Cost and Effectiveness of Intrapartum

Group B Streptococcus Polymerase

Chain Reaction Screening for Term

Deliveries
Najoua El Helali, PharmD, Yves Giovangrandi, MD, Kathleen Guyot, PharmD, Karine Chevet,
PharmD, Laurent Gutmann, MD, and Isabelle Durand-Zaleski, MD
OBJECTIVE: To estimate the cost and consequences of intrapartum polymerase chain reaction (PCR)
screening on early-onset group B streptococcal (GBS) disease com- pared with the antenatal lower vagina
culture screening recommended in France. METHODS: This was a single-institution study compar- ing the
intrapartum PCR screening strategy implemented in 2010 with antenatal culture strategy in place in 2009.
Early-onset GBS disease in newborns was monitored exhaustively. We estimated direct costs, including
screening test costs and hospital costs, for deliveries of healthy newborns compared with those infected
with GBS. Costs in 2009 and 2010 were compared on an intention-to-treat basis. RESULTS: Term deliveries
were 2,761 and 2,814 in 2009 and 2010, respectively. Among the screened mothers, the vaginal GBS
colonization rate was 11.7% based on ante- natal GBS culture screening in 2009 compared with 16.7% in 2010
using the intrapartum PCR testing. The overall probabilities of neonatal GBS disease were 0.9% com- pared
with 0.5%, and the average total cost per delivery was $1,759 1,209 in 2009 compared with $1,754 842 in 2010
(P .9) in antenatal and intrapartum screening strat- egies, respectively. The number and severity of cases of
early-onset GBS disease and the resulting hospital costs were higher in 2009. CONCLUSION: Polymerase
chain reaction intrapartum screening strategy was cost-neutral when compared with
the 2009 antenatal lower vagina culture screening, with a significant decrease in early-onset GBS disease.
(Obstet Gynecol 2012;119:822–9) DOI: 10.1097/AOG.0b013e31824b1461

E arly-onset
newborns is
group
acquired
B streptococcal
from the colonized
(GBS) disease
maternal
in

birth canal during labor or after membrane rupture. Clinical trials showed that intrapartum antibiotic pro- phylaxis
administered to GBS–colonized mothers was highly effective in preventing early-onset GBS disease in newborns.1
Since then, the main challenge has been to identify which women should receive intrapartum antibiotic phophylaxis.
Until recently, a rapid, sensitive, and specific GBS detection test was not available and intrapartum screening was
not feasible. Therefore, since 2002, the Center of Dis- ease Control in the United States recommended a universal
vagina–rectum GBS screening at 35–37 weeks of gestation.2,3 In France, since 2001, a universal lower vagina culture
screening is recom- mended at 35–38 weeks.4
In Paris-Saint Joseph hospital, monitoring for early-onset GBS disease of 8,048 live newborns be- tween April 2007
and December 2009 found that 65% of the newborns infected with GBS had mothers whose antenatal screening had
been negative. During From the Groupe Hospitalier Paris-Saint-Joseph, Service de Microbiologie and Service de Gynécologie-Obstétrique, the
AP-HP Groupe Hospitalier Henri Mondor Albert Chenevier, Service de Santé Publique, and the URC Eco Ile-de-France (AP-HP), Paris, France.
the same period, we conducted a prospective study comparing antenatal vagina culture screening with intrapartum
vagina screening using a rapid real-time
The authors thank Karen Brigham and Celine Quelen for the bootstrap analysis
polymerase chain reaction (PCR) GBS assay on the and Gilles Rejasse and Maryse Bobin for technical advice in collecting the data.
GeneXpert system. The study revealed that the posi- Corresponding author: Najoua El Helali, Clinical Microbiologist, Service de
tive predictive value of our antenatal vagina screening Microbiologie, Groupe Hospitalier Paris-Saint-Joseph, 185 rue Raymond
Losserand, 75674 Paris Cedex 14, France; e-mail: nelhelali@hpsj.fr.
