Oral microflora and pregnancy: a systematic review and meta analysis
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
www.nature.com/scientificreports
OPEN Oral microflora and pregnancy:
a systematic review
and meta‑analysis
Hoonji Jang1, Alexa Patoine1, Tong Tong Wu2, Daniel A. Castillo3 & Jin Xiao1,4*
Understanding changes in oral flora during pregnancy, its association to maternal health, and its
implications to birth outcomes is essential. We searched PubMed, Embase, Web of Science, and
Cochrane Library in May 2020 (updated search in April and June 2021), and conducted a systematic
review and meta-analyses to assess the followings: (1) oral microflora changes throughout pregnancy,
(2) association between oral microorganisms during pregnancy and maternal oral/systemic conditions,
and (3) implications of oral microorganisms during pregnancy on birth outcomes. From 3983 records,
78 studies were included for qualitative assessment, and 13 studies were included in meta-analysis.
The oral microflora remains relatively stable during pregnancy; however, pregnancy was associated
with distinct composition/abundance of oral microorganisms when compared to postpartum/non-
pregnant status. Oral microflora during pregnancy appears to be influenced by oral and systemic
conditions (e.g. gestational diabetes mellitus, pre-eclampsia, etc.). Prenatal dental care reduced the
carriage of oral pathogens (e.g. Streptococcus mutans). The Porphyromonas gingivalis in subgingival
plaque was more abundant in women with preterm birth. Given the results from meta-analyses were
inconclusive since limited studies reported outcomes on the same measuring scale, more future
studies are needed to elucidate the association between pregnancy oral microbiota and maternal oral/
systemic health and birth outcomes.
Pregnancy is a unique physiological state, accompanied by temporary changes in women’s physical structure,
hormone levels, metabolism and immune s ystems1,2. The changes during pregnancy are vital to maintaining the
stable status of mother and fetus, however, some physiological, hormonal and dietary changes associated with
pregnancy, in turn, alter the risk for oral diseases, such as periodontal disease and dental c aries3. The delicate and
complex changes during pregnancy also affect the microbial composition of various body sites of the expectant
mothers4, including the oral cavity2. The oral cavity is colonized with a complex and diverse microbiome of over
700 commensals that have been identified in the Human Oral Microbiome Database (HOMD)5 and recently
expanded HOMD (eHOMD), including bacterial and fungal species6. Given a balanced microbial flora helps to
maintain stable oral and general health, alterations in the oral microbial community during pregnancy might
impact maternal oral health7,8, birth outcomes9, and the infant’s oral health10. Therefore, understanding changes of
oral flora during pregnancy, its association to maternal health, and its implications to birth outcomes is essential.
First, despite the speculated associations between oral flora and oral diseases during pregnancy, two critical
questions that remain to be answered are (1) what changes in the oral microbiota occur during pregnancy; (2)
whether the changes are associated with increased risk for oral diseases during pregnancy. Studies that evalu-
ated the stability of the oral microbiome during pregnancy revealed that the composition and diversity of oral
microbiome components remained stable without significant change11,12. However, on the contrary, some studies
reported that pregnant women experienced a significant increase in Streptococcus mutans, a well-known culprit
for dental caries13,14. In addition, researchers also reported an increased level of periodontal pathogens, e.g.,
Aggregatibacter actinomycetemcomitans, Porphyromona gingivalis and Prevotella intermedia, among pregnant
women15–17. Nevertheless, comprehensive evaluations of available evidence are needed to provide conclusive
consensus.
Second, a clear understanding of the association between oral microorganisms and adverse birth outcomes
conveys significant health implications. A systematic review from Daalderop et al., reported an association
between periodontal disease and various adverse pregnancy outcomes18. Women who have periodontal diseases
1
Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA. 2Department of
Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, USA. 3Miner Library,
University of Rochester Medical Center, Rochester, NY, USA. 4Perinatal Oral Health, Eastman Institute for Oral
Health, University of Rochester, 625 Elmwood Ave, Rochester 14620, USA. *email: jin_xiao@urmc.rochester.edu
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 1
Vol.:(0123456789)
www.nature.com/scientificreports/
during pregnancy are at higher risk for delivering preterm and low birth-weight infants19–21. In terms of oral
microorganisms, researchers reported a higher level of P. gingivalis among women with preterm d eliveries22,23. A
higher risk of preterm delivery was also observed among pregnant women with detection of periodontal anaer-
obes in subgingival p laque24. In contrast, Costa et al. reported that the risk of preterm birth is not correlated to
an increased amount of periodontopathogenic b acteria25. Therefore, a thorough review of all available evidence
on the topic of prenatal oral microorganisms and adverse birth outcomes is critical.
Furthermore, maternal oral health is closely associated with children’s oral health, including maternal related-
ness and vertical transmission of oral pathogens from mothers to infants26. Thus, in theory, reducing maternal
oral pathogens during pregnancy is paramount, since it could potentially reduce or delay the colonization of
oral pathogens in the infant’s oral cavity. Interestingly, although some s tudies27,28 demonstrated that expectant
mothers who received atraumatic dental restorative treatment during pregnancy resulted in significant reductions
of S. mutans carriage, and pregnant women who received periodontal treatment (scaling and root planning)
had a lowered periodontal pathogen level, a study from Jaramillo et al., failed to indicate decreased periodontal
bacteria in pregnant women following periodontal t reatment29.
Therefore, this study aims to comprehensively review the literature on oral microorganisms and pregnancy.
We are focusing on analyzing the evidence on the following subcategories: (1) oral microbial community changes
throughout pregnancy, including changes of key oral pathogens, the abundance, and diversity of the oral fungal
and bacterial community; (2) association between oral microorganisms during pregnancy and maternal oral/
systemic diseases; (3) implications of oral microorganisms during pregnancy on adverse birth outcomes.
Methods
This systematic review followed the PRISMA guidelines30, the protocol was registered for in the PROSPERO
(CRD42021246545) (https://www.crd.york.ac.uk/prospero/).
Search methods. Database searches were conducted in May 2020 and updated in April and June 2021
to identify published studies on changes in oral microbiome during pregnancy. A medical reference librarian
(DAC) developed the search strategies and retrieved citations from the following databases: Medline via Pub-
Med, Embase via embase.com, All databases (Web of Science Core Collection, BIOSIS Citation Index, Current
Contents Connect, Data Citation Index, Derwent Innovation Index, KCI-Korean Journal Database, Medline,
Russian Science Citation Index, SciELO Citation Index, and Zoological Record) via Web of Science, Cochrane
Central Register of Controlled Trials via Cochrane Library. A combination of text words and controlled vocabu-
lary terms were used (oral microbiota, oral health, bacterial diversity, pregnancy, periodontal pathogens, preg-
nancy complication). See “ESM Appendix” for detailed search methods used.
