Static and functional hemodynamic profiles of women with abnormal uterine artery doppler at 22-24 weeks of gestation

Published version. Source at http://doi.org/10.1371/journal.pone.0157916. License CC BY 4.0.Objective To compare cardiac function, systemic hemodynamics and preload reserve of women with increased (cases) and normal (controls) uterine artery (UtA) pulsatility index (PI) at 22–24 weeks of gestation. Materials and Methods A prospective cross-sectional study of 620 pregnant women. UtA blood flow velocities were measured using Doppler ultrasonography, and PI was calculated. Mean UtA PI ≥ 1.16 (90th percentile) was considered abnormal. Maternal hemodynamics was investigated at baseline and during passive leg raising (PLR) using impedance cardiography (ICG). Preload reserve was defined as percent increase in stroke volume (SV) 90 seconds after passive leg raising compared to baseline. Results Mean UtA PI was 1.49 among cases (n = 63) and 0.76 among controls (n = 557) (p < 0.0001). Eighteen (28.6%) cases and 53 (9.5%) controls developed pregnancy complications (p <0.0001). The mean arterial pressure and systemic vascular resistance were 83 mmHg and 1098.89±293.87 dyne s/cm5 among cases and 79 mmHg and 1023.95±213.83 dyne s/cm5 among controls (p = 0.007 and p = 0.012, respectively). Heart rate, SV and cardiac output were not different between the groups. Both cases and controls responded with a small (4–5%) increase in SV in response to PLR, but the cardiac output remained unchanged. The preload reserve was not significantly different between two groups. Conclusion Pregnant women with abnormal UtA PI had higher blood pressure and systemic vascular resistance, but similar functional hemodynamic profile at 22–24 weeks compared to controls. Further studies are needed to clarify whether functional hemodynamic assessment using ICG can be useful in predicting pregnancy complications

Differences in Gene Expression between First and Third Trimester Human Placenta: A Microarray Study

BACKGROUND: The human placenta is a rapidly developing organ that undergoes structural and functional changes throughout the pregnancy. Our objectives were to investigate the differences in global gene expression profile, the expression of imprinted genes and the effect of smoking in first and third trimester normal human placentas. MATERIALS AND METHODS: Placental samples were collected from 21 women with uncomplicated pregnancies delivered at term and 16 healthy women undergoing termination of pregnancy at 9-12 weeks gestation. Placental gene expression profile was evaluated by Human Genome Survey Microarray v.2.0 (Applied Biosystems) and real-time polymerase chain reaction. RESULTS: Almost 25% of the genes spotted on the array (n = 7519) were differentially expressed between first and third trimester placentas. Genes regulating biological processes involved in cell proliferation, cell differentiation and angiogenesis were up-regulated in the first trimester; whereas cell surface receptor mediated signal transduction, G-protein mediated signalling, ion transport, neuronal activities and chemosensory perception were up-regulated in the third trimester. Pathway analysis showed that brain and placenta might share common developmental routes. Principal component analysis based on the expression of 17 imprinted genes showed a clear separation of first and third trimester placentas, indicating that epigenetic modifications occur throughout pregnancy. In smokers, a set of genes encoding oxidoreductases were differentially expressed in both trimesters. CONCLUSIONS: Differences in global gene expression profile between first and third trimester human placenta reflect temporal changes in placental structure and function. Epigenetic rearrangements in the human placenta seem to occur across gestation, indicating the importance of environmental influence in the developing feto-placental unit

