Pediatrics and Neonatology 62 (2021) 465e475

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Review Article

Updates in prevention policies of early-onset

group B streptococcal infection in newborns
Yao Zhu a,b, Xin-Zhu Lin a,b,*

a
Department of Neonatology, Women and Children’s Hospital, School of Medicine, Xiamen University,
Xiamen, Fujian Province, China
b
Xiamen Key Laboratory of Perinatal-neonatal Infection, Xiamen, Fujian Province, China

Received Nov 17, 2020; received in revised form Mar 20, 2021; accepted May 17, 2021
Available online 23 May 2021

Key Words Invasive disease owing to group B Streptococcus (GBS) is a major cause of illness and death
early-onset disease; among newborns. Maternal GBS colonization of gastrointestinal tract and/or vagina is the pri-
group B mary risk factor for neonatal GBS early-onset disease (EOD). In Europe and America, there are
Streptococcus; marked declines in neonatal GBS-EOD through widespread implementation of guidelines for
guideline; maternal GBS screening and subsequent intrapartum antibiotic prophylaxis (IAP). The key mea-
newborn; sures necessary for prevention of GBS-EOD include correct specimen collection and processing,
prevention nucleic acid amplification testing (NAAT) for GBS identification, regimens for mothers with pre-
mature rupture of membranes (PROM), preterm labor or penicillin allergy, and coordination
between obstetrics and pediatrics. Antibiotic prophylaxis has some disadvantages, so re-
searchers should develop other preventive measures. Maternal vaccines to prevent perinatal
GBS infection are currently under development. However, as large, population-based sampling
studies are rarely conducted, the colonization rate and the disease burden of GBS in perinatal
period are poorly understood in developing countries. The harm of GBS to newborns has been
recognized in recent years in mainland China, but authorized prevention measures are still
lacking. In order to enhance the understanding of GBS-EOD prevention, the most recent guide-
lines updates by the American College of Obstetricians and Gynecologists (ACOG) and Amer-
ican Academy of Pediatrics (AAP) in 2019e2020 are summarized in this article.
Copyright ª 2021, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/
by-nc-nd/4.0/).

* Corresponding author. Department of Neonatology, Women and Children’s Hospital, School of Medicine, Xiamen University, No.10
Zhenhai Road, Siming District, Xiamen, Fujian Province, China.
E-mail address: xinzhufj@163.com (X.-Z. Lin).

