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 systems1,2. 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 caries3. 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 evaluated 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 women15,16,17. 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 during pregnancy are at higher risk for delivering preterm and low birth-weight infants19,20,21. In terms of oral microorganisms, researchers reported a higher level of P. gingivalis among women with preterm deliveries22,23. A higher risk of preterm delivery was also observed among pregnant women with detection of periodontal anaerobes in subgingival plaque24. In contrast, Costa et al. reported that the risk of preterm birth is not correlated to an increased amount of periodontopathogenic bacteria25. 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 relatedness 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 studies27,28 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 treatment29.
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.
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 PubMed, 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 vocabulary terms were used (oral microbiota, oral health, bacterial diversity, pregnancy, periodontal pathogens, pregnancy 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 independent reviewers completed the article selection in accordance with the inclusion/exclusion criteria. Disagreements were resolved by consensus between the two reviewers or by the third reviewer.
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; randomized and non-randomized controlled trials.
Types of statistical data: detection and carriage [colony forming unit (CFU)] of individual microorganisms; Confidence Intervals (CI); p values.
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.
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 trials31. Articles were scaled for the following 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.brown.edu/openmeta/). The 95% CI and p values were estimated using an unconditional generalized linear 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.
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).
The characteristics of studies11,12,13,14,15,16,17,21,22,23,24,25,27,28,29,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98 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 114,15,16,17,36,37,38,39,40,41,42,43,44,45,46,47,48,49; 11 studies on oral microbial differences between pregnant stages in Table 211,12,13,50,51,52,53,54,55,56,57; 8 studies on oral microbial differences responding to prenatal dental treatment in Table 327,28,29,58,59,60,61,62; 16 studies on association between oral microorganisms during pregnancy and adverse birth outcome in Table 421,22,23,24,25,63,64,65,66,67,68,69,70,71,72,73; eight studies on impact of periodontal disease on oral microorganisms during pregnancy in Table 574,75,76,77,78,79,80,81; six studies on impact of gestational diabetes mellitus (GDM) on oral microorganisms during pregnancy in Table 682,83,84,85,86,87; 11 studies on impact of systemic health conditions on oral microorganisms during pregnancy in Table 788,89,90,91,92,93,94,95,96,97,98. 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 Collaboration’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-pregnant 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 carriage 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 women17,42. 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 group42,43.
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 sequencing 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 studies13,52. The levels of S. mutans and Lactobacilli increased in both studies, but without statistical signficance52.
Some studies12,39,51 indicated significant differences from pregnancy to the postpartum period. A total bacterial 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 statistical 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 treatment, 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 studies29,60,61 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.
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 microbiome 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 group79.
Association between oral microorganism during pregnancy and adverse birth outcome
Five studies22,23,24,71,72 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. actinomycetemcomitans were highly related to the preterm births compared to term deliveries22,24.
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. denticola, 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 mellitus (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 bacteria, 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 differences84.
Two studies88,89 performed in Colombia and three studies81,94,95 performed in India revealed the influence of pre-eclampsia on the levels of the oral microbiome. Specifically, the birth weight of newborns were significantly lower in women with pre-eclampsia (p < 0.001)88. P. gingivalis and E. corrodens were more prevalent in the pre-eclampsia group than in the control group88,89. Further, the women with pre-eclampsia had a higher frequency of periodontal disease and chronic periodontitis (p < 0.001)88.
Preterm premature rupture of membranes (PPROM)
No statistically significant differences in the oral microbiome were observed in women with PPROM and those without at any time of measurement. However, in the PPROM group, significant decreases in the level of major periodontopathogens were noted from 20 to 35 weeks of gestation to within 48 h after parturition92.
Rheumatic valvular disease, smoking, and HPV
The frequency of periodontal disease in women with rheumatic valvular disease was not significantly different compared to women without the disease90. Smoking was associated with lower levels of gram negative facultative and higher levels of gram-negative anaerobes93. The presence of HPV infection and potential pathogens in oral microbiota composition were positively associated96.
A limited number of studies were included for meta-analysis due to the requirement of the same comparisons and outcome measures. Meta-analyses were performed to assess differences of total bacteria carriage, periodontal or cariogenic pathogens between pregnant and non-pregnant women, or between pregnancy stages, and following prenatal dental treatment.
First, no statistical difference was detected in terms of total bacteria carriage in subgingival plaque (Fig. 3)36,39,51 and saliva (Fig. 4)38,42 between different stages of pregnancy and between pregnant and non-pregnancy groups. Second, although more subgingival periodontal pathogens (P. gingivalis, T. forsythia, and T. denticola) were seen among pregnant women in their early stage of pregnancy, and more A. actinomyctemcomitans was seen in the later stage of pregnancy and in postpartum, no statistical significance was detected between groups (Fig. 5)15,51,54. Third, regarding oral Candida, no statistical difference was seen throughout the pregnancy and between non-pregnant and pregnant women (Fig. 6)42,43,45. Lastly, the effects of prenatal dental treatment on salivary S. mutans carriage were evaluated in three studies (Fig. 7)27,28,62. Although no significant difference was found, the reduction of salivary S. mutans was reported upon receiving prenatal dental treatment.
Are pregnant women at more risk for oral disease due to oral microbial changes?