© 2012 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.
for identifying colonization status at delivery was only 58.3%, whereas the negative predictive value was imperfect
(92.1%),5 leading to inappropriate intrapar- ISSN: 0029-7844/12
tum antibiotic prophylaxis. Because term deliveries
822 VOL. 119, NO. 4, APRIL 2012 OBSTETRICS & GYNECOLOGY
early-onset account for nearly 75% of early-onset GBS disease
GBS disease and the medical records of cases,6 these results led us to perform around-the-
the mothers were reviewed. clock GBS intrapartum PCR screening for all term
Diagnosis of early-onset GBS disease was based deliveries since January 2010.
on criteria of the French Health Authority. 7 Proven Our next objective was to estimate the effective-
early-onset GBS disease was defined by positive ness and costs of systematic intrapartum vagina PCR
results of blood or cerebrospinal fluid in the presence screening for term deliveries by comparing the 2010
of clinical signs, biological abnormalities, or both strategy with the 2009 antenatal vagina screening.
clinical signs and biological abnormalities consistent
MATERIALS AND METHODS
with sepsis. Probable early-onset GBS disease was defined by positive results of GBS culture of gastric The
effectiveness of early-onset GBS disease–preven-
fluid aspiration, deep ear specimen, or both, in the tion strategies (antenatal and intrapartum screenings)
presence of clinical signs, biological abnormalities, or in term deliveries and the costs related to the diagno-
clinical signs and biological abnormalities consistent sis and treatment of newborns were compared in a
with sepsis in which the blood, cerebrospinal fluid, or before-and-after study. This study was conducted in a
blood and cerebrospinal fluid cultures were negative. single institution without a control group. The ap-
Data collection of the characteristics of the moth- proval of Paris-Saint Joseph Institutional Review
ers was performed using the database of the maternity Board was not required because of the routine use of
ward, which included the following information: ges- intrapartum PCR screening.
tational age at delivery, parity, duration of labor, In the 2009 antenatal vagina culture screening
duration of membrane rupture before delivery, intra- strategy, intrapartum antibiotic prophylaxis was ad-
partum fever, antibiotic prophylaxis or antibiotic ther- ministered if the antenatal screening was positive or in
apy, number of doses of penicillin G, and previous case of bacteriuria during the current pregnancy or a
child with early-onset GBS disease. Group B strepto- previous child with early-onset GBS disease. If GBS
coccus screening results and incidence of bacteriuria status is unknown at the time of delivery, a risk-factor
during the current pregnancy were collected from assessment (eg, membrane rupture more than 12
laboratory software. hours, intrapartum fever higher than 38°C) is used to
We estimated the cumulative costs for the mother determine whether intrapartum antibiotic prophy-
and the newborn during the index admission from the laxis should be administered.4
perspective of a third-party payer. We did not include In the 2010 intrapartum vagina PCR screening
the costs of informal care supplied by family members strategy, intrapartum antibiotic prophylaxis is admin-
or time lost from work or usual activities associated istered to women who screened positive, to those
with early-onset GBS disease. All costs were adjusted presenting obstetrical risk factors when their vaginal
to 2011 dollars. We estimated costs of inpatient care samples did not give a PCR result (eg, PCR invalid or
based on reimbursement rates of the diagnosis-related error), and to mothers with a history of neonatal GBS
group (DRG). In France, as in other countries, this infection. Intrapartum antibiotic prophylaxis is not
 DRG price is calculated by multiplying standard indicated in the following cases: negative intrapartum
amounts for operating and capital expenses found in screening result, absence of obstetrical risk factors
yearly surveys by a national “weight” associated with when the sample did not give a PCR result, and
the DRG for each hospitalization.8 Additional pay- positive screening in a previous pregnancy.
ments to public hospitals cover medical education or For both strategies, penicillin G (5 million inter-
service to lower-income populations. Direct costs national units followed by 2.5 million international
included screening test costs, costs for well newborn units every 4 hours until delivery) was used for
care, and hospital expenditures associated with treat- intrapartum antibiotic prophylaxis. In case of high
ing neonates with early-onset GBS disease. We ex- anaphylaxis risk, in 2009, clindamycin was used if
cluded the costs of treatment for the maternal out- GBS was susceptible and vancomycine if not; in 2010,
comes of postpartum bacteremia and endometritis vancomycine was the only possible alternative.
