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10.1576/toag.7.1.034.

27040

REVIEW
The Obstetrician
& Gynaecologist
2005;7:3439

Keywords
group B
streptococcus,
intrapartum
antibiotic
prophylaxis,
neonatal sepsis

Author details

www.rcog.org.uk/togonline

Group B streptococcal
disease: screening and
treatment in pregnancy
Bassel Abd El Malek, Nicholas D Embleton,
Andrew D Loughney
Intermittent, asymptomatic colonisation of the vagina and rectum with
group B streptococci is common in pregnancy. Vertical transmission of
the bacterium from mother to fetus may lead to neonatal sepsis,
characterised by pneumonia, meningitis and death in the most severely
affected babies. Intrapartum prophylaxis with penicillin reduces the
burden of disease when given to women with risk factors for the
development of group B streptococcal sepsis such as preterm labour,
prolonged rupture of the membranes or maternal pyrexia in labour.
Some professionals advocate the universal screening of all pregnant
women for group B streptococci near term and the administration of
intrapartum antibiotic prophylaxis to all women testing swab-positive.
This article summarises the salient features of group B streptococcal
disease and explores the rationale behind the use of intrapartum
antibiotics for the prevention of neonatal infection.
Introduction
Maternal colonisation

Specialist
Registrar in Obstetrics and
Gynaecology, Royal Victoria
Infirmary, Newcastle upon Tyne, UK.

Bassel Abd El Malek MRCOG,

Nicholas D Embleton MD MRCPCH,


Consultant in Neonatal Medicine,
Royal Victoria Infirmary, Newcastle
upon Tyne, UK.

Group B streptococci (GBS) are facultatively


anaerobic, Gram-positive bacteria. They colonise
the rectum or vagina in approximately 28% of the
pregnant population,1 although their presence in
the genital tract tends to be transient or
intermittent rather than chronic.2 Carriage rates
vary between different countries and ethnic
groups, with rates as high as 41% being reported in
African American populations1,3 but rates as low as
12% being reported on the Indian subcontinent.4
For most women, GBS colonises the lower vagina
or rectum as an asymptomatic commensal
organism. Occasionally, however, clinical evidence
of maternal infection with GBS arises in the form
of urinary tract infection,5 chorioamnionitis6,7 or
postpartum endometritis.7 Maternal symptoms
tend to be mild, although systemic sepsis and
meningitis have been described.

the bacterium ascends or as the fetus descends


through the genital tract. This process is
facilitated by the ability of GBS to adhere to
chorionic membranes,6 although infection is
more likely following prolonged membrane
rupture. Congenital pneumonia resulting in fetal
demise before or during labour is well
documented.8 More commonly, however,
clinical evidence of sepsis does not become
apparent until birth. Early-onset group B
streptococcal sepsis (EOGBSS) is defined as
presentation within the first 72 hours of life, the
majority of babies developing signs of infection
within a few hours of birth. Most babies with
EOGBSS present with nonspecific signs of
systemic infection including poor feeding,
lethargy and temperature instability. Pneumonic
and meningitic presentations are also common,
while rarer complications such as osteomyelitis
and septic arthritis are occasionally encountered.
All babies developing EOGBSS are at risk of
death or long-term neurodevelopmental
impairment and this is especially so for those
who develop meningitis (Figure 1).

Andrew D Loughney PhD MRCOG,

Consultant Obstetrician, The Royal


Victoria Infirmary, University of
Newcastle upon Tyne, Richardson
Road, Newcastle upon Tyne NE1
4LP, UK.
email: andrew.loughney@nuth.
northy.nhs.uk
(corresponding author)

34

Clinical features of perinatal


infection
When GBS colonisation occurs during
pregnancy, the fetus may be exposed in utero as

GBS sepsis has been recognised as an important


cause of neonatal morbidity for over 30 years and
is now known to be the most common serious
neonatal infection in the developed world. The
current UK prevalence of EOGBSS confirmed by