Our study examined the currently available literature that reported oral microbial changes in relation to pregnancy. A fair number of studies reported an increased carriage of total oral bacteria and some disease-specific oral pathogens among pregnant women compared to the non-pregnant or postpartum group. However, meta-analyses only confirmed an increased total bacterium in saliva among pregnant women. Undetected statistical differences of subgingival total bacteria counts and specific oral pathogens between comparing groups could be due to a limited data set. Future studies are warranted to obtain conclusive findings of the association between pregnancy and oral microbial changes.
The oral cavity represents a substantial and diversified microbiota as a result of various ecologic determinants9. The cluster of oral microorganisms harmonizes to maintain oral microbial balance through a symbiotic relationship with their host in a state of health9,99. This balance has a crucial role in maintaining functions and fighting against infections in the oral cavity99. An imbalanced oral microbial community environment could lead to overgrowth of pathogenic bacteria or opportunistic pathogens, causing oral diseases, such as dental caries and periodontal diseases7,8. Previous studies suggested that during pregnancy, women are at higher risk for oral diseases14, due to the hormonal changes, such as estrogen, progesterone, relaxin, and gonadotropin100, and the increased pH in oral cavity from vomiting and craving snacks with high sugar28. It is speculated that pregnancy presents as a special physiological state for women, which could induce changes of the normal flora in the oral cavity1,2. For instance, the significantly higher detection of P. gingivalis and P. intermedia during pregnancy explains the tendency of more significant gingival inflammation in pregnant women15,44. Furthermore, the elevation of A. actonomycetemcomitans and P. gingivalis during the early stage of pregnancy predispose pregnant women to be at higher risk for periodontal diseases42.
Are oral microorganisms harbinger for adverse birth outcome?
Our study also evaluated the association between adverse birth outcomes and the oral microbial community. A significant question is whether oral microbial changes in pregnancy could be a harbinger for adverse birth outcomes. High levels of periodontal pathogens during pregnancy were evidently associated with an increased risk for preterm delivery24,64. The level of P. gingivalis, specifically, was higher in the preterm delivery group in three studies22,23,24. This bacterium could potentially influence a diagnosis of threatened premature labor through invasion of the amniotic cavity due to the presence in both the subgingival and respective amniotic fluid samples in those pregnant women with an increased risk74. Women with pre-eclampsia who developed an adverse birth outcome tended to have more diagnoses of periodontal disease with higher P. gingivalis and E. corrodens88. Hence, careful monitoring of expectant mothers with pre-eclampsia is advised to prevent further complications related to birth outcomes. However, a lack of meta-analysis due to insufficient consistent data suggests that further studies are needed to clarify the role of the microbial change in pregnancy as related to adverse birth outcome.
Preterm birth is defined as the birth of a baby before 37 weeks gestational age22,23. Many identified risk factors for low birth weight and preterm birth have been identified, such as maternal age, hypertension, usage of drug, alcohol or tobacco, genetics or environmental factors101. Also, early studies stated that periodontal inflammation is associated with pregnancy complications by affecting systemic inflammation from anaerobes and gram-negative periodontopathic bacteria20,63,102. More recent studies, however, reported no association with increased risk of adverse birth outcomes with periodontal bacteria103,104. As much as this topic is controversial, included studies described different results as well. Some studies showed that women with preterm delivery had a higher level of few microorganisms21,22,23,24,74; whereas alternatively, other studies did not succeed to present a positive relationship between higher subgingival bacterial level and the risk of adverse birth outcome25,64,75,79.
Interestingly, a few studies revealed that preterm birth prevalence was lower among women who had dental cleaning during pregnancy and that periodontal treatment provided to mothers with mild to moderate periodontal disease before 21 gestational weeks may reduce preterm births by 6%105,106. Considering these results, some may quickly conclude that these treatments are effective and have benefits in lowering adverse birth outcomes. However, it is still inconclusive how these procedures bring changes in the microbiological levels.
How systemic and oral diseases during pregnancy impact oral flora?
GDM is diabetes or any degree of glucose intolerance occurring during pregnancy84, and one of the most common obstetric complications, seen in 7% of all pregnancies in the United States every year82. GDM is associated with adverse birth outcomes and long-term consequences for pregnant women and their child85. The increased risk of future metabolic disorders in women with GDM has been studied85. Also, recent reports indicated that hyperglycemic pregnant women have an altered placental microbiota compared with normoglycemic pregnant women107,108. Consequently, risk of disorders in the offspring may be increased with changed salivary microbiota influenced by GDM, which affects the placental microbiota. Pregnant women with GDM should be carefully monitored for periodontal diseases84, since both diseases are associated with adverse birth outcomes109,110. However, the positive correlation between GDM and the altered oral microbial community is unclear.
Therefore, further studies on this topic are highly encouraged to provide sufficient quantitative data to predict the power and demonstrate this relationship at a demographic level since particular ethnic communities, such as Native Americans, Asians, and Hispanics, present higher prevalence than African Americans and Caucasians85.
Does prenatal dental treatment lead to modified oral microflora?
Routine dental care during pregnancy has been recommended as important and safe to perform by multiple medical and dental professional organizations111,112. Prenatal dental treatment includes dental prophylaxis, dental fillings to restore decayed teeth, root canal therapy and extractions for severely decayed and/or periodontally compromised teeth1. Maintaining good prenatal oral health is essential for mothers and their offspring1, since maternal oral health is strongly associated with children’s oral health. However, due to various barriers, such as lack of awareness, social hardships, lack of access to prenatal care, prenatal dental care is largely underutilized. Xiao et al. reported that more than 80% of underserved US pregnant women have at least one untreated decayed tooth, and average number of decayed teeth is 3.945. Similar data indicates that more than 70% of underserved pregnant women in Florida have unmet oral health needs113.
