International Journal of Gynecology and Obstetrics 119 (2012) 145148

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International Journal of Gynecology and Obstetrics

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CLINICAL ARTICLE

Maternal and perinatal outcome in cases of fulminant viral hepatitis in late pregnancy
Liuzhi Deng a, Xiaomao Li a,, 1, Zhongjie Shi a, b, 1, Peiru Jiang c, d, Dunjin Chen e, Lin Ma a
a
Department of Obstetrics and Gynecology, Third Afliated Hospital of Sun Yat-sen University, Guangzhou, China
b
Department of Biology, Temple University, Philadelphia, USA
c
Department of Obstetrics and Gynecology, Shanghai Public Health Clinical Center, Shanghai, China
d
Public Health Clinical Center Afliated to Fudan University, Shanghai, China
e
Department of Obstetrics and Gynecology, Third Afliated Hospital of Guangzhou Medical College, Guangzhou, China

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To investigate maternal and perinatal outcomes in cases of fulminant viral hepatitis in late preg-
Received 12 February 2012 nancy (FVHILP). Methods: A multicenter retrospective study was conducted. The records of 40 patients
Received in revised form 27 May 2012 with FVHILP were retrieved from 3 hospitals in China. To analyze the inuence of mode of delivery on mater-
Accepted 24 July 2012 nal and perinatal outcomes, women were allocated to the cesarean delivery group or the spontaneous vaginal
delivery (SVD) group. To study the relationship between maternal outcome and perinatal outcome, patients
Keywords:
were allocated to the maternal survival group or the non-survival group. Results: There were no signicant
Fulminant hepatitis
Maternal outcome
differences between the cesarean group and the SVD group in clinical manifestations or laboratory indices
Mode of delivery before delivery, or in fatality rate (P > 0.05 for all), whereas there were signicant differences in newborn
Perinatal outcome weight, 1-minute Apgar score, and incidence of severe perinatal asphyxia between the maternal survival
Pregnancy group and the non-survival group (P b 0.05 for all). Conclusion: Maternal and perinatal outcomes in cases of
FVHILP were not inuenced by mode of delivery, whereas perinatal outcome signicantly correlated with
maternal outcome.
2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction 2. Materials and methods

Fulminant viral hepatitis in pregnancy is a rare disease characterized
by acute onset, rapid progression, complicated clinical symptoms, and
high fatality rate [14]. The condition is seen most often in patients
infected with hepatitis B virus (HBV) or hepatitis E virus in low-
resource countries in Asia and Africa, with a reported maternal fatality
rate of 56%75% and a perinatal mortality rate of 37%49% [5,6]. Patients
with fulminant viral hepatitis in late pregnancy (FVHILP), which occurs
at 28 weeks of gestation or later, often present with coagulation dis-
orders, hepatic encephalopathy, hepatorenal syndrome, paralytic ileus,
and infection [7,8].
Because of the low incidence of FVHILP, only a few studies analyzing
the prognosis of the condition are available [1,9,10]. The aim of the
present study was to investigate the inuence of mode of delivery
on maternal and perinatal outcomes, in addition to determining the
relationship between maternal and perinatal outcomes.
Corresponding author at: Department of Obstetrics and Gynecology, Third Afliated
Hospital of Sun Yat-sen University, Guangzhou 510630, China. Tel.: +86 20 85252292.
E-mail address: house.triangle@gmail.com (X. Li).
1
Zhongjie Shi and Xiaomao Li contributed equally to this paper.
A retrospective study of patients with FVHILP associated with
HBV infection (serum hepatitis B surface antigen and/or HBV DNA
positive) was conducted. The records of affected patients who were
admitted and delivered at the Third Afliated Hospital of Sun
Yat-sen University (n = 19), Shanghai Public Health Clinical Center &
Public Health Clinical Center Afliated to Fudan University (n = 8),
and the Third Afliated Hospital of Guangzhou Medical College
(n = 13), China, between January 1, 2000, and June 31, 2011, were
consecutively retrieved. Approval for the study was obtained from
the institutional ethics committee of each of the study hospitals.
All patients met the Chinese Medical Association clinical diagnostic
criteria of fulminant viral hepatitis before delivery [11]. Patients were
excluded if they had other virus co-infections or other pre-existing
medical conditions (except hepatitis-related diseases), surgery (acute
abdomen) during pregnancy, or additional pregnancy-specic liver dis-
eases (acute fatty liver of pregnancy; intrahepatic cholestasis of preg-
nancy; pre-eclampsia; or hemolysis, elevated liver enzymes, and low
platelet count [HELLP] syndrome) [4]. Patients were also excluded if
fetal anomalies were detected, in order to exclude the false perinatal
mortality rate due to such anomalies. Principles of treatment were
comparable among all study hospitals during the period investigated,
including dynamic monitoring (comprehensive physical exams and
blood tests), supportive therapy (from several hours to several days,