and focused on newborn-related costs. We obtained In 2009 and 2010, all term deliveries and early-
the DRG for each hospitalization from our institu- onset GBS disease in newborns were monitored.
tion’s database and used the national standard euro Exclusion criteria were preterm delivery before 37
amount. weeks of gestation. We used data from the medical
The cost of antenatal culture screening was com- information department and the microbiology labo-
puted from the following resource utilization: Colum- ratory. All medical records of the newborns with
bia nalidixic acid, colimycin sheep blood agar and
VOL. 119, NO. 4, APRIL 2012 El Helali et al GBS Intrapartum PCR Screening 823
commercial latex agglutination tests (bioMerieux) to identify G
ß-hemolytic and suspected nonhemo- lytic colonies and the able b 1. Unit Costs of Hospital Resources
Mueller Hinton agar and antibiotics discs used for susceptibility t
Personnel costs included the time required for each step: 5 minuteariable Cost per Unit
agar plating and looking for suspected GBS colonies; 5 minutesysis was performed to estimate an incremental cost-effectiveness
identifying suspected colonies; and 7 minutes for susceptibility t and to assess the uncertainty on costs and effectiveness (newborn
9,10
The hourly rate of a senior technician in our laboratory was basections averted). Statistical analyses performed on Excel 2007 or
a gross salary of $63,291 per 1,820 hours per year. statistical software for the bootstrap analysis.
Costs of intrapartum PCR screening included the acquisition co
SULTS During the study period, out of 2,961 and 3,017
the Xpert GBS test cartridge (which incorporates sample proces
control and internal control), costs of GBS culture and identifica veries in 2009 and 2010, respectively, 2,761 and 2,814 were term
for samples with either positive results or without PCR resultveries corresponding to 2,824 and 2,842 live births. Vaginal
invalid or error). Time required for each step was 5 minutes forveries
P represented 82.5% of all term deliveries. The characteristics
sample processing and communicating the result to midwives anomen with term deliveries presented in Table 2 did not show
minutes for culture and identification of suspected colonies.erences in the population in terms of gestational age at delivery,
GeneXpert machine capital cost was allocated per test, assumiy, time from rupture of membranes to delivery, and presence of
6-year depreciation and 10% salvage value based on approxima etrical risk factors at delivery. The GBS colonization rate found
3,000 deliver- ies per year. Table 1 summarizes the unit costs. Eg intrapartum PCR screening was 16.7% ( 4% 95% confidence
were converted into U.S. dollars using the OECD purchasing po rval [CI]), whereas antena- tal GBS colonization rate based on
parity index ($1 U.S. 0.79 euros). The unit of analysis was the mo ures was 11.7% ( 3% 95% CI). Screening tests were performed in
(not the newborn, because in case of twin births we assumed of term deliveries in 2009 and in 85% in 2010. The number of
prevention strategy would benefit both twins). We compared 2009 men receiving intrapartum antibi- otic prophylaxis in term
2010 costs between patients with and without intrapartum screeveries was 311 (11% 3% 95% CI) in 2009 and 436 (16% 4% 95%
4
on an inten- tion-to-treat basis. We compared health care utiliza-n 2010 (P 10 ). Characteristics of GBS-infected newborns are
and costs using two-sided t tests for continuous variables and ented
X in Table 3.
