Placental size at gestational week 27 and 37: The associations with pulsatility index in the uterine and the fetal-placental arteries.

INTRODUCTION: Fetal growth restriction is known to be related to decreased fetal and placental blood flow. It is not known, however, whether placental size is related to fetal and placental blood flow. We studied the correlations of intrauterine placental volume and placental-fetal-ratio with pulsatility index (PI) in the uterine arteries, fetal middle cerebral artery, and umbilical artery. METHODS: We followed a convenience sample of 104 singleton pregnancies, and we measured placental and fetal volumes using magnetic resonance imaging (MRI) at gestational week 27 and 37 (n = 89). Pulsatility index (PI) was measured using Doppler ultrasound. We calculated cerebroplacental ratio as fetal middle cerebral artery PI/umbilical artery PI and placental-fetal-ratio as placental volume (cm3)/fetal volume (cm3). RESULTS: At gestational week 27, placental volume was negatively correlated with uterine artery PI (r = -0.237, p = 0.015, Pearson's correlation coefficient), and positively correlated with fetal middle cerebral artery PI (r = 0.247, p = 0.012) and cerebroplacental ratio (r = 0.208, p = 0.035). Corresponding correlations for placental-fetal-ratio were -0.273 (p = 0.005), 0.233 (p = 0.018) and 0.183 (p = 0.064). Umbilical artery PI was not correlated with placental volume. At gestational week 37, we found weaker and no significant correlations between placental volume and the pulsatility indices. CONCLUSIONS: Our results suggest that placental size is correlated with placental and fetal blood flow at gestational week 27.

Maternal plasma pro-atrial and C-type natriuretic peptide levels and their associations with cardiovascular and renal function in the second half of normal pregnancy: a longitudinal study.

BACKGROUND: Physiological adaptation in pregnancy is characterized by remodeling of endocrine, cardiovascular and renal functions leading to fluid retention, volume expansion, altered cardiac loading conditions and hyperdynamic circulation. Natriuretic peptides have been used as biomarkers of cardiovascular function, but their associations with gestational age-related changes in maternal cardiac, endothelial and renal function have not been elucidated. The aim of this study was to establish longitudinal reference values for maternal plasma atrial natriuretic peptide (proANP) and C-type natriuretic peptide (CNP) and investigate their temporal association with cardiovascular and renal function in the second half of pregnancy. METHODS: This study was a prospective longitudinal study of 53 low-risk pregnancies. Women were examined every 3-5 weeks during 22-40 weeks of gestation (252 observations). Fasting maternal blood samples were obtained to measure proANP, CNP, creatinine, cystatin C, uric acid, and fibrinogen levels. Cardiac function and systemic hemodynamics were assessed noninvasively by impedance cardiography (ICG) and vascular endothelial function by flow-mediated vasodilation of brachial artery (FMD). RESULTS: The plasma proANP (R2adj = 0.79; P = 0.007), CNP (R2adj = 0.54; P = 0.005) decreased between 22 and 40 weeks. The creatinine (R2adj = 0.90; P < 0.001), cystatin C (R2adj = 0.93; P = < 0.001) and uric acid (R2adj = 0.83; P < 0.001) increased significantly, whereas the estimated glomerular filtration rate (R2adj = 0.93; P < 0.001) decreased with gestational age. The FMD did not change significantly but fibrinogen (R2adj = 0.79; P < 0.001) increased with advancing gestation. The maternal systemic vascular resistance index (R2adj = 0.50; P < 0.001) increased, stroke index (R2adj = 0.62; P < 0.001) decreased, whereas the cardiac index (R2adj = 0.62; P = 0.438) and thoracic fluid content (R2adj = 0.72; P = 0.132) did not change significantly with gestation. The proANP was associated with thoracic fluid content (R2adj = 0.74; P < 0.001) and fibrinogen (R2adj = 0.78; P = 0.034) but not with other variables of systemic hemodynamics, endothelial function, or renal function. The CNP was not associated significantly with parameters of cardiovascular or renal function. CONCLUSION: Longitudinal reference values for maternal plasma proANP and CNP were established. These natriuretic peptides decreased slightly with advancing gestation, but they did not reflect the temporal physiological changes in maternal systemic hemodynamics, vascular endothelial function and renal function during the second half of pregnancy. The proANP correlated with the thoracic fluid content reflecting volume load in pregnancy.

Capacity and patient flow planning in post-term pregnancy outpatient clinics: a computer simulation modelling study.

