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Measurement of Area Difference Ratio of Photoplethysmographic Pulse Wave in Patients With Pre-Eclampsia

This study investigates the area difference ratio (ADR) derived from photoplethysmography (PPG) in women with and without preeclampsia during the third trimester of pregnancy. Results show that the ADR is significantly lower in patients with preeclampsia compared to those without, indicating its potential as a diagnostic tool for assessing maternal arterial stiffness. The findings suggest that measuring ADR may help in understanding the pathophysiology of preeclampsia and its associated risks.
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0% found this document useful (0 votes)
12 views5 pages

Measurement of Area Difference Ratio of Photoplethysmographic Pulse Wave in Patients With Pre-Eclampsia

This study investigates the area difference ratio (ADR) derived from photoplethysmography (PPG) in women with and without preeclampsia during the third trimester of pregnancy. Results show that the ADR is significantly lower in patients with preeclampsia compared to those without, indicating its potential as a diagnostic tool for assessing maternal arterial stiffness. The findings suggest that measuring ADR may help in understanding the pathophysiology of preeclampsia and its associated risks.
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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Feng et al.

BMC Pregnancy and Childbirth (2018) 18:280


https://doi.org/10.1186/s12884-018-1914-y

RESEARCH ARTICLE Open Access

Measurement of area difference ratio


of Photoplethysmographic pulse wave
in patients with pre-eclampsia
Ying Feng1, Dan Drzymalski2, Baihui Zhao3, Xuan Wang4 and Xinzhong Chen5*

Abstract
Background: Preeclampsia (PE) is associated with an increase in maternal arterial stiffness, which may be reflected
by photoplethysmography (PPG) of the pulse wave. The aim of this study was to investigate area difference ratio
(ADR), a novel parameter derived from PPG, in women with and without preeclampsia.
Methods: Patients with and without preeclampsia in the third trimester were enrolled. All patients had
photoplethysmography of the pulse wave assessed. ADR was compared between the two groups.
Results: Seventy-two patients in the third trimester of gestation, of which 36 had preeclampsia and 36 did not, were
enrolled. The ADR was lower in the preeclampsia group vs. the non-preeclampsia group (0.725 [IQR 0.681–0.779]
vs. 0.752 [IQR 0.717–0.910], P < 0.01).
Conclusions: Measuring the ADR through analyzing PPG of the pulse wave may be a useful diagnostic tool in patients
with preeclampsia.
Keywords: Photoplethysmography, Area difference ratio, Hypertension, Preeclampsia

Background Photoplethysmography (PPG) is a non-invasive and


Preeclampsia remains one of the leading causes of readily available optical technique that uses infrared light
maternal and fetal morbidity and mortality worldwide, af- to illuminate the fingertip tissue and measures variations
fecting 2–3% of all pregnancies in the USA and 7.5% glo- in light intensity that correspond to blood vessel volume
bally [1, 2]. The disease is characterized by hypertension, [16, 17]. Previous studies have demonstrated that the
proteinuria and vascular dysfunction [3–5], and the patho- contour of the PPG contains similar information to that
physiology of preeclampsia may involve an increase in ar- of the peripheral pressure wave and may be used to
terial wall rigidity as a result of maternal endothelial evaluate arterial stiffness [18–20].
dysfunction [6, 7]. Arterial stiffness can be assessed by The diastolic decay constant (a function of vessel re-
measuring various parameters, including pulse wave vel- sistance and compliance) [21, 22] is associated with
ocity (PWV) and augmentation index (AIx) [6, 8–12]. As physiological changes of the cardiovascular system and
arterial stiffness is associated with an increased risk of is useful in vascular assessment [20, 22–25]. However, it
having a cardiovascular event in healthy non-pregnant is difficult to extract from the finger PPG pulse wave-
subjects [13], PWV and Aix may be helpful in predicting form. As such, the area difference ratio (ADR) was de-
morbidity and mortality in preeclampsia. Similarly, PWV veloped using a novel, non-iterative, shape method from
and Aix may also be used to provide information on arter- the PPG waveform to serve as a parameter that is more
ial compliance in preeclampsia [8, 11, 14, 15]. readily established than the diastolic decay constant.
The aim of this study was to better understand the
pathophysiology of preeclampsia by measuring the ADR
in patients with or without preeclampsia at the time of
* Correspondence: [email protected]
5
Department of Anaesthesia, Women’s Hospital, School of Medicine,
disease. Our hypothesis was that the ADR would be
Zhejiang University, Xueshi Rd 1, Hangzhou 310006, China lower in patients with preeclampsia.
Full list of author information is available at the end of the article

© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Feng et al. BMC Pregnancy and Childbirth (2018) 18:280 Page 2 of 5

Methods
Study population
The study protocol was approved by the Research Ethics
Committee of the Women’s Hospital, School of Medi-
cine, Zhejiang University, and written informed consent
was obtained from all patients who participated in the
study. Patients with singleton pregnancies of at least
28 weeks gestational age were enrolled during a routine
prenatal screening at the obstetrics clinic into one of
two groups: the preeclampsia group (PE) or the
non-preeclampsia group (Non-PE). Patients were en-
rolled in the PE group if they had a systolic blood pres-
sure (SBP) ≥140 mmHg or diastolic blood pressure
(DBP) ≥90 mmHg measured on two separate occasions
at least 6 h apart, and proteinuria of ≥0.3 g/L in a 24 h
urine collection that started after 20 weeks of pregnancy Fig. 1 A representive beat of pulse photoplethysmographic
[26]. Pregnant women were excluded if they had gesta- waveform. Baseline is corrected to 0. Point A, P and B are the onset,
tional diabetes, essential hypertension, renal disease, his- peak and end position of pulse, respectively. Point O is the vertical
tory of tobacco use, and alcohol or illicit drug abuse. projection of point P on the baseline. PPG signal (−) is shown with
PPG magnitude in arbitrary units (au)

Pulse wave analysis


Women who consented to the study were instructed to interquartile range (IQR) for normally and non-normally
fast for at least 12 h prior to the study. Baseline demo- distributed data, respectively. Comparisons between
graphic data were gathered upon the start of the study. groups were performed using Student’s t-test and the
All participants were instructed to sit comfortably with Chi-squared test were used for parametrically distributed
her arm supported on a table in a room whose continuous and categorical variables, respectively, and the
temperature was maintained at 24 °C. After at least Mann-Whitney U test was used for non-parametrically
10 min of rest, the SBP and DBP were measured twice distributed continuous variables. A multivariate regression
and the mean calculated. An adult oxygen sensor model was used to analyze the association of ADR with
(DS-100A Durasensor, OxiMax, Nellcor Puritan Bennett, maternal demographic and hemodynamic data.
Inc.) was placed on the index finger of the
non-dominant arm of pregnant woman to detect and Results
collect PPG signal at a rate of 250 Hz. PPG measure- A total of 72 pregnant women, 36 in the PE group and
ments were performed 3 times over 5 min intervals and 36 in the Non-PE group, enrolled in the study between
the mean calculated. Data was stored on a computer June 1 and December 31, 2016. The PE group consisted
with specialized software we developed to calculate of 30 patients with mild and 6 patients with severe pre-
ADR, PPG amplitude (PPGA) and pulse beat interval eclampsia. Twenty-three patients in the PE group were
(PBI). ADR was calculated as the difference between the taking antihypertensive medications, including
area of the triangle (St) formed by points B, P, and O, β-blockers (14 patients), β-blockers and Calcium channel
and the area under the curve of the pulse (Sp) but above blockers (9 patients), or Calcium channel blockers (3 pa-
the horizontal line formed by points B and O, divided by tients). A total of 26 patients had early onset (< 34 weeks)
St, as follows (see Fig. 1 for points referenced) [21]: preeclampsia and 10 had late onset (> 34 weeks)
ADR = (St – Sp) / St. PPGA was calculated as the differ- preeclampsia.
ence of magnitude between point P and baseline. PBI Baseline demographic data of study participants are
was calculated as the time difference between point A presented in Table 1. There were no statistically signifi-
and point B. cant differences between the groups in maternal age,
gestational age at enrollment, or fetal sex. The PE group
Statistical analysis exhibited higher weight, higher body mass index, shorter
All statistical analyses were performed using Graphpad height, and lower birth weight. Gestational age at deliv-
Prism 4 (Graphpad software Inc., San Diego, CA, USA). ery was significantly earlier in the PE group than in nor-
A P-value of < 0.05 was considered statistically signifi- mal pregnant women.
cant. The Kolmogorov-Smirnov test was used to assess Multivariate regression analysis found no significant
for Gaussian distribution. Data were expressed as mean associations between ADR and height (P = 0.94), weight
± standard deviation (S.D.) or as median and (P = 0.83), SBP (P = 0.85), and DBP,(P = 0.83).
Feng et al. BMC Pregnancy and Childbirth (2018) 18:280 Page 3 of 5