0020-7292/$ see front matter 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ijgo.2012.05.041
146 L. Deng et al. / International Journal of Gynecology and Obstetrics 119 (2012) 145148

involving treatments such as intensive care unit [ICU] input; replenish- Table 1
ment of serum albumin and globulin; restoration of coagulation Comparison of pre-delivery blood indicators between cesarean and spontaneous vagi-
nal delivery groups.a
function; and reduction of transaminases and toxins using herbal
medicines [Ganlixin injection, the major content of which is diam- Cesarean delivery Spontaneous vaginal t value P value
monium glycyrrhizinate]) [12], antiviral medication (lamivudine), and delivery

symptom-relieving treatment. Indications for delivery included 1 or AST/ALT ratio 1.55 0.74 1.37 0.48 0.662 0.512
more of the following [11]: full-term pregnancy (37 weeks of gesta- TBIL, mol/L 222.09 88.50 300.60 142.08 1.976 0.056
Alb, g/L 25.90 4.75 27.49 3.32 0.888 0.380
tion), with the patient receiving supportive treatment and with clinical
Tch, mmol/L 2.58 0.98 2.51 1.08 0.157 0.876
symptoms and signs (including laboratory indices such as coagulation Cr, mmol/L 112.67 78.14 87.35 61.28 0.850 0.400
function, serum albumin, transaminase, and total bilirubin) remaining PTA, % 31.47 13.56 28.29 24.21 0.496 0.642
steady for 2448 hours (n= 6); fetal distress if the fetus was viable CHE, IU/L 3405.76 804.68 3759.17 1250.14 0.860 0.397
(more than 28 weeks of gestation) (n= 12, with 2 twin pregnancies Bs, mmol/L 5.02 3.58 4.97 4.49 0.035 0.972
WBC, 109/L 11.56 3.51 13.26 5.11 1.114 0.272
and 1 triplet pregnancy); no improvement in clinical condition after
active treatment with medication, with the condition deteriorating Abbreviations: Alb, albumin; ALT, alanine aminotransferase; AST, aspartate amino-
transferase; Bs, blood glucose; CHE, cholinesterase; PTA, prothrombin activity; Scr,
(e.g. deterioration of hepatic encephalopathy) (n= 11) [7,13]; patient
serum creatinine; TBIL, serum total bilirubin; Tch, total cholesterol; WBC, white blood
in labor (n= 11, with 1 twin pregnancy). cell count.
Cesarean under general anesthesia was the preferred mode of deliv- a
Values are given as mean SD unless otherwise indicated.
ery; vaginal delivery was considered for patients who had already entered
the labor process and in whom the cervix was mature and delivery was
imminent [11,14]. Peripartum subtotal hysterectomy was performed in results between the SVD group and the cesarean group (Table 1).
cases of intractable postpartum hemorrhage [15]. If necessary, viable There were 14 (43.8%) cases involving 3 or more complications in
newborns received neonatal resuscitation, and live newborns were the cesarean group, and 4 (50.0%) such cases in the SVD group (P =
transferred to the neonatal ICU (NICU) of the corresponding hospital. 0.938). The similar pre-delivery clinical parameters in the SVD and
Data on maternal and perinatal outcomes (death, complications, and cesarean groups enabled the inuence of delivery on maternal and
evaluation of newborns) were retrospectively collected and compared perinatal outcomes to be analyzed without bias.
between different delivery groups. Comparisons between the groups In the SVD group, 5 (62.5%) mothers survived, and 5 (62.5%) new-
were carried out for clinical data at admission, including liver function borns survived and remained alive. In the cesarean group, which
and blood coagulation indices such as aspartate aminotransferase, alanine included 3 cases of twin pregnancy and 1 case of triplet pregnancy,
aminotransferase, and their ratio; albumin; total cholesterol (Tch); serum 22 (68.8%) mothers survived and 31 (83.8%) newborns survived.
total bilirubin; prothrombin activity (PTA); cholinesterase; serum creati- There were no signicant differences between the groups in maternal
nine (Scr); blood glucose; and white blood cell count (WBC). Also fatality rate (P = 0.933), postpartum hemorrhage (P = 0.937), infection
