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Assessment of uterine activity in ambulatory patients at high risk of preterm labor and delivery.

With use of an ambulatory tocodynamometer, prelabor uterine activity was recorded daily during pregnancy in 34 patients at increased risk of preterm labor and delivery. The data indicate that the frequency of contractions was significantly greater among women who subsequently developed preterm labor when compared to that observed among women who labored at term. This difference was present up to several weeks before the onset of labor. An additional significant rise in frequency of contractions could be observed within the last 24 hours before the development of clinically apparent preterm labor, as evidenced by progressive cervical dilation and effacement. If these results can be reproduced in a larger sample, intermittent ambulatory monitoring may offer an effective way to better identify patients at risk of preterm labor as well as enhance the early diagnosis of this event.

Adult↗

A multicenter evaluation of intramuscular ritodrine hydrochloride as initial parenteral therapy for preterm labor management.

Ninety-four patients in documented preterm labor received three intramuscular injections of ritodrine hydrochloride over an interval of 6 hours. They subsequently received the tocolytic agent intravenously for a minimum of 6 hours. The effects of ritodrine on uterine activity and the cardiovascular system were determined. Intramuscular ritodrine hydrochloride elicited a prompt and sustained reduction in the frequency of uterine contractions. The transition to intravenous treatment was achieved without an increase in uterine activity. Seventy percent of the patients had a sustained interval of uterine quiescence, and 96% had at least a 24-hour delay in delivery. Initial parenteral therapy with intramuscular ritodrine hydrochloride is safe and effective and may provide an alternative to intravenous therapy and a means of managing preterm labor during interhospital transport of a patient.

Adult↗

Amniotic fluid intercellular adhesion molecule-1 is a marker for Ureaplasma infection in women with preterm labor.

OBJECTIVE: The objective of the study was to determine the amniotic fluid soluble intercellular adhesion molecule-1 concentrations in women with preterm labor in relation to intra-amniotic infection. STUDY DESIGN: Amniotic fluids from 125 women with preterm labor (78 with preterm delivery and 47 with term deliveries) were examined for both soluble intercellular adhesion molecule-1 concentrations and intra-amniotic infection with Ureaplasma species. A chi2 test, or Fisher's exact test, when appropriate, was used for statistical analysis. RESULTS: In the preterm delivery group, 45% (35 of 78) had intra-amniotic infection with Ureaplasma species, compared with 19% (9 of 47) in the term delivery group (P = .004). In women with intra-amniotic infection, 26% (9 of 38) had soluble intercellular adhesion molecule-1 levels above 1290 ng/ml. Only 2.3% (1 of 43) in the preterm delivery group without intra-amniotic infection attained this diagnostic level (P = .004). In contrast, there was no significant difference in soluble intercellular adhesion molecule-1 levels between those with or without intra-amniotic infection in the term delivery group. CONCLUSION: Amniotic fluid soluble intercellular adhesion molecule-1 concentrations exceeding 1290 ng/ml can be used as a marker for intra-amniotic infection with Ureaplasma in patients with preterm labor.

Adult↗

Inflammatory cytokine mRNA in human gestational tissues: implications for term and preterm labor.

OBJECTIVE: To determine if inflammatory cytokine mRNA in gestational tissues is present only in the setting of infection-associated preterm labor or under several other clinical conditions. METHODS: Human gestational tissues were collected from 51 women experiencing 1) term cesarean delivery without labor, 2) normal term vaginal delivery, 3) preterm cesarean delivery without labor, 4) preterm vaginal delivery without chorioamnionitis, and 5) preterm vaginal delivery with concomitant chorioamnionitis. Decidua, chorion, and amnion were isolated, total RNA from each tissue was extracted, and the presence of inflammatory cytokine mRNA was determined by polymerase chain reaction. Interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor-alpha mRNA was detected using specific oligonucleotide primers. RESULTS: Interleukin-1 beta mRNA was rarely found in tissues preterm without labor but was readily detected in both maternal and fetal tissues after labor, regardless of gestational age. Interleukin-6 mRNA was rare in tissues from the nonlaboring patient but was found in almost all tissues after labor. Interleukin-8 mRNA was detected in all tissues at term, both in nonlaboring and laboring patients. Tumor necrosis factor-alpha mRNA was detected in only 20-50% of tissues after labor, and was rarely detected in the absence of labor. CONCLUSIONS: Inflammatory cytokine mRNA is commonly expressed in human gestational tissues after normal labor and preterm labor with or without associated intrauterine infection. There was no difference in the pattern of expression of mRNA inflammatory cytokine in women who did or did not have clinically evident intrauterine infection.

