Cost-Effectiveness of Maternal Treatment to
Prevent Perinatal Hepatitis B Virus Transmission
Elizabeth Ramsey Unal, MD, Gweneth B. Lazenby, MD, Anne E. Lintzenich,
Kit N. Simpson, DrPH, Roger Newman, MD, and Laura Goetzl, MD, MPH
OBJECTIVE: To estimate the cost-effectiveness of maternal
lamivudine or hepatitis B immune globulin (HBIG) treat-
Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 07/04/2021
ment, in addition to standard neonatal immunoprophylaxis,
for the prevention of perinatal hepatitis B virus transmission.
METHODS: A decision-tree model was created to esti-
mate the cost-effectiveness of maternal administration of
either lamivudine or HBIG in the third trimester to
prevent perinatal hepatitis B transmission compared with
no maternal treatment. The model was first estimated for
each treatment using overall transmission rates, and then
stratified by maternal hepatitis B virus DNA viral load.
RESULTS: The model estimated that for each 100 hepa-
titis B surface antigen positive pregnant women treated
with lamivudine, 9.7 cases of chronic hepatitis B virus
infections are prevented, with a cost-savings of $5,184
and 1.3 life-years gained per patient treated. For HBIG,
9.5 cases of chronic hepatitis B virus infections are
prevented for each 100 pregnant women treated, with a
cost-savings of $5,887 and 1.2 life-years gained per pa-
tient treated. Under baseline assumptions, lamivudine
remains cost-saving unless the reduction in perinatal
transmission is less than 18.5%, and HBIG remains cost-
saving unless the reduction in perinatal transmission is
less than 9.6%.
CONCLUSION: In this decision analysis, administration
of lamivudine or HBIG to hepatitis B surface antigen
positive pregnant women for the prevention of perinatal
transmission of hepatitis B is cost-savings across a wide
range of assumptions.
(Obstet Gynecol 2011;118:655–62)
DOI: 10.1097/AOG.0b013e31822ad2c2
LEVEL OF EVIDENCE: III
From the Departments of Obstetrics and Gynecology, Pediatrics, and Health Science
and Research, Medical University of South Carolina, Charleston, South Carolina.
Corresponding author: Elizabeth Ramsey Unal, MD, 96 Jonathan Lucas Street,
Suite 634 MSC 619, Charleston SC 29425; e-mail: unal@musc.edu.
Financial Disclosure
The authors did not report any potential conflicts of interest.
© 2011 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/11
VOL. 118, NO. 3, SEPTEMBER 2011
MD,
H epatitis B virus is a major global health concern,
with prevalence rates as high as 10 –15% in some
regions of the world.1,2 Even in the United States,
which overall is a low-prevalence region (less than
2%),2 certain immigrant populations have much
higher rates, reflective of their countries of origin.2,3
Perinatal transmission is an important cause of
chronic hepatitis B, accounting for 35–50% of the
disease in endemic countries.4 Whereas adults in-
fected with hepatitis B virus infections have less than
a 5% chance of developing chronic infection, 90% of
perinatally infected children become chronic carri-
ers.5–9 Chronically infected individuals are at high risk
for cirrhosis and hepatocellular carcinoma. Approxi-
mately 25% of chronic hepatitis B carriers die prema-
turely as a result of one or both of these complica-
tions,2 and this rate may be up to 40% for perinatally
infected individuals.10
Currently recommended active-passive immu-
noprophylaxis for all newborns of women positive for
hepatitis B surface antigen is 85–95% effective in pre-
venting perinatal transmission.11 However, multiple
studies have shown that women with high levels of viral
replication remain at elevated risk. Perinatal transmis-
sion rates despite appropriate neonatal prophylaxis in
these highest-risk women have been reported to be
13– 62.5%,12–19 with most estimates between 15% and
30%. The transition point in maternal viral load at which
transmission rates begin to rise dramatically is approxi-
mately 106–108 copies/mL.12,13,16
A significant proportion of perinatal transmission
in women with high viral loads is now believed to be
intrauterine.13,14,17,20 –22 Therefore, studies have been
conducted to evaluate the benefit of maternal admin-
istration of either lamivudine or hepatitis B immune
globulin (HBIG) in the third trimester to decrease
transmission rates. Most of these studies have been in
Asia, and the results have been promising. In 2010,
Shi et al published two meta-analyses on the use of
third-trimester maternal lamivudine or HBIG in
OBSTETRICS & GYNECOLOGY 655
 Maternal treatment

