Keywords
pregnancy - noninvasive cardiac output monitoring - obesity - hemodynamic - pilot
study
The obesity pandemic continues unabated, and according to the latest assessments,
300 million female people worldwide have obesity.[1] In the general population, obesity is defined as a body mass index (BMI) greater
than 30 kg/m2. Obesity can alter hemodynamic function by causing higher cardiac output (CO)[2]
[3] and higher stroke volume (SV).[4]
[5] Obesity is also associated with altered myocardial geometry[6] and heart failure.[7]
[8]
Obesity in pregnancy is defined as a BMI greater than or equal to 30 kg/m2 at the first antenatal consultation and confers a high-risk status on the pregnancy.[9] In the United States, alone half of all pregnant people have overweight or obesity.[10] Pregnant people with obesity are at increased risk for gestational hypertension,[11] preeclampsia,[12] gestational diabetes,[11]
[13] maternal mortality,[14] and are more likely to have caesarean births.[15]
[16] There are also serious implications for the fetus including risk of stillbirth,[17] macrosomia,[18] and congenital abnormalities.[19] Infants born to people with obesity more often demonstrate fetal distress in labor,
meconium aspiration, and low Apgar's scores,[20] and, in future, life as adults with an increased risk of premature death.[21]
Identifying cardiovascular differences between pregnant people with and without obesity
might assist in identifying targets for intervention to improve outcomes in these
cohorts of patients.
Traditionally, the gold standard for central hemodynamic monitoring has been invasive
through the use of a pulmonary artery catheter (PAC). Placement of these lines and
the interpretation of the readings require considerable specialist expertise.[14] The development of transthoracic bioreactance monitoring has been revolutionary,
as it permits noninvasive, bedside monitoring of the SV, and CO. Transthoracic bioreactance
methods have been validated against open heart porcine models,[22] pulse contour analysis,[23] and the PAC.[22]
[24] Transthoracic bioreactance monitoring has been safely used in pregnancy[25]
[26]
[27]
[28] where it has demonstrated hemodynamic differences between preeclamptic and normotensive
pregnant people.[25]
[28]
We hypothesized that by using noninvasive cardiac output monitoring (NICOM), we would
be able to detect hemodynamic differences between pregnant people with and without
obesity during the course of pregnancy.
Methods
Study Population
This prospective comparative cohort pilot study was conducted at a large tertiary
care referral center (Mount Sinai Hospital, Toronto, Canada). We recruited two cohorts
of pregnant people with and without obesity. At the time of initial booking into local
antenatal clinic, people with obesity were identified by BMI greater than or equal
to 30 kg/m2 and people without obesity by BMI 18 to 25 kg/m2.
All recruited patients were at least 18 years old and were followed longitudinally
throughout their pregnancies. All patients agreed to participation by giving informed
consent. The study was approved by the local institutional review board.
Study Procedures
Patients were interviewed and pertinent past medical and social history were collected.
Height was measured at the patient's first visit. Once per trimester (12–14, 21–23,
and 34–36 weeks), all enrolled patients underwent the following assessments:
Anthropometric Measurements
Cardiovascular Measurements
-
Resting systolic and diastolic blood pressure was measured with a standard sphygmomanometer
with an appropriately sized cuff.
-
Hemodynamic assessment was performed with the bioreactance-based NICOM system (NICOM,
Cheetah Medical Inc.). The NICOM noninvasively measured cardiac function parameters
including mean arterial pressure (MAP), CO, cardiac index (CI), SV index (SVI), total
peripheral resistance (TPR), and TPR index (TPRI). The definitions, units, and normal
values of these parameters are as follows:
-
– MAP (mm Hg) defined as the average pressure in a patient's arteries during one cardiac
cycle. It is considered a better indicator of perfusion to vital organs than systolic
blood pressure (SBP; normal range: 70–105 mm Hg).
-
– CO (L/min) is the amount of blood the heart pumps through the circulatory system
in 1 minute (normal range: 4–8 L/min).
