Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01142752 |
| Other study ID # |
KEK091/10 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
June 7, 2010 |
| Last updated |
August 2, 2016 |
| Start date |
November 2011 |
| Est. completion date |
May 2015 |
Study information
| Verified date |
August 2016 |
| Source |
University Hospital Inselspital, Berne |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Switzerland: Ethikkommission |
| Study type |
Observational
|
Clinical Trial Summary
The prevalence of preterm birth is not decreasing in the last decades despite of improving
health care. Intrauterine infections are important in the etiology of preterm birth but the
interconnection of systemic inflammation and preterm birth is not clear. Mechanisms of
preterm birth should be assessed as preterm birth is the major risk factor for morbidity and
mortality during birth, thus being important for the individual and regarding health costs.
No interventions will be carried out in this study.
Hypotheses:
1. There is a common etiology between oral and vaginal inflammation
2. Bacterial species are similar in vagina and oral cavity
3. There are similar oral and systemic immune reactions which provoke preterm birth
4. Inflammatory markers are found in pregnant women at risk and get back to normal post
partum In this matched case control study of pregnant women local, systemic and oral
inflammation markers and bacterial load are assessed to find out interconnections
between these body compartments to allow for explanation of the etiology of preterm
birth.
Description:
Vaginal, oral and systemic inflammation in preterm birth
1. Summary
The prevalence of preterm birth (PTB) is increasing. While intrauterine infections may
be the primary cause of PTB, remote infections may also be part of the aetiology and
risk for gestational complications. Predicting and identifying women at risk for
delivering preterm is difficult. Comprehensive studies are needed to study all
infectious and inflammatory processes that may be involved in birth complications.
Social, ethnic and behavioural risks are part of the factors involved. Thus,
case-control studies of infection in pregnancy must acknowledge and control for such
other factors.
The oral cavity provides a unique study model of periodontal infection and
inflammation. Gingivitis and periodontitis have been associated with an elevated risk
for PTB. A large entity of bacteria including both aerobic and anaerobic bacteria
competent to elicit a systemic hyper-inflammatory host immune response can be
identified in periodontal infection. Inflammation of the gingival tissues increases in
pregnancy. Knowledge obtained through studies of clinical parameters as well as studies
of bacteria and cytokines in oral, vaginal and blood samples in pregnant women at risk
for preterm birth would establish evidence-based background for successful clinical
strategies to prevent or reduce the risk for PTB.
The objectives of the present matched case-control study of pregnant women are to
investigate local and remote infection (microbiological analysis by culture, and
DNA-DNA checkerboard) and inflammation (cytokine assays in samples from vaginal and
oral samples), and routine clinical data in three groups of pregnant women:
I. Women medically considered at risk for and WITH actual preterm birth delivery
II. Women medically considered at risk for preterm birth delivery but who deliver
WITHOUT birth complications
III. Women with a normal uneventful pregnancy (control group)
The investigators aim to test the following hypotheses regarding associations between
oral infection and PTB:
I. There is a shared infectious aetiology between oral and vaginal infections (primary
outcome)
II. In women at risk for PTB the vaginal and oral bacterial microbiota are similar
III. There are similar systemic and/or local inflammatory responses (haematogenous
dissemination and bacteraemia, feto-maternal immune response) that can be induced by
vaginal and/or oral infection, contributing to PTB.
IV. Elevated inflammatory markers are found at the onset of symptoms in pregnant women
at risk for PTB and normalize after birth.
2. Current status in this field of research
2.1. Introduction
Preterm birth (PTB) is defined as delivery before 37 weeks of gestation and a birth
weight of < 2500 grams. PTB is the most important determinant of perinatal morbidity
and mortality. Among those born before 32 weeks of gestation many children will suffer
from lifelong sequelae of prematurity ranging from mild to severe developmental
disorders.
3. Detailed Research Plan
3.1. Scientific objectives (Aims)
The investigators aim to test the following hypotheses regarding associations between oral
infection and PTB:
I. There is a shared infectious aetiology between oral and vaginal infections (primary
outcome)
II. In women at risk for PTB the vaginal and oral bacterial microbiota are similar
III. There are similar systemic and/or local inflammatory responses (haematogenous
dissemination and bacteraemia, feto-maternal immune response) that can be induced by vaginal
and/or oral infection, contributing to PTB
IV. Elevated inflammatory markers are found at the onset of symptoms in pregnant women at
risk for PTB and normalize after birth
3.2. Patient grouping
The study design is a longitudinal, non-interventional case-control study of pregnant women
including (I) a control group of women with uneventful pregnancy
(II) a group of women medically considered at risk for PTB and actually delivering preterm
(III) a group of women medically considered at risk for PTB but with uneventful pregnancy.
Subjects will be examined at three time points (I) within 18-34 weeks of pregnancy when they
get symptomatic
(II) within two days after delivery and
(III) 4-6 weeks post-partum. This would allow the investigators to compare all examined
parameters between and within groups over the defined time frame.
Due to the medical inclusion criteria clinical medical/dental examinators cannot be blinded.
At the first examination the clinicians will not know whether subjects belong to group II or
group III. All laboratory processes will, however, be performed with no knowledge of group
assignment.
The investigators intend to enrol a total of 180 pregnant women with a clinically perceived
risk for PTB or at no/low risk based on routine clinical assessment criteria. Consecutive
consenting pregnant women seeking care at, or are being referred to the Frauenspital,
University of Berne will be asked to participate when admitted to the prenatal care unit
because of risks for PTB, e.g. shortening of the cervical length, preterm contractions or
prelabor premature rupture of membranes. The investigators anticipate a 10% dropout rate.
They intend to continuously match subjects in the control group to those in the risk groups.
Consenting women will receive study examinations as well as obstetric standard of care
during pregnancy provided by medical faculty investigators. Dental faculty investigators at
the Department of Periodontology, University of Bern will perform dental examinations, data
and sample collections from the participating subjects at either the Clinics of the Dental
School or at the Frauenspital for bedridden pregnant women. There will be no specific dental
interventions as part of the study. The dentists who normally provide care for study
subjects will continue to do so. There are currently no known dental procedures that can
reduce the risk for PTB. Dental procedures during pregnancy are considered at low or no risk
to the pregnant women or the fetus.
The investigators will collect information on all medical and dental treatments performed
during pregnancy. They will assess obstetric and dental clinical conditions, using
procedures that they follow in both clinics. The investigators will also assess bacteria and
fungi in vaginal and oral compartments, and serum and local vaginal/oral inflammatory
markers (cytokines and C-reactive protein). They recognize that genetic and socio-economic
factors as well as ethnicity are important factors in risks for PTB. The control group will
therefore be paired and matched for gestational age, ethnicity, age, parity and smoking. The
investigators anticipate that some of these subjects in the assigned no risk control group
may actually deliver with PTB. Only women who deliver uneventfully will be included in the
control group.