Adolescent↗

The association of subclinical infection with preterm labor: the role of C-reactive protein.

The role of subclinical intrauterine infection in preterm labor was evaluated prospectively in 40 patients and appropriate control subjects. The 24 preterm labor patients (60%) with a negative C-reactive protein value responded to tocolysis 95.8% of the time, with a mean delay of delivery of 35.5 days and a mean gestational age of 36.9 weeks. The 16 patients (40%) with a positive C-reactive protein value responded to tocolysis only 37.5% of the time, with a mean delay of delivery of 14.4 days and a mean gestational age of 33.2 weeks. Pathologic evidence of chorioamnionitis was present in 32.9% of 310 preterm deliveries as compared to only 22.3% of 1631 term deliveries. The presence of subclinical infection must be considered in cases of preterm labor, especially among patients for whom tocolytic therapy is unsuccessful.

Adult↗

[Relation between cervical conization, microbial colonization and threatening preterm labor].

UNLABELLED: The relationship between prior cervical conization, the cervical microbial colonization and threatening preterm delivery was investigated in 35 women with preterm premature rupture of the membranes (PPROM), 38 women with idiopathic preterm labor and 75 normal pregnant women at 26-34 weeks of gestation. Prior cervical conization occurred with a significantly higher frequency in PPROM patients than in patients with preterm labor (p < 0.01) and normal pregnant women (p < 0.001). The prevalence of lactobacilli was lower in patients with PPROM than in patients with preterm labor (p < 0.05) and control patients (p = 0.05)--and lower in patients with prior cervical conization than in patients without prior conization (p < 0.05). All other microorganisms occurred with the same frequencies in all groups. CONCLUSIONS: Prior conization was associated with PPROM. Women with prior conization and women with PPROM had a reduced prevalence of lactobacilli in the cervix. The "absence" of lactobacilli may indicate changes in the cervical microflora, which could be of importance for PPROM.

Adult↗

Intermittent weekly contraction monitoring to predict preterm labor in low-risk women: a blinded study.

To assess the predictive value of uterine activity as a marker for subsequent preterm labor, 139 black, inner city women were monitored at least three times for 1 hour between 28-32 weeks' gestation using a portable tocodynamometer. All had singleton gestations and gave no previous history of preterm labor or delivery. They were monitored between 8 and 10 AM while sitting in the clinic waiting area. Uterine activity records, numbered randomly, were transmitted by telephone to a site remote from the hospital. No one having any clinical contact with the participants saw or received feedback regarding the contraction data. Tocodynamometry records were then mailed to another center where they were read by one investigator blinded to all clinical information. The mean contraction frequency during the single hour of weekly testing was significantly greater for the 16 women who developed preterm labor than for women who delivered at term at each point between weeks 28-32. Using greater than six contractions per hour on at least one occasion between 28-32 weeks' gestation as a predictor would have identified 12 of 16 women (sensitivity 75%) who subsequently developed preterm labor. This contraction frequency was noted in 26 of 123 women (21%) who labored at term (specificity 79%; P = .0003).

Female↗

Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor.

High-dosage, tocolytic magnesium sulfate (MgSO4) administered to pregnant women during preterm labor can be toxic, and sometimes lethal, for their newborns (Cochrane Database of Systematic Reviews (relative mortality risk 2.82, 95% confidence interval 1.2-6.6)). Based on the results of the Magnesium and Neurologic Endpoints Trial and the work of many others, a unifying triangular concept is proposed to account for the increased prevalence of brain lesions, with their likely resultant mortality, in neonates and infants exposed to high-dose MgSO4 in the context of preterm labor. We review the evidence that: (1) elevated circulating levels of serum ionized magnesium occurring in mothers, and therefore in their babies, at the time of delivery are associated with subsequent neonatal intraventricular hemorrhage (IVH); (2) neonatal IVH is strongly associated with lenticulostriate vasculopathy (LSV), an unusual mineralizing lesion involving the thalami and basal ganglia of the neonate; and, (3) exposure to 50 g or more of tocolytic MgSO4 during preterm labor is associated with the development of LSV.

Basal Ganglia Cerebrovascular Disease↗

Evaluation of a risk-scoring system for prediction of preterm labor.

