Comparison of the Electrophysiological Myoelectrical Activity

Evolution in Induction of Labor with Pharmacological and

Mechanical Methods

Alba Diaz-Martinez

, Yiyao Ye-Lin

, Rogelio Monfort-Ortiz

, Javier Garcia-Casado

Iria Rey-Ferreira

, Felix Nieto-del-Amor

, Vicente Diago-Almela

Jose Luis Martinez-de-Juan

and Gema Prats-Boluda

Centro de Investigación e Innovación en Bioingeniería, Universitat Politècnica de València, Valencia 46022, Spain

Servicio de Obstetricia, H.U.P. La Fe, Valencia 46026, Spain

Keywords: Electrohysterography, Induction of Labour, Foley, Dinoprostone, EHG-Biomarker.

Abstract: Induction of labour (IOL) refers to triggering the contractions onset, either by pharmacological (PIOL) or

mechanical methods (MIOL), and is indicated when maternal and foetal well-being is compromised. There is

great uncertainty regarding the success of IOL regardless of the method. In current clinical practice, it is based

on assessment of cervical status by Bishop's score and degree of uterine activity by tocography. However,

Bishop's score has been shown to be subjective and poorly reproducible and tocography requires constant

repositioning and is severely affected by obesity. Meanwhile, electrohysterography (EHG) has surpassed

traditional clinical measures in monitoring PIOL progress and predicting its outcome. Although there is no

evidence of uterine myoelectric activity response of MIOL. Therefore, this work aimed to identify EHG-

biomarkers to help to determine possible differences in myoelectric response between PIOL and MIOL

success. For this purpose, the uterine response during the first 5h after Dinoprostone (PIOL) administration

and Foley catheter (MIOL) insertion was compared by EHG. For PIOL, a significantly lower time to achieve

active phase of labor and delivery, together with faster myoelectric response was found: slightly higher

contraction force, significantly higher Mean Frequency and lower Spectral Entropy after 2.5h. Between-group

differences were especially marked in Spectral Entropy (90-150 and 210-300min). Overall, this pioneering

work has demonstrated the feasibility of EHG for the characterisation of evolution also in MIOL. Furthermore,

the results suggest that EHG biomarkers may be useful in the IOL method comparison, although they should

be cross-checked with expanded databases and further investigations.

1 INTRODUCTION

Induction of labour (IOL) refers to the process of

artificially stimulating the uterus to initiate labour by

pharmacological or mechanical agents when

continuation of gestation compromises maternal-fetal

well-being (Reshme, Samal, Padmaja, Shalini, &

Radhika, 2022). Indications for IOL include elective

induction at 40 weeks, prolonged pregnancy,

https://orcid.org/0000-0002-4605-6048

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https://orcid.org/0000-0001-7931-8609

https://orcid.org/0000-0003-1410-2721

https://orcid.org/0000-0003-0050-9360

https://orcid.org/0000-0003-1882-1176

https://orcid.org/0000-0001-9133-3123

https://orcid.org/0000-0002-9362-5055

pregnancy-induced hypertension or diabetes,

oligohydramnios, intrauterine growth restriction and

Rh isoimmunisation (Liu et al., 2019; Reshme et al.,

2022).

The global incidence of IOL tripled between 1990

and 2019, going from 9.5% in 1990 to 29.4% in 2019

in the United States (Martin, Hamilton, Osterman, &

Driscoll, 2021), while the worldwide prevalence is

estimated by the WHO at 25% (World Health

Diaz-Martinez, A., Ye-Lin, Y., Monfort-Ortiz, R., Garcia-Casado, J., Rey-Ferreira, I., Nieto-del-Amor, F., Diago-Almela, V., Martinez-de-Juan, J. and Prats-Boluda, G.

Comparison of the Electrophysiological Myoelectrical Activity Evolution in Induction of Labor with Pharmacological and Mechanical Methods.

