Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes

Amniotic fluid was retrieved by amniocentesis from 264 patients with preterm labor and intact membranes admitted to Yale-New Haven Hospital from Jan. 1, 1985, to July 31, 1988. The prevalence of a positive amniotic fluid culture was 9.1% (24/264). A total of 111 patients (42%) delivered preterm neonates, and 24 (21.6%) of those had positive amniotic fluid cultures. The diagnostic indexes of the Gram stain of amniotic fluid in the prediction of a positive amniotic fluid culture were as follows: sensitivity, 79.1%; specificity, 99.6%; positive predictive value, 95%; and negative predictive value, 98%. Endotoxin was detected with the limulus amebocyte lysate assay in 4.9% (13/264) of patients with preterm labor. All patients with endotoxin in the amniotic fluid delivered preterm neonates. The three most frequently isolated organisms were Ureaplasma urealyticum (n = 6), Fusobacterium species (n = 5), and Mycoplasma hominis (n = 4). Clinical chorioamnionitis was present in only 12.5% of the patients with positive amniotic fluid cultures. Women with positive amniotic fluid cultures had lower gestational ages and more advanced cervical dilatation on admission than women with negative cultures. Preterm infants born to mothers with positive amniotic fluid cultures had a higher incidence of respiratory distress syndrome and infectious complications than preterm neonates born after negative amniotic fluid cultures. These data underscore the frequency and importance of intraamniotic infections in women with preterm labor.     

The prevalence and clinical significance of intraamniotic infection with Candida species in women with preterm labor

Summary Intraamniotic infection is considered a major etiologic factor of preterm birth. Positive amniotic fluid cultures are rarely contaminated with Candida species. The presence of this microorganism is associated with a poor pregnancy outcome. Out of 773 transabdominal amniocenteses performed in women presenting with preterm labor and intact membranes, 77 patients (9.9%) had positive amniotic fluid cultures and in 5 women (6.5%) Candida species were identified. On the other hand, 625 amniocenteses were performed in women with preterm premature rupture of membranes and 178 (28%) had positive cultures. Only in 4 patients was Candida isolated (2.2%) (P=0.13 Fisher’s exact test). The importance of early and accurate diagnosis of intraamniotic infection with Candida is pointed out. A transabdominal amniocentesis for microbiological examination is suggested for every woman presenting with preterm labor or preterm premature rupture of membranes and especially for those who conceived with a retained IUD or cervical cerclage.     

Infection and labor. IV. Cachectin-tumor necrosis factor in the amniotic fluid of women with intraamniotic infection and preterm labor

A growing body of evidence supports a causal link between subclinical intrauterine infection and preterm labor. The mechanisms responsible for the onset of parturition in this setting have not been elucidated. The conventional view has been that bacterial products increase prostaglandin biosynthesis by intrauterine tissues and this, in turn, leads to the onset of labor. An alternative or complementary mechanism is that microbial products activate the host monocyte-macrophage system and that cytokines released during this process signal the initiation of parturition by stimulating prostaglandin biosynthesis by intrauterine tissues. This study was conducted to determine if cachectin-tumor necrosis factor is present in the amniotic fluid of women with intraamniotic infection and whether this cytokine can alter the rate of prostaglandin biosynthesis by intrauterine tissues. Amniotic fluid from 54 women was assayed for tumor necrosis factor. Tumor necrosis factor was not detectable in the amniotic fluid of women without intraamniotic infection regardless of the presence or absence of term or preterm labor. On the other hand, the amniotic fluid of 11 of 15 women with preterm labor and intraamniotic infection had measurable tumor necrosis factor. This cytokine stimulated prostaglandin E2 biosynthesis by amnion cells in monolayer culture in a dose-dependent fashion. These data support the concept that macrophage activation is involved in the onset of human parturition in the setting of infection. We propose that the host (fetus and/or mother) signals the onset of parturition through the secretion of inflammatory cytokines released in response to bacterial invasion.     

