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Monitoring women at risk for preterm labor.

BACKGROUND: Preterm birth is a major cause of perinatal morbidity and mortality. Whether the rate of preterm birth can be reduced by frequent contact between nurses and pregnant women or home monitoring of uterine activity is not known. METHODS: We randomly assigned 2422 pregnant women with known risk factors for preterm labor (including 844 women who were pregnant with twins) to receive education and to have one of the following: weekly contact with a nurse, daily contact with a nurse, or daily contact with a nurse and home monitoring of uterine activity. The nurses elicited the women's own assessments of their symptoms and signs of preterm labor. The primary end point was the incidence of birth at less than 35 weeks' gestation. Secondary end points included cervical status at the time preterm labor was diagnosed and birth weight. RESULTS: There were no significant differences among the groups in the incidence of birth at less than 35 weeks (14 percent in the weekly-contact group, 13 percent in the daily-contact group, and 14 percent in the home-monitoring group), in the mean amount of cervical dilatation at the time preterm labor was diagnosed (1.8 cm, 1.5 cm, and 1.4 cm, respectively), or in such neonatal outcomes as birth weights of less than 1500 g or less than 2500 g. However, daily contact with a nurse increased the mean number of unscheduled visits to obstetricians (1.2 in the weekly-contact group, 1.8 in the daily-contact group, and 2.3 in the home-monitoring group) and the proportion of women who received prophylactic tocolytic drugs (12 percent, 14 percent, and 19 percent, respectively). CONCLUSIONS: Women who have daily contact with a nurse, with or without home monitoring of uterine activity, have no better pregnancy outcomes than women who have weekly contact with a nurse.

Adult↗

Expression of myometrial activation and stimulation genes in a mouse model of preterm labor: myometrial activation, stimulation, and preterm labor.

Myometrial contractions of labor result from an increase in myometrial activation and stimulation. Activation develops through the expression of contraction associated proteins (CAPs), including oxytocin receptors (OTR), connexin-43 (Cx-43), and prostaglandin F2 alpha, receptors (FP). Stimulation involves increases in contractile agonists including prostaglandin E2 (PGE2) and prostaglandin F2 alpha. (PGF2 alpha) that may result from increases in prostaglandin endoperoxide H synthase (PGHS)-2. A mouse model of preterm birth was used to study gene expression involved in myometrial activation and stimulation. To induce preterm birth, pregnant C57BL/6J mice were intubated with 6 g/kg ethanol on gestational day 16 and were killed every 6 h from treatment until birth. RIA was used to measure uterine PGE2 and PGF2 alpha, while PGHS-2, OTR, Cx-43, and FP messenger RNA levels were measured by ribonuclease protection assay. Increases in CAP mRNA were associated with term and preterm birth. There were differences in stimulation effectors associated with preterm and term birth. Uterine PGF2 alpha values were increased only at the time of term birth, but PGE2 was elevated during both preterm and term labor. These data suggest that existing levels of PGF2 alpha are sufficient for preterm birth when CAP expression is increased, but term labor requires increases in PGE2, PGF2alpha, and CAPs. The PGHS-2 messenger RNA expression pattern suggests that it is a CAP.

Animals↗

[Placental corticotropin releasing-hormone and urocortin--possible role in mechanism of preterm labor].

The preterm labor is a very important clinical problem, both in the diagnostic, prophylactic and therapeutic aspect. It is the leading cause of prenatal morbidity and mortality. Despite of numerous studies and hypotheses mechanisms responsible for human parturition and pre-term labor are unclear. More than 30 years ago it was documented, that placenta is the important source of hormones, cytokins and growth factors. Corticotropin-relasing hormone (CRH) and urocortin (new ligand of CRH receptor) secreted during pregnancy by placenta, chorion, amnion and uterine decidua probably plays important role in human parturition and preterm labor. Possibly the combined hormonal markers profile to predict preterm labor can be used in the future.

Animals↗

The role of chorioamnionitis and prostaglandins in preterm labor.

