Periodontal infection and preterm low

birth weight infants

Submitted by :
Tamanna
(intern 2006 batch)
 Introduction
 Preterm low-birth weight (PLBW), as defined by the 29th
World Health assembly in 1976, is a birth weight of less
than 2500 g with a gestational age of less than 37 weeks.
 very preterm -Delivery at less than 32 weeks,

 Extremely preterm -delivery at less than 28 weeks .

 Birth weights are considered to be:

 low if <2500 g,

 very low if <1500 g,

 extremely low if <1000 g.

 Causes of PLBW
 Premature rupture of membrane.
 Preterm labour
 Risk factors
 Maternal age <17 yrs or >34 yrs
 genetic factors
 the use of alcohol
 poor prenatal care
 poor maternal nutrition
 urinary tract infection
 smoking and
 low socioeconomic status
• Recently periodontal infection has been identified
as a risk factor for PLBW
 Mechanism
 Bacterial vaginosis- it is a gram
negative, predominantly anaerobic
infection of the vagina, usually diagnosed
from clinical signs and symptoms.
 It is a relatively common condition that
occurs in about 10 % of all pregnancies.
 It may ascend from vagina to the cervix
and even result in inflammation of the
maternal- fetal membranes
(chorioamnionitis)
 Extending beyond the membranes,
the organisms may appear in the
amniotic fluid compartment that is
shared with the fetal lungs and or
may involve placental tissues and
result in exposure to the fetus via
the blood stream.
 It appears that inflammation of the
uterus and membranes represent a
common effector mechanism that
results in preterm birth, and thus,
either clinical or subclinical infection
is a likely stimulus for increased
inflammation.
How periodontal infection leads to
PLBW1
 Microorganisms along with their
virulence factors have the capability
to disseminate:
• Directly
• Indirectly
Posing a threat to the feto-placental
unit.
 Indirect mechanism
A periodontal infection may influence
the pregnancy outcomes by
providing a source of gram-negative
anaerobic organisms and bacterial
components such as
lipopolysaccharides .
 These can trigger the release of
immune modulators such as PGE2
and TNF-α, which are normally
involved in normal parturition, and in
turn, may influence the course of
pregnancy
Entry of inflammatory products (PgE2, Il-6, TNF- α),
endotoxin, and/or periodontal bacteria into the bloodstream
and their translocation to the fetus and decidual tissues
 Periodontal disease is a low-grade
infection dominated by Gram-
negative anaerobic and
microaerophilic bacteria resulting in
local and systemic inflammatory and
immune responses.
 Inflamed periodontal tissues serve as
reservoirs for periodontal pathogens,
endotoxins, and inflammatory
mediators.
 Hence, maternal periodontal disease may be
connected with preterm delivery through
mechanisms involving inflammatory
mediators or a direct bacterial assault on the
amnion.
 Upregulation of proinflammatory cytokines
resulting from the normal host response to an
infectious agent may represent the key
mechanism linking periodontal disease to
PLBW.
 Microbiological products such as endotoxin
will trigger a host immune response, causing
both local inflammation and activation of
soluble proinflammatory mediators such as IL-
1, TNF-alpha, and MMPs.
 These inflammatory markers have been shown
to cross the placental barrier and to cause fetal
toxicity, resulting in preterm delivery and low-
birth-weight babies.
 Therefore, fetal exposure to oral pathogens, as
evidenced by an IgM response, is associated
with preterm birth, and the risk for preterm
birth is greatest among fetuses that
demonstrate an inflammatory response.
 Other studies have also provided evidence that
distant, low-grade oral infection might trigger
inflammation of the human maternal-fetal unit
in a manner analogous to that seen with
bacterial vaginosis
 Indirect mechanism

microorganisms

Triggering factors

TNF α , cytokines etc.

Premature labour
Direct mechanism
 Bacterial invasion of the choriodecidual space can
activate the fetal membranes or trigger the maternal
immune system to produce a variety of cytokines and
growth factors.
 The combination of increased fetal adrenal cortisol
production, increased prostaglandin production, the
release of MMPs, and increased cytokines and
chemokines may lead to myometrial contractions,
membrane rupture, cervical ripening, and preterm
delivery.
 Furthermore, the inflammatory burden results
in distress and fetal growth restriction.
 Madianos et al. extended the work of
Socransky et al.,shifting the focus to examine
the potential role of maternal infection with
specific organisms within both the “orange”
and “red” complexes, because these are the
complexes most strongly correlated to severe
periodontal disease
 The highest rate of prematurity (66.7%) was
observed among those mothers without a
protective “red” complex IgG response
coupled with a fetal immunoglobulin M (IgM)
response to “orange” complex microbes.
 These data support the concept that maternal
periodontal infection in the absence of a
protective maternal antibody response is
associated with the systemic distribution of
oral organisms to the fetus, resulting in
preterm birth.
 The high prevalence of elevated fetal IgM to
C. rectus among premature infants raises the
possibility that this specific maternal oral
pathogen may serve as a primary fetal
infectious agent eliciting preterm birth. More
recent findings support this claim: when
subgingival bacteria were evaluated together,
P. micros and C. rectus were found to play a
significant role in increasing the risk for
PLBW.
 Recently, F. nucleatum, a gram-negative
anaerobe ubiquitous to the oral cavity, was
isolated from the amniotic fluid, placenta, and
chorioamnionic membranes of women
delivering prematurely.2 To test the strength of
this finding, pregnant mice were infected with
F. nucleatum, resulting in premature delivery,
stillbirths, and non sustained live births .(2)
 The bacterial infection was restricted inside
the uterus, without spreading systemically,
although invasion of the endothelial cells
lining the blood vessels was also observed.
The bacteria then crossed the endothelium,
proliferated in surrounding tissues, and finally
spread to the amniotic fluid. This pattern of
infection paralleled that observed in humans
Direct mechanism