https://doi.org/10.1016/j.pedneo.2021.05.007
1875-9572/Copyright ª 2021, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-
NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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 Y. Zhu and X.-Z. Lin
1. Introduction
Group B Streptococcus (GBS; Streptococcus agalactiae) is a
leading cause of intraamniotic infection (IAI), neonatal
early-onset pneumonia, sepsis and meningitis. Western
countries have attached great importance to the preven-
tion and treatment of perinatal GBS disease since the 1970s
because of its great harm and high mortality. In 1996, the
Centers for Disease Control and Prevention (CDC), in
collaboration with the American College of Obstetricians
and Gynecologists (ACOG), first published guidelines for the
prevention of perinatal GBS infection.1,2 With advances in
clinical practice, guidelines were revised in 2002 and 2010,
respectively.3,4 In 2018, the management and responsibility
for updating the GBS prevention guidelines were trans-
ferred from the CDC to ACOG and the American Academy of
Pediatrics (AAP). From 2019 to 2020, maternal GBS pro-
phylaxis was revised in ACOG Committee Opinion No.782
and No.797,5,6 and management of infants at risk for GBS
disease was issued by AAP.7 Most European countries
adopted the screening and processing guidelines of the
United States.8 However, the prevention guidelines for
neonatal GBS-EOD in the United Kingdom (UK) in 2017 and
Queensland, Australia in 2020 have some different, impor-
tant advancements which are also summarized and dis-
cussed in this review.9,10
With continuous updating of prevention and treatment
measures, the overall incidence of neonatal GBS early-onset
disease (GBS-EOD) occurring 0e6 days after birth in the
United States declined from 1.8 cases per 1000 live births in
the 1990s to 0.23 cases per 1000 live births in 2015, with a
decrease rate of 80%.11 The universal GBS screening policy,
along with intrapartum antibiotic prophylaxis (IAP) strategy,
can significantly reduce the incidence and mortality of GBS-
EOD but this can not eliminate the disease.12 GBS late-onset
disease (GBS-LOD) among infants aged 7e89 days is not
prevented by IAP. The incidence of GBS-LOD remained sta-
ble overall (mean, 0.31 per 1000 live births) over the
2006e2015 Active Bacterial Core surveillance (ABCs) study
period in the United States, surpassing GBS-EOD as the most
common presentation of invasive GBS disease during in-
fancy.11 In addition to preterm birth, maternal rectovaginal
colonization, maternal age < 20 years, African American
race and contaminated human milk are variably associated
with GBS-LOD.7 In contrast to GBS-EOD infection, there are
currently no effective strategies to reduce the incidence of
GBS-LOD. Maternal vaccination might be effective at pre-
venting both EOD and LOD in a nonantibiotic way.13
Despite limited data on the burden of maternal and
neonatal GBS infection, particularly from developing coun-
tries, serial data show that mainland China has the high
colonization rate in pregnant women at 14.52%,14 the second
largest absolute number of GBS cases and deaths among in-
fants globally at 25,000 (uncertainty range 0e59,000) and a
case fatality rate (CFR) ranging from 6.45 to 7.1%.15 Due to the
occurrence of serious events and research results,16,17 more
attention has been paid to perinatal GBS infection in mainland
China. Some hospitals and regions have carried out a universal
maternal GBS screening, which has proven to be valuable for
the prevention of GBS-EOD. Nevertheless, there is still a lack
466
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of standardized guidelines for GBS-EOD prevention in main-
land China that might result in death and severe complications
of GBS infection in mothers and newborns.16,17 Here, we re-
view the epidemiology, screening approach and prevention
policies of perinatal GBS infection with reference to the latest
international GBS prevention strategies.
2. Epidemiology of perinatal GBS infection in
mainland China
Owing to differences of geographic location, detection
method and research sample size, the colonization rate of
GBS in pregnant women and the incidence of GBS-EOD
varies greatly in Asia, including mainland China. Within
these subregions, Myanmar (9%), India (10%), Korea (11.6%),
and Iran (13.65%) had lower prevalence of maternal GBS
colonization, with higher prevalence found in Bangladesh
(15%), Japan (16%), Pakistan (20%), Hong Kong (21.8%), and
Taiwan (23.7%).18e23 In mainland China, the maternal GBS
colonization varies in different regions: 3.7% in Shanghai,
7.1% in Beijing, 14.52% in Xiamen, Fujian Province, and
9.1e19.1% in Guangdong Province.24 The incidence rates
per 1000 live births of GBS-EOD were 0.2 in Thailand, 0.3 in
the Philippines, and 0.24 in Hong Kong, which were signif-
icantly higher than the rate reported in Japan (0.09).22,25,26
The overall incidence of invasive GBS disease among
infants < 3 months of age in China, according to a multi-
center study involving 16 provinces, was 0.31 (95% CI
0.27e0.36) cases/1000 live births.27 The incidence of GBS-
EOD was 0.18 (95% CI 0.15e0.22) cases/1000 live births and
GBS-LOD was 0.13 (95% CI 0.11e0.16) cases/1000 live
births.27 The authors estimated that there were 13,604
cases of GBS and 1142 GBS-associated deaths in infants < 3
months of age annually in China.27 The incidence rate
varied from 0.01 to 0.53 cases/1000 live births in different
regions of China.27 A GBS-EOD incidence rate of 1.48 per
1000 live births was reported in Xiamen, Fujian Province,
which was higher than other regions of China.28
On the basis of the composition of capsular poly-
saccharide (CPS), GBS isolates can be divided into ten CPS
serotypes (Ia, Ib, and II－IX). A meta-analysis on the sero-
type distribution of maternal GBS colonization showed that
serotype III, the most prevalent, accounted for 25% of se-
rotypes globally.18 The study on the serotype distribution of
GBS infection in pregnant women noted that serotype Ia
(31%) was predominant.29 A multicenter study from Shanghai
reported that serotypes III, V and Ia, accounting for 79.7%
totally, were the main types in pregnant women.30 In a
recent study in Beijing by Wang et al., serotype III accounted
for 32.1% of all GBS isolates from pregnant women, followed
by 17.9% of serotype Ia, and 16.1% of serotype Ib.31 In terms
of the serotype distribution in neonates with GBS invasive
disease, a retrospective study of 40 newborns diagnosing
invasive GBS infection in Shenzhen and Beijing described
that serotype III accounted for 85%, followed by Ia (7.5%), Ib
(5%), and V (2.5%), of which 60% of GBS-EOD was caused by
serotype III.32 From a Chinese multicenter study in 2019, the
top three serotypes of invasive GBS infection in infants were
as follows: III, 61.5%; Ib, 28.7%; and Ia, 5.7%.27 In the current
 Pediatrics and Neonatology 62 (2021) 465e475
study in Xiamen, serotype III (55.0%) was found to be the
most common of 298 GBS strains from pregnant women,
followed by Ib (16.4%), Ia (11.1%), V (9.4%), and II (5.0%); the
study also showed that III and Ia were the predominant se-
rotypes in 32 GBS strains from newborns with GBS-EOD, ac-
counting for 81.3% of all serotypes.33 In addition, their study
revealed that the vaginal colonization rate of serotype Ia
was lower, whereas the vertical transmission capability of
serotype Ia was stronger compared with serotype III, which
was more likely to result in neonatal GBS-EOD with an
adjusted standardized residual as 2.7 (>2).33
To date, there are more than 1000 GBS sequence type
(ST), and the most common genotypes are ST1, ST17, ST19
and ST23. Several previous Chinese epidemiological studies
reported that ST19 was the main genotype of GBS strain
colonized in pregnant women, and ST17 was the most
prevalent type of GBS strain leading to invasive neonatal GBS
infection.34e36 In Taiwan, Lee et al. found that ST1, ST12
and ST23 were related to GBS colonization in healthy preg-
nant women, while ST17, ST23 and ST12 were related to
neonatal invasive disease in the era of nationwide GBS
screening and IAP.37 A Chinese multicenter study identified
that the top three genotypes of invasive GBS infection in
infants were as follows: ST17, 36.5%; ST19, 13.9%; and ST10,
13.5%.27 A recent study from Xiamen assessed genotype
distributions of 266 GBS strains isolated from pregnant
women and identified a total of 42 STs, with ST19 being the
most prevalent (19.9%), followed by ST862 (9.4%), ST12
(7.9%), ST17 (7.5%), ST10 (7.1%), and ST23 (4.9%).34 The
same study also found 10 STs in 32 cases of GBS-EOD, with
ST17, ST23, and ST19 together accounting for 75.1% of the
total isolates. Moreover, a further analysis showed that the
adjusted standard residuals of ST17 and ST23 genotypes had
the largest absolute values (6.1 and 3.0, respectively),
indicating that both genotypes had a stronger pathogenicity
in vertical transmission and in causing neonatal GBS-EOD
than other STs in this study.34
3. Primary prevention policies of neonatal
GBS-EOD
Currently, strategies focus on the prevention of GBS trans-
mission during labor and delivery through the maternal
rectovaginal screening and use of antibiotics.5,6 In 1996, the
CDC issued guidelines recommending either an antenatal
culture-based or risk factor-based approach for the admin-