Table 1 Demographic data for pregnant women: normal and preeclampsia


parameter Non-PE (n = 36) PE (n = 36) P Value
Maternal age (years) 30.0 ± 3.6 31.3 ± 3.9 0.195
Gestational age at enrollment (weeks) 30.8 ± 2.2 31.5 ± 2.5 0.207
Gestational age at delivery (weeks) 39.1 ± 0.9 34.1 ± 3.2 < 0.0001
Maternal height (m) 1.63 ± 0.05 1.60 ± 0.05 0.045
Maternal weight (kg) 67.1 ± 9.4 73.3 ± 7.5 0.005
Body mass index (kg/m2) 25.4 ± 3.2 28.7 ± 2.3 < 0.001
Birth weight (g) 3514 ± 375 2283 ± 1010 < 0.0001
Fetal sex (male/female) (16/20) (19/17) 0.479
Values are given as mean ± S.D. or as median (IQR) for normally and non-normally distributed data, respectively

SBP, DBP, mean arterial pressure, PPGA, PBI, and ADR The major advantage of PPG is that it is a
are presented in Table 2. The PPGA and PBI were not sig- non-invasive technique that can measure various param-
nificantly different between the groups. Conversely, pa- eters associated with the pulse wave. While several pa-
tients in the PE group had a lower ADR decreased and rameters from the PPG pulse wave have been measured,
higher SBP, DBP, and MAP. The ADR returned to baseline including the PPG amplitude and the PPG notch
42 days postpartum in the PE group (see Fig. 2). position and notch relative amplitude, none have dem-
onstrated clinical utility [31–34]. Furthermore, environ-
mental factors, metabolic state, motion artifact and
Discussion psychological wellbeing all influence these parameters
In this study, we observed that patients with preeclampsia and make interpretation of those parameters unreliable
have a lower ADR compared to those without preeclamp- [35, 36]. On the other hand, the major advantage of the
sia during the early third trimester. No differences were ADR is that the effect of PPG magnitude is eliminated in
observed in PPGA and PBI between the two groups. its calculation and therefore makes it more reliable [21].
Our primary finding that preeclampsia was associated The only limitation of the ADR is that pre-calibration is
with a lower ADR is consistent with our initial hypothesis. essential for a reliable measurement.
The ADR is closely correlated to the diastolic decay con- Preeclampsia is characterized by a marked increase in
stant, a parameter that describes the exponential rate at peripheral vascular resistance and vasoconstriction [3–5],
which arterial pressure decreases during diastole [21, 22]. and increased sympathetic vasoconstrictor activity has
An accelerated diastolic decay constant is associated been demonstrated with measurements of muscle sympa-
with greater arterial stiffness and therefore hyperten- thetic nerve activity [3, 37]. The etiology of the increased
sion. By measuring the diastolic decay constant with in- sympathetic tone is likely endothelial dysfunction [38–41].
vasive arterial blood pressuring monitoring we can It is important to note that endothelial dysfunction may
further characterize resistance and total arterial compli- be present in preeclampsia as this is an important step in
ance [27]. In addition, one of the major advantages of the development of atherosclerosis in patients with
the diastolic decay constant is that local factors, includ- chronic hypertension [42]. In non-pregnant patients with
ing perfusion, do not significantly alter its value [28– chronic hypertension, vascular disease or diabetes, vascu-
30]. However, the invasive nature of this test limits its lar stiffness may be due to the decline of vascular compli-
clinical utility on the labor and delivery unit. ance [43–46].
Table 2 Vascular characteristics of the study populations
parameter Non-PE (n = 36) PE (n = 36) P Value
Heart rate (beats/min) 75.9 ± 9.7 76.4 ± 9.2 0.679
SBP (mmHg) 115.8 ± 9.2 152.6 ± 14.8 < 0.001
DBP (mmHg) 69.6 ± 7.6 99.3 ± 3.0 < 0.001
Mean arterial pressure (mmHg) 85.0 ± 7.5 117.1 ± 6.1 < 0.001
PPGA(au) 280.4 (215–372.4) 268.4 (158.6–428.1) 0.853
PBI(s) 0.628(0.543–0.651) 0.625 (0.608–0.699) 0.205
ADR 0.752 (0.717–0.910) 0.723 (0.681–0.779) < 0.01
ADR (postpartum) 0.778 (0.723–0.813) 0.789 (0.742–0.810) 0.404
Values are presented as mean ± S.D. or as median (IQR) for normally and non-normally distributed data, respectively
Feng et al. BMC Pregnancy and Childbirth (2018) 18:280 Page 4 of 5

