Nghiên cứu tỷ lệ mang HBsAg ở người mẹ mang thai lây nhiễm sang con và đáp ứng miễn dịch ở trẻ sau tiêm vắc xin viêm gan b tại huyện định hóa – thái nguyên tt tieng anh

MINISTRY OF EDUCATION &TRAINING
THAI NGUYEN UNIVERSITY

NONG THI TUYEN

THE PROPORTION OF MOTHER
TO CHILD TRANSMISSION OF HBsAg CARRIER
MOTHERS AND THE IMMUNE RESPONSE TO
HEPATITIS B VACCINE IN INFANTS IN DINH HOA
DISTRICT - THAI NGUYEN

Speciality: Internal Digestion
Code: 62.72.01.43


SUMMARY OF DOCTORAL THESIS
Thai Nguyen - 2019


The dissertation was completed in:
Thai Nguyen University of Medicine &Pharmacy
Thai Nguyen University
Scientific Supervisors:
1. Assoc Prof, PhD Duong Hong Thai
2. Assoc Prof, PhD Tran Viet Tu
Opponent 1:.............................................................................................
.............................................................................................
Opponent 2:.............................................................................................
.............................................................................................
Opponent 3:.............................................................................................
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The dissertation will be defended at the Dissertation Committee
In National Level held in Thai Nguyen University of Medicine & Phrmacy
Time ….. date …….. month……year 20……
The information from this dissertation can be found at:
- National Library ;
- Learning Resource Center - Thai Nguyen University
- Library of Thai Nguyen University of Medicine &Pharmacy


LIST OF REPORTED WORKS RELATED TO THESIS

1. Nong Thi Tuyen, Phung Thi Tuyet Nga, Duong Hong Thai, Hoang
Anh Tuan (2016),“ Clinical and paraclinical features of prenant
women with HbsAg (+) at Dinh Hoa district in Thai Nguyen
province”, Viet Nam Medical Journal, No special /449 (2016),
pp.188-194.
2. Nong Thi Tuyen, Duong Hong Thai, Tran Viet Tu (2018),
“Assessment of immune response after hepatitis B vaccine
injection in infants born to mothers with HBsAg (+)”, Viet
Nam Medical Journal, No 2/472 (2018), pp. 71-75.
3. Nong Thi Tuyen, Duong Hong Thai, Tran Viet Tu (2018),“Study
on prevalence of HBV in pregnant women and infants with
mothers with HBsAg (+) infants in Dinh Hoa district – Thai
Nguyen province”, Viet Nam Medical Journal, No 2/472
(2018), pp.115-118.



1
INTRODUCTION

Viral hepatitis is a common and dangerous infectious disease
group. Hepatitis virus infection, especially Hepatitis B virus (HBV)
is a global health problem. According to World Health Organization
(WHO), there are approximately 240 million chronic HBV carriers
worldwide and 650000 people die each year due to hepatitis B,
mainly from chronic complications such as liver cirrhosis and
hepatocellular carcinoma (HCC). 20 to 30% people with chronic
hapatitis B develop these complications.
The are 3 common routes of HBV infection: blood
transfusion, sexual transmission and vertical transmission from
mother to child. Vertical transmission is mostly observed in people
with high HBV DNA load or HBeAg positive. In countries with high
prevalence of HBsAg (>8%) before the implementation of Expanded
program on immunization (EPI), HBV infection is mostly through
vertical transmission or household transmission. Perinatal
transmission is also present in countries with lower HBV prevalence
where pregnant women are not examined regularly and HBV
vaccinated.
In Vietnam, domestic plasma-derived hepatitis B vaccine was
first introduced in the Expanded program on immunization for infants
under 1 years old in some provinces in 1997. By the end of 2001,
approximately 370.000 infants had been vaccinated against hepatitis
B, accounted for 25% of infants under 1 years old in the country. The
first dose of hepatitis B vaccine within first 24 hours after birth are
recommended for all infants according to WHO.
However, there are still mother-to-child transmission despite
of adequate hepatitis B vaccination. Immune response in infants
depends on many factors, but hepatitis B vaccination are still the
most important measure to prevent vertical transmission. In Vietnam,
there have been not many studies on the effectiveness of Gene

HBvax and Quinvaxem vaccine in infants under 1 years old. Their
effectiveness in infants born to HBsAg(+) mothers also needs to
study more thoroughly as these two vaccine are used extensively in
the Expanded program on immunization.