DOI: 10.5220/0011664700003414

In Proceedings of the 16th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2023) - Volume 4: BIOSIGNALS, pages 66-73

ISBN: 978-989-758-631-6; ISSN: 2184-4305

 2023 by SCITEPRESS – Science and Technology Publications, Lda. Under CC license (CC BY-NC-ND 4.0)

Organization, 2018). Out of the three and a half

million newborn registered in 2021 only in the USA,

between twenty thousand and forty thousand will end

the IOL process as failed, which in the broadest sense

is defined as the non-achievement of vaginal delivery

(Ayala & Rouse, 2022; Hamilton, Martin, &

Osterman, 2022). This entails an elevated risk of

maternal and perinatal complications, including higher

rates of obstetric intervention, cesarean delivery,

chorioamnionitis, admission to the neonatal intensive

care unit, and increased blood loss (Ayala & Rouse,

2022). If the IOL is unsuccessful, the protocol is to

perform a cesarean section which can cost up to $7,595

(1.3 times a standard cesarean section) in the USA

(Nicholson & Cyr, 2013). Not only does it have a major

impact on maternal and neonatal health, but IOL also

overburdens delivery rooms and affects health care

costs, costing more than $2 billion annually in the USA

(Kaimal et al., 2011). Given the volume of IOLs

performed each year, the development of a robust and

reliable system to aid in procedural decision making

would be a key factor in enabling clinicians to better

plan and manage deliveries, prevent maternal and fetal

complications, and optimize hospital resources.

IOL methods can be broadly divided into

pharmacological (PIOL) and mechanical (MIOL)

(Liu et al., 2019). The former involve the

administration of prostaglandins, orally or vaginally,

to stimulate the onset of contractions. Among the

most commonly employed options, the use of E2

(PGE2-Dinoprostone) is distinguished by its slow-

release vaginal application, which allows clinicians to

respond quickly in case a complication arises

(Geethanjali & Palli, 2022; Reshme et al., 2022).

Whereas the latter consist of the use of balloon

devices and hygroscopic dilators that, applying

pressure to the internal face of the cervix so as to

increase endogenous prostaglandin secretion. c Of

these, the Foley catheter stands out for its low cost,

simplicity, reversibility and lack of serious side

effects. In comparison with PIOL, IOL with amniotic

balloons requires a subsequent oxytocin

augmentation procedure in many cases, which is

associated with a significant rate of dysfunctional

deliveries and caesarean sections (Geethanjali &

Palli, 2022; Salim et al., 2011). Despite of this, the

literature suggests that mechanical methods have

similar efficacy, incur fewer adverse events (such as

uterine tachycardia) and have lower costs compared

to pharmacological agents (Jozwiak et al., 2012).

On the other hand, in order to assess IOL

evolution in current clinical practice, the most

commonly used method consists of the assessment of

cervical status and uterine dynamics, as measured by

Bishop Score (BS) and tocography respectively

(Euliano et al., 2013; Geethanjali & Palli, 2022).

Despite being widely employed, BS has been shown

to be subjective and has poor reproducibility, making

it a poor predictor of IOL outcome (Marconi, 2019).

In terms of contraction detection, it should be noted

that electrohysterography (EHG) is a promising

research technique that has been shown to outperform

tocography in both pregnancy and childbirth (Mas-

Cabo et al., 2020; Song et al., 2021; J. Xu, Chen, Lou,

Shen, & Pumir, 2022), especially in the growing

population of obese patients (Krogh et al., 2022; Mas-

Cabo et al., 2020). EHG consists of recording uterine

myoelectric activity generated by billions of

myometrial cells on the abdominal surface. Its energy

is distributed over a bandwidth ranging from 0.1 to 4

Hz (Devedeux, Marque, Mansour, Germain, &

Duchêne, 1993). EHG-bursts are composed by the

slow wave (SW) -which has a period equal to the

duration of the contraction and whose bandwidth

overlaps with the baseline being difficult to analyse

and extract reliable information from it (Nieto-Del-

Amor et al., 2021)- and by the fast wave (FW), which

can be further divided into two components

(Devedeux et al., 1993; Terrien, Marque, & Karlsson,

2007): the Fast Wave Low (FWL) which ranges from

0.13 to 0.26 Hz and is associated with the propagation

of the contraction, and the Fast Wave High (FWH)

