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PubMed1992

[Experimental and clinical study on chorioamnionitis as a cause of preterm labor].

I performed the following studies to confirm the recent recognition of chorioamnionitis as a cause of preterm labor and to evaluate the effect of antibiotics in the treatment of this disease. 1. Models of chorioamnionitis were prepared using prepartal rabbits by directly inoculating bacteria at various concentrations into the amniotic cavity. Preterm deliveries occurred 2-3 days after inoculation in most of the animals when given no antibiotic, but not when treated with antibiotic after inoculation at 10(3) cells/ml or less. 2. These results were confirmed pathologically and bacteriologically in animals sacrificed 3 days after inoculation. 3. When morphologies of the placenta and umbilical cord obtained at various gestational weeks were examined, it was revealed that patients developing preterm labor or PROM before 33 gestational weeks had significantly severer inflammation than did others. 4. While I have undertaken antibiotic therapy in PROM patients since April, 1985, it has been noted that the length of time between its diagnosis and delivery can be prolonged by antibiotic therapy and that such treatment can also prevent neonatal infection. Thus it is concluded that infection is a cause of preterm labor and should therefore be treated with antibiotics to prevent preterm labor without hesitation.

Animals↗
PubMed2006

Ritodrine in oral maintenance of tocolysis after active preterm labor: randomized controlled trial.

AIM: To assess the efficacy of oral ritodrine in the form of sustained-release capsules for maintenance of uterine quiescence after successful treatment of threatened preterm labor. METHODS: We randomized 120 women with singleton pregnancy who were successfully treated for threatened preterm labor before 34 completed weeks to receive either maintenance tocolysis with two 40 mg ritodrine sustained release capsules three times a day (study group, n=62) or no treatment (control group, n=58) for three days. The primary outcome measure was the recurrent episode of threatened preterm labor within 72 hours, which was defined as regular palpable uterine contractions and change in cervical effacement or cervical dilatation on clinical examination. Secondary outcome measures included the incidence of preterm birth, neonatal adverse outcomes, and maternal side effects. RESULTS: There was no difference in the frequency of recurrent episodes of threatened preterm labor requiring another course of intravenous treatment between the study (8/62) and control (6/58) group of women (P=0.879). No differences were found between the study and control groups in any of the predefined secondary outcome measures, ie, delivery before 37 weeks (13/62 vs 7/58, respectively; P=0.288), delivery before 34 weeks (3/62 vs 1/58, respectively; P=0.682) and birth weight (3037-/+573 g vs 3223-/+423 g, respectively, P=0.862). There were more reported maternal side effects in the study group than in control group (47/62 vs 23/58, respectively; P(<0.001). CONCLUSIONS: Additional maintenance ritodrine therapy was unnecessary in women with singleton pregnancy who had an episode of threatened preterm labor successfully treated with intravenous tocolytic therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00290173.

Administration, Oral↗
PubMed1992

[Evaluation of the usefulness of enzymatic determination of estriol in urine and placental lactogen in serum of pregnant women with threatened preterm labor].

The authors studied 60 pregnant women in the pregnancy period from 29-37 weeks with threatened preterm labor. The control group formed 40 healthy pregnant women in the same pregnancy period. In all pregnant women the values of oestriol in 24-hour urine and placental lactogen in the serum was measured. Statistically significantly lower values of placental lactogen were found in the serum of pregnant women with threatened preterm labor. The values of oestriol in 24-hour urine were also lower, but the differences were not statistically significant. In 40 pregnant women in the pregnancy period from 16 to 28 weeks with threatened in the serum is a useful method of monitoring of pregnancy with threatened preterm labor. Determination of oestriol was without any greater diagnostic significance in the case threatened preterm labor.

Adult↗
PubMed2005

Arg16 homozygosity of the beta2-adrenergic receptor improves the outcome after beta2-agonist tocolysis for preterm labor.