2
Dinh Hoa is a mountainous district of Thai Nguyen province.
People in this district are almost from ethnic minorities who have
poor living condition and inadequate knowledge about disease
prevention including the prevention of HBV vertical transmission. In
addition, the current prevention of HBV vertical transmission include
only the use of those two vaccine in EPI without any other measure.
Because of those reasons, we conduct the study "Assess the
proportion of mother-to-child transmission of HBsAg carrier
mothers and the immune response to hepatitis B vaccine in
infants in Dinh Hoa district - Thai Nguyen" for the following
purposes:
1. To determine the prevalence of HBsAg(+) in pregnant women
in Dinh Hoa district - Thai Nguyen during the years 2015 - 2017.
2. To determine the proportion of HBsAg(+) in infants born
to HBsAg(+) mothers in Dinh Hoa district - Thai Nguyen.
3. To assess the post-vaccination immune response after
administering 2 vaccine Gene HBvax and Quinvaxem in infants born
to HBsAg(+) mothers.
STRUCTURE OF DISSERTATION

The key part of the dissertation is 131 pages, including the
following parts:
Introduction: 2 pages

Chapter 1. Literature review: 39 pages
Chapter 2. Subjects and method: 25 pages
Chapter 3. Results: 24 pages
Chapter 4. Discussion: 38 pages
Conclusions and recommendations:3 pages
The dissertation has 130 references, including 25 Vietnamese and 105
documents in English. The dissertation includes 35 tables and 4 charts, 4
pictures.The appendix includes 4 subappendices with 12 pages.


3

Chapter 1: LITERATURE REVIEW
1.1. Overview of Hepatitis B virus
In 1964, Blumberg S.M was found antigen Australia in
Australia aborginical that were transmitted many time blood. After
that, scientists proved Australia antigen that was surface HBV
antigen, international signal was HBsAg (Hepatitis B surface antigen).
After 11 years, in 1975, Dane discoveried little corns by
electromicroscopy that had 42nm diameter, they were called Dane
corns. Afterwards, scientists carried out many studies for HBV and
determined Dane corns were completed virus corns.
1.1.1. Structure of Hepatitis B virus
HBV belongs to Hepadnaviridae, are virus affinity to liver
that AND structure is composed by 3.200 couple of acid nucleotids,
weight of molecule are 2 x 106 dalton.
1.1.2. Genome of Hepatitis B virus
HBV genotypes caused heterogenerous in clinical signs and
therapy responses in patient with chronic hepatitis B in another area
over the world. Up-to-now, there were 10 genotypes of HBV (A-J)

that were determined and some another sub-genotypes. These
genotypes were determined by separating to whole of HBV genotype
family and distributing distincted geography.
1.2. Transmission of Hepatitis B virus
Mode of transmission of HBV are as following:
1.2.1. Transmission by blood transfusion
Before 60s in XX century, because there were not tests of
HBV screening for blood donors, HBV infected proportion of blood
receiver was over 30%, and patients that had to recurrent blood
transmission (such as patient with Hemophilia) catched up to 60%
infecting HBsAg(+). Since 1970, after blood transmission, HBV
prevalence decreased clearly for using HBV screening in serum.
1.2.2. Mother to child transmission
Mother to child transmission is a important epidemic
characteristic in area of high HBV prevalence including Vietnam.


4
The transmission can occur in foetus period, in and after delivery. So
that, beside of expand vaccination for kids we had to care about
vaccination for reproducing women.
1.2.3. Sexual transmission
HBsAg was found in sperm, secreting fluid form vagina, blood from
menopause. HBV infiltrated the body into minimal scratching trace by
intercourse. HBV transmission can occur homosexual intercourse and sexual
intercourse.
1.2.4. Intra-familial transmission
According to Hà Thị Minh Thi et al. showed that prevalence of
people with positive HBsAg in the family having at least a person with HBV
catched up to 47.8%.

1.3. Clinical manifestations of Hepatitis B
1.3.1.Clinical presentation
Chronic Hepatitis B is hepatitis being made by situation of
long lasting infected HBV. Duration of infected HBV is at least 6
months and these patients have chronic inflamation and necrosis in
liver. Chronic Hepatitis B is divided two sorts being positive and
negative HBeAg.
1.3.2. Laboratory tests
* AST/ ALT increased high continuously or intermittently in Chronic
Hepatitis B.
* Other tests of liver function also changed if liver was injuried such
as high bilirubin, low albumine, low prothrombine.
* Blood cell count: anaemia, low white blood count, decreasing
plalete. Ultrasound: maybe cirrhosis image. Liver biopsy: maybe
injuried liver on histopathology.
* There were markers of HBV.
1.4. Hepatitis B, pregnancy and newborn infants:
1.4.1. Hepatitis B in pregnancy
Characteristics of acute Hepatitis B in pregnant women: ro
ret clinical sign was jaudice, especially biliruibin icterus with itching.
Pregnancy was not increasing of infected HBV.