Inclusion and exclusion criteria. This systematic review included case–control studies, cross-sectional
studies, retrospective and prospective cohort studies, randomized or non-randomized controlled trials that
examined the changes of oral microorganisms in relation to pregnancy, oral diseases during pregnancy, adverse
birth outcome and the effect of prenatal oral health care on oral microorganisms’ carriage. Two trained inde-
pendent reviewers completed the article selection in accordance with the inclusion/exclusion criteria. Disagree-
ments were resolved by consensus between the two reviewers or by the third reviewer.
Inclusion criteria. Types of participants: women during reproductive age (pregnant and non-pregnant women).
Types of intervention(s)/phenomena of interest: pregnancy.
Types of comparisons:
• oral microbiota changes throughout pregnancy;
• oral microbiota profiling between pregnancy and non-pregnancy phases;
• oral microbiota changes following prenatal oral health care;
• association between oral microorganisms during pregnancy and adverse birth outcome;
• impact of systematic or oral health conditions on oral microbiota in pregnancy.
Types of outcomes: detection and carriage of oral microorganisms, oral microbiota diversity and composition.
Types of studies: case–control study; cross-sectional study; retrospective and prospective cohort study; ran-
domized and non-randomized controlled trials.
Types of statistical data: detection and carriage [colony forming unit (CFU)] of individual microorganisms;
Confidence Intervals (CI); p values.
Exclusion criteria. In vitro studies; animal studies; papers with abstract only; literature reviews; letters to the
editor; editorials; patient handouts; case report or case series, and patents.
Data extraction. Descriptive data, including clinical and methodological factors such as country of origin,
study design, clinical sample source, measurement interval, age of subjects, outcome measures, and results from
statistical analysis were obtained.
Qualitative assessment and quantitative analysis. The quality of the selected articles was assessed
depending on the types of studies. For randomized controlled trials, two methodological validities were used. (1)
Cochrane Collaboration’s tool for assessing risk of bias in randomized t rials31. Articles were scaled for the follow-
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 2
Vol:.(1234567890)www.nature.com/scientificreports/
Total identified records (n=3983)
Identification
PubMed (n=911)
Embase (n=1434)
Web of Science (n=1546)
Cochrane (n=91)
Manually added (n=1)
Duplicate records removed (n=1821)
Screening
Records screened
(n=2162)
Met exclusion criteria (n=2050)
Abstract not accessible (n=2)
Full-text articles assessed
Eligibility
for eligibility
(n=110) Full text not accessible (n=7)
Study group not clearly defined (n=8)
Sampling not meeting criteria (n=8)
No oral microbial related data (n=5)
Studies included in Short communication (n=3)
qualitative synthesis Dataset published in duplicates(n=1)
(n=78)
Included
Records without the same outcome
quantifiable unit were excluded (n=65)
Studies included in quantitative
synthesis (meta-analysis)
(n=13)
Figure 1. Flow diagram of study identification. The 4-phase preferred reporting items for systematic reviews
and meta-analyses (PRISMA) flow diagram was used to determine the number of studies identified, screened,
eligible, and included in the systematic review and meta-analysis (http://www.prisma-statement.org).
ing bias categories: selection bias, performance bias, detection bias, attrition bias, reporting bias, and other bias.
(2) Adapted Downs and Black scoring that assesses the methodological quality of both randomized and non-
randomized studies of health care interventions32. A total score of 26 represents the highest study quality. For
cohort and cross-sectional studies, a quality assessment tool for observational cohort and cross-sectional studies
was used33. Additionally, GRADE34,35 was used to assess articles used clinical interventions during pregnancy.
For the articles selected for quantitative analysis, the OpenMeta[Analyst] was used for meta-analysis (http://
cebm.b penme ta/). The 95% CI and p values were estimated using an unconditional generalized linear
rown.e du/o
mixed effects model with continuous random effects via DerSimonian–Laird method. Heterogeneity among
the studies was evaluated using I2 statistics and tested using mean difference values. Forest plots were created
to summarize the meta-analysis study results of mean difference of viable counts (converted to log value) of
microorganisms.
Results
The literature analyses identified a total of 3983 records from database searches (3982) and manual additions (1).
A total of 1821 duplicate references were removed. From the remaining 2162 records, 2050 were excluded after
title and abstract screening. The remaining 110 studies proceeded to a full text review; 32 studies were eliminated
based on the exclusion criteria and 78 articles were chosen for qualitative assessment (Fig. 1).
Study characteristics. The characteristics of studies11–17,21–25,27–29,36–98 included in the qualitative review
are summarized in Tables. A total of 78 studies are categorized into the following subgroups: 18 studies on oral
microbial differences between pregnant and non-pregnant women in Table 114–17,36–49; 11 studies on oral micro-
bial differences between pregnant stages in Table 211–13,50–57; 8 studies on oral microbial differences responding
to prenatal dental treatment in Table 327–29,58–62; 16 studies on association between oral microorganisms during
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 3
Vol.:(0123456789)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
The subgingival flora
evolved to a compo-
sition that has more
anaerobes as preg-
nancy progressed
The anaerobe/aer-
obe ratio increased
significantly at an
early stage of preg-
Pregnant group nancy and remained
T1: < 13 weeks GA A. naeslundii, A. high until the third
Follow-ups: odontolyticus, trimester
monthly after until A. viscosus, B. Only B. melanino-
Pregnant (20)
Kornman and USA, prospective delivery asaccharolyticus, genicus ss. inter-
Non-pregnant Subgingival plaque Culturing Fair
Loesche (1980)36 cohort Non-pregnant P. intermedi), midius (currently
(11)
group B. ochraceus, F. P. intermedia) sig-
Monthly visit for nucleatum, S. nificantly increased
4 consecutive sanguis during pregnancy
months compared between
trimesters
In the 2nd trimester,
the anaerobe/aer-
obe ratio and the
proportions of B.
melaninogenicus ss.
intermedius different
significantly from the
non-pregnant group
Significant differ-
ences in proportions
of Actinomyces were
found between
P. intermedia, pregnant and non-
Pregnant (19)
Pregnant group Black-pigmented pregnant group and
Muramatsu and Japan, cross- Non-pregnant Supragingival
One time point anaerobic rods, Culturing between 2nd tri- Fair
Takaesu (1994)37 sectional (12) plaque, saliva
during pregnancy Actinomyces mester pregnant and
Postpartum (8)
streptococcus postpartum group
No statistically
significant changes
in proportions of P.