A scoring system was used prospectively to screen 7329 patients for risk of preterm labor over a 6-year period. When 15.8% of patients (1156 of 7329) were scored as high risk, sensitivity was 42.4% (multiparas, 55.2%, nulliparas, 29.8%) and positive predictive value was 22.8%. The incidence of preterm labor increased with increasing risk score; gestational age at delivery was negatively correlated with risk score. Analysis of individual factors revealed that more than half were not of predictive value in the population under investigation. A simplification of the system, defining 12 of the factors as major (high risk) and six as minor (2 or more indicates high risk) yielded a high risk group of 14.1%, sensitivity of 41.0%, and positive predictive value of 24.6%. Thus, although risk scoring does predict a substantial proportion of patients with preterm labor, its sensitivity is less than ideal. No advantage was gained with a larger and more complex system. Planning for preterm birth prevention programs should include recognition of the limitations of risk scoring, consideration of simplified systems, and investigation of additional biochemical or biophysical screening methods.

Female↗

Serum ionized magnesium during magnesium sulfate administration for preterm labor and preeclampsia.

OBJECTIVE: The purpose of this study is to estimate the relations between ionized and total Mg levels during MgSO4 administration in patients with preterm labor and preeclampsia. METHODS: Forty-three pregnant patients who were candidates for MgSO4 were studied (preterm labor, 27; preeclampsia, 16). The administration method was intravenous injection of MgSO4 4 g over 30 min followed by 1-2 g/h. Ionized Mg was measured by the selective ion electrode method at bedside, and compared it with total Mg levels. RESULTS: Significant correlation was existed between levels of ionized and total Mg throughout therapy for both preterm labor (ionized Mg=0.19 x total Mg+0.19; r=0.61, p<0.001) and preeclampsia (ionized Mg=0.20 x total Mg+0.14; r=0.60, p<0.001). CONCLUSION: There are correlations between ionized and total Mg levels during administration of MgSO4 for both preterm labor and preeclampsia.

Female↗

Maternal and perinatal outcome of patients with preterm labor and meconium-stained amniotic fluid.

OBJECTIVE: To determine the clinical significance of meconium-stained amniotic fluid (AF) observed at amniocentesis in patients with preterm labor. METHODS: A nested case-control study was constructed based on the color of AF during amniocentesis. Forty-five women admitted with preterm labor and meconium-stained AF were matched for gestational age at admission and compared with 135 women with preterm labor and clear AF. All AF samples were cultured for aerobic and anaerobic bacteria and mycoplasma. RESULTS: The rates of positive AF cultures for microorganisms, overall preterm birth (before 36 weeks), preterm birth before 32 weeks, and clinical chorioamnionitis were all significantly higher in patients with meconium-stained AF than in those with clear AF (positive AF cultures, 38 versus 11%, P < .001; preterm delivery before 36 weeks, 73 versus 41%, P < .001; preterm delivery before 32 weeks, 51 versus 17%, P < .001; and clinical chorioamnionitis, 22 versus 6%, P = .003). In contrast, no significant differences were observed between groups with respect to maternal age, gravidity, parity, abruptio placentae, placenta previa, fetal distress, cesarean rate, or puerperal morbidity. CONCLUSION: Patients with preterm labor and meconium-stained AF had higher rates of microbial invasion of the amniotic cavity, clinical chorioamnionitis, and premature deliveries than those with clear AF.

Adult↗

Production of prostaglandin E2 by human amnion in vitro in response to addition of media conditioned by microorganisms associated with chorioamnionitis and preterm labor.

To examine the potential role of bacterial infection in the cause of spontaneous preterm labor, human amnion cells in tissue culture were exposed to medium conditioned by culturing each of 21 microorganisms previously found in association with chorioamnionitis and preterm labor. At a final concentration of 0.1% bacterial conditioned medium, a significant stimulation of prostaglandin E2 production from amnion cells was observed for this range of microorganisms. Conditioned medium obtained from culturing Bacteroides fragilis caused a dose-related increase in prostaglandin production, final concentrations of 0.02% to 0.1% being stimulatory but greater concentrations (0.1% to 10%) causing a progressive inhibition of prostaglandin synthesis. A similar concentration-related response in which stimulation was followed by inhibition occurred on addition of increasing concentrations of phospholipase A2 to amnion cells. These data suggest that bacterial phospholipase may release arachidonic acid from amnion leading to prostaglandin E2 synthesis, but excessive addition of phospholipase and consequent increased arachidonic acid availability may give rise to substrate inhibition of cyclooxygenase enzyme and inhibit prostaglandin E2 synthesis. Overall it appears that a wide variety of microorganisms associated with preterm labor may secrete phospholipase, which liberates amnion arachidonic acid for conversion to the oxytocic agent prostaglandin E2.