5
1.4.2. Pregnancy outcomes of hepatitis B
Affecting to infected acute hepatitis B in pregnant women
and foetus were abortion, prematurity, stillbirths, acute hepatitis in
infant, cirrhosis but it was not made congenital defects.
1.4.3. Hepatitis B in newborn infants
Hepatitis B in newborn infants usually was serious and

included three sorts such as urgent, acute, semi-acute disease
1.5. Hepatitis B vaccine
1.5.1. First-generation hapatitis B vaccine
The First-generation hepatitis B vaccine was produced from
plasma of people with chronic HBsAg. The vaccine was found the first
time in France and the USA and was used broadly from 1981 to 1982.
1.5.2. Second-generation hapatitis B vaccine
The second-generation hapatitis B vaccine was studied at the
end of 70s. In 1986 this vaccine was proceduced the first time in the
USA. There was a vaccine recombination ADN that displayed S
genotype to code for surface antigen HBsAg on cellulars of yeast, or
biocellular of mammals to start-up HBsAg synthetic process.
1.5.3. Third-generation hapatitis B vaccine
The third-generation hapatitis B vaccine was a vaccine of
origin of S, Pre S1 and S2 genotype of HBV, its immune response
making better. There were two surface protein including Pre S1 and
Pre S2 that had important role to stimulate T-help making anti-HBs.
1.6. Immune response to hepatitis B vaccine in
infants under 1 years old
1.6.1. The implementation of hepatitis B vaccination in Vietnam
national program on immunization
On 18th August 1997, The Prime Minister officially approved to
allow developing hepatitis B vaccine in national expand vaccination
program. Pilot deployment of hepatitis B vaccine was applied in Hà Nội
city and Hồ Chí Minh city. In 2003, 100% villages in the nation carried
our hepatitis B vaccine for 1.500.113 infants under 1 years old.
1.6.2. Hepatitis B vaccination schedule
Today, almost of cases, we used hepatitis B vaccination
schedule as following 0 - 1 - 6 or 0 - 1 - 2 - 12.

6

1.6.3. Post-vaccination immune response
Children was called received immune response with hepatitis
B vaccine if test of anti HBs was ≥ 10 mUI/ml in post-vaccination.
These children had anti-HBs protection, it means they can prevent
from infecting HBV in the future.
1.6.4. Factors affecting immune response
There were many studies in children (including infants of
pregnant women with chronic HBV) showed that, there was a big
changing for post-vaccination immune response after hepatitis B
vaccine for many affecting factors to make immune after this
vaccination.
1.7. Effectiveness of hepatitis B vaccination coverage in expanded
program on immunization
Annually, many nations over the world have to inform their
vaccination schedule and estimated its fee thông qua WHO and
UNICEF. According to UNICEF, up to 2016, there were 101 nations
(accounted for 52% of 194 nations being members of WHO) had
policy of hepatitis B vaccine management for all infants.
1.8. Indication and contraindication of hepatitis B vaccination in
Vietnam
Up-to-now, all children and people under 18 years old have
not had injected hepatitis B vaccine will be indicated this vaccine.
Hepatitis B vaccine also used for high risk infected HBV.
Hepatitis B vaccine was not used for people having allergy to
hepatitis B vaccine. No contra-indication for pregnant women or
breastfeeding women.
Chapter 2: MATERIALS AND METHODS

2.1. Subjects
* Pregnant women
We enrolled all the pregnant women giving birth at Dinh Hoa
General Hospital in the period from 4-2015 to 6-2017 who were


7
positive with HBsAg qick test and were confirmed by HBsAg ELISA
test. These women were explained the study and agreed to join.
+ Inclusion criteria: Pregnant women came to give birth at Dinh Hoa
General Hospital, had normal course of pregnancy, family registration
in Dinh Hoa, T.hai Nguyen and had clear address.
+ Exclusion criteria: Women who were co-infected with HCV, HIV;
women who had severe toxemia of pregnancy, gestational diabetes;
women who were administered antiviral drugs during pregnancy;
women who refused to join the study.
Among 3818 pregnant women came to the hospital during
that time, 239 women were positive to HBsAg quick test, 129 out of
239 HBsAg(+) women were unable to take blood samples or refused
to join the study, so the number of subjects was 110.
* Newborn infants
+ Inclusion criteria: Infants whose mother was infected
with HBV and had HBsAg(+); no congenital heart disease or
other congenital defect was discovered after birth; had adequate
doses of EPI hepatitis B by 6 months old, no asphyxia after birth.
+ Exclusion criteria: Infants who were not taken blood
sample after vaccination or their family refused to join the study
110 newborn infants were enrolled to population-based
trial on vaccination and were assessed immune response at 6
months old. However, 8 infants were not taken blood sample