BACKGROUND: Beta(2)-adrenergic receptor (beta(2)AR) agonists are not consistently successful when administered as tocolytic therapy. The beta(2)AR displays genetic variability; an arginine-to-glycine substitution at codon 16 (Arg16Gly) has been shown to increase receptor desensitization in response to agonist exposure, whereas a substitution of glutamate for glutamine at codon 27 (Gln27Glu) decreases down-regulation. We have demonstrated that homozygosity for Arg16 protects against preterm delivery. Our goal was to determine whether beta(2)-agonists are more effective in women with the Arg16 genotype and preterm labor. METHODS: Sixty white women with preterm labor between 24 and 34 weeks' gestation were treated for 48 hours with intravenous hexoprenaline. The effect of tocolysis and outcome of pregnancy were recorded. The beta(2)AR genotypes at codons 16 and 27 of ADRB2 were determined. A control group of 116 women delivered at term was also genotyped. RESULTS: Preterm labor was not associated with beta(2)AR genotype at codon 16 (17% of patients with preterm labor were Arg16 homozygotes versus 19% of control subjects) or codon 27. Gestation was significantly prolonged in Arg16 homozygotes (median, 69 days; interquartile range, 63-79 days) compared with the other 2 genotypes (median, 58 days; interquartile range, 2-72 days) (P = .04). Tocolysis was 100% successful in delaying delivery for 48 hours in Arg16 homozygotes (n = 10), just failing to achieve statistical significance (P = .069). In contrast, only 37 of 50 women carrying 1 or 2 glycine alleles (74%) had delivery delayed by more than 48 hours with tocolysis. Neonatal outcomes were significantly better in babies born to mothers homozygous for arginine than in women with 1 or 2 Gly16 alleles. CONCLUSIONS: This is the first study examining the pharmacogenetics of beta(2)AR agonist therapy for preterm labor. It appears that Arg16 homozygosity improves pregnancy outcome after beta(2)-agonist tocolysis. The relatively low frequency of Arg16 homozygotes in our population limited the power of this investigation. Future assessments of tocolytic therapy may need to assess beta(2)AR genotype.

Adrenergic beta-2 Receptor Agonists↗
PubMed2001

Pregnancy outcome in women with preterm labor symptoms without cervical change.

OBJECTIVE: This study was undertaken to determine pregnancy outcome in women who have preterm labor symptoms without cervical change according to fetal fibronectin status. STUDY DESIGN: Patients who were examined at the obstetric emergency department with symptoms of preterm labor but without cervical change underwent fetal fibronectin collection. Pregnancy outcome and fetal fibronectin results were analyzed after delivery. RESULTS: Of the 235 patients sampled, 20% (n = 48) had positive fetal fibronectin results. The mean +/- SD gestational age at delivery was lower in women with positive fetal fibronectin results (34.2 +/- 4.1 vs 37.7 +/- 2.3 weeks; P <.001); these women were more likely to deliver preterm as a result of preterm labor than women with other obstetric indications (46% vs 19%; P <.001). Infants born to these women demonstrated lower birth weight (2317 +/- 895 g vs 2877 +/- 557 g; P =.003), were more likely to be admitted to the neonatal intensive care unit (42% vs 14%; P <.001), and were more likely to die in the neonatal period (11% vs 0%; P <.001). CONCLUSION: Patients with symptoms of preterm labor but without cervical change who have negative fetal fibronectin results are less likely to deliver preterm. Therefore in women with symptoms but without cervical change fetal fibronectin should be considered for risk assessment.

Adult↗
PubMed2000

Maternal serum interleukin 6 levels in preterm labor: prediction of admission-to-delivery interval.