Amnion↗

A double-blind study comparing ritodrine and terbutaline in the treatment of preterm labor.

One hundred women in preterm labor were randomly treated with ritodrine or terbutaline in a double-blind fashion. The drugs were comparably effective during intravenous therapy but, in women with intact membranes, an oral dose of terbutaline, 30 mg daily, was significantly more effective than ritodrine, 120 mg daily, in preventing recurrent labor during a 5-day course of oral therapy (one of 19 versus 12 of 23, p less than 0.001). In women with intact membranes, pregnancy was prolonged 40 +/- 25 days (mean +/- SD) in women receiving terbutaline orally and only 22 +/- 24 days in women receiving ritodrine orally (p less than 0.01). In women with intact membranes, a heart rate greater than or equal to 130 bpm occurred in in a higher proportion of women receiving intravenous treatment with ritodrine than among those receiving terbutaline (20 of 31 versus 8 of 27, p less than 0.05). Terbutaline-treated women, however, were significantly more likely to have a serum glucose level in excess of 140 mg/dl than were women treated with ritodrine (13 of 26 versus 6 of 29, p less than 0.05). Side effects commonly observed during intravenous therapy included nausea (22%), chest pain (15%), and shortness of breath (15%). Side effects were significantly (p less than 0.025) more likely to occur during periods when the infusion rate was being increased rather than during periods when the infusion rate was constant.

Blood Glucose↗

Predictive value of maternal serum and vaginal interleukin-6 levels in preterm labor.

OBJECTIVE: The aim of the current study was to evaluate the predictive value of maternal serum and vaginal interleukin 6 (IL-6) levels for preterm delivery before 37 gestational weeks in patients with preterm labor and to determine the probable relationship between IL-6 concentrations and delivery interval. METHODS: In this prospective study, maternal serum and vaginal IL-6 levels were measured in 40 patients with the diagnosis of preterm labor between the 28th and 36th gestational weeks (study group) and in 20 pregnant women between the same gestational weeks attending the antenatal clinic with no complaints (control group). The gestational age at the time of admission and delivery, as well as the delivery interval, were evaluated and compared with the concentration of IL-6 on admission. RESULTS: There were no significant relationships between maternal serum concentrations of IL-6 and preterm delivery. Vaginal IL-6 levels were significantly higher in the study group as compared with the control group (P < .001). The optimal cut-off value for vaginal IL-6 (172 pg/mL) gave a sensitivity level of 73.9% (95% confidence interval [CI], 67-82%) at a specificity of 100% (95% CI, 91-100%) with positive and negative predictive values of 94.1% and 83.7%, respectively. In the study group, the interval from collection to delivery was significantly shortened when the maternal vaginal IL-6 levels increased. CONCLUSION: The ease of measurement, feasibility, cost-effectiveness, and success of identifying pregnancies at risk for preterm labor with vaginal IL-6 make this a useful biochemical marker for preterm labor and delivery.

Adult↗

The presence of amniotic fluid leukoattractants accurately identifies histologic chorioamnionitis and predicts tocolytic efficacy in patients with idiopathic preterm labor.

OBJECTIVES: We tested these hypotheses: (1) that amniotic fluid from patients with idiopathic preterm labor and histologic chorioamnionitis contains leukoattractants and (2) that the detection of amniotic fluid leukoattractants is an accurate predictor of tocolytic efficacy. STUDY DESIGN: Amniotic fluid from 86 patients in idiopathic preterm labor was evaluated by microbiologic tests and leukotaxis assay. The tests' ability to predict histologic chorioamnionitis and response to tocolysis (51 tocolytic candidates) is established. Statistical analysis was performed with Fisher's exact test and unpaired Student t test. RESULTS: The detection of amniotic fluid leukoattractants was a better predictor of histologic chorioamnionitis (97%) than were amniotic fluid microbiologic tests (62%) (p less than 0.01). Also, in patients with detectable amniotic fluid leukoattractants tocolysis failed significantly more often than in patients without detectable leukoattractants (93% vs 7%, p less than 0.01). CONCLUSION: The presence of leukoattractants in amniotic fluid detected by the leukotaxis assay accurately identifies histologic chorioamnionitis and can additionally predict tocolytic efficacy in patients with idiopathic preterm labor.

Amniotic Fluid↗

Course of maternal serum magnesium levels in low-risk gestations and in preterm labor and delivery.