when they were 6 months old because they did not have adequate
doses of vaccination, some infants migrated out of the district.
So the number of infants in the trial was 102.
* Time and place: from 4/2015 to 6/2017.
2.2. Methods
2.2.1. Design
The study include two consecutive stages: cross-sectional
study to assess the prevalence and population-based trial:
* Cross-sectional: to assess the prevalence of HBV infection
among pregnant women and the proportion of vertical transmission
from mother to child.
* Population-based trial


8
2.2.2. Sample size
* Sample size for objective 1: all the pregnant women giving
birth at Dinh Hoa General Hospital in the period from 4/2015 to
6/2017, who had family registration in Dinh Hoa district, Thai
Nguyen
* Sample size for objective 2 and 3:
Equation:

n



Z 2 1

2

 �p � 1  p 

d2

Z = 1,96 at confidence level 95%
p = 0,93 (proportion of immune response according to previous studies: 93 96% [9], [10], [130])
d = 0,05 expected error
α = 0,05 probability of type 1 error
From the formula: n = 97. We estimated that up to 10% of the subject
might drop out, so the minimal sample size was 110.
2.3. Conducting research steps
-Step 1: Selecting a research objects
-Step 2: Explaining and consulting the benefits of
participating in research to pregmant women
-Step 3: Setting up a research case-record
-Step 4: Taking the pregnant women’s blood in labor
-Step 5: Taking blood from the newborns’ umbilical cord
-Step 6: Vaccinating the newborns with Gene HBvax
-Step 7: Injecting vaccine Quinvasee to infants of 2, 3, 4
months old
-Step 8: Taking blood from 6-month-old infants
-Step 9: Analysing results and completing the thesis.
2.4. Variables, indexes and methods of collection
* General information in study group
- Age of pregnant women: Being divided three groups as
following: < 18 years old; From 18 – 35 years old; > 35 years old.
- Occupation: Being divided three groups as following:
Farmer; Civil servant; other.

9
- Ethnic: Being divided five groups as following: Kinh;
Tay; San chi; Nung; other ethnic.
Mode of delivery: Being divided three groups as following:
- Normal labour; C-section; Vaginal delivery with
episiotomy.
- Young genders: Being divided two groups as following:
Male and female.
- Birthweight of neonata: Being divided four groups as following
(unit by gram): < 2500gr; 2500 - < 3000gr; 3000-3500gr; ≥ 3500gr.
Author or doctor in Department of gynecology in Dinh Hoa
General Hospital: examination, medical record and taking note study record.
* Prevalence of HBsAg in pregnant women in Dinh Hoa district,
Thai Nguyen
- HBsAg Marker in plasma in pregnant mother: Being
divided two groups as following: Positive and negative HBsAg. The
1st step: Quick test in all pregnant mother who give birth in deparment of
obstetrics in Dinh Hoa general hospital. The 2nd step: ELISA test in Center
of Hematology, Thai Nguyen central hospital.
- Number of years since diagnosis of HBV infection: Being
divided four groups as following: under 5 years; 5 – 10 years; over 10
years; no information. Author or doctor in Department of gynecology
in Dinh Hoa General Hospital: examination, medical record and taking
note study record.
- HBeAg Marker in plasma in pregnant mother: Being
divided two groups as following: HBeAg(+); HBeAg(-).Quick test in
all pregnant mother with positive HbsAg in deparment of obstetrics in
Dinh Hoa general hospital.
- HBV DNA load in plasma in pregnant mother: Being

divided four groups as following: (unit by copies/ml): < 3x10 2;
From 3x10 2 to < 103; From 103 to < 10 4; From 10 4 to < 105; From
105 to < 106;> 106. Test by Realtime PCR.
* Prevalence of positive HBsAg in pregnant women with HBsAg at
Dinh Hoa general hospital
HBsAg Marker In infant: Being divided two groups as
following: Positive and negative HBsAg. Umbilical cord blood test by
ELISA in Center of Hematology, Thai Nguyen central hospital.