Despite the importance of prenatal dental care to the mothers and their children, the magnitude of benefits in obtaining prenatal oral health care, particularly, the modification of oral flora towards a healthier composition, has not been classified. Although the majority of studies indicated a lower carriage of S. mutans after receiving oral health care intervention and prevention27,28,58, the result from the meta-analysis does not indicate statistically significant changes of S. mutans following prenatal dental treatment. The fact that only two studies27,28 were included in the meta-analysis should be taken into consideration. Interestingly, studies29,60,61 that provided SRP to pregnant women had inconsistent results with the changes in the detection of periodontal pathogens. However, different microbial detection methods, measurement interval, subject groups should be considered.
Nonetheless, despite a wide range of prenatal dental treatment provided, ranging from fluoridation to oral environment stabilization, pregnant women in most of these reported studies did achieve oral disease-free status before delivery. Future clinical studies and clinical trials that provide total oral rehabilitation during pregnancy are warranted to comprehensively assess prenatal dental care's impact on maternal oral flora. Positive results will provide more evidence to support providing prenatal oral health care to mothers, which may potentially lead to a reduction in the vertical transmission of cariogenic bacteria and fungi to children58.
The following limitations should be cautiously considered when interpreting the results of this review: (1) studies included utilized inconsistent and heterogeneous approaches in grouping study data and reporting findings. Various methodologies for detecting and analyzing microorganisms were reported. The dissimilarity of recording the carriage of microorganisms, e.g., total counts, detection rate in percentages of different species of bacteria, frequency, normalization of the CFU data by using log10 (CFU/mg), for example, complicates the comparison of findings and data across the studies. Therefore, conducting a meta-analysis for each subgroup becomes unlikely, and this compromises a better quantitative understanding of the data; (2) variability of methodologies for bacteria and yeast quantification. As the quantification of bacteria and yeast was the meta-analysis outcome measure in this systematic review, it is worth noting that clinical sample collection and processing methods can significantly affect these microbiological outcomes. In addition, since both culture-dependent and culture-independent methods were used to detect and quantify multiple microorganisms, different levels of sensitivity and specificity across the studies are seen and reflected in the heterogeneity of studies included in the meta-analysis. Standardized methods for both identification and quantification are needed to ensure comparable results while enhancing study reproducibility; (3) due to the lack of study subject’s data on other possible determinants, e.g., race, ethnicity, demographic, socioeconomic, etc., the meta-analyses performed in this review did not adjust potential confounders mentioned above when comparing mean difference in CFUs, which might under- or over-estimate the effect of pregnancy on oral microflora; (4) as most of the studies did not report sample size calculation, study power to detect differences is questionable.
In summary, studies have shown that the oral microflora during pregnancy stages remain relatively stable; however, distinctive patterns of microorganisms’ presence and abundance have been observed between pregnancy and postpartum stages and between pregnant and non-pregnant women. Oral microflora during pregnancy appears to be influenced by oral and systemic disease status. Given prenatal dental care decreases specific oral pathogens, more studies are needed to define the outcome magnitude. Future efforts are needed to understand pregnancy and its relationship with the oral microbial community and the association between maternal oral microflora and adverse birth outcomes. Gaining knowledge on this topic could contribute to modifying health care strategies and policies at both community and individual levels to improve mother and child health outcomes.
Kandan, P. M., Menaga, V. & Kumar, R. R. R. Oral health in pregnancy (guidelines to gynaecologists, general physicians & oral health care providers). JPMA J. Pakistan Med. Assoc. 61, 1009 (2011).
Nuriel-Ohayon, M., Neuman, H. & Koren, O. Microbial changes during pregnancy, birth, and infancy. Front. Microbiol. 7, 1031–1031. https://doi.org/10.3389/fmicb.2016.01031 (2016).
Silva de Araujo Figueiredo, C., Goncalves Carvalho Rosalem, C., Costa Cantanhede, A. L., Abreu Fonseca Thomaz, E. B. & Fontoura Nogueira da Cruz, M. C. Systemic alterations and their oral manifestations in pregnant women. J. Obstet. Gynaecol. Res. 43, 16–22. https://doi.org/10.1111/jog.13150 (2017).
Neuman, H. & Koren, O. in Intestinal Microbiome: Functional Aspects in Health and Disease Vol. 88 Nestle Nutrition Institute Workshop Series (eds E. Isolauri, P. M. Sherman, & W. A. Walker) 1–9 (2017).
Dewhirst, F. E. et al. The human oral microbiome. J. Bacteriol. 192, 5002–5017. https://doi.org/10.1128/JB.00542-10 (2010).
Escapa, I. F., Chen, T., Huang, Y., Gajare, P., Dewhirst, K. P & Lemon, K. P. New insights into human nostril microbiome from the expanded Human Oral Microbiome Database (eHOMD): A resource for species-level identification of microbiome data from the aerodigestive tract. mSystems, 3(6), e00187–18 (2018).
Wade, W. G. The oral microbiome in health and disease. Pharmacol. Res. 69, 137–143 (2013).