No Yes
Fig. 1. Decision tree for maternal
treatment with lamivudine or hep-
No hepatitis B Hepatitis B No hepatitis B Hepatitis B atitis B immune globulin to pre-
transmission transmission transmission transmission
vent perinatal hepatitis B virus
transmission.
Resolved Chronic hepatitis B Resolved Chronic hepatitis B
Unal. Preventing Perinatal HBV
Transmission. Obstet Gynecol 2011.

women with high viral loads.18,19 These meta-analyses
found a 69% and 67% reduction in infant hepatitis B
surface antigen positivity at age 9 –12 months with the
use of lamivudine and HBIG, respectively. Despite
this evidence, use of these agents to reduce perinatal
hepatitis B virus transmission is not standard of care
in the United States. Our objective was to estimate the
cost-effectiveness of maternal treatment with lamivu-
dine or HBIG.
MATERIALS AND METHODS
We created a decision-tree model to estimate the
cost-effectiveness of maternal administration of lami-
vudine or HBIG in the third trimester to prevent
perinatal hepatitis B transmission compared with no
maternal treatment (Fig. 1). The decision tree was
created and run using Microsoft Excel 2008 12.2.3.
This project was not submitted to our institutional
review board, as all data used were extracted from
published studies, and no institutional or individual
patient information is included in this analysis. The
Medical University of South Carolina Office of Re-
search Integrity states that a study of this kind is not
considered to be human subjects research and thus
does not require University IRB approval.
Our baseline assumptions are outlined in Table 1.
The overall perinatal hepatitis B transmission rate
without maternal treatment (15.7%) was obtained by
averaging the transmission rates in the control groups
from two recent meta-analyses, one on lamivudine
and the other on HBIG, both by Shi et al.18,19 Both
meta-analyses included randomized controlled trials
of maternal lamivudine or HBIG compared with no
maternal treatment, in English language or Chinese
peer-reviewed literature. Transmission rates without
treatment stratified by maternal viral load were taken
from a study by Yuan et al.12 The odds ratios for
perinatal transmission with maternal treatment com-
pared with no treatment (0.31 and 0.33 for lamivu-
dine and HBIG, respectively) were taken from the
meta-analyses18,19 and applied to the averaged trans-
mission rate without maternal treatment to obtain

Table 1. Model Inputs: Probabilities

Perinatal Odds Ratio
Transmission Perinatal for Transmission
Without Transmission if Treatment
Viral Load (Copies/mL) Treatment* With Treatment* Is Given Study Range References

Lamivudine
Overall 15.7 4.9 0.31 0.06–0.94 (ie, 6–94% 18, 19
HBV DNA less than 108 3.3 1.0 0.31 reduction) 12, 18
HBV DNA 108–109 14 4.3 0.31 12, 18
HBV DNA 109–1010 42.9 13.3 0.31 12, 18
HBV DNA 1010–1011 53.3 16.5 0.31 12, 18
HBV DNA more than 1011 62.5 19.4 0.31 12, 18
HBIG
Overall 15.7 5.2 0.33 0.06–0.84 (ie, 16–94% 18, 19
HBV DNA less than 108 3.3 1.1 0.33 reduction) 12, 19
HBV DNA 108–109 14 4.6 0.33 12, 19
HBV DNA 109–1010 42.9 14.2 0.33 12, 19
HBV DNA 1010–1011 53.3 17.6 0.33 12, 19
HBV DNA more than 1011 62.5 20.6 0.33 12, 19
HBV, hepatitis B virus; HBIG, hepatitis B immune globulin.
Data are % unless otherwise specified.
* Defined as positive for hepatitis B surface antigen at 9 –12 months of age.