Management of recurrent preterm labor in twin gestations with nifedipine tocolysis

We examined outcomes of twin pregnancies complicated by recurrent preterm labor receiving nifedipine tocolysis. In a retrospective study design, twin pregnancies receiving outpatient preterm labor surveillance services and oral nifedipine tocolysis following a diagnosis of preterm labor were identified from a database ( N = 1421). Eligible for inclusion were patients subsequently rehospitalized with recurrent preterm labor symptoms ( N = 862). Included were patients at < 35 weeks' gestation, having intact membranes, and remaining undelivered for > 48 hours after recurrent preterm labor ( N = 656). Pregnancy outcomes of women resuming nifedipine tocolysis ( N = 418) following hospitalization were compared with those having an alteration in treatment ( N = 238) to continuous subcutaneous terbutaline. Alteration of tocolytic treatment versus resuming nifedipine resulted in increased pregnancy prolongation (34.7 +/- 18.8 days versus 27.5 +/- 19.9 days, P < 0.001), with delivery of fewer low birth weight (67.2% versus 78.3%, P < 0.001) and very low birth weight infants (6.5% versus 15.0%, P < 0.001) and a decreased incidence of neonatal intensive care unit admission (44.7% versus 52.9%, P = 0.005). In twin pregnancies receiving nifedipine tocolysis, alteration of tocolytic treatment to subcutaneous terbutaline following hospitalization for recurrent preterm labor symptoms had a positive impact on pregnancy prolongation and neonatal outcomes.     

Accuracy of fetal fibronectin to predict preterm birth in twin gestations with symptoms of labor

OBJECTIVE: To investigate accuracy of fetal fibronectin testing to predict preterm birth in twin gestations with symptoms of preterm labor. METHODS: We reviewed charts of all patients with twin gestations who underwent fetal fibronectin testing and presented with complaints of preterm labor between January 1, 2000, and June 30, 2004. We also reviewed the charts of all singleton gestations with similar complaints that had fetal fibronectin testing between January 1, 2000, and December 31, 2001. All samples were processed using a rapid fetal fibronectin detection system. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of fetal fibronectin testing in singleton and twin gestations in predicting delivery within 14 days of testing. RESULTS: Four hundred twenty-nine singletons and 87 twins met the inclusion criteria. The birth rate before 34 weeks of gestation for singletons was 3.5% compared with the rate of twin pregnancies of 28.7%. Fetal fibronectin predicted delivery within 14 days of testing with a sensitivity, specificity, and positive and negative predictive values in singleton gestations of 82%, 90%, 17%, and 99%, respectively. In twin gestations, fetal fibronectin predicted delivery within 14 days of testing with a sensitivity, specificity, and positive and negative predictive values of 71%, 74%, 19%, and 97%, respectively. CONCLUSION: As noted in singleton pregnancies, fetal fibronectin testing in twins has a high negative predictive value. Fetal fibronectin evaluation may be a useful tool in screening twins with symptoms of preterm labor, because a negative result places these women at a low risk for delivering within 2 weeks of testing.     

The frequency and clinical significance of intra-amniotic inflammation in twin pregnancies with preterm labor and intact membranes

Objective: The objective of this study is to evaluate the frequency and clinical significance of intra-amniotic inflammation in twin pregnancies with preterm labor and intact membranes.

Study design: Amniotic fluid (AF) was retrieved from both sacs in 90 twin gestations with preterm labor and intact membranes (gestational age between 20 and 34 6/7 weeks). Preterm labor was defined as the presence of painful regular uterine contractions, with a frequency of at least 2 every 10?min, requiring hospitalization. Fluid was cultured and assayed for matrix metalloproteinase-8. Intra-amniotic inflammation was defined as an AF matrix metalloproteinase-8 concentration >23?ng/mL.

Results: The prevalence of intra-amniotic inflammation for at least 1 amniotic sac was 39% (35/90), while that of proven intra-amniotic infection for at least one amniotic sac was 10% (9/90). Intra-amniotic inflammation without proven microbial invasion of the amniotic cavity was found in 29% (26/90) of the cases. Intra-amniotic inflammation was present in both amniotic sacs for 22 cases, in the presenting amniotic sac for 12 cases, and in the non-presenting amniotic sac for one case. Women with intra-amniotic inflammation observed in at least one amniotic sac and a negative AF culture for microorganisms had a significantly higher rate of adverse pregnancy outcome than those with a negative AF culture and without intra-amniotic inflammation (lower gestational age at birth, shorter amniocentesis-to-delivery interval, and significant neonatal morbidity). Importantly, there was no significant difference in pregnancy outcome between women with intra-amniotic inflammation and a negative AF culture and those with a positive AF culture.

