Risk assessment for preterm delivery in pregnant women with active periodontitis

INTRODUCTION: Premature labor has been regarded as a highly problematic clinical event not only due to its relation with perinatal mortality but also in the light of the remote results of the prematurity. Therefore many ongoing studies concentrate on evaluation of potentially avoidable risk factors of premature labor. Relatively few studies have suggested chronic periodontitis as such a determinant. OBJECTIVES: Prospective evaluation of periodontium changes in the course of otherwise normal pregnancy. Assessment of potential influence of periodontium pathology, and its severity, on the obstetrical complications. The authors have made literature search on the relation of active periodontitis and premature labor. MATERIALS AND METHODS: Study involved 120 randomized gravidae attending electively dental clinic for a routine control. Inclusion criteria: single pregnancy, no preterm delivery in a history, mother's age 18 to 35 years, gestational age 10 to 20 weeks based on a last menstrual period date--confirmed on ultrasound. Every patient underwent dental examination twice--at the inclusion date and 48 hours after delivery. Patients were divided into three groups. Group I (n = 25)--healthy patients. Group II (n = 61)--patients with mild or moderate periodontitis. Group III (n = 39) patients with a severe periodontitis. Progression of lesions was recognized if the post-delivery dental assessment revealed increase of the pockets depth higher than 2mm and in at least 4 places compared with the initial findings. RESULT: In the course of otherwise normal pregnancy women with signs of inflammation within periodontium revealed progression of this pathology proportional to its severity in early pregnancy. This increase was associated with 4-fold higher rate of preterm deliveries in Group II and 12-fold in Group III compared with healthy patients. CONCLUSION: Active and severe periodontitis should be regarded as independent and highly influential risk factor of the preterm delivery.     

Impact of threatened preterm labor and lower genital tract biocenosis on the concentrations of selected proinflammatory cytokines in cervicovaginal fluid of pregnant women

AIM: Recent studies have suggested that proinflammatory cytokines might play a crucial role in the mechanism of preterm labour and delivery. Lower genital tract infection could also influence the cytokines levels. The main aim of this study was to compare the concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6 and IL-8 in cervicovaginal fluid of pregnant women with threatened preterm labour (TPL) with group of women with normal course of pregnancy (reference group) and to determine impact of lower genital tract microflora on cytokines concentration. MATERIAL AND METHODS: Cervicovaginal fluids were obtained by lavage from 40 pregnant women at 22 to 34 weeks' gestation. Those samples were analyzed for the concentrations of selected cytokines using standard enzyme-linked immunosorbent assay technique. Lower genital tract microbiology was diagnosed using Gram stain method according to Spiegel's criteria. TPL was defined as uterine contractions treated by tocolysis. RESULTS: Threatened preterm labour (TPL) was diagnosed in 22 (55.0%) cases. Mean gestational age at the time of cytokines measurement was 28.6 weeks. Mean concentrations of IL-1 alpha, IL-1 beta and IL-8 measured in cervicovaginal fluid of pregnant women with TPL and in reference group were similar (89.43 vs. 91.17 pg/ml; 42.05 vs. 41.01 pg/ml and 621.8 vs. 697.8 pg/ml, respectively). Vaginal levels of IL-6 was higher among women with preterm labour (21.1 pg/ml vs. 13.9 pg/ml) as compared to reference group. Bacterial vaginosis (BV) was diagnosed in 11 women (27.5%) while grade I microflora in 19 (47.5%). There was a positive correlation between BV and IL-1 alpha and IL-1 beta concentration but no with IL-6 and IL-8. CONCLUSIONS: Vaginal levels of IL-6 were found to be significantly elevated among women with threatened preterm labour while IL-1 alpha and IL-1 beta among women with BV. The usefulness of cytokines measurement in cervicovaginal fluid of pregnant women for prediction of preterm delivery should be clarified in further after excluding the impact of lower genital tract infections on cytokines concentrations.     