intermedia
Positive correlations
between bacteria
carriage and estra-
diol concentrations
C. rectus (r = 0.443,
C. rectus, P. gin- p = 0.006)
Pregnant (22) Pregnant group givalis, A. actino- P. gingivalis
Yokoyama et al. Japan, cross- Unstimulated
Non-pregnant 27.4 ± 5.1 weeks mycetemcomitans, Real-time PCR (r = 0.468, p = 0.028) Fair
(2008)38 sectional whole saliva
(15) GA F. nucleatum, P. F. nucleatum
intermedia (r = 0.452, p = 0.035)
Positive correlations
between C. rectus
levels and sites of
4 mm-pocket depth
(r = 0.568, p = 0.006)
Carriage of subgin-
gival P. intermedia
doubled in the 2nd
trimester, comparing
Pregnant group to the 1st trimester;
T1: 12–14 weeks continued increas-
GA ing till after the
T2: 25–27 weeks delivery (p < 0.05);
GA and decreased to the
T3: 34–38 weeks lowest point after
P. intermedia, P.
Pregnant (30) GA 16s rDNA lactation
Gürsoy et al. Finland, prospec- Subgingival nigrescens (former
Non-pregnant T4: 4–6 weeks sequencing and Carriage of Fair
(2009)16 tive cohort plaque, saliva Bacteroides inter-
(24) postpartum; culturing salivary P. intermedia
medius)
T5: After lactation remained stable dur-
Non-pregnant ing the pregnancy
group and decreased
T1–T3 (once (p < 0.05) after lacta-
per subsequent tion to the same level
month) as the non-pregnant
group
P. nigrescens is likely
associated with preg-
nancy gingivitis
Continued
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 4
Vol:.(1234567890)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
No significant
changes in total
bacterial counts in
the pregnant group
either during or after
pregnancy
Pregnant group Significant reduction
T1: 12–14 weeks in A. actinomyce-
GA temcomitans after
T2: 23–25 weeks C. rectus, P. gin- delivery (p = 0.039)
GA givalis, A. actino- No statistically sig-
Carrillo-de- Pregnant (48) T3: 33–36 weeks mycetemcomitans, nificant differences
Spain, prospective
Albornoz et al. Non-pregnant Subgingival plaque GA F. nucleatum, P. Culturing during pregnancy Fair
cohort
(2010)39 (28) T4: 3 months intermedia, T. for any of the
postpartum forsythensis, P. pathogens evaluated;
Non-pregnant micra however, significant
group changes from the
2 visits 6 months third trimester to
apart postpartum for all
the pathogens
Subjects who were
positive for P.
gingivalis had higher
levels of gingival
inflammation
The organisms
which were most
commonly detected
in both the groups
were: Vielonella, T.
Veillonella, T.
forsythia, P. inter-
forsythia, P.
media, P. gingivalis,
Pregnant group intermedia, P.
Peptosreptococcus
Pregnant (15) T1: during preg- gingivalis, Pepto-
Basavaraju et al. India, prospective and F. nucleatum
Non-pregnant Subgingival plaque nancy screptococcus, F. Culturing Poor
(2012)40 cohort P. gingivalis was
(15) T2: 3 weeks post- nucleatum, Pro-
present in 5 patients
partum pionebactierum,
out of 15 in the
Mobiluncus,
pregnant-group as
Candida spp.
compared to 1 in the
non pregnant group
and the count was
reduced to 3 during
postpartum
No significant
difference in mean
A. actinomyce-
total bacterial count
temcomitans,
between pregnant
T. forsythia, C.
Pregnant (20) Fluorescence and non-pregnant
Machado et al. Brazil, cross- Pregnant group rectus, P. gingi-
Non-pregnant Subgingival plaque in situ hybridiza- group Fair
(2012)41 sectional 14–24 weeks GA valus, T. denticola,
(20) tion No significant dif-
F. nucleatum, P.
ferences between
intermedia, P.
groups in the num-
nigrescens
bers of all bactieral
species evaluated
P. intermedia sig-
nificantly increased
in pregnant women
who were in their
second and third tri-
A. actinomyce- mesters as compared
Pregnant (30, 10 temcomitans, with first trimester
Pregnant group
Emmatty et al. India, cross- in each trimester) P. gingivalis, P. and non-pregnant
Subgingival plaque One time point Culturing Fair
(2013)17 sectional Non-pregnant intermedia, F. women
during pregnancy
(10) nucleatum, P. Proportions of the
micra pathogens assessed
did not show any
significant difference
among pregnant
and non-pregnant
women
The detection of
Pregnant group A. actinomycetem-
T1: Second A. actinomyce- comitans in pregnant
trimester (15– temcomitans, women at 2nd and
Borgo et al. Brazil, prospective Pregnant (9)
Subgingival plaque 26 weeks GA) P. gingivalis, P. Real-time PCR 3rd trimester was Fair
(2014)15 cohort Non-pregnant (9)
T2: Third trimes- intermedia, F. significant higher
ter (30–36 weeks nucleatum than that in the non-
GA) pregnant women
(p < 0.05)
Continued
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 5
Vol.:(0123456789)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
A significant dif-
ference in total
cultivable microbial
number between
non-pregnant and
each stage of preg-
nancy
More total bacteria
counts at early stage
of pregnancy (T1),
comparing to the
non-pregnant group
(p < 0.05)
Significant higher
Subgingival prevalence of
A. actinomyce- Candida spp. in the
Pregnant group temcomitans, middle (T2) and
T1: 7–16 weeks P. gingivalis, P. late (T3) pregnancy,
Pregnant (132) GA intermedia, F. comparing to the
Fujiwara et al. Japan, prospective Subgingival Culturing and
Non-pregnant T2: 17–28 weeks nucleatum non-pregnant group Fair
(2017)42 cohort plaque, saliva real-time PCR
(51) GA Saliva (p < 0.05)
T3: 29–39 weeks Above 4 + Strepto- The number of peri-
GA cocci, Staphylo- odontal species was
cocci, Candida significantly lower in
spp. late pregnancy (T3),
comparing to the
early (T1) and mid-
dle (T2) pregnancy
(p < 0.05)
The prevalence of
P. gingivalis and A.
actinomycetemcomi-
tans was significantly
higher in the early
(T1) and middle
(T2) stage of preg-
nancy, comparing
to the nonpregnant
women (p < 0.05)
A significant increase
Pregnant group in S. mutans during
T1: 6 weeks GA the 2nd and 3rd
Pregnant (50)
Kamate et al. India, prospective T2: 18 weeks GA trimester and post-
Non-pregnant Saliva S. mutans Culturing Fair
(2017)14 cohort T3: 30 weeks GA partum period of
(50)
T4: 6 weeks post- pregnancy compared
partum to the non-pregnant
group (p < 0.01)
No difference in
oral yeast detection
within pregnancy
stages and between
pregnant and non-
pregnant stages
(p < 0.05)
Pregnant (30) Pregnant group More oral yeast were
Portugal, prospec- Unstimulated
Rio et al. (2017)43 Non-pregnant T1: 1st trimester Yeast Culturing found in the 3rd Fair
tive cohort saliva
(30) T2: 3rd trimester trimester than the
1st trimmest, but no
difference comparing
to the non-pregnant
stage (p < 0.05)
Saliva flow rate did
not change in both
groups
Pregnant group
Significant higher
T1: 11–14 weeks
bacterial diversity
GA
of the supragingival
T2: 20–25 weeks
microbiota in third
GA
trimester compared
T3: 33–37 weeks
Quantity of OUT to the non-pregnant
China, prospec- Pregnant (11) Supragingival GA 16s rDNA
Lin et al. (2018)44 and microbiota group Fair
tive cohort Non-pregnant (7) plaque, saliva T4: 6 weeks post- sequencing
diversity Neisseriaceae and
partum
Porphyromonadaceae
Non-pregnant
and Spirochaetaceae
group
were significantly
4 visits (same
enriched in pregnant
intervals of the
group
pregnant group)
Continued
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 6
Vol:.(1234567890)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
Salivary S. mutans
carriage was higher
in pregnant than
non-pregnant
women (p < 0.05)
No difference
between pregnant
and non-pregnant
salivary C. albicans
carriage (p > 0.05)
Whole non- C. albicans, C.