BACKGROUND: The demand for a large Norwegian hospital's post-term pregnancy outpatient clinic has increased substantially over the last 10 years due to changes in the hospital's catchment area and to clinical guidelines. Planning the clinic is further complicated due to the high did not attend rates as a result of women giving birth. The aim of this study is to determine the maximum number of women specified clinic configurations, combination of specified clinic resources, can feasibly serve within clinic opening times. METHODS: A hybrid agent based discrete event simulation model of the clinic was used to evaluate alternative configurations to gain insight into clinic planning and to support decision making. Clinic configurations consisted of six factors: X0: Arrivals. X1: Arrival pattern. X2: Order of midwife and doctor consultations. X3: Number of midwives. X4: Number of doctors. X5: Number of cardiotocography (CTGs) machines. A full factorial experimental design of the six factors generated 608 configurations. RESULTS: Each configuration was evaluated using the following measures: Y1: Arrivals. Y2: Time last woman checks out. Y3: Women's length of stay (LoS). Y4: Clinic overrun time. Y5: Midwife waiting time (WT). Y6: Doctor WT. Y7: CTG connection WT. Optimisation was used to maximise X0 with respect to the 32 combinations of X1-X5. Configuration 0a, the base case Y1 = 7 women and Y3 = 102.97 [0.21] mins. Changing the arrival pattern (X1) and the order of the midwife and doctor consultations (X2) configuration 0d, where X3, X4, X5 = 0a, Y1 = 8 woman and Y3 86.06 [0.10] mins. CONCLUSIONS: The simulation model identified the availability of CTG machines as a bottleneck in the clinic, indicated by the WT for CTG connection effect on LoS. One additional CTG machine improved clinic performance to the same degree as an extra midwife and an extra doctor. The simulation model demonstrated significant reductions to LoS can be achieved without additional resources, by changing the clinic pathway and scheduling of appointments. A more general finding is that a simulation model can be used to identify bottlenecks, and efficient ways of restructuring an outpatient clinic.

Maternal cardiac function, uterine artery hemodynamics and natriuretic peptides at 22-24 weeks of gestation and subsequent development of hypertensive disorders of pregnancy.

INTRODUCTION: Maternal cardiac dysfunction as well as abnormal uterine artery (UtA) Doppler are associated with hypertensive disorders of pregnancy (HDP), but their relation is unclear. We investigated the correlation between maternal cardiac function, UtA hemodynamics and natriuretic peptides, and explored differences between women who subsequently developed HDP and those who did not. MATERIAL AND METHODS: This was a prospective cross-sectional cohort study of 347 pregnant women at 22-24 weeks. Maternal cardiac function and systemic hemodynamics were investigated at baseline and after 90 seconds of passive leg raising using impedance cardiography. Preload reserve was defined as percent change (Δ%) in stroke volume and cardiac output from baseline to passive leg raising. UtA hemodynamics was studied using Doppler ultrasonography. UtA blood flow, resistance and pulsatility index were calculated. Fasting venous blood samples were analyzed for natriuretic peptides (pro atrial natriuretic peptide [proANP], N-terminal pro brain natriuretic peptide [Nt-proBNP] and C-type natriuretic peptide [CNP]). The course and outcome of pregnancy were recorded. RESULTS: At baseline, ProANP correlated significantly with cardiac output (r = -0.122; P = .023) and left cardiac work index (r = -0.112; P = .037), whereas Nt-ProBNP correlated significantly with acceleration index (r = .127; P = .018) and velocity index (r = -0.111; P = .039. CNP correlated significantly with UtA blood flow (r = .118; P = .028) and resistance (r = -0.112; P = .037) but not with UtA pulsatility index (r = .034; P = .523). None of the natriuretic peptides correlated with preload reserve. At 22-24 weeks, women who subsequently developed HDP had lower UtA blood flow (552 vs 692 mL/min; P = .028), higher UtA resistance (0.28 vs .17 mmHg/mL/min; P = .004) and higher mean UtA pulsatility index (1.12 vs .84; P < .001) compared with those who did not; however, the natriuretic peptide levels were similar in the two groups. Women developing HDP had a significantly higher increase in stroke volume and cardiac output and more reduction in systemic vascular resistance following passive leg raising compared with the reference group. Left cardiac work index, acceleration index and velocity index decreased following passive leg raising in the reference group but increased in women who later developed HDP. CONCLUSIONS: ProANP correlated with cardiac output and cardiac work, Nt-proBNP with indices of cardiac contractility, and CNP with UtA blood flow and resistance. None of these natriuretic peptides measured at 22-24 weeks of gestation reflected cardiac preload reserve or predicted development of HDP.