istration of IAP to prevent invasive neonatal GBS-EOD.1 By
2002, the superiority of a universal culture-based screening
method was recognized and endorsed for all pregnant
women.3 The key changes in the 2010 guidelines include the
following: adopting nucleic acid amplification testing
(NAAT) for the identification of GBS; updating prophylaxis
regimens for women with penicillin allergy; and a revised
algorithm for management of newborns with respect to risk
of GBS-EOD.4 The most recent guidelines for prevention
were updated in 2019e2020 and are reviewed below.
3.1. Timing and methods of maternal GBS screening
The guidelines for the prevention of GBS-EOD being
revised in 2020 in the United States still recommended
467
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the culture-based universal screening strategy, but the
screening time was changed to 36 0/7e37 6/7 weeks of
gestation by removing 35 0/7e35 6/7 weeks of gesta-
tion.5,6 The time adjustment of GBS screening is based on
two factors: 1) the use of antibiotic prophylaxis is rec-
ommended as a default for women with unknown GBS
status who give birth before 37 0/7 weeks of gestation;
and 2) this new screening timing provides a 5-week
window for valid culture results that include births that
occur up to the gestational age of at least 41 0/7
weeks.5,6 In the United States, 1.9% of women give birth
between 35 0/7 and 35 6/7 weeks of gestation versus
6.7% who give birth at 41 0/7 weeks of gestation or
more.38 Research proved that GBS cultures have a high
degree of accuracy in predicting GBS colonization status
at delivery if cultures are collected within 5 weeks of
birth, but this will decrease significantly when the
culture-to-birth interval is longer than 5 weeks.39 It is
reasonable to repeat GBS screening if a pregnant woman
whose original culture was negative does not give birth
within this 5-week screening accuracy window.
There were few epidemiological studies on late preterm
infants or pregnant women giving birth beyond 41 0/7 weeks
of gestation in mainland China. Multiple studies revealed
that the proportion of late preterm infants was 3.9% of live
births and the proportion of infants born between 35 0/7
and 35 6/7 weeks of gestation was 48.6% of late preterm
infants,40,41 so it was speculated that 1.9% of pregnant
women gave birth at 35 0/7e35 6/7 weeks’ gestation in
mainland China. The incidence of postterm pregnancy (42
weeks gestation) in China was about 7.2% in 2000, which has
decreased due to termination of pregnancy in recent
years.42 For late pregnancy, it was recommended to termi-
nate pregnancy at 41 0/7 and 41 6/7 weeks’ gestation to
reduce perinatal complications with reference to the Chi-
nese guideline.43 The above data revealed that there were
significantly more pregnant women who gave birth after 41
weeks of gestation in China than those who gave birth within
35 weeks of gestation, which is consistent with the data
from the United States.38 It is suggested that the adjustment
of GBS screening time to 36 0/7 and 37 6/7 weeks’ gestation
is also suitable for Chinese GBS screening policies.
We should pay attention to the following factors in the
screening GBS culture5,6: 1) to maximize the likelihood of
GBS recovery, a single swab is used to obtain the culture
specimen first from the lower vagina and then from the
rectum (through the anal sphincter) without use of a spec-
ulum; 2) the laboratory requisition of the screening GBS
culture should be marked for ensuring that GBS drug sensi-
tivity test is performed if the pregnant woman is allergic to
penicillin, especially at high risk of anaphylaxis; and 3) in
order to optimize sensitivity of subsequent culture results,
the sample swabs should be incubated first onto selective
enrichment broth before inoculation onto agar culture
plates. At present, the low positive screening rate in China
is related to the inappropriate method by which the swabs
were directly cultured onto agar culture plates without first
being put into the selective enrichment broth, which may
lead to the omission of nearly 50% of pregnant women with
GBS colonization.44
Although culture-based testing remains the standard for
maternal GBS screening, it may also use NATT on the
 Y. Zhu and X.-Z. Lin
enriched selective broth as an alternative method for pro-
cessing of antepartum GBS cultures. A key step of NAAT
methods is using an enrichment process before the assay is
performed, which can reduce the detection failure rate by
7%e10%.45 A study in Xiamen showed that the rate of NAAT
detection without incubating onto selective enrichment
broth was 14.13%, slightly lower than the 14.43% from
culture-based testing.14 NAAT offers a rapid and more sen-
sitive alternative to a culture for antepartum GBS screening
to reflect the intrapartum GBS colonization status and avoid
the overuse or omission of antibiotics prophylaxis. However,
the inability to obtain antibiotic susceptibility results with
NAAT limits the value of these tests for women who re-
ported a high-risk penicillin allergy. Therefore, NAAT can
not completely replace traditional culture-based methods
as a routine prenatal screening.
3.2. Indications for intrapartum antibiotic
prophylaxis
A systematic review indicated that 60 of 95 (63%) countries
had a national IAP policy, including 35 of 60 (58%) that used
microbiological screening, and 25 of 60 (42%) that used
clinical risk factors.46 Both universal culture-based screening
strategies and risk-based protocols are effective to prevent
GBS-EOD.47 However, Schrag et al. published a retrospective
analysis of more than 600,000 live births in 2002 and found
universal screening for GBS was >50% more effective at
preventing GBS-EOD compared to a risk-based approach
Table 1 Indications and non-indications for IAP to prevent neonatal GBS-EOD.
Indications for IAP
Maternal history
1. Previous neonate with invasive GBS disease.
Current pregnancy
1. Positive GBS culture obtained at 36 0/7 weeks of
gestation or more during current pregnancy;
2. GBS bacteriuria during any trimester of the current pregnancy.
Intrapartum
1. Intrapartum NAAT result positive for GBS;
2. Unknown GBS status at the onset of labor (culture not done,
or results unknown) or negative NAAT result, but
has any of the following risks:
1) birth at less than 37 0/7 weeks gestation;
2) PROM  18 h;
3) intrapartum temperature 38.0  Cb;
4) known GBS positive status in a previous pregnancy.
Abbreviations: IAP, intrapartum antibiotic prophylaxis; GBS, group B streptococcus; EOD, early-onset disease; NAAT, nucleic acid
amplification test; PROM, prelabor rupture of membranes.
Table cited from ACOG guideline.6
a
Intrapartum risk factors: 1) birth at less than 37 0/7 weeks of gestation; 2) PROM 18 h; 3) intrapartum temperature 38.0  C.
b
If intraamniotic infection is suspected, broad-spectrum antibiotic therapy that includes an agent known to be active against GBS
should replace GBS prophylaxis.
468
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(morbidity was 0.33 and 0.59 per 1000 live births, respec-
tively).48 Thus, CDC revised the guidelines in 2002 and ACOG
continued to endorse the universal antenatal culture-based
approach to identify women who would receive IAP to pre-
vent GBS-EOD in 2019.3,5
The indications of GBS IAP for universal screening are
listed in Table 1: 1) positive GBS culture or NAAT result
obtained at 36 0/7 weeks of gestation or more during cur-
rent pregnancy (unless a cesarean birth is performed before
onset of labor for a woman with intact amniotic mem-
branes); 2) GBS bacteriuria during any trimester of the
current pregnancy; 3) previous neonate with invasive GBS
disease; and 4) unknown GBS status at onset of labor (cul-
ture not done, or results unknown) or negative NAAT result,
but with any of the following risks－birth at less than 37 0/7
weeks’ gestation; premature rupture of membranes (PROM)
18 h; intrapartum temperature 38.0  C; and known GBS
positive status in a previous pregnancy.
GBS bacteriuria during pregnancy can significantly in-
crease the risk of premature delivery (RR, 1.98; 95% CI,
1.45e2.69; P < 0.001).49 Thus, this risk factor should be
highlighted in the medical record, and antibiotic prophy-
laxis should be administered empirically during labor
based on three key points: 1) GBS bacteriuria at any
concentration identified at any time during pregnancy
represents heavy maternal vaginal-rectal colonization and
indicates the need for IAP without the need for a GBS
screening; 2) GBS bacteriuria at levels of  105 CFU/mL,
either asymptomatic or symptomatic, warrants acute
treatment during the antepartum period, while
Non-indications for IAP
1. Colonization with GBS during a previous pregnancy
(unless colonization status in current pregnancy is
unknown at onset of labor at term).
1. Negative GBS culture obtained at 36 0/7 weeks of
gestation or more during the current pregnancy;
2. Cesarean birth performed before onset of labor on
a woman with intact amniotic membranes, regardless
of GBS colonization status or gestational age.
1. Negative GBS culture obtained at 36 0/7 weeks of
gestation or more during the current pregnancy,
regardless of intrapartum risk factorsa;
2. Unknown GBS status at onset of labor, NAAT result
negative and no intrapartum risk factors presenta.
 Pediatrics and Neonatology 62 (2021) 465e475