Fisher exact tests for dichotomous and categorical variable Patients with severe symptoms had presented rapid
probabilistic sensitcal deterioration with respiratory distress or cardiovascular
ability leading to an intensive care survey in which the average
duration of antibiotic therapy was 10 days (except the meningitiy-onset GBS disease among the 30 remaining women without any
Mildly ill patients had mild respiratory distress with biologicetrical risk factors at delivery. Severe cases also occurred among
abnormalities consistent with sepsis; they were hospi- talized inmen
t who had negative screening results antepar- tum: two GBS
neonatal ward unit, where the average duration of antibiotic theraeremia, one GBS meningitis, and
was 7 days. ost of penicillin intrapartum antibiotic
The flow diagram in Figure 1 provides the results of t prophylaxis
antenatal screening strategy in 2009. Of the 101 women who did n
undergo antenatal screening, 40 were treated. Of these, 20 had GBreening per test costs
bacteriuria during the current pregnancy, eight had a previo PCR 48.7 GBS culture 4.76 In-hospital care costs by diagnosis-
newborn infected with GBS, and 12 had obstetrical risk factors The flow diagram in Figure 1 provides the results of the
delivery. Of the 61 women who did not receive intrapartum antibiotnatal screening strategy in 2009. Of the 101 women who did not
prophylaxis, 21 had GBS bac- teriuria and 10 had had a previoergo antenatal screening, 40 were treated. Of these, 20 had GBS
neonatal early- onset GBS disease, but no cases of early-onset GB eriuria during the current pregnancy, eight had a previous
disease occurred among them. We recorded two severe probabborn infected with GBS, and 12 had obstetrical risk factors at
early-onset GBS disease among the 30 remaining women without an very. Of the 61 women who did not receive intrapartum antibiotic
obstetrical risk factors at delivery. Severe cases also occurred amonhylaxis, 21 had GBS bac- teriuria and 10 had had a previous
women who had negative screening results antepar- tum: two GB natal early- onset GBS disease, but no cases of early-onset GBS
bacteremia, one GBS meningitis, and ase occurred among them. We recorded two severe probable
Well (non-infected) newborn
y-onset GBS disease among the 30 remaining women without any
(cesarean delivery)
etrical risk factors at delivery. Severe cases also occurred among
men who had negative screening results antepar- tum: two GBS
GBS meningitis 39,837 Severe early-onset GBS disease eremia, one GBS meningitis, and
12,049 Mildly ill early-onset GBS disease 2,120 The flow diagram in Figure 1 provides the results of the
natal
PCR, polymerase chain reaction; GBS, group B streptococcus. All costs ar
screening strategy in 2009. Of the 101 women who did not
from 2011 in U.S. dollars. ergo antenatal screening, 40 were treated. Of these, 20 had GBS
The flow diagram in Figure 1 provides the results of teriuria during the current pregnancy, eight had a previous
antenatal screening strategy in 2009. Of the 101 women who did nborn infected with GBS, and 12 had obstetrical risk factors at
undergo antenatal screening, 40 were treated. Of these, 20 had GB very. Of the 61 women who did not receive intrapartum antibiotic
bacteriuria during the current pregnancy, eight had a previohylaxis, 21 had GBS bac- teriuria and 10 had had a previous
newborn infected with GBS, and 12 had obstetrical risk factorsnatal early- onset GBS disease, but no cases of early-onset GBS
delivery. Of the 61 women who did not receive intrapartum antibiotase occurred among them. We recorded two severe probable
prophylaxis, 21 had GBS bac- teriuria and 10 had had a previoy-onset GBS disease among the 30 remaining women without any
neonatal early- onset GBS disease, but no cases of early-onset GB etrical risk factors at delivery. Severe cases also occurred among
disease occurred among them. We recorded two severe probab who had negative screening results antepar- tum: two GBS
men
early-onset GBS disease among the 30 remaining women without an eremia, one GBS meningitis, and
obstetrical risk factors at delivery. Severe cases also occurred amon related group (including delivery) Well