Abbreviations
ADR: area difference ratio; Aix: augmentation index; AS: arterial stiffness;
DBP: distolic blood pressure; MBP: mean blood pressure; PBI: pulse beat
interval; PE: preeclampsia; PPG: photoplethysmography;
PPGA: photoplethysmography amplitude; PWV: pulse wave velocity;
SBP: systolic blood pressure

Funding
The present study was supported by the funding from National Natural Science
Foundation of China (NSFC, No 81271237 and No 81471126) and the fund from
Science Technology Department of Zhejiang Province (No 2014C33171N).

Availability of data and materials


The datasets used and/or analysed during the current study are available
from the corresponding author on reasonable request.

Authors’ contributions
FY helped in designing and conducting the study, collecting the data and
writing the manuscript. DD helped in analyzing and interpreting the data
and revising the manuscript critically. ZB helped in conducting the study and
collecting the data. WX helped in designing the study and analyzing the
data. CX helped in designing the study, analyzing the data and writing the
manuscript. All authors have read and approved the manuscript.

Ethics approval and consent to participate


Fig. 2 Box and whisker plots comparing the ADR in the PE group The study protocol was approved by the local Research Ethics Committee of
during pregnancy (left), and postpartum (right). Boxes represent IQR, the Women’s Hospital, School of Medicine, Zhejiang University and written
where the line represents the median. Whiskers at top and bottom informed consent was obtained from all patients who participated in the study.
of the box represent the highest and lowest values
Consent for publication
Not applicable.

Competing interests
It is important to note that our study has several The authors declare that they have no competing interests.

limitations. First, given the study design (cross-sec-


tional study of women with preeclampsia at 30 weeks Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
gestational age), our results describe pathophysio- published maps and institutional affiliations.
logical changes of preeclampsia but do not necessarily
indicate that the ADR is a useful tool in the predic- Author details
1
Department of Anaesthesia, Women’s Hospital, School of Medicine,
tion of preeclampsia. Second, while we believe that Zhejiang University, Xueshi Rd 1, Hangzhou 310006, China. 2Tufts Medical
ADR may be a useful measure of arterial stiffness, we Center, Tufts University School of Medicine, 800 Washington Street, Boston,
did not correlate the ADR to other established mea- MA 02111, USA. 3Department of Obstetrics, Women’s Hospital, School of
Medicine, Zhejiang University, Xueshi Rd 1, Hangzhou 310006, China. 4School
sures of arterial stiffness (e.g. PWV, Aix). Future stud- of Medical Instruments, Shanghai University of Medicine & Health Sciences,
ies should attempt to make that correlation. Third, 257 TianXiong Rd, Pudong, ShangHai 201318, China. 5Department of
given that increased sympathetic activity may be char- Anaesthesia, Women’s Hospital, School of Medicine, Zhejiang University,
Xueshi Rd 1, Hangzhou 310006, China.
acteristic of pregnancy in the absence of neurological
disease, digital blood flow and thus the waveform Received: 4 January 2018 Accepted: 22 June 2018
may have been affected by peripheral vasoconstriction.
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