-
– CI (L/min/m2) is a hemodynamic parameter that describes the CO from left ventricle in 1 minute
to body surface area, thus relating heart performance to the size of the individual
(normal range: 2.5–4 L/min/m2).
-
– SVI (mL/m2/beat) is the amount of blood pumped by left ventricle in one contraction (beat) to
body surface area (normal range: 33–47 mL/m2/beat).
-
– TPR (dyne.s/cm3) is the resistance to blood flow offered by all of the systemic vasculature, excluding
pulmonary vascular system. TPR is equivalent to systemic vascular resistance (SVR)
when the central venous pressure (CVP) is low. NICOM monitor estimates TPR assuming
CVP is negligible (e.g., equals to 0) and uses same calculation of SVR.
SVR = (MAP − CVP) × 80 / CO (normal range: 800–1,200 dyne.s/cm3)
-
– TPRI (dyne.s/cm3/m2) is the TPR by patient's body surface area (normal range: 1,970–2,390 dyne.s/cm3/m2).
The patient interfaced with the NICOM system through four disposable surface pregelled
and glued double electrodes placed on the patient's skin, providing the connection
for measurements of current flowing along the thorax. Two electrodes were placed on
upper chest and two were placed on the upper abdomen to act as the source of a constant
magnitude and, high-frequency current that provided homogeneous coverage of the thorax
with an HF electrical field.
Data Analysis
Continuous variables with normal distribution were expressed as means with standard
deviations. The significance of comparison was assessed by Student's t-test. All p-values were two-sided and a value of less than or equal to 0.05 was considered statistically
significant. Associations between hemodynamic and anthropometric characteristics were
calculated using Pearson's correlation coefficient (r). Statistical analyses were completed using commercially available software (SAS
Version 9.2, SAS Institute, Cary, NC).
Results
Seven pregnant people with obesity and eight with normal weight were enrolled in the
study. In the group with obesity, six (6/7) patients completed the study, whereas
in the group without obesity, seven (seven of eight) completed the study. One patient
with normal weight and one patient with obesity presented with preterm births at 36
and 35 weeks, respectively, before they could be studied during the third trimester.
All remaining patients in both groups completed their pregnancies without adverse
obstetrical events and all had healthy term infants (> 37 weeks). All neonates were
discharged with mothers and no admission to neonatal intensive care unit (NICU) was
reported. Both groups of women were age-matched at the time of enrolment and were
of similar gravidity, parity and gestational age ([Table 1]).
Table 1
Demographic and anthropometric data of pregnant people with and without obesity at
the time of study enrollment
|
Obese
|
Nonobese
|
p
|
|
n
|
7
|
8
|
NA
|
|
Age (y)
|
33.7 ± 5.2
|
33.1 ± 2.5
|
0.79
|
|
BMI (kg/m2)
|
39.8 ± 3.9
|
22.2 ± 2.5
|
< 0.0001
|
|
Fat mass (%)
|
40.6 ± 3.6
|
28.6 ± 5.9
|
< 0.0001
|
|
Gravity
|
3.4 ± 2.1
|
1.6 ± 0.5
|
0.06
|
|
Parity
|
1.4 ± 0.4
|
1.2 ± 0.5
|
0.07
|
|
Gestational age at enrollment (weeks)
|
14.7 ± 1.7
|
14.7 ± 1.9
|
0.97
|
Abbreviations: BMI, body mass index; NA, indicates not applicable.
Note: Data are expressed as mean ± standard deviation.
Of note, chronic hypertension was identified currently during pregnancy in three of
seven (42.8%) patients with obesity and one of eight (12.5%) of patients without obesity.
In regard to clinical history, people with obesity had higher rates of family history
of diabetes (five of seven, 71.4% vs. five of eight, 62.5%), hypertension (six of
seven, 85.7% vs, two of eight, 25%), cardiovascular events (five of seven, 71.4% vs.
two of eight, 25%), stroke (four of seven, 57.1% vs. two of eight, 25%), and sickle-cell
disease (one of seven, 14.2% vs. 0).
