and self-limiting; however, the case fatality rate is reportedly higher among pregnant women.Methods: Our study, a retrospective observational study, was conducted in a tertiary care centre for over a period of 3 years (Jan 2017 to Jan 2020) to find out the fetal and maternal outcome in pregnant women with HEV infection.Results: A total of 38antenatal cases with Anti-HEV IgM-positive were included, and the maternalfetal outcome was analyzed. The maternal mortality was 52.63% especially during 3 rd trimester and post-partum period, including 5 antenatal death. The most common maternal complication was acute fulminant hepatitis (39.5 %), DIC (36.8 %) and hepatic encephalopathy (31.6%). Prematurity (33.3% of total live births) and Still births (32.3 %) including4fresh still births were the commonest fetal complications noted.

\end{abstract}


\keywords{Hepatitis E, pregnancy, fulminant hepatic failure, maternal mortality, still births, hepatic encephalopathy, coagulopathy.}

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\let\tabcellsep& 	 	 		 \par
Introduction epatitis E virus is a major cause of hepatitis and death in developing world and disproportionate cause of deaths among pregnant women \hyperref[b0]{1} .It is a non-enveloped, single-stranded RNA virus and is only virus within the genus Hepevirus and family hepaviridae \hyperref[b1]{2} . HEV infectionis primarily transmitted through the feco-oral route \hyperref[b2]{3} . The infection primarily occurs in young adults and is generally mild and selflimiting; however, the mortality rate is higher among pregnant women. \hyperref[b3]{4} The nutritional, immunological and genetic factors play role in pathophysiology of fulminant HEV during pregnancy in developing countries \hyperref[b4]{5} .\par
Diminished cellular immunity (lowered CD4/CD8 cell ratio) and a high level of steroid hormones that influence viral replication during pregnancy appear to be the plausible reasons for severity of the disease \hyperref[b5]{6} .\par
The incidence and severity during pregnancy vary widely around the world. The case fatality rate is 1-2 \% in outbreaks of waterborne Hepatitis E in India and Asia, which increases up to 10-20 \% in pregnant women \hyperref[b6]{7} . Reason for the difference in the outcome of HEV in different geographical areas remains unclear \hyperref[b7]{8} but could be due to early childhood HEV exposures, producing long-lasting immunity and/or modifying subsequent responses to exposure to the virus. HEV is known to have five genotypes, four of which have been detected in humans; genotypes 1 and 2 are more virulent, genotypes 3 and 4 are more attenuated and accountable for subclinical infections \hyperref[b8]{9} .\par
This disease presents a challenging situation to the obstetrician because of the complications such as postpartum haemorrhage (PPH), preterm labour, preterm premature rupture of membrane (PPROM), maternal coagulopathy, acute fulminant liver failure, spontaneous abortion and intrauterine fetal death (IUFD). 
\section[{II.}]{II.} 
\section[{Methods \& Materials}]{Methods \& Materials}\par
A retrospective observational study was conducted at a tertiary care centre for over a period of 3 years (Jan 2017 to Jan 2020) to analyse the fetal and maternal outcome in all antenatal patients with Anti-HEV IgM-positive. 
\section[{Inclusion criteria:}]{Inclusion criteria:}\par
1. All antenatal patients with Anti-HEV IgM-positive. Associated thrombocytopenia (platelet count ranging between 21000 to 101000) was seen among 13 (34 \%) patients with 4 having severe thrombocytopenia (< 50000).\par
IV. 
\section[{Data and Statistical Analysis}]{Data and Statistical Analysis}\par
Computer based data analysis was done. Data entry sheet was designed and statistical analyses were   b) Mode of delivery Induction of labour was done in 14 cases by intracervical foleys catheter insertion. Reason for IOL were IUFD, PROM, patients with acute fulminant hepatitis with 37 completed weeks of gestation.\par
Most of the patients delivered vaginally 25/38 i.e 65.8\%. 1 patient required instruemental delivery due to maternal exhaustion in 2 nd stage of labour.\par
There were 6 patients who required lower segment c-section which makes 15.8 \%. The indication were meconium stained liquor -1, previous LSCS with PROM -1, previous 2 lscs with ovarian mass-1, severe oligohydramnios -2, previous LSCS with breech -1. 1 patient who underwent LSCS died. 1 patient required exploratory laparotomy for drainage of pelvic haematoma and required blood and fresh frozen plasma. 2 patient who underwent LSCS were transfused blood and fresh frozen plasma both pre and postoperatively .\par
5 In our study, maternal mortality rate was 52.63 \% including 5 antenatal deaths. Most of these patients (75 \% i.e 15 out of 20 deaths) presented with acute fulminant hepatitis with hepatic encephalopathy.\par
Highest bilirubin level observed was 28. Median bilirubin value was 18.7.\par
Bilirubin level was ranging between 8.7 to 28 with grossly elevated liver transaminases (highest being SGOT-4406, SGPT-3491) among the expired patients.\par
The most common maternal complication was acute fulminant hepatitis (39.5 \%) , DIC (36.8 \%) and hepatic encephalopathy (31.6\%).\par
Cases complicated by DIC were found to have Prothrombin time ranging between 16.5 to 70, with median value as 39.3. Thrombocytopenia was also seen in association in 92.8 \% patients with DIC.\par
Post partum haemorrhage (18.4 \%) and Acute kidney injury (15.8 \%) were the other complications which added to mortality and morbidity.\par
Most of the cases of PPH were managed medically and blood \& blood products transfusion. Only 1 case required exploratory laparotomy with devascularisation of uterus.\par
68 \% cases required blood and blood products transfusion reasons being post partum haemorrhage, anemia, disseminated intravascular coagulation. 90 \% cases who died were referred from peripheral hospitals with hyperbilirubinemia, hepatic encephalopathy, acute fulminant hepatitis and DIC.\par
2 cases referred from peripheral hospital with acute fulminant hepatitis with hepatic encephalopathy with coagulopathy died within 6 hours of admission.  