Cervical gland area as an ultrasonographic marker for preterm delivery.

OBJECTIVE: To assess the association between spontaneous preterm delivery (SPTD) in the general population and the measurement of the cervix length, cervical funneling, and absence of the cervical gland area (CGA). METHOD: A prospective cohort of 338 women carrying uncomplicated pregnancies was evaluated by transvaginal sonography between 21 and 24 weeks' gestation. RESULTS: Measurement of cervical length with less than 20 mm and the presence of cervical funneling presented a statistically significant association with SPTD before 35 weeks. The non-detection of CGA demonstrated a strong association with SPTD before 37 weeks' (p < 0.001; OR = 194.5) and before 35 weeks' gestation (p < 0.001; OR = 129.6). The multiple logistic regression analysis suggested the non-detection of CGA as the only variable to reveal statistically significance association with SPTD. CONCLUSION: The results seem to indicate that the absence of CGA can be a new and important ultrasound marker for SPTD, to be confirmed by future multicenter investigations.     

The role of amniotic fluid assessment in indicated preterm delivery

Measuring amniotic fluid pockets with ultrasound is an efficient and reasonably reliable method of evaluating amniotic fluid volume and categorizing relative risk of perinatal morbidity. The most commonly used ultrasound criteria for oligohydramnios, SDP <2 cm and AFI <5 cm, assign approximately 2%-3% and 4%-5% of late preterm pregnancies into the "low amniotic fluid" category. The AFI offers somewhat greater sensitivity and greater precision but has less specificity for predicting perinatal morbidity than does the SDP. Thus, before 34 weeks, use of the AFI <5 cm as a criterion for intensive fetal monitoring, but not as sole criteria for delivery, is recommended. In pregnancies beyond 34 weeks, use of either AFI or SDP to diagnose oligohydramnios can be expected to reliably identify fetuses at risk for compromised perinatal outcome especially if replicate measurements are confirmatory. In such cases, care must be taken to identify comorbid conditions that, together with oligohydramnios, may place the fetus at significant risk. In such cases, delivery is the recommended intervention.     

17alpha-hydroxy-progesterone effects on cervical proinflammatory agents in women at risk for preterm delivery

We evaluated if the inhibitory effect of 17alpha-hydroxyprogesterone caproate (17P) on cervical ripening is mediated by cervical proinflammatory agents. Women with singleton pregnancy and intact membranes, between 25 and 33 weeks + 6 days, were randomly allocated either to observation (22 cases, controls) or to receive 341 mg of intramuscular 17P (23 cases, 17P group), twice a week, until 36 weeks. Just before randomization, 7 and 21 days later, a cervical swab for interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and nitrates/nitrites (NOx) assays was collected. Moreover, an ultrasound measure of cervical length (CL) was performed at the same time. At randomization, both groups of women showed similar levels of cervical ILs and NOx. In the 17P group, cervical IL-1beta levels were significantly decreased at day 21 ( P = 0.036); in controls, they remained stable throughout the observation period. There was no significant change in IL-6, IL-8, TNF-alpha, and NOx in either group. Women in the control group had a progressive CL shortening until day 21 (median shortening of 4 mm), and this shortening was significantly less in the 17P group (median shortening of 2 mm; P = 0.017). In patients at risk of preterm labor, high-dose 17P simultaneously inhibits both cervical proinflammatory IL-1beta secretion and the progressive shortening of the cervix.     