which ranges from 0.26 to 0.88 Hz and is related to

the excitability of the uterine cells (Benalcazar-Parra

et al., 2018; Mas-Cabo et al., 2020). Although the

frequency content of FWH is thought to extend up to

3-4 Hz (Fele-Žorž, Kavšek, Novak-Antolič, & Jager,

2008), a high proportion of studies focus down to 1Hz

perhaps as a consequence of maternal cardiac

interference (1.38-1.5 Hz) (J. Xu et al., 2022).

Considering the aforementioned, the aim of the

present work is therefore to characterize and compare

the uterine electrophysiological response to IOL by

Dinoprostone and by Foley catheter during the first 5

hours of induction by electrohysterography and its

associated EHG-Biomarkers of women who achieve

Active Period of Labour (APL). Given the large

increase in the rate of inductions in recent years,

improving the understanding of the myoelectric

response to pharmacological and mechanical

inductions is becoming increasingly relevant to

clinical practice. Not only to guide clinical practices,

but also to delve deeper into the underlying

physiological mechanism and thus promote a better

understanding of the optimal methods for IOL in each

case.

Comparison of the Electrophysiological Myoelectrical Activity Evolution in Induction of Labor with Pharmacological and Mechanical

Methods

2 MATERIALS AND METHODS

2.1 Study Design

A prospective observational cohort study was

conducted in pregnant women admitted for cervical

ripening at the Hospital Universitario y Politécnico

La Fe (Valencia, Spain). Either they were candidates

for pharmacological induction with Dinoprostone

(10mg, Propess, Ferring SAU) or mechanical

induction with a Foley catheter (Folysil, Coloplast).

Both methods were withdrawn after 12 hours. In case

the catheter fell out on its own during the MIOL

procedure it ended earlier. In this study only IOLs that

reached the active period of labor were considered.

Fetal macrosomia, multiple pregnancies, advanced

maternal age (>45 years), severe preeclampsia,

placenta previa, premature rupture of membranes,

vaginal bleeding during pregnancy and active cardiac,

renal, pulmonary or hepatic disease; were exclusion

factors for this study due to bias. This work adhered

to the guidelines of the Declaration of Helsinki and

was approved by the hospital's Institutional Review

Board (Registration Number 2018/0530). Patients

were informed of the nature of the study and gave

written informed consent.

The following clinical information was included:

maternal age, body mass index (BMI), number of

previous pregnancies, parity, gestational age at

delivery, initial BS, increase in BS during IOL (12 h

after insertion), time to achieve APL, time to delivery

and completion of vaginal delivery. The chi-square

test was used to detect statistically significant

differences in nominal variables between groups.

Ordinal variables were compared using the Wilcoxon

rank sum test. Continuous variables were compared

with Student's t test or the Wilcoxon rank sum test,

depending on whether they were considered normal

or not by the Shapiro-Wilk test.

2.2 Signal Acquisition

For EHG recording, the abdominal surface was

exfoliated using abrasive gel (Nuprep, Weaver and

Company, Aurora, CO, USA) and cleaned with

isopropyl alcohol to reduce skin-electrode

impedance. Four single-use Ag/AgCl electrodes (Red

Dot 2660-5, 3M, St. Paul, MN, USA) were then

placed as shown in Figure 1. Two electrodes (M1 and

M2) were placed symmetrically with respect to the

mid-axis at a distance of 6 cm from each other. The

other two electrodes were placed on each hip to

provide reference and ground biopotentials.

Figure 1: Electrodes positioning for uterine myoelectrical

recording. M1: monopolar electrode 1. M2: monopolar

electrode 2. REF: Reference electrode. GND: Ground

electrode.