\section[{VI.}]{VI.} 
\section[{Comparative Study}]{Comparative Study} 
\section[{VII. Conclusion and Recommendation}]{VII. Conclusion and Recommendation}\par
Our study shows that pregnant women with acute viral hepatitis due to hepatitis E had a high mortality rate especially when infected in 3 rd trimester and post-partum period. They also had poor obstetrics and fetal outcome.\par
Early diagnosis and active management can improve the outcome. Pregnant women should be closely monitored for fetal well-being and signs of fetal distress by periodic ante-natal scan, biophysical profile , non-stress test. They should be counselled about daily fetal kick count.\par
Hepatitis E is a preventable disease so emphasis should be on sanitation, personal hygiene, hand washing, proper sewage disposal, facilities for clean drinking water and awareness regarding these.\par
Vaccine against hep-E is available and can reduce the morbidity and mortality associated with pregnancy \hyperref[b11]{12} . HEV 239 vaccine is safe for both mother and fetus and there was no hepatitis E infection in immunised pregnant women \hyperref[b12]{13} . India being an endemic area for hepatitis E with high mortality rate this may be considered as an option. 
\section[{Special cases:}]{Special cases:}\par
1.21 year old, primigravida, with 34 weeks of gestation in a known case of rheumatic heart disease s/p MVR, with c/o fever with chills, jaundice, altered sensorium and moderate anemia referred from periphery. 
\section[{On admission -}]{On admission -}\par
Bili-13.8 SGOT-821 SGPT-219 Hb-8.3 TLC-19600 PLT-61000\par
Patient was diagnosed to be anti-HEV-IgM positive with hepatic encephalopathy with dengue haemorrhagic fever.\par
Patient had PPH, developed AKI and died on Day 6 post-natal day.\par
2.25 year old, G3P2L2 with previous 2 LSCS with 35 weeks of gestation with right ovarian cyst was referred in view of threatened preterm and jaundice. 
\section[{On admission}]{On admission}\par
Bili-2.6 SGOT-48 SGPT-26, Tumor markersnegative, Viral markers -anti-HEV-IgM positive USG abdomen s/o right adnexal solid cystic mass (15x10x15cm) likely to be mucinous cystadenoma.\par
Elective LSCS with right ovarian cystectomy with right salpingoopherectomy with left tubal ligation was done at 37 completed weeks. Histopathological report was s/o right mucinous cystadenoma.\par
Patient was discharged with Bili-0.6 SGOT-12 SGPT-25 3.38 year old, G2P1L1 with previous LSCS with 32 weeks of gestation with PROM with breech presentation with hyperbilirubinemia was referred from periphery. \begin{figure}[htbp]
\noindent\textbf{}\includegraphics[]{image-2.png}
\caption{\label{fig_2}}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{} \par 
\begin{longtable}{P{0.43727556596409056\textwidth}P{0.16190476190476188\textwidth}P{0.08294301327088212\textwidth}P{0.01128024980483997\textwidth}P{0.07166276346604215\textwidth}P{0.009289617486338797\textwidth}P{0.03848555815768931\textwidth}P{0.03715846994535519\textwidth}}
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Year 2020\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep 17\\
\multicolumn{7}{l}{57.9 \% belong to the age group 20-25 years followed by 36.8 \% belong to 26-30 years and the minimum 5.3\% belong to >30 years. In our study maximum patients belong to third trimester, 42 \% presented at > 36 weeks of gestation and 23.7 \% between 24-36 weeks and 34.2 \% in 12-24 weeks. No patient was found in the first trimester. Lab parameters Highest Lowest Median Mean Hb 13.8 4.6 -9.09 Total leucocyte count 54000 2500 -19680 Platelet 5.57 lac 21000 -1.81 lac Bilirubin 28 0.5 18.7 25.7 SGOT 4406 29 -713 SGPT 3491 14 -507 Prothrombin Time 70 11.3 39.3 27.48}\tabcellsep Volume XX Issue VI Version I\\
\tabcellsep INR Creatinine\tabcellsep 8.78 -\tabcellsep \tabcellsep 0.79 4.4\tabcellsep 2.12 -\tabcellsep 2.68 -\tabcellsep ( D D D D )\\
H\tabcellsep \multicolumn{2}{l}{Fever Nausea, vomiting Lethargy}\tabcellsep \tabcellsep \tabcellsep 9 6 2\tabcellsep Medical Research\\