10
* Post-vaccination immune response in infants born to HBsAg
positive mothers
- HBsAg marker in infants under 6 months old: Being
divided two groups as following: Positive and negative HBsAg.
Umbilical cord blood test by ELISA for 6-month-old infants who were
injected enough HBV vaccine in Center of Hematology, Thai Nguyen
central hospital.
- Anti HBs marker in infants under 6 months old: Being
divided three groups as following: Anti HBs < 10(mIU/ml); From 10
to 100(mIU/ml); Anti HBs > 100(mIU/ml). Umbilical cord blood test
by ECLIA for 6-month-old infants, in Center of Hematology, Thai Nguyen
central hospital
2.5. Data collection techniques
2.5.1. Clinical examination
All pregnant mother who give birth in deparment of obstetrics,
in Dinh Hoa general hospital were examinated, taken note study and
medical record by author or doctor in here. The mothers with toxaemia
pregnancy, pregnant diabetes were excluded the study.
As soon as being delivery, infants were exminated carefully.

The infans had unusual signs such as congetinal defect, congenital
heart defect, circulator and breathing failure were excluded the study.
2.5.2. Hepatitis B vaccination
- Neonatas that were selected in the study were injected one Gene
Hbvax vaccine by mid-wife, taking note to HBV vaccination book in
Department of Obstetrics, in Dinh Hoa general hospital.
- The infants in the study were injected 1 st, 2nd, 3rd Quinvaxem
vaccine in turn at 2-month-old, 3-month old and 4-month-old time at
medical station where the infants lived.
2.5.3. Laboratory tests
2.5.3.1. For mothers: HBsAg test (quick test); anti HCV test
(quick test); anti HIV test (quick test); HbsAg test (ELISA);
HBeAg (quick test); HBV DNA test.
2.5.3.2. For infants: HbsAg test (ELISA) at neonatas by umbilical
cord blood; HbsAg test (ELISA) by vein in 6 –month-old infant;
anti HBs test by ECLIA in 6–month-old infant.


11
2.5.4. Data analysis:
The data were entered into pre- designed data templates
using Epidata software and analysed using SPSS 20.0.
2.6. Definition of variables:
2.6.1. Chronic hepatitis B
Chronic hepatitis B was necrosis and chronic in liver that was caused
by HBV and long lasting over 6 months. Chronic hepatitis B was
divided two group that Chronic hepatitis B with positive HbeAg and
negative HBeAg.
2.6.2. Immune response
To distribute post-vaccination results:

+ Infants having Hepatitis B post-vaccination: the infant with
HBsAg(+) at 6-month old.
+ Infant having non-hepatitis B post-vaccination: the infant
with HBsAg(-) at 6-month old.
+ Infants were achieved successful post-vaccination results:
the infants with HBsAg(-) and level of anti HBs in plasma ≥ 10
mIU/ml at 6-month-old.
+ Infants were had unsuccessful post-vaccination results: the
infants with HBsAg(+) or HBsAg(-) and level of anti HBs in plasma
< 10 mIU/ml at 6-month-old.
+ Infants having immune respond under protecting: the
infants with anti HBs level < 10 mIU/ml at 6-month-old.
+ Infants having weak immune respond: the infants with anti
HBs being from ≥ 10 mIU/ml to ≤ 100 mIU/ml at 6-month-old.
+ Infants having good immune respond: the infants with anti
HBs ≥ 100 mIU/ml at 6-month-old.
2.6.3. Dependent variable
* Level of anti HBs in infants after injecting Gene – HBvax and
Quinvaxem vaccine: The level of anti HBs at 2,3,4 –month-old was
quantity variable. Anti HBs was measured by mIU/ml and minimal
level was 10 mIU/ml.
* HbsAg infants after injecting Gene – HBvax and Quinvaxem
vaccine: qualitative variable were positive and negative.
2.6.4. Independent variable
- Neonatal HBV vaccine (Gene – HBvax) and Quinvaxem
vaccine were independent variable.


12
- HBV DNA load: was divided two degrees as following that

HBV DNA: ≥ 3x102 coppies/ml and HBV DNA: < 3x102coppies/ml
2.7. Materials in research
- Thermostat (PCR) Mastercycler of Germany, at Department of
Microbiology Thai Nguyen University of Medicine and Pharmacy.
- ARCHITECT PLUS machine of the United States, at Blood
Transfusion Center, Thai Nguyen Central Hospital.
- Vaccine Gene HBvax and Quinvaxem
2.8. Ethical approval
We only selected infants that had their mother with
HBsAg(+) and they agreed spontanously after being talked careful
consultant for objective study, schedule of the study, their rights and
responsibility. They can be out of the study any time and were kept
secret individual for all objects.
2.9. Limitations of the thesis
No 6-month infant blood was obtained from children of
HBsAg mothers (-) to compare immune responses.
Chapter 3: RESULTS
3.1. General characteristics of the subjects:
Table 3.1. Age of the pregnant women
Age group
Frequency
Percent (%)
< 18
1
0.9
18 - 35
106
96.4
> 35
3