Conclusion: Intra-amniotic inflammation is present in 39% of twin pregnancies with preterm labor and intact membranes and is a risk factor for impending preterm delivery and adverse outcome, regardless of the presence or absence of bacteria detected using cultivation techniques.     

Coitus, twin pregnancy, and preterm labor

The effect of coitus on precipitation of preterm labor was studied prospectively in 126 women with twin pregnancies. All of the women attended a special antenatal clinic in a tertiary referral center and were questioned about the frequency of coitus. Of the participants, 40% reported coitus early in the third trimester; the rate decreased to 24% by 36 weeks' gestation. There were no significant differences in the frequency of positive responses between those who went into labor before term when contrasted with those who were delivered of infants at term. The data indicate that coitus is not an important precipitant of preterm labor in this high-risk group and that coitus need not be discouraged in women with twin pregnancies.     

Prediction and prevention of spontaneous preterm birth in twin gestations

The incidence of twin gestation has increased significantly over the past 30 years. One of the most significant public health implications of this trend is the increased incidence of preterm birth (PTB). Efforts to improve neonatal outcomes must address the rate of PTB, particularly among multiple gestations, which contribute a disproportionate share to the burden of PTB and neonatal morbidity. There is evidence that sonographic cervical length assessment and fetal fibronectin testing can identify twin pregnancies at risk for PTB, but, to date, there are no proven interventions for prevention of PTB in this population. Perhaps the most promising is vaginal progesterone, which has been shown to reduce the risk of PTB in a cohort of women that included twin gestations. However, the study lacked statistical power to definitively answer this question. Identification of an appropriate treatment for twin gestations recognized to be at increased risk for prematurity will help to decrease overall rate of PTB, a significant public health problem in the United States.     

Clinical and cost-effectiveness of continuous subcutaneous terbutaline versus oral tocolytics for treatment of recurrent preterm labor in twin gestations.

OBJECTIVE: To compare the clinical and cost-effectiveness of treating recurrent preterm labor with continuous subcutaneous terbutaline versus oral tocolytics in twin gestations. STUDY DESIGN: In a retrospective, matched-cohort design, twin pregnancies treated as outpatients with continuous subcutaneous terbutaline were identified from a perinatal database, then matched 1:1 by gestational age at recurrent preterm labor to those receiving oral tocolytics. There were 353 patients per treatment group. A cost model was used to compare antepartum hospital, nursery, and outpatient charges. RESULTS: Infants of the subcutaneous terbutaline group had greater gestational age at delivery, higher birth weights, and less frequent neonatal intensive care unit admission. Charges for antepartum hospitalization and nursery were significantly less in the subcutaneous terbutaline group, while charges for outpatient services were less for the oral group. Mean total estimated charges were US$17,109 less for those receiving subcutaneous terbutaline. CONCLUSION: Improved clinical outcomes and decreased nursery utilization suggest cost-effectiveness of outpatient continuous subcutaneous terbutaline versus oral tocolytics for the treatment of recurrent preterm labor.     

Case series of labor induction in twin gestations with an Intrauterine Balloon catheter.

The efficacy and safety of labor induction using an intrauterine balloon catheter in twin pregnancies has been evaluated. During the study period (1992-1997), labor was induced at 36-42 weeks in 17 twin gestations. Labor induction was indicated for preeclampsia (n = 10), birth weight discordance (n = 3), suspected fetal distress (n = 2) and postdates (n = 2). Twin A was in vertex presentation in all cases. An intrauterine balloon catheter was inserted transcervically followed by augmentation whenever required. Vaginal delivery was achieved in 15 (88.2%) patients. The mean interval from balloon insertion to delivery was 17.05 h, with 80% deliveries occurring within 24 h of catheter insertion and 80% occurring within 12 h of catheter expulsion. Birth weight was 2,514+/-244 and 2,421+/-367 g for twin A and B, respectively. Oxytocin was required in 4 patients. Postpartum hemorrhage was noted in 1 patient. One patient with no progress of labor and 1 with suspected intrapartum fetal distress required cesarean section. All neonates had a 5-min Apgar score of 10. The data suggest that an intrauterine balloon catheter appears to be safe and effective to induce labor in twin gestations.     