2005 Royal College of Obstetricians and Gynaecologists

bacteriological culture is approximately 0.58 cases


per 1000 live births,9 although some authors
believe the true prevalence to be significantly
higher at around 3.6 per cases 1000 live births.10
Case fatality rates have improved in recent years,
with advances in neonatal care, but still stand at
between 4% and 10%, with higher rates
recognised for babies born prematurely.8 Seminal
studies in the USA in the mid-1980s were able to
show that the number of babies developing
EOGBSS could be reduced dramatically by
administering intrapartum antibiotic prophylaxis
to women, thereby decreasing bacterial
transmission to the fetus rather than treating fetal
infection itself.There are essentially two strategies
for the prevention of EOGBSS that have been
developed around this idea. In the risk-based
approach, intrapartum antibiotic prophylaxis is
given to any woman whose clinical history
suggests that her baby is at high risk of developing
EOGBSS, such as a woman with prolonged
membrane rupture. In the universal prenatal
screening approach, intrapartum antibiotic
prophylaxis is given to all women known to be
colonised with GBS, even in the absence of
clinically based risk factors.

The risk-based strategy


Risk factors for EOGBSS are well established and
have been confirmed in casecontrol studies
(Table 1).8 In addition, babies born to women
with a previously affected child are also at an
increased risk.11 The risk-based strategy requires
women with any one of these risk factors to be

given intrapartum antibiotic prophylaxis. The


strategy also allows for women with a positive
urine culture and women with a fortuitous finding
of GBS on any vaginal or cervical swab taken
during the index pregnancy to be treated. If these
criteria were strictly applied to the UK
population, at least 16% of women8,12 would
receive antibiotics in labour. It is estimated that
approximately 625 women with one or more of
these risk factors would need to be treated to
prevent one case of EOGBSS, and one neonatal
death would be prevented for every 5882 women
treated.13

REVIEW
The Obstetrician
& Gynaecologist
2005;7:3439

Although the number of women requiring


treatment in this scheme appears high, in 1996
the US Centers for Disease Control and
Prevention (CDC) published guidelines
accepting the risk-based approach as a viable
alternative for the prevention of EOGBSS.14 The
principle that a calculation of risk should be used
to inform maternal choice was later endorsed by
the Public Health Laboratory Service (PHLS)
GBS Working Group in the UK15 and forms the
basis of advice given in the present RCOG
Guideline.12 Subsequent experience in the USA
confirmed that, when rigorously applied,
intrapartum antibiotic prophylaxis given to
women with risk factors for EOGBSS could
deliver a clear reduction in neonatal morbidity
and mortality.16,17 Reflecting this, implementation of the risk-based treatment strategy
measurably reduced high-dependency neonatal
special care cot occupancy in US states
implementing the strategy. Given the high cost

Figure 1. Outcome
following maternal group
B streptococcal
colonisation

35
2004 Royal College of Obstetricians and Gynaecologists

REVIEW
The Obstetrician
& Gynaecologist
2005;7:3439

of neonatal intensive care and supportive


treatments such as extracorporeal membrane
oxygen, a similar experience in the UK might
effectively make the exercise cost neutral to the
NHS.
While this approach has many advocates,
3040% of babies with EOGBSS are born to
women with no identifiable risk factors. Even
rigorous application of the risk-based strategy

Table 1. Risk factors for early onset group B streptococcal disease; from
Oddie and Embleton8
Factor
Preterm birth 37 weeks
Preterm birth 34 weeks
Rupture of the membranes
18 hours
Preterm prolonged rupture
of the membranes
Intrapartum fever 38C
Any antenatal maternal
culture of GBS
Previously affected child

Odds ratio

95% confidence
interval

10.4
33.6
25.8

3.927.6
4.0283.3
10.264.8

30.3

6.3144.5

10.0
17.7

2.440.8
1.9163.5

Presently
unquantified

cannot, therefore, reduce the incidence of


EOGBS by more than 6070%. Experience
from the USA suggests that this is true in
practice, leading the CDC to publish guidelines
backing the potentially more effective alternative
strategy of universal prenatal screening.17