(non-infected) newborn (vaginal
women who had negative screening results antepar- tum: two GB
delivery)
bacteremia, one GBS meningitis, and
The flow diagram in Figure 1 provides the results of t
The flow diagram in Figure 1 provides the results of the
antenatal screening strategy in 2009. Of the 101 women who did n
natal screening strategy in 2009. Of the 101 women who did not
undergo antenatal screening, 40 were treated. Of these, 20 had GB
ergo antenatal screening, 40 were treated. Of these, 20 had GBS
bacteriuria during the current pregnancy, eight had a previo
eriuria during the current pregnancy, eight had a previous
newborn infected with GBS, and 12 had obstetrical risk factors
born infected with GBS, and 12 had obstetrical risk factors at
delivery. Of the 61 women who did not receive intrapartum antibiot
very. Of the 61 women who did not receive intrapartum antibiotic
prophylaxis, 21 had GBS bac- teriuria and 10 had had a previo
hylaxis, 21 had GBS bac- teriuria and 10 had had a previous
neonatal early- onset GBS disease, but no cases of early-onset GB
natal early- onset GBS disease, but no cases of early-onset GBS
disease occurred among them. We recorded two severe probab
disease occurred among them. We recorded two severe probabborn infected with GBS, and 12 had obstetrical risk factors at
early-onset GBS disease among the 30 remaining women without an very. Of the 61 women who did not receive intrapartum antibiotic
obstetrical risk factors at delivery. Severe cases also occurred amonhylaxis, 21 had GBS bac- teriuria and 10 had had a previous
women who had negative screening results antepar- tum: two GB natal early- onset GBS disease, but no cases of early-onset GBS
bacteremia, one GBS meningitis, and ase occurred among them. We recorded two severe probable
The flow diagram in Figure 1 provides the results of y-onset
t GBS disease among the 30 remaining women without any
antenatal screening strategy in 2009. Of the 101 women who did netrical risk factors at delivery. Severe cases also occurred among
undergo antenatal screening, 40 were treated. Of these, 20 had GB men who had negative screening results antepar- tum: two GBS
bacteriuria during the current pregnancy, eight had a previoeremia, one GBS meningitis, and

824 El Helali et al GBS Intrapartum PCR Screening OBSTETRICS & GYNECOLOGY

Table 2. Characteristics of Women in the Study Group, Including Group B Streptococcus Status
and
Intrapartum Antibiotic Prophylaxis
2009 2010 P
Full-term deliveries 2,761 2,814 Gestational age (wk) 40 (39.1–40.6) 40 (39.1–40.6) NS Parity1 1,420 (58) 1,473 (62) .004
2 723 (29) 604 (25) 3 or more 330 (13) 301 (13) Time from rupture of membranes to delivery (h) median (Q1–Q3) 4.46
(2.56–8.43) 4.06 (2.18–7.75) NS Membranes rupture more than 12 h before delivery 445 (16) 478 (17) NS Membranes
rupture more than 12 h before delivery or intrapartum
temperature higher than 38°C, or both
489 (18) 552 (19) NS
Duration of labor (h) median (Q1–Q3) 5 (3.5–6.16) 4.25 (3–6) NS Cesarean delivery 484 (17.5) 491 (17.4) NS 35–38 wk
vagina culture screening 2,372 Positive antenatal vagina culture screening n (%, 95% CI) 277 (11.6, 8.6–14.6) Women
without antenatal vagina culture screening n (%, 95% CI) 101 (4.1, 3.1–5.1)
Unknown GBS status at delivery 42 Bacteriuria 41 Previous child with early-onset GBS disease 18 Intrapartum vagina PCR
screening 2,378
Positive intrapartum vagina screening n (%, 95% CI) 397 (16.7, 11.7–20.7) Without PCR result (invalid or error) n (%, 95%
CI) 212 (8.9, 5.9–11.9) Antibiotic prophylaxis in term deliveries n (%, 95% CI) 311 (11, 8–14) 436 (16, 11–20) 10 4 Women
who had received two or more penicillin doses (%) 55 50 10 4
NS, not significant; Q, quartile; CI, confidence interval; GBS, group B streptococcus; PCR, polymerase chain reaction. Data are n,
median (25th–75th percentile), or n (%) of women unless otherwise specified.
two severe probable early-onset GBS disease. The 16
cases were found among mothers who had negative remaining cases of GBS infections among newborns
screening results, three of whom delivered more than in 2009 were mildly ill probable early-onset GBS
22 hours after screening and were administered anti- disease.
