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Uterine electrical activity as predictor

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European Journal of Obstetrics & Gynecology and
Reproductive Biology 95 (2001) 149±153
Uterine electrical activity as predictor of
preterm birth in women with preterm contractions
Ivan Verdenik*, Marjan Pajntar, Brane LeskosÏek
Department of Obstetrics & Gynecology, University Medical Center, Ljubljana, Slovenia
Accepted 14 June 2000
Abstract
Objective: To estimate the risk of preterm birth in women admitted to the tertiary maternity hospital for preterm contractions by
measuring electrical uterine activity. Study design: The study included 47 patients with contractions between the 25th and 35th week of
gestation and additional risk factors for preterm delivery. Uterine electrical activity was recorded using bipolar electrodes placed on the
abdominal surface. A logistic model with the electromyographic and obstetric data was built, preterm delivery before 37th week of
gestation being the outcome measure. Results: Seventeen patients (36%) delivered before term. Logistic regression model suggested only
the intensity of electrical uterine activity and woman's body weight to be signi®cant predictors of preterm delivery, with high values related
to preterm birth. They predict preterm delivery with the sensitivity of 47% and speci®city of 90%. Conclusion: We propose uterine EMG as
a simple, non-invasive means to estimate the risk of preterm birth in a high-risk population with multiple risk factors present.
# 2001 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Preterm birth; Uterine electrical activity; Preterm contractions
1. Introduction
2. Materials and methods
Preterm birth is the single most important contributor to
infant morbidity and mortality [1]. Although the majority of
risk factors for preterm birth have been identi®ed [1±3], the
prediction models exhibit a relatively poor performance. On
the other hand, the effectiveness of tocolytic agents depends on
early introduction of therapy [1], therefore, timely recognition
of the process leading to active labor is of prime importance.
Uterine contractions are a necessary, but not suf®cient
condition to recognize the onset of labor [4]. Monitoring of
uterine contractions [5] does not help to identify patients
who are likely to deliver prematurely.
Over the last 10 years, uterine and cervical electrical
activity have become the object of many research studies
[6±8], offering a better insight into the pregnant uterus and
the process of labor.
Electrical activity of uterine muscles precedes mechanical
activity [6,8,9] and is together with cervical electrical
activity [7,10] related to initiation of labor [11±13]. Therefore, the purpose of this study was to attempt to de®ne
factors that could identify the women in the high-risk
population in danger to deliver before term.
This study was approved by the National Ethical Committee, and all patients were enrolled in the trial after giving
informed consent. The enrolment took place in the main
tertiary center in the Republic of Slovenia between May
1996 and June 1997. The patients came to hospital for
uterine contractions in the third trimester of pregnancy.
When contractions were con®rmed by tocography or when
the obstetrician judged the mother should be hospitalized for
closer monitoring (possibly also for additional risk factors)
she was admitted to the obstetric ward, where there they
were recruited for the study. Only about 10% of the
approached patients refused to participate. The exclusion
criteria were severe obstetric pathology and cervical dilatation over 3 cm (labor in progress). All together, 49 patients
were enrolled in the study. For the analysis we also excluded
two patients with induced preterm labor, therefore, data are
based on the remaining 47 patients.
Before any medication for uterine relaxation was given,
recording of the electrical uterine activity was done. The
time elapsed from the initial check to the recording was
usually a few hours. All the patients were white. The mean
gestational age, estimated by the last menstrual period
(LMP) or ultrasound examination was 30.0 weeks (range
25±35 weeks). The average maternal age was 26.95.2
*
Corresponding author. Fax: ‡386-1-4397590.
E-mail address: [email protected] (I. Verdenik).
0301-2115/01/$ ± see front matter # 2001 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 0 1 - 2 1 1 5 ( 0 0 ) 0 0 4 1 8 - 8
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I. Verdenik et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 95 (2001) 149±153
years; 47% were nulliparous; 45% had abortion (either
spontaneous or induced) in their medical history; 4% had
conisation; 4% were smokers; as much as 34% had preterm
delivery in their obstetric history.
At the time of recording the electrical activity, only 23.4%
still had uterine contractions at a rate of at least 1 per 10 min.