2.7
Mean age (X  SD)
26.36  4.54
*Comment: Age of pregant women in the study was from 16 to 38
years old. In which proportion of 18-to-35 year-old group was the
highest (96.4%). Mean age was 26.36  4.54 years old.
Table 3.3. Ethnicity of the subjects
Ethnic group
Frequency
Percent (%)
Kinh
17
15.5
Tay
55
50.0
San chi
21
19.1
Nung
5
4.5


13
Others
12
10.9
Total
110

100.0
* Comment: Tay group accounted for the highest in the women of
the study up to 50.0%, proprotion of San group only was 19.1%,
Kinh group was 15.5%. Besides, there were other ethnic group such
as Nung, Dao, Thai, Muong....
Table 3.6. Mode of delivery
Mode of delivery
Frequency
Percent (%)
Normal labour
7
6.4
Vaginal delivery with episiotomy
62
56.4
C – section
41
37.2
Total
110
100.0
* Comment: Pregnant women in the study were had vaginal delivery with
episiotomy accounted for 56.4% (meant 62/110 cases). The women with
C-section were 41/110 cases, accounted for 37.2%. Normal labour had the
lowest proportion that was 6.4% (7/110 cases).
Table 3.7. Gender of infants
Gender
Frequency
Percent %
Male

63
57.3
Female
47
42.7
Total
110
100.0
* Comment: In 110 infants. males were 63 people (57.3%) and females
were 47 people (42.7%).
Table 3.8. Birthweight of infants
Birthweight (gr)
Frequency (n)
Percent (%)
2500 - < 3000
42
38.2
3000 - < 3500
44
40.0
≥ 3500
24
21.8
Total
110
100.0
3131.64 ± 395.73
Mean birthweight ( X  SD)
* Comment: No infant had birthweight under 2500grams. Proportion of
infants that weighed from 3000grams to under 3500grams was the

highest (40.0%). Mean infant-birthweight was 3131.64 ± 395.73 grams.


14
3.2. Prevalence of HBsAg in pregnant women in Dinh Hoa
district, Thai Nguyen
Table 3.9. Prevalence of HBsAg in pregnant women who give birth
at Dinh Hoa general hospital
Pregnant women
Frequency
Percent (%)
HBsAg(+)
239
6.3
HBsAg(-)
3579
93.7
Total
3818
100.0
* Comment: There were 239/ 3818 pregantn women with positive
HbsAg, accounted for 6.3 %.
Table 3.11. HBeAg test result in HBsAg-positive pregnant women
HBeAg test result
Frequency (n)
Percent (%)
HBeAg(+)
40
36.4
HBeAg(-)

70
63.6
Total
110
100.0
* Comment: Number of woment with positive HbeAg were 40/110
cases (36.4 %).
Table 3.12. HBV DNA load in HBsAg-positive pregnant women
HBV DNA load in mother
Frequency (n)
Percent (%)
< 3x102 (copies/ml)
45
40.9
2
3
From 3 x10
to < 10
11
10.0
(copies/ml)
From 103 to < 104 (copies/ml)
9
8.2
4
5
From 10 to < 10 (copies/ml)
2
1.8
5

6
From 10 to < 10 (copies/ml)
5
4.5
> 106 (copies/ml)
38
34.6
Total
110
100.0
6
* Comment: Number of woment with HBV DNA > 10 copies/ml were
38/110 cases (34.6%). Number of woment with HBV DNA < 3x102
copies/ml were 45/110 case (40.9%).
Table 3.13. Relationship between HBV DNA load and HBeAg in
HBsAg-positive pregnant women (n=110)
HBeAg(+)
HBeAg(-)


15
HBeAg
Frequency
Percent
Frequency
Percent
(n)
(%)
(n)
(%)

HBV DNA
2
≥
3x10
38
95.0
27
38.6
copies/ml
<
3x102
2
5.0
43
61.4
copies/ml
Total
40
100.0
70
100.0
p, OR,CI
p<0.001; OR = 30.3; CI (6.74 – 135.76)
* Comment: Number of HBV DNA copies had a closed relationship
with level of HBeAg in plasma in pregnant women with infected
HBV. The difference was significant with p < 0.001. OR was 30.3;
95%CI (6.74 – 135.76).
Table 3.15. Relationship between HBV DNA load and ethnicity in
HBsAg-positive pregnant women (n=110)
HBV ≥ 3x102 copies/ml