asymptomatic GBS bacteriuria at a level of < 105 CFU/mL
does not require maternal antibiotic therapy; and 3)
clindamycin susceptibility test needs to be done before
using GBS IAP during labor on women who have a reported
penicillin allergy. Owning to low concentration in the
urethra, clindamycin is not recommended for the treat-
ment of a urinary tract infection or bacteriuria.
When women present with unknown GBS culture status
during labor at term (37 0/7 weeks’ gestation), or even do
not have any established indication for IAP (i.e., GBS
bacteriuria or previous newborn affected by GBS disease),
there are three ways to identify those for IAP: 1) depending
on the intrapartum risk factors (i.e., a temperature of
38  C, or duration of PROM  18 h), if suspected or
confirmed IAI develops, IAP targeted against GBS should be
converted to a more broad-spectrum antibiotic regimen for
treatment of IAI that includes activity against GBS (i.e.,
ampicillin and an aminoglycoside); 2) NAAT test was per-
formed, and women with a positive intrapartum NAAT
result for GBS should receive IAP; 3) based on women’s
history of GBS colonization, it was demonstrated that there
was a higher risk of recurrence of GBS colonization if

Obtain vaginal-rectal swab for GBS culture

and start latency antibiotics which include
coverage for GBS prophylaxis

Patient entering labor?