biotic therapy because of fever higher than 38°C and The flow diagram in Figure 2 provides the results
prolonged membrane rupture. All early-onset GBS of the intrapartum screening strategy in 2010. Poly-
disease in the intrapartum screening strategy were merase chain reaction test results were not available
mildly ill cases. for 212 (8.9%) women because of invalid PCR or
Probabilities of GBS infection presented in Table errors in PCR. Of these, although 46 had obstetrical
4 showed an overall probability of 0.9% and 0.5% for risk factors, only 41 were treated and no GBS infec-
antenatal screening and intrapartum screening strate- tion was recorded. Of the 171 women who did not
gies, respectively (P 10 4). The probability of new- receive intrapartum antibiotic prophylaxis, 166 did
born infection given negative GBS screening de- not present any obstetrical risk factor and two prob-
creased from 0.6% in 2009 to 0.17% in 2010 (P 10 4). able early-onset GBS disease cases occurred among
Prolonged hospital admissions for neonates asso- them. Only four probable early-onset GBS disease
ciated with early-onset GBS disease occurred in 23 in
Table 3. Characteristics of Group B Streptococcus–Infected Term Newborns in the Study Group
Variable 2009 (n 2,824) 2010 (n 2,842) P
Early-onset GBS disease in term newborns 23 (0.81, 0.48–1.14) 12 (0.42, 0.18–0.66) .034
Proven 3 (0.11, 0–0.23) 0 Probable 20 (0.71, 0.4–1.02) 12 (0.42, 0.18–0.66) Total hospital days 177 94 Average length of
stay of GBS-infected newborns (d) 7.69 (2.89–12.49) 7.83 (6.35–9.31) NS Median (IQR) 7 (6–7) 8 (6–8)
GBS, group B streptococcus; NS, not significant; IQR, interquartile range. Data are n (%, 95% CI) or n unless otherwise specified.
VOL. 119, NO. 4, APRIL 2012 El Helali et al GBS Intrapartum PCR Screening 825
Negative n=2,095
Did not receive IAP n=22
Early-onset GBS disease? Early-onset GBS disease? Early-onset GBS disease? Early-onset GBS disease? Early-onset GBS disease? Early-onset GBS disease?
Yes n=5
Received IAP, ATB, or both
† Did not receive IAP
n=40
n=61
‡
Received IAP, ATB, or both n=21

Fig. 1. Flow diagram providing the results of antenatal group B streptococcus (GBS) culture screening, the number of
women who received intrapartum antibiotic prophylaxis (IAP) or antibiotic therapy (ATB), and outcomes in newborns
in terms of early-onset GBS disease. *Of 101, 42 had not been screened, 41 had GBS bacteriuria, and 18 had a
previous child with early-onset GBS disease. †Twenty of 41 with bacteriuria and 8 of 18 with a previous early-onset
GBS disease were treated; 12 of 42 who had not been screened had presented risk factors and were treated.
‡
Twenty-one women with membrane rupture for more than 24 hours, fever, or membrane rupture for more than 24
hours and fever. El Helali. GBS Intrapartum PCR Screening. Obstet Gynecol 2012.
Received IAP n=370
Did not receive IAP n=2,074
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No n=250
n=1
n=21
n=0
n=40
n=2
n=59
n=1
n=20
n=14
n=2,060
2009 and in 12 in 2010, among the 2,824 and 2,842 live births, respectively. Of the 23 early-onset GBS disease
cases in 2009, one was GBS meningitis, six were severe neonatal GBS infections including two bacteremia cases,
and 16 were mildly ill cases. In 2010, all 12 neonatal GBS infections were mildly ill cases.
The corresponding total days of hospitalization for infected newborns was 177 days in 2009 com- pared with 94
days in 2010, or average day per newborn of 7.7 days in 2009 compared with 7.8 days
Women with term pregnancies included in intrapartum molecular screening strategy in 2010 N=2,378
Positive n=397
Negative n=1,769
Did not receive IAP n=27
Early-onset GBS disease? Early-onset GBS disease? Early-onset GBS disease? Early-onset GBS disease? Early-onset GBS disease? Early-onset GBS disease?
