Probiotic interventions to reduce antepartum Group B streptococcus colonization: A systematic review and meta-analysis
Midwifery XXXXXXXXXX
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Midwifery
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Probiotic interventions to reduce antepartum Group B streptococcus
colonization: A systematic review and meta-analysis ✩
Lisa Hanson a , ∗, Leona VandeVusse b , Emily Malloy c , Mauricio Garnier-Villa
eal d ,
Lauren Watson e , Alissa Fial f , Marie Forgie g , Katrina Nardini h , Nasia Safdar i
a Klein Endowed Professor and Associate Director, Marquette University College of Nursing, Midwifery Program, Milwaukee, WI USA
Associate Professor Emerita, Marquette University College of Nursing Milwaukee, WI USA
c PhD student, Marquette University College of Nursing; Nurse-Midwife, Midwifery and Wellness Center, Department of Obstetrics and Gynecology, Advocate
Aurora Health Care, Milwaukee, WI, USA
d Assistant Professor, Sociology department, Vrije Universiteit Amsterdam
e Laboratory Manager, UW Madison School of Medicine and Infectious Disease, Madison, WI, USA
f Research & Instruction Services, Associate Li
arian, Raynor Memorial Li
aries, Marquette University, Milwaukee, WI, USA
g Physician, Department of Obstetrics and Gynecology, Advocate Aurora Women’s Health Care, Milwaukee, WI, USA
h Associate Chief, Midwifery Division, University of New Mexico Health Sciences Center, Department of Obstetrics and Gynecology, Albuquerque, New
Mexico, USA
i Professor, Infectious Disease, UW Madison School of Medicine. Madison WI, USA
a r t i c l e i n f o
Article history:
Received 29 April 2021
Revised 21 October 2021
Accepted 18 November 2021
Keywords:
Probiotics
Antenatal
GBS
in vitro, Systematic Review, Meta-analysis
a b s t r a c t
Objective: To systematically review and meta-analyse studies of the efficacy of probiotics to reduce ante-
natal Group B Streptococcus (GBS) colonisation.
Participants: Antenatal participants with known positive GBS colonisation or unknown GBS status.
Intervention: Probiotic interventions containing species of Lactobacillus or Streptococcus .
Design: Systematic review and meta-analysis.
Measurements and findings: The systematic review included 10 studies. Five articles contained in vitro
studies of probiotic interventions to determine antagonistic activity against GBS. Six clinical trials of pro-
iotics to reduce antenatal GBS were systematically reviewed and meta-analysed. The meta-analysis re-
vealed that the use of an antenatal probiotic decreased the probability of a positive GBS result by 44%
( OR = 0.56, 95% CI = 8.7%, 194.1%, p = XXXXXXXXXXn = 709). However, only one clinical trial of 10 had a low
isk of bias.
Key conclusions: The probiotic interventions subjected to in vitro testing showed antagonistic activity
against GBS through the mechanisms of acidification, immune modulation, and adhesion. The findings of
the meta-analysis of the clinical trials revealed that probiotics are a moderately effective intervention to
educe antenatal GBS colonisation. More well-controlled trials with diverse participants and with better
elucidation of variables influencing GBS colonisation rates are needed.
Implications for practice: Probiotic interventions appear to be a safe and effective primary prevention
strategy for antenatal GBS colonisation. Application of this low-risk intervention needs more study but
may reduce the need for intrapartum antibiotic prophylaxis in countries or regions where antenatal GBS
screening is used. Midwives can be instrumental in conducting and supporting larger well-controlled
clinical trials.
© 2021 Elsevier Ltd. All rights reserved.
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✩ Midwifery Probiotic interventions to reduce antepartum Group B Streptococcus
olonisation: A systematic review and meta-analysis –Manuscript Draft– Manuscript
umber: YMIDW-D XXXXXXXXXXArticle Type: Original Research
∗ Co
esponding author.
E-mail address: XXXXXXXXXX (L. Hanson).
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doi.org/10.1016/j.midw XXXXXXXXXX
XXXXXXXXXX/© 2021 Elsevier Ltd. All rights reserved.