Yes No

Continue antibiotics until birth PPROM Without PPROM

Continue intravenous Discontinue GBS

Latency antibiotic regimen:
latency antibiotics antibiotic prophylaxis
1. Penicillin(first 48 hours of intravenous
use, subsequent a 5-day oral regimen)
2. First-generation cephalosporin
Obtain GBS culture result
(low risk of penicillin allergya)
3.Clindamycin or azithromycin
(high risk of penicillin allergyb)
4.Broad-spectrum antibiotics
Positive Not available with labor onset Negative
(considered IAI)

GBS antibiotic prophylaxis at No GBS antibiotic prophylaxis,

onset of labor repeat vaginal-rectal culture once
the 5-week screening accuracy
window has passed if delivery
has not occurred

Figure 1 Antibiotic prophylaxis of GBS-EOD prevention in pregnant women with preterm labor or PPROM. Abbreviations: GBS,
group B streptococcus; PPROM, preterm prelabor rupture of membranes; IAI, intraamniotic infection. aIndividuals with a history of
any of the following: 1) nonurticarial maculopapular (morbilliform) rash without systemic symptoms; 2) pruritis without rash; 3)
nonspecific symptoms unlikely to be allergic (gastrointestinal distress, headaches, yeast vaginitis); 4) patient reports history but
has no recollection of symptoms or treatment; 5) family history of penicillin allergy but no personal history. bIndividuals with a
history of any of the following: 1) anaphylactic reactions are IgE mediated and typically occur within 1-6 hours after exposure to a
penicillin: pruritic rash, urticaria (hives), immediate flushing, hypotension, angioedema, respiratory distress or anaphylaxis; 2)
severe rare delayed-onset reactions are non IgE-mediated (T-cell mediated) occur days to weeks after initiation of a penicillin:
eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, Stevens-Johnson syndrome, or toxic epidermal
necrolysis; 3) recurrent reactions, reactions to multiple beta-lactam antibiotics, or positive penicillin allergy test. Figure adapted
from ACOG guideline.6

469

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 Y. Zhu and X.-Z. Lin
Table 2 Recommended antibiotic regimens for GBS prophylaxis in labor.
Antimicrobial agents
Penicillin G (first-line agent)
Ampicillin (alternative agent)
Cefazolin (low risk of penicillin allergya)
Clindamycin (high risk of penicillin allergyb, and
susceptible to clindamycin)
Vancomycin (high risk of penicillin allergyb, and not
susceptible to clindamycin)
Abbreviations: GBS, group B streptococcus; IV, intravenous.
Options for unknown risk of penicillin allergy include: 1) penicillin allergy testing; 2) administration of a cephalosporin (ie, cefazolin); 3)
administration of clindamycin if isolate susceptible; 4) administration of vancomycin if the GBS isolate is not susceptible to clindamycin.
ab
Low risk or high risk of penicillin allergy is listed in the explanation of Fig. 1.
women reported a GBS-positive outcome in a previous
pregnancy compared with GBS-negative ones (50.2% vs
14.1%; OR, 6.05; 95%CI, 4.84e7.55).50
A GBS screening culture should be obtained immedi-
ately when a woman presents with either preterm labor
or preterm PROM (PPROM). GBS screening must be done
within 5 weeks before an anticipated medically indicated
preterm birth date (e.g., multiple pregnancy, or chronic
hypertension). ACOG recommended that all women with
preterm labor should be given empiric prophylaxis and an
antibiotic susceptibility test if reporting an allergy to
penicillin.51 According to a large multicenter randomized
controlled trial,52 women with PROM between 34 0/7 and
38 6/7 weeks of gestation should be given immediate in-
duction rather than extended expectant management. If
expectant management is being considered when PPROM
occurs before 34 0/7 weeks of gestation, an initial GBS
culture should be obtained, and a latency antibiotic
regimen that incorporates agents which are active against
GBS should be started. If a woman has PPROM and IAI,
administration of broad-spectrum intrapartum antibiotics
that provides coverage for polymicrobial infections as
well as GBS is recommended.5,6 The implementation
process of IAP in women with preterm labor or PPROM is
shown in Fig. 1.
3.3. Antibiotic regimens for intrapartum GBS
prophylaxis (Table 2)
Penicillin is the preferred priority agent for intrapartum
GBS prophylaxis because it has a narrower, more targeted
spectrum of antimicrobial activity and a lower likelihood
of inducing resistance in other vaginal organisms, with
intravenous ampicillin as an acceptable alternative. The
drug levels of both agents can reach above the minimal
inhibitory concentration (MIC) for GBS in amniotic fluid
and fetal blood while minimizing the risk of maternal
toxicity. If a pregnant woman is allergic to penicillin, the
recommended antibiotic for intrapartum GBS prophylaxis
is based on two factors. 1) Risk of penicillin allergy in
women with GBS: for those with low risk, penicillin al-
lergy testing should be carried out. It is safe and benefi-
cial for pregnant women to be given cefazolin, which can
reduce the medical expenditure and avoid complications
470
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Antibiotic regimens
Initial dosage 5 million units, IV; then 2.5e3 million units, IV,
every 4 h, until delivery
Initial dosage 2-g, IV; then 1 g, IV, every 4 h, until delivery
Initial dosage 2-g, IV; then 1 g, IV, every 8 h, until delivery
900 mg, IV, every 8 h, until delivery
20 mg/kg, IV, every 8 h, maximum single dose is 2-g； minimum
infusion time is 1 h, or 500 mg/30 min for a dose > 1 g
associated with such broad-spectrum agents.53 For those
with high risk, antibiotics are selected according to the
results of drug sensitivity.53 2) The susceptibility of the
GBS isolate to clindamycin: for women reported to have
high risk of penicillin allergy, clindamycin is an alterna-
tive agent only if the GBS strain is known to be susceptible
to clindamycin because resistance rates approach 42% or
greater.54 Vancomycin remains the only option for intra-
partum GBS prophylaxis for women who report a high-risk
penicillin allergy and whose GBS strain is resistant to
clindamycin. Careful consideration should be given
before using vancomycin, because unnecessary exposure
of vancomycin is related to the emergence of resistant
organisms, such as vancomycin-resistant enterococci.
Erythromycin is no longer recommended because the
resistance rate continues to increase to 54% or higher.54
Additionally, erythromycin could not penetrate the
placental barrier well and does not produce therapeutic
drug levels in either amniotic fluid or fetal blood.55
3.4. Effectiveness and duration of intrapartum GBS
prophylaxis
Mechanisms of IAP for preventing neonatal GBS-EOD are
hypothesized to be as follows: 1) reducing maternal vaginal
GBS colonization burden, which requires levels in maternal
bloodstream above the MIC of the antibiotic for killing GBS;
2) preventing the colonization of fetal or neonatal skin or
mucous membrane, which requires adequate drug levels in
amniotic fluid; and 3) decreasing the risk of neonatal sepsis,
which requires adequate antibiotic levels in the fetus and
newborn. Neither antepartum nor intrapartum oral or
intramuscular regimens have been shown to be comparably
effective in reducing GBS-EOD.56 Other suggested alterna-
tives such as vaginal washing with chlorhexidine have also
proven ineffective in the prevention of GBS-EOD according
to a meta-analysis of randomized controlled trials.57
Therefore, only intravenous antibiotics can be used to pre-
vent GBS-EOD. There was a doseeeffect relationship be-
tween interval time of IAP and blood drug concentration for
preventing GBS-EOD. One pharmacokinetic trial demon-
strated that peak umbilical cord serum concentrations of
penicillin were reached within 60 min of administration of
maternal loading dose.58 A cohort study of 7691 births from
 Pediatrics and Neonatology 62 (2021) 465e475