Pentraxin 3 in plasma and vaginal fluid in women with preterm delivery

OBJECTIVE To investigate the role of pentraxin 3 (PTX3), an acute-phase protein produced by cells of innate immunity in response to inflammatory signals, in spontaneous preterm delivery (PTD). DESIGN Cohort study. SETTING Department of Obstetrics and Gynecology of the University of Milano-Bicocca. POPULATION Forty-six pregnant women with preterm rupture of membranes (n=33) or preterm labour with intact membranes (n=13) delivering at <34 weeks of gestation and 34 women with uncomplicated pregnancies (control group). METHODS We compared plasma and vaginal PTX3 levels between study group and controls, and in women with versus women without clinical or histologic evidence of intrauterine infection using statistical analysis. MAIN OUTCOME MEASURES Peak PTX3 concentration. RESULTS Peak PTX3 concentration in plasma samples of study group was significantly higher than that in controls (1175, 0-9630 versus 650, 0-1450 pg/ml; P=0.0003) but not in vaginal swabs (1660, 0-6604 versus 457, 0-4649 pg/ml; P=0.386). PTX3 levels in plasma were significantly higher in women with placenta vasculopathy compared with that in women with no placental lesions (2910, 0-9630 versus 636, 0-5692 pg/ml; P=0.04). Peak plasma and vaginal PTX3 concentrations were not significantly different in women with versus women without intrauterine infection (1168, 0-7110 versus 845, 0-9630 pg/ml, P=0.34 and 1975, 471-6604 versus 1919, 0-4150 pg/ml, P=0.38, respectively). CONCLUSIONS Spontaneous PTD is associated with a significant increase of maternal plasma concentrations of PTX3. PTX3 seems to be a marker of placenta vasculopathy rather than intrauterine infection.     

Serum ferritin level as a marker of preterm labor.

Objective: To compare the serum ferritin levels in women with preterm labor (PTL) or preterm premature rupture of membranes with those in normal gravid women. Method: The study group consisted of 50 consecutive subjects with preterm labor and 49 subjects with preterm premature rupture of membranes (PROM). The control group consisted of 50 subjects matched with the study group for hemoglobin (Hb) and gestation who did not have PTL or preterm PROM. Serum ferritin levels were assayed in both the groups. Results: Mean serum ferritin levels in patients with preterm labor and preterm premature rupture of membranes were 23.24+/-12.13 ng/ml and 29.44+/-28.41 ng/ml, respectively. The mean serum ferritin in control subjects was 8.69+/-3.7 ng/ml. The difference was evaluated by Student's t-test and was found to be statistically significant. Conclusion: The serum ferritin level is significantly raised in pregnant women with preterm labor and preterm PROM.     

Increased neopterin level and chitotriosidase activity in pregnant women with threatened preterm labor

Objectives: To determine whether the cellular inflammatory markers of activated macrophages, neopterin (NEO), chitotriosidase activity and the acute-phase inflammatory marker C-reactive protein (CRP) are elevated in pregnancy with threatened preterm labor (TPL).

Methods: Thirty-two pregnant women with TPL and 32 women with uncomplicated pregnancy (UP) were included this study. The primary aim was to compare the NEO, chitotriosidase activity and CRP levels between women with TPL and women with UP.

Results: NEO levels were all significantly elevated in patients with TPL compared to UP (median 25–75%; 9.61 [8.47–12.29] versus 4.46 [3.59–6.92], respectively; p?p?=?0.036). However, CRP levels were not different in women with TPL compared to UP (p?=?0.573). Furthermore, a significant moderate negative correlation was found between delivery week and NEO level (r?=??0.557, p?=?0.001). However, a significant correlation was not seen between delivery week and chitotriosidase activity (r?=??0.042, p?=?0.741).

Conclusions: Inflammatory markers such as NEO and chitotriosidase activity, which are markers of macrophages, are more elevated in pregnant women with TPL than in women with UP. These data suggest that there are striking increases in inflammation and cellular immune activation in TPL.     