Comparison of active phase labor between triplet, twin, and singleton gestations

OBJECTIVE: To characterize the active phase of labor in triplet pregnancies and compare it with gestational age-matched twins and singletons. METHODS: Active phase rates were calculated beginning at 5 cm of dilation for women with triplet gestations longer than 24 weeks who labored and reached the second stage. Twin and singleton cohorts that also completed the first stage of labor were matched for gestational age at delivery (+/-1 week), parity, and epidural use. Intrapartum variables included oxytocin use (induction or augmentation, duration of infusion, and maximum dosage), cervical dilation at membrane rupture, and active phase dilation rate. RESULTS: Thirty-two triplet pregnancies met inclusion criteria between January 1994 and September 1998 and were each compared with twin and singleton cases in a 1:2 ratio. Triplet and twin active phase rates, while similar (1.8 versus 1.7 cm/hour, respectively), were significantly lower than the mean singleton dilation rate (2.3 cm/hour, P =.02). No other intrapartum variables differed between the three groups. Despite controlling for gestational age at delivery, mean birth weights were significantly higher in singletons and correspondingly lower in twins and triplets (2,493 versus 2,112 and 1,968 g, respectively; P =.001). An analysis of active phase dilation rates as a function of the cumulative birth weight per pregnancy demonstrated an inverse correlation, with slower progress in active labor associated with increasing total fetal weight (R = -.24; P =.002). CONCLUSIONS: Triplet and twin active phase dilation proceeds at a slower rate than that observed in singleton pregnancies. The rate of active phase dilation is inversely correlated to total fetal weight.     

Amniotic fluid glucose concentration: a rapid and simple method for the detection of intraamniotic infection in preterm labor.

The purpose of this study was to determine whether amniotic fluid glucose concentrations is of value in the rapid diagnosis of intraamniotic infection. Amniocenteses were performed in 168 patients with preterm labor and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as Mycoplasma species. The prevalence of positive amniotic fluid cultures was 13.6% (23/168). Patients with positive amniotic fluid cultures for microorganisms had significantly lower median amniotic fluid glucose concentrations than patients with negative amniotic fluid cultures (median 11 mg/dl, range 2 to 30 mg/dl vs median 28 mg/dl, range 3 to 74, respectively; p less than 0.001). Amniotic fluid glucose concentrations below 14 mg/dl had a sensitivity of 86.9% (20/23), a specificity of 91.7% (133/145), a positive predictive value of 62.5% (20/32), and a negative predictive value of 97.8% (133/136) in the detection of a positive amniotic fluid culture. Amniotic fluid glucose determination is a rapid, sensitive, inexpensive, and simple test for the detection of intraamniotic infection in women with preterm labor and intact membranes.     

Contributions of ischaemic placental disease to preterm birth in twin gestations

Objective.?To evaluate the extent to which ischaemic placental disease (IPD) – defined as women or newborns diagnosed with pre-eclampsia, small for gestational age (SGA), or abruption, is associated with preterm birth in twin gestations.

Methods.?A population-based study of women who delivered twin live births and stillbirths at 20–44 weeks gestation from 1995–2004 in the US was performed (n?=?1,105,666). We compared the frequency of IPD in term and preterm (<37 weeks) twin births. SGA was defined as twins with birthweight <10th percentile for gestational age, and corrected for infant sex. The association between IPD and preterm birth was expressed as hazard ratio, derived from Cox proportional hazard regression models after adjusting for potential confounders.

Results.?The overall rate of twin preterm birth was 57%. IPD was present in 20% of twin preterm births in comparison to a rate of 16% at term. Both pre-eclampsia and abruption, but not SGA, were associated with increased preterm birth rates. Women with two or more of the IPD conditions were more likely to deliver at preterm than at term gestations.

Conclusion.?In comparison to twin births delivered at term, IPD is more common in preterm births. Efforts to understand the role of IPD in twin gestations based on preterm birth subtypes may reveal important insights.     

Frequency and significance of preterm delivery in twin pregnancies.