OBJECTIVE: To evaluate the diagnostic value of maternal serum interleukin 6 (IL-6), C-reactive protein (CRP) levels and white blood cell (WBC) count for the prediction of preterm labor and length of admission-to-delivery interval in patients with preterm labor. METHODS: Maternal serum IL-6, CRP and WBC count were prospectively determined in eighty-two patients in preterm labor and 21 controls. Data was analyzed in study and control groups, and for the assessment of clinical and laboratory risk factors in the prediction of admission-to-delivery interval in the study group. RESULTS: Maternal serum IL-6 levels were significantly higher in the study group than controls. The IL-6 value associated with the highest percent of true positives and true negatives for the prediction of preterm labor was 5 pg/ml. The area under curve of maternal IL-6 was significantly higher than the area under curve of of CRP and WBC count. In the study group maternal serum IL-6 levels were significantly higher in patients delivered within 2 and 7 days than the nondelivering ones and a cut off value of 8.3 pg/ml was determined for estimation of preterm delivery. CONCLUSION: Maternal serum IL-6 is a reliable marker in the prediction and management of preterm labor and delivery.

C-Reactive Protein↗
PubMed1991

Vaginal Bacteroides species are associated with an increased rate of preterm delivery among women in preterm labor.

The relationship of high concentrations of vaginal microorganisms with an increased rate of preterm delivery (less than or equal to 34 weeks) among women in preterm labor was evaluated. Quantitative vaginal cultures were obtained from 211 women in preterm labor between gestational ages of 22 and 34 completed weeks. Preterm delivery occurred in 139 (66%). The rate of preterm delivery was determined by Cox proportional hazards models. Women with greater than 10(7) cfu/ml of vaginal fluid of facultative lactobacilli had a 40% decreased rate of preterm delivery (rate ratio [RR] = 0.6, 95% confidence interval (CI) = 0.4-0.9). An increased rate of preterm delivery occurred among women with Bacteroides bivius at concentrations of greater than 10(4) cfu/ml (RR = 2.0, 95% CI = 1.4-2.9) and Bacteroides fragilis (RR = 1.7, 95% CI = 1.0-2.8). Other microorganisms, including Gardernella vaginalis, the genital mycoplasmas, group B streptococci, Escherichia coli, and Peptostreptococcus species, were not associated with an increased rate of preterm delivery for women in preterm labor.

Adolescent↗
PubMed2001

Abnormality of calcium channel inhibitor released from fetal membranes in preterm labor.

OBJECTIVE: This study was undertaken to test the hypothesis that an inhibitor of uterine contractions acting at the level of the dihydropyridine receptor of the uterine L -type uterine calcium channel is released in greater amounts from fetal membranes before term than at term. STUDY DESIGN: Endogenous calcium channel inhibitor activity was generated with standardized 25-cm2 surface area fetal membrane samples from the following 4 categories of women: preterm in labor, preterm not in labor, term in labor, and term not in labor. The amount of inhibitor in each membrane category was quantified by means of a competitive binding assay. Inhibition of uterine contractions induced by Bay K 8644 (an L -type calcium channel agonist) was used as another test of endogenous calcium channel inhibitor activity released from fetal membranes of all 4 groups of patients. RESULTS: Endogenous calcium channel inhibitor activity was most variable but present in the greatest amount in fetal membranes of women who were preterm not in labor followed by those in women at term not in labor and at term in labor. Fetal membranes from women in preterm labor had the least amount of measured endogenous calcium channel inhibitor activity. Consistent with the competitive binding assay, endogenous calcium channel inhibitor activity from fetal membranes from women who were preterm not in labor, at term not in labor, and at term in labor inhibited Bay K 8644-induced uterine contractions. Fetal membranes from women in preterm labor did not inhibit Bay K 8644-induced contractions. Endogenous calcium channel inhibitor activity was present in the chorion, the decidua, and the placenta, with little activity in the amnion. CONCLUSION: The down-regulation of endogenous calcium channel inhibitor activity with advancing gestation is consistent with a potential role for this inhibitor in maintaining uterine quiescence and in regulating the transition into labor. One possible cause of idiopathic preterm labor may be an abnormally low amount of endogenous calcium channel inhibitor activity in fetal membranes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

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.

