Introduction
Asthma is a multifactorial, immune-mediated inflammatory disease. The
pathophysiology of the disease is reversible lower airway constriction
due to intermittent smooth muscle constriction in response to
environmental allergens, infections, and irritants 1.
Asthma is a common chronic inflammatory disease in pregnancy and has
become one of the most common public health problems worldwide. In
general, asthma is thought to worsen with pregnancy in one-third of
patients, improve in one-third, and have no significant change in the
remaining patients. However, recent multiple case-control studies show
that the percentage of asthma patients who worsen during pregnancy,
18.8%, is lower than previous data and is related to disease severity2.
The diaphragm rises by 4-5 cm, and the subcostal angle increases by 50%
with pregnancy. As a result, total lung volume and functional residual
capacity decreased by 5% and 20%, respectively. Increased body weight
also contributes to dyspnea during pregnancy. Progesterone is a
stimulant of respiratory dynamics that can increase the sensitivity of
the respiratory center to carbon dioxide, while estrogen increases the
sensitivity of progesterone receptors in the respiratory system and is
jointly involved in altering respiratory function 2.
Studies have shown that maternal asthma increases the risk of
complications, including small for gestational age, low birth weight,
congenital malformations, preterm birth, gestational hypertension and
preeclampsia, diabetes, and perinatal mortality in fetuses and mothers.
The cesarean section rate is higher in patients with severe or
uncontrolled asthma during pregnancy than in the healthy pregnant
population due to adverse perinatal outcomes 3.
Mediators of human basophil cells interact with environmental factors,
allergens, and irritants. These mediators are associated with oxidative
stress in the cord blood of newborns of mothers with atopic asthma4. Chronic fetal infections and hypoxia are examples
of adverse conditions that impair cardiac myogenesis during complicated
pregnancy and increase the lifetime risk of heart disease5. In one study, neutrophil-triggered inflammation of
the placenta was found to lead to inadequate placental development and a
lack of barrier function. As a result, maternally derived inflammatory
monocytes from the placenta may migrate into the embryonic heart and
alter the structure of cardiac tissue and the normal composition of
resident cardiac macrophages 6.
The circulatory physiology of the fetus is different from that of the
newborn. The right ventricle provides greater cardiac output from the
second half of pregnancy until delivery 7. Assessment
of cardiac function by fetal echocardiography allows earlier detection
of changes in cardiac morphology and may help predict perinatal and
long-term cardiovascular outcomes. We hypothesized that chronic
inflammation in pregnant women with asthma might affect fetal cardiac
function. This study aimed to assess fetal cardiac function in pregnant
women with asthma compared with a healthy group.
Methods
Study PopulationThis study was performed on 90 fetuses without cardiac abnormalities,
including 30 fetuses of mothers with asthma and 60 fetuses of the
uncomplicated healthy pregnant population. thirty pregnant women with
asthma who visited the perinatology outpatient department of Ankara City
Hospital in Ankara from May 2022 to October 2022 were included in the
study. Fetal examinations were performed between 33 and 35 weeks of
gestation. The study protocol was approved by the Medical Research
Ethics Department of Ankara City Hospital and was conducted according to
the guidelines of the Declaration of Helsinki. (E2-22-2392). Written
informed consent was obtained from the study participants.
Pregnant women diagnosed with preeclampsia, diabetes mellitus, and other
chronic maternal and pregnancy-related diseases, multiple pregnancies,
fetal growth restriction, fetal structural or chromosomal abnormalities,
premature rupture of membranes, and taking medications other than
antiasthmatic drugs were excluded from the study. Other exclusion
criteria included maternal tobacco use and signs of fetal infection.
Healthy pregnant women in a similar gestational week range were randomly
selected as a control group. Maternal information, sociodemographic
characteristics, and obstetric history were recorded. The year of asthma
diagnosis and medication of the patients were recorded. Based on risk
and exacerbation, asthma is classified as intermittent, mild persistent,
moderate persistent, and severe persistent 8. Our
study included only patients receiving combination drugs such as inhaled
corticosteroids and long-acting B2 agonists. Well-controlled asthma
patients were included in the study according to the ACOG guideline9. All patients were asymptomatic at the time of the
study. Asthma controls were intermittent throughout pregnancy, and no
attack was observed.MeasurementsAll ultrasound examinations were performed with the Voluson E8
ultrasound system (GE Medical System, Milwaukee, WI, USA) with a convex
2-5-MHz ultrasound transducer. All ultrasound examinations were
performed by a perinatology fellow BLK and checked by FDÖ who is an
associate professor and has almost ten years of experience in
maternal-fetal medicine. First, the fetus was anatomically examined with
2DUS, the biophysical profile of all fetuses showed fetal well-being,
and the estimated fetal weights were appropriate for gestational age.