compared were major complications such as hepatic encephalopathy, (P = 0.693), hepatic encephalopathy (P = 0.936), or hepatorenal syn-
hepatorenal syndrome, disseminated intravascular coagulation, drome (P = 0.804) (Table 2). Subtotal hysterectomy was performed
bleeding (obstetric hemorrhage, upper gastrointestinal bleeding, in 13 cases (5 in the non-survival group [all during cesarean delivery]
brain hemorrhage, and abdominal hematoma), and infections (peri- and 8 in the survival group [7 during cesarean and 1 after SVD]).
toneal, uterine, pelvic, biliary, and urinary). The relationship between There were higher rates of perinatal death (P = 0.380) and severe
maternal and perinatal outcomes was also evaluated. asphyxia (P = 0.638) in the SVD group than in the cesarean group but
Measurement data were expressed as mean SD or median. the difference was not signicant (Table 3).
Quantitative data were compared via Student t test or rank-sum The 45 perinatal outcomes were analyzed according to the associ-
test. The 2 test was used to analyze enumeration data. Statistical ated maternal outcomes. Twenty-nine newborns from 27 mothers
analyses were carried out using SPSS version 15.0 (IBM, Armonk, who survived after delivery (including 2 twin pregnancies) were allo-
NY, USA). For all comparisons, P b 0.05 in any 2-sided statistical test cated to the maternal survival group; 16 newborns from 13 mothers
was considered to be statistically signicant. who died after delivery (including 1 twin and 1 triplet pregnancy)
were allocated to the maternal non-survival group. There were sig-
3. Results nicant differences in birth weight (P = 0.003), 1-minute Apgar
score (P = 0.025), and severe asphyxia (P = 0.045) between the 2
The clinical characteristics of 40 eligible patients were analyzed. All groups (Table 4). Thirteen live newborns from 11 women, including
patients were Han Chinese and from east or south China. Average mater- 4 newborns from 2 cases of twin pregnancy and 1 newborn from
nal age at delivery was 27.24.2 years, and mean gestational age at de- a triplet pregnancy, were admitted to the NICU. Twenty-three
livery was 35.32.9 weeks. There were 3 twin pregnancies and 1 live newborns were not admitted to the NICU. The other 9 cases
triplet pregnancy. There were no cases of HIV infection, hepatocellular involved fetal death or stillbirth, including 2 fetal deaths from a
carcinoma, or prior FVHILP history. Transfusion or infusion of blood- triplet pregnancy.
derived medicine was carried out after delivery in all cases as treatment
for coagulation dysfunction. All women were admitted to the ICU, either
before or after delivery. All cases involved infection with HBV only. Aver- Table 2
Maternal outcomes according to delivery group.a
age time between onset of fulminant viral hepatitis and delivery was
14.514.1 days. Twenty-seven women experienced complete recovery Spontaneous Cesarean 2 value P value
or an improvement in clinical conditions at discharge (mother survived vaginal delivery delivery
(n = 8) (n = 32)
at 6 months: survival group), with an average hospital stay of 30
21 days. Thirteen women died or experienced a deterioration in Maternal death 3 (37.5) 10 (31.3) 0.007 0.933
Postpartum hemorrhage 5 (62.5) 17 (53.1) 0.006 0.937
clinical conditions at discharge (conrmation of maternal death within
Infection 4 (50.0) 16 (50.0) 0.156 0.693
6 months: non-survival group), with an average hospital stay of 8 Hepatic encephalopathy 4 (50.0) 19 (59.4) 0.006 0.936
8 days. The total maternal fatality rate was 32.5%. Of the 45 newborns, Hepatorenal syndrome 2 (25.0) 12 (37.5) 0.062 0.804
b
36 survived and 9 died, giving a mortality rate of 20.0%. Previous parity 1.75 0.71 2.06 1.29 0.516
There were 8 spontaneous vaginal deliveries (SVDs) and 32 cesar- a
Values are given as number (percentage) or mean SD unless otherwise indicated.
ean deliveries. There were no signicant differences in blood test b
t test.
 L. Deng et al. / International Journal of Gynecology and Obstetrics 119 (2012) 145148 147