Dynamic functional assessment of maternal hemodynamics in human pregnancy

Pregnancy causes significant changes in maternal circulation and cardiac function. In healthy pregnancy the blood volume, heart rate, stroke volume and cardiac output are known to increase and these physiological alterations are largely complete by mid-gestation. Investigation into cardiovascular response to dynamic changes in the loading condition of heart during pregnancy might contribute to better understanding of gestational cardiac adaption and help to identity women at risk of developing pregnancy complications such as hypertension, pre-eclampsia, or gestational diabetes. Normal heart is preload responsive and generally responds to an increase in ventricular filling (volume load) by a corresponding increase in stroke volume and cardiac output. We investigated functional hemodynamic response of the maternal heart to a volume load caused by passive leg raising in healthy women in the second half of pregnancy to establish reference values. Furthermore, we evaluated functional hemodynamic response to passive leg raising in pregnancies at risk of developing pregnancy complications as identified by abnormal uterine artery Doppler. We found significantly higher heart rate, stroke volume and cardiac output, and lower systemic vascular resistance and blood pressure among pregnant women compared to non-pregnant women at rest. The functional hemodynamic response to passive leg raising was similar among healthy pregnant and non-pregnant women, indicating that the physiological response is not modified in pregnancy at 22-24 weeks of gestation. However, we observed that healthy pregnant women have reduced cardiac contractility and preload reserve, especially in the last trimester. This makes pregnant women vulnerable to fluid overload and heart failure. Assessment of systemic functional hemodynamics may help identifying women who have cardiovascular maladaptation in pregnancy. Whether it helps to predict pregnancy complications and to improve management by risk stratification merits further investigation

Agreement between preload reserve measured by impedance cardiography and echocardiography during pregnancy

Purpose: Accurate assessment of cardiac function is important during pregnancy. Echocardiography and impedance cardiography (ICG) are commonly used noninvasive methods to measure stroke volume (SV) and cardiac output (CO). The diference in stroke volume (ΔSV) or cardiac output (ΔCO) measured at baseline and after passive leg raising (PLR) is a measure of preload reserve that predicts volume responsiveness. However, the agreement between these two methods in measuring preload reserve during pregnancy is unclear. The aim of our study was to investigate the correlation and the agreement between Doppler echocardiography and ICG in assessing preload reserve in pregnant women. Methods: In this prospective observational cross-sectional study, preload reserve was assessed by measuring the SV and CO during baseline and 90 s after PLR simultaneously by Doppler echocardiography and ICG in healthy pregnant women during the second and third trimesters. Bland–Altman analysis was used to determine the agreement between the two methods. Bias was calculated as the mean difference between two methods and precision as 1.96 SD of the difference. Results: A total of 53 pregnant women were included. We found a statistically signifcant correlation between ΔSV (R=0.56, pR=0.39, p=0.004) measured by ICG and Doppler echocardiography. The mean bias for ΔSV was 2.52 ml, with a precision of 18.19 ml. The mean bias for ΔCO was 0.21 l/min, with a precision of 1.51 l/min. Conclusion: There was a good agreement and a statistically signifcant correlation between ICG and Doppler echocardiography for measuring preload reserve

Effect of Passive Leg Raising on Systemic Hemodynamics of Pregnant Women: A Dynamic Assessment of Maternal Cardiovascular Function at 22–24 Weeks of Gestation

OBJECTIVE: To investigate functional hemodynamic response to passive leg raising in healthy pregnant women and compare it with non-pregnant controls. MATERIALS AND METHODS: This was a prospective cross-sectional study with a case-control design. A total of 108 healthy pregnant women at 22-24 weeks of gestation and 54 non-pregnant women were included. Cardiac function and systemic hemodynamics were studied at baseline and 90 seconds after passive leg raising using non-invasive impedance cardiography. MAIN OUTCOME MEASURES: Trends and magnitudes of changes in impedance cardiography derived parameters of cardiac function and systemic hemodynamics caused by passive leg raising, and preload responsiveness defined as >10% increase in stroke volume or cardiac output after passive leg raising compared to baseline. RESULTS: The hemodynamic parameters in both pregnant and non-pregnant women changed significantly during passive leg raising compared to baseline, but the magnitude and trend of change was similar in both groups. The stroke volume increased both in pregnant (p = 0.042) and non-pregnant (p = 0.018) women, whereas the blood pressure and systemic vascular resistance decreased (p<0.001) following passive leg raising in both groups. Only 14.8% of pregnant women and 18.5% of non-pregnant women were preload responsive and the difference between groups was not significant (p = 0.705). CONCLUSION: Static measures of cardiovascular status are different between healthy pregnant and non-pregnant women, but the physiological response to passive leg raising is similar and not modified by pregnancy at 22-24 weeks of gestation. Whether physiological response to passive leg raising is different in earlier and later stages of pregnancy merit further investigation

Nitric oxide, oxidative stress and streptococcus mutans and lactobacillus bacterial loads in saliva during the different stages of pregnancy: A longitudinal study

