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Article history: Background and objective: Induction of labor (IOL) is a medical procedure used to initiate uterine contrac-
Received 1 August 2016 tions to achieve delivery. IOL entails medical risks and has a significant impact on both the mother’s and
Revised 31 January 2017
newborn’s well-being. The assistance provided by an automatic system to help distinguish patients that
Accepted 21 March 2017
will achieve labor spontaneously from those that will need late-term IOL would help clinicians and moth-
ers to take an informed decision about prolonging pregnancy. With this aim, we developed and evaluated
Keywords: predictive models using not only traditional obstetrical data but also electrophysiological parameters de-
Electrohysterogram rived from the electrohysterogram (EHG).
SVM Methods: EHG recordings were made on singleton term pregnancies. A set of 10 temporal and spectral
Majority voting
parameters was calculated to characterize EHG bursts and a further set of 6 common obstetrical param-
Labor management
eters was also considered in the predictive models design. Different models were implemented based
on single layer Support Vector Machines (SVM) and with aggregation of majority voting of SVM (double
layer), to distinguish between the two groups: term spontaneous labor (≤41 weeks of gestation) and IOL
late-term labor. The areas under the curve (AUC) of the models were compared.
Results: The obstetrical and EHG parameters of the two groups did not show statistically significant dif-
ferences. The best results of non-contextualized single input parameter SVM models were achieved by
the Bishop Score (AUC = 0.65) and GA at recording time (AUC = 0.68) obstetrical parameters. The EHG
parameter median frequency, when contextualized with the two obstetrical parameters improved these
results, reaching AUC = 0.76. Multiple input SVM obtained AUC = 0.70 for all EHG parameters. Aggrega-
tion of majority voting of SVM models using contextualized EHG parameters achieved the best result
AUC = 0.93.
Conclusions: Measuring the electrophysiological uterine condition by means of electrohysterographic
recordings yielded a promising clinical decision support system for distinguishing patients that will spon-
taneously achieve active labor before the end of full term from those who will require late term IOL. The
importance of considering these EHG measurements in the patient’s individual context was also shown
by combining EHG parameters with obstetrical parameters. Clinicians considering elective labor induction
would benefit from this technique.
© 2017 Elsevier B.V. All rights reserved.
1. Introduction tality [1]. Induction of labor (IOL) is used before labor begins spon-
taneously to incite uterine contractions during pregnancy [2]. Med-
Late-term pregnancies are those that extend beyond the 40 + 6 ical indications for IOL are usually given in clinical situations in
weeks of gestational age (GA) up to 41 GA + 6 weeks, and are asso- which the benefits of expediting birth outweigh the risks of con-
ciated with an increase in fetal and maternal morbidity and mor- tinuing the pregnancy, as could be the case in a late term preg-
nancy [3]. There is an increasing trend in the use of IOL; from 1990
to 2012 the ratio doubled in the United States [4] from 9.5% to
∗
Corresponding authors. 22.5%, at an estimated cost of $2 billion [4].
E-mail addresses: palberola.rubio@gmail.com (J. Alberola-Rubio), IOL is not without certain risks. It entails the possible conse-
jgarciac@eln.upv.es (J. Garcia-Casado). quences of excessive uterine activity: C-section (cesarean section),
1
The author reports no conflict of interest.
http://dx.doi.org/10.1016/j.cmpb.2017.03.018
0169-2607/© 2017 Elsevier B.V. All rights reserved.
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128 J. Alberola-Rubio et al. / Computer Methods and Programs in Biomedicine 144 (2017) 127–133
risk of postpartum hemorrhage, and adverse effects on the new- predictors of cervical ripening, whose goal is to facilitate the pro-
born such as fetal infection and respiratory distress syndrome [1]. cess of cervical softening, thinning and dilating [28]. Also, nullpar-
Late term pregnancies also involve risks. A review of the GA of all ity, advanced maternal age and obesity are known to be strong risk
live infants in the United States (1995–2005) [5] and the Amer- factors in late-term pregnancies [29]. Our hypothesis is therefore
ican College of Obstetricians and Gynecologists [6] related a rise that when characterizing the uterine electrophysiological condition
in stillbirths, neonatal and perinatal deaths at 41 GA compared to by means of EHG analysis, the EHG parameters cannot be fully ex-
early and full term labor. In this regard, prior knowledge of when plained and interpreted outside the maternal clinical context char-
a pregnancy will exceed the term period would be very useful ex- acterized by common obstetrical parameters.