Universal prenatal screening


The 2002 CDC guidelines recommended
bacteriological screening for all pregnant women
and the use of intrapartum antibiotic prophylaxis
for all screen-positive women, regardless of the
presence or absence of other risk factors for
EOGBSS. To achieve this, low vaginal and
endoanal swabs must be taken at 3537 weeks of
gestation. This relatively late gestation is
necessary because the positive and negative
predictive values of swabs taken more than 5
weeks before delivery are insufficiently high in
most populations to guide treatment.
Since the site of colonisation does not influence
the decision to use intrapartum antibiotic
prophylaxis, screening can be performed by
passing a swab into the lower part of the vagina
then passing the same swab into the anus before
placing it in culture medium. Separate swabs may
also be used, but both swabs should then be
placed into the same culture medium so that a
single bacteriological report is generated. Studies
have shown that, with appropriate instruction,
most pregnant women can take their own swabs,
improving the acceptability of the procedure
without affecting its sensitivity.18 A sample of

urine should also be analysed in the third


trimester, since GBS bacteriuria is associated with
exposure of the fetus to a high bacterial load.19
For screening to be effective, a method of
culture must be employed that is both sensitive
and specific. Standard bacteriological swabs
plated directly on to agar fail to detect GBS in
up to 50% of colonised women. In contrast, by
placing swabs directly into a selective enriched
broth,20 the assay sensitivity can be increased
dramatically.
Some babies exposed to GBS will develop earlyonset disease even after optimal antibiotic
prophylaxis, particularly when infection has
arisen in utero.21 Nevertheless, US states
employing the screening strategy have reported a
reduction in rates of EOGBSS of up to 86%, a
decline that is significantly better than that found
in states following the risk-based strategy.17
In the UK, implementation of a universal
prenatal screening policy would impact
significantly upon the provision of antenatal care.
The organisational challenge of obtaining and
processing swabs from a large number of women
and ensuring that results are available to care
providers during labour would be considerable.
The screening system would also have to comply
with the NICE guidelines on the provision of
routine antenatal care.22 Access to written
information and personal, professional advice
would be needed before swabs were obtained,
when results were available and prior to
instituting antibiotic prophylaxis. While these
requirements could be met in the course of
present antenatal care arrangements for most
women, some additional time allocation would
inevitably be required to fulfil the counselling
obligations attendant to the screening
programme.
Although the National Screening Committee in
the UK is currently considering adoption of the
universal screening approach, this is unlikely to be
their favoured option because it would almost
certainly lead to the treatment of more women
with intrapartum antibiotic prophylaxis than
would adoption of the risk-based approach, with
up to 30% being offered antibiotics in labour.23
The finding of a positive swab would also impact
upon the womans care in labour in a wider sense,
influencing the womans decision regarding place
of confinement and possibly colouring clinicians
views when choosing management options in
labour. Furthermore, the cost implications of
universal prenatal screening would be significant,
even though a reduction in usage of highdependency neonatal care might be expected to

36
2004 Royal College of Obstetricians and Gynaecologists

offset these costs to some degree. Perhaps, more


pertinently, the balance may lie between the
inconvenience to the mother and to the health
service of implementing a screening programme,
set against achieving the maximum possible
reduction in neonatal morbidity and mortality.

Combining universal prenatal


screening and the risk-based
strategy
The Canadian Task Force on Preventative Health
Care has shown that by adopting a universal
screening strategy but then only offering
intrapartum antibiotic prophylaxis to women
who test swab-positive and who have additional
risk factors for EOGBSS, the number of women
treated with penicillin in labour can be reduced
to as little as 3.4%.24 Although this approach is
likely to cause less morbidity in labouring
women by reducing antibiotic usage, it retains
the financial and organisational obstacles
inherent in implementing a universal antenatal
screening programme and has the potential to
reduce the incidence of EOGBSS by only a little
over 50%.25 Because of these limitations, the
approach is rarely encountered in UK or US
practice.

Chemoprophylaxis and therapy


Intrapartum antibiotic prophylaxis
Several studies have confirmed the efficacy of
intrapartum antibiotic prophylaxis for EOGBSS
prevention, with most concluding that the use
of antibiotics significantly reduces the rate of
neonatal colonisation and sepsis.16,25 To be
effective, it may be necessary for drug
administration to commence 4 or more hours
before delivery, since efficacy increases with
both the length of time the fetus has been
exposed to antibiotics in labour and the number
of doses administered. This 4-hour rule should
not be adhered to dogmatically, since clear
evidence defining the minimum necessary time
exposure to intrapartum antibiotic prophylaxis
to achieve neonatal benefit is lacking.16,26
To date, there has been no reported resistance of
GBS to either penicillin or ampicillin in vivo and
virtually no resistance in vitro. Since ampicillin
has a relatively broad spectrum of antimicrobial
activity, its widespread use has the potential to
select for resistant organisms. Because of this,
penicillin remains the drug of choice for
intrapartum antibiotic prophylaxis, given at an
intravenous dose of 3 g (5 MU) initially then 1.5 g
(2.5 MU) 4-hourly until delivery.