Sex differences in umbilical artery Doppler indices: a longitudinal study.

BACKGROUND: Sexual dimorphism in placental size and function has been described. Whether this influences the clinically important umbilical artery (UA) waveform remains controversial, although a few cross-sectional studies have shown sex differences in UA pulsatility index (PI). Therefore, we tested whether fetal sex influences the UA Doppler indices during the entire second half of pregnancy and aimed to establish sex-specific reference ranges for UA Doppler indices if needed. METHODS: Our main objective was to investigate gestational age-associated changes in UA Doppler indices during the second half of pregnancy and compare the values between male and female fetuses. This was a prospective longitudinal study in women with singleton low-risk pregnancies during 19-40 weeks of gestation. UA Doppler indices were serially obtained at a 4-weekly interval from a free loop of the umbilical cord using color-directed pulsed-wave Doppler ultrasonography. Sex-specific reference intervals were calculated for the fetal heart rate (HR), UA PI, resistance index (RI), and systolic/diastolic ratio (S/D) using multilevel modeling. RESULTS: Complete data from 294 pregnancies (a total of 1261 observations from 152 male and 142 female fetuses) were available for statistical analysis, and sex-specific reference ranges for the UA Doppler indices and fetal HR were established for the last half of pregnancy. UA Doppler indices were significantly associated with gestational age (P < 0.0001) and fetal HR (P < 0.0001). Female fetuses had 2-8% higher values for UA Doppler indices than male fetuses during gestational weeks 20+0-36+6 (P < 0.05), but not later. Female fetuses had higher HR from gestational week 26+0 until term (P < 0.05). CONCLUSIONS: We have determined gestational age-dependent sex differences in UA Doppler indices and fetal HR during the second half of pregnancy, and correspondingly established new sex-specific reference ranges intended for refining diagnostics and monitoring individual pregnancies.

Sexual Dimorphism in Umbilical Vein Blood Flow During the Second Half of Pregnancy: A Longitudinal Study.

OBJECTIVES: To investigate gestational age-specific serial changes in umbilical vein (UV) volume blood flow during the second half of normal pregnancy and establish sex-specific reference ranges. METHODS: This work was a prospective longitudinal study of singleton low-risk pregnancies. The UV diameter and maximum blood flow velocity were serially measured by sonography at the intra-abdominal portion of the UV over 19 to 41 weeks. Umbilical vein volume blood flow was calculated and normalized for estimated fetal weight. RESULTS: One hundred seventy-nine women and their fetuses (87 male and 92 female) were included in the final analysis, and a total of 746 observations were used to construct sex-specific reference intervals. We found no statistically significant sex-specific differences in the UV parameters examined. However, the temporal development patterns of normalized UV volume blood flow appeared to differ between male and female fetuses during the second half of pregnancy, with crossovers at 24 and 32 weeks' gestation. CONCLUSIONS: Umbilical vein volume blood flow is similar among male and female fetuses in quantitative terms, but the pattern of gestational age-dependent temporal changes may be different, which may have important physiologic implications with regard to in utero development and maturation of the fetoplacental unit.

Placental pulsatility index: a new, more sensitive parameter for predicting adverse outcome in pregnancies suspected of fetal growth restriction.

INTRODUCTION: The pulsatility indices of the umbilical and uterine arteries are used as the surrogate measures of utero-placental perfusion. Combining the two might simplify the evaluation of total placental vascular impedance, possibly improve prediction of adverse outcomes, and help identify pregnancies with suspected fetal growth restriction that need more intense surveillance. MATERIAL AND METHODS: Umbilical and uterine blood flow velocities were recorded using pulsed-wave Doppler in a longitudinal study of 53 low-risk pregnancies (248 observations) during 20-40 weeks of gestation. Pulsatility indices was calculated for each of these vessels. A new placental pulsatility index was constructed as: (umbilical artery pulsatility index + mean of the left and right uterine artery pulsatility indices)/2, and mean +2 SD defined as abnormal. Gestational age-specific reference percentiles were calculated for the second half of pregnancy and related to values obtained from 340 pregnancies with suspected intra-uterine growth restriction to test its ability to predict adverse pregnancy outcome. RESULTS: The placental pulsatility index was closely associated with gestational age and decreased with advancing gestation in normal pregnancy. The placental pulsatility index had a higher sensitivity and comparable specificity in predicting adverse outcome in pregnancies suspected of intra-uterine fetal growth restriction when compared with conventional umbilical and uterine artery pulsatility indices. CONCLUSIONS: The new placental pulsatility index, reflecting placental vascular impedance on both the fetal and maternal side of placenta, improves prediction of adverse outcome in pregnancies suspected of intra-uterine fetal growth restriction.

