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.