As much as 10% of the UK population claims to be


allergic to penicillin. Although true allergic
reactions probably occur in less than 1%,
anaphylaxis has been reported in women receiving
intrapartum antibiotic prophylaxis for GBS27 and
might be expected to arise in 1/100 000 women
treated.28 The RCOG estimates that, if a universal
screening policy were adopted leading to the
administration of intrapartum antibiotic
prophylaxis to 30% of parturients, two anaphylaxisrelated maternal deaths could be expected annually
in the UK.12 In the search for a suitable alternative
antibiotic, up to 25% of GBS isolates have been
found to be resistant to erythromycin, which also
fails to achieve bactericidal levels in the amniotic
fluid. Up to 15% are resistant to clindamycin, the
currently recommended second-line drug in the
UK.12 First-generation cephalosporins such as
cefazolin may be more effective and have the
advantage of achieving high intra-amniotic
concentrations while retaining a relatively narrow
spectrum of antimicrobial activity.

REVIEW
The Obstetrician
& Gynaecologist
2005;7:3439

In theory, the widespread use of intrapartum


antibiotic prophylaxis could lead to an increase in
the incidence of early-onset non-GBS sepsis in
neonates, negating any beneficial effect. Clinicians
might also expect to encounter an increase in the
prevalence of drug-resistant bacteria causing
disease. In reality, these phenomena have rarely
been observed and some centres following CDC
guidelines have actually recorded a fall in the
incidence of non-GBS sepsis.17 To preserve this
advantage, however, the use of antibiotics with a
broad spectrum of activity should be reserved for
women with true penicillin allergy and close
surveillance should be kept of the range of
bacteria causing neonatal disease.

Treating the neonate


Combining infant antimicrobial prophylaxis (100
mg/kg intravenous penicillin given daily in two
divided doses)15 with intrapartum antibiotic
prophylaxis reduces the rate of EOGBSS in both
term and preterm infants when compared with a
strategy of no intervention29 but such routine
neonatal prophylaxis has not gained wide support
and its benefits remain uncertain. At present, the
PHLS, RCOG and CDC recommend that, in
general, whether concern arises because of the
presence of maternal risk factors or maternal
swab results, babies who have received
intrapartum antibiotic prophylaxis before birth
require heightened observation alone for 1248
hours after delivery, with intravenous penicillin
reserved for babies developing signs of
disease.15,17 As exceptions to this rule, penicillin
should also be considered for babies who are
otherwise well but who have a combination of

2004 Royal College of Obstetricians and Gynaecologists

37

REVIEW
The Obstetrician
& Gynaecologist
2005;7:3439

risk factors such as maternal GBS bacteriuria in


the presence of prolonged membrane rupture.
Most paediatricians also treat babies born to
mothers with unequivocal features of
chorioamnionitis, babies with twin siblings
affected by EOGBSS and babies with siblings
who have had previously confirmed EOGBSS.

Obstetric issues
The risk of fetal infection in women with intact
membranes who are not in labour is low.
Because of this, antibiotic cover for GBS need
not be administered routinely to women
undergoing an elective caesarean section, even in
the presence of positive swabs. A dilemma may
arise when, for example, a woman who is swab
positive or has EOGBSS risk factors and who is
due to be delivered by caesarean section presents
with rupture of the membranes or in labour. In
these circumstances, GBS cover may be given,
accepting that delivery is likely to take place
below the theoretical 4-hour prophylaxis
threshold. Delaying delivery to achieve this
threshold would be illogical, since fetal bacterial
exposure increases with time.
Standard obstetric practice dictates that some
women with positive GBS swabs or risk factors for
neonatal sepsis will undergo one of a number of
common obstetric interventions during the course
of pregnancy and labour. For example, induction of
labour is as likely in this group of women as in the
general population.There is no present evidence to
suggest that antenatal vaginal examination,
membrane sweeping or insertion of prostaglandin
pessaries for labour induction increase the rate of
transmission of GBS from the mother to the fetus.
In labour, although neonatal infection rates increase
in association with the frequency of vaginal
examinations and the placement of fetal scalp
electrodes, cause and effect have not been proven in
these circumstances. Furthermore, there are few
data available specifically relating GBS sepsis to
these intrapartum procedures. There is, therefore,
no clear evidence to suggest that women whose
babies are at risk of EOGBSS should receive
anything other than normal obstetric or midwifery
care in labour in addition to antibiotic prophylaxis.