Low SES pregnant Tonsil (57%) was the
stimulated saliva, Pregnant group glabrata, C. tropi-
USA, cross- (48) Culturing and most prevalent site
Xiao et al. (2019)45 supragingival 3rd trimester calis, C. krusei, Fair
sectional Low SES Non- Colony PCR for C. albicans detec-
plaque, mucosal (> 28 weeks GA) C. dubliniensis, S.
pregnant (34) tion among pregnant
swabs mutans
women
Untreated decayed
teeth is associ-
ated with higher
carriage of salivary
S. mutans and C.
albicans detection in
both pregnant and
non-pregnant groups
(p < 0.05)
S. aureus, N.
catarrhalis, K.
E. coli was the most
pneumonia,
common species in
E. coli, P. mel-
Pregnant (26) non-pregnant group
Aikulola et al. Nigeria, cross- Pregnant group aninogenicus, P.
Non-pregnant Oral swab Culturing while N. catarrhalis Poor
(2020)46 sectional 20–28 weeks GA propionicum, V.
(32) was the most com-
pervula, S. viri-
mon in the pregnant
dans, Coagulase
group
negative Staphylo-
coccus
P. nigrescens had
higher prevalence in
the pregnant group
(p < 0.01)
P. nigrescens
exhibited more
frequently in late
pregnancy than
early and middle
P. gingivalis, P.
Huang et al. China, cross- Pregnant (84) Unstimulated Pregnant group pregnancy (p < 0.05
intermedia, P. 16s rRNA PCR Fair
(2020)47 sectional Postpartum (33) saliva One time point and p < 0.01)
nigrscens
P. gingivalis in the
postpartum group
exceeds all of the
pregnant stages
(p < 0.01)
P. intermedia did not
show any significant
differences among
groups
Significant differ-
ences in the relative
abundance of oral
microbiome in
pregnant women
A significant
dominance of
Streptococcus and
Pregnant (42) Quantity of OUT
Sparvoli et al. Brazil, cross- Pregnant group 16s rRNA Gemella in pregnant
Non-pregnant Oral swab and microbiota Fair
(2020)48 sectional 28–36 weeks GA sequencing women (p < 0.01 and
(18) diversity
0 = 0.03)
Shannon diversity
index were higher
in the non-pregnant
group, while the
Simpson diversity
index was higher in
the pregnant group
S. mutans were
more abundant in
pregnant women
Pregnant (38)
Wagle et al. Norway, cross- Pregnant group S. mutans, Lacto- (p = 0.03)
Non-pregnanr Saliva Culturing Fair
(2020)49 sectional 18–20 weeks GA bacillus Lactobaciilus did not
(50)
have the significant
difference between
the groups
Table 1. Oral microbial differences between pregnant and non-pregnant women.
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 7
Vol.:(0123456789)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
A. naeslundii gsp
2 level decreased
with increased GA
(p = 0.05)
L. casei carriage
increased with
increased GA
(p = 0.04)
L. casei levels at the
third trimester were
positively associated
S. mutans, S. sobri-
with birth weight
nus, S. sanguinus,
(β = 34.1 g; SE = 16.4;
L. acidophilus,
p = 0.04)
Dasanayake et al. USA, prospective First time preg- T1: 3rd trimester L. casei, A.
Stimulated saliva Culturing Total Streptococci Fair
(2005)50 cohort nant women (297) T2: Delivery naeslundii, Total
and total cultivable
Streptococci, Total
organism levels at
cultivable organ-
delivery were nega-
isms
tively associated with
birth weight
After multivariate
analysis with average
bacterial levels, A.
naeslundii gsp 2,
L. casei, pregnancy
age, and infant
gender remained sig-
nificantly associated
with birth weight
N. mucosa increased
throughout the preg-
nancy (p < 0.001)
Total bacterial
counts
No significant dif-
ferences between T1
and T2
Significant reduc-
37 species includ- tion from T1 to
ing T3 (p < 0.05), and
T1: 12 weeks GA
S. mutans, F. further reduction to
T2: 28 weeks GA
Adriaens et al. Switzerland, pro- Healthy pregnant Subgingival nucleatum, P. DNA–DNA T4 (p < 0.01)
T3: 36 weeks GA Fair
(2009)51 spective cohort women (20) plaque intermedia, P. hybridization Between T1 and T4,
T4: 4–6 weeks
gingivalis, A. significant differ-
postpartum
actinomycetem- ences were found
comitans for 8 of 37 species,
including S. mutans,
S. aureus, polymor-
phum, P. micra
Between measure-
ment intervals, no
statistical differences
identified for the
levels of four peri-
odontal pathogens
Increase of S. mutans
during the 2nd and
3rd trimester among
women 25–35 years
old
T1: 1st trimester
Increase of Lacto-
(11–12 weeks GA)
bacilli in the 2nd
Molnar-Varlam Romania, pro- Healthy pregnant T2: 2nd trimester S. mutans, Lacto-
Stimulated saliva Culturing trimester among Fair
et al. (2011)13 spective cohort women (35) (20–22 weeks GA) bacillus
women 20–24 years
T3: 3rd trimester
old and 30–35 years
(34–35 weeks GA)
old
The salivary pH
increased as the
pregnancy pro-
gresses
No statistically sig-
nificant changes in
counts of S. mutans
and Lactobacillus
spp., but a tendency
T1: Between 2nd
of higher numbers
Martinez-Pabon Colombia, pro- Pregnant women and 3rd trimester S. mutans, Lacto-
Stimulated saliva Culturing during pregnancy Fair
et al. (2014)52 spective cohort (35) T2: 7 months bacillus spp.
A statistically signifi-
postpartum
cant difference in the
pH and the buffering
capacity of saliva;
both lower during
pregnancy (p < 0.05)
Continued
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 8
Vol:.(1234567890)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
The progression of
Saliva, vaginal, Weekly from pregnancy is not
Pregnant women
stool, oral swab early pregnancy associated with a
DiGiulio et al. (49) 16 s rDNA
USA, case–control from molar tooth until delivery and Not specified; dramatic remodeling Fair
(2015)11 Full term (34) sequencing
surface & gum monthly until 12 of the diversity and
Preterm (15)
lines postpartum composition of a
woman’s microbiota
Klebsiella species
was the predomi-
nant isolate from
101 (25.6%) of the
women
Pregnant women
Klebsiella spp., The pattern of
(395)
E. coli, S. albus, microbial culture
1st trimester (3) Culturing, API
Okoje-Adesomoju Nigeria, cross- Proteus spp., S. whether normal
2nd trimester Mucosal swab One time point 20A identifica- Poor
et al. (2015)53 sectional aureus, Streptococ- for the oral cavity
(100) tion kits
cus spp., Pseu- or not did not vary
3rd trimester
domonas spp. significantly with
(292)
parity (p = 0.98),
trimester of preg-
nancy (p = 0.94) or
oral hygiene status
(p = 0.94)
Changes in the
percentage of P.
intermedia, F. nuclea-
tum, P. gingivalis, T.
denticola, C. rectus
and an increase in
A. actinomycetem-
T. forsythia, C.
comitans was noted,
T1: 19 ± 3.3 weeks rectus, P. gingivalis,
but differences were
GA; T. denticola, F.