Spontaneous preterm labor remains a significant cause of high morbidity and mortality in the newborn. Chorioamnionitis with an associated rise in prostaglandins (PGs) is thought to be one of the factors responsible for the onset of preterm labor. In this study, 52 placentas and membranes from gestations of 35 weeks' or fewer were collected. Tissue samples of membranes and placentas were incubated in pseudoamniotic fluid, and the levels of PGs and leukotriene B4 were assayed. Swallowed amniotic fluid aspirated from the infants' stomachs was analyzed for PGs and examined microscopically for the presence of degenerate neutrophilic polymorphonuclear leukocytes (pus cells) and bacterial organisms. Prostaglandins E and F and leukotriene B4 production were significantly higher in the membranes and placentas with chorioamnionitis than in those without. Although the comparison of PG levels in the gastric fluid of infants with and without chorioamnionitis did not reach statistical significance, there was a trend toward higher levels of PGs with chorioamnionitis. Prostaglandin E levels from membranes and placentas and PGF from placentas were significantly elevated in the gastric fluid of infants with pus cells and organisms. These findings support the hypothesis that chorioamnionitis may initiate preterm labor.

Chorioamnionitis↗

Circulating erythroblasts in maternal blood are not elevated before onset of preterm labor.

OBJECTIVE: Preterm labor has recently been reported to be associated with an increased release of cell free fetal deoxyribonucleic acid (DNA) into the maternal circulation. We have previously observed increases in both fetal cell traffic and cell free fetal DNA in preeclamptic pregnancies. In this study, we investigated whether fetal cell traffic is also disturbed in pregnancies with preterm labor. METHODS: In a case-control study, we examined 47 pregnancies complicated by preterm contractions that occurred between 20 and 34 weeks' gestation and an equal number of matched controls. Erythroblasts were enriched for by magnetic cell sorting and enumerated. These values were then correlated with subsequent pregnancy outcome. RESULTS: In the study group 16 patients delivered prematurely (subgroup A). The other 31 (subgroup B) delivered at term, as did all those in the control group. No significant difference was noted in erythroblast numbers between either one of the subgroups and the controls. CONCLUSION: Contrary to the reported increased levels of free fetal DNA in maternal serum, erythroblasts in maternal blood are not elevated significantly in pregnancies with threatened premature labor or in those that deliver preterm.

Abortion, Threatened↗

Mechanism of parturition and preterm labor.

UNLABELLED: Preterm birth occurs in 5 to 10 percent of all pregnancies and accounts for 75 percent of neonatal mortality and morbidity, including long-term handicap. Thirty percent of preterm birth may be associated with an underlying infective process, and approximately 50 percent are idiopathic. Preterm birth corresponds to a syndrome with a variety of causes. The factors contributing to preterm birth may vary at different "windows" of gestation. Glucocorticoids seem to have a central role in processes of birth at term and preterm, and alter synthesis and/or activity of key enzymes in prostaglandin synthesis and metabolism as well as increasing corticotropin-releasing hormone output by intrauterine tissues. This new information should facilitate development of improved methods of diagnosis and therapy for patients at risk of preterm labor. TARGET AUDIENCE: Gynecologists and Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe potential mechanisms of partition and preterm labor and to list the various substances that can inhibit and promote myometrial contractions.

Adult↗

Intercellular adhesion molecule-1 (ICAM-1) in cervicovaginal fluid of women presenting with preterm labor: predictive value for preterm delivery.

PROBLEM: Clinically useful tests for the prediction and diagnosis of preterm labor and delivery remain to be established. We have hypothesized that soluble intercellular adhesion molecule-1 (sICAM-1) in the cervicovaginal fluid of women with preterm labor may be a useful diagnostic tool. METHOD OF STUDY: The cervicovaginal fluid of 103 women between 24(0) and 33(6) weeks gestation with preterm contractions and intact membranes was assayed for sICAM-1. RESULTS: Elevated sICAM-1 concentrations predicted short intervals to delivery (area under receiver operator characteristic (ROC) curves, 0.70-0.72 for delivery within 3, 7 and 10 days), with high specificity. Characteristics for delivery within 3 days at a 3 ng/mL threshold for a positive test were sensitivity 33.3%, specificity 98.9%, and positive and negative predictive values of 75.0% and 93.9%, respectively. Predictive ability was independent of and complementary to that of fetal fibronectin (fFN). CONCLUSIONS: Measurement of sICAM-1 in cervicovaginal fluid has potential as a predictor of preterm delivery in women with symptoms of preterm labor, particularly in conjunction with fFN testing.