S-relaxin as a predictor of preterm delivery in women with symptoms of preterm labour

Objective To evaluate whether serum relaxin (S-relaxin) can predict spontaneous delivery before 34 weeks of gestation in high risk pregnancies.
Design A prospective cohort study.
Setting Calculated sample size was reached over a two-year period, during which 9507 women gave birth. Of these, 157 healthy women were eligible for the study as they were admitted with symptoms of delivery before 34 weeks of gestation. Ninety-three women were included. Overall participation rate was 59%.
Population Healthy women with singleton pregnancies with symptoms of delivery before 34 weeks of gestation.
Methods S-relaxin was measured using a standard sandwich ELISA.
Main outcome measures End points were preterm delivery before 34 weeks of gestation and delivery within three days from initiation of symptoms. The best possible prediction of preterm delivery was established using logistic regression for risk factors individually associated with preterm delivery before 34 weeks of gestation. S-relaxin was dichotomised to obtain best possible fit and then entered into the model. The same analyses were done for delivery within three days.
Results Median S-relaxin levels varied significantly in the women with preterm prelabour rupture of membranes (PPROM) (316 pg/mL), contractions (222 pg/mL) or ripe cervices (203 pg/mL) (   P < 0.05  ). S-relaxin above the 80th centile (≥300 pg/mL) was associated with an increased risk of preterm delivery [crude  OR = 4.8; (95% CI: 1.9–12)  ]. Likelihood ratio of a positive test is 2.6 (1.5–4.9) and S-relaxin resulted in a post-test probability of preterm delivery of 0.72, compared with a pre-test probability of 0.49. S-relaxin contributed to the identification of delivery within three days [adj.  OR = 11 (95% CI: 1.8–64)  ].
Conclusion S-relaxin may be a useful predictor in women with symptoms of delivery before 34 weeks of gestation.     

Usefulness of quantitative polymerase chain reaction in amniotic fluid as early prognostic marker of fetal infection with Toxoplasma gondii

OBJECTIVE: Our purpose was to evaluate Toxoplasma gondii concentration in amniotic fluid (AF) samples as a prognostic marker of congenital toxoplasmosis. STUDY DESIGN: A retrospective study was carried out in 88 consecutive AF samples from 86 pregnant women, which were found positive by prospective polymerase chain reaction (PCR) testing. Parasite AF concentrations were estimated by real-time quantitative PCR and analyzed in relation to the clinical outcome of infected fetuses during pregnancy and at birth, taking into account the gestational age at maternal infection. RESULTS: A significant negative linear regression was observed between gestational age at maternal infection and T gondii DNA loads in AF. After adjusting for time at maternal seroconversion by multivariate analysis, higher parasite concentrations were significantly associated with a severe outcome of congenital infection (odds ratio [OR]=15.38/log (parasites/mL AF) [95% CI=2.45-97.7]). CONCLUSION: PCR quantification of T gondii in AF can be highly contributive for early prognosis of congenital toxoplasmosis. Maternal infections acquired before 20 weeks with a parasite load greater than 100/mL of AF have the highest risk of severe fetal outcome.     

Pentraxin 3 in amniotic fluid as a marker of intra-amniotic inflammation in women with preterm premature rupture of membranes

Objective

To determine whether amniotic fluid levels of pentraxin 3 (PTX3) are of value in the prenatal diagnosis of acute histological chorioamnionitis in preterm premature rupture of membranes (PPROM).

Methods

Forty pregnant women with PPROM between 24 and 36 weeks of pregnancy without (n = 21) and with (n = 19) histological chorioamnionitis (PPROM group) and 42 women between 16 and 20 weeks of pregnancy (midtrimester group) were included in the study. We compared amniotic fluid PTX3 levels in the PPROM group with versus without histological chorioamnionitis, and between the PPROM and the midtrimester groups using nonparametric tests (Mann-Whitney test), given the non-normal distribution of the analyte.

Results

Patients with histological chorioamnionitis had a significantly higher median amniotic fluid PTX3 concentration than patients without the histological signs of chorioamnionitis (3.69 ng/mL [0.51-106.8] versus 0.8 ng/mL [0.36-121.0]; P = 0.015). Patients in the PPROM group reached a significantly higher median amniotic fluid concentration of PTX3 compared with those in the midtrimester group (1.0 ng/mL [0.36-121.0] versus 0.67 ng/mL [0.4-2.8]; P = 0.007).

