Low saliva progesterone concentrations are associated with spontaneous early preterm labour (before 34 weeks of gestation) in women at increased risk of preterm delivery.

Saliva progesterone and oestriol concentrations were determined weekly from 24 weeks of gestation in women at increased risk of preterm delivery. Samples were analysed from 28 women with spontaneous onset of labour and delivery before 37 weeks of gestation, and 64 who delivered at term. Saliva progesterone was lower in the 12 women delivering before 34 weeks than in those delivering later, between 34 and 37 weeks (P = 0.007) or at term (P = 0.009). Measurement of saliva progesterone may be of value in the prediction of early preterm labour and in determining which women might benefit from progesterone supplementation.

Serial salivary estriol to detect an increased risk of preterm birth.

OBJECTIVE: To evaluate serial measurements of salivary estriol (E3) to detect increased risk of spontaneous preterm labor and preterm birth. METHODS: A masked, prospective, multicenter trial of 956 women with singleton pregnancies was completed at eight United States medical centers. Saliva was collected weekly, beginning at the 22nd week of gestation until birth, and tested for unconjugated E3 by enzyme-linked immunosorbent assay. Women were separated into high-risk and low-risk groups using the Creasy scoring system. RESULTS: A single, positive (at or above 2.1 ng/mL) salivary E3 test predicted an increased risk of spontaneous preterm labor and delivery in the total population (relative risk [RR] 4.0, P <.005), in the low-risk population (RR 4.0, P < or =.05), and in the high-risk population (RR 3.4, P =.05). Two consecutive positive tests significantly increased the RR in all study groups, with a dramatic improvement in test specificity and positive predictive value but only a modest decrease in sensitivity. In women who presented with symptomatic preterm labor, salivary E3 identified 61% of those who delivered within 2 weeks, using a threshold of 1.4 ng/mL. CONCLUSION: Elevated salivary E3 is associated with increased risk of preterm birth in asymptomatic women and symptomatic women who present for evaluation of preterm labor.

ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October 2001. (Replaces Technical Bulletin number 206, June 1995; Committee Opinion number 172, May 1996; Committee Opinion number 187, September 1997; Committee Opinion number 198, February 1998; and Committee Opinion number 251, January 2001).

Preterm birth is the second leading cause of neonatal mortality in the United States (1) (second only to birth defects), and preterm labor is the cause of most preterm births (2). Neonatal intensive care has improved the survival rate for babies at the cusp of viability, but it also has increased the proportion of survivors with disabilities. The incidence of multiple births also has increased along with the associated risk of preterm delivery (4). Interventions to delay preterm delivery in these settings have not shown conclusive effectiveness. Because the morbidity of babies born after 34-35 weeks of gestation has diminished, most efforts to identify preterm deliveries have focused on deliveries before this age. This document describes the various methods proposed for predicting preterm birth and the evidence for their roles in clinical practice.

Biochemical predictors of preterm labor: fetal fibronectin and salivary estriol.

Preterm birth is a major complication of pregnancy and remains a leading cause of neonatal morbidity and mortality worldwide. Improvements in the authors' understanding of the pathophysiology of preterm labor have led to the development of novel diagnostic tools of use to identify women at greatest risk for preterm birth. Currently two FDA-approved biochemical tests are available in the United States: (1) fetal fibronectin and (2) salivary estriol. The presence of a positive fetal fibronectin test in the midtrimester of pregnancy is strongly associated with early spontaneous preterm birth. In contrast, a positive salivary estriol test is associated with late preterm birth, thus limiting its clinical use. Both tests have low test sensitivity and are currently used clinically for their negative predictive values. That is, women who screen negative are at very low risk for preterm birth and, thus, no interventions are indicated to prevent preterm birth. Women with a positive test are at increased risk and would be candidates for intervention. One of the main limitations of fetal fibronectin and salivary estriol, and an array of other proposed markers, is the fact that while these markers may aid in identification of women at increased risk for preterm birth, the authors currently have no clearly effective obstetric interventions for preterm-birth prevention in these high-risk women. Use of tocolytics, antimicrobials, or progesterone therapy currently has limited or unproven benefit in the management of women deemed at increased risk using these markers. Thus, until effective targeted obstetric interventions are available, the use of biochemical markers to identify women at increase risk for preterm birth remains largely research tools.