656 Unal et al Preventing Perinatal HBV Transmission OBSTETRICS & GYNECOLOGY

Table 2. Model Inputs: Costs
Cost References
Lamivudine* $1,640 23
†
HBIG $731 23
HBV DNA serum viral load $234 46
Lifetime cost of chronic $72,384 25–34, 45
HBV infection
HBIG, hepatitis B immune globulin; HBV, hepatitis B virus.
* 100 mg orally once daily from 28 weeks of gestation until 4
weeks after delivery.
†
200 international units intramuscularly monthly starting at 28
weeks of gestation; assume four doses
transmission rates with treatment (4.9% and 5.2% for
lamivudine and HBIG, respectively). These numbers
were all based on infant hepatitis B surface antigen
positivity at age 9 –12 months. We also used the odds
ratios for perinatal transmission from the two meta-
analyses18,19 and applied those numbers to transmis-
sion rates without treatment by maternal viral load to
estimate the cost-effectiveness of treatment stratified
by maternal viral load.
We assumed that 90% of infants infected perina-
tally would become chronic carriers.5–9 Because peri-
natal transmission rates are very low in women with
low viral loads16 and thus additional treatment with
lamivudine or HBIG is most beneficial in patients
with high viral activity, we made the assumption that
maternal hepatitis B virus DNA viral load would be
assessed before initiating third-trimester maternal
treatment.
We assumed 100% compliance with current rec-
ommendations for active-passive immunoprophylaxis
(HBIG and vaccination) for all newborns of women
positive for hepatitis B surface antigen. Thus our
model applies the current standard of immunopro-
phylaxis to both groups. We assumed maternal dos-
ing regimens of lamivudine 100 mg orally once daily
from 28 weeks of gestation through 4 weeks postde-
livery and HBIG 200 international units administered
intramuscularly once monthly starting at 28 weeks of
gestation, as these have been the most commonly
studied regimens. Costs for lamivudine and HBIG
were taken from the 2010 Red Book.23 The model
also assumes no maternal or fetal risk from third-
trimester use of lamivudine or HBIG.
The model was designed to estimate the lifelong
medical costs of chronic hepatitis B infection from a
health systems perspective. Life expectancy in pa-
tients with chronic hepatitis B was taken from 2006 –
2007 Florida State hospital discharge data, and life
expectancy in a general population was taken from
2007 National Vital Statistics data.24,25 The lifelong
cost of chronic hepatitis B infection was calculated
based on published yearly costs by different hepatitis
B health states defined from a health systems perspec-
tive,26 using previous studies to determine the number
of patients who would progress to compensated cir-
rhosis, decompensated cirrhosis, hepatocellular carci-
noma, hepatic transplant, or a combination of these
over a lifetime.27–34 We assumed that all hepatocellu-
lar carcinoma cases arose in the setting of cirrhosis.
Because the lifelong natural history of perinatal hep-
atitis B virus infection is not well described, we
derived most of these assumptions from the literature
on chronic hepatitis B in general, rather than litera-
ture specific to perinatally transmitted chronic hepa-
titis B. Although serious childhood complications do
occur, most perinatally infected children do not ex-
perience significant complications until adulthood.35,36
For the model, we made the conservative assumption
that no medical complications and therefore no costs
accrue until age 20. Cost calculations are outlined in
Tables 2 and 3.
A sensitivity analysis was then performed by
varying the estimates for degree of reduction in
perinatal transmission with maternal treatment, med-