Standard fetoplacental Doppler indices were performed, including the
determination of the pulsation index for the umbilical artery and middle
cerebral artery. The fetal echocardiographic assessment was performed
with two-dimensional (2D) imaging, M-mode imaging, pulsed-wave Doppler
(PW), and tissue Doppler imaging (TDI). Doppler parameters were assessed
in the absence of fetal motion. The angle of insonation was less than 20
degrees from the direction of blood flow, and measurements were made on
at least three consecutive waveforms. These parameters were collected
prospectively at 33 to 35 weeks gestation. Recorded perinatal outcomes
included gestational age at delivery, body mass index (BMI), mode of
delivery, birth weight, and APGAR scores.
Mitral and tricuspid valve early diastole (E) and atrial contraction (A)
were measured with PW Doppler by placing the cursor directly under the
tricuspid and mitral valve leaflets in the apical four-chamber view. The
E/A ratio was calculated 10. Tissue Doppler was
examined at the tricuspid annuli in the apical or basal four-chamber
view in spectral Doppler mode. Peak velocities of the tricuspid valve in
early diastole (E’), atrial contraction (A’), and systole (S’) were
measured with an insonation angle of less than 30 degrees without
angular correction by placing the cursor on the lateral side of the
tricuspid valve, adjusting the sample volume by 2-4 mm with TDI.
Tricuspid velocity parameters were recorded in the same cardiac cycle11. The three most distinct waveforms and valve click
with a fetal heart rate in the normal range (120-160 beats/min) were
measured, and the values were averaged. E/E’ indices were calculated for
the tricuspid valve. After obtaining a clear image of the mitral and
aortic valves in the five-chamber view of the heart, the sample volume
was placed on the medial wall of the ascending aorta containing the
aortic and mitral flows. Valvular clicks were used as cues for the
calculation of each period. Myocardial performance index (MPI) was
calculated from the waveform obtained (isovolumetric contraction time
(IVCT) + isovolumetric relaxation time (IVRT)/ejection time (ET))12.
Sample volumes were placed in the basal part of the right ventricular
wall (tricuspid annulus). All velocities were measured during the same
cardiac cycle, and no angular correction was applied. To calculate the
right MPI’ with TDI, the following time periods were examined:
isovolumetric contraction time (IVCT’), ejection time (ET’), and
isovolumetric relaxation time (IVRT’). MPI’ was calculated as (IVCT’ +
IVRT’) / ET’ 11. Measurements of mitral annular plane
systolic excursion (MAPSE) and tricuspid annular plane systolic
excursion (TAPSE) were performed on the free walls in the four-chamber
view with apical or basal position of the fetal heart with M-mode
imaging. The cursor was placed vertically at the atrioventricular
junction, and measurements were performed. The maximum amplitude motion
was considered as the magnitude of displacement between the end-systolic
and end-diastolic regions and was measured in millimeters13.
Statistical analysis
IBM SPSS version 25 software (IBM Corp. Released 2017. IBM SPSS
Statistics for Windows, version 25.0. Armonk, NY: IBM Corp.) was used
for statistical analyses. The sample size was calculated using G Power
software (version 3.1 Franz Foul, Kiel University). It was determined
that at least 30 participants had to be included to achieve a mean
effect size of 0.50 and 95% power at a significance level of
< 0.05 14. Control cases were planned as 60
participants as well. The Kolmogorov-Smirnov test was used whether the
variables were normally distributed or not. Because the variables were
normally distributed, descriptive analyses were reported as mean and
standard deviation. A percentile calculation was performed for asthma
duration. The top quartile (75th percentile) over twelve years of asthma
duration was determined. Comparison of nonnormally distributed
quantitative data (asthma duration) between two independent groups was
performed using the Mann-Whitney U test, and the data were expressed as
the median (interquartile range). Student’s t-test was used to compare
the measured values of two independent groups, and Pearson’s test was
used for correlation coefficients. P value below 0.05 was accepted as
statistically significant.