Manju Puri

Maternal and Fetal Outcomes in Pregnant Women with Acute Hepatitis E Virus Infection

Context Hepatitis E virus (HEV) infection causes severe liver disease in pregnant women. Contribution In a case series of 220 pregnant women with jaundice and acute viral hepatitis, the authors observed that women with HEV infection more often died and had more obstetric complications and worse fetal outcomes than did women with other forms of viral hepatitis. Caution The series was restricted to symptomatic women at a referral center. Implication Infection with HEV not only causes more severe liver disease in pregnant women but also appears to contribute to worse obstetric and fetal outcomes compared with other forms of viral hepatitis. The Editors Hepatitis E virus (HEV) is a single-stranded RNA virus that causes large-scale epidemics and sporadic cases of acute viral hepatitis in developing countries (1, 2). Infection with HEV also poses a significant risk for acute viral hepatitis to travelers in endemic areas (3). The main source of transmission of HEV is contaminated drinking water (4, 5). In men and nonpregnant women, the disease is usually self-limited and has a low case-fatality rate (<0.1%) (6). However in pregnant women, HEV infection is more severe, often leading to fulminant hepatic failure and death in up to 15% to 20% of cases. This high mortality rate was first reported in an epidemic setting in the early 1980s (7) and was reported again in a sporadic setting in 2003 (8). Information is limited and conflicting on the effect of HEV infection on maternal, obstetric, and fetal outcomes (9, 10). Therefore, we describe the prevalence and clinical outcomes of acute viral hepatitis in a series of HEV-infected pregnant women and compare their maternal, obstetric, and fetal outcomes with those of pregnant women without HEV infection. Methods Setting and Participants The study was conducted at the Department of Obstetrics and Gynecology, Lady Hardinge Medical College, and Shrimati Sucheta Kriplani Hospital, New Delhi, India (a large tertiary care hospital), in collaboration with the Department of Gastroenterology, G.B. Pant Hospital, New Delhi. Consecutive pregnant women at any gestational stage who presented between January 2003 and July 2005 with acute viral hepatitis were systematically assessed for hepatitis virus infection by using liver function tests and serologic analysis. Acute viral hepatitis was diagnosed (7) by a serum bilirubin level of 34 mol/L or greater (2 mg/dL); a serum alanine aminotransferase level 2.5 times the upper limit of normal or greater; and positivity for any hepatotropic virus by using the following serologic tests: hepatitis B surface antigen; antibody to hepatitis C virus; and IgM antibodies to hepatitis A virus, hepatitis B core antigen, hepatitis delta virus, and HEV. We excluded patients with negative results on viral serologic examination, those with dual viral infection, those with clinical evidence of other causes of jaundice (such as biliary obstruction, the HELLP syndrome [hemolytic anemia, elevated liver enzyme level, low platelet count], acute fatty liver of pregnancy, hemolytic jaundice, and drug-induced jaundice), and those with clinical or laboratory evidence of chronic liver disease. Women who met the case definition of acute viral hepatitis were managed in a separate hepatitis hospital ward. Management depended on whether the patients acute viral hepatitis was complicated by fulminant hepatic failure, which was diagnosed when hepatic encephalopathy developed in a patient with acute viral hepatitis within 4 weeks of the onset of jaundice (11). Patients without fulminant hepatic failure were given standard care and were monitored for signs and complications of acute viral hepatitis (fever, edema, ascites, paralytic ileus, nasal and gastrointestinal hemorrhage, high leukocyte count, high creatinine concentration, hepatic encephalopathy, clinically significant coagulation defect [international normalized ratio> 2.0], hypoglycemia, hyponatremia, hypernatremia, hypokalemia, hyperkalemia, and hypocalcemia), and obstetric complications (antepartum, intrapartum, or postpartum hemorrhage; premature rupture of membranes; and intrauterine death). If their condition improved, patients were discharged and instructed to return for regular outpatient follow-up visits until delivery. Patients with fulminant hepatic failure were managed with supportive care in the intensive care unit because liver transplantation facilities are not available in the hospital. They were monitored for increased intracranial tension along with other medical and obstetric complications. They received 20% mannitol, lactulose, antibiotics, parenteral nutrition, and ventilatory support, as needed. Women without fulminant hepatic failure who had fetal distress, meconium staining of amniotic fluid, no progress of labor, or obstructed labor underwent cesarian section. Termination of pregnancy was considered in cases of intrauterine death, severe