International Session Award. Non-invasive cutaneous cardiovascular dynamics (CVD) as a predictor of preterm delivery: a pilot study

AIM: To assess the clinical value of cardiovascular dynamics (CVD) pattern of 'positive cycling' in predicting true preterm labor. METHODS: Patients with a clinical diagnosis of preterm labor had CVD measurement with a non-invasive miniature pressure transducer applied to the fingertip concomitantly with uterine activity monitoring. Based on previous work by our group, the rapid ejection time (RET) reflects arterial compliance; an elevated RET is suggestive of vasoconstriction. Positive cycling is present when the RET shows elevation with uterine contractions and negative cycling is present when there are no changes in the RET with uterine contractions. RESULTS: Twenty-seven women had negative CVD cycling and nine had positive CVD cycling. There was no difference between the two groups in initial gestational age, cervical effacement or cervical dilation at testing. However, the mean interval from testing to delivery was 1.56 (SEM+/-0.29) days for positive cycling and 39 days (+/-5.25) for negative cycling (P < 0.001). CONCLUSION: Non-invasive cardiovascular patterns of positive cycling appear predictive of preterm delivery.     

Changes in electromyographic activity of the cervix after stimulation of labour with oxytocin

The electrical activity of the cervix can be measured during labour. The influence of oxytocin on electromyographic (EMG) activity of the cervical musculature was studied in 80 primiparous women after induction of labor. The highest electrical activity registered at the time of uterine contraction and between two contractions was used for analysis. The basic pattern of oxytocin-produced changes in muscular contractions in the cervix observed via EMG activity is that of the activity increasing with contractions of the uterine corpus and diminishing between contractions. The effect of oxytocin on cervical musculature is different in ripe and unripe cervices.     

Instrumentation for the diagnosis of term and preterm labour

The problems associated with labor during pregnancy are among the most important health issues facing physicians. Understanding the role of the uterus and cervix in labor and developing methods to control their function is essential to solving problems relating to labor. At the moment, only crude, inaccurate and subjective methods are used to assess changes in the uterus and cervix that occur in preparation for or during labor. In the past several years, we have developed noninvasive methods to quantitatively evaluate the uterus and cervix based respectively on recording of uterine electrical signals from the abdominal surface (uterine EMG) and measurement of light-induced cervical collagen fluorescence (LIF) with an optical device (Collascope). The methods are rapid and allow assessment of uterine contractility and cervical ripening. Studies in rats and humans indicate that uterine and cervical function can be successfully monitored during pregnancy using these approaches and that these techniques might be used in a variety of conditions associated with labor to better define management. The potential benefits of the proposed instrumentation and methods include a reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean section rate and improving research methods to understand uterine and cervical function.     

Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery.

OBJECTIVE: The study was conducted to investigate whether the strength of uterine contractions monitored invasively by intrauterine pressure catheter could be determined from transabdominal electromyography (EMG) and to estimate whether EMG is a better predictor of true labor compared to tocodynamometry (TOCO). STUDY DESIGN: Uterine EMG was recorded from the abdominal surface in laboring patients simultaneously monitored with an intrauterine pressure catheter (n = 13) or TOCO (n = 24). Three to five contractions per patient and corresponding electrical bursts were randomly selected and analyzed (integral of intrauterine pressure; integral, frequency, amplitude of contraction curve on TOCO; burst energy for EMG). The Mann-Whitney test, Spearman correlation and receiver operator characteristics (ROC) analysis were used as appropriate (significance was assumed at a value of p < 0.05). RESULTS: EMG correlated strongly with intrauterine pressure (r = 0.764; p = 0.002). EMG burst energy levels were significantly higher in patients who delivered within 48 h compared to those who delivered later (median [25%/75%]: 96,640 [26,520-322,240] vs. 2960 [1560-10,240]; p < 0.001), whereas none of the TOCO parameters were different. In addition, burst energy levels were highly predictive of delivery within 48 h (AUC = 0.9531; p < 0.0001). CONCLUSION: EMG measurements correlated strongly with the strength of contractions and therefore may be a valuable alternative to invasive measurement of intrauterine pressure. Unlike TOCO, transabdominal uterine EMG can be used reliably to predict labor and delivery.     

