Fetal immune response to oral pathogens and risk of preterm birth

doi:10.1016/j.ajog.2005.05.050

American Journal of Obstetrics and Gynecology

Volume 193, Issue 3, Supplement, September 2005, Pages 1121-1126

https://doi.org/10.1016/j.ajog.2005.05.050 Get rights and content

Objective

The purpose of this study was to determine the relationship between fetal inflammatory and immune responses to oral pathogens and risk for preterm birth.

Study design

Six hundred and forty umbilical cord blood specimens were prospectively collected. Cord serum levels of C-reactive protein, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, Prostaglandin E₂, and 8-isoprostane were determined by enzyme-linked immunosorbent assay and categorized as > median (high) versus ≤ median (low). Presence of fetal immunoglobulin M (IgM) antibody against oral pathogens was determined by checkerboard immunoblot assay; detection of ≥1 oral pathogen specific antibody was categorized as positive. Preterm birth was defined as spontaneous delivery at <35 weeks. Chi-square analysis was used to determine association between cord serum mediator or IgM category and preterm birth. Odds ratios (OR) for preterm birth were calculated, stratified by mediator and IgM category.

Results

Of 640 births, 48 (7.5%) delivered preterm. Preterm birth rates were higher if categorized as high versus low 8-isoprostane or TNF-α (23 vs 5%, P < .001 and 10 vs 4%, P < .01, respectively). Preterm birth rates were also higher if categorized as IgM positive versus negative (10.6 vs 5.8%, P = .04). The joint effects of fetal IgM seropositivity, detectable C-reactive protein, or high 8-isoprostane, PGE₂, or TNF-α resulted in significantly increased risk for preterm birth (adjusted OR [95% CI]: 6.0 [2.2-16.5], 4.3 [1.6-11.5], 4.1 [1.5-11.6], and 7.6 [2.3-20.8], respectively).

Conclusion

Fetal exposure to oral pathogens evidenced by an IgM response is associated with preterm birth, and the risk for preterm birth is greatest among fetuses that also demonstrate an inflammatory response.

Section snippets

Materials and methods

The Oral Conditions and Pregnancy study was a prospective, observational study designed to study maternal oral health in pregnancy and association with adverse pregnancy outcomes. Detailed methodology has been published elsewhere.¹ Briefly, 1115 women were enrolled at <26 weeks' gestation. A systematic dental examination, maternal oral, vaginal, and blood specimens were collected and demographic and medical data recorded. At delivery, 10 to 20 mL of mixed arterial and venous umbilical cord was

Results

Of 1115 women enrolled in the Oral Conditions and Pregnancy study, 640 (57.4%) had umbilical cord blood collected and complete information available. Of these 640, 48 (7.5%) delivered preterm (<35 weeks). The mean, median, and range of serum inflammatory markers for the study cohort, and stratified by delivery <35 or ≥35 weeks' are shown in Table I. Increasing levels of umbilical cord serum C-reactive protein and TNF-α were associated with delivery <35 weeks' gestation (OR, 95% CI 1.8, 1.3-2.5

Comment

Our study demonstrates that fetal exposure to oral pathogens evidenced by an IgM response is associated with preterm birth at <35 weeks. Fetuses with high TNF-α or 8-isoprostane levels also demonstrate an increased risk for preterm birth, independent of fetal IgM response. Previous studies have demonstrated that a fetal inflammatory response, evidenced by umbilical cord levels of TNF-α, IL-6, or C-reactive protein, is associated with preterm birth.10, 11, 12 Our study is the first to

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Periodontal infection and preterm birth: results of a prospective study
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Cited by (76)