Adult↗

Elevation of amniotic fluid interleukin-4 concentrations in women with preterm labor and chorioamnionitis.

Preterm labor associated with intrauterine infection is characterized by increased amniotic fluid concentrations of various proinflammatory cytokines, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage inflammatory protein-1alpha (MIP-1alpha). The purpose of this study was to determine if preterm labor in women with clinically evident chorioamnionitis is marked by elevations of the anti-inflammatory cytokine interleukin-4 (IL-4) and the T cell growth factor IL-2. Amniotic fluid samples were obtained from (1) women at term, not in labor (n = 10); (2) women at term, in labor (n = 10); (3) women with preterm contractions but undelivered within 1 week of amniotic fluid collection (n = 10); (4) women with preterm labor and delivery without clinically evident chorioamnionitis (n = 10); (5) women with preterm labor associated with chorioamnionitis (n = 8); and (6) women with preterm labor and delivery without infection matched with patients with chorioamnionitis (n = 8). Amniotic fluid concentrations of IL-4 and IL-2 were determined for each sample with a specific and sensitive enzyme-linked immunoassay. We found that women with infection-associated preterm labor and delivery had significantly higher concentrations of IL-4 when compared to appropriately matched controls (p < 0.05). Additionally, women with preterm labor and delivery not associated with infection had higher amniotic fluid IL-4 concentrations than women with preterm contractions but no labor (p < 0.05). Women with term labor had rare modest elevations of amniotic fluid IL-4. No IL-2 was detected in any sample. Our data indicate that amniotic fluid IL-4 is elevated in women with preterm labor and delivery, particularly in association with chorioamnionitis. We suggest that IL-4, although previously considered an anti-inflammatory agent, may have a paradoxical proinflammatory role in the pathogenesis of infection-associated preterm labor.

Adult↗

A critical assessment of preterm labor prevention strategies.

Preterm birth is second only to congenital diseases in causing morbidity and mortality in infants. To prevent preterm labor and delivery, a number of strategies have been developed. When choosing a strategy to prevent preterm birth, however, physicians must remember that preterm delivery arises from three separate conditions: iatrogenic preterm labor, premature rupture of membranes, and idiopathic preterm labor. Many of the programs that have been developed focus on patients who are at high risk for iatrogenic preterm birth and premature rupture of membranes, but do not include patients who are likely to experience idiopathic preterm labor. Since idiopathic preterm labor is the most common cause of preterm birth and is the most amenable to early intervention with tocolytic agents, more preterm labor education efforts should be included in prenatal care programs. In addition, further research is needed to delineate which features of preterm birth prevention programs are responsible for the beneficial effects that have been observed.

Clinical Trials as Topic↗

Does extra-amniotic infection cause preterm labor? Gas-liquid chromatography studies of amniotic fluid in amnionitis, preterm labor, and normal controls.

Gas-liquid chromatography (GLC) was used to identify short-chain organic acid byproducts of bacterial metabolism in amniotic fluid from seven normal control patients, six women with overt amnionitis, and six preterm labor patients. Microbiologic culture for aerobic and anaerobic bacteria was also carried out. Positive GLC findings were generally associated with positive cultures, except in five of the preterm labor patients whose GLCs were positive despite negative cultures. The origin of the short-chain organic acids found in these women is unclear; extra-amniotic bacterial growth may explain this finding.

Amniotic Fluid↗

An increase in fetal plasma cortisol but not dehydroepiandrosterone sulfate is followed by the onset of preterm labor in patients with preterm premature rupture of the membranes.