Controlled trial of hydration and bed rest versus bed rest alone in the evaluation of preterm uterine contractions

Patients who are seen with uterine contractions but without documented change in cervical dilation or effacement are often treated with intravenous hydration before the initiation of intravenous tocolytic therapy. This is done with the intention of stopping uterine activity in patients with false preterm labor. A prospective randomized study was conducted to evaluate the effect of hydration on preterm uterine contractions in patients without proved preterm labor. A total of 28 patients were treated with bed rest and an intravenous bolus and subsequent continuous infusion of 5% dextrose in lactated Ringer's solution. A control group of 20 patients were treated with bed rest alone. Uterine activity and arrest of uterine contractions were compared between the two groups. Contractions stopped in 54% of the patients treated with hydration, whereas contractions stopped in 40% of the patients in the control group. This difference was not statistically significant. As a crossover study, those in the control group with contractions that continued after the initial observation period were subsequently treated with intravenous fluids. Only one patient in this group stopped contracting. Of all patients whose contractions with either therapy, 18% eventually were delivered of preterm infants. This included 20% of the hydration group and 14% of the control group. The use of hydration as a pretherapy indicator to differentiate true preterm labor from false preterm labor could not be supported by this study. In addition, patients whose contractions stopped with either hydration or bed rest are at increased risk of subsequent preterm delivery.     

Active contractions of the cervix in the latent phase of labour.

OBJECTIVE: To study the activity of the human uterine cervix at the onset of labour and further characterise cervical asynchronous electromyographic (EMG) activity in the latent phase. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: Clinical hospital in Ljubljana. PARTICIPANTS: Forty-seven healthy nulliparous women with relatively unripe cervices requiring induction of labour. METHODS: Simultaneous registration of a cervical EMG and of the intrauterine pressure at the very early stage of labour; subsequent EMG signal processing to determine its time, amplitude and frequency parameters. MAIN OUTCOME MEASURES: Simultaneous comparison of the cervical EMG and the mechanical activity of the uterine corpus to deduce electrical properties of the cervical smooth muscle tissue and its activity. RESULTS: EMG bursts, asynchronous with the contractions of the uterine corpus, were registered in 20 out of 47 women. In 14 women bursts appeared independent of uterine corpus contractions and in six they followed the peak of contractions. The bursts had low average median frequency (0.3 Hz). In seven women bursts were superimposed onto a background EMG (median frequency = 1.2 Hz). CONCLUSIONS: Bursts in the cervical EMG may appear asynchronously with the uterine contractions. Bursts not related to contractions suggest active and independent cervical muscle activity. The bursts which follow contractions may be an active response of the cervical musculature to passive stretching during a contraction. The EMG frequency content suggests two different contraction mechanisms or a different origin of the EMG in the cervix.     

Active contractions of the cervix in the latent phase of labour

Objective To study the activity of the human uterine cervix at the onset of labour and further characterise cervical asynchronous electromyographic (EMG) activity in the latent phase.
Design Prospective observational study.
Setting Clinical hospital in Ljubljana.
Participants Forty-seven healthy nulliparous women with relatively unripe cervices requiring induction of labour.
Methods Simultaneous registration of a cervical EMG and of the intrauterine pressure at the very early stage of labour; subsequent EMG signal processing to determine its time, amplitude and frequency parameters.
Main outcome measures Simultaneous comparison of the cervical EMG and the mechanical activity of the uterine corpus to deduce electrical properties of the cervical smooth muscle tissue and its activity.
Results EMG bursts, asynchronous with the contractions of the uterine corpus, were registered in 20 out of 47 women. In 14 women bursts appeared independent of uterine corpus contractions and in six they followed the peak of contractions. The bursts had low average median frequency (0.3 Hz). In seven women bursts were superimposed onto a background EMG (median frcquency = 1–2 Hz).
Conclusions Bursts in the cervical EMG may appear asynchronously with the uterine contractions. Bursts not related to contractions suggest active and independent cervical muscle activity. The bursts which follow contractions may be an active response of the cervical musculature to passive stretching during a contraction. The EMG frequency content suggests two different contraction mechanisms or a different origin of the EMG in the cervix.     