Endocrine assays to predict preterm delivery.

Advances in the understanding of the endocrine and hormonal mechanisms involved in normal and abnormal labor have led to clinical research into the roles of hormones and cytokines in preterm labor. This article reviews the current status of assays for estriol, activin, corticotropin-releasing hormone, interleukin-6, and relaxin as predictors of preterm labor and delivery.

Biochemical markers (without markers of infection) of the risk of preterm delivery. Implications for clinical practice.

BACKGROUND: New biochemical markers for the risk of spontaneous preterm birth (SPB) give a more precise and earlier diagnosis than the usual ones. We reviewed the data about the principal markers. RESULTS: Using studies with good methodology and a large number of subjects, we observe that the predictive value of these new markers is somewhat higher than those of the usual markers. Fetal fibro-nectin (FNf) and cervical ultrasound undeniably improve the identification of patients at risk of preterm birth, both in the general population and in these threatened preterm delivery. However no management has yet been demonstrated efficacious, especially in a general population so any recommendations for their systematic utilisation is premature. Other biochemical markers (salivary estriol, serum CRH, etc.) are still under assessment and should not be used outside research protocols. IMPLICATION FOR PRACTICE: It is appropriate to integrate either FNf or cervical ultrasound into daily clinical practice for patients with signs of preterm labor. These new indicators are of special use when the diagnosis is uncertain with the standard markers (uterine contractions, digital examination). Among these patients, they should reduce the number of hospitalizations and of useless treatments, because of their good negative predictive value. At the same time, for patients poorly 'labeled' by the clinical examination, they should allow the application of intensive management (intravenous tocolysis, corticoids, in utero transfers). CONCLUSION: Future studies should evaluate these tests in everyday practice. The objective is not to predict preterm birth but to prevent either it or its negative consequences. This goal will be met when we have an effective treatment, without associated adverse effects, to offer patients after a positive test result.

Salivary markers of systemic disease: noninvasive diagnosis of disease and monitoring of general health.

Because of interest in the link between oral and general health, clinicians are increasingly using salivary analyses to diagnose systemic disease and to monitor general health. The reason for this interest lies in the ability of new diagnostic tools, such as sensitive enzyme-linked immunosorbent assays, as well as other technologies, to distinguish a range of salivary components that are biomarkers for changes in the body's health. The noninvasive nature of salivary testing has made it an attractive and effective alternative to blood and urine testing, and home testing kits have made it possible for people to monitor their own health using this diagnostic medium. This paper explores what saliva can reveal about general health, drawing examples from recent research on salivary biomarkers of systemic illness and highlighting the current use, and potential clinical and research applications, of diagnostics based on oral fluids.

Can preterm labour be predicted in low risk pregnancies? Role of clinical, sonographic, and biochemical markers.

BACKGROUND AND OBJECTIVES: This is a prospective nested cohort study conducted over a period of 3 years. 2644 women were recruited, out of which final analysis was done for 1884 women. METHODS: Cervicovaginal and blood samples were collected for all recruited women. Out of these, 137 women who delivered before 35 weeks were treated as cases and equal number of matched controls were chosen. Analysis of samples for serum G-CSF, AFP, ferritin, and cervicovaginal interleukin-6 and IGFBP-1 was done. RESULTS: Poor orodental hygiene, which can be a social marker, was significantly more common in women who delivered preterm (P = 0.008). Serum alkaline phosphatase and serum ferritin were found to be significantly associated with preterm deliveries. The 90th percentile value of these parameters was considered as cut-off as there is no specific cut-off. CONCLUSIONS: Our study did not prove usefulness of any predictive marker. Serum ferritin and alkaline phosphatase were found to have correlation but their values are affected in many conditions and need to be elucidated with caution. Larger studies are needed for predicting preterm labour in asymptomatic women.