Gao, L. et al. Oral microbiomes: More and more importance in oral cavity and whole body. Protein Cell 9, 488–500. https://doi.org/10.1007/s13238-018-0548-1 (2018).
Cobb, C. M. et al. The oral microbiome and adverse pregnancy outcomes. Int. J. Womens Health 9, 551–559. https://doi.org/10.2147/ijwh.S142730 (2017).
Xiao, J., Fiscella, K. A. & Gill, S. R. Oral microbiome: Possible harbinger for children’s health. Int. J. Oral Sci. 12, 12. https://doi.org/10.1038/s41368-020-0082-x (2020).
DiGiulio, D. B. et al. Temporal and spatial variation of the human microbiota during pregnancy. Proc. Natl. Acad. Sci. USA 112, 11060–11065. https://doi.org/10.1073/pnas.1502875112 (2015).
Balan, P. et al. Keystone species in pregnancy gingivitis: A snapshot of oral microbiome during pregnancy and postpartum period. Front. Microbiol. 9, 2360. https://doi.org/10.3389/fmicb.2018.02360 (2018).
Molnar-Varlam, C., Cristina, M.-V., Loana-Gabriela, B. & Tohati, A. Risk assessment of caries in pregnancy. Acta Medica Marisiensis 57, 685–689 (2011).
Kamate, W. I., Vibhute, N. A. & Baad, R. K. Estimation of DMFT, salivary streptococcus mutans count, flow rate, Ph, and salivary total calcium content in pregnant and non-pregnant women: A prospective study. J. Clin. Diagn. Res. 11, Zc147–Zc151. https://doi.org/10.7860/jcdr/2017/24965.9516 (2017).
Borgo, P. V., Rodrigues, V. A. A., Feitosa, A. C. R., Xavier, K. C. B. & Avila-Campos, M. J. Association between periodontal condition and subgingival microbiota in women during pregnancy: A longitudinal study. J. Appl. Oral Sci. 22, 528–533. https://doi.org/10.1590/1678-775720140164 (2014).
Gürsoy, M. et al. Does the frequency of Prevotella intermedia increase during pregnancy?. Oral Microbiol. Immunol. 24, 299–303 (2009).
Emmatty, R., Mathew, J. J. & Kuruvilla, J. Comparative evaluation of subgingival plaque microflora in pregnant and non-pregnant women: A clinical and microbiologic study. J. Indian Soc. Periodontol. 17, 47–51. https://doi.org/10.4103/0972-124x.107474 (2013).
Daalderop, L. et al. Periodontal disease and pregnancy outcomes: Overview of systematic reviews. JDR Clin. Transl. Res. 3, 10–27 (2018).
Corbella, S. et al. Adverse pregnancy outcomes and periodontitis: A systematic review and meta-analysis exploring potential association. Quintessence Int. 47, 193–204. https://doi.org/10.3290/j.qi.a34980 (2016).
Offenbacher, S. et al. Periodontal infection as a possible risk factor for preterm low birth weight. J. Periodontol. 67, 1103–1113. https://doi.org/10.1902/jop.1996.67.10s.1103 (1996).
Dortbudak, O., Eberhardt, R., Ulm, M. & Persson, G. R. Periodontitis, a marker of risk in pregnancy for preterm birth. J. Clin. Periodontol. 32, 45–52. https://doi.org/10.1111/j.1600-051X.2004.00630.x (2005).
Cassini, M. A. et al. Periodontal bacteria in the genital tract: Are they related to adverse pregnancy outcome?. Int. J. Immunopathol. Pharmacol. 26, 931–939. https://doi.org/10.1177/039463201302600411 (2013).
Ye, C. et al. The anti-phospholipid antibody-dependent and independent effects of periodontopathic bacteria on threatened preterm labor and preterm birth. Arch. Gynecol. Obstet. 288, 65–72. https://doi.org/10.1007/s00404-013-2741-z (2013).
Andonova, I. et al. Can oral anaerobic bacteria cause adverse pregnancy outcomes?. Pril. (Makedon. Akad. Nauk. Umet. Odd. Med. Nauki.) 36, 137–143 (2015).
Costa, E. M. et al. Periodontopathogenic microbiota, infectious mechanisms and preterm birth: analysis with structural equations (cohort-BRISA). Arch. Gynecol. Obstet. 300, 1521–1530. https://doi.org/10.1007/s00404-019-05355-x (2019).
Xiao, J. et al. Candida albicans carriage in children with severe early childhood caries (S-ECC) and maternal relatedness. PLoS ONE 11, e0164242. https://doi.org/10.1371/journal.pone.0164242 (2016).
Volpato, F. C. et al. Effects of oral environment stabilization procedures on Streptococcus mutans counts in pregnant women. Braz. Dent. J. 22, 280–284. https://doi.org/10.1590/s0103-64402011000400003 (2011).
Asad, R. et al. Effect of atraumatic restorative treatment on Streptococcus mutans count in saliva of pregnant women: A randomized controlled trial. Ann. King Edward Med. Univ. 24(4), 957–960 (2018).
Jaramillo, A., Arce, R., Contreras, A. & Herrera, J. A. Effect of periodontal therapy on the subgingival microbiota in preeclamptic patients. Biomedica 32, 233–238 (2012).
Page, M. J. et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Int. J. Surg. https://doi.org/10.1016/j.ijsu.2021.105906 (2021).