Yes n=4
Unknown GBS status n=212*
Received IAP, ATB, or both
Did not receive IAP

Received IAP, ATB, or both

†
Did not receive IAP n=41 n=171
‡
n=33
n=1,736
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No n=366
n=2
n=25
n=0
n=41
n=2
n=169
n=3
n=30
n=1
n=1,735
Fig. 2. Flow diagram providing the results of intrapartum group B Streptococcus (GBS) polymerase chain reaction
(PCR) screening, the number of women who received intrapartum antibiotic prophylaxis (IAP) or antibiotic therapy
(ATB), and outcomes in newborns in terms of early-onset GBS disease. *Two hundred twelve women without a PCR
result (eg, invalid or error). †Of 46 women with membrane rupture for more than 12 hours or fever or a previous child
with early-onset GBS disease, 41 were treated. ‡Thirty-three women with membrane rupture for more than 24 hours
or fever, or both. El Helali. GBS Intrapartum PCR Screening. Obstet Gynecol 2012.
826 El Helali et al GBS Intrapartum PCR Screening OBSTETRICS & GYNECOLOGY
Received IAP n=255
Women with term pregnancies included in antenatal culture screening strategy in 2009 N=2,473
Positive n=277
Unknown GBS status n=101*
in 2010. The total cost of delivery and treatment of infected newborns was reduced from $146,057 in 2009 to
$25,433 in 2010, reflecting the reduction both in caseload and severity.
When costs were estimated over the entire pop- ulation, the average total costs per delivery were identical for
patients in 2009 with antenatal vagina screening and in 2010 with intrapartum vagina screening ($1,759 compared
with $1,754). All results are presented in Table 5. The cost-effectiveness ratio
Table 4. Probabilities of Newborn Infection Given Group B Streptococcus Status and Intrapartum
Antibiotic Prophylaxis
Probability of Newborn Infection
2009 Antenatal Vagina Culture Screening
2010 Intrapartum Vagina
PCR Screening P
GBS-positive, received intrapartum antibiotic prophylaxis 2.10 3 (0–8.10 3) 2.10 3 (0–6.10 3) NS GBS-positive, did not receive
intrapartum antibiotic
prophylaxis
4.10 4 (0 3.10 3) 8.10 4 (0–4.10 3) NS
Unknown GBS status, did not receive intrapartum
antibiotic prophylaxis
8.10 4 (0–7.10 3) 8.10 4 (0–5.10 3) NS
GBS-negative, received intrapartum antibiotic
prophylaxis
4.10 4 (0–10 3) 10 3 (0–3.10 3) NS
GBS-negative, did not receive intrapartum antibiotic
prophylaxis
6.10 3 (3.10 3–9.10 3) 4.10 4 (0–10 3) .003
PCR, polymerase chain reaction; GBS, group B streptococcus; NS, not significant.
Table 5. Costs of Antenatal Vagina Culture Strategy and Intrapartum Vagina Polymerase Chain

Reaction Strategy
2009: Antenatal Vagina Culture Screening Strategy
2010: Intrapartum Vagina PCR Screening Strategy
 Total costs of screening 11,295 (2,372) 115,736 (n 2,378) Total costs of intrapartum antibiotic prophylaxis 621 (311) 867
(436) Total costs of treating GBS-infected newborns 146,057 (23) 25,433 (12) Total costs of deliveries for healthy newborns
4,698,626 (2,738) 4,793,720 (2,802) Average total cost per delivery (mean SD) 1,759 1,209 (P 0.9) 1,754 842
PCR, polymerase chain reaction; GBS, group B streptococcus. Data are cost in U.S. dollars (n) unless otherwise specified.
was estimated using a probabilistic sensitivity analysis with 2,000 bootstrap replications. The results are presented in
Figure 3. More than half of the replica- tions were in the bottom right quadrant, indicating that intrapartum screening
was a dominant (both cost-saving and infection reducing) strategy.
DISCUSSION This study demonstrated the feasibility of intrapartum PCR screening, which resulted in a
significant de- crease in probability of GBS infection in newborns with fewer severe cases and the same average
costs compared with the antenatal lower vagina culture screening strategy recommended in France.
The key element for success was that the proba- bility of newborn infection considering negative GBS screening
decreased dramatically from 0.6% to 0.17%. This may be attributable to false-negative results in the antenatal
culture screening, as described in previ- ous studies,5,11–14 which found that more than 60% of GBS-infected newborn
were born to mothers with negative antenatal screening results,6,15–17 even when the vagina–rectum swabbing was
used.