Periodontal disease and bacterial vaginosis as genetic and environmental markers for the risk of spontaneous preterm labor and preterm birth.

OBJECTIVE: The aim of this study was to review the evidence associating periodontal disease, and bacterial vaginosis with preterm birth, and the link with gene polymorphism, as well as the preventions and interventions which might reduce the risk of spontaneous preterm labor and preterm births in women with periodontal disease and/or bacterial vaginosis. BACKGROUND: Preterm birth accounts for 70% of perinatal mortality, nearly 50% of long term neurological morbidity, and a significant impact on health care costs. There is evidence that spontaneous preterm labor and preterm birth are associated with intrauterine infection due to abnormal genital and/or oral colonization. Periodontal disease and bacterial vaginosis share microbiological similarities, and both conditions are associated with spontaneous preterm labor and preterm birth. In addition, periodontal disease and bacterial vaginosis have been linked through gene polymorphism. METHODS: A review of the literature using widely accepted scientific search engines in English language. RESULTS: Studies evaluating antibiotic administration to eradicate periodontal disease and/or bacterial vaginosis responsible organisms, and minimize the risk of preterm births have yielded conflicting results. With respect to bacterial vaginosis, the timing and the choice of antibiotic administration might partly explain the conflicting results. The use of scaling and/or root planning for women with periodontal disease appears to reduce the risk of preterm birth, but routine administration of antibiotics has not demonstrated any impact on preterm birth. CONCLUSION: Prospective studies evaluating the association of gene polymorphism with preterm birth, and the contribution of periodontal disease and bacterial vaginosis are needed.

[Analysis of periodontal status in pregnant women with a diagnosis of threatened premature labor].

PURPOSE: To evaluate the associations between periodontal conditions and delivery outcomes in pregnant women with a diagnosis of threatened premature labor (TPL). METHODS: Eighty systemically healthy pregnant women were enrolled in the study. The case group was composed of 40 pregnant women hospitalized with the diagnosis of TPL and the control group was composed of 40 normal pregnant women. Periodontal examinations included assessments of plaque index (PLI), clinical attachment loss (CAL), probing depth (PD), bleeding index (BI) and the percentage of periodontitis sites (PD > 3 mm, CAL > or = 2mm). The serum level of IL-6 was determined using commercially available enzyme-linked immunoassays (ELISA). The data were analyzed with SPSS11.0 software package for chi2 test, Student's t test and Pearson correlation analysis. RESULTS: 40 subjects were clarified as TPL and 14 as TPL-PB. 26 TPL women subsequently delivered TB infants. No infants were delivered as PB in 40 subjects clarified as non-TPL. There were no significant differences in the mean ages and gestational age at examination between the non-TPL and TPL groups or between the TPL-TB, and TPL-PB groups. There were significant differences in gestational age at delivery and birth weight between the non-TPL and TPL groups or between the TPL-TB, and TPL-PB groups (P < 0.05). The mean PLI, percentage of periodontitis sites and IL-6 levels were significantly higher in the TPL group than those of the non-TPL group. The mean PLI, BI, and percentage of periodontitis sites were significantly higher in the TPL-PB group than those of the TPL-TB group. Significant negative correlations were observed between the gestational age at delivery and percentage of periodontitis sites as well as BI (P < 0.05). CONCLUSION: Periodontal inflammation might be involved in the pathogenesis of preterm birth.

Increased saliva oestriol to progesterone ratio before preterm delivery: a possible predictor for preterm labor?