Amniocentesis↗
PubMed2007

Targeted therapy for threatened preterm labor based on sonographic measurement of the cervical length: a randomized controlled trial.

OBJECTIVE: False positive diagnosis of preterm labor is common. As a consequence, medications including corticosteroids to promote fetal lung maturity and tocolysis are prescribed unnecessarily. We tested the hypothesis that management of threatened preterm labor based on measurement of cervical length by ultrasonography can reduce the number of women who receive inappropriate treatment. METHODS: Forty-one women with threatened preterm labor for whom a clinical decision was made to prescribe antenatal corticosteroids and tocolysis were randomized to have their cervical length measured by transvaginal ultrasound (n=21) or to receive therapy as planned (n=20). Fourteen women in the ultrasound group had a cervix longer than 15 mm and the therapy was withheld, while the other seven with a short cervix were managed in the same way as the control group. RESULTS: Three women (14%) in the ultrasound group were treated inappropriately with antenatal corticosteroids because they remained undelivered for more than a week. This compared favorably with the control group where 18 out of 20 (90%) received corticosteroids unnecessarily (relative risk (RR) 0.16; 95% confidence interval (CI), 0.05-0.39). Tocolysis was given to only seven women (33.3%) in the ultrasound group compared with 20 (100%) in the control group (RR 0.3; 95% CI, 0.15-0.54). There were no babies in either group who were born prematurely without being given a full course of antenatal corticosteroid therapy. CONCLUSION: Women with threatened preterm labor and cervical length more than 15 mm should not receive tocolysis. The issue of the safety of withholding corticosteroid therapy in this clinical scenario warrants further study.

Adrenal Cortex Hormones↗
PubMed2000

[Relationship between the alteration of 6-keto-PGF1 alpha and TXB2 in cervical mucus of patients with threatened preterm labor and the efficacy of magnesium sulfate treatment].

This study was conducted to observe the relationship between the alteration of 6-keto-PGF 1 alpha and TXB2 in cervical mucus of patients with threatened preterm labor and the efficacy of magnesium sulfate treatment, and to examine whether they could act as markers of efficacy and prognosis in treatment of preterm labor. Cervical mucus was collected from 28 patients with threatened preterm labor before and after magnesium sulfate treatment, the levels of 6-keto-PGF1 alpha and TXB2 were determined by radioimmunoassay (RIA). The results showed that the levels of 6-keto-PGF1 alpha and TXB2 decreased in patients successfully treated with magnesium sulfate (P < 0.01), and the ratio of 6-keto-PGF1 alpha to TXB2 increased significantly (P < 0.001). The levels of 6-keto-PGF1 alpha and TXB2 increased in patients with failed magnesium sulfate treatment (P < 0.01), and the relevant ratio decreased significantly (P < 0.001). The results indicate that the levels of 6-keto-PGF1 alpha and TXB2 in the cervical mucus of patients with threatened preterm labor may change significantly before and after magnesium sulfate treatment and they could be used as markers of efficacy and prognosis in treatment of preterm labor.

6-Ketoprostaglandin F1 alpha↗
PubMed2003

Detection of Ureaplasma urealyticum in second-trimester amniotic fluid by polymerase chain reaction correlates with subsequent preterm labor and delivery.

Ureaplasma urealyticum is the microorganism most frequently isolated from the amniotic fluid of women in preterm labor. The relationship between intra-amniotic U. urealyticum in healthy second-trimester pregnant women and subsequent pregnancy outcome was investigated. Transabdominal amniotic fluid obtained from 254 asymptomatic women at 15-17 weeks' gestation were tested by polymerase chain reaction (PCR). U. urealyticum was identified in 29 subjects (11.4%). A subsequent preterm labor occurred in 17 U. urealyticum-positive women (58.6%), compared with 10 (4.4%) U. urealyticum-negative women (P<.0001). Preterm birth was documented in 7 (24.1%) U. urealyticum-positive women compared with only 1 U. urealyticum-negative woman (0.4%) (P<.0001). U. urealyticum-positive women also had a higher prevalence of preterm labor in a prior pregnancy (20.7%) than did the negative women (2.7%; P=.0008). PCR testing of second-trimester amniotic fluid for U. urealyticum can identify women at risk for subsequent preterm labor and delivery.