tra information to help clinicians manage pregnancies, especially in In this study, a set of individual and aggregation of support
conditions such as high-risk gestations, advanced maternal age or vector machines (SVM) classifiers using EHG recordings and ob-
human-assisted reproductive technology gestations. Similarly, cur- stetrical parameters from term pregnancies was implemented and
rent international recommendations encourage mothers to make compared to discern patients that will achieve active labor sponta-
an informed decision about the management of their own pro- neously before the end of full term (<41 GA [6]) from those that
longed pregnancies [7]. The lack of clear evidence on the outcome will need late term IOL (between 41 weeks 0 days and 41 weeks 6
of each pregnancy management strategy complicates the mother’s days [6]). We studied the influence of the set of input variables on
informed decision between the risks associated with a late-term the performance of the classifiers with single input and groups of
pregnancy and the risks associated with IOL. We develop a method i) obstetrical parameters only, ii) EHG parameters only and iii) the
that helps to determine, in term pregnancies, if active labor will be combination of EHG parameters and their obstetrical parameters
spontaneously achieved before the end of full term (<41 GA [6]) (clinical context).
or if the patient will have a prolonged gestation, becoming a late- The experimental results showed that the classifier that uses as
term pregnancy requiring IOL. This method would have consider- inputs the combination of contextualized EHG parameters in an
able benefits for obstetricians considering management strategies aggregation of support vector machines with the majority voting
and help mothers take decisions. method gave the best performance.
Previous studies attempted to develop models based on ul-
trasound technologies that predict the labor onset type: spon- 2. Material and methods
taneous vs C-section [8] or predict spontaneous vaginal delivery
[9]. Other authors have used the Bishop Score (BS) and other 2.1. Patients
maternal or fetal parameters to predict failed induction [10] or
time to onset of labor in prolonged pregnancies [11]. To date, This study was approved by the Hospital Universitario y Politéc-
these models have shown limited predictive accuracy. One of the nico La Fe de Valencia Ethics Committee and adheres to the Dec-
alternatives now available is to use the information derived from laration of Helsinki. All the patients involved signed written con-
electrohysterographic recordings. Surface recording of the electro- sent forms. Inclusion criteria were: healthy women, with singleton
hysterogram (EHG) is a noninvasive technique for monitoring the pregnancy, term GA, and non-high-risk pregnancies. Patients with
electrical activity of the myometrium and provides reliable infor- previous C-section, elective cesarean, pregnancy complication ei-
mation on uterine contractions [12]. These contractions are the ther maternal or fetal, or those who delivered in a different hospi-
result of bursts of myometrial electrical activity and are associ- tal were excluded from the study. All the patients presented uter-
ated with an increase in the intrauterine pressure [13]. The uter- ine dynamics when recorded and were followed up until the end
ine electrophysiological conditions are reflected in the character- of the delivery. In accordance with ACOG Guidelines Committee
istics of the EHG signal and their evolution along gestation [14]. Opinion No 579: Definition of Term Pregnancy [6], each patient’s
A large number of studies have used EHG parameters and clas- recording was assigned to one of two following categories: those
sification methods mainly to discriminate labor contractions from expected to achieve active labor spontaneously before the end of
non-labor contractions [15], and term from preterm deliveries [14– full term (<41 GA) and those expected to need late term.
16], and in a minor extent to study the effect of different drugs Of the 72 pregnant patients who consented to participate in the
[17,18]. Although results have shown great potential of EHG, so study, 10 were excluded as their delivery was by elective caesarian
far clinical application is very limited. This is probably due to in- section due to breech presentation. Of the 62 analyzed, 38 sponta-
commodities derived of some recording protocols and equipment’s neously entered into labor before the end of full term and 24 late
used in research studies, and also because clinicians are not fa- term deliveries were induced by standard medical criteria.
miliar with EHG signals, and physiological interpretation of some
EHG parameters and analysis procedures could also complex and 2.2. Electrohysterography signal acquisition
not straight forward. Usually temporal and spectral parameters are
used to characterize EHG signals [14,16,19,20], especially EHG con- For each recording session, the subject’s abdominal surface was
tractions bursts. Some authors also include non-linear characteris- prepared with abrasive gel (Nuprep, Weaver and Company, USA).
tics in the EHG study [21,22]. There is also a recent trend on the A bipolar signal was captured from two Ag/AgCl disposable elec-
study of coupling and propagation of EHG by means of multichan- trodes (Kendal, USA) placed subumbilically (2.5 cm apart) in the
nel recordings [23–25]. median axis (Fig. 1). The electrodes were connected to commer-
When characterizing the uterine electrophysiological condi- cial biosignal amplifiers (ECG100C, Biopac, USA) in which the sig-
tion during pregnancy and determining the possible labor on- nals were amplified and filtered between [0.05, 35] Hz to be subse-
set, it should be considered that pregnancy is composed of two quently acquired at a sampling frequency of 500 Hz. Conventional
steps: preparatory (long conditioning) and active labor. In the my- pressure recordings on abdominal surface were also performed
ometrium, this preparatory process involves changes in the trans- with a commercial maternal monitor Corometrics 250cx (General
duction mechanisms [26], and so the spectral and temporal EHG Electric Healthcare). All the recording sessions lasted 30 min.