Hormonal changes associated with pregnancy promote oral bacterial growth, which may affect salivary nitric oxide (NO) levels, oxidative stress (OS), and antioxidant capacity (AC). We hypothesized that caries-related bacterial load, NO level, and OS in the saliva change with advancing gestation. The aim of this study was to investigate longitudinal changes in salivary NO, OS, and AC during pregnancy and correlate them with Streptococcus mutans (SM) and Lactobacillus (LB) colonization at different stages of pregnancy. We assessed NO level by Griess method, OS by measuring malondialdehyde (MDA), AC by ABTS radicals and bacterial load by culturing SM and LB in the saliva of pregnant women (n = 96) and compared with non-pregnant women (n = 50) as well as between different stages of pregnancy. Compared with non-pregnant women, NO was 77% higher (4.73 ± 2.87 vs. 2.67 ± 1.55 µM; p < 0.001), MDA was 13% higher (0.96 ± 0.27 vs. 0.85 ± 0.22 nM; p = 0.0055), and AC was 34% lower (60.35 ± 14.33 vs. 80.82 ± 11.60%; p < 0.001) in the late third trimester. NO increased with advancing gestation, but AC and OS did not change significantly during pregnancy. SM were more abundant in pregnant women compared with non-pregnant (p = 0.0012). Pregnancy appears to have an adverse impact on oral health emphasizing the importance optimal oral healthcare during pregnancy

Maternal functional hemodynamics in the second half of pregnancy: A longitudinal study

Objective: Cardiovascular response to passive leg raising (PLR) is useful in assessing preload reserve, but it has not been studied longitudinally during pregnancy. We aimed to investigate gestational age associated serial changes in maternal functional hemodynamics and establish longitudinal reference ranges for the second half of pregnancy. Materials and Methods: This was a prospective longitudinal study on 98 healthy pregnant women who were examined 3–5 times during 20–40 weeks of gestation (a total of 441 observations). Maternal cardiac function and systemic hemodynamics were assessed at baseline and 90 seconds after PLR using impedance cardiography (ICG). The main outcome measures were gestational age specific changes in ICG-derived variables of maternal cardiovascular function and functional hemodynamic response to PLR. Results: Hemodynamic response to PLR varied during pregnancy. PLR led to an insignificant increase in stroke volume during 20+0 to 31+6 weeks, but later in gestation the stroke volume was slightly lower at PLR compared to baseline. PLR caused no significant change in cardiac output between 20+0 and 23+6 weeks and a significant decrease after 24+0 weeks. A decrease in heart rate, mean arterial pressure, and cardiac contractility was observed during PLR throughout the second half of pregnancy. Systemic vascular resistance was reduced by PLR up to 32+0 weeks, but increased slightly thereafter. Conclusion: Healthy pregnant women appear to have limited preload reserve and reduced cardiac contractility, especially in the third trimester, which makes them vulnerable to fluid overload and cardiac failure

Hemodynamic parameters measured by impedance cardiography at baseline and 90 seconds after passive leg raising (PLR) in pregnant and non-pregnant women.

<p>Data are presented as mean ± SD. % Change is the difference between values obtained at baseline and after PLR in percent.</p>#<p>Represents the p-value for the difference between baseline and PLR (paired sample t-test) within pregnant and non-pregnant groups.</p><p>^*Represents the p-value for the difference in % change between pregnant and non-pregnant groups (independent sample t-test). SI, stroke index; CI, cardiac index; BPS, systolic blood pressure; BPD, diastolic blood pressure; SVRI, systemic vascular resistance index; ACI, accelerated cardiac index; LWCI, left ventricular work index; PEP, pre-ejection period; LVET, left ventricular ejection time; VI, velocity index and STR, systolic time ratio.</p

Baseline characteristics of the study population.

<p>Data presented as n (%), median (range) or mean ± SD as appropriate.</p

Positioning of the study participant for functional hemodynamic evaluation.

<p>Hemodynamic measurements were obtained using impedance cardiography with the women in a supine semi-recumbent position (A) after 10 minutes of rest (baseline) and 90 seconds after passively elevating both legs to 45° with the head and trunk lowered to the supine position (B) using an electronically pivotable bed.</p