Table 3. Calculation of Lifetime Cost of Hepatitis B Virus Infection

Annual Years in
Health State Base Case Distribution Range (%) Costs* Health State References
†
Chronic hepatitis without cirrhosis 75% of chronic hepatitis B 58.5–85 $1,170 57.9 24, 26
Chronic hepatitis with cirrhosis 25% of chronic hepatitis B 15–41.5 $1,519 44.9‡ 25–27, 29, 30, 33
Decompensated cirrhosis 16% of cirrhosis 16–30 $17,623 2 26, 28, 29, 47
Hepatocellular carcinoma 20% of cirrhosis 9–21.7 $11,585 1.67 26, 27, 29, 31, 33
Hepatic transplant 1.4% of all chronic hepatitis B — $133,117 1 26, 32
Posthepatic transplant — $19,317 10 26, 34
* Year 2010 dollars, converted from year 2000 dollars as reported in Lee et al,26 using medical cost–specific Consumer Price Index
(www.bls.gov).45
†
Assuming no costs for first 20 years of life and life expectancy of 77.9 years.
‡
Assuming no costs for first 20 years of life and life expectancy of 64.9 years. To calculate the contribution of cirrhosis to overall
lifetime cost, we assumed onset of cirrhosis at age 4829 and costs were distributed accordingly.

VOL. 118, NO. 3, SEPTEMBER 2011 Unal et al Preventing Perinatal HBV Transmission 657
ical severity of chronic hepatitis B infection, and
lifelong cost of chronic hepatitis B. We also varied the
percentage of women who would warrant treatment
after viral load determination, to evaluate the cost of
checking viral loads in all patients to determine need
for treatment in some.
Because HBIG and lamivudine are hypothesized
to have different mechanisms of action in reducing
perinatal hepatitis B transmission, it has been sug-
gested that additive benefit may be expected if both
HBIG and lamivudine are administered in combina-
tion.20 To our knowledge, this hypothesis has not
been evaluated in prospective studies. To evaluate
whether this strategy would be cost-effective, we
estimated a model using both HBIG and lamivudine
in combination, assuming varying levels of additional
benefit in reducing perinatal hepatitis B transmission.
RESULTS
Using our base-case estimates, use of either lamivudine
or HBIG was not only cost-effective, but also cost-
saving, for all situations except lamivudine at a maternal
viral load of less than 108 copies/mL. For every 100
pregnant women positive for hepatitis B surface antigen
treated with lamivudine, 9.7 cases of chronic hepatitis B
virus infections are prevented, with a cost-savings of
$5,184 and 1.3 life-years gained per patient treated. For
HBIG, 9.5 cases of chronic hepatitis B virus infections
are prevented for each 100 pregnant women treated,
with a cost savings of $5,887 and 1.2 life-years gained
per patient treated. The only instance in which no cost
savings was achieved (lamivudine at a maternal viral
load of less than 108 copies/mL) had a cost per patient of
$390 to prevent two cases of chronic hepatitis B virus
infections for each 100 patients treated, well within the
limits of what is commonly considered to be cost-
effective. For each of the other cases considered, use of
lamivudine or HBIG provided a cost savings, in addi-
tion to preventing chronic hepatitis B and its sequelae.
Detailed results for the base-case estimates are outlined
in Table 4.
One-way and multi-way sensitivity analyses were
performed by altering estimates for the percentage of
women whose viral load would warrant treatment (ie,
the cost of checking viral loads in all women to
determine need for maternal treatment in some), the
degree of reduction in perinatal transmission with
maternal treatment, the medical severity and life
expectancy in chronic hepatitis B infection, and life-
long cost of chronic hepatitis B. The results are
summarized in Table 5.
Adjustment of parameters related to percentage
of chronic hepatitis B patients developing cirrhosis,
decompensated cirrhosis, or hepatocellular carcinoma
had modest effects on lifetime cost of chronic hepatitis B
infection. Altering these parameters yielded a lowest
lifetime cost of $72,045 and highest lifetime cost of
$74,600. If both life expectancy (ranging from 50 years
to 64.9 years) and distribution of chronic hepatitis B
health states were altered, the lowest lifetime cost was
$64,295 and highest was $74,600.
Altering the proportion of women who would
have a viral load drawn, but not warrant maternal
treatment, was also evaluated in the sensitivity analy-
sis. The base-case estimates assumed that all women
having a third-trimester viral load would be treated
with lamivudine or HBIG. Because most experts
recommend reserving third-trimester maternal treat-