Adult↗
PubMed1989

A randomized trial of electronic fetal monitoring in preterm labor: mothers' views.

To determine if perceptions of preterm labor and birth differed between women who were monitored by electronic fetal monitoring (EFM) or by periodic auscultation, 135 subjects were randomly assigned to one of two treatment groups on admission to a tertiary perinatal care setting. The first group received external monitoring by continuous Doppler and tocodynamometer when membranes were intact, and with an internal fetal scalp electrode and pressure catheter once membranes were ruptured. The second group received periodic monitoring with a DeLee fetoscope or amplified Doppler. All women were cared for on a one-to-one basis by expert study nurses. Subjects completed a questionnaire about their labor experience during their postpartum hospital stay. There was no statistically significant difference between the two groups on the study measures [T2(7,81) = 13.65; F = 1.82; P greater than 0.05]. Forty-four percent of the variance in women's global evaluation of labor was explained by their perceptions of nursing support. These findings suggest that mothers' perceptions of their preterm labor are less influenced by the technologic interventions used than by the supportive care received from nurses.

Adolescent↗
PubMed1990

Uterine activity and symptoms as predictors of preterm labor.

Women enrolled in a previously reported prospective trial of ambulatory tocodynamometry who developed preterm labor while using an ambulatory tocodynamometer were candidates for this analysis. Data from 51 women who met these entry criteria were evaluated and placed into four groups according to the initial reason for evaluation for preterm labor: monitored uterine activity, symptoms, both contractions and symptoms, or cervical examination at a routine office visit. Less than half (43%) had both subjective symptoms and an increase in monitored contraction frequency; 24% were initially identified by symptoms, 24% by uterine activity, and 10% at a routine office visit. We conclude that waiting for both an increase in uterine activity and subjective symptoms of labor will delay diagnosis in 50% or more of preterm labor patients and that women at risk of preterm birth should be evaluated promptly if either contractions or symptoms persist.

Adult↗
PubMed2006

Preterm labor is induced by intraamniotic infusions of interleukin-1beta and tumor necrosis factor-alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model.

OBJECTIVES: The purpose of this study was to determine the relative contributions of individual proinflammatory cytokines and chemokines to the triggering of preterm labor. STUDY DESIGN: Eighteen chronically instrumented pregnant rhesus monkeys at 135 +/- 3 days gestation (term = 167 days) received 1 of 5 intraamniotic infusions: (1) interleukin-1beta (IL-1beta) (10 microg; n = 5), (2) tumor necrosis factor-alpha (TNF-alpha) (10-100 microg; n = 5), (3) IL-6 (20 microg twice a day; n = 2), (4) IL-8 (20 microg twice a day; n = 2), and (5) saline control (n = 4). Primary study outcomes were the mean uterine hourly contraction area (mm Hg x s/h) in 24 hours during peak response to cytokine infusion (all groups) and the interval from cytokine infusion until labor onset (IL-1beta, IL-6, and IL-8 groups). Secondary outcomes were quantities of amniotic fluid cytokines and chemokines (IL-1beta, TNF-alpha, IL-6, and IL-8), prostaglandins E2 and F2alpha, leukocytes, and matrix metalloproteinase-9 (MMP-9). Histopathology of fetal lungs and placental membranes was assessed. RESULTS: IL-1beta stimulated the most intense contraction patterns, resulting in preterm labor in all cases. TNF-alpha induced a variable degree of uterine activity among individual animals stimulating either preterm labor (n = 2) or a uterine contraction pattern of moderate intensity (n = 3). Despite prolonged elevations in amniotic fluid levels, neither IL-6 nor IL-8 induced preterm labor or an increase in uterine activity until near term. The mean interval from the initiation of IL-6 and IL-8 infusion to the onset of labor was significantly longer than after IL-1beta (21.9 vs 1.1 days; P < .01), and did not differ from the saline control group (27.6 days; P = NS). Intraamniotic infusion of IL-1beta or TNF-alpha was associated with significant elevations in all tested amniotic fluid cytokines, IL-8, prostaglandins, MMP-9 and leukocytes compared with gestational age-matched saline controls. IL-6 and IL-8 infusions were not associated with increases in IL-1beta or TNF-alpha and only produced a moderate increase in amniotic fluid prostaglandins. All cytokine infusions induced histologic chorioamnionitis and an accumulation of neutrophils in fetal lungs. CONCLUSION: Preterm labor was induced by intraamniotic infusions of IL-1beta and TNF-alpha, but not by IL-6 or IL-8 although inflammatory changes in fetal membranes and lungs were uniformly present. Our results indicate a primary role for IL-1beta and TNF-alpha in the triggering of preterm labor associated with inflammation or infection.