Higgins, J. P. T. et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343, d5928. https://doi.org/10.1136/bmj.d5928 (2011).
Downs, S. H. & Black, N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J. Epidemiol. Community Health 52, 377–384. https://doi.org/10.1136/jech.52.6.377 (1998).
NIH. Quality Assessment Tool for Observational Cohort and Cross-Sectinal Studies National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-toolshttps://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
Guyatt, G. et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J. Clin. Epidemiol. 64, 383–394. https://doi.org/10.1016/j.jclinepi.2010.04.026 (2011).
Guyatt, G. H. et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336, 924–926. https://doi.org/10.1136/bmj.39489.470347.AD (2008).
Kornman, K. S. & Loesche, W. J. The subgingival microbial flora during pregnancy. J. Periodontal Res. 15, 111–122 (1980).
Muramatsu, Y. & Takaesu, Y. Oral health status related to subgingival bacterial flora and sex hormones in saliva during pregnancy. Bull. Tokyo Dent. Coll. 35, 139–151 (1994).
Yokoyama, M. et al. Relationship between Campylobacter rectus and periodontal status during pregnancy. Oral Microbiol. Immunol. 23, 55–59 (2008).
Carrillo-de-Albornoz, A., Figuero, E., Herrera, D. & Bascones-Martinez, A. Gingival changes during pregnancy: II. Influence of hormonal variations on the subgingival biofilm. J. Clin. Periodontol. 37, 230–240. https://doi.org/10.1111/j.1600-051X.2009.01514.x (2010).
Basavaraju, A., Durga, V. S. & Vanitha, B. Variations in the oral anaerobic microbial flora in relation to pregnancy. J. Clin. Diagnostic Res JCDR 6, 1489–1491. https://doi.org/10.7860/jcdr/2012/4609.2540 (2012).
Machado, F. C., Cesar, D. E., Assis, A. V., Diniz, C. G. & Ribeiro, R. A. Detection and enumeration of periodontopathogenic bacteria in subgingival biofilm of pregnant women. Braz. Oral Res. 26, 443–449. https://doi.org/10.1590/s1806-83242012000500011 (2012).
Fujiwara, N. et al. Significant increase of oral bacteria in the early pregnancy period in Japanese women. J. Investigative Clin. Dentistry 8, e12189 (2017).
Rio, R. et al. Oral yeast colonization throughout pregnancy. Medicina Oral. Patol. Oral y Cirugia Bucal 22, E144–E148. https://doi.org/10.4317/medoral.21413 (2017).
Lin, W. et al. Ecological shifts of supragingival microbiota in association with pregnancy. Front. Cell Infect. Microbiol. 8, 24. https://doi.org/10.3389/fcimb.2018.00024 (2018).
Xiao, J. et al. Oral health and Candida carriage in socioeconomically disadvantaged US pregnant women. BMC Pregnancy Childbirth 19, 480. https://doi.org/10.1186/s12884-019-2618-7 (2019).
Aikulola, O. O., Okoje, V. N. & Adesina, O. A. Comparative study of oral health and microbial flora in pregnant and non-pregnant women in Ibadan, Nigeria. Afr. J. Biomed. Res. 23, 31–35 (2020).
Huang, Z. et al. Impact of periodonto-pathogenic microbiota and sociodemographic variables on periodontal status during pregnancy and postpartum period. Oral Health Prev. Dent. 18, 855–864. https://doi.org/10.3290/j.ohpd.a45355 (2020).
Sparvoli, L. G. et al. Women’s multisite microbial modulation during pregnancy. Microb. Pathog. https://doi.org/10.1016/j.micpath.2020.104230 (2020).
Wagle, M., Basnet, P., Vartun, Å., Trovik, T. A. & Acharya, G. Oxidative stress levels and oral bacterial milieu in the saliva from pregnant vs non-pregnant women. BMC Oral Health 20, 245. https://doi.org/10.1186/s12903-020-01230-3 (2020).
Dasanayake, A. P., Li, Y. H., Wiener, H., Ruby, J. D. & Lee, M. J. Salivary Actinomyces naeslundii genospecies 2 and Lactobacillus casei levels predict pregnancy outcomes. J. Periodontol. 76, 171–177. https://doi.org/10.1902/jop.2005.76.2.171 (2005).
Adriaens, L. A., Alessandri, R., Spoerri, S., Lang, N. P. & Persson, G. R. Does pregnancy have an impact on the subgingival microbiota?. J. Periodontol. 80, 72–81. https://doi.org/10.1902/jop.2009.080012 (2009).
Martínez-Pabón, M. C., Martínez Delgado, C. M., López-Palacio, A. M., Patiño-Gómez, L. M. & Arango-Pérez, E. A. Características fisicoquímicas y microbiológicas de la saliva durante y después del embarazo. Revista de Salud Pública 16, 128–138 (2014).
Okoje-Adesomoju, V. N., Ifesanya, J. U. & Alonge, T. O. Antimicrobial susceptibility pattern of oral microbial isolates among pregnant women in Ibadan South-East local government area, Nigeria. Afr. J. Biomed. Res. 18, 29–35 (2015).
Machado, F. C., Cesar, D. E., Morais Apolonio, A. C., Ribeiro, L. C. & Ribeiro, R. A. Longitudinal study on clinical and microbial analysis of periodontal status in pregnancy. Braz. Oral Res. https://doi.org/10.1590/1807-3107BOR-2016.vol30.0087 (2016).