Fluorescence not statistically
Machado et al. Brazil, prospective Healthy pregnant Supragingival & T2: 48 h postpar- nucleatum, P.
in situ hybridiza- significant Fair
(2016)54 cohort women (31) subgingival plaque tum; intermedia, P.
tion - A significant reduc-
T3: 8 weeks post- nigrescens A.
tion was seen for P.
partum actinomycetem-
nigrescens when all
comitans
three time points
were compared
(p = 0.01, Friedman
test), with a reduc-
tion from T1 to T3
(p = 0.002), and T2
to T3 (p = 0.037)
Species richness
and diversity of the
subgingival plaque
and saliva samples
were relatively stable
across the pregnancy
The abundance of
Prevotella, Strepto-
T1: 1st trimester
coccus and Veillonella
(< 12 weeks GA)
Pregnant women in both subgingival
T2: 2nd trimester
(30) Subgingival plaque and saliva
Balan et al. Singapore, pro- (21–24 weeks GA) 12 Phyla, 65 gen- 16s rDNA
1st trimester (10) plaque, unstimu- samples were more Fair
(2018)12 spective cohort T3: 3rd trimester era, 131 species sequencing
2nd trimester (10) lated saliva during pregnancy
(32–36 weeks GA)
3rd trimester (10) A significant decline
T4: 6 weeks post-
in the abundance of
partum
pathogenic species,
e.g., Veillonella
parvula, Prevotella
species and Actinob-
aculum species, was
observed from preg-
nancy to postpartum
period
Alpha diversity, both
inter-individual and
Pregnant (10) Every 3 weeks
Goltsman et al. USA, retrospec- Saliva, vaginal, 16 s rDNA intra-individual,
Term delivery (6) over the course of 1553 taxa Fair
(2018)55 tive cohort stool, rectal swabs sequencing remained stable
Preterm (4) gestation
across the pregnancy
and postpartum
Continued
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 9
Vol.:(0123456789)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
No significant
differences in total
amount of bacteria
between the groups
T. forsythia showed
significant differ-
ences in quantifica-
Pregnant (52) A. actinomyce- tion between 1st
1st trimester (16) temcomitans, trimester and 3rd
de Souza Massoni Brazil, cross- Subgingival
2nd trimester (21) One time point P. gingivalis, T. qPCR trimester, and 1st Fair
et al. (2019)56 sectional plaque
3rd trimester (15) forsythia, S. oralis, trimester and non-
Non-pregnant (15) Universal pregnant (p = 0.048
and p = 0.014)
Amount of T.
forsythia positively
correlated with the
diagnosis of gin-
givitis in pregnant
women (p = 0.031)
No difference in
Chao1 and Shannon
diversity for the
vaginal, oral, or gut
microbiome across
pregnancy for the
group overall
For the oral micro-
biota, having a low
African American Vaginal, oral T1: 8–14 weeks
level of education
Dunlop et al. USA, retrospec- Pregnant women (tongue, hard pal- GA 16S rDNA
Not specified and receipt of antibi- Fair
(2019)57 tive cohort (122) ate, gum line) and T2: 24–30 weeks sequencing
otics between study
Oral samples (97) rectal swabs GA
visits were associated
with greater Bray–
Curtis dissimilarity,
with some attenu-
ation of the effect
of education when
additionally control-
ling for prenatal
antibiotics
Table 2. Oral microbial differences between pregnancy stages.
pregnancy and adverse birth outcome in Table 421–25,63–73; eight studies on impact of periodontal disease on oral
microorganisms during pregnancy in Table 574–81; six studies on impact of gestational diabetes mellitus (GDM)
on oral microorganisms during pregnancy in Table 682–87; 11 studies on impact of systemic health conditions on
oral microorganisms during pregnancy in Table 788–98. Quality and risk of bias for randomized controlled trials
was assessed and are shown in Fig. 2. Quality assessment for cohort and cross-sectional studies are included in
the last column of all tables.
The quality of the selected articles was assessed using two methodological validities: (1) Cochrane Collabora-
tion’s tool for assessing risk of bias in randomized trials31. (2) Adapted Down and Black scoring32 that assess the
methodological quality of both randomized and non-randomized studies of health care interventions. A total
score of 26 represents the highest study quality.
Oral microbial differences between pregnant and non‑pregnant women. Evident changes of
oral microbiota were seen among pregnant women, comparing to those of non-pregnant women. A significantly
higher amount of total cultivable microorganisms were found in pregnant women comparing to the non-preg-
nant at each stage of pregnancy42. The plaque bacterial community was more diverse in 3rd trimester pregnant
women compared to non-pregnant women44.
Regarding oral pathogens, the prevalence of A. actinomycetemcomitans was significantly higher in pregnant
women in each stage compared to non-pregnant women (p < 0.05)15,42. Two studies14,45 assessed S. mutans car-
riage in saliva, and found that S. mutans carriage increased significantly throughout the pregnancy; particularly,
significant differences were seen between women in their first trimester and non-pregnant women (p < 0.0114 and
p < 0.0545). The detection of P. gingivalis and P. intermedia increased significantly in pregnant women compared
to non-pregnant w omen17,42. Although no difference was found in terms of C. albicans carriage between pregnant
and non-pregnant women45, two studies revealed a higher detection of Candida spp. among women in their late
pregnancy stage, comparing to the non-pregnant g roup42,43.
Oral microbial differences throughout pregnancy stages. Interestingly, seven studies11,12,51,52,54,55,57
revealed a stable oral microbial community during pregnancy. All four studies11,12,55,57 that performed sequenc-
ing analysis revealed that microbiota species richness, diversity and composition were relatively stable across the
pregnancy stages. The level of S. mutans and Lactobacillus spp. were assessed in two s tudies13,52. The levels of S.
mutans and Lactobacilli increased in both studies, but without statistical signficance52.