2003 to 2004 compared the clinical effectiveness of peni-
cillin or ampicillin when administered at different intervals
(4; 2－< 4; or < 2 h before delivery) and found that 2 h of
antibiotic exposure reduced the frequency of GBS-EOD, with
highest effectiveness under administration of IAP at  4 h
before delivery.59 In one retrospective cohort study, longer
durations of GBS IAP reduced the incidence of neonatal
sepsis in a doseeresponse relationship: 1.6% for those who
received < 2 h of intrapartum antibiotics, 0.9% for durations
of 2e4 h, and 0.4% for durations of 4 h.60 Those studies
supported the effectiveness of antibiotics administered for
GBS-EOD prophylaxis at least 4 h before delivery. Thus,
duration of intravenous antibiotic agents (i.e., penicillin,
ampicillin or cefazolin)  4 h is defined as adequate GBS
IAP; while the intravenous interval < 4 h or using other
antibiotics (i.e., clindamycin or vancomycin) is considered
inadequate GBS IAP by CDC guideline definitions. Notably,
the efficacy of clindamycin and vancomycin in prevention of
GBS-EOD has not been demonstrated definitively.
4. Secondary prevention policies of neonatal
GBS-EOD
The secondary preventions of GBS-EOD recommended by
CDC guidelines in 2010 has been extended to prevent all
early-onset bacterial infections.4 It is a challenge for neo-
natologists to implement the management of GBS-EOD
prevention since diagnosis of chorioamnionitis and IAI is
difficult in clinical situations. According to the latest
guidelines, the infants given strategies for preventing GBS-
EOD are divided into neonates born at or near term (35
weeks of gestation) and those preterm (34 6/7 weeks of
gestation),7 as shown in Fig. 2.

Infants irrespective of maternal GBS status

Infants born at ≥ 35 weeks’ gestation Infants born at ≤ 34 weeks’ gestation

Any of the following?

Any of the following? Yes Yes 1. preterm labor
1. Signs of clinical illness Blood culturesa
2. Prelabor ROM
2. Maternal intrapartum Empiric antibiotics
3. Concern for intraamniotic infectionc
temperature ≥ 38.0°C
No
No Infants born by induction of labor

GBS IAP indicated for mother? with or without cervical ripening

Yes

Yes No
Yes
Adequate GBS IAPb given? Infants born by cesarean section for
maternal/fetal indications with ROM at
Any of the following?
time of delivery
1. Inadequate indicated
Yes No GBS IAP Yes
2. Concern for Approaches included:
Routine Clinical observation No
intraamniotic infectionc 1. Routine newborn care
newborn care for 36－48 hours
3. Signs of clinical illness 2. Blood cultures or clinical monitoring
after birth

Figure 2 An algorithm for neonatal management of GBS-EOD. Abbreviations: GBS, group B streptococcus; ROM, rupture of
membranes; IAP, intrapartum antibiotic prophylaxis. aConsider lumbar puncture and CSF culture before initiation of empiric an-
tibiotics for infants who are at the highest risk of infection, especially those with critical illness. Lumbar puncture should not be
performed if the infant’s clinical condition would be compromised, and antibiotics should be administered promptly and not
deferred because of procedure delays. bAdequate GBS IAP is defined as the administration of penicillin G, ampicillin, or cefazolin
4 hours before delivery. cIntraamniotic infection should be considered when a pregnant woman presents with unexplained
decreased fetal movement and/or there is sudden and unexplained poor fetal testing. dFor infants who do not improve after initial
stabilization and/or those who have severe systemic instability, the administration of empiric antibiotics may be reasonable but is
not mandatory. Figure adapted from AAP guideline.7

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 Y. Zhu and X.-Z. Lin

Table 3 Differences among the three guidelines in preventing GBS-EOD.

Aspect ACOG (2020)6 Queensland, Australia The UK (2017)9
(2020)10
Maternal management of GBS-EOD
Routine screening for Universal screening Risk factor approach Risk factor approach
GBS
Timing of maternal GBS 36 0/7e37 6/7 weeks of gestation 35 0/7e37 6/7 weeks of 35 0/7e37 6/7 weeks of
screening gestation (if requested) gestation (if requested)
NAAT-based testing Recommended Not recommended Not recommended
GBS carriage detected in IAP was required when colonization IAP was not required Depending on the
a previous pregnancy status in current pregnancy even if GBS status is choices of pregnant
is unknown at onset of labor unknown in the current women and the outcome
pregnancy of bacteriological testing
The antibiotic chosen Cefazolin (low riska) Clindamycin Cefazolin (low riska) Cephalosporin (low riska)
with penicillin (high riskb, and susceptible Lincomycin or Vancomycin
anaphylaxis to clindamycin) Vancomycin (high riskb, clindamycin (high riskb) (high riskb)
and not susceptible to clindamycin)
Neonatal management of GBS-EOD
Previous baby with GBS- Not emphasized, only routine newborn Blood cultures, Babies should be
EOD care if mother receiving adequate IAP commence antibiotics evaluated their vital
within 30 min signs at 0, 1 and 2 h, and
then 2 hourly until 12 h
Abbreviations: ACOG, American College of Obstetricians and Gynecologists; UK, United Kingdom; GBS, group B streptococcus; EOD,
early-onset disease; NAAT, nucleic acid amplification test; IAP, intrapartum antibiotic prophylaxis.
ab
Low risk or high risk of penicillin allergy is listed in the explanation of Fig. 1.

There are three current approaches to risk assessment
among infants born at  35 weeks’ gestation including cat-
egorical risk assessment, multivariate risk assessment (the
neonatal early-onset sepsis calculator), and risk assessment
based on newborn clinical condition. Because the multivar-
iate risk assessment model is required to combine
population-based data on the incidence of early-onset sepsis,
the calculator is used only if epidemiological data are
available in mainland China. The other two assessment
models can be adopted, in which the risk factor of PROM in
term infants was not emphasized differentiating from pre-
vious guidelines, considering the following two factors: 1)
PROM of late pregnancy is usually caused by normal physio-
logical thinning of membranes and uterine contraction, fol-
lowed by spontaneous labor, and it is often considered to be
weakly associated with infection61; 2) for women with PROM
who are GBS-positive, administration of antibiotics for GBS
prophylaxis should be given as a routine measure. Blood
culture and empirical antibiotics should be given to neonates
relying on the following conditions: 1) newborns with the
sepsis symptoms of respiratory and/or cardiovascular insta-
bility; 2) maternal intrapartum temperature 38.0  C: fever
is simplified as a single index representing IAI in the latest
guidelines of ACOG. For well-appearing newborns born to
mothers who had an indication for GBS prophylaxis but
received either no or inadequate IAP, the newborns should be
observed for 36e48 h, and no routine diagnostic testing is
recommended except for developing signs of illness. Well-
appearing newborns whose mothers had no IAI and no indi-
cation for GBS prophylaxis should be managed according to
routine clinical care.
For the GBS-EOD risk assessment among infants born 34
weeks’ gestation, a blood culture should be obtained and
empirical antibiotic treatment started under the following
conditions: 1) whether delivery or cesarean section, infants
born preterm especially due to cervical insufficiency; 2)
occurrence of PPROM before birth is usually related to IAI
caused by a variety of pathological mechanisms, especially
when delivered at  34 weeks’gestation62; 3) presence of
factors related to IAI (such as unexplained reduction of fetal
movements or otherwise unexplained onset of non-
reassuring fetal status); 4) infants delivered after efforts to
induce labor for maternal and/or fetal indications with or
without cervical ripening resulting in either vaginal or ce-
sarean section. If any of the following are present: inade-
quate GBS IAP; concern for IAI; or infant with respiratory
and/or cardiovascular instability, it is necessary to obtain a
blood culture and to initiate antibiotic therapy for infants.
In infants born by cesarean section for maternal/fetal in-
dications with PROM at time of delivery, acceptable initial
approaches to these infants include: 1) no laboratory eval-
uation and no empiric antibiotic therapy; 2) blood culture
and clinical monitoring, and the administration of empirical
antibiotics, if infants do not improve after initial stabiliza-
tion and/or have severe systemic instability.
5. Advances of guidelines from the UK and
Queensland in preventing GBS-EOD
Most information on preventing GBS-EOD policies from the
Europe and Australia is consistent with ACOG and AAP