Issues relating to infants born


prematurely
Approximately 6% of women give birth after
spontaneous labour before 37 weeks of
gestation and, of these, one-third give birth
before 32 weeks.30 Premature babies are at
particularly high risk of developing EOGBSS
and they are also more likely to die or develop
long-term sequelae as a result. The CDC

recommends administration of intrapartum


antibiotic prophylaxis to all women who seem
likely to give birth because of preterm labour,
regardless of the presence of membrane
rupture, while the PHLS and the RCOG
concur that intrapartum antibiotic prophylaxis
should be considered in this group.12 When
tocolytics are used in an attempt to arrest
labour, low vaginal and rectal swabs should be
taken to determine the womans colonisation
status, although reliable results may not be
available in time to influence the use of
antibiotic prophylaxis.After delivery, continued
treatment with penicillin is essential for babies
showing signs of infection. In practice, signs of
infection are frequently non-specific and it is
also impossible readily to distinguish
surfactant-deficient lung disease from
congenital pneumonia, so it is common for
preterm babies to receive antibiotics
immediately after delivery.

Future perspectives
Rapid detection of GBS
Because of the transient or intermittent pattern
of maternal colonisation normally encountered,
an intrapartum assay for GBS could hold a
significant advantage over an earlier screening test
by more accurately reflecting the colonisation
status of a woman in labour. For this, an assay
would be required that could provide a result
rapidly, that was highly sensitive to the presence
of GBS and that was sufficiently specific to give a
low false-positive result rate. Such a test would
also allow the accurate assessment of women
presenting with threatened preterm labour and
preterm rupture of the membranes.
A number of GBS rapid detection kits are
commercially available but, for many, their
sensitivity is too low to allow effective
intervention based on their results.31,32 A new
polymerase chain reaction assay has been studied,
which is sensitive to the presence of GBS in 97%
of cases and claims 100% specificity.33
Furthermore, assay results are available within 45
minutes. The assay is not, however, currently
commercially available so a true analysis of benefit
remains to be determined.

Immunisation
Maternal immunisation against GBS prior to or
during pregnancy has the potential to prevent
fetal colonisation in utero, thereby eliminating
GBS-mediated stillbirth in addition to
EOGBSS. It could also impact significantly on
late-onset disease firstly by reducing vertical

38
2004 Royal College of Obstetricians and Gynaecologists

transmission of the bacterium and secondly by


providing the neonate with passive immunity
against infection acquired ex utero. At least eight
different GBS serotypes exist, based upon the
specific structure of the capsular polysaccharide
and embedded proteins. Although only three or
four serotypes are responsible for the majority of
disease, a vaccine would nevertheless have to be
multivalent to be effective. Current phase one
and two clinical trials have generally investigated
the use of monovalent vaccines, with limited
potential for widespread disease prevention.34

Conclusions
In order to meet the challenge of reducing
morbidity and mortality caused by group B
streptococcal disease after birth, the RCOG has
proposed that a woman should be offered

intrapartum antibiotic prophylaxis based upon


maternal risk factor assessment.12 This contrasts
with the current US CDC strategy based upon the
use of universal prenatal screening. It is likely that
the former policy will be cheaper to implement,
easier to administer and less likely to impact
adversely upon a womans care in labour, while the
latter would possibly deliver greater reductions in
neonatal disease. In the future, rapid assays for
maternal GBS colonisation may be available for
use in labour while vaccination against GBS
represents the greatest hope of reducing the
burden of neonatal and maternal disease. While
GBS remains the most prevalent organism causing
early-onset infections, it should be remembered
that more than 50% of early-onset infections are
caused by non-GBS organisms,35 so the
eradication of EOGBSS should not be seen as the
endpoint in combating neonatal sepsis.

REVIEW
The Obstetrician
& Gynaecologist
2005;7:3439

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