Ovarian reserve in women with a previous history of severe pre-eclampsia.

PURPOSE: Severe pre-eclampsia affects maternal health with long-term consequences. It is postulated that during the process of implantation and cell differentiation, embryos resulting from the fertilization of ageing oocytes produce malfunctioning trophoectoderm leading to placental dysfunction. Therefore, severe pre-eclampsia may be associated with a decreased ovarian reserve. The objective of this study was to compare serum markers of ovarian reserve and function between women who had severe pre-eclampsia and those who had normal pregnancies. METHODS: Twenty women who had severe pre-eclampsia (PE) and 20 who had uncomplicated pregnancies (controls) matched for age and body mass index were included in the study. Fasting blood samples were taken during the follicular phase (day 5) of the menstrual cycle 6 months to 5 years after the delivery. Serum was separated and frozen at -70 °C until analyzed for anti-Mϋllerian hormone (AMH), total and free testosterone (TT), free-androgen index (FAI), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) hormone to evaluate ovarian reserve and function, and the results were compared between two groups. RESULTS: The median AMH was 0.91 ng/mL in PE group compared to 0.72 ng/mL in controls (p = 0.995). No significant differences were found between the two groups in the levels of LH (5.65 vs. 5.4 IU/L, respectively, p = 0.897) and FSH (4.95 vs. 5.1 IU/L, respectively, p = 0.523). However, total and free-TT levels as well as FAI were significantly lower in the PE group compared to controls (p = 0.017, p = 0.006, and p = 0.011, respectively). CONCLUSIONS: Ovarian reserve and function are not altered significantly in women with a previous history of pre-eclampsia compared with women who had an uncomplicated pregnancy.

Exploring sexual dimorphism in placental circulation at 22-24 weeks of gestation: A cross-sectional observational study.

INTRODUCTION: Placental blood flow is closely associated with fetal growth and wellbeing. Recent studies suggest that there are differences in blood flow between male and female fetuses. We hypothesized that sexual dimorphism exists in fetal and placental blood flow at 22-24 weeks of gestation. METHODS: This was a prospective cross-sectional study of 520 healthy pregnant women. Blood flow velocities of the middle cerebral artery (MCA), umbilical artery (UA), umbilical vein (UV) and the uterine arteries (UtA) were measured using Doppler ultrasonography. UV and UtA diameters were measured using two-dimensional ultrasonography and power Doppler angiography. Volume blood flows (Q) of the UV and UtA were calculated. Maternal haemodynamics was assessed with impedance cardiography. UtA resistance (Ruta) was computed as MAP/Quta. RESULTS: UA PI was significantly (p = 0.008) higher in female fetuses (1.19 ± 0.15) compared with male fetuses (1.15 ± 0.14). MCA PI, cerebro-placental ratio (MCA PI/UA PI), Quv, UtA PI, Quta and Ruta were not significantly different between groups. At delivery, the mean birth weight and placental weight of female infants (3504 g and 610 g) were significantly (p = 0.0005 and p = 0.039) lower than that of the male infants (3642 g and 634 g). DISCUSSION: We have demonstrated sexual dimorphism in UA PI, a surrogate for placental vascular resistance, at 22-24 weeks of gestation. Therefore, it would be useful to know when this difference emerges and whether it translates into blood flow differences that may impact upon the fetal growth trajectory.

Longitudinal reference ranges for maternal plasma laeverin, and its role as a potential biomarker of preeclampsia.