People with obesity had significantly higher enrollment BMI (39.8 ± 3.9 vs. 22 ± 2.5 kg/m2, p < 0.0001) and fat mass (40.6 ± 3.6 vs. 28.6 ± 5.9%, p < 0.0001) when compared with people with normal weight ([Table 1]).
In the first trimester assessments, people with obesity had higher SBP, diastolic
blood pressure (DBP), MAP, SV, TPRI, and CO ([Table 2]).
Table 2
Hemodynamic data of pregnant people with and without obesity at the time of study
enrollment (first trimester 12–14 weeks)
|
Obese
|
Nonobese
|
p
|
|
n
|
7
|
8
|
NA
|
|
SBP (mm Hg)
|
128 ± 15
|
99 ± 13
|
< 0.01
|
|
DBP (mm Hg)
|
75 ± 10
|
59 ± 12
|
0.02
|
|
MAP (mm Hg)
|
92 ± 13
|
72 ± 13
|
0.01
|
|
SV (mL)
|
101 ± 20
|
75 ± 13
|
0.01
|
|
TPR (dyn/s/cm5)
|
1,003 ± 128
|
997 ± 189
|
0.95
|
|
TPRI (dyn/s/cm5/m2)
|
2,158 ± 298
|
1,665 ± 394
|
0.03
|
|
CO (L/min)
|
7.34 ± 1.15
|
5.93 ± 0.73
|
0.01
|
|
CI (L/min/m2)
|
3.49 ± 0.59
|
3.61 ± 0.42
|
0.64
|
Abbreviations: CI, cardiac index; CO, cardiac output; DBP, diastolic blood pressure;
MAP, mean arterial pressure; NA, indicates not applicable; SBP, systolic blood pressure;
SV, stroke volume; TPR, total peripheral resistance; TPRI, total peripheral resistance
index.
Note: Data are expressed as mean ± standard deviation.
In the second and third trimesters, people with obesity demonstrated higher SVs and
CI, while other parameters remained similar ([Table 3]). BMI increased during the latter portions of pregnancy for both groups of people
([Table 3]). Fat mass increased between the second and third trimesters for people with normal
weight, whereas people with obesity demonstrated a reduction. ([Table 3]).
Table 3
Anthropometric and hemodynamic data of pregnant people with and without obesity in
the second (21–23 weeks) and third trimesters (34–36 weeks)
|
Trimester 2 (21–23 weeks)
|
Trimester 3 (34–36 weeks)
|
|
Obese
|
Nonobese
|
p
|
Obese
|
Nonobese
|
p
|
|
n
|
7
|
8
|
NA
|
6
|
7
|
NA
|
|
BMI (kg/m2)
|
41.9
|
25.9
|
< 0.01
|
43.6
|
27.2
|
< 0.01
|
|
Fat mass (%)
|
40
|
26.3
|
< 0.01
|
38.9
|
29.9
|
0.01
|
|
SBP (mm Hg)
|
118 ± 15
|
105 ± 11
|
0.09
|
116 ± 16
|
103 ± 12
|
0.10
|
|
DBP (mm Hg)
|
70 ± 13
|
61 ± 8
|
0.10
|
73 ± 11
|
66 ± 11
|
0.32
|
|
MAP (mm Hg)
|
80 ± 7
|
74 ± 10
|
0.25
|
87 ± 12
|
78 ± 11
|
0.19
|
|
SV (mL)
|
99 ± 22
|
73 ± 11
|
0.01
|
96 ± 21
|
73 ± 15
|
0.04
|
|
TPR (dyn/s/cm3)
|
756 ± 151
|
942 ± 69
|
0.01
|
842 ± 188
|
1,043 ± 168
|
0.07
|
|
TPRI
|
1,634 ± 312
|
1,568 ± 222
|
0.65
|
1,826 ± 367
|
1,732 ± 266
|
0.6
|
|
CO (L/min)
|
8.16 ± 1.56
|
6.46 ± 0.82
|
0.02
|
8.55 ± 1.50
|
6.23 ± 1.43
|
0.02
|
|
CI (L/min/m2)
|
4.49 ± 1.65
|
3.88 ± 0.40
|
0.44
|
3.98 ± 0.71
|
3.7 ± 0.66
|
0.47
|
Abbreviations: CI, cardiac index; CO, cardiac output; DBP, diastolic blood pressure;
MAP, mean arterial pressure; NA, indicates not applicable; SBP, systolic blood pressure;
SV, stroke volume; TPR, total peripheral resistance; TPRI, total peripheral resistance
index.