Oral status of pregnant women and consequences on pregnancy
2023, Sages-Femmes
Les femmes enceintes sont insuffisamment sensibilisées à l’importance d’une bonne santé bucco-dentaire pour elles-mêmes et pour leur futur enfant. Les professionnels de santé qui les accompagnent durant leur grossesse, notamment les sages-femmes, doivent les inciter à réaliser un bilan de prévention et à se faire suivre par un chirurgien-dentiste.
Pregnant women are not sufficiently aware of the importance of good oral health for themselves and their future child. The health professionals who accompany them during their pregnancy, especially midwives, must encourage them to have a preventive check-up and to be followed by a dental surgeon.
Tooth and pregnancy, a public health issue
2019, Presse Medicale
La grossesse est un moment particulièrement à risque du point de la santé parodontale et bucco-dentaire.
Les principales pathologies rencontrées sont l’apparition et/ou l’aggravation de lésions carieuses ainsi que les parodontopathies gravidiques telles que la gingivite, les épulis ou la parodontite gravidique.
Il existe un manque de connaissance des professionnels de santé et de leurs patientes d’une part sur le lien entre une mauvaise hygiène bucco-dentaire et les répercussions sur la grossesse et d’autre part sur la faisabilité des soins bucco dentaires au cours de la grossesse.
Il existerait un lien entre maladie parodontale et l’augmentation du risque d’accouchement prématuré, d’enfants de petits poids de naissance et de pré-éclampsie.
Les soins parodontaux durant la grossesse permettraient de diminuer ce risque. En revanche, aucun lien n’a été mis en évidence à ce jour entre les soins bucco-dentaires réalisés au cours de la grossesse et la diminution du risque de prématurité ni même de pré-eclampsie.
L’anesthésie loco régionale et la réalisation de clichés radiologiques – y compris la radiographie panoramique dentaire – ne sont pas contre indiqués chez la femme enceinte.
Tous les soins parodontaux et bucco-dentaires peuvent être réalisés au cours de la grossesse et ceci quel que soit l’âge gestationnel.
Pregnancy is a particularly risky moment for periodontal and oral healthcare.
The main diseases encountered are the development or worsening of carious lesions and gestational periodontal diseases such as gingivitis, epulis or gestational periodontitis.
There is a lack of knowledge from health professionals and their patients, firstly on the link between poor oral hygiene and the impact on pregnancy, and secondly on the feasibility of oral care during pregnancy.
There is a link between periodontal diseases and the increase of premature delivery risk, child with low birth weight and pre-eclampsia.
Periodontal care during pregnancy would lower this risk. However, no link has been highlighted to date between oral care provided during pregnancy and the reduction of premature delivery or even of pre-eclampsia.
Loco-regional anaesthesia and taking x-ray images–even dental panoramic radiography–are not contraindicated for pregnant women.
All periodontal and oral care can be performed during pregnancy, at all gestational ages.
Effects of periodontal disease on systemic health
2019, Disease-a-Month
About one in two adults in the United States has periodontal disease. Chronic periodontitis is an oral disease affecting the supporting structures of the teeth leading to progressive loss of the attachment apparatus and bone around teeth. It is characterized by gingival pocket formation and/or gingival recession. The disease is initiated by bacteria and their components like lipopolysaccharide and causes a heightened host inflammatory response. This cascade of inflammatory response ultimately leads to an increased osteoclastic activity and bone loss. Individuals with periodontitis have increased systemic levels of acute phase proteins, plasma antibody levels, coagulation factor, total white blood cell count, neutrophils, C reactive protein (CRP), and cytokines such as INF- gamma (Interferon gamma), TNF-α (Tumor necrosis Factor- Alpha), IL (Interleukin)-1β, IL-2 and IL-6. As periodontitis works on the same chronic inflammation model seen in systemic diseases, there is sufficient evidence to suggest a bi-directional link between the two. This article summarizes the established associations between periodontal disease and systemic health.
Acute chorioamnionitis and funisitis: Definition, pathologic features, and clinical significance
2015, American Journal of Obstetrics and Gynecology
Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intraamniotic infection generally has been considered to be the cause of acute chorioamnionitis and funisitis; however, recent evidence indicates that “sterile” intraamniotic inflammation, which occurs in the absence of demonstrable microorganisms induced by “danger signals,” is frequently associated with these lesions. In the context of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient that favors the migration of neutrophils from the maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals that are released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and present in 3–5% of term placentas and in 94% of pacentas delivered at 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks of the fetal inflammatory response syndrome, a condition characterized by an elevation in the fetal plasma concentration of interleukin-6, and associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multiorgan fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults: a risk factor for short- and long-term complications (ie, sterile inflammation in fetuses, neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided.
Identification of a gene in Mycoplasma hominis associated with preterm birth and microbial burden in intraamniotic infection
2015, American Journal of Obstetrics and Gynecology
Microbial invasion of the amniotic cavity is associated with spontaneous preterm labor and adverse pregnancy outcome, and Mycoplasma hominis often is present. However, the pathogenic process by which M hominis invades the amniotic cavity and gestational tissues, often resulting in chorioamnionitis and preterm birth, remains unknown. We hypothesized that strains of M hominis vary genetically with regards to their potential to invade and colonize the amniotic cavity and placenta.
We sequenced the entire genomes of 2 amniotic fluid isolates and a placental isolate of M hominis from pregnancies that resulted in preterm births and compared them with the previously sequenced genome of the type strain PG21. We identified genes that were specific to the amniotic fluid/placental isolates. We then determined the microbial burden and the presence of these genes in another set of subjects from whom samples of amniotic fluid had been collected and were positive for M hominis.
We identified 2 genes that encode surface-located membrane proteins (Lmp1 and Lmp-like) in the sequenced amniotic fluid/placental isolates that were truncated severely in PG21. We also identified, for the first time, a microbial gene of unknown function that is referred to in this study as gene of interest C that was associated significantly with bacterial burden in amniotic fluid and the risk of preterm delivery in patients with preterm labor.
A gene in M hominis was identified that is associated significantly with colonization and/or infection of the upper reproductive tract during pregnancy and with preterm birth.
Association between maternal periapical lesions and brain inflammation in rat pups
2013, Archives of Oral Biology
Citation Excerpt :
Tumour necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 are commonly associated with oral infections involving both periodontal1–9 and periapical10,11 tissues.
The objective of this study was to determine whether the presence of maternal tooth periapical lesions was associated with foetal brain inflammation in a pregnant rat model.
Sprague–Dawley rats were divided into two groups: pregnant rats with induced periapical abscesses (E, n = 8) and sham-operated control pregnant rats (S, n = 8). The pulps of the first and second maxillary right molars had been exposed and the tooth left open to the oral environment for two weeks prior to initiation of the pregnancy. Following delivery of the pups (E, n = 99; S, n = 101), each pup was decapitated and the brain was removed and immediately frozen in liquid nitrogen. The tissues were solubilized in PBS containing a protease inhibitor, and norepinephrine (NE), IL-6, IL-1-β, TNF-α, and myelin basic protein (MBP) were determined by ELISA. Group means were compared by factorial analysis of variance, a post hoc Tukey test, and Pearson's correlation test. p < 0.05 was used to reject the null hypothesis.
E pups were significantly heavier than S pups. Brain tissue concentrations of IL-6, IL-1-β, and TNF-α were significantly higher and MBP and norepinephrine concentrations significantly lower in E pups than S pups. Concentrations of IL-6, TNF-α and IL-1-β were significantly correlated between E serum, pup birthweight, and E pup brain tissue. MBP, NE and IL-6 were significantly correlated within the brain tissues of E pups.
The data suggest that brain inflammation may be associated with maternal periapical inflammation. This association identifies a modifiable risk factor for adverse pregnancy outcomes.