Cervix and tocography screening in basic pregnancy monitoring

Report about a myometrial contractility-screening in 2462 asymptomatic pregnancies at 30 weeks of gestation. A cervical examination was performed in the 26th and 33th weeks of gestation. An increased uterine contraction frequency was obtained in 3% and a cervical opening in 5.6%. Uterine contractions with cervical opening are a high-risk factor of prematurity (52%-70%) whereas uterine contractions alone are of low-risk. The prevention of preterm birth is useful. We found a significant decrease of early neonatal mortality in 487 singleton preterm deliveries after treatment. A classification of unexplained preterm delivery, iatrogenic or elective preterm delivery and complicated preterm labor is recommended for controlled outpatient and clinical trials.     

Plasma prostaglandin F2 alpha and plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha levels in women during induction of labor with i.v. infusion of prostaglandin F2 alpha in relation to uterine contractions

The concentrations of plasma PGF2 alpha and its main metabolite, 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured in serial samples of blood collected in 10 pregnant women at term who were given iv infusions of low doses of PGF2 alpha for induction of labor. Six other women served as controls and were given saline infusions. Uterine contractions began with a mean latency of 62 min in the PGF2 alpha infused women, in controls uterine activity remained unchanged. Plasma PGFM levels had increased significantly 30 min after PGF2 alpha infusion began, rising thereafter in a dose dependent manner. Plasma PGF2 alpha also rose reaching a steady state at 2 hours. No significant changes were observed in the controls. The 6-h infusion resulted in delivery in 5 of the 10 women, in the 5 others the cervical scores increased only by 1.25 points on the average and further treatment was needed to achieve delivery, although prostanoid levels rose to similar levels in all. The data show that when uterine contractions are induced by systemic PGF2 alpha, the levels of PGFM are significantly raised. In spontaneous labor uterine contractions begin long before plasma PGFM rises. Thus, if endogenous PGF2 alpha generation is involved in the initiation of uterine contractions during spontaneous labor, it must be synthetized in the myometrium at quantities too low to raise the levels of circulating PGFM.     

Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery

Objective: The study was conducted to investigate whether the strength of uterine contractions monitored invasively by intrauterine pressure catheter could be determined from transabdominal electromyography (EMG) and to estimate whether EMG is a better predictor of true labor compared to tocodynamometry (TOCO).

Study design: Uterine EMG was recorded from the abdominal surface in laboring patients simultaneously monitored with an intrauterine pressure catheter (n?=?13) or TOCO (n?=?24). Three to five contractions per patient and corresponding electrical bursts were randomly selected and analyzed (integral of intrauterine pressure; integral, frequency, amplitude of contraction curve on TOCO; burst energy for EMG). The Mann–Whitney test, Spearman correlation and receiver operator characteristics (ROC) analysis were used as appropriate (significance was assumed at a value of p <?0.05).

Results: EMG correlated strongly with intrauterine pressure (r?=?0.764; p?=?0.002). EMG burst energy levels were significantly higher in patients who delivered within 48?h compared to those who delivered later (median [25%/75%]: 96?640 [26?520–322?240] vs. 2960 [1560–10?240]; p <?0.001), whereas none of the TOCO parameters were different. In addition, burst energy levels were highly predictive of delivery within 48?h (AUC?=?0.9531; p <?0.0001).

Conclusion: EMG measurements correlated strongly with the strength of contractions and therefore may be a valuable alternative to invasive measurement of intrauterine pressure. Unlike TOCO, transabdominal uterine EMG can be used reliably to predict labor and delivery.     

Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts

The cervix serves as a protective barrier from invading microorganisms and as a structural barrier to delivery of the fetus. Among all biological processes, the phenomenal connective tissue remodeling that occurs in the cervix during and after parturition is unparalleled in scope and magnitude. The process of connective tissue remodeling in the cervix during pregnancy occurs in four stages: softening, ripening, dilation, and repair. Although overlapping in time, each stage is uniquely regulated. Results from studies using serial measurements of cervical length indicate that cervical ripening precedes myometrial contractions of labor by several weeks, suggesting that parturition in women is a process of long duration and that uterine contractions of labor are late events in the parturition process. A clear understanding of the biologic mechanisms that regulate cervical remodeling during pregnancy is needed to influence the preterm birth rate and to develop strategies to prevent preterm dilation of the cervix.     

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.     

Effect of spasmoanalgetic Dolantin on the electromyographic activity of the cervix during labour.

The influence of spasmoanalgetic Dolantin on electrical activity of the smooth musculature of the cervix during labour was studied in 50 primiparous women after induction of labour. The highest electrical activity was measured at the time of uterine contraction (AC) and between contractions (BC). The basic pattern of Dolantin-produced changes in muscular contractions in the cervix observed via EMG activity is that of the EMG activity diminishing with contractions of the uterine corpus and even more so in the period between contractions. Dolantin administered during the latent phase of induced labour did not accelerate cervical dilatation either in the latent or in the active phase of amniotomy- and Oxytocin-induced labour.     

Cervicovaginal fistula formation: a new complication of Shirodkar cerclage

In this article, cervicovaginal fistula formation is reported for the first time as a complication of failure to remove a cervical cerclage during labor. Along with the available literature, the case presented here suggests the value of timely removal of a cerclage in the face of strong uterine contractions. Should cervical laceration/rupture occur, immediate repair should be attempted. If chronic cervicovaginal fistula occurs, preterm delivery through the defect and frank uterine rupture are risks with succeeding pregnancies.     

The sequential use of estradiol and prostaglandin E2 topical gels for cervical ripening in high-risk term pregnancies requiring induction of labor

We compared the safety and efficiency of 200 mg of estradiol valerate prepared as a topical cervical gel as a preripening agent when used 6 hours before the application of 2 mg of prostaglandin E2 gel for the purpose of cervical ripening in 40 high-risk obstetric patients before indicated oxytocin induction of labor. When compared with a placebo prostaglandin E2 dosage, the estradiol had no effect on the change of Bishop score, length of labor, amount of oxytocin required, or the cesarean delivery rate. While no uterine contractions were noted after the application of the estradiol, 85% of patients had recordable uterine activity after the application of prostaglandin E2, suggesting that even at the 2 mg dosage this sequential regimen is not appropriate for local cervical ripening.     

Dysfunctional labor and myometrial lactic acidosis

OBJECTIVE: Inefficient uterine contractions are the most common cause of poor progress in labor. The global increase in cesarean delivery rate is a cause of considerable concern, and the greatest reason for increase is the result of failure to progress in labor. Following in vitro studies that showed acidification could depress uterine contraction, we hypothesized that it could contribute to dysfunctional labors. METHODS: A blood sample was taken from the lower segment of the uterus from women having a cesarean delivery, either electively or as a result of dysfunctional labor, and from those having a normal labor. This blood sample was analyzed for pH, O(2) saturation, and lactate levels. Contraction was recorded in myometrial strips, taken from women having elective cesarean delivery, at the pH of normally and dysfunctionally contracting uteri. RESULTS: The pH of myometrial capillary blood from women having a dysfunctional labor was significantly lower (7.35) than that from women having elective cesarean delivery (7.49) or cesarean delivery with normal contractions, with (7.47) or without (7.48) oxytocin (P <.001). The women in dysfunctional labor had higher capillary lactate and lower capillary O(2) saturation. Furthermore, in vitro, reducing the pH value from 7.5 to 7.3 changes regular uterine contractions to irregular ones of reduced amplitude. CONCLUSIONS: Myometrial lactic acidosis and a small decrease in O(2) saturation may be contributing factors to dysfunctional labor. Our data may also account for the ineffectiveness in management of dysfunctional labor with oxytocin. Oxytocin with a background of lactate acidosis may not be successful. LEVEL OF EVIDENCE: II-2     

Relationship of measured external tocodynamometry with measured internal uterine activity.