Conclusion

Histological chorioamnionitis is associated with a significant increase of amniotic fluid pentraxin 3 levels. Amniotic fluid pentraxin 3 appears to be a marker of intra-amniotic inflammation.     

Cervical immunoglobulin A and altered vaginal flora in pregnant women with threatened preterm delivery

The aim of our study was to investigate the cervical immunoglobulin A concentration in women with threatened preterm delivery. Immunoglobulin A concentration in the cervical mucus of 80 women with symptoms of preterm delivery was measured using radial immunodiffusion. The results were compared with those of 60 healthy pregnant women. Concentrations of immunoglobulins in maternal serum were also measured. There was no significant difference of cervical immunoglobulin A (IgA) concentration between women with threatened preterm delivery and controls: 53.98 (0.0-189.7) mg/l vs. 61.7 (1.4-400.9; p<0.4) mg/l (median, range). The median of cervical IgA levels in the group of threatened preterm delivery did not differ significantly between patients delivered preterm (n=34) or at term (n=46): 38.3 (0.0-187.9) vs. 65.7 (1.4-189.7; p<0.2) mg/l. Women with a normal vaginal flora showed a significantly higher cervical IgA concentration than those with a pathological colonization: 72.7 (0.0-187.9) vs. 42.5 (0.0-189.7) mg/l. Patients with a pathological vaginal smear and preterm delivery had the lowest IgA levels (35.0; 0.0-187.9 mg/l). Measurement of cervical IgA concentration does not differentiate between women who deliver before or at term.     

Presentation to delivery interval in women with early preterm delivery presenting with preterm labor: the effect of gestational age

Background: To evaluate the association between gestational age at presentation and interval to delivery in women with early spontaneous preterm delivery (PTD).

Methods: A retrospective cohort study of women who presented with threatened preterm labor (tPTL) and intact membranes and had a spontaneous PTD <34 weeks in a university-affiliated hospital (2009–2015). The interval from presentation to delivery was compared between different gestational age subgroups.

Results: Of 67 550 deliveries during the study period, 252 met inclusion criteria. This cohort was divided to three gestational age subgroups at presentation: 24–28^6/7 weeks (n?=?83), 29–31^6/7 weeks (n?=?61) and 32–33^6/7 weeks (n?=?108). Median time from presentation to delivery was 24.5?h. An inverse relation was observed between gestational age at presentation and admission–delivery interval (group A: 74.7?h, group B: 21.0?h, group C: 14.0?h, p?Conclusion: Gestational age at presentation is inversely related to admission–delivery interval in women with tPTL and intact membranes.     

Proinflammatory cytokines and other indications of inflammation in cervico-vaginal secretions and preterm delivery.

OBJECTIVES: To compare the usefulness of evaluating cervico-vaginal concentrations of proinflammatory cytokines (interleukin [IL]-1alpha, IL-1beta, IL-6 and IL-8) and procalcitonin (PCT), as well as serum levels of C-reactive protein (CRP), leucocytosis and band form granulocytes in the prediction of preterm delivery (PTD). METHODS: A total of 65 pregnant women experiencing preterm labor (PTL) were enrolled in the study. Concentrations of the studied markers in women who delivered prematurely and in women who, after treatment, delivered at term were compared. Receiver operator characteristic (ROC) curve analysis was used for all study parameters. RESULTS: Cervico-vaginal IL-6 and procalcitonin as well as serum CRP concentrations were higher in women who delivered prematurely than in those who delivered near term. A cervico-vaginal IL-6 level greater than 660 pg/ml was the best predictive value of preterm delivery (sensitivity, 50%; specificity 90%; positive predictive value [PPV], 85%; NPV, 62%; likelihood ratio, 5.17). Moreover, the area under the ROC curve of 0.75 for cervico-vaginal IL-6 was greater than for other markers. CONCLUSION: Although cervico-vaginal concentrations of procalcitonin and serum concentration of CRP are higher in women who deliver prematurely, only cervico-vaginal concentration of IL-6 is a good predictor of preterm delivery.     