Goltsman, D. S. A. et al. Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome. Genome Res. 28, 1467–1480. https://doi.org/10.1101/gr.236000.118 (2018).
de Souza Massoni, R. S. et al. Correlation of periodontal and microbiological evaluations, with serum levels of estradiol and progesterone, during different trimesters of gestation. Sci. Rep. https://doi.org/10.1038/s41598-019-48288-w (2019).
Dunlop, A. L. et al. Stability of the vaginal, oral, and gut microbiota across pregnancy among African American women: The effect of socioeconomic status and antibiotic exposure. PeerJ 7, e8004. https://doi.org/10.7717/peerj.8004 (2019).
Brambilla, E. et al. Caries prevention during pregnancy: Results of a 30-month study. J. Am. Dent. Assoc. 129, 871–877. https://doi.org/10.14219/jada.archive.1998.0351 (1998).
Mitchell-Lewis, D., Engebretson, S. P., Chen, J., Lamster, I. B. & Papapanou, P. N. Periodontal infections and pre-term birth: Early findings from a cohort of young minority women in New York. Eur. J. Oral. Sci. 109, 34–39. https://doi.org/10.1034/j.1600-0722.2001.00966.x (2001).
Offenbacher, S. et al. Effects of periodontal therapy during pregnancy on periodontal status, biologic parameters, and pregnancy outcomes: A pilot study. J. Periodontol. 77, 2011–2024. https://doi.org/10.1902/jop.2006.060047 (2006).
Novak, M. J. et al. Periodontal bacterial profiles in pregnant women: Response to treatment and associations with birth outcomes in the obstetrics and periodontal therapy (OPT) study. J. Periodontol. 79, 1870–1879. https://doi.org/10.1902/jop.2008.070554 (2008).
Escalante-Medina, R. P., Asmat-Abanto, A. S. & Ruiz-Barrueto, M. A. Efecto de una Pasta Dental Comercial Conteniendo Xilitol Sobre el Recuento de Streptococcus mutans en Saliva de Gestantes: Ensayo Clínico Controlado Aleatorizado Streptococcus mutans in saliva of pregnant women: Randomized controlled clinical trial. Int. J. Odontostomatol. 13, 316–320 (2019).
Hasegawa, K. et al. Associations between systemic status, periodontal status, serum cytokine levels, and delivery outcomes in pregnant women with a diagnosis of threatened premature labor. J. Periodontol. 74, 1764–1770. https://doi.org/10.1902/jop.2003.74.12.1764 (2003).
Lin, D., Moss, K., Beck, J. D., Hefti, A. & Offenbacher, S. Persistently high levels of periodontal pathogens associated with preterm pregnancy outcome. J. Periodontol. 78, 833–841. https://doi.org/10.1902/jop.2007.060201 (2007).
Durand, R., Gunselman, E. L., Hodges, J. S., DiAngelis, A. J. & Michalowicz, B. S. A pilot study of the association between cariogenic oral bacteria and preterm birth*. Oral Dis. 15, 400–406. https://doi.org/10.1111/j.1601-0825.2009.01559.x (2009).
Hasegawa-Nakamura, K. et al. The possible mechanism of preterm birth associated with periodontopathic Porphyromonas gingivalis. J. Periodontal. Res. 46, 497–504. https://doi.org/10.1111/j.1600-0765.2011.01366.x (2011).
Sadeghi, R., Rabiee, M., Saderi, H. & Jafari, M. The relationship between salivary bacterial flora and adverse pregnancy outcomes. Tehran Univ. Med. J. 69, 49–54 (2011).
Hassan, K. S., El Tantawi, M. M., Alagl, A. S., Alnimr, A. M. & Haseeb, Y. A. Sensitivity and specificity of subgingival bacteria in predicting preterm birth—A pilot cohort study. Int. J. Health Sci. IJHS 10, 532–541 (2016).
Matilde Usin, M. et al. Association between maternal periodontitis and preterm and/or low birth weight infants in normal pregnancies. J. Maternal Fetal Neonatal Med. 29, 115–119. https://doi.org/10.3109/14767058.2014.987751 (2016).
Gomez, L. A. et al. Porphyromonas gingivalis placental atopobiosis and inflammatory responses in women with adverse pregnancy outcomes. Front. Microbiol. https://doi.org/10.3389/fmicb.2020.591626 (2020).
Ye, C. et al. The periodontopathic bacteria in placenta, saliva and subgingival plaque of threatened preterm labor and preterm low birth weight cases: A longitudinal study in Japanese pregnant women. Clin. Oral Investig. 24, 4261–4270. https://doi.org/10.1007/s00784-020-03287-4 (2020).
Ye, C. et al. The relationship between the anti-Porphyromonas gingivalis immunoglobulin G subclass antibody and small for gestational age delivery: A longitudinal study in pregnant Japanese women. Int. Dent. J. 70, 296–302. https://doi.org/10.1111/idj.12548 (2020).
Ye, C. et al. Unculturable and culturable periodontal-related bacteria are associated with periodontal inflammation during pregnancy and with preterm low birth weight delivery. Sci. Rep. 10, 15807. https://doi.org/10.1038/s41598-020-72807-9 (2020).
León, R. et al. Detection of Porphyromonas gingivalis in the amniotic fluid in pregnant women with a diagnosis of threatened premature labor. J. Periodontol. 78, 1249–1255. https://doi.org/10.1902/jop.2007.060368 (2007).