microorganisms

Hematogenous spread
Fetoplacental unit
infection

chorioamnionitis

Premature rupture of
membrane
Proposed biological model of periodontal disease and preterm low birth
weight .
 Review of literature
 Offenbacher et al.(3)were the first to report a link
between poor maternal periodontal health and adverse
pregnancy outcomes, including preterm birth, in
humans. They compared the periodontal conditions of
women who had delivered a low-birth-weight infant
with women who had given birth to a full-term,
normal-weight infant.
 Women with 60 or more sites with clinical
attachment loss of ≥3 mm were much
more likely than periodontally healthy
women to experience an adverse
pregnancy outcome
Case – No No. findings Obstetrcal
control . of of Def of
study sbj cntr case
l
Offenba- 93 31 Cases had significantly Birth weight <2500 g
cher et more (3.1 mm vs. and PTB <37 weeks
Al 1996(3) 2.8 mm) and extensive or PTL or PROM
CAL than controls
PTB <37, <35, and
Significant odds ratios <32 weeks
Jeffcoat NS NS (comparing severe
et al. 2001
periodontitis (90+ sites
(1,313
with CAL ≥3 mm) to
patients) (4)
health (<3 sites with
CAL >3 mm)) for PTB
<37 (4.5), <35 (5.3)
and <32 weeks (7.1)
BOP, bleeding on probing; CAL, clinical attachment loss; CPITN, Community Periodontal
Index of Treatment Needs; NS, not specified; PD, probing depth; PROM, premature rupture
of membranes; PTB, preterm birth; PTL, preterm labor; SPTB, spontaneous preterm birth
Cohort No. No. findings Periodontitis
studies Expo- unex exposure definition
sed posd
Offenbacher 735 285 PTB (<37 weeks) Moderate/severe
(mild to rate significantly disease: 15+ sites with
et al. 2006 severe higher in moderate- PD >4 mm Healthy: all
disease) to-severely diseased PD ≤4 mm with no BOP
(3)
subjects (28.6%) at sites with PD = 3 or
than healthy 4 mm Mild disease:
controls (11.2%). intermediate
Rate in mildly phenotypes
diseased was 19.0%

11 PTB (<37 week) Disease: 1+ sites with

25
and/or LBW rates PD ≥5 mm in each
Dörtbudak higher in diseased quadrant and high
et al. (5/11) than in levels of putative
2005(5) healthy subjects microbial pathogens
(1/25) Health: not specified

BL, bleeding scores; BOP, bleeding on probing; CAL, clinical attachment loss; PD, probing
depth; PTB, preterm birth; PTLBW, preterm low birth weight
 Significance
 Expectant mothers should be
counseled in the importance of oral
health.
 Regular dental examinations for all
pregnant patients
 Aggressive periodontal therapy for
infections
 Frequent reinforcement of oral hygiene
and dental care by medical providers
 Preventive oral care services should be
provided as early in pregnancy as
possible.
 If examination indicates a need for
periodontal therapy, these
procedures should be scheduled
early in the 2nd trimester.
 The presence of acute infection,
abscess, or other potentially
disseminating sources of sepsis may
warrant prompt intervention,
irrespective of the stage of
pregnancy.
 Mitchell-Lewis et al. (6) found that women
who received dental cleanings during
pregnancy were less likely than untreated
women to give birth to a preterm, low-
birth-weight infant (13.5% vs. 18.9%,
P = 0.36). Lopez et al. (7) reported that a
regimen of scaling, chlorhexidine
mouthrinses, and frequent maintenance
care in women with gingivitis reduced the
rate of preterm birth/low birth weight
when compared to women with untreated
periodontitis (2.5% vs. 8.6%,
P < 0.001).
 Referrences
1. Gibbs RS. The relationship between infections and
adverse pregnancy outcomes: an overview. Ann
Periodontol 2001: 6: 153–163.
2. Hill GB: investigating the source of amniotic fluid
isolates of fusobacteria , clin infect dis 16(suppl
4):423, 1993
3. Offenbacher S, Katz V, Fertik G, Collins J, Boyd D,
Maynor G, McKaig R, Beck J. Periodontal infection
as a possible risk factor for preterm low birth
weight. J Periodontol 1996: 67: 1103–1113.
4. Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP,
Goldenberg RL, Hauth JC. Periodontal infection and
preterm birth: results of a prospective study. J Am Dent
Assoc 2001: 132: 875–880.
5. Dortbudak O, Eberhardt R, Ulm M, Persson GR.
Periodontitis, a marker of risk in pregnancy for preterm
birth. J Clin Periodontol 2005: 32: 45–52.
6. Mitchell-Lewis D, Engebretson SP, Chen J, Lamster IB,
Papapanou PN. Periodontal infections and pre-term
birth: early findings from a cohort of young minority
women in New York. Eur J Oral Sci 2001: 109: 34–39.
7. Lopez NJ, Da Silva I, Ipinza J, Gutierrez J.
Periodontal therapy reduces the rate of preterm
low birth weight in women with pregnancy-
associated gingivitis. J Periodontol 2005: 76:
2144–2153.
8. Douglass C. Does periodontal disease relate to
preterm low birth weight babies? The Colgate Oral
Care Report 2002;11:1-3.