Medical intervention went on regardless of the recording
of uterine electrical activity. Different uterine relaxation
drugs were given according to the doctor in charge of a
particular patient: 17% (eight patients) received tocolytic
drugs (Mg sulfate, Ritodrine), 49% spasmolytics (butyl
scopolamine). Simultaneously, 15% received dexamethasone for fetal lung maturation.
The sites of electrode attachment were carefully cleansed
and brushed with a ®ne abrasive paper and treated with the
electrode gel. Bipolar silver±silver-chloride electrodes (in
vivo Metrics Inc., USA) 5 mm in diameter were applied to
the abdominal wall by the adhesive tape 7 cm apart, approximately 12 cm above the symphysis. The reference electrode
was placed on the patient's right thigh. The electromyographic activity was ampli®ed, acquired and digitized using
DAS-8/PGA (Keithley Metrabyte Co., Taunton, MA) and
PC. The data were bandpass ®ltered in the 0.1±4 Hz frequency range. The sampling frequency was set at 20 Hz. At
the same time, cardiotocographic monitoring was applied
(Hewlett Packard 8030; Hewlett-Packard Co., Cupertino,
CA), and digitized and stored simultaneously. The recording
lasted 30 min.
The root mean square (RMS) value of the signal is a
standard measure to quantify signals [14]. It is equivalent to
the intensity of constant voltage applied to a pure resistance
and is used to assess the intensity of electrical activity. As the
uterine activity is changing with the time, it is important to
analyze also in the frequency domain [15]. As the second
quantitative measure of frequency of uterine electrical
activity, the median frequency of power spectra was chosen.
The signal analysis was done using MATLAB software package
(MathWorks Inc., Natick, MA), using supplied routines,
adapted for the task at hand. Recorded sequences were
analyzed en-bloc, because the identi®cation of bursts in this
stage of gestation is usually impossible. Fig. 1. illustrates
signal processing procedure, with raw EMG signal on upper
Fig. 1. Top trace: raw uterine EMG signal as detected transabdominally. Second trace: intrauterine pressure as detected with cardiotocograph (contractions).
Third trace: RMS value calculated from the filtered uterine EMG signal. Horizontal line represents mean RMS over the observed period (30 min). Bottom
trace: median frequency of the uterine EMG. Horizontal line represents mean MF in the observed period.
I. Verdenik et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 95 (2001) 149±153
151
Table 1
Comparition of groupsa
Maternal age (years)
Body weight (kg)
Smoking
Conization
Primiparous
Previous preterm delivery
Previous abortion
Gestational age at admission (weeks)
Uterine contractions
Median frequency (Hz)
RMS value (mV)
Birthweight (g)
Spasmolytics
Tocolytics
a
Preterm group (Nˆ17)
Term group (Nˆ30)
Statistical significance P
27.35.5
72.77.30
1 (6%)
2 (12%)
9 (53%)
5 (29%)
7 (41%)
30.13.2
3 (18%)
0.360.068
17.57.78
2200747
9 (53%)
3 (18%)
26.75.1
67.88.42
1 (3%)
0
13 (43%)
11 (37%)
14 (47%)
29.92.8
8 (27%)
0.370.049
12.26.25
3069460
14 (47%)
5 (17%)
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
<0.05
<0.05
NS
NS
Numbers are meanS.D., or N with percents. Statistical significance was obtained by t-test or w2-test as appropriate for given variable.
trace, intrauterine pressure (contractions) on second, RMS
on the third and median frequency on the bottom trace.
Of the 47 patients in the study, 30 (63.8%) managed to
complete 37 weeks of pregnancy, whereas the remaining 17
(36.2%) had a preterm delivery. The average prolongation of
pregnancy from the time of recording to delivery was 47
days, range from 1 to 113 days. None of the newborns died.
Three patients in the term group had induced labor, in others
the onset of labor was spontaneous. Of the 47, 13 labors
(28%) had to be ended by a cesarean delivery.
The general data on patients and the two parameters
computed from the recorded uterine electrical activity were
entered into the statistical package SPSS v8.01 (SPSS Inc.,
Chicago IL). Pearson correlation coef®cients were ®rst computed to explore univariate relationship between the parameters. For building the logistic regression model, a forward
stepwise method was used, where the variables describing
the patient's general condition and medical history together
with the parameters of uterine electrical activity were proposed to the model. The ®rst group of variables consisted of
the patient age (years), weight at admission (kg), smoking
status (smoking/non-smoking), gynecological history of
uterine anomalies, conisation, parity, previous abortions
(either spontaneous or induced), previous preterm deliveries,
gestational week at admission, membrane status, presence of
contractions at arrival to the obstetric ward (at least one per
10 min, con®rmed by tocography), treatment with spasmolytics and/or tocolytics. Of the electrical myographic parameters, RMS value and median frequency were used.