Santa Cruz, I., Herrera, D., Martin, C., Herrero, A. & Sanz, M. Association between periodontal status and pre-term and/or low-birth weight in Spain: Clinical and microbiological parameters. J. Periodontal Res. 48, 443–451. https://doi.org/10.1111/jre.12024 (2013).
Tellapragada, C. et al. Prevalence of clinical periodontitis and putative periodontal pathogens among South Indian pregnant women. Int. J. Microbiol. 2014, 420149. https://doi.org/10.1155/2014/420149 (2014).
Lima, D. P. et al. Occurrence of socransky red complex in pregnant women with and without periodontal disease. Oral Health Prev. Dent. 13, 169–176. https://doi.org/10.3290/j.ohpd.a32989 (2015).
Lu, H. et al. Putative periodontopathic bacteria and herpesviruses in pregnant women: A case–control study. Sci. Rep. 6, 27796. https://doi.org/10.1038/srep27796 (2016).
Yang, I., Knight, A. K., Dunlop, A. L. & Corwin, E. J. Characterizing the subgingival microbiome of pregnant African American women. J. Obstet. Gynecol. Neonatal. Nurs. 48, 140–152. https://doi.org/10.1016/j.jogn.2018.12.003 (2019).
Balan, P. et al. Subgingival microbiota during healthy pregnancy and pregnancy gingivitis. JDR Clin. Trans. Res. https://doi.org/10.1177/2380084420948779 (2020).
Tanneeru, S., Mahendra, J. & Shaik, M. V. Evaluation of microflora (viral and bacterial) in subgingival and placental samples of pregnant women with preeclampsia with and without periodontal disease: A cross-sectional study. J. Int. Soc. Prev. Community Dent. 10, 171–176. https://doi.org/10.4103/jispcd.JISPCD_341_19 (2020).
Dasanayake, A. P. et al. Periodontal pathogens and gestational diabetes mellitus. J. Dent. Res. 87, 328–333. https://doi.org/10.1177/154405910808700421 (2008).
Ganiger, K., Sridharan, S., Rahul, A. & Satyanarayana, A. Quantitative analysis of key periodontopathic bacteria in gestational diabetic and non-diabetic women. J. Diabetes Metab. Disord. 18, 363–369. https://doi.org/10.1007/s40200-019-00420-3 (2019).
Yao, H., Xu, D., Zhu, Z. & Wang, G. Gestational diabetes mellitus increases the detection rate and the number of oral bacteria in pregnant women. Medicine https://doi.org/10.1097/md.0000000000014903 (2019).
Crusell, M. K. W. et al. Gestational diabetes and the human salivary microbiota: A longitudinal study during pregnancy and postpartum. BMC Pregnancy Childbirth https://doi.org/10.1186/s12884-020-2764-y (2020).
Xu, Y. et al. Differential intestinal and oral microbiota features associated with gestational diabetes and maternal inflammation. Am. J. Physiol. Endocrinol. Metab. 319, E247–E253. https://doi.org/10.1152/ajpendo.00266.2019 (2020).
Li, X. et al. The oral microbiome of pregnant women facilitates gestational diabetes discrimination. J. Genet. Genom. https://doi.org/10.1016/j.jgg.2020.11.006 (2021).
Contreras, A. et al. Periodontitis is associated with preeclampsia in pregnant women. J. Periodontol. 77, 182–188. https://doi.org/10.1902/jop.2006.050020 (2006).
Herrera, J. A. et al. Periodontal disease severity is related to high levels of C-reactive protein in pre-eclampsia. J. Hypertens. 25, 1459–1464. https://doi.org/10.1097/HJH.0b013e3281139ea9 (2007).
Ávila, W. S. et al. Periodontal disease in pregnant patients with rheumatic valvular disease—Clinical and microbiological study. Arq. Bras. Cardiol. 96, 307–311. https://doi.org/10.1590/S0066-782X2011005000034 (2011).
Merglova, V., Hecova, H., Stehlikova, J. & Chaloupka, P. Oral health status of women with high-risk pregnancies. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 156, 337–341. https://doi.org/10.5507/bp.2012.045 (2012).
Stadelmann, P. F. et al. Increased periodontal inflammation in women with preterm premature rupture of membranes. Clin. Oral. Investig. 19, 1537–1546. https://doi.org/10.1007/s00784-014-1371-6 (2015).
Paropkari, A. D., Leblebicioglu, B., Christian, L. M. & Kumar, P. S. Smoking, pregnancy and the subgingival microbiome. Sci. Rep. 6, 30388. https://doi.org/10.1038/srep30388 (2016).
Jaiman, G., Nayak, P. A., Sharma, S. & Nagpal, K. Maternal periodontal disease and preeclampsia in Jaipur population. J. Indian Soc. Periodontol. 22, 50–54. https://doi.org/10.4103/jisp.jisp_363_15 (2018).
Parthiban, P. S. et al. Association between specific periodontal pathogens, Toll-like receptor-4, and nuclear factor-κB expression in placental tissues of pre-eclamptic women with periodontitis. J. Investig. Clin. Dent. https://doi.org/10.1111/jicd.12265 (2018).