View all citing articles on Scopus

Supported by K08 HD043284 (K. A. B.), R01 DE12453 (S. O.), and the University of North Carolina General Clinical Research Center grant RR00046.

Presented at the Twenty-Fifth Annual Meeting of the Society for Maternal Fetal Medicine, February 7-12, 2005, Reno, Nev.

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American Journal of Obstetrics and Gynecology

Objective

Study design

Results

Conclusion

Section snippets

Materials and methods

Results

Comment

References (18)

Maternal periodontal disease is associated with an increased risk for preeclampsia

Obstet Gynecol

Periodontal infection and preterm birth: results of a prospective study

J Am Dent Assoc

The tumor necrosis factor alpha and its soluble receptor profile in term and preterm parturition

Am J Obstet Gynecol

Antenatal microbiologic and maternal risk factors associated with prematurity

Am J Obstet Gynecol

The oral conditions and pregnancy study: periodontal status of a cohort of pregnant women

J Periodontol

A prospective study to investigate the relationship between periodontal disease and adverse pregnancy outcome

Br Dent J

Periodontal infection as a possible risk factor for preterm low birth weight

J Periodontol

The association between Porphyromonas gingivalis-specific maternal serum IgG and low birth weight

J Periodontol

Periodontal disease and upper genital tract inflammation in early spontaneous preterm birth

Obstet Gynecol

Cited by (76)

Oral status of pregnant women and consequences on pregnancy

Tooth and pregnancy, a public health issue

Effects of periodontal disease on systemic health

Acute chorioamnionitis and funisitis: Definition, pathologic features, and clinical significance

Identification of a gene in Mycoplasma hominis associated with preterm birth and microbial burden in intraamniotic infection

Association between maternal periapical lesions and brain inflammation in rat pups

Transactions of the Twenty-Fifth Annual Meeting of the Society for Maternal-Fetal MedicineFetal immune response to oral pathogens and risk of preterm birth

Objective

Study design

Results

Conclusion

Section snippets

Materials and methods

Results

Comment

Obstet Gynecol

J Am Dent Assoc

Am J Obstet Gynecol

Am J Obstet Gynecol

The oral conditions and pregnancy study: periodontal status of a cohort of pregnant women

J Periodontol

A prospective study to investigate the relationship between periodontal disease and adverse pregnancy outcome

Br Dent J

Periodontal infection as a possible risk factor for preterm low birth weight

J Periodontol

The association between Porphyromonas gingivalis-specific maternal serum IgG and low birth weight

J Periodontol

Periodontal disease and upper genital tract inflammation in early spontaneous preterm birth

Obstet Gynecol

Transactions of the Twenty-Fifth Annual Meeting of the Society for Maternal-Fetal Medicine
Fetal immune response to oral pathogens and risk of preterm birth