Saliva oestriol, oestradiol, and progesterone concentrations were measured in 23 women who went into spontaneous preterm labour. The patients fell clinically and biochemically into two groups. The 13 who went into preterm labour with intact membranes had a saliva oestriol to progesterone ratio greater than one in every case and greater than the 95th centile for their length of gestation in 12 cases; by contrast, all those who went into spontaneous preterm labour after prolonged rupture of the membranes had an oestriol to progesterone ratio less than one and below the 50th centile for their period of gestation in the one to four days before delivery. Saliva oestradiol to progesterone ratios were randomly distributed throughout the normal range in both groups. It appears that preterm labour without prior prolonged rupture of the membranes is, like term labour, preceded by an increase in the saliva oestriol to progesterone ratio. It may therefore be possible to use this ratio to predict preterm labour.

Salivary estriol as risk assessment for preterm labor: a prospective trial.

OBJECTIVE: Increased understanding of human parturition allows for novel approaches to (1) identification of women at increased risk for preterm birth and (2) development and controlled testing of etiology-based strategies to prevent preterm birth. STUDY DESIGN: Five hundred forty-two women were enrolled at five study sites in a prospective evaluation of salivary estriol in samples obtained weekly beginning at 22 weeks' gestation (Salest, Biex, Inc., Boulder, Colo.). Estriol concentrations were determined with a well-characterized enzyme-linked immunoassay. Women adjudged at either high risk or low risk for prematurity were evaluated through to delivery. RESULTS: A total of 267 women submitted serial samples that were analyzed; 241 women with singleton pregnancies submitted sufficient samples. Twenty-three women with singleton fetuses went into idiopathic preterm labor (without prior rupture of membranes) and were delivered preterm (mean 35 weeks' gestation); 182 were delivered at term (> or = 37 weeks' gestation). Mean (geometric) estriol concentrations were higher from 24 to 34 weeks in women with singleton pregnancies delivering preterm (p < 0.05). A surge in estriol concentrations occurred approximately 3 weeks before the onset of labor in both women delivering at term and those delivering preterm. This increase occurred approximately 4 weeks earlier in women delivered preterm versus term. Receiver-operator curve analyses showed that exceeding a 2.3 ng/ml saliva estriol level was associated with occurrence of preterm labor (71% sensitivity, 77% specificity, 23% false-positive rate). CONCLUSION: Detection of an early estriol surge or increased level (> or = 2.3 ng/ml) may be clinically helpful in identifying women at elevated risk for preterm labor and birth, allowing for evaluation of biologically based interventions in controlled trials.

Doença periodontal e intercorrências gestacionais / Periodontal disease and adverse pregnancy outcomes: a critical review

A doença periodontal, por se tratar de uma doença infecciosa inflamatória crônica, tem sido relatada como um fator de risco para certas condições sistêmicas. O objetivo deste estudo foi avaliar a associação entre doença periodontal (DP) e intercorrências gestacionais: o parto pré-termo (PPT), o baixo peso ao nascimento (BPN) e a pré-eclâmpsia (PEC). Foi realizada uma revisão bibliográfica nas principais bases de dados dos últimos 15 anos. Foram selecionados estudos observacionais (caso-controle, transversal e longitudinal), estudos de intervenção e revisões sistemáticas. Os dados na literatura são controversos. A maior parte dos estudos transversais, caso-controle e longitudinais mostram associação positiva entre DP e as intercorrências gestacionais, reportando taxas de risco variadas. Alguns estudos observacionais falharam em demonstrar tal associação. Estudos de intervenção mostraram redução na incidência das intercorrências gestacionais após terapia periodontal durante a gestação. Entretanto, existem ensaios clínicos que falharam em demonstrar a efetividade do tratamento periodontal na redução do risco para as intercorrências gestacionais. As revisões sistemáticas reportam a possibilidade de uma associação moderada entre DP e as intercorrências citadas, mas apontam a necessidade de realização de estudos com metodologias mais rigorosas, abrangendo diferentes populações, para a confirmação desta associação e da efetividade do tratamento periodontal na redução do risco destas intercorrências gestacionais. Assim, os estudos indicam uma evidência moderada de associação entre DP e as intercorrências gestacionais. Entretanto, mais estudos, principalmente de coorte e intervenção, se fazem necessários.