intrauterine growth retardation, a nonreactive nonstress test result, postdated pregnancy, and premature rupture of membrane at term only if the patient had improving liver function and a coagulation profile that could be further corrected by giving fresh frozen plasma. Termination of pregnancy was not considered for women with fulminant hepatic failure. All women with manifestations of bleeding were infused with fresh frozen plasma and packed red cells. In keeping with the policy of our institutions, the study did not require institutional review board approval or documented informed consent from patients for study participation because patients received care according to a standard clinical protocol, their care was not influenced by their inclusion in the study, and data were collected and recorded according to ethical standards and norms in India and were analyzed with total anonymity of patients. Statistical Analysis We used the t test and the MannWhitney U test to compare normally distributed data and non-normally distributed data, respectively, of HEV-infected and nonHEV-infected patients. The chi-square test was used to compare discrete values between groups. A P value less than 0.05 was considered significant. Relative risk was calculated for all complications in HEV-infected pregnant women versus nonHEV-infected pregnant women. Statistical analyses were done by using SPSS, version 13.0 (SPSS, Chicago, Illinois). Role of the Funding Source The study received no external funding. Results Patients Of the 33385 pregnant women who were admitted during the study period, 316 (0.9%) presented with jaundice. Ninety-two were excluded for causes of jaundice other than viral hepatitis (intrahepatic cholestasis of pregnancy [41 women], the HELLP syndrome [6 women], acute fatty liver of pregnancy [3 women], drug hepatotoxicity [7 women], hemolytic jaundice [14 women], choledocholithiasis [6 women], and unknown cause [15 women]), and 4 were excluded for dual viral infection. The remaining 220 pregnant women with jaundice met the inclusion criteria for acute viral hepatitis. None had evidence of autoimmune disease. Table 1 shows patient characteristics. The mean maternal age was 22.4 years (SD, 3.2). Sixty-one women (28%) were in the second trimester of pregnancy (mean gestational age, 26.2 weeks [SD, 2.0]) and 159 (72%) were in the third trimester (mean gestational age, 34.2 weeks [SD, 2.6]). The mean duration of jaundice before hospitalization was 4.9 days (SD, 2). Table 1. Patient Characteristics* Cause of Hepatitis Infection with HEV was the most common cause of acute viral hepatitis (132 participants [60%]) (Table 1). Hepatitis B virus (HBV) infection was the most common cause of nonHEV acute viral hepatitis (72 participants [33%]). Fewer HEV-infected patients than nonHEV-infected patients were in their third trimester of pregnancy, corresponding to a lower mean gestational age for HEV-infected patients (31 weeks [SD, 4.1] vs. 33 weeks [SD, 4.4]; P= 0.004) (Table 1). The median duration of jaundice did not differ between HEV-infected women and nonHEV-infected women (4 days [range, 1 to 15 days] vs. 4.5 days [range, 2 to 10 days]; P= 0.68). Fulminant Hepatic Failure Ninety-one women (41%) had fulminant hepatic failure, of whom 54 (59%) had fulminant hepatic failure on admission and 37 (41%) developed fulminant hepatic failure during hospitalization. Fulminant hepatic failure was more common among HEV-infected women than nonHEV-infected women (73 of 132 [55%] vs. 18 of 88 [20%]; relative risk, 2.7 [CI, 1.7 to 4.2]; P< 0.001) (Table 1) and among HEV-infected women in their third trimester (46 of 88 [52%] vs. 11 of 71 [15%] noninfected women; relative risk, 3.4 [CI, 1.9 to 6.0]; P< 0.001). The frequency of fulminant hepatic failure did not statistically significantly differ between HEV-infected women and nonHEV-infected women in their second trimester (27 of 44 [61%] vs. 7 of 17 [41%]; P= 0.26). Jaundice before hospital admission was of longer duration in women with fulminant hepatic failure than in those without fulminant hepatic failure (5.4 days [SD, 2.6] vs. 4.6 days [SD, 1.5]; P= 0.010). In women who developed fulminant hepatic failure, the mean interval from onset of jaundice to onset of encephalopathy was 108 hours (SD, 58) and was similar in HEV-infected and nonHEV-infected women (112 hours [SD, 60] vs. 93 hours [SD, 50]; P= 0.18). The mean duration of encephalopathy before admission was 20 hours (SD, 15) and was similar in HEV-infected and nonHEV-infected women. Maternal Mortality and Complications of Infection Maternal mortality was higher in HEV-infected women and occurred exclusively in women with fulminant hepatic failure (Table 2). Signs and complications of infection that differed by HEV status were an international normalized ratio greater than 2.0, nasal or gastrointestinal hemorrhage, leukocyte count of 11109 cells/L or greater, high serum creatinine concentration (34 mol/L [2 mg/dL]), ascites, and signs of increased intracranial tension. Differenc