The use of home uterine activity monitoring for patients at high risk for preterm labor and delivery has become common in clinical perinatology. The ability of the monitoring devices to detect accurately uterine contractions in early pregnancy has not previously been reported. Ten women in labor between 20 and 35 weeks' gestation underwent simultaneous monitoring of uterine activity with a guard-ring tocodynamometer and an intrauterine pressure monitor. When compared with internal monitoring, the external monitor detected 90.8% of uterine contractions with a specificity for uterine quiescence of 98.1%. The predictive value of external monitoring was 97.3% for detecting uterine contractions and 93.6% for recording the absence of uterine contractions. The contractions detected externally were similar in duration: mean 63.7 +/- 23.0 seconds for internal monitoring and 62.2 +/- 22.6 seconds for external monitoring (p greater than 0.05). The intensity of contractions detected externally was less than internally measured contractions, mean difference, 19.7 +/- 15.9 mmHg (p less than 0.001). External tocodynamometry using this guarding tocodynamometer reliably distinguishes between uterine contractions and uterine quiescence in preterm pregnancies but does not adequately measure the intensity of contractions.     

The influence of uterine motility upon cervical dilatation in labor

Intrauterine tocometry was used to study the influence of uterine motility on the relationship between the frequency and strength of contractions upon cervical dilatation. As it was not possible to collect sufficient material for valid conclusions on a series of patients with similar uterine activity, fetal size, uterine volume, cervical resistance, and lower uterine segment development; only women in normal labor without disproportion and delivered of infants in the occipitoanterior vertex presentation were included in the study. The average intensity and frequency of contractions and the average uterine activity were calculated for each woman. The patients were divided with regard to parity and ruptured or unruptured membranes. It was learned that the most rapid cervical dilatation occurs, for unchanged uterine activity, at the frequency of 21-23 contractions per hour. The observation is important for understanding the 1st stage of labor for proper treatment, by drugs, of dystocia.     

Uterine electromyography and light-induced fluorescence in the management of term and preterm labor

OBJECTIVE: Understanding the physiology of the uterus and cervix during term and preterm parturition is crucial for developing methods to control their function and is essential to solving clinical problems related to labor. To date, only crude, inaccurate, and subjective methods are used to assess changes in uterine and cervical function in pregnancy. METHODS: In the past several years, we have developed noninvasive methods to quantitatively evaluate the uterus and cervix based on recording of uterine electrical signals from the abdominal surface (uterine electromyography) and measurement of light-induced fluorescence (LIF) of cervical collagen (Collascope), respectively. Both methods are rapid and allow immediate assessment of uterine contractility and cervical ripening. RESULTS: Studies in animals and humans indicated that uterine and cervical performance can be monitored successfully during pregnancy using those approaches and that these techniques can be used during labor to better define management in a variety of conditions associated with labor. CONCLUSION: The potential benefits of the proposed instrumentation and methods include reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean rate and providing research methods to understand uterine and cervical function.     

The cervix uteri in pregnancy

It is during labor that the most dramatic changes to the cervix are apparent, yet the cervix begins its process of adapting early on in pregnancy. From an anatomic perspective, the gravid cervix is changed little in the beginning of pregnancy. It is strikingly less muscular than the rest of the uterus and its connective tissue is comprised essentially of collagen fibers and a matrix rich in proteoglycans. Cervical maturation begins imperceptibly during pregnancy but does not become noticeable until shortly before labor. These changes result from biochemical modifications of the cervical constituents with dissolving of collagen fibers and changes in the respective levels of different proteoglycans. The regulation of this maturation is still poorly understood; steroid hormones, prostaglandins, and collagenases have all been implicated. The effacement and dilatation of the cervix occur with labor. Effacement corresponds with thinning and opening of the internal os and dilatation corresponds with opening of the external os. These phenomena are passive, resulting from physical pressure from fetal engagement under the effects of uterine contractions. Our material understanding of cervical maturation and dilatation are still insufficient, for although we are better and better able to guide the induction and course of labor, it still is impossible for us to arrest premature cervical maturation in the setting of a threatened abortion or premature delivery.