ntroduction
Streptococcus agalactiae , more commonly known as Group B
treptococcus (GBS) is an encapsulated, beta-haemolytic, gram-
ositive coccus, and a facultative anaerobe that is part of the com-
ensal microbiome of humans. The gastrointestinal (GI) tract is
he source for vaginal GBS colonisation in women (American Col-
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L. Hanson, L. VandeVusse, E. Malloy et al. Midwifery XXXXXXXXXX
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G
ege of Obstetrics and Gynaecology, ACOG, 2019 ; Picard and Berg-
on, XXXXXXXXXXPrenatal GBS colonisation is generally asymptomatic
Armistead et al., 2019 ; Marziali et al., 2019 ), and may be transient
persistent (ACOG, 2019 ; Armistead et al., 2019 ; Marziali et al.,
019 ; Meyn et al., 2009 ; Picard and Bergeron, XXXXXXXXXXBrzychczy-
łoch et al., XXXXXXXXXXconducted a descriptive study with a sample
f 42 healthy adult pregnant women without signs of clinical gen-
tourinary infection. Separate vaginal and rectal GBS swabs were
ollected in each trimester. Fifteen participants were GBS positive
t some point in pregnancy and 27 were GBS negative. The re-
earchers found that vaginal GBS colonisation was relatively sta-
le throughout pregnancy, averaging 7.42 × 10 4 CFU/ml in the first
imester and 1.74 × 10 4 CFU/ml in the third trimester, while rec-
al colonisation changed substantially during pregnancy with an
verage 2.8 × 10 4 CFU/ml in the first trimester and 4.37 × 10 5
FU/ml in the third trimester. Several risk factors have been asso-
iated with GBS colonisation, including but not limited to: people
ho are employed in healthcare, of African descent, overweight or
ese, have low vitamin D levels, have poor vaginal hygiene, en-
aging in oral sex, or have frequent sexual intercourse ( Akoh et al.,
017 ; Capan-Melser et al., 2015 ; Foxman et al., 2007 ; Le Doare and
eath, 2013 ; Stapleton et al., 2005 ).
During normal vaginal birth, GBS can be vertically transmitted
o the fetus. Approximately 50% of neonates born to GBS culture
ositive women will become colonized with GBS but of these only
–2% will develop Early Onset Group B Streptococcus Disease (EOG-
SD) ( Chan et al., 2006 ; Illuzzi & Bracken, 2006 ; Vi
anniemi et al.,
019 ). EOGBSD can result in significant neonatal mo
idity and
ortality ( Verani et al., 2010 ).
Worldwide, GBS colonizes up to 65% of healthy nonpregnant
eople and between 15-40% of pregnant people ( Russell et al.,
017 ; Seale et al., XXXXXXXXXXThe global estimate of antenatal GBS is
8% with a large range of regional prevalence; the lowest rates
f colonisation (11–13%) are in Southern and Eastern Asia while
he Cari
ean has the highest rate (35%) ( Russell et al., 2017 ).
eale et al XXXXXXXXXXperformed an extensive analysis of the world-
ide burden of perinatal GBS. Of the 10 GBS serotypes, III is the
ost virulent and accounts for 48% of the EOGBSD cases world-
ide, while serotypes 1a and 1b are responsible for 30%, and seven
erotypes (II, IV, V, VI, VII, VIII, and IX) account for the remaining
ases.
The United States (US) Centers for Disease Control and Pre-
ention (CDC) 2010 guidelines recommended universal vaginal to
ectal screening at 35-37 weeks gestation and intrapartum an-
ibiotic prophylaxis (IAP) for those who test positive. Implemen-
ation of these guidelines resulted in an 80% reduction in EOG-
SD in the US, from 1.8 newborns per 1,0 0 0 live births in the
990s to 0.23 per 1,0 0 0 live births in XXXXXXXXXXNanduri et al.,
019 ; Verani et al., XXXXXXXXXXResidual GBS, including missed or tran-
ient GBS and late onset neonatal GBS disease, remain persis-
ent challenges despite the introduction of the CDC guidelines
Berardi et al., 2013 ; Parente et al., 2017 ; Van Dyke et al., 2009 ).
n 2019, ACOG American College of Obstetricians and Gynecolo-
ists (ACOG) 2019 American Academy of Pediatrics (AAP) 2019 as-
umed stewardship of GBS recommendations for all maternity care
oviders and newborns respectively, replacing and updating the
DC 2010 guidelines. Subsequently, the American Society for Mi-
obiology (ASM) issued new recommendations for standard labo-
atory practices related to GBS ( Filkins et al., XXXXXXXXXXAn important
hange in the recent ACOG guidelines is that of later vaginal to
ectal antenatal GBS screening between 36 0/7 and 37 6/7 weeks
estation to assure that the culture result is valid for a five-week
eriod before anticipated birth (ACOG, 2019 ).
Strategies used to prevent EOGBSD vary based on the recom-
endations of guideline-setting organizations and by regional vari-
tions in GBS prevalence. Three main EOGBSD prevention strate-
2
ies are used worldwide: (a) universal antenatal screening for GBS
ccording to the ACOG guidelines, (b) the risk-based approach, or
c) a combination of both ( Kolkman et al., XXXXXXXXXXAlthough con-
idered a standard of care in the US, the CDC and ACOG/AAP uni-
ersal screening approaches are both considered cost-effective in
egions where the prevalence of newborn GBS infection is high
> 1.2/1,0 0 0 births) ( Santhanam et al., XXXXXXXXXXIn regions where the
ate of newborn GBS infection is considered low, a risk-based ap-
oach is often used to determine candidates for IAP administra-
ion ( Santhanam et al., XXXXXXXXXXRisk