Note: Data are expressed as mean ± standard deviation.
Anthropometric and hemodynamic data were interrogated for degree of change between
trimesters. Between the first and second trimester, blood pressure (SBP and MAP) significantly
decreased for people with obesity but remained comparatively higher when compared
with people with normal weight. The TPR and TPRI significantly decreased for both
groups between the first and second trimester but the degree of decrease was more
pronounced for people with obesity.
Correlation analysis was done per trimester and showed that BMI and fat mass were
more closely related to hemodynamic measures during the first trimester. In the first
trimester BMI positively correlated with SV (r = 0.54, p = 0.04), TPRI (r = 0.56, p = 0.04), and CO (r = 0.53, p = 0.04). Fat mass showed a strong correlation with TPRI during the first trimester
(r = 0.68, p = 0.01).
BMI positively correlated with CO during the second trimester (r = 0.53, p = 0.04) as did fat mass (r = 0.55, p = 0.03). During the third trimester, BMI, as well as fat mass, negatively correlated
with TPR (r = − 0.56, p = 0.05; r = − 0.59, p = 0.04, respectively).
Further correlation analysis showed that the change in fat mass over the course of
pregnancy significantly correlated with changes in TPR (r = 0.63, p = 0.04), TPRI (r = 0.64, p = 0.03), CO (r = − 0.71, p = 0.01), and CO (r = − 0.68, p = 0.02; [Figs. 1],[2],[3],[4]).
Fig. 1 Correlation between fat mass change and total peripheral resistance (TPR) change
during pregnancy.
Fig. 2 Correlation between fat mass change and total peripheral resistance index (TPRI)
change during pregnancy.
Fig. 3 Correlation between fat mass change and cardiac output (CO) change during pregnancy.
Fig. 4 Correlation between fat mass change and cardiac index (CI) change during pregnancy.
Discussion
The aim of this study was to profile hemodynamic parameters longitudinally throughout
pregnancy in people with obesity and normal weight using NICOM and to record pregnancy
outcomes.
In this small pilot study, we identified important cardiovascular differences in pregnant
people with and without obesity throughout gestation. Given the small numbers, we
were not able to correlate these hemodynamic changes to maternal and fetal outcomes.
Classically, obesity has been associated with a higher cardiovascular workload. To
offset this, several hemodynamic changes take place. For example, the Frank–Starling
curve shows a leftward shift, with afterload reduction which is mainly due to decreased
TPR. In some populations, the higher levels of the adipocytokine leptin which is released
by fat cells have been associated with this drop in TPR.[29]
With higher levels of adiposity, individuals with obesity have higher circulating
blood volume, as well as a higher SV.[30] There is also a tendency toward higher resting heart rate. As CO is the product
of SV and heart rate, individuals with obesity typically have a higher CO than age-
and sex-matched normal weight individuals. Over time, this compensatory mechanism
can affect the myocardium causing left and right ventricular enlargement and hypertrophy.
Unchecked, chamber dilation can progress to diastolic and systolic ventricular dysfunction
which in severe cases can lead to overt heart failure.