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 10
Vol:.(1234567890)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
A reduction in
salivary S. mutans
levels in treatment
Treatment group group became sig-
(33) Dietary coun- nificant (p < 0.01)
seling + Dental six months
Prophy + system- after the study
atic fluoride (1 mg began (at T3); S.
per day from the T1: 3rd month GA mutans reduction
last week of 6th T2: 6th month GA remained signifi-
month GA) + daily T3: 9th month GA cant (p < 0.001) at
fluoride and CHX T4: 6 months the end of the
Brambillia et al. Unstimulated
Italy, RCT mouth rinse postpartum S. mutans Culturing study See Fig. 2
(1998) saliva
Control group T5-T7: 12, 18, Children of
(32) 24 months mothers in
Dietary coun- postpartum, treatment group
seling + Dental respectively had significantly
Prophy + system- lower salivary S.
atic fluoride (1 mg mutans levels than
per day from the those of control-
last week of 6th group mothers
month GA) at 18 months old
(p < 0.05) and
24 months old
(p < 0.01)
Treatment group
(74) P. gingivalis, P.
Mothers who
Prenatal Peri- intermedia, P.
had pre‐term
odontal interven- nigrescens, B. for-
low birth weight
tion (Hygiene Treatment group sythus, A. actino-
DNA-DNA had significantly
instruction + full T1: During preg- mycetemcomitans,
Mitchell-Lewis USA, prospective Subgingival hybridization higher levels of
mouth debride- nancy F. nucleatum, Fair
et al. (2001)59 cohort plaque checkerboard B. forsythus and
ment) Control group T. denticola, P.
method C. rectus, and
Control group T1: After delivery micros, C. rectus,
elevated counts
(90) E. corrodens,
for the other spe-
Postpartum E. nodatum, S.
cies examined
periodontal inter- intermedius
vention
No significant
changes from
Treatment group baseline to
(40) postpartum in the
SRP + polish- levels of any single
ing + OHI + sonic Red cluster bacterial species
power toothbrush P. gingivalis, T. or cluster among
during 2nd forsythensis, T. control mothers
trimester denticola DNA-DNA P. intermedia
Gingival cervical
Offenbacher et al. Control group T1: < 22 weeks GA Orange cluster hybridization and P. nigrescens
USA, RCT fluid, subgingival See Fig. 2
(2006)60 (34) T2: Postpartum F. nucleatum, P. checkerboard reduction
plaque
(Supragingi- intermedia, P. method detected in the
val debride- nigrescens, C. treatment group
ment + manual rectus, A. actino- (p < 0.05)
toothbrush during mycetemcomitans A composite
pregnancy) + (SRP score of orange-
6 weeks postpar- cluster organisms
tum) decreased in
treatment group
(p = 0.03)
Women in
treatment group
P. gingivalis, had significantly
Treatment group
T. denticola, T. greater reductions
(413): SRP before T1: 13–16 weeks
forsythia, P. inter- (p < 0.01) in
Novak et al. 21 weeks GA Subgingival GA
USA, RCT media, C. rectus, Realtime PCR counts of P. gingi- See Fig. 2
(2008)61 Control group plaque T2: 29–32 weeks
F. nucleatum, A. valis, T. denticola,
(410): SRP after GA
actinomycetem- T. forsythia, P.
delivery
comitans intermedia, and
C. rectus than
untreated women
Treatment group A statistically sig-
(30) nificant decrease
Oral Environ- T1: Before treat- (p < 0.0001) in S.
ment Stabilization ment (70% in 2nd mutans counts
Volpato et al. Brazil, prospec-
(atraumatic caries Saliva trimester) S. mutans Culturing between saliva Fair
(2011)27 tive cohort
excavation and T2: 1 week after samples before
fillings + extrac- treatment and after oral
tion of retained environment
roots) stabilization
Continued
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 11
Vol.:(0123456789)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
The detection
Pregnant women P. gingivalis, P.
of assessed
with preeclamp- intermedia, P.
microorganisms
sia (57) nigrescens, T.
T1: Before treat- did not decrease
Jaramillo et al. Treatment group forsythia, C. rectus,
Colombia RCT Subgingival fluid ment PCR following peri- See Fig. 2
(2012)29 (26): SRP E. Corrodens, D.
T2: Postpartum odontal treatment
Control group pneumosintes, A.
in control group
(31): Supragingi- actinomycetem-
and intervention
val prophy comitans
group
Salivary S. mutans
was reduced after
Pregnant women
the atraumatic
with a minimal of
restorative treat-
3 decayed teeth
T1: Before treat- ment (p < 0.001)
Treatment group
Asad et al. ment Salivary S.
Pakistan, RCT (32): atraumatic Stimulated saliva S. mutans Realtime PCR See Fig. 2
(2018)28 T2: 1 week after mutans remained
restorative treat-
treatment the same level
ment
between the two
Control group
study time point
(32): no treatment
in the control
group (p = 0.29)
No difference in
S. mutans among
the pregnant
women who used
xylitol toothpaste
compared to those
who used tooth-
Treatment group T1: Before the
paste without
(23): toothpaste use of xylitol
xylitol (p = 0.062)
Escalante-Medina with 10% xylitol toothpaste
Peru, RCT Saliva S. mutans Culturing Both toothpastes, See Fig. 2
et al. (2019)62 Control group T2: 14 days after
with and without
(22): toothpaste the use of the
xylitol, were effec-
without xylitol toothpaste
tive to decrease
the count of S.
mutans in the
saliva of pregnant
women (p = 0.001
and p = 0.005,
respectively)
Table 3. Oral microbial differences responding to prenatal dental treatment.
Some studies12,39,51 indicated significant differences from pregnancy to the postpartum period. A total bacte-
rial count reduced significantly after delivery (p < 0.01)51. Several species, like S. mutans and Parvimonas micra,
showed significant differences in postpartum compared to the early stages of pregnancy51. This finding was also
noticed in another study where A. actinomycetemcomitans, P. gingivalis, Tannerella forsythia, P. micra showed an
abrupt decline after delivery39. A. actonomycetemcomitans, especially, dropped significantly in its amount after
delivery (p = 0.039)39. A significant decline in the abundance of pathogenic species from pregnancy to postpartum
period was observed as well12.
Impact of prenatal dental treatment on maternal oral flora. Four studies27,28,58,62 revealed lower
S. mutans carriage in the group with oral health care intervention during pregnancy compared to the control
group. Fluoride and chlorhexidine treatment as a caries-preventive regimen during pregnancy showed a statisti-
cal difference in the salivary S. mutans levels between the study and control groups by the end of the 3-month
treatment period58. At the end of the pregnancy, the reduction in S. mutans level was still significant in the study
group (p < 0.01)58.
Two studies27,28 which conducted oral environmental stabilization, including atraumatic restorative treat-
ment, revealed statistically significant decrease in S. mutans (p < 0.000127 and p < 0.00128) before and after the
intervention. Comparatively, there was no significant reduction in salivary S. mutans count in the group who
did not get the treatment (p = 0.29)28. Interestingly, children of treated group mothers had significantly lower
salivary S. mutans levels than those of untreated group mothers (p < 0.05)58.
Periodontal pathogenic microbiomes did not reveal consistent results. Three s tudies29,60,61 performed SRP as
treatment. Some microbiomes had significantly greater reductions where counts of P. gingivalis, P. intermedia, T.
denticola, T. forsythia, and C. rectus was significantly lower in treated women (p < 0.01)61. A similar result was also
found with detection of P. intermedia and P. nigrescens reduced significantly in the treatment group (p < 0.05)60.