OBJECTIVE: The role of steroid hormones in the control of human parturition has been a subject of debate. Activation of the fetal hypothalamic-pituitary-adrenal axis leading to an increase in plasma cortisol is followed by the onset of parturition in sheep. In contrast, androgens, specifically, dehydroepiandrosterone sulfate, have been implicated in the control of parturition in nonhuman primates. The purpose of this study was to determine the relationship between human fetal plasma cortisol and dehydroepiandrosterone sulfate and the onset of preterm labor in patients with preterm premature rupture of the membranes. STUDY DESIGN: Fetal blood sampling was performed in 51 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. Corticosteroids had not been administered before fetal blood sampling. Cortisol and dehydroepiandrosterone sulfate were measured with sensitive and specific immunoassays. Analysis was conducted with nonparametric statistics and survival analysis. RESULTS: (1) Patients who went into spontaneous labor and delivered within 7 days of cordocentesis had a significantly higher median level of fetal plasma cortisol but not of dehydroepiandrosterone sulfate than those delivered after 7 days (for fetal plasma cortisol: median 8.35 [4.7 to 12.4] micrograms/dL vs median 4.75 [3.0 to 10.4] micrograms/dL, P <.0001; for fetal plasma dehydroepiandrosterone sulfate: median 154.4 [8.6 to 333.8] micrograms/dL vs median 194.6 [96.7 to 402.5] micrograms/dL, P =.09). (2) The cordocentesis-to-delivery interval was significantly shorter in patients with a fetal plasma cortisol value of >/=7 micrograms/dL (derived by receiver-operating characteristic curve analysis) than in those with fetal cortisol <7 micrograms/dL (median 49 [4 to 1849] hours vs median 325 [11 to 2590] hours, P <.001). (3) Fetal plasma cortisol, but not maternal cortisol, was an independent predictor of the duration of pregnancy after we adjusted for gestational age and the results of amniotic fluid culture (hazards ratio 2.9, P <.05). (4) There was a significant correlation between fetal plasma cortisol and fetal plasma interleukin-6 (r = 0.3, P <.05). (5) A strong relationship was found between the fetal plasma cortisol/dehydroepiandrosterone sulfate ratio and the interval to delivery (P <.005). CONCLUSION: An elevation in fetal plasma cortisol but not dehydroepiandrosterone sulfate was followed by the onset of spontaneous preterm labor in patients with preterm premature rupture of the membranes.

Adult↗

IL-15, a novel cytokine produced by human fetal membranes, is elevated in preterm labor.

PROBLEM: Interleukin (IL)-15 is a novel cytokine known to have functions similar to those of IL-2 in the cell-mediated immune response. The objectives of this study were to determine whether IL-15 levels change in labor or preterm labor and to identify the regulatory agents and the site of production of IL-15. METHOD OF STUDY: Amniochorionic membranes were cultured in an organ explant system and were stimulated with lipopolysaccharides (LPSs). Samples were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers for IL-15 and IL-2. The localization of mRNA and protein was accomplished by in situ hybridization and immunocytochemistry. IL-15 was measured in culture media and amniotic fluid from term and preterm gestations by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: RT-PCR indicated the expression of IL-15 mRNA in the amniochorion. In situ hybridization and immunocytochemistry documented that mRNA and peptide for IL-15 are found in amnion, chorion, and decidual cells. ELISA results indicated no significant increase of IL-15 peptides in the culture media after LPS stimulation. Maximum levels of this cytokine were seen in the amniotic fluid (AF) of women with preterm labor compared to term labor. AF levels were not higher in preterm-labor patients with proved infection compared with those without infection. RT-PCR-based detection also showed the presence of two isoforms of IL-15 mRNA known to code for two different leader peptide sequences. IL-2 mRNA expression was not observed in the fetal membranes. CONCLUSIONS: The presence of IL-15 mRNA and peptide in the amniochorion and decidua and its increased presence in the AF during preterm labor suggests a possible role for IL-15 in preterm labor. Amniochorion is also shown to possess two IL-15 isoform leader sequences, the differential expression of which may be involved in the regulation of IL-15 secretion.

Amnion↗

[Risk factors for preterm labor].