OBJECTIVE: We investigated the frequency of preterm delivery and its influence on the neonatal outcome in twin pregnancies at a perinatal center. Are there differences in the course of twin pregnancies with preterm or term delivery? METHOD: A retrospective investigation was carried out at the Department of Obstetrics on 502 twin pregnancies and deliveries between 1978 and 1993. Pregnancy history and clinical parameters were compared among preterm (<37+0 weeks) and term deliveries. RESULT: Median duration of all twin pregnancies was 36+3 weeks of gestation. In the preterm group, preterm labor was more frequent, both, the first and the second neonate had lower birth weight and were more often admitted to the neonatal intensive care unit (NICU) where they stayed longer than full-term neonates needing intensive care. Perinatal deaths occurred only in the preterm group. CONCLUSIONS: The incidence of preterm delivery is significantly elevated in twin pregnancies and consequently the incidence of low- and very-low-birth-weight-infants and perinatal mortality. Preterm delivery is the main reason why twin pregnancies are at a higher risk for an adverse neonatal outcome and thereby cause considerable costs.     

Intraamniotic infection in patients with intact membranes and preterm labor.

The purpose of this review was to determine the frequency of intraamniotic infection in women with preterm labor and intact membranes and to assess the need for amniocentesis in these patients. We reviewed reports in the English language literature from the past 10 years in which the frequency of intraamniotic infection was determined by transabdominal amniocentesis. The 16 studies reviewed demonstrated frequencies of positive cultures that varied from 0 to 61 per cent. This extreme variability seems to be the result of diverse patient populations, dissimilar microbiologic techniques, and different definitions of preterm labor. Advanced cervical dilation and poor response to tocolytic agents were two factors associated with a higher frequency of intraamniotic infection. We conclude that each institution must determine the frequency of intraamniotic infection associated with preterm labor in their patient population. In populations with a high frequency of infection, amniocentesis for microbiologic evaluation is recommended for management of preterm labor, especially in patients who have advanced cervical dilatation or who are unresponsive to tocolytic therapy.     

Use of cervical ultrasonography in prediction of spontaneous preterm birth in twin gestations

OBJECTIVE: This study was undertaken to compare various ultrasonographic cervical parameters with respect to ability to predict spontaneous preterm birth in twin gestations. STUDY DESIGN: This prospective study involved 131 women carrying twins who were longitudinally evaluated on 524 occasions between 15 and 28 weeks' gestation with transvaginal cervical ultrasonography and transfundal pressure. The following cervical parameters were obtained: funnel width and length, cervical length, percentage of funneling, and cervical index. Receiver operating characteristic curve analysis was used to determine the ultrasonographic cervical parameter evaluated at 15 to 20 weeks' gestation, 21 to 24 weeks' gestation, and 25 to 28 weeks' gestation that were best for prediction of spontaneous preterm birth at <28 weeks' gestation, <30 weeks' gestation, <32 weeks' gestation, and <34 weeks' gestation. RESULTS: The median gestational age at delivery was 36 weeks' gestation (range, 21-41 weeks' gestation). Receiver operating characteristic curve analysis indicted that a cervical length of < or =2.0 cm, regardless of gestational age category at cervical measurement, was at least as good as other ultrasonographic cervical parameters at predicting spontaneous preterm birth. Between 15 and 20 weeks' gestation a cervical length cutoff value of < or =2.0 cm had specificities of 97%, 98%, 99%, and 100% and negative predictive values of 99%, 98%, 95%, and 89% for delivery at <28, <30, <32, and <34 weeks' gestation, respectively. The positive predictive values for delivery at <32 and <34 weeks' gestation were 80% and 100%, respectively. Between 21 and 24 weeks' gestation a cervical length of < or =2.0 cm had specificities of 84%, 84%, 85%, and 86% and negative predictive values of 99%, 99%, 94%, and 87% for delivery at <28, <30, <32, and <34 weeks' gestation, respectively. Between 25 and 28 weeks' gestation cervical length had excellent negative predictive values of 99%, 98%, 95%, and 93% for delivery at <28, <30, <32, and <34 weeks' gestation, respectively. CONCLUSIONS: In twin gestations a cervical length of < or =2.0 cm measured between 15 and 28 weeks' gestation was at least as good as other ultrasonographic cervical parameters at predicting spontaneous preterm birth. The high specificities indicate that cervical length was better at predicting the absence than the presence of various degrees of spontaneous prematurity.