Table 4. Results of Base-Case Assumptions

Cases of Chronic Hepatitis B Cost Savings per Life-Years Saved per
Viral Load (Copies/mL) Prevented per 100 Patients Treated Patient Treated Patient Treated

Lamivudine
Overall 9.7 $5,184 1.3
HBV DNA less than 108 2.0 ⫺$390* 0.3
HBV DNA 108–109 8.7 $4,419 1.1
HBV DNA 109–1010 26.6 $17,410 3.5
HBV DNA 1010–1011 33.1 $22,085 4.3
HBV DNA more than 1011 38.8 $26,220 5.0
HBIG
Overall 9.5 $5,887 1.2
HBV DNA less than 108 2.0 $475 0.3
HBV DNA 108–109 8.4 $5,145 1.1
HBV DNA 109–1010 25.9 $17,760 3.4
HBV DNA 1010–1011 32.1 $22,299 4.2
HBV DNA more than 1011 37.7 $26,314 4.9
HBV, hepatitis B virus; HBIG, hepatitis B immune globulin.
* Additional cost.

658 Unal et al Preventing Perinatal HBV Transmission OBSTETRICS & GYNECOLOGY

Table 5. Results of Sensitivity Analysis
Cases of
Lifetime Chronic
Cost of Hepatitis B Cost
Chronic Prevented Savings
Hepatitis per 100 per
B per Women Woman
Model Assumption Range of Assumptions Patient Treated Treated

Lamivudine
Base estimates $72,384 9.7 $5,184
Altering chronic hepatitis B health states All lowest estimates $72,045 9.7 $5,150
across the ranges given in Table 3 All highest estimates $74,600 9.7 $5,400
Altering chronic hepatitis B health states Lowest cost equals life expectancy of $64,295 9.7 $4,395
across the ranges given in Table 3, as 50 y for chronic hepatitis B
well as varying life expectancy of cirrhosis, highest estimate for
patients with chronic hepatitis B proportion of chronic hepatitis B
cirrhosis from 50–64.9 y having compensated cirrhosis,
lowest estimate for proportion of
decompensated cirrhosis and
hepatocellular carcinoma
Highest cost equals life expectancy of $74,600 9.7 $5,400
64.9 y for chronic hepatitis B
cirrhosis, highest estimates for all
chronic hepatitis B health states
Altering degree of reduction in perinatal 6% reduction 0.8 ⫺$1,260*
transmission with maternal treatment 94% reduction 13.3 $7,741
across range given in Table 1
Altering the proportion of women 10% 9.7 $3,078
warranting treatment after third- 100% 9.7 $5,184
trimester viral load determination
Altering the proportion of women Lowest benefit equals 6% reduction 0.8 ⫺$3,366*
warranting treatment after third- and 10% warrant treatment
trimester viral load determination, as Highest benefit equals 94% reduction 13.3 $7,741
well as varying benefit from treatment and 100% warrant treatment
HBIG
Base estimates $72,384 9.5 $5,887
Altering chronic hepatitis B health states All lowest estimates $72,045 9.5 $5,855
across the ranges given in Table 3 All highest estimates $74,600 9.5 $6,097
Altering chronic hepatitis B health states Lowest cost equals life expectancy of $64,295 9.5 $5,122
across the ranges given in Table 3, as 50 years for chronic hepatitis B
well as varying life expectancy of cirrhosis, highest estimate for
patients with chronic hepatitis B proportion of chronic hepatitis B
cirrhosis from 50–64.9 years having compensated cirrhosis,
lowest estimate for proportion of
decompensated cirrhosis and
hepatocellular carcinoma
Highest cost equals life expectancy of $74,600 9.5 $6,097
64.9 y for chronic hepatitis B
cirrhosis, highest estimates for all
chronic hepatitis B health states
Altering benefit from treatment across the 16% reduction 2.3 $671
ranges given in Table 1 94% reduction 13.3 $8,649
Altering the proportion of women 10% 9.5 $3,781
warranting treatment after third- 100% 9.5 $5,887
trimester viral load determination
Altering the proportion of women Lowest benefit equals 16% reduction 2.3 ⫺$1,435*
warranting treatment after third- and 10% warrant treatment
trimester viral load determination, as Highest benefit equals 94% reduction 13.3 $8,649
well as varying benefit from treatment and 100% warrant treatment
* Additional cost.