Both monopolar signals were conditioned with a

custom-made wireless recording module, which

provided a gain of 2059 V/V in the 0.1-150 Hz

bandwidth and digitized with a 24-bit analog-to-

digital converter at 500 Hz (Ye-Lin, Bueno-

Barrachina, Prats-boluda, Rodriguez de Sanabria, &

Garcia-Casado, 2017). The recording starts 30

minutes before the start of the IOL and ends 5 hours

later. Unlike other research settings where up to 16

electrodes are placed (Muszynski et al., 2018; Y. Xu,

Hao, & Zheng, 2020), this simplified protocol was

chosen because it does not compromise routine

clinical practice or add additional complexity to the

highly stressful situation faced by women due to the

imminence of labor (Benalcazar-Parra et al., 2018).

Digitalized monopolar EHG signals were filtered

between 0.1-4 Hz (5th order zero-phase Butterworth

bandpass filter) and then downsampled to 20 Hz to

maintain a balance between temporal resolution and

computational cost (Diaz-Martinez et al., 2021; Mas-

Cabo et al., 2020). A bipolar signal was then

computed as its difference (M2-M1) to reduce

common-mode interference and increase signal

quality (Mas-Cabo et al., 2020; J. Xu et al., 2022).

Finally, two experts identified the onset and end of

the EHG bursts, which were related to uterine

contractions. They were associated with substantial

changes in amplitude and frequency with respect to

the reference tone with durations longer than 40

seconds and without respiratory interference or

motion artefacts (Diaz-Martinez et al., 2021; Mas-

Cabo et al., 2020; J. Xu et al., 2022).

2.3 EHG Parametrisation

In order to characterize uterine contractions, a set of

temporal, spectral and nonlinear parameters were

BIOSIGNALS 2023 - 16th International Conference on Bio-inspired Systems and Signal Processing

calculated from the EHG-Bursts. The Root Mean

Square (RMS) calculated at 0.1-4 Hz was included as

a measure of amplitude related to uterine contraction

intensity (Diaz-Martinez et al., 2021; Mas-Cabo et al.,

2020). As labor progresses, contractions are more

frequent and of greater intensity, which is equivalent

to a higher signal amplitude (Diaz-Martinez et al.,

2021; J. Xu et al., 2022). The RMS is therefore

expected to show an upward trend throughout the

IOL. In addition, the Mean Frequency (MNF) was

calculated in order to characterise the expected shift

in spectral content towards higher frequencies due to

enhanced cell excitability as parturition approaches.

It was calculated at 0.2-1 Hz (Horoba et al., 2016;

Mas-Cabo et al., 2020) to minimise the influence of

cardiac interference and baseline fluctuation (J. Xu et

al., 2022). Successful IOL is associated with an

increase in MNF (Diaz-Martinez et al., 2021).

Finally, Spectral Entropy (SpEn) (Diaz-Martinez et

al., 2021; J. Xu et al., 2022) and Higuchi Fractal

Dimension (HFD) (Diaz-Martinez et al., 2021; Kesić

& Spasić, 2016) were computed as non-linearity

parameters. It was done in the FWH bandwidth to

provide a robust characterisation of the EHG (Mas-

Cabo et al., 2020; J. Xu et al., 2022). It is due to the

fact that as delivery approaches, myoelectric activity

also tends to become more organised and predictable,

resulting in a downward trend of non-linearity

parameters (Benalcazar-Parra et al., 2018; Diaz-

Martinez et al., 2021).

EHG parameters were calculated for each section

identified as contraction during the first five hours of

induction. Then, in order to reduce the effect of

intrinsic variability of uterine contractility, uterine

contractility was analysed at 30-minute time (from

now on, analysis window) (Benalcazar-Parra et al.,

2018; Diaz-Martinez et al., 2021). There were 11

windows per recording: 1 in the baseline condition

(before drug administration or probe placement) and

10 to assess the response during the first five hours of

IOL. Median values of the EHG-burst parameters

were calculated for each 30-minute window in order

to obtain a single representative value per analysis

window for each recording session. Then, the mean

of each parameter in each 30-minute window was

calculated for each group (MIOL and PIOL).