The effectiveness of any screening strategy de- pends on timely administration of antibiotic prophy- laxis. In our
population, 75% of the women delivered
VOL. 119, NO. 4, APRIL 2012 El Helali et al GBS Intrapartum PCR Screening 827
their newborns in more than 3 hours. When compar- ing the two approaches, 50% in 2010 and 55% in 2009 of
women who received prophylaxis were treated with at least two penicillin doses. Although duration of 4 hours of
intrapartum antibiotic prophylaxis be- fore delivery was considered the optimal time to interrupt GBS transmission,
several studies showed that a duration of 2 hours or less is still effective.18,19 Our survey showed a significant
increase in the number of women receiving intrapartum antibiotic prophylaxis with the intrapartum PCR screening
ap- proach. Even though the wider use of prophylaxis could raise concerns about the potential increase in antibiotic
resistance among Gram-negative organisms, it was shown that ampicillin-resistant Escherichia coli infec- tions
increased in preterm newborns and not in term newborns, possibly as a result of prolonged maternal ampicillin
treatment before delivery.20 In our maternity department, a continued survey did not show any increase in
Gram-negative-resistant neonatal sepsis.
Probable early-onset GBS diseases were taken into account in our analysis because, in the era of intrapartum
antibiotic prophylaxis, a portion of new- borns have probable GBS sepsis diagnosed, possibly as a result of
intrapartum antibiotic prophylaxis treat- ment that inhibits growth in blood and cerebrospinal
) $(s tsoce garevan ere can be false-negative blood cultures related to the small volume
40
ie cnereffi
D200 –20
blood inoculated. Thus, the real burden of disease is under-
timated if only proven early-onset GBS diseases are evaluated, as
–40–0.15 –0.10 –0.05 –0.00 0.05 0.10 0.015 ggested by some studies22,23; in our study, four severe GBS
Difference in infections prevented (per 1,000) fections were recorded among probable early-onset GBS disease
ses.
Fig. 3. Sensitivity analysis showing the incremental cost- effectiven
ratio as a difference in cost per additional infection prevented. The Early-onset GBS disease cases in 2009 were found to be
bootstrap analysis shows that the strategy of intrapartum moleculaore severe (7 out of 23, including 1 meningitis and 2 bacteremia
screening is either cost- saving (reduction in total hospital costs anses), whereas only mildly ill cases and no proven infections were
reduction in infections) or cost-effective (increased costs and - corded in 2010. As a result, the overall hospital care cost of
decreased infections). The difference in average costs does not rly-onset GBS disease was nearly six times higher in 2009 than in
exceed $20 per patient for an average 0.05 infections averted per 10. When the costs of screening and antibiotic prophylaxis were
1,000 newborns. El Helali. GBS Intrapartum PCR Screening. Obstet Gyncluded, we found that intrapartum PCR was cost-neutral compared
2012.
th antenatal vagina culture screening. The probabilistic sensitivity
alysis showed a high probabil- ity that intrapartum screening was
fluid but does not alleviate clinical symptoms or death.21 Furthermst-saving.
 Our results do not entirely match results from prev of early-onset GBS disease and its associated long-term medical
analyses based on decision models. Daniels et al24 showed costs.
antenatal culture strategy was cost-effective but not cost-neu Group B streptococcus intrapartum PCR screen- ing
compared with in- trapartum PCR screening. In their analysis, theg the GeneXpert system has been imple- mented successfully
costs of delivery were close to our figures, but the diagnostic accue March 2011 at the point of care around the clock in the delivery
of the PCR test differed dramat- ically. The sensitivity and specif m. A key success factor was the empowerment of the midwives in
of the Xpert GBS management of PCR processing without losing time either in
test in our previous study were found to be 98.5% and 99.6% ging the sample to the laboratory or in waiting for the
whereas in the analysis by Daniels et al the sensitivity and specificimunication of the screening result.
of the Smart GBS test (Smartcycler system) on vaginal samples we
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