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BackgroundThe 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 MethodsPlacental 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.ResultsAlmost 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.ConclusionsDifferences 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.

Objective To study serial changes in maternal systemic and uterine artery haemodynamics and establish reference ranges for the second half of pregnancy.Design Prospective longitudinal observational study.Setting University hospital in Norway.Population Low-risk pregnant women.Methods Fifty-three low-risk pregnancies were evaluated at approximately 4-weekly intervals. Maternal systemic haemodynamics was assessed with impedance cardiography. Uterine artery blood velocity and diameter were measured using Doppler ultrasonography and uterine artery volume blood flow (Q uta ) was calculated as the product of mean velocity and crosssectional area of the uterine artery. The fraction of cardiac output (CO) distributed to the uterine circulation was calculated as: Q uta /CO · 100.Main outcome measures CO, Q uta , uterine vascular resistance (R uta ) and the fraction of CO distributed to the uterine circulation.Results The CO increased (P = 0.0063) until 34 weeks and remained stable until term. Total Q uta increased from 299 to 673 ml/minute and R uta halved from 0.26 to 0.13 mmHg/ml/ minute (P < 0.0001). The fraction of CO distributed to the uterine circulation increased from 5.6% to 11.7% (P < 0.0001).Conclusion During the second half of pregnancy, Q uta and the fraction of maternal CO distributed to the uterine circulation increase approximately two-fold, mainly as a result of decrease in R uta .

Please cite this paper as: Flo K, Wilsgaard T, Vårtun Å, Acharya G. A longitudinal study of the relationship between maternal cardiac output measured by impedance cardiography and uterine artery blood flow in the second half of pregnancy. BJOG 2010;117:837–844. Objective  To study serial changes in maternal systemic and uterine artery haemodynamics and establish reference ranges for the second half of pregnancy. Design  Prospective longitudinal observational study. Setting  University hospital in Norway. Population  Low‐risk pregnant women. Methods  Fifty‐three low‐risk pregnancies were evaluated at approximately 4‐weekly intervals. Maternal systemic haemodynamics was assessed with impedance cardiography. Uterine artery blood velocity and diameter were measured using Doppler ultrasonography and uterine artery volume blood flow (Quta) was calculated as the product of mean velocity and cross‐sectional area of the uterine artery. The fraction of cardiac output (CO) distributed to the uterine circulation was calculated as: Quta/CO × 100. Main outcome measures  CO, Quta, uterine vascular resistance (Ruta) and the fraction of CO distributed to the uterine circulation. Results  The CO increased (P = 0.0063) until 34 weeks and remained stable until term. Total Quta increased from 299 to 673 ml/minute and Ruta halved from 0.26 to 0.13 mmHg/ml/minute (P < 0.0001). The fraction of CO distributed to the uterine circulation increased from 5.6% to 11.7% (P < 0.0001). Conclusion  During the second half of pregnancy, Quta and the fraction of maternal CO distributed to the uterine circulation increase approximately two‐fold, mainly as a result of decrease in Ruta.

We evaluated global placental gene expression in intrauterine growth restriction (IUGR; n = 8) compared to normal pregnancies (n = 8) and studied possible additional effect of preeclampsia. Placental samples were collected from IUGR pregnancies due to placental insufficiency ascertained by hemodynamic studies. Four IUGR pregnancies were associated with preeclampsia. Gene expression profile was evaluated by 30k oligonucleotide microarrays. Principal component analysis (PCA) showed good separation in terms of gene expression patterns between the groups. Pathway analysis showed upregulation of inflammation mediated by chemokine and cytokine signaling pathway in the IUGR placentas. Genes involved in placental glucocorticoid metabolism were also differentially expressed. None of the known imprinted placental genes were differentially expressed. Subgroup analysis between IUGR placentas with and without preeclampsia showed few (n = 27) differentially expressed genes. In conclusion, IUGR due to placental insufficiency appears to alter placental glucocorticoid metabolism, upregulates inflammatory response in placenta, and shares common pathogenic mechanisms with severe early-onset preeclampsia.

The duration of pregnancy and initiation of labour are thought to be controlled by fetal, maternal and placental factors. The aim of this study was to investigate whether labour influences gene expression in placenta near term. Placental samples were obtained from 27 women after vaginal delivery (labouring) and 17 women after elective Caesarean section (non-labouring). All women were Caucasian and had uncomplicated pregnancies. For global gene expression analysis, 17 human oligo-arrays were used, representing 24 650 genes each. An empirical Bayes analysis was applied in order to find differentially expressed genes. About 8000 genes that were represented on the arrays met our quality criteria. Ninety two genes were down-regulated and 94 genes were up-regulated in labouring placentas compared to non-labouring placentas. However, none of these was differentially expressed at a significant level (>2.5-fold change and a P-value of <0.01). We conclude that gene expression in near term human placenta is not significantly altered by labour.

ObjectiveTo investigate functional hemodynamic response to passive leg raising in healthy pregnant women and compare it with non-pregnant controls.Materials and MethodsThis 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 measuresTrends 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.ResultsThe 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).ConclusionStatic 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.

ObjectiveCardiovascular 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 MethodsThis 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.ResultsHemodynamic 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.ConclusionHealthy 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.