BACKGROUND: Laeverin is a placenta-specific membrane-bound aminopeptidase. In this study we wanted to: 1) serially measure plasma levels of laeverin in healthy women during the second half of pregnancy and postpartum, 2) determine whether laeverin is differently expressed at 22-24 weeks in women who later develop preeclampsia compared to controls, 3) compare laeverin protein expression in placenta and umbilical vein serum in healthy and preeclamptic pregnancies at birth. METHODS: Plasma was obtained serially, approximately every 4-weeks, from 53 healthy women with uncomplicated pregnancies during 22+0 to 39+6 weeks of gestation, and at 22-24 weeks from 15 women who later developed preeclampsia. Enzyme-linked immunosorbent assay was used to measure laeverin protein concentration. Serum from healthy non-pregnant premenopausal women (n = 10), menopausal women (n = 10) and men (n = 11) were used as negative controls. Protein extracts from placental tissue were obtained after birth from healthy- (n = 11) and preeclamptic women (n = 13). Paired umbilical artery and vein serum samples from the neonates (n = 10) of healthy mothers were also analyzed. Multilevel modeling was used to determine the reference centiles. Differences between groups were analyzed using Student's t-test. RESULTS: Healthy pregnant women at term (37-40 weeks) had significantly higher plasma levels of laeverin (mean 4.95 ± 0.32 ng/mL; p < 0.0001) compared to men (mean 0.18 ± 0.31 ng/mL), non-pregnant premenopausal women (mean 0.77 ± 0.26 ng/mL) and postmenopausal women (mean 0.57 ± 0.40 ng/mL). Maternal plasma laeverin levels decreased with advancing gestation, from 6.96 ± 0.32 ng/mL at 22-24 weeks to 4.95 ± 0.32 ng/mL at term (p < 0.0001) in uncomplicated pregnancies. Half of the women who developed preeclampsia had plasma laeverin levels below the 5th percentile at 22-24 weeks gestation. However, laeverin levels were 1.6 fold higher in preeclamptic compared to healthy placentas (p = 0.0071). Umbilical venous samples of healthy neonates (n = 38) had higher (p = 0.001) mean levels of laeverin (16.63 ± 0.73 ng/mL), compared to neonates of preeclamptic (n = 14) mothers (12.02 ± 1.00 ng/mL). Postpartum plasma levels of laeverin decreased in healthy and preeclamptic women with a half-life of 3 and 5 days, respectively. CONCLUSIONS: Maternal plasma levels of laeverin decrease with advancing gestation during the second half of normal pregnancy and lower levels measured at 22-24 weeks might be associated with the development of preeclampsia later in gestation.

Static and Functional Hemodynamic Profiles of Women with Abnormal Uterine Artery Doppler at 22-24 Weeks of Gestation.

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.

Hemodynamic aspects of normal human feto-placental (umbilical) circulation.

Understanding the changes in normal circulatory dynamics that occur during the course of pregnancy is essential for improving our knowledge of pathophysiological mechanisms associated with feto-placental diseases. The umbilical circulation is the lifeline of the fetus, and it is accessible for noninvasive assessment. However, not all hemodynamic parameters can be reliably measured in utero using currently available technology. Experimental animal studies have been crucial in validating major concepts related to feto-placental circulatory physiology, but caution is required in directly translating the findings of such studies into humans due to species differences. Furthermore, it is important to establish normal reference ranges and take into account gestational age associated changes while interpreting the results of clinical investigation. Therefore, it is necessary to critically evaluate, synthesize and summarize the knowledge available from the studies performed on human pregnancies to be able to appropriately apply them in clinical practice. This narrative review is an attempt to present contemporary concepts on hemodynamics of feto-placental circulation based on human studies.

A longitudinal study of maternal endothelial function, inflammatory response and uterine artery blood flow during the second half of pregnancy.

INTRODUCTION: The objective of this study was to investigate serial changes in maternal endothelial function, inflammatory response and uterine artery blood flow in normal pregnancy, and to explore their inter-relation. MATERIAL AND METHODS: In this prospective longitudinal observational study, 53 women with uncomplicated pregnancies were examined at 4-weekly intervals (248 observations) during 22-40 weeks of gestation. Uterine artery blood flow was measured using Doppler ultrasonography. Maternal endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. Circulating endothelial progenitor cells (EPC), defined as CD34(+) CD133(+) VEGFR2(+) cells, were quantified by flow cytometry. Biomarkers of inflammation, such as leptin and high sensitivity C-reactive protein (hsCRP), were measured in plasma samples. Multilevel modeling was used to investigate gestational-age-associated serial changes. RESULTS: The EPC increased from 6.5 to 12.3 per million mononuclear cells (p < 0.01) and FMD decreased from 16.3 to 13.4% (p = 0.20). Leptin increased from 18 to 22 ng/mL (p < 0.01), and hsCRP did not change significantly (p = 0.61). There was no significant association between FMD and EPC (p = 0.66). FMD was significantly associated with hsCRP (p = 0.002) and leptin (p = 0.003), but the EPC were not. Neither FMD nor EPC were significantly associated with uterine artery blood flow. CONCLUSION: Changes in FMD were significantly associated with inflammatory biomarkers, suggesting that the reduced nitric oxide-dependent vasodilatation in late gestation is related to maternal inflammatory response