< 3x102 copies/ml
DNA
Frequency
Percent
Frequency
Percent
Ethnic
(n)
(%)
(n)
(%)
group
Kinh
12
18.5
5
11.1
Tay
24
36.9
31
68.9
Nung
4
6.1
1
2.2
San chi
18
27.7

3
6.7
Others
7
10.8
5
11.1
Total
65
100.0
45
100.0
p
p < 0.05
* Comment: There was relationship between ethnic with number of HBV
DNA copies in the women of the study, significantly with p < 0.05.
3.3. Prevalence of HBsAg in newborn infants born to HBsAg
positive mothers in Dinh Hoa district, Thai Nguyen.
Table 3.16. Prevalence of newborn infants whose umbilical cord blood
were HBsAg positive
Infants
Frequency
Percent (%)
HBsAg(+)
45
40.9
HBsAg(-)
65
59.1

16
Total
110
100.0
* Comment: In the 110 infants, there were 45 children with positive
HBsAg (40.9%).
Table 3.17. Prevalence of newborn infants with HBsAg-positive
umbilical cord blood born to mother with HBsAg(+) and HBeAg(+)
Umbilical
HBsAg(+)
HBsAg(-)
cord
Frequenc
Percent
Frequenc Percent
Blood
y (n)
(%)
y (n)
(%)
Mother
HBeAg(+)
20
44.4
20
30.8
HBeAg(-)
25
55.6

45
69.2
Total
45
100.0
65
100.0
p, OR, CI
p > 0.05; OR = 1.8; CI (0.817 – 3.964)
* Comment: Women with positive HBeAg(+) were no affection to transmit
HBV to infant by Umbilical cord blood, insignificant with p > 0.05.
Table 3.18. Prevalence of HBsAg(+) umbilical cord blood in the
infected HBV mother with HBV DNA > 3x102 copies/ml
Umbilical
HBsAg(+)
HBsAg(-)
cord
Frequency
Percent
Frequency
Percent
Blood HBV
(n)
(%)
(n)
(%)
DNA Mother
≥
3x102
32

71.1
33
50.8
copies/ml
<
3x102
13
28.9
32
49.2
copies/ml
Total
45
100.0
65
100.0
p, OR, CI
p < 0.05; OR = 2.39; CI (1.065 – 5.352)
* Comment: The mother with HBV DNA ≥ 3x10 2 copies/ml had
tranmitted HBV from mother to infant by umbilical cord blood was
2.39 times compared with the other mother with HBV DNA < 3x10 2
copies/ml. The difference was singnificant with p < 0.05; OR = 2.39;
CI (1.065 – 5.352).
Table 3.21. Relationship between maternal age group and HBV
transmission to infants through umbilibal cord blood (n=110)


17
Umbilibal
cord

Blood
Maternal age
≤ 26 years

HBsAg(+)

HBsAg(-)

Frequency
(n)

Percent
(%)

Frequency
(n)

Percent
(%)

30

66.7

27

41.5

> 26 years
15

33.3
38
58.5
Total
45
100,0
65
100,0
P, OR, CI
p < 0.05; OR = 2.82; CI (1.275 – 6.216)
* Comment: The under 26-year-old women with infected HBV had
transmitted HBV to infant was 2.82 times compared with the other
women in the study. The difference was significant with p < 0.05,
95%CI (1.275 – 6.216).
3.4. Post-vaccination immune response in infants born to HBsAg
positive mothers
Table 3.22. HBsAg test results in infants under 6 months old
Test results
HBsAg(+)
HBsAg(-)
Total

Frequency
44
58
102

Percent (%)
43.1
56.9

100.0

* Comment: In which 102 infants, there were 44 infants (43.1%) had in 6month-old infant with positive HBsAg.
Table 3.23. Relationship between post-vaccination anti HBs levels
and HBsAg in infants under 6 months old
HBsAg 6
HBsAg(+)
HBsAg(-)
months old
Anti HBs level
(mIU/ml)
< 10
10 - 100
> 100

Frequency
(n)

Percent
(%)

Frequency
(n)

Percent
(%)

22
13
9

50.0
29.5
20.5

7
28
23

12.1
48.3
39.6


18
Total
Mean
concentration
of anti HBs, p

44

100.0
58
218.58 ± 134.28; p < 0.001

100.0

* Comment: Level of anti HBs in plasma in post-vaccination children
had a closed relationship to level of their HBsAg in plasma. The

difference was significant with p < 0.001.
Table 3.25. Relationship between maternal HBe and HBsAg in 6-month-old
infants after vaccination
HBsAg in 6HBsAg(+)
HBsAg(-)
month-old
infants Frequency
Percent
Frequency
Percent
Maternal
(n)
(%)
(n)
(%)
HBeAg
HBeAg(+)
21
47.7
18
31.0
HBeAg(-)
23
52.3
40
69.0
Total
44
100.0
58