OBJECTIVES: Most studies investigating preterm risk factors include medically induced preterm labor due to fetal or maternal complications and do not distinguish preterm labor from preterm premature rupture of membranes. Thus, the objective of this study was to determine the proportion of the three types of preterm birth and identify risk factors for spontaneous preterm labor in a sample of pregnant women who delivered at two level III units. STUDY DESIGN: From January to October 1996, we interviewed 385 women with live preterm newborns and, as controls, 357 mothers of term newborns. Preterm births were classified as preterm labor, preterm premature rupture of membranes and iathrogenic preterm. Independent associations between maternal sociodemographic, constitutional, nutritional and obstetric characteristics and preterm labor were identified using logistic regression analysis. RESULTS: In this sample of preterm births, 29% corresponded to preterm labor, 49% to preterm premature rupture of the membranes and 22% were iathrogenic preterm. The identified risk factors for preterm labor were multiple gestation, no paid work during pregnancy, less than six prenatal care visits, arm circumference less than 26 cm and previous preterm or low birth-weight. Gestational bleeding during the first or third trimester was significantly associated with preterm labor. CONCLUSIONS: As previously recognized, multiple gestation, prior preterm or low birthweight and gestational bleeding are established risk factors for preterm labor. However, prenatal care, maternal work and nutritional status have also been revealed as important issues in preterm risk, deserving special interest since they are susceptible to preventive intervention.

Adult↗

Maternal plasma procalcitonin concentrations in patients with preterm labor and intact membranes--prediction of preterm delivery and admission-to-delivery interval.

The purpose of this study was to evaluate procalcitonin (PCT) plasma levels in pregnancy complicated by preterm labor and to determine their value in the prediction of preterm delivery and the length of the admission-to-delivery interval. The study population consisted of 53 patients with preterm labor and 31 healthy pregnants. The study patients were divided according to the delivery time and to the admission-to-delivery interval. Plasma PCT concentrations were higher in preterm labor than in healthy pregnants. Although at the onset of preterm labor plasma PCT concentrations in patients who delivered prematurely were higher than in patients who, after tocolytic treatment, delivered at term, the difference was not significant. Also in cases of preterm labor delivered within and after three and seven days of admission no differences were observed. The highest values in the prediction of preterm delivery and the length of admission-to-delivery interval corresponded to a PCT concentration of 1.7 ng/ml. These findings suggest that although preterm labor is associated with increased PCT concentrations in maternal plasma, there is no significant association either between plasma concentration of PCT at the moment of threat and preterm delivery, or the admission-to-delivery interval. The predictive value of plasma PCT determinations is unsatisfactory.

Adult↗

Role of cytokines in preterm labor and birth.

Preterm birth (defined as delivery prior to 37 weeks' gestation) complicates 5-10% of all births. It is a major cause of perinatal mortality and morbidity. Approximately 20% of all preterm births are iatrogenic resulting from obstetric intervention for maternal and/or fetal indications. Of the remainder, 2/3 are spontaneous preterm labor with or without preterm premature rupture of the membranes (pPROM). Preterm labor is a syndrome rather than a diagnosis since the etiologies are varied. Risk factors include, among others, pPROM, cervical insufficiency, pathologic uterine distention (polyhydramnios, multiple gestation), uterine anomalies, intrauterine infection/inflammation, and social factors (stress, smoking, heavy work). The final common pathway appears to be activation of the inflammatory cascade. Bacterial colonization and/or inflammation of the choriodecidual interface induces production of pro-inflammatory cytokines that, in turn, lead to neutrophil activation and the synthesis and release of uterotonins such as prostaglandins (which cause uterine contractions) and metalloproteinases (that weaken fetal membranes and remodel cervical collagen). This monograph reviews the role of cytokines in the pathophysiology of preterm labor and delivery.

Adolescent↗

Does evidence of inflammation on Papanicolaou smears of pregnant women predict preterm labor and delivery?