VOL. 118, NO. 3, SEPTEMBER 2011 Unal et al Preventing Perinatal HBV Transmission 659
ment for women at highest risk of perinatal transmis-
sion from high viral activity, all women would need to
have a viral load drawn to determine need for treat-
ment. The proportion of women with viral loads high
enough to warrant treatment would vary by popula-
tion. Even if only 10% of women qualified for third-
trimester maternal treatment based on high viral
loads, one-way sensitivity analysis demonstrates that
this strategy remains cost-saving for both lamivudine
and HBIG.
The parameter most sensitive to changes in base-
line estimates was the degree of reduction in perinatal
transmission with treatment. One-way sensitivity
analysis for lamivudine showed that for a baseline
transmission rate without treatment of 15.7%,18 if the
risk reduction with treatment is at least 18.5% (ie,
from 15.7% to 12.8%), this strategy remains cost-
saving. For HBIG, using the baseline transmission
rate without treatment of 15.7%, treatment remains
cost-saving if the reduction in perinatal transmission is
at least 9.6% (ie, from 15.7% to 14.2%). When two-
way sensitivity analysis was performed, as long as the
degree of risk reduction was at least 39.5% for lami-
vudine and at least 30.6% for HBIG, treatment re-
mained cost-saving even if only 10% of women tested
with a third-trimester viral load warrant treatment.
When combination therapy of HBIG and lami-
vudine was evaluated using baseline estimates, this
strategy remained cost-saving even if the degree of
reduction was only 1% more than with either lamivu-
dine or HBIG alone. Assuming a baseline transmis-
sion rate without treatment of 15.7%, and a reduction
in transmission of 70% (compared with 69% for
lamivudine), the cost savings are $2,278 per patient
treated. If only 10% of patients in whom a viral load
is drawn warrant treatment, using lamivudine and
HBIG in combination remains cost-saving with $1,225
saved per patient treated.
DISCUSSION
Despite evidence of benefit, use of lamivudine or
HBIG to reduce perinatal transmission of hepatitis B
virus is not common practice in the United States.
Our analysis demonstrates that adoption of maternal
third-trimester treatment with either agent in women
with high viral loads would be not only cost-effective,
but also cost-saving.
Perinatal transmission of hepatitis B is uncom-
mon in women with low viral loads, with some series
even reporting no cases of transmission in women
with viral loads less than 105 copies/mL.12,16 However,
the literature is consistent in revealing a dramatic rise
in perinatal transmission, despite appropriate neona-
660 Unal et al Preventing Perinatal HBV Transmission
tal prophylaxis, beginning at maternal viral loads
around 106–108 copies/mL.12,13,16 The transmission
rates range from 5% to 13% between 106 and 107
copies/mL, and rise to the 40 –50% range in women
with viral loads of 108 copies/mL or higher.12,13
Our model does have limitations. The model
assumes no significant maternal or fetal risk from
lamivudine or HBIG. Based on currently available
data, this is a reasonable assumption, but potential
concerns remain. Studies in both pregnant and non-
pregnant patients show that short courses of lamivu-
dine (12–16 weeks) are well tolerated and safe.18,37
Because a strategy of lamivudine to prevent perinatal
transmission would not be initiated until the third
trimester, birth defects should not be a concern,
although data regarding teratogenesis are also reas-
suring.38 One serious theoretical concern regarding
use of lamivudine is development of resistance. Long-
term lamivudine use is associated with high rates of