Tuominen, H., Rautava, S., Syrjanen, S., Collado, M. C. & Rautava, J. HPV infection and bacterial microbiota in the placenta, uterine cervix and oral mucosa. Sci. Rep. https://doi.org/10.1038/s41598-018-27980-3 (2018).
Tanneeru, S., Mahendra, J., Mahaboob Vali, S. K. & Mahendra, L. Red complex bacteria in preeclamptic pregnant women with and without periodontal disease: A cross sectional microbiological study. Res. J. Pharm. Biol. Chem. Sci. 11, 81–88. https://doi.org/10.33887/rjpbcs/2020.11.1.13 (2020).
Wang, B. et al. Oral and intestinal microbial features in pregnant women with hypothyroidism and their correlations with pregnancy outcomes. Am. J. Physiol. Endocrinol. Metab. 319, E1044–E1052. https://doi.org/10.1152/ajpendo.00234.2020 (2020).
Arweiler, N. B. & Netuschil, L. The oral microbiota. Adv. Exp. Med. Biol. 902, 45–60. https://doi.org/10.1007/978-3-319-31248-4_4 (2016).
Hashim, R. & Akbar, M. Gynecologists’ knowledge and attitudes regarding oral health and periodontal disease leading to adverse pregnancy outcomes. J. Int. Soc. Prev. Community Dent. 4, S166–S172. https://doi.org/10.4103/2231-0762.149028 (2014).
Toygar, H. U., Seydaoglu, G., Kurklu, S., Guzeldemir, E. & Arpak, N. Periodontal health and adverse pregnancy outcome in 3576 Turkish women. J. Periodontol. 78, 2081–2094. https://doi.org/10.1902/jop.2007.070092 (2007).
Daly, C. G., Mitchell, D. H., Highfield, J. E., Grossberg, D. E. & Stewart, D. Bacteremia due to periodontal probing: A clinical and microbiological investigation. J. Periodontol. 72, 210–214. https://doi.org/10.1902/jop.2001.72.2.210 (2001).
Davenport, E. S. et al. Maternal periodontal disease and preterm low birthweight: Case–control study. J. Dent. Res. 81, 313–318. https://doi.org/10.1177/154405910208100505 (2002).
Madianos, P. N., Bobetsis, G. A. & Kinane, D. F. Is periodontitis associated with an increased risk of coronary heart disease and preterm and/or low birth weight births?. J. Clin. Periodontol. 29(Suppl 3), 22–36. https://doi.org/10.1034/j.1600-051x.29.s3.2.x (2002) (discussion 37–28).
Zhang, X., Lu, E., Stone, S. L. & Diop, H. Dental cleaning, community water fluoridation and preterm birth, Massachusetts: 2009–2016. Matern. Child Health J. 23, 451–458. https://doi.org/10.1007/s10995-018-2659-y (2019).
Merchant, A. T., Sutherland, M. W., Liu, J., Pitiphat, W. & Dasanayake, A. Periodontal treatment among mothers with mild to moderate periodontal disease and preterm birth: Reanalysis of OPT trial data accounting for selective survival. Int. J. Epidemiol. 47, 1670–1678. https://doi.org/10.1093/ije/dyy089 (2018).
Bassols, J. et al. Gestational diabetes is associated with changes in placental microbiota and microbiome. Pediatr. Res. 80, 777–784. https://doi.org/10.1038/pr.2016.155 (2016).
Zheng, J. et al. The placental microbiota is altered among subjects with gestational diabetes mellitus: A pilot study. Front. Physiol. 8, 675. https://doi.org/10.3389/fphys.2017.00675 (2017).
Novak, K. F., Taylor, G. W., Dawson, D. R., Ferguson, J. E. 2nd. & Novak, M. J. Periodontitis and gestational diabetes mellitus: Exploring the link in NHANES III. J. Public Health Dent. 66, 163–168. https://doi.org/10.1111/j.1752-7325.2006.tb02574.x (2006).
Xiong, X., Buekens, P., Vastardis, S. & Pridjian, G. Periodontal disease and gestational diabetes mellitus. Am. J. Obstet. Gynecol. 195, 1086–1089. https://doi.org/10.1016/j.ajog.2006.06.035 (2006).
New York State Department of Health Practice Guidelines-Oral Health Care during Pregnancy and Early Childhood (2006). Available at: https://www.health.ny.gov/publications/0824.pdf.
Oral Health Care During Pregnancy: A National Consensus Statement. Available at: https://www.mchoralhealth.org/PDFs/OralHealthPregnancyConsensus.pdf.
Gold, J. & Tomar, S. L. Interdisciplinary community-based oral health program for women and children at WIC. Matern. Child Health J. 22, 1617–1623. https://doi.org/10.1007/s10995-018-2557-3 (2018).
Dr. Xiao’s work is supported by the National Institute for Dental and Craniofacial Research K23 DE027412. Dr. Wu’s work is supported by Grant from the National Science Foundation NSF-CCF-1934962. The funding agencies had no role in the study design, data collection, analyses, decision to publish, or preparation of the manuscript. We greatly appreciate Ms. Lorraine Porcello for her support to the updated article search.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Jang, H., Patoine, A., Wu, T.T. et al. Oral microflora and pregnancy: a systematic review and meta-analysis. Sci Rep 11, 16870 (2021). https://doi.org/10.1038/s41598-021-96495-1
This article is cited by
Identification of the specific microbial community compositions in saliva associated with periodontitis during pregnancy
Clinical Oral Investigations (2022)