Yet, the study by Jaramillo et al.29 did not detect a significant decrease in the levels of bacterial species between
treated and untreated groups. Quality of evidence and strength of recommendation by GRADE assessment
is described in ESM Appendix 4. Quality of evidence was assessed with the study design and factors to either
increase or reduce the quality for clinical interventional studies. Strength of recommendation was evaluated based
on whether all individuals will be best served by the recommended course of action. Depending on whether the
course is conditional or discretionary, the recommendation was given either strong or weak.
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 12
Vol:.(1234567890)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
-Detection of
Pregnant women T. forsythia was
(88) A. actinomyce- significantly higher
Threatened pre- temcomitans, among Threatened
Hasegawa et al. Japan, cross- Subgingival
mature labor Not specified P. gingivalis, P. PCR premature labor Fair
(2003)63 sectional plaque
Full term (22) intermedia, T. preterm delivery
Preterm (18) forsythia group than the
Healthy (48) full-term group
(p < 0.05)
Detection of
pathogens in
orange and red
clusters of sub-
gingival plaque
samples was lower
in full-term group
(16.7%) compared
to preterm group
(83.3%) (p < 0.01)
Carriage of
pathogens orange
Red cluster and red clusters
Women at risk
P. gingivalis, T. of subgingival
for miscarriage
forsythensis, T. plaque samples
or preterm deliv-
Amniotic fluid, denticola was higher in
Dörtbudak et al. Austria, cross- ery (36)
vaginal smears 15–20 weeks GA Orange cluster: Culturing, PCR preterm group Poor
(2005)21 sectional Preterm delivery
and dental plaque F. nucleatum, P. (p < 0.01)
(6)
intermedia, P. The levels of
Full-term delivery
nigrescens, C. Amniotic IL-6
(30)
rectus and PGE2 were
significantly
higher in women
delivering pre-
term (p < 0.001);
Amniotic IL-6
(r = 0.56, p < 0.01)
and PGE2
(r = 0.50, p < 0.01)
cytokine levels
were correlated
with subgingival
bacterial counts
Postpartum bacte-
rial carriage dif-
ference between
preterm and
full-term groups
P. gingivalis, T.
forsythensis, P.
intermedia, and
P. nigrescens
P. gingivalis, P.
Women with (p < 0.05)
intermedia, P.
periodontal T. denticola
nigrescens, T. for-
disease (31) Checkerboard and C. rectus
USA, nested case– Subgingival T1: 22 weeks GA sythensis, T. den-
Lin et al. (2007)64 Preterm delivery DNA–DNA (p < 0.065) Fair
control plaque T2: Postpartum ticola, C. rectus,F.
(14) hybridization Patients with
nucleatum, A.
Full-term delivery a high level of
actinomycetem-
(17) C. rectus at T1
comitans
showed a non-sig-
nificant tendency
to have a higher
risk for preterm
births (odds
ratio [OR] = 4.6;
95% confidence
interval [CI]
0.99–21.1)
Preterm group
had lower level
Pregnant women
One time point at of Lactobacilli
(107)
recruitment (from Culturing using (p = 0.009)
Durand et al. Preterm delivery S. mutans, Lacto-
USA, case–control Saliva 1st trimester to commercially kit No difference in Fair
(2009)65 (34) bacilli spp.
8 weeks postpar- (CRT bacteria®) S. mutans carriage
Full-term delivery
tum) between preterm
(73)
and full-term
groups (p = 0.053)
Continued
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 13
Vol.:(0123456789)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
P. gingivalis was
detected in saliva
among 7 out
the 15 low birth
weight group, and
3 of the 8 normal
High risk (hospi- delivery group
talized) Pregnant P. gingivalis was
women (23) detected in plaque
Hasegawa et al. Japan, cross- Saliva and Subgin-
Normal birth 2nd trimester P. gingivalis PCR among 8 out Fair
(2011)66 sectional gival plaque
weight (8) the 15 low birth
Low birth weight weight group, and
(15) 4 of the 8 normal
delivery group
No report on
statistical data
regarding oral
P. gingivalis and
birth weight
A significant sta-
tistical difference
between the mean
of gram-negative
cocci and intrau-
Gram-positive
terine fetal death
and negative cocci,
Pregnant women cases (p = 0.04)
Gram-positive
(243) A significant
and negative
Sadeghi et al. Iran. prospective Premature deliv- Culturing, Bacte- relationship in
Saliva 20–30 weeks GA bacilli, Spirilla, Fair
(2011)67 cohort ery (10) ria gram staining the presence of
Spirochetes,
Full-term delivery spirochetes in
Fusiform bacteria,
(233) saliva between
Actinomycetes,
premature and
Yeasts
normal delivery
(p < 0.05)
No significant
relationship for
other bacteria
The amount of
subgingival P.
gingivalis of pre-
Pregnant women A. actinomycetem- term women was
(80) 14–30 weeks GA comitans, P. gingi- higher than that
Subgingival
Cassini et al. Italy, prospective Preterm delivery (One time point valis, T. forsythia, of term women
plaque, vaginal Realtime PCR Fair
(2013)22 cohort (8) for microbial T. denticola, None of assessed
samples
Full-term delivery analysis) F. nucleatum, P. periodontopatho-
(72) intermedia gen resulted as
correlated to
preterm low
birthweight
P. gingivalis
detection was
Pregnant women more frequently
(95) detected among
Threatened prema- preterm group
ture labor (TPL) than full-term
Preterm delivery group among TPL
Subgingival A. actinomyce-
(13) women
Japan, cross- plaque, unstimu- temcomitans,
Ye et al. (2013)23 Full-term delivery 26–28 weeks GA ELISA No significant dif- Good
sectional lated saliva and P. gingivalis, T.
(34) ference in detec-
peripheral blood denticola
Healthy women tion frequency
Preterm delivery of A. actinomy-
(1) cetemcomitans, P.
Full-term delivery gingivalis and T.
(47) denticola between
TPL and healthy
groups
Continued
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 14
Vol:.(1234567890)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
A sevenfold
higher risk of
development of
preterm delivery
in women with
periodontal
P. gingivalis, P.
anaerobes in sub-
intermedia, F.
Pregnant women gingival plaque
nucleatum, Bacte-
(70) than women
roides sp., Veillon-
Andonova et al. Croatia, case– Preterm delivery Subgingival 28–36 + 6 weeks without
ela sp., P. micros, Culturing Fair
(2015)24 control (30) plaque GA Levels of P.
S. intermedius,
Full-term delivery gingivalis, F.