parameters exhibit a longitudinal evolution throughout pregnancy To eliminate low- and high-frequency interference and noise,
[27], i.e. they are GA-dependent. On the other hand, maternal age, the signals were bandpass filtered between 0.2 and 1 Hz with a 5th
body mass index (BMI), parity, and gestations also influence the order Butterworth filter and subsequently down-sampled at 20 Hz
pregnancy and labor processes underlying the changes of the uter- [30]. All the EHG bursts were then segmented manually according
ine electrical activity during pregnancy. BMI and parity are good to the following rules: the EHG bursts had to correspond in time
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J. Alberola-Rubio et al. / Computer Methods and Programs in Biomedicine 144 (2017) 127–133 129
2.5. Classifiers
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130 J. Alberola-Rubio et al. / Computer Methods and Programs in Biomedicine 144 (2017) 127–133
Fig. 2. Abdominal surface recording during contractile period: TOCO signal (upper), and EHG signal (lower).
Fig. 3. Classifiers developed to predict ≤full term spontaneous labor or IOL in late term pregnancies. SVM models depicted in descending order: a) 16 NCSP: non-
contextualized single input (obstetrical and EHG) parameters (P), b) 10 CSP: contextualized single EHG input parameters with obstetrical parameters (Bishop Score and
GA at recording) for contextualization, c) 3 SLMP: single layer with multiple input parameter, d) 4 DLMP: double layer (majority voting) with multiple input parameter.
Table 1 Table 2
Patient characteristics for ≤full term and late term labor Mean ± SD values of EHG parameters for both ≤full term and late
groups. term labor groups.
Obstetrical parameters ≤Full term Late term EHG parameters ≤Full term Late term
(n = 38) (n = 24) (n = 38) (n = 24)
Gestations 2.34 ± 1.36 2.08 ± 1.34 Contraction duration (s) 85.2 ± 46.0 85.7 ± 34.1
Parity 0.84 ± 1.02 0.54 ± 0.77 Number of contractions in 30min 2.89 ± 2.45 2.25 ± 1.56
Bishop 2.42 ± 1.95 1.08 ± 1.34 Mean frequency (Hz) 0.36 ± 0.67 0.38 ± 0.71
Maternal age (y) 31.4 ± 6.2 32.3 ± 4.3 Median frequency (Hz) 0.33 ± 0.66 0.33 ± 0.61
BMI (kg/m2 ) 28.8 ± 4.6 28.6 ± 3.7 Standard deviation frequency (Hz) 0.14 ± 0.35 0.15 ± 0.04
GA at recording (days) 277 ± 4 280 ± 5 Dominant frequency (Hz) 0.32 ± 0.06 0.31 ± 0.04
GA at birth (days)∗ 282 ± 4 288 ± 2 Normalized Energy [0.2–0 0.34] Hz 0.57 ± 0.17 0.54 ± 0.20
Normalized Energy [0.34–1] Hz 0.42 ± 0.17 0.45 ± 0.20
∗
Statistical differences (p<0.05). Power [0.2–0.34] Hz 0.25 ± 0.68 0.26 ± 0.57
Power [0.34–1] Hz 0.09 ± 0.29 0.09 ± 0.22
two groups (spontaneous ≤full term labor and IOL late term la-
bor). Furthermore, as can be seen in Table 1, the GA at the time of
recording for both groups were almost identical. Similar EHG pa- stetrical nor EHG parameters achieve good results when used as
rameters were also obtained for both groups (see Table 2), there single inputs. BS (AUC = 0.65) and GA at recording (AUC = 0.68) -
were no statistically significant differences between the EHG pa- from obstetrical parameters- are provide the best information to
rameters of the two groups. the decision model with the best results. As the AUC values from
Table 3 (non-contextualized column) summarizes the perfor- all the EHG parameters ranged between 0.46 and 0.58, we can con-
mance of the 16 SVM models with a single input. Neither the ob- sider that a single EHG input parameter does not provide enough
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132 J. Alberola-Rubio et al. / Computer Methods and Programs in Biomedicine 144 (2017) 127–133
Our study is not exempt from certain limitations: Firstly, so as [5] J.A. Martin, P.D. Sutton, H.B.E. Hyattsville MD, Births: final data for 2010: Na-
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◦ Role: Financial support only. tion of coupling and directionality between signals: application to uterine EMG
• Grant from the Universitat Politècnica de Valencia propagation, in: Conference proceedings of the Annual International Confer-
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(SP20120490) and by a VLC_Campus grant (Prematuro ID34).
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