Table 1 shows the values of variables for both groups.
Univariate tests show that statistically signi®cant were only
lower birthweight and higher RMS value of the uterine EMG
in the preterm group.
Table 2 con®rms independence of electrical parameters of
weight, age, parity and gestational age. Asterisk denotes
Spearman (non-parametric) correlation, as parity does not
follow normal distribution, and other r's are Pearson correlation coef®cients. No statisticaly signi®cant correlation was
found. On the other hand, the correlation between two
electrical parameters, namely the RMS value and median
frequency of uterine electrical activity, was signi®cant and
negative (rˆÿ0.435; Pˆ0.002).
The results of the stepwise logistic regression are shown
in Table 3. From the 14 independent variables proposed
initially to the procedure, only two of them, namely the RMS
value and weight of the woman, ful®lled the conditions
necessary to be entered into the model (probability of F to
enter was set at 0.05). The procedure was executed with term
delivery as the dependent variable. Resulting logistic model
therefore, consists of only two terms.
The accuracy of prediction of preterm delivery with the
above described logistic model is given in Table 4. Standard
measures of predictive parameters are therefore: sensitivity
47.1%, speci®city 90.0%, positive predictive value 72.7%
and negative predictive value 75.0%.
Table 2
Correlation of the parameters of the electrical uterine activity to age,
weight, parity and gestational age of the patienta
3. Results
Of the electrical myographic parameters, the RMS value
and median frequency were used. The mean RMS value
observed was 14.2 mV (S.D. 7.2); the mean recorded
median frequency was 0.36 Hz (S.D. 0.06). Both were
normally distributed.
Age
Weight
Parity
Gestational age
RMS value of the uterine
electrical activity
Median frequency of the
uterine electrical activity
rˆÿ0.053 (0.723)
rˆ0.048 (0.750)
rˆÿ0.170 (0.254)
rˆ0.139 (0.353)
rˆ0.142 (0.342)
rˆ0.169 (0.256)
rˆ0.312 (0.066)
rˆÿ0.234 (0.113)
a
r: Pearson correlation coefficient; r: Spearman correlation coefficient; statistical significance P is given in the parenthesis.
152
I. Verdenik et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 95 (2001) 149±153
Table 3
Results of stepwise logistic regression with term delivery as the dependent
variable
Variables in the model
RMS value
Body weight
Ba
S.E. (B)
Sig.
R2b
ÿ0.1189
ÿ0.0842
0.0535
0.0445
0.026
0.0586
0.048
0.026
Variables not in the model
Conization
Age of the women
Previous preterm delivery
Median frequency
Uterine anomalies
Previous abortion
Parity
Gestational age
Uterine contractions
Spasmolytics
Tocolytics
Smoking
0.2665
0.3764
0.4321
0.4766
0.5142
0.6110
0.6182
0.6465
0.7401
0.7486
0.9084
0.9711
a
B: regression coefficient; S.E.: standard error; Sig.: statistical
significance.
b 2
R : variation of preterm delivery explained by particular factor.
Table 4
Predicted and actual outcome of pregnancy
Actual preterm delivery
Actual term delivery
Predicted preterm
delivery by the
logistic model
Predicted term
delivery by the
logistic model
8 (True positives)
3 (False positive)
9 (False negative)
27 (True negative)
4. Comment
The patient's individual perception of uterine contractions
varies too much to be useful for predicting the closeness to
delivery. It depends on sensitivity of the woman and her
previous obstetric experiences. At admission to the ward,
contractions were recorded in only 23.4% of the patients,
although they all came to the maternity hospital for preterm
contractions. In our institution, women who come for uterine
contractions in the third trimester of pregnancy, routinely
undergo cardiotocography. According to the fetal and maternal condition, course of pregnancy and medical history, the
decision is made whether she should be hospitalized or not.