Maternal and perinatal outcome in patients with severe anemia in pregnancy.

Anemia is a major health problem among women of reproductive age particularly in developing countries. The prevalence of anemia among pregnant women is 55.9% worldwide and varies between 35% and 100% in developing countries. Anemia is responsible for 15% to 20% of total maternal mortality. This study assesses maternal and perinatal outcomes among women who were severely anemic in their third trimester of pregnancy with a hemoglobin concentration less than 5 g/dL. The 130 women admitted with severe anemia during the study period represented 9% of all hospital admissions. Such a high prevalence in an urban setting where obstetric services are freely available emphasizes the need to look into the deeper causes of the condition. (excerpt)

MTHFR C677T polymorphism, folate, vitamin B12 and homocysteine in recurrent pregnancy losses: a case control study among north Indian women

Abstract Aim: The present study attempts to understand the role of methylenetetrahydrofolate reductase C677T (MTHFR C677T) in recurrent pregnancy losses in North Indian women because of hyperhomocysteinemia in light of serum folate and vitamin B12. Methods: One hundred and seven women with three or more consecutive unexplained recurrent pregnancy losses and 343 women with two or more successful and uncomplicated pregnancies were recruited. Plasma homocysteine, serum folate and vitamin B12 were analyzed using chemiluminescence. MTHFR C677T detection was completed in all subjects. Results: MTHFR genotypic distribution among cases and controls showed no significant difference (P=0.409). However, MTHFR C677T polymorphism was found to be significantly associated with increased homocysteine in the case group (P=0.031). Hyperhomocysteinemia and vitamin B12 deficiency were found to be significant risk factors for recurrent pregnancy loss (RPL) (OR=7.02 and 16.39, respectively). Folate deficiency was more common in controls (63.47%) as compared to the case group (2.56%). Conclusion: Low vitamin B12 increases homocysteine, specifically among T allele carrying case mothers, suggesting T allele is detrimental with B12 deficiency. The study emphasizes the importance of vitamin B12 in the prevention of RPL in North Indian women.

A rare case of vesicovaginal fistula following illegal abortion.

It is estimated that 50-60 million induced abortions take place annually in the world and 19 million are still performed illegally. According to WHO about one quarter to one third of maternal deaths are due to complications of induced abortion. The morbidity and mortality related to criminal abortions is due to complications like haemorrhage perforation sepsis shock and visceral injuries. Bladder injuries due to instrumental perforation of the uterus have been reported but development of a urinary fistula without any instrumentation in induced abortion is rare. We came across such a presentation. A 35-year P/5A/1L/5 illiterate woman presented with continuous dribbling of urine per vaginum following an illegal abortion at 3 months of gestation by a quack 7 months back. According to her some paste was applied in the vagina following which she aborted spontaneously and noticed watery discharge per vaginum. She consulted a doctor for persistent vaginal discharge and was diagnosed as a case of vesicovaginal fistula. Earlier Obstetrc history was uneventful. Her menstrual cycles were normal however following abortion she developed amenorrhoea. Abdominal examination was unremarkable. Speculum examination showed a blind vagina about 6 cm long. Cervix could not be visualized. A small opening (6 mm in diameter) about 4.5 cm from the urethral meatus was seen at the vault. On bimanual examination vagina ended blindly with cicatrization in upper part cervix could not be felt. The margins of the fistula were fibrosed and irregular. On per rectal examination uterus and cervix could not be appreciated properly instead a transverse band was felt. (excerpt)

Herlyn-Werner-Wunderlich syndrome with pregnancy : A rare presentation

ABSTRACT  Müllerian duct anomalies are infrequently encountered clinical problems and often present with difficulty in diagnosis. A high level of suspicion is the key to diagnosis, which is usually made soon after menarche. However, this is the first reported case of uterus didelphys with obstructed hemivagina and pyocolpos with ipsilateral renal agenesis in which the diagnosis was delayed until pregnancy.