Finally, statistically significant differences in

uterine myoelectric response between MIOLs and

PIOLs were analysed. For this purpose, significant

changes from baseline activity of EHG parameters

throughout the recording session were determined for

each window of analysis and for each induction

method using the Wilcoxon signed-rank test

(α=0.05). The same statistical test was employed to

evaluate the differences between induction methods,

comparing each parameter in each window of

analysis between the methods.

3 RESULTS

A total of 73 patients were recruited, of which 52

were induced by pharmacological methods and the

remaining 21 by mechanical methods. Their obstetric

and delivery variables are summarised in

Table 1.

Significant differences have been found for parity,

gestational age at delivery, time to reach the active

period of labour and time to delivery between MIOL

and PIOL.

Table 1: Obstetric data and outcomes of labour induction of

women enrolled in the study, mean ± standard deviation or

number of cases. BMI: Body Mass Index. GAD:

Gestational Age at Delivery in weeks. BS: Bishop Score.

APL: Active Period of Labour. p: Wilcoxon Rank-sum or

t-student test p-value (in bold: statistically significant

difference, p<0.05).

Variable MIOL PIOL p

Mat. age

ears

)

µ±σ 32.2±5.5 34.0±5.6 0.241

BMI (kg/m2) µ±σ 24.6±4.2 26.05±7.5 0.124

Gestations µ±σ 2.1±0.7 2.0±1.4 0.212

Parity µ±σ 0.1±0.4 0.6±0.7 0.009

GAD (weeks) µ±σ 39.4±1.5 40.7±0.5 <0.005

Initial BS µ±σ 3.1±1.2 2.6±2.6 0.427

ΔBS µ±σ 2.1±1.8 3.3±4.6 0.967

Time to

APL (h)

µ±σ 25.9±6.9 16.4±9.1 <0.005

Time to

Del. (h)

µ±σ 29.2±6.0 20.8±12.1 <0.005

Vag. Ending N 19/21 46/52 0.806

The uterine myoelectric activity parameters in

response to the IOL is represented in Figure 2 for the

MIOL (blue) and PIOL (red) groups. An increasing

trend is described for the RMS in both groups,

although it is slightly more accentuated for PIOL. No

differences were found with respect to baseline or

between IOL methods.

The MNF shows a more pronounced upward trend

again for the PIOL group, in which case differences

with respect to baseline are identified at 150 and

maintained from 210 to 300. By contrast, the MIOL

shows no significant evolution. Differences between

groups are found at 150 and 210-300.

Comparison of the Electrophysiological Myoelectrical Activity Evolution in Induction of Labor with Pharmacological and Mechanical

Methods

Figure 2: Temporal evolution of temporal, spectral and non-linear parameters for mechanical (MIOL) and Pharmacological

Induction of Labour (PIOL) groups. Statistical differences between groups are indicated by black downward-pointing

triangles and with respect to basal activity by blue leftward (MIOL) and red rightward (PIOL) triangles.

As for the non-linearity parameters, the trends are

also more noticeable for PIOL. For both parameters,

difference with respect to baseline were identified for

PIOL from 210 and for MIOL only at 180 and 300.

By contrast, MIOL did not show any trend during the

first 5 hours. When comparing MIOL and PIOL

groups, significant differences were found for SpEn

from 90 except for 180, and for HFD from 150.

4 DISCUSSION

In this work we have analysed and compared the

difference in uterine myoelectric response between

the induction methods of Dinoprostone and Foley

catheter. As far as we are concerned, this is the first

study to report this type of EHG-biomarker in the

comparison between IOL methods. These initial

results in this line of research will need to be

corroborated with expanded databases and future

studies, such as the comparison of MIOL successes

and failures. We believe that the EHG-biomarker

information proposed could lead to the design of

robust and generalizable systems for predicting the

success of labour induction.