Amniotic Fluid↗
PubMed2004

Oral salbutamol for treatment of preterm labor.

OBJECTIVE: The aim of this study was to assess the value of oral salbutamol for the inhibition of preterm labor. MATERIAL AND METHOD: Medical records of the department from January 1, 1991 to December 31, 1999 were reviewed for all idiopathic preterm labors that were inhibited by oral salbutamol and statistically analyzed. RESULTS: Of 132 pregnancies, 81.1% (95%CI, 74.4, 87.7) were prolonged for more than 24 hours, 59.8% (95%CI, 51.5, 68.2) for more than 2 days, 32.6% (95%CI, 24.6, 40.6) for more than 1 week, and 8.3% (95%CI, 4.2, 14.4) for more than 4 weeks. Tachycardia (pulse rate > 100 beats/min) occurred in 85.6% of the patients, but those with a pulse rate higher than 140 beats/min occurred in only 3%. Hypotension occurred in only 0.8%. Neonatal complications occurred in 28%, while respiratory distress syndrome occurred in 22.7% of the babies. Perinatal mortality in the present study was 7.6 per 1,000 births. When comparing the pregnancy outcome between groups regarding the prolongation time, the pregnancy outcome was significantly better in the group that had a prolongation time of at least 48 hours. CONCLUSION: Oral salbutamol proved to be another effective method that inhibits preterm labor and consequently prolongs pregnancy. Because it requires no intensive medical nursing care and observations, and no discomfort of an intravenous line, oral salbutamol may be an alternative drug in the management of preterm labor.

Administration, Oral↗
PubMed1990

The prevalence of substance abuse in patients with suspected preterm labor.

Premature labor is a recognized complication of substance abuse in pregnancy. However, the prevalence of substance abuse in patients first seen with symptoms of preterm labor and who deny use of illicit drugs is unknown. Between July 1, 1988, and December 15, 1988, 141 patients first seen at Northwestern Memorial Hospital in suspected preterm labor and a comparison group of 108 uncomplicated laboring term patients had urine toxicology screening performed to detect substance abuse. Positive urine toxicology screenings were found in 24 of 141 (17.0%) patients with suspected preterm labor and in 3 of 108 (2.8%) patients in the comparison group. The most common substance identified was cocaine (14/24 and 1/3, respectively). Of those patients in suspected preterm labor, 22 of 86 (25.6%) clinic patients had positive urine toxicology screenings as did 2 of 55 (3.6%) private patients. On the basis of our observations, we recommend that patients admitted in possible preterm labor be encouraged to submit to screening for substance abuse so that appropriate counseling and prenatal and neonatal care become available for these high-risk patients.

Adolescent↗