OBJECTIVES: To describe the course of total and ionized magnesium and total calcium levels in maternal serum during low-risk pregnancies and to compare women who developed preterm labor and delivery with those who delivered at term. METHODS: 209 women with low-risk pregnancies were enrolled in a prospective trial before the 18th week of gestation. No woman received oral magnesium supplementation. The ionized and total magnesium and total calcium levels in maternal serum were measured every 4-6 weeks. The data were grouped into 3 gestational periods (</=18, 19-27 and >/=28 weeks of gestation) for overall comparison and analyzed with the general linear model for repeated measurements and ANOVA. p values of < 0.05 were considered statistically significant. RESULTS: 145 gestations were available for analysis. 27 women were hospitalized for preterm labor and in 16 of these preterm delivery occurred. Ionized and total magnesium and calcium levels were significantly lower after the 18th week of gestation than before. The cation levels in women with preterm labor and delivery did not differ from those with term delivery. CONCLUSION: Ionized and total magnesium and calcium levels decrease with increasing gestational age. Preterm labor and delivery do not seem to be related to changes in serum cation levels.

Adult↗

Sulindac to prevent recurrent preterm labor: a randomized controlled trial.

OBJECTIVE: To assess the efficacy of oral sulindac in low doses for prolonged duration to decrease the risk of recurrent preterm labor and extend gestation. METHODS: This was a randomized, double-blind, placebo-controlled study of patients between 24 and 34 weeks' gestation with preterm labor treated with intravenous magnesium sulfate. After successful tocolysis, patients were randomized by the pharmacy to receive either oral sulindac (100 mg) or placebo orally every 12 hours until 34 weeks' gestation. A power analysis required 43 patients in each group. RESULTS: Ninety-five patients were enrolled (46 in the sulindac group, 49 controls). No significant differences were found with respect to time gained in utero (39 +/- 25 versus 45 +/- 26 days, P = .29), delivery at more than 35 weeks' gestation (61% versus 74%, P = .29), recurrent preterm labor (20% versus 18%, P = .86), birth weight (2562 +/- 623 versus 2624 +/- 543 g, P = .62), or time spent in the neonatal intensive care unit (2.8 +/- 9.2 versus 2.4 +/- 8.6 days, P = .83) for the sulindac and control groups, respectively. CONCLUSION: The use of oral sulindac until 34 weeks' gestation after successful parenteral tocolysis failed to reduce the incidence of readmission for preterm labor.

Administration, Oral↗

Relationship of amniotic fluid markers of intra-amniotic infection with histopathology in cases of preterm labor with intact membranes.

OBJECTIVE: To evaluate the correlation of amniotic fluid (AF) markers (AFMs) of intra-amniotic infection with histopathologic findings in cases of preterm labor with intact membranes, between 22 and 36 weeks' gestation. STUDY DESIGN: We reviewed the charts of patients admitted in preterm labor with intact membranes between January 1993 and December 1996. Those having amniocentesis were identified, and AFMs were compared with histopathology in patients who delivered within 48 hours of the amniocentesis. The AFMs evaluated were glucose, polymorphonuclear leukocytes, Gram stain, and culture. All placentae were reviewed by a single pathologist blinded to the AF findings. Histologic evidence of acute inflammation was defined by findings of both subchorial intervillositis and marginating choriodeciduitis. The sensitivities, specificities, and positive and negative predictive values of the various AFMs were calculated. RESULTS: Of 556 women with intact membranes presenting in preterm labor, 181 (32.6%) had amniocentesis and 88 delivered within 48 hours of the amniocentesis. Histopathologic chorioamnionitis was seen in 53 patients (60.2%). The findings (with their sensitivity, specificity, and positive and negative predictive values) were: polymorphonuclear leukocytes at > 10/high-power field (22.6%, 97.2%, 92.3%, and 46.1%), positive Gram stain (26.4%, 94.6%, 87.5%, and 47.3%), culture (28.3%, 92.1%, 83.3%, and 47.9%), and glucose of < 15 mg/dl (28.3%, 94.6%, 88.2%, and 47.9%), respectively. Using a receiver-operator characteristic curve for different level of AF glucose, a glucose level of < 20 mg/dl was the most sensitive AF predictor of histologic chorioamnionitis. CONCLUSION: Histopathologic evidence of chorioamnionitis was present in 60.2% of cases of preterm births due to preterm labor in women who at our institution were offered and accepted amniocentesis and subsequently delivered within 48 hours. AFMs may be useful predictors of histologic chorioamnionitis. The most efficient AFM for chorioamnionitis in this group of patients was glucose at < 20 mg/dl.

Adult↗