resistance: 12.8% after 1 year and 76% with 5 or more
years of use.39,40 Resistance has not been reported to
be an issue after short-term use of lamivudine in
pregnancy for perinatal transmission prevention, but
it remains a theoretical concern.
Another potential concern is postpartum flare of
disease activity in hepatitis B virus–positive women
treated with lamivudine. In one Dutch study,41 against
a historical background flare rate of 10 –27% per year,
36% of women not treated with lamivudine experi-
enced a flare (3-fold increase in alanine aminotrans-
ferase) in the 6 months after delivery. Among women
treated with lamivudine, this incidence was 62%. This
study was retrospective, and the women in the lami-
vudine group were at greater risk of postpartum flares
by virtue of higher disease activity. Nonetheless,
withdrawal flares are known to occur in 17–25% of
nonpregnant individuals after cessation of lamivu-
dine therapy,42,43 and this risk will likely need to be
evaluated in a prospective fashion in women treated
to prevent perinatal transmission. The women in the
study described above41 stopped lamivudine imme-
diately after delivery, and the now more common
regimen of continuing therapy until 4 weeks post-
partum may provide some protection from post-
treatment flare.
With regard to HBIG, its safety profile is also
good. There has been no reported increase in hepa-
titis B virus mutation among infected newborns of
mothers treated with HBIG.19 However, because
HBIG is made from human plasma, there is a small
theoretical risk of infectious disease transmission, and
anaphylactic reactions are also theoretically possible.
OBSTETRICS & GYNECOLOGY
Significant adverse effects have not been reported in
studies administering HBIG to pregnant women.19
An additional limitation of our model is that the
lifelong history of congenitally acquired chronic hep-
atitis B is not clearly defined in the literature. We
therefore used studies of chronic hepatitis B in general
to derive our assumptions for prognosis and life
expectancy. Because it is believed that perinatal trans-
mission may lead to earlier onset of severe hepatic
sequelae, our use of the general literature on chronic
hepatitis B would, if anything, lead to more conser-
vative conclusions. Likewise, we also made the con-
servative assumption that congenitally infected chil-
dren would not have serious sequelae, and thus not
accrue cost, until age 20. In fact, children with chronic
hepatitis B do require periodic monitoring of their
disease,44 and there can be rare serious sequelae
during childhood.35,36 The costs of this surveillance
were not included in our analysis. Again, the omission
of these costs from our model would only underesti-
mate cost savings from prevention of perinatal hepa-
titis B virus transmission.
Although our results are subject to the above
limitations as well as the inherent limitations of cost-
effectiveness analyses, our analysis demonstrates im-
pressive cost savings across a wide range of assump-
tions. Based on our findings and the current literature
demonstrating a consistent rise in perinatal transmis-
sion beginning at maternal viral loads around 106
copies/mL despite appropriate neonatal immunopro-
phylaxis,12,13,16 we recommend screening women pos-
itive for hepatitis B surface antigen at 24 –28 weeks of
gestation and initiating prophylaxis with either lami-
vudine or HBIG if the viral load is at least 106
copies/mL. Maternal prophylaxis to prevent perinatal
hepatitis B virus transmission is both medically ben-
eficial and cost-saving, and this strategy should be
strongly considered in the United States.
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