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 Pediatrics and Neonatology 62 (2021) 465e475
guidelines. In Table 3, we summarize some different advances
of guidelines published by Royal College of Obstetricians and
Gynaecologists (RCOG) from the United Kingdom (UK) in 2017
and from Queensland, Australia in 2020.9,10 Both sets of
guidelines still recommended risk-based protocols rather than
a universal GBS screening strategy for pregnant women. This is
based on an assessment of the rate of GBS-EOD, the likely
cost-effectiveness of both strategies, the quality of the evi-
dence in support of both approaches and issues of current
practice, compliance and uptake.63 However, many studies
have indicated that screening-based protocols were associ-
ated with lower incidence of GBS-EOD compared to risk-based
protocols, while not clearly overexposing women to antibi-
otics.47,48 This information is of relevance for future policy-
making. If requested, GBS screening at 35e37 weeks’
gestation may be appropriate for individual women, recom-
mended by both guidelines. NAAT-based testing was not
mentioned for maternal antepartum GBS screening. Use of
GBS rapid testing is only in an evaluation or research setting in
Queensland, Australia. Even in the UK policy, polymerase
chain reaction or other near-patient testing at the onset of
labour is not recommended. When GBS was detected in a
previous pregnancy irrespective of carrier status in the cur-
rent pregnancy, IAP was not required according to the
Queensland, Australia guideline. However, it depended on the
choice of pregnant women and the outcome of bacteriological
testing to determine whether women should be offered IAP in
the UK guideline. For women with a high risk of penicillin
anaphylaxis, lincomycin was the recommended antimicrobial
agent in Queensland, Australia guideline and it was the
accepted alternative to clindamycin. Clindamycin can no
longer be recommended as the current resistance rate in the
UK is 16%.9 In terms of neonatal management of GBS-EOD, the
Queensland, Australia guideline recommended that newborns
should be obtained blood cultures and commenced antibiotic
therapy within 30 min if the mother had had a previous baby
with GBS-EOD. The measures from the UK guideline suggested
mothers who had a previous baby with GBS disease be offered
IAP, and following careful clinical assessment the baby’s vital
signs and clinical condition should be monitored closely for at
least 12 h.
6. Conclusion and future of GBS prevention
GBS disease is a worldwide problem, particularly in devel-
oping countries with limited resources. At present, the pre-
vention of neonatal GBS-EOD is still in the exploratory stage
in mainland China. Culture-based universal screening and IAP
strategies are the most effective ways to reduce the inci-
dence of the neonatal GBS-EOD, which is especially impor-
tant because GBS is a major infectious cause of morbidity
and mortality among infants in the Chinese population.16,27
However, studies also showed that GBS IAP resulted in gut
microbiota changes with increased risks of allergies, asthma,
and obesity in mothers and infants.64 Moreover, it was also
associated with the increase of bacterial drug resistance and
gram-negative bacilli.46 Therefore, the guidelines for pre-
vention of GBS in Europe and America strictly limit in-
dications for IAP, and the emphasis on reducing vertical
transmission of GBS tends to be on research and develop-
ment of GBS vaccine. Effective, multivalent vaccines
473
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2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
administered to pregnant women and at-risk nonpregnant
adults could be an ideal strategy for the prevention of GBS-
EOD.13 The trivalent GBS vaccine (Ia, Ib and III) has entered
the phase 1b/2 trial and appears to be well-tolerated and
immunogenic. The hexavalent vaccine covering the most
common serotypes (Ia, Ib, II, III, IVand V) has gone through
phase I and II trials in the United States, and has proved the
effective and safe.65,66 Many problems need to be overcome
before entering phase III trial, such as large sample size,
serotype coverage, and ethical issues. In summary, appro-
priate vaginal-rectal screening methods, indicated IAP
strictly and enhanced education among pregnant women are
still the key measures to reduce the risk of GBS-EOD.
Furthermore, future work and continuous surveillance are
warranted to better understand the epidemiological distri-
bution of GBS and identify the prevalent serotypes and ge-
notypes in perinatal GBS infection in mainland China, which
are essential for the development of an effective GBS vac-
cine and for preventing neonatal GBS-EOD.
Declaration of competing interest
The authors have no conflicts of interest relevant to this
article.
Acknowledgments
This study was supported by Guiding Project of Science and
Technology of Fujian Province (#2018D0011) and The Sci-
ence and Technology Planning Project of Xiamen 2017
(#3502Z20171006).
References
1. Prevention of perinatal group B streptococcal disease: a public
health perspective. Centers for Disease Control and Preven-
tion. MMWR Recomm Rep 1996;45:1e24.
2. ACOG committee opinion. Prevention of early-onset group B
streptococcal disease in newborns. Number 173–June 1996.
Committee on Obstetric Practice. American College of ob-
stetrics and Gynecologists. Int J Gynaecol Obstet 1996;54:
197e205.
3. Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of
perinatal group B streptococcal disease. Revised guidelines
from CDC. MMWR Recomm Rep 2002;51:1e22.
4. Verani JR, McGee L, Schrag SJ, Division of Bacterial Diseases,
National Center for Immunization and Respiratory Diseases,
Centers for Disease Control and Prevention (CDC). Prevention
of perinatal group B streptococcal diseaseerevised guidelines
from CDC, 2010. MMWR Recomm Rep 2010;59:1e36.
5. Prevention of Group B Streptococcal early-onset disease in
newborns: ACOG committee opinion, number 782. Obstet
Gynecol 2019;134:1.
6. Prevention of Group B Streptococcal early-onset disease in
newborns: ACOG committee opinion, number 797. Obstet
Gynecol 2020;135:e51e72.
7. Puopolo KM, Lynfield R, Cummings JJ, American Academy of
Pediatrics, Committee on fetus and newborn, Committee on
infectious diseases. Management of infants at risk for group B
streptococcal disease. Pediatrics 2019;144:e20191881.
8. Di Renzo GC, Melin P, Berardi A, Blennow M, Carbonell-
Estrany X, Donzelli GP, et al. Intrapartum GBS screening and
 Y. Zhu and X.-Z. Lin
antibiotic prophylaxis: a European consensus conference. J
Matern Fetal Neonatal Med 2015;28:766e82.
9. Prevention of early-onset neonatal group B streptococcal dis-
ease: green-top guideline No. 36. BJOG 2017;124:e280e305.
10. Queensland Health. Queensland clinical guidelines: early onset
group B streptococcal disease. Available at http://www.
health. qld. gov. au. Accessed April 1, 2020.
11. Nanduri SA, Petit S, Smelser C, Apostol M, Alden NB,
Harrison LH, et al. Epidemiology of invasive early-onset and
late-onset group B streptococcal disease in the United States,
2006 to 2015: multistate laboratory and population-based
surveillance. JAMA Pediatr 2019;173:224e33.
12. Chiu NC. Prevention of group B streptococcus infection.
Pediatr Neonatol 2019;60:233e4.
13. Dzanibe S, Madhi SA. Systematic review of the clinical devel-
opment of group B streptococcus serotype-specific capsular
polysaccharide-based vaccines. Expert Rev Vaccines 2018;17:
635e51.
14. Lin XZ, Wu JN, Zhang XQ, Huang QY, Jiang Y, Huang J, et al.
Relationship between group B Streptococcus colonization in
late pregnancies and neonatal infection. Chin J Perinat Med
2016;19:491e6.
15. Seale AC, Bianchi-Jassir F, Russell NJ, Kohli-Lynch M, Tann CJ,
Hall J, et al. Estimates of the burden of group B streptococcal
disease worldwide for pregnant women, stillbirths, and chil-
dren. Clin Infect Dis 2017;65:S200e19.
16. Zhang J, Kang K, Guo JZ, Li ZK. A case of neonatal early-onset
GBS septicemia and bacterial meningitis complicated with
large areas of cerebral infarction. Chin J Prev Med 2014;17:
430e1.
17. Zhou J, Lu G, Chen C, Lu Z, Yan X, Yan G, et al. Successful
extracorporeal membrane oxygenation in one neonate with
cardiorespiratory failure resulting from early-onset group B
streptococcal sepsis. Chin J Prev Med 2016;19:544e7.
18. Russell NJ, Seale AC, O’Driscoll M, O’Sullivan C, Bianchi-Jassir F,
Gonzalez-Guarin J, et al. Maternal colonization with group B
streptococcus and serotype distribution worldwide: systematic
review and meta-analyses. Clin Infect Dis 2017;65:S100e11.
19. Kim DH, Min BJ, Jung EJ, Byun JM, Jeong DH, Lee KB, et al.
Prevalence of group B streptococcus colonization in pregnant
women in a tertiary care center in Korea. Obstet Gynecol Sci
2018;61:575e83.
20. Hossein YektaKooshali M, Hamidi M, Mohammad Taghi Razavi
Tousi S, Nikokar I. Prevalence of group B streptococcus
colonization in Iranian pregnant women: a systematic review
and meta-analysis. Int J Reprod Biomed 2019;16.
ijrm.v16i12.3679.
21. Saha SK, Ahmed ZB, Modak JK, Naziat H, Saha S, Uddin MA,
et al. Group B streptococcus among pregnant women and
newborns in Mirzapur, Bangladesh: colonization, vertical
transmission, and serotype distribution. J Clin Microbiol 2017;
55:2406e12.
22. Ma TWL, Chan V, So CH, Hui ASY, Lee CN, Hui APW, et al.
Prevention of early onset group B streptococcal disease by
universal antenatal culture-based screening in all public hos-
pitals in Hong Kong. J Matern Fetal Neonatal Med 2018;31:
881e7.
23. Hsu JF, Chen CL, Lee CC, Lien R, Chu SM, Fu RH, et al. Char-
acterization of group B Streptococcus colonization in full-term