BACKGROUND: Preterm delivery is the most common cause of neonatal morbidity and mortality in the United States. There is evidence that cervicovaginal infection could predispose to preterm labor. This study explored a possible association of evidence of inflammation on an otherwise normal Papanicolaou smear obtained during pregnancy with subsequent preterm labor and preterm delivery. METHODS: Using a retrospective matched cohort design, we studied women who gave birth to live singleton infants at the University of Missouri Hospital and Clinics during a 21-month period. Papanicolaou smears were obtained from 1 to 8 months before delivery and were interpreted in the same cytopathology laboratory. Data pertaining to outcome variables and potential confounding variables were collected from hospital charts. RESULTS: Incidence rates were 14.4 percent for labor < 37 weeks' gestation (preterm labor), 12.3 percent for hospitalization for preterm labor, 9.9 percent for delivery < 37 weeks (preterm delivery), 2.6 percent for delivery < 34 weeks, and 7.5 percent for birth weight < 2500 g. On univariate and multivariate analyses, there were no significant differences in any outcome between the 293 women with inflammation and the 284 women without inflammation on Papanicolaou smear. Results were unchanged when the analysis was limited to the 412 women who received no antibiotics during pregnancy. Among the 38 women with a history of preterm labor or preterm delivery, those with cervical inflammation had a higher rate of preterm labor than those without inflammation. CONCLUSIONS: In the sample as a whole, there was little evidence that findings of inflammation on Papanicolaou smear constituted a risk factor for preterm labor or preterm delivery. The data suggest that inflammation could be associated with an increased risk in a subgroup of women at higher risk by virtue of their obstetric history.

Adult↗

The preterm labor index and fetal fibronectin for prediction of preterm delivery with intact membranes.

OBJECTIVE: To compare the preterm labor index with the biochemical marker fetal fibronectin in predicting preterm delivery. METHODS: In 185 women with preterm labor and intact membranes, the preterm labor index was determined based on clinical findings of uterine contractions, bleeding, and cervical dilatation. An immunosorbent assay was used to measure oncofetal fibronectin. RESULTS: A significant negative correlation was noted between the preterm labor index and the interval from hospitalization to delivery. Based on a receiver operating characteristic curve, a preterm labor index 4 or higher was defined as positive. Rates of preterm delivery overall and of delivery within 1 week in the preterm labor index-negative group were 55.2% and 13.8%, respectively. Those in the preterm labor index-positive group were significantly higher (88.4% and 56.5%). With respect to predicting when a delivery would occur during the first week of hospitalization, the preterm labor index and fetal fibronectin did not differ in sensitivity (77.7% and 73.8%, respectively), specificity (79.5% and 74.2%), positive predictive value (66.7% and 60.8%), or negative predictive value (84.5% and 83.9%). However, within the preterm labor index-negative group, the rates of preterm delivery (68.4%), delivery within 1 week (28.9%), and neonatal treatment in an intensive care unit (36.8%) were significantly higher in fetal fibronectin-positive than in fibronectin-negative cases (46.2%, 9.0%, and 10.3%, respectively). CONCLUSION: The preterm labor index was similar to the fetal fibronectin assay in its ability to predict preterm delivery.

Adult↗

Ultrasonographic and Biochemical Markers of Preterm Labor.

> At present preterm delivery is the leading cause of perinatal morbidity and mortality and its incidence is remained stable during the past 10 years. Conventional methods of identifying patients at risk of preterm delivery such as obstetrics history, demographic factors or evaluation of uterine contractions and cervix by digital examination show disappointintly low sensitivity and positive predictive value. In this review we describe new ultrasonographic and biochemical approaches that have been recently proposed to screen for preterm labor both in patients with intact and with premature rupture of the membranes. The ultrasonographic detection of a short uterine cervix and/or of a dilation of the internal os, expression of weakening of the lower uterine segment or cervical ripening, seems to efficiently predict patients at risk of preterm delivery. The efficiency of this marker may be improved by the association with the assay of fetal fibronectin or pro inflammatory cytokines (interleukin-6 and interleukin-8) in cervical secretions. Further by the concentrations of interleukin-6 and interleukin-8 in cervical secretions seems to be possible to predict among patients in preterm labor those secondary to subclinical endoamniotic infection or chorioamnionitis. The use of these new markers in the future may allow a better identification of patients at risk of preterm labor and a proper selection of the treatment (medical or surgical) required for such patients.

Journal Article↗