100.0
p, OR,CI
p > 0.05; OR = 2.03; CI (0.901 – 4.570)
*Comment: Maternal HBeAg was affected to transmit HBV to
children after vaccination. The difference was insignificant with p >
0.05.
Table 3.26. Relationship between maternal HBV DNA load and
HBsAg in 6-month-old infants after vaccination
HBsAg in 6HBsAg(+)
HBsAg(-)
month-old
Infant
s Frequenc Percent Frequenc Percent
Maternal
y (n)
(%)
y (n)
(%)
HBV DNA
(copies/ml)
≥ 3x102
32
72.7
30
51.7


19
< 3x102

12

27.3

28

48.3

Total

44

100.0

58

100.0

p, OR,CI

p < 0.05; OR = 2.49; CI (1.075 – 5.765)

* Comment: The infected HBV mother with positive HBV DNA
transmitted to HBV to infants as high as 2.49 times compared with
the mother with negative HBV DNA. The difference was significant
with p < 0.05; OR = 2.49; CI (1.075 – 5.765).
Table 3.32. Relationship between maternal HBV DNA load and
immunization result in 6-month-old infants
6-monthUnsuccessful
Successful

old infants
immunization
immunization
Frequenc Percent Frequenc Percent
Maternal
y (n)
(%)
y (n)
(%)
HBV DNA
≥
3x102
35
68.6
27
52.9
copies/ml
<
3X102
16
31.4
24
47.1
copies/ml
Total
51
100.0
51
100.0
p,OR, CI

p > 0.05; OR = 1.94; CI (0.876 – 4.36)
* Comment: In maternal HBV DNA load ≥ 3x102 copies/ml, the 6month-old infant was unsuccessful immunization as high as 1.94
times compared with the other maternal. The difference was
insignificant with p > 0.05.
Chapter 4: DISCUSSION
4.1 General characteristics of the subjects
According to the table 3.1, 110 hepatitis B infection mothers
mostly was in the age of 18-35 years old (96.4%), the youngest and
the oldest was 16 and 38 years old. The average age of pregnancy
was 26.364.54.


20
In the table 3.3, most of subjects was ethnic minority, Tay
was the dominant (49.1%). Others was San Chi, Dao, Nung, Thai,
Muong, Hoa. It was easy to give the advice and prevention technique
for them.
In table 3.6, 55.5% woman with episiotomy. 38.2% woman
had cesar, 6.4% with normal labor. There was no case with forceps.
There was no relation between the method of labor and the risk of
HBV infection in the previous research. However, there was some
recommendation of avoiding the lesion. In 110 cases, there was no
case had complication.
In table 3.7, in 110 newborn babies, there was 57.3%
(63/110) boys, and 42.7% (47/110) girls. This results was also the
same with others studies in Vietnam.
Table 3.8 showed that there was no baby weighted under
2500 g, mostly from 2500 to 3500 g, 24 babies weighted over 3500 g.
Other studies showed the lighter babies had low antibody level.
4.2 The prevalence of HBsAg in pregnant woman in Dinh Hoa

district, Thai Nguyen
Table 3.9 showed that there was 239 in 3818 pregnant
woman from April, 2015 to June, 2017 with HBsAg (+) took 6.3%,
lower than Chu Thi Thu Ha study at Hospital of Gynecology Ha Noi
(12%), Nguyen Thi Tuyet Nga (12.59%), higher than Nguyen Van
Hien (0.16%). These differences might be caused by the high
mountain area.
Table 3.11 showed 36.4% woman with HBsAg (+), lower
than Chu Thi Thu Ha (40.5%), Purusotam Raj Shedain in Nepal high
mountain with HBV positive and HBeAg positive (40%). It was also
higher than Phi Duc Long in Ha Noi and Thai Binh (26.7%).
Table 3.12 showed that the HBV DNA (-) woman was 45
cases (40.9%), 38 woman (34.6%) with HBV DNA > 10 6 copies/ml.
It could raise the concern among the chronic HBV, the high level one
was young (16 years old). This study also showed the woman ≤ 26
had higher virus level than > 26 year-old individuals.
Table 3.13 showed the close relation between HBV DNA
level and HBeAg in pregnant HBV infection woman (p<0.001; CI
(6.74-135.76)). These was the same with other studies, when HBeAg