and Late-Preterm neonates in Taiwan. Pediatr Neonatol 2019;
60:311e7.
24. Huang J, Lin XZ, Zhu Y, Chen C. Epidemiology of group B
streptococcal infection in pregnant women and diseased
infants in mainland China. Pediatr Neonatol 2019;60:
487e95.
25. Villanueva-Uy ME, Wongsiridej P, Sangtawesin V, Chiu V,
Tallo V, Nazaire-Bermal N, et al. The burden of invasive
neonatal group B streptococcal (GBS) disease in Thailand and
474
Downloaded for Anonymous User (n/a) at University of the Andes from ClinicalKey.com by Elsevier on March 08,
2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
the Philippines. Southeast Asian J Trop Med Public Health
2015;46:728e37.
26. Matsubara K, Hoshina K, Kondo M, Miyairi I, Yukitake Y, Ito Y,
et al. Group B streptococcal disease in infants in the first year
of life: a nationwide surveillance study in Japan, 2011e2015.
Infection 2017;45:449e58.
27. Ji W, Liu H, Madhi SA, Cunnington M, Zhang Z, Dangor Z, et al.
Clinical and molecular epidemiology of invasive group B
streptococcus disease among infants, China. Emerg Infect Dis
2019;25:2021e30.
28. Zhu Y, Huang J, Lin XZ, Chen C. Group B streptococcus colo-
nization in late pregnancy and invasive infection in neonates in
China: a population-based 3-year study. Neonatology 2019;
115:301e9.
29. Hall J, Adams NH, Bartlett L, Seale AC, Lamagni T, Bianchi-
Jassir F, et al. Maternal disease with group B streptococcus and
serotype distribution worldwide: systematic review and meta-
analyses. Clin Infect Dis 2017;65:S112e24.
30. Yan Y, Hu H, Lu T, Fan H, Hu Y, Li G, et al. Investigation of
serotype distribution and resistance genes profile in group B
Streptococcus isolated from pregnant women: a Chinese
multicenter cohort study. APMIS 2016;124:794e9.
31. Wang P, Tong JJ, Ma XH, Song FL, Fan L, Guo CM, et al. Sero-
types, antibiotic susceptibilities, and multi-locus sequence
type profiles of Streptococcus agalactiae isolates circulating in
Beijing, China. PloS One 2015;10:e0120035.
32. Wang P, Ma Z, Tong J, Zhao R, Shi W, Yu S, et al. Serotype
distribution, antimicrobial resistance, and molecular char-
acterization of invasive group B Streptococcus isolates
recovered from Chinese neonates. Int J Infect Dis 2015;37:
115e8.
33. Lin XZ, Wu JY, Zhu Y, Tang LX, Chen L, He MY, et al. Serotype
features of group B Streptococcus vaginal colonization in late
pregnant women and their correlation with early-onset
neonatal infection. Chin J Prev Med 2020;23:232e8.
34. Yao Z, Jiayin W, Xinyi Z, Ling C, Mingyuan H, Simin M, et al.
Identification of group B streptococcus serotypes and geno-
types in late pregnant women and neonates that are associated
with neonatal early-onset infection in a south China popula-
tion. Front Pediatr 2020;8:265.
35. Su JZ, Wu WY, Ding L, Huang JJ, Wang SH, Zhang JS, et al. Drug
resistance, serotypes, virulence-associated genes and geno-
types of infection or colonization of group B Streptococcus in
perinatal pregnant women. Chin J Obstet Gynecol Pediatr
(Electron Ed) 2016;12:583e9.
36. Lu B, Li D, Cui Y, Sui W, Huang L, Lu X. Epidemiology of group B
streptococcus isolated from pregnant women in Beijing, China.
Clin Microbiol Infect 2014;20:O370e3.
37. Lee CC, Hsu JF, Prasad Janapatla R, Chen CL, Zhou YL, Lien R,
et al. Clinical and microbiological characteristics of group B
streptococcus from pregnant women and diseased infants in
intrapartum antibiotic prophylaxis era in Taiwan. Sci Rep 2019;
9:13525.
38. Martin JA, Osterman MJ, Kirmeyer SE, Gregory EC. Measuring
gestational age in vital statistics data: transitioning to the
obstetric estimate. Natl Vital Stat Rep 2015;64:1e20.
39. Virranniemi M, Raudaskoski T, Haapsamo M, Kauppila J,
Renko M, Peltola J, et al. The effect of screening-to-labor in-
terval on the sensitivity of late-pregnancy culture in the pre-
diction of group B streptococcus colonization at labor: a
prospective multicenter cohort study. Acta Obstet Gynecol
Scand 2019;98:494e9.
40. Zhang Y, He YD, Chen Q. Risk factors of late preterm birth and
perinatal complications among late preterm infants. Chin J
Prev Med 2014;17:379e83.
41. Cai LM, He Y, Wang H, Mu DZ. Analysis of late preterm new-
borns with hyperbilirubinemia. Chin J Obstet Gyneeol Pediatr
(Electron Ed) 2018;14:151e7.
 Pediatrics and Neonatology 62 (2021) 465e475
42. Cao ZY. Chinese obstetrics and gynecology. 3rd ed. Beijing:
People’s Medical Publishing House; 2014.
43. Obstetric Subgroup, Society of Obstetrics and Gynecology,
Chinese Medical Association and the Society of Perinatal
Medicine, Chinese Medical Association. Expert consensus on
the timing of termination for pregnancy complications. Chin J
Obstet Gynecol (Electron Ed) 2020;55:320e6.
44. Xie Y, Yang J, Zhao P, Jia H, Wang Q. Occurrence and
detection method evaluation of group B streptococcus from
prenatal vaginal specimen in Northwest China. Diagn Pathol
2016;11:8.
45. El Helali N, Habibi F, Azria E, Giovangrandi Y, Autret F, Durand-
Zaleski I, et al. Point-of-care intrapartum group B strepto-
coccus molecular screening: effectiveness and costs. Obstet
Gynecol 2019;133:276e81.
46. Le Doare K, O’Driscoll M, Turner K, Seedat F, Russell NJ,
Seale AC, et al. Intrapartum antibiotic chemoprophylaxis pol-
icies for the prevention of group B streptococcal disease
worldwide: systematic review. Clin Infect Dis 2017;65:S143e51.
47. Hasperhoven GF, Al-Nasiry S, Bekker V, Villamor E, Kramer B.
Universal screening versus risk-based protocols for antibiotic
prophylaxis during childbirth to prevent early-onset group B
streptococcal disease: a systematic review and meta-analysis.
BJOG 2020;127:680e91.
48. Schrag SJ, Zywicki S, Farley MM, Reingold AL, Harrison LH,
Lefkowitz LB, et al. Group B streptococcal disease in the era of
intrapartum antibiotic prophylaxis. N Engl J Med 2000;342:15e20.
49. Bianchi-Jassir F, Seale AC, Kohli-Lynch M, Lawn JE, Baker CJ,
Bartlett L, et al. Preterm birth associated with group B strep-
tococcus maternal colonization worldwide: systematic review
and meta-analyses. Clin Infect Dis 2017;65:S133e42.
50. Turrentine MA, Colicchia LC, Hirsch E, Cheng PJ, Tam T,
Ramsey PS, et al. Efficiency of screening for the recurrence of
antenatal group B streptococcus colonization in a subsequent
pregnancy: a systematic review and meta-analysis with inde-
pendent patient data. Am J Perinatol 2016;33:510e7.
51. Committee Opinion No. 712: intrapartum management of
intraamniotic infection. Obstet Gynecol 2017;130:e95e101.
52. Tajik P, van der Ham DP, Zafarmand MH, Hof MH, Morris J,
Franssen MT, et al. Using vaginal group B streptococcus colo-
nisation in women with preterm premature rupture of mem-
branes to guide the decision for immediate delivery: a
secondary analysis of the PPROMEXIL trials. BJOG 2014;121:
1263e72. discussion 1273.
53. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and
management of penicillin allergy: a review. JAMA 2019;321:
188e99.
475
Downloaded for Anonymous User (n/a) at University of the Andes from ClinicalKey.com by Elsevier on March 08,
2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
54. Centers for Disease Control and Prevention. Active bacterial
core surveillance (ABCs) : bact facts interactive. Available at
https://wwwn.cdc.gov/BactFacts/index.html. Accessed
February 20, 2019.
55. Bulska M, Szczesniak P, Pie˛ta-Dolin ska A, Oszukowski P, Ors-
zulak-Michalak D. The placental transfer of erythromycin in
human pregnancies with group B streptococcal infection.
Ginekol Pol 2015;86:33e9.
56. Baecher L, Grobman W. Prenatal antibiotic treatment does not
decrease group B streptococcus colonization at delivery. Int J
Gynaecol Obstet 2008;101:125e8.
57. Ohlsson A, Shah VS, Stade BC. Vaginal chlorhexidine during
labour to prevent early-onset neonatal group B streptococcal
infection. Cochrane Database Syst Rev 2014;(12):CD003520.
58. Barber EL, Zhao G, Buhimschi IA, Illuzzi JL. Duration of intra-
partum prophylaxis and concentration of penicillin G in fetal
serum at delivery. Obstet Gynecol 2008;112:265e70.
59. Fairlie T, Zell ER, Schrag S. Effectiveness of intrapartum anti-
biotic prophylaxis for prevention of early-onset group B
streptococcal disease. Obstet Gynecol 2013;121:570e7.
60. Turrentine MA, Greisinger AJ, Brown KS, Wehmanen OA,
Mouzoon ME. Duration of intrapartum antibiotics for group B
streptococcus on the diagnosis of clinical neonatal sepsis.
Infect Dis Obstet Gynecol 2013;2013:525878.
61. Moore RM, Mansour JM, Redline RW, Mercer BM, Moore JJ. The
physiology of fetal membrane rupture: insight gained from the
determination of physical properties. Placenta 2006;27:1037e51.
62. Prelabor rupture of membranes: ACOG practice bulletin,
Number 217. Obstet Gynecol 2020;135:e80e97.
63. Chen JC, Jenkins-Marsh S, Flenady V, Ireland S, May M,
Grimwood K, et al. Early-onset group B streptococcal disease in
a risk factor-based prevention setting: a 15-year population-
based study. Aust N Z J Obstet Gynaecol 2019;59:422e9.
64. Vornhagen J, Adams Waldorf KM, Rajagopal L. Perinatal
group B streptococcal infections: virulence factors, immu-
nity, and prevention strategies. Trends Microbiol 2017;25:
919e31.
65. Madhi SA, Cutland CL, Jose L, Koen A, Govender N, Wittke F,
et al. Safety and immunogenicity of an investigational
maternal trivalent group B streptococcus vaccine in healthy
women and their infants: a randomised phase 1b/2 trial.
Lancet Infect Dis 2016;16:923e34.
66. Absalon J, Segall N, Block SL, Center KJ, Scully IL, Giardina PC,
et al. Safety and immunogenicity of a novel hexavalent group B
streptococcus conjugate vaccine in healthy, non-pregnant adults:
a phase 1/2, randomised, placebo-controlled, observer-blinded,
dose-escalation trial. Lancet Infect Dis 2021;21:263e74.