Value of endocervical ureaplasma species colonization as a marker of preterm delivery

AIMS: To study the predictive value for preterm delivery of colonization of the cervix and vagina by ureaplasmas and other potentially pathogenic microorganisms. METHODS: Prospective analysis of a study group of 200 pregnant women with preterm labor and intact membranes, and a control group of 50 pregnant women. The subjects in both groups were between 24 and 34 weeks of gestation. Ureaplasma spp. and Mycoplasma hominis endocervical cultures were performed for both groups. RESULTS: In the study group, 70 of the women delivered preterm, and all women in the control group carried their pregnancies to full term. Cervical cultures for Ureaplasma spp. were positive in 119 women, and were isolated more frequently in the study group (51.5%) than in the control group (32%), and more frequently in subjects in the study group who delivered preterm (65%) than in those who had a full-term delivery (45%), differences that were statistically significant. CONCLUSION: Detection of Ureaplasma spp. in the endocervix has a statistically significant relationship to preterm labor (p = 0.03) and preterm delivery (p = 0.02) in pregnant women with preterm labor and intact membranes.     

PAPP-A levels as an early marker of idiopathic preterm birth: a pilot study.

OBJECTIVE: To evaluate late PAPP-A levels as predictive of preterm birth in symptomatic women. STUDY Design: Prospective cohort study of singleton gestations, 23 to 34 weeks, and symptoms of preterm labor. PAPP-A, IGF-I and IGF-III analysis were performed. Primary end point was delivery < or =7 days. Accuracy and optimally predictive PAPP-A values were based on receiver operator characteristic (ROC) curves. RESULT: In all, 26 women (51%) delivered < or =7 days post-admission (Group 1); 25 women (49%) >7 days (Group 2). Group 1 mean PAPP-A=38 000 vs 55 333 for Group 2 (P<0.04). Group 1 mean gestational age at delivery=29 weeks vs 37 weeks for Group 2 (P<0.00014). PAPP-A level < or =30,000 mU l(-1) had highest specificity (88%), sensitivity (50%), and positive predictive (81%) and negative predictive (62%) values for delivery < or =7 days. ROC area under curve=0.703. CONCLUSION: PAPP-A levels < or =30,000 mU l(-1) at admission was associated with increased risk for preterm birth < or =7 days, supporting active management and therapeutic approach in these women.     

Influence of an education program of pregnant women on delivery

Abstract

Objectives: To assess whether an education program of pregnant women influences factors related to delivery and health behavior with newborns after delivery, such as the establishment of early skin-to-skin contact between the mother and newborn.

Methods: A multicenter observational study was carried out with primiparous women in four hospitals in southern Spain in 2011. Data on sociodemographic and obstetric variables were collected from interviews and clinical charts. In the analysis, crude and logistic regression adjusted odds ratios (ORs) were estimated.

Results: The study population comprised 520 women, 354 of whom attended the education program (68.1%). The program favored the establishment of early skin-to-skin contact between the mother and newborn (aOR 1.95, 95% CI 1.25–3.02, after adjusting for sociodemographic characteristics and the presence of pathology during pregnancy). Mothers who attended the program participated more actively during delivery (aOR 1.64, 95% CI 1.16–2.31). No association was observed between attending the program and the type of delivery (aOR 0.79, 95% CI 0.53–1.1) or with the frequency of cesarean section (aOR 0.81, 95% CI 0.49–1.34). The duration of delivery was also unrelated to maternal education.

Conclusions: Maternal education did not influence the type of delivery, but it favored women's participation during delivery and early skin-to-skin contact between the mother and newborn.