Labour induction with 25 micrograms versus 50 micrograms intravaginal misoprostol in full term pregnancies

We undertook this study in order to compare the efficacy of 25 µg versus 50 µg of intravaginal misoprostol for cervical ripening and labour induction at term. The study population consisted of 120 women with term singleton pregnancies in vertex presentation booked for caesarean section. They had a Bishop scoring of <6 and a reactive fetal heart rate tracing. They were randomized into two groups, A and B, to receive 25 µg and 50 µg of vaginal misoprostol, respectively, 4 hourly with a maximum of five doses until the patient had three contractions in 10 minutes. There was no significant difference in the induction delivery interval between the two groups (12.52± 7.05 h in the 25 µg group versus 11.72± 6.74 h in the 50 µg group; P = 0.58). Of the women in the 25 µg group, 83.3% delivered vaginally as did 71.67% of those in the 50 µg group, but the difference was not statistically significant (P = 0.128). There were significantly more women requiring oxytocin augmentation in the 25 µg group than in the 50 µg group (P = 0.03). However, there were no significant differences in the rates of caesarean and operative vaginal delivery, meconium stained liquor, fetal distress or in the incidences of hyperstimulation between the two groups. Neonatal outcomes were similar. The intravaginal administrations of 25 µg, as well as 50 µg of misprostol, are equally efficacious in inducing labour. The 25 µg group more often required oxytocin as an adjunct.

Unruptured term pregnancy with a live fetus with placenta percreta in a non-communicating rudimentary horn.

ABSTRACT  Pregnancy in a non‐communicating rudimentary horn is rare and such a pregnancy culminating in the delivery of a live fetus is even rarer. Despite advances in ultrasonography, the accuracy of ultrasound in diagnosing rudimentary horn pregnancy at advanced gestation remains elusive. Confirmatory diagnosis is made only at laparotomy. We report a multigravidae who presented at 37 weeks with transverse lie oligoamnios and decreased perception of fetal movement since quickening. Laparotomy for placenta accreta suspected on ultrasound revealed non‐communicating unruptured rudimentary horn pregnancy with a live fetus and placenta percreta. Successful extraction of a term live fetus weighing 2.7 kg with excision of the rudimentary horn was carried out.

Effects of different doses of intraumbilical oxytocin on the third stage of labor

To determine the optimal dose of oxytocin to be injected intraumbilically after fetal delivery for active management of the third stage of labor.

A rare case of intact rudimentary horn pregnancy presenting as hemoperitoneum.

The availability of technological advances like ultrasonography (USG) and magnetic resonance imaging (MRI) has made the diagnosis of rudimentary horn pregnancy possible at an early gestation. However, in advanced pregnancy, such cases can sometimes pose a diagnostic dilemma and are recognized only when patient presents with abdominal pain and collapse and is taken for laparotomy. We report one such rare case of a nulliparous female who was carrying on well with her pregnancy till she developed symptoms of acute abdomen at 28 weeks of gestation. She underwent USG and MRI but it was only after laparotomy that a final diagnosis of a pregnancy in a rudimentary horn with placenta percreta perforating through the fundus could be made. There was a significant amount of hemoperitoneum; however, the horn was intact and the fetus could be salvaged. We excised the rudimentary horn with ipsilateral tube and ovary. Post operatively, both the mother and the baby were discharged in healthy condition.

Septate uterus with hypoplastic left adnexa with cervical duplication and longitudinal vaginal septum: Rare Mullerian anomaly.

A large analysis of all the studies in the period from 1950 to 2007 suggests that the prevalence of congenital uterine anomalies in the general population is 6.7%; and in the infertile population, 7.3%. We report a rare case of unilateral hypoplastic fallopian tube and ovary with septate uterus, cervical duplication, longitudinal vaginal septum. To the best of our knowledge, this is the first report of such a congregation of anomalies.