Regarding obstetric variables, differences were

found in parity and gestational age at delivery. This

can be explained because after a previous caesarean

section, IOL is associated with a higher risk of uterine

dehiscence, uterine rupture and repeat caesarean

section compared to women with spontaneous onset

of labour. Mechanical methods are suggested to this

group because they are associated to lower risk of

hyperstimulation and uterine rupture (Kruit,

Wilkman, Tekay, & Rahkonen, 2017). Thus, at equal

gestations, there are fewer vaginal deliveries in the

MIOL group. Despite this, we believe that the

differences found in myoelectric activity are not due

to the difference in gestational age, as it is considered

that in both groups the uterus are sufficiently mature,

in addition to the fact that no significant differences

are found at the basal analysis window. We therefore

attribute the differences found to the IOL method

It should be added that previous studies in the

PIOL field have suggested that the differences that

might be due to the number of previous deliveries are

minimal, especially in RMS, MNF, SpEn and HFD

(Diaz-Martinez et al., 2021). On the other hand, the

lower gestational age in the MIOL group is again due

to protocol indications, as the use of the Foley

BIOSIGNALS 2023 - 16th International Conference on Bio-inspired Systems and Signal Processing

catheter was used in case of the fetal growth

restrictions, which requires induction at 37 weeks,

with a favourable safety profile compared to

Dinoprostone (Villalain et al., 2019).

Finally, the time from the induction onset to the

active period of labor was significantly shorter for

PIOL. Our results are consistent with Wang's meta-

analysis (Wang, Hong, Liu, Duan, & Yin, 2015) of up

to 731 women induced with controlled-release

Dinoprostone and 722 with Foley, which suggests

that PIOL results in a reduction in time to delivery

and oxytocin use. Lastly, our results seem consistent

with other studies in terms of BS modification, as in

Pennell's study (Pennell et al., 2009), we found no

significant changes between induction methods.

Of note, while the uterine electrophysiological

response to PIOL has been researched previously

(Benalcazar-Parra et al., 2018; Diaz-Martinez et al.,

2021), studies on myoelectric uterine response to

MIOL are limited and primarily focused on obstetric

output. MIOL is known to be associated with a

decreased risk of uterine hyperstimulation. This could

be consistent with the lower contraction strength

obtained in the present work, although no differences

were found in the first 5 hours of IOL. In addition,

MIOL has been associated with a higher oxytocin

requirement than PIOL (Reshme et al., 2022; Wang

et al., 2015), suggesting that cells are less excitable

after this procedure. This is consistent with our

results, as MIOL MNF shows no difference from

baseline, while PIOL MNF does.

On the other hand, non-linearity results obtained

suggest lower complexity in the case of PIOL uterine

activity, a trait associated with shorter time to

delivery. The literature points out that the use of

prostaglandins is associated with an acceleration of

gap junction formation, which in turn leads to more

coordinated uterine contractions (Rayburn, 2002). In

addition, Pennell (Pennell et al., 2009) described by

Kaplan-Meier curves a higher proportion of

deliveries in PIOL compared to MIOL before 10

hours from the start of the IOL process, which is

consistent with our results.

5 CONCLUSIONS

In this work, the EHG technique and its associated

EHG-biomarkers have demonstrated their feasibility

to characterise the evolution of uterine dynamics also

during the MIOL process. They have been shown to

provide new relevant information on cellular

excitability and the coordination of contractile

activity that could not be perceived with the

traditional tocography technique. Our results suggest

that PIOL triggers a faster uterine myoelectric

response than MIOL, with contractions of higher

amplitude, a significantly higher MNF after 2.5h of

IOL onset and a higher degree of regularity and less

complexity, with also statistically significant

differences for both groups also after about 2.5h from

the start of induction.

Therefore, this accurate and quantitative

assessment of the IOL process based on EHG could

lead to more reliable IOL success prediction systems

and help to improve maternal-fetal wellbeing. In

addition to helping to better understand the

electrophysiological response in the IOL

environment.

ACKNOWLEDGEMENTS

This work was supported by the Spanish Ministry of

Economy and Competitiveness and the European

Regional Development Fund (MCIU/AEI/FEDER,

UE RTI2018-094449-A-I00-AR and PID2021-

124038OB-I00).

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