To obtain a better insight into the uterine activity leading to
preterm delivery, some authors investigated continuous
monitoring of uterine contractions. As a result, home uterine
monitoring study [5] revealed that everyday monitoring of
contractions with electronic devices is not linked to earlier
diagnosis of preterm labor. We believe that the prediction of
preterm labor was not successful because of weak and
irregular mechanical uterine activity in pregnancy. Therefore, we decided to measure the parameter which underlies
contractility, i.e. the electrical uterine activity.
As the time of delivery approaches, uterine electrical
activity becomes more and more synchronous, acting
towards expulsion of the fetus. This synchronous activity
is known as `uterine contractions' in mechanical sense and
as `signal bursts' in electrical sense. However, during normal
pregnancy until 36th week, there is almost no synergy of
muscular ®bers, and contractions or bursts can only seldom
be detected [8]. In our previous study [10] we have found
that during labor the activity between two bursts is related to
the course of labor. Therefore, the analysis of signals during
bursts only is not suf®cient. By analyzing the overall signal
in certain (we chose 30 min) time period it is possible to get
insight into the preparedness of the uterus for labor, even in
the state without contractions.
Our study group patients were at high risk for preterm
delivery; as much as 34% of them had (at least) one before,
and almost a half had abortions in their medical history. The
therapy for this group was administered according to everyday care, regardless of our study; 17% of patients received
tocolytics, 49% spasmolytics, and bedrest and observation
was prescribed in the remaining ones. The distribution of
drugs was similar in those who delivered before term and in
those who delivered at term.
All recordings we made, were done in 25th±35th week of
pregnancy, with majority around 30th week. Therefore, the
conclusions we reached are valid for this gestational age
only.
The correlation between EMG parameters and gestational
age shows that with duration of pregnancy the frequency
contents of electrical activity becomes lower, which is
expressed as lower median frequency of uterine electrical
activity. At the same time the RMS value does not statistically signi®cantly correlate with gestational age. These
results are different from those of Buhimschi and coworkers
[13,15], who found that the frequency power spectrum
moves higher as the time of labor approaches. This difference occurred because we measured the complete 30 min
interval and not only bursts, which are by and large nonexistent in this stage of gestation. The second source of
differences could be signal ®ltering; namely, Buhimschi and
Gar®eld [13] used signal bandpass 0.3±50 Hz, whereas we
chose the 0.1±4 Hz frequency band. The reasoning behind
this decision was the report published by Devedeaux et al.
[6], who found signi®cant part of power spectrum density as
low as 0.1 Hz. Also, at frequencies close to 50 Hz (60 Hz in
US), electromagnetic noise could signi®cantly contaminate
the signal.
We have found that weight, age and parity of the patient
do not correlate with the recorded electrical activity.
Predictive logistic regression model shows the most
important risk factor for preterm delivery to be high RMS
value followed by the weight of the woman. We believe that
with the closeness to delivery the electrical activity of the
uterus becomes more vigorous, despite yet weak and/or
irregular contractions (mechanical activity measured by
tocodynamometer). Regarding body weight we found a
I. Verdenik et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 95 (2001) 149±153
positive correlation between body weight and risk for preterm delivery, as was also found by Carmichael et al. [16].
Data on weight were obtained at the time of measurement.
For more accurate analysis, one should also take into
account prepregnancy weight, height, body mass index,
etc. but that was beyond the scope of this study.
It is surprising that all other factors, which are usually
considered risk factors for preterm delivery, did not contribute signi®cantly and were therefore not entered into the
model. We believe that this is because almost all of the
patients had one or more risk factors for preterm birth
present, and 17 of them (36.2%) delivered before term.
Strong correlation between the median frequency of the
uterine electrical activity and gestational age would also
suggest the importance of median frequency for preterm
delivery. However, it seems that during pregnancy the
median frequency changes (decreases) with gestation in
linear fashion, whereas the RMS value changes only a
few days before the true labor begins. A higher RMS value
of the uterine electrical activity in the patients who delivered
before term suggests that this could be a sign of physiological characteristics of women prone to preterm labor,
independent of other well-known risk factors. This is an
important ®nding because the RMS value of the electrical
uterine activity is neither signi®cantly related to the duration
of gestation, nor to the time left to delivery. It is a static
marker, denoting the woman's risk for preterm delivery,
independent of other possible causes.
The analysis of electrical uterine activity is therefore a
promising method for evaluating evolution of uterine contractility, determining preparedness of uterus for labor and
identifying patients at risk for preterm delivery.
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