It is important to note that in normal pregnancies, some of the hemodynamic changes
seen with obesity are also present. For example, there is a 40 to 50% increase in
circulating blood volume. SV and CO also increase while TPR falls.[30]
SV fell consistently throughout pregnancy in our study patients. SV is physiologically
the difference between end-diastolic volume (EDV) and end-systolic volume (ESV); (SV = EDV − ESV).[31] None of study patients showed clinical signs of heart failure, suggesting that ventricular
systolic function remained adequate. We speculate that the decrease in SV may be related
to mild ventricular diastolic impairment.
In our study, we observed an association between changes in fat mass and hemodynamic
indices. With fat mass gain, there is a trend toward higher TPR and lower CO. These
changes may be related to adipocytokines (e.g., leptin, ghrelin, and adiponectin)
which are secreted from adipose tissue and are present in higher concentration in
individuals with obesity. Adipocytokines, such as leptin, are also higher in pregnancy
in people with and without obesity[32] due to secretion by the placenta. Leptin levels rise during pregnancy and peak during
the second trimester. Elevated leptin levels have been seen with gestational diabetes[33] and gestational hypertension/preeclampsia.[34] Leptin levels were not measured in this study, so it is unknown what role they may
have played in maternal hemodynamic alterations.
It is also noteworthy that most of the hemodynamic and anthropometric changes noted
in the study group occurred between the first and second trimesters. An epidemiological
study by Villamor and Cnattingius[35] suggested that weight gain between pregnancies was associated with higher incidence
of adverse fetal outcome. Intrapregnancy weight gain has also been associated with
adverse maternal and fetal outcome.[36]
[37]
Although our numbers are too small to draw specific conclusions, we speculate that
fat mass gain between the first and second trimesters, in addition to the hemodynamic
changes already present due to obesity and pregnancy, may have caused some degree
of left ventricular diastolic dysfunction and therefore, lower SVs.
This hypothesis could not be confirmed due to lack of echocardiographic studies on
both cohorts. The hypothetical causality between obesity gain and altered NICOM parameters,
and the potential for left ventricular diastolic dysfunction, can be better explored
in future studies. Our study suggests that incorporating echocardiographic parameters
with NICOM in pregnant populations with obesity may clarify this matter.
We identified that our patients with obesity maintained stable CO and CI. This fact
might be reflective of young age and the ability to compensate with higher heart rates.
Extrapolating from this, for people with obesity at the start of pregnancy, more focused
fat mass management between the first and second trimesters could confer better hemodynamic
function, mitigating the higher TPR, and lower CO/CI.
This pilot study was designed to assess the clinical utility of NICOM in pregnant
people with and without obesity. It was possible to identify that NICOM was useful
in tracking cardiovascular and hemodynamic changes throughout the course of gestation.
Further studies, including echocardiographic assessments, are necessary to corroborate
these findings. It would be interesting to observe whether the hemodynamic changes
identified in this pilot study are resolved in the postpartum period and how such
resolution might be explained by changes in weight, BMI, and/or fat mass.
Limitations
Future work with larger patient groups could investigate the possible causative role
of the adipocytokines (leptin and adiponectin) in the cardiovascular changes seen
in pregnancy affected by obesity. It is well known that leptin can cause chronic oxidative
stress in endothelial cells, stimulate migration and proliferation of vascular smooth
cells, and induce calcification of vascular cells, thus contributing to vascular pathology.[38]
[39]
[40] In patients with obesity and diabetes, the elevation of leptin levels also causes
a reduction of nitric oxide (NO) and attenuation of NO vasodilation, contributing
to increased vascular resistance.[41]
[42]
Conclusion
Obesity remains one of the major health care concerns of our time and obesity in pregnancy
has serious adverse implications for our patients and maternal cardiac health. Although
our numbers are too small in this pilot study to draw inference, we suggest that further
investigation into the role of weight gain and fat mass management between the first
and second trimesters is warranted, as this period coincides with potentially detrimental
cardiovascular changes.