A. actinomyce-
(40) nucleatum, A.
temcomitans E.
actinomycetem-
lentum
comitans were
statistically sig-
nificantly higher
in preterm births
compared to full-
term deliveries
A. meyeri and
C. bifermentans
P. oralis, V. were significantly
parvula, P. associated with
Pregnant women melanionogenica, higher odds of
(94) P. anaerobius, P. preterm birth
Hassan et al. Saudi Arabia, Pro- Preterm delivery Subgingival asaccharolticus, (11.2 and 5.1),
2nd trimester Culturing Fair
(2016)68 spective cohort (22) plaque C. subterminate, with the estimate
Full-term delivery C. perfringens, C. of C. bifermentans
(72) clostridioforme, C. showing greater
bifermentans, E. precision (95%
lenta, A. meyeri confidence inter-
val = 1.5, 17.5)
(p < 0.05)
Pregnant women
P. gingivalis and
(134)
P. gingivalis, P. T. denticola were
Preterm low birth
intermedia, T. significantly more
Argentina, cross- weight delivery Subgingival
Usin et al. (2016)69 3rd trimester forsythia, T. denti- PCR prevalent in Full- Fair
sectional (18) plaque
cola, A. actinomy- term normal birth
Full-term normal
cetemcomitans weight delivery
birth weight
group
delivery (116)
Pregnant women Higher peri-
P. gingivalis, P.
(330) T1: During preg- odontopathogenic
intermedia, F.
Costa et al. Brazil, case– Preterm delivery Gingival crevicu- nancy DNA-DNA bacteria burden
nucleatum, A. Fair
(2019)25 control (110) lar fluid, blood T2: at the time of hybridization (PBB) did not
actinomycetem-
Full-term delivery delivery increase the risk
comitans
(220) of preterm birth
P. gingivalis-
related placenta
infection with
Pregnant women P. gingivalis, T.
adverse pregnancy
(94) forsythia, T. denti-
Subgingival outcome group
Gomez et al. Colombia, case– Adverse birth cola, E. nodatum,
plaque, placental During pregnancy PCR reflects high levels Good
(2020)70 control outcome (23) A. actinomyce-
samples of IFN-γ with
Non-adverse birth temcomitans, F.
a significative
outcome (17) nucleatum
decreasing of NK-
related cytokines
(p < 0.05)
Quantity of P.
gingivalis and
T. forsythia in
Pregnant women
plaque samples
(64)
and detection
Threatened
P. gingivalis, P. frequency of P.
preterm labor
intermedia, T. intermedia in
(TPL) (Low birth Saliva, Subgingival
Japan, prospective forsythia, T. denti- saliva were higher
Ye et al. (2020)71 weight) (9) plaque, placental During pregnancy qPCR, ELISA Good
cohort cola, A. actinomy- in TPL- Low
Threatened samples
cetemcomitans, F. birthweight deliv-
preterm labor
nucleatum ery than those
(Normal weight
in TPL-Healthy
delivery) (19)
delivery group
Control (36)
and/or in control-
healthy delivery
group
Continued
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 15
Vol.:(0123456789)www.nature.com/scientificreports/
Microbial
Country, study Groups (no. of Measurement Microorganisms detection Quality
Author (year) design subjects) Sample source interval evaluated methods Study findings assessment
The detection fre-
quency of P. gin-
givalis in plaque
and placenta
were significantly
correlated with
Pregnant women
low birthweight
(95)
delivery in TPL
Threatened pre-
group. In the
term labor (TPL)
receiver operating
(Low birthweight) Saliva, Subgingival
Japan, prospective characteristic
Ye et al. (2020)72 (14) plaque, placental 26–28 weeks GA P. gingivalis qPCR Good
cohort curve analysis, an
Threatened samples
amount of P. gin-
preterm labor
givalis in plaque
(Healthy delivery)
≥ 86.45 copies
(33)
showed a sensitiv-
Control (48)
ity of 0.786 and a
specificity of 0.727
(AUC 0.792)
for predicting
low birthweight
delivery in TPL
There was no sig-
nificant difference
in periodontal
parameters and
P. gingivalis, P.
serum IgG levels
intermedia, T.
for periodon-
forsythia, T. den-
Pregnant women tal pathogens
ticola, A. actino-
(90) between PLBW
mycetemcomitans,
Preterm low birth and healthy deliv-
China, prospec- F. nucleatum, Culturing, qPCR,
Ye et al. (2020)73 weight (PLBW) Saliva 2nd trimester ery (HD) groups Good
tive cohort E. saphenum, ELISA
(22) The amount of
Fretibacterium sp.,
Healthy delivery E. saphenum in
R. dentocariosa
(68) saliva and serum
Human oral taxon
IgG against A.
(HOT) 360, TM7
actinomyce-
sp. HOT 356
temcomitans
were negatively
correlated with
PLBW
Table 4. Association between oral microorganisms during pregnancy and adverse birth outcome—preterm
delivery.
Impact of periodontal disease on oral microorganisms during pregnancy. Three studies75,79,80 did
not identify any significant findings that the clinical periodontal condition and the levels of subgingival micro-
biome during pregnancy are related to pregnancy complications.
However, when subgingival plaque in women with threatened premature labor was assessed, P. gingivalis was
found in the half of patients with periodontal disease74. The presence of Eikenella corrodens and Capnocytophaga
spp. were significantly related to preterm birth and low birth weight respectively (p = 0.022 and p = 0.008)75. No
statistical significance was found in overall microbiome diversity in comparison of healthy gingiva and gingivitis
groups. However, bacterial taxa like Mogibacteriaceae and genera Veillonella and Prevotella were more prevalent
in the gingivitis g roup79.
Association between oral microorganism during pregnancy and adverse birth outcome. Five
studies22–24,71,72 showed that the amount of P. gingivalis in subgingival plaque was significantly higher in women
with preterm birth than women with term birth. Also, CFU counts of red and orange complex pathogens,
in which P. gingivalis belongs, from dental plaque in women with preterm delivery was significantly higher
(p < 0.01)21. The levels of Fusobacterium nucleatum, T. forsythia, Treponema denticola, and A. actinomycetem-
comitans were highly related to the preterm births compared to term d eliveries22,24.
However, higher periodontopathogenic bacteria burden did not increase the risk of preterm birth, despite the
increase in periodontal disease activity25. The levels of microorganisms like P. gingivalis, T. forsythensis, T. denti-
cola, P. intermedia, and F. nucleatum were not significantly higher in the preterm group than in the term group64.
Impact of systemic diseases on oral microorganism during pregnancy. Gestational diabetes mel-
litus (GDM). Two studies82,85 did not find significant differences in either clinical periodontal disease nor in
the diversity and richness between women with GDM and non-GDM. The detection rate and the number of
oral bacteria in women with GDM were higher than in non-GDM women, especially in the second trimester
of pregnancy84. Oral bacterial detection rate and total number in several species, such as black-pigmented bac-
teria, were significantly higher in pregnant women with GDM than those in non-diabetic pregnant women84.
Conversely, oral bacterial detection of oral streptococci and lactobacilli did not show any significant d
ifferences84.
Scientific Reports | (2021) 11:16870 | https://doi.org/10.1038/s41598-021-96495-1 16
Vol:.(1234567890)You can also read