Table 3 mortality rate, or severe perinatal asphyxia between the SVD group
Perinatal outcomes according to delivery group.a and the cesarean group, indicating that the methods of delivery have
Spontaneous Cesarean t/2 value P value similar inuences on maternal and perinatal prognosis, which cannot
vaginal delivery delivery be attributed solely to the control of postpartum hemorrhage. However,
(n = 8) (n = 37) there were signicant differences in newborn weight, 1-minute Apgar
Weight, g 2301 568 2441 508 0.567 0.574 score, and severe asphyxia between the maternal survival group and
One-minute Apgar score 5.4 3.8 3.5 3.9 1.292 0.203 the non-survival group, indicating that maternal outcome may inuence
Five-minute Apgar score 7.8 3.1 5.3 4.6 1.498 0.171
perinatal outcome.
Fetal death 2 (25.0) 4 (10.8) 0.247 0.619
Perinatal death 3 (37.5) 6 (16.2) 0.770 0.380 In conclusion, both maternal and perinatal outcomes were affected
Severe asphyxia 3/6 (50.0) 10/33 (30.3) 0.222 0.638 by FVHILP. Compared with mode of delivery, maternal outcome
a
Values are given as mean SD or number (percentage) unless otherwise indicated.
had more inuence on perinatal outcome. During pregnancy, special
attention should be paid to monitoring maternal liver function, with
regular follow-up and timely treatment to prevent chronic hepatitis
4. Discussion from progressing into fulminant hepatitis in pregnancy. Doing so
would improve maternal outcome, reduce the rate of severe neonatal
During pregnancy, the liver processes the increased amount of asphyxia, and increase the perinatal survival rate. The most effective
maternal and fetal metabolites and degrades large amounts of endog- way to prevent HBV-related diseases includes education on lifestyle
enous hormones [16,17]. When liver function decreases, biliary ex- and sexual behavior, universal screening of pregnant women for HBV
cretion is affected, often leading to cholestasis. High concentrations infection, and comprehensive immunoprophylaxis during pregnancy
of bilirubin and bile acid in the circulation easily accumulate within or at birth [22,23].
placental chorionic villi. The resultant reduction in placental perfusion
may lead to fetal distress, perinatal death, or neonatal asphyxia [18]. In
the present study, the maternal fatality rate was 32.5% and the perinatal Acknowledgments
death rate was 20.0%. These rates have previously been reported
as 45.0% and 48.4%, respectively, according to 19842006 data from The study was supported by grants from the Technological Project of
China [10]. The lower maternal and perinatal fatality rates in the present Guangdong Province (No. 2005B340201006 and No. 2007B030502012)
study compared with those from previous reports [13] may reect the and the Bureau of Traditional Chinese Medicine and Drugs of Guangdong
progress in FVHILP research and improvement in the treatment of pre- Province (No. 1060166).
term delivery. However, FVHILP remains a major threat to maternal and
perinatal prognosis in low-resource countries owing to its deteriorating Conict of interest
nature and the difculty in treating it [6].
No consensus exists on the preferred mode of delivery with regard to The authors have no conicts of interest.
improvement of maternal and perinatal outcomes. Most patients with
FVHILP already have severe coagulation disorders and hypoproteinemia;
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