\tabcellsep \multicolumn{3}{l}{Loss of consciousness Altered sensorium Pruritus Convulsions Jaundice Breathlessness Obstetrics reasons(PROM, PT labour, decreased}\tabcellsep \multicolumn{3}{l}{Exclusion criteria: 2. Patients with Anti-HEV IgM-positive who lost follow up. 2 6 4 1 34 2 4+5+2}\tabcellsep Global Journal of\\
\tabcellsep \multicolumn{2}{l}{fetal movement)}\tabcellsep \tabcellsep \tabcellsep \\
\multicolumn{3}{l}{III. Some degree of anemia was seen in 74 \% cases.}\tabcellsep \multicolumn{2}{l}{Observations}\tabcellsep \\
\tabcellsep Age Total cases with Anaemia 28 (74 \%)\tabcellsep \multicolumn{4}{l}{Age and parity distribution Parity Mild(8-10.9) Moderate(5-7.9) Gestational Age primi Multi 1 st tri 2 nd tri 10 16}\tabcellsep Severe(<5) 3 rd tri 2\\
\tabcellsep 20-25\tabcellsep 10\tabcellsep 12\tabcellsep -\tabcellsep 7\tabcellsep 15\\
\tabcellsep 26-30\tabcellsep 4\tabcellsep 10\tabcellsep -\tabcellsep 6\tabcellsep 8\\
\tabcellsep 30-40\tabcellsep 1\tabcellsep 1\tabcellsep -\tabcellsep -\tabcellsep 2\\
\multicolumn{2}{l}{Author: e-mail: reach.drsampada@gmail.com}\tabcellsep \tabcellsep \tabcellsep \tabcellsep \end{longtable} \par
 
\caption{\label{tab_0}}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{} \par 
\begin{longtable}{P{0.08011494252873563\textwidth}P{0.23448275862068965\textwidth}P{0.029310344827586206\textwidth}P{0.05275862068965517\textwidth}P{0.02540229885057471\textwidth}P{0.006839080459770114\textwidth}P{0.3898275862068965\textwidth}P{0.01954022988505747\textwidth}P{0.011724137931034483\textwidth}}
\tabcellsep \multicolumn{5}{l}{performed by using statistical package for the social}\tabcellsep Quantitative variables e.g. age, gestational age,\\
\tabcellsep \multicolumn{5}{l}{sciences software version 16.0 (Chicago IL, USA). Variables considered are age, gestational age at presentation, parity, fetal and maternal outcome.}\tabcellsep laboratory parameters were analysed using simple Gestational age at descriptive statistics like mean, median. Qualitative presentation variables e.g. fetal and maternal outcome were\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep 0 calculated using frequency and percentage.\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep V.\tabcellsep \multicolumn{2}{l}{Results}\\
\tabcellsep a) Pregnancy outcome\tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
\tabcellsep \tabcellsep \tabcellsep Alive \& well\tabcellsep \tabcellsep \tabcellsep 34.20\% 14 (45.16\%)\tabcellsep 42\%\\
\tabcellsep \tabcellsep \tabcellsep NICU\tabcellsep \tabcellsep \tabcellsep 07 (22.58\%)\\
\tabcellsep \tabcellsep \tabcellsep Still births\tabcellsep \tabcellsep \tabcellsep 10 (32.25\%)\\
\tabcellsep \tabcellsep \multicolumn{2}{l}{Total delivered}\tabcellsep \tabcellsep \tabcellsep 31 (100\%)\\
Year 2020\tabcellsep \tabcellsep \tabcellsep Undelivered Abortion\tabcellsep \tabcellsep \tabcellsep 23.70\% 5/38 (13.15\%) 2/38 (5.26 \%)\\
18\tabcellsep \tabcellsep Primi\tabcellsep Multi\tabcellsep \tabcellsep \tabcellsep >36 wks 24-36wks 12-24 wks <12 wks\\
Volume XX Issue VI Version I\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
D D D D )\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
(\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
Medical Research\tabcellsep Total live birth 21\tabcellsep \multicolumn{2}{l}{>/=2.5kg 5}\tabcellsep \multicolumn{3}{l}{>1.5kg to <2.5kg(LBW) 14}\tabcellsep </=1.5KG(VLBW) 2\tabcellsep <1KG(ELBW) 0\\
Global Journal of\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \end{longtable} \par
  {\small\itshape [Note: 1. 76 \% had low birth weight including 2 very low birth weight.2. 33\% of total live borns were admitted to NICU, reasons being prematurity, very low birth weight and respiratory distress. 3.]} 
\caption{\label{tab_1}}\end{figure}
 			\footnote{© 2020 Global Journals} 			\footnote{© 2020 Global JournalsFetomaternal Outcome in Pregnancy with Hepatitis E Infection} 		 		\backmatter  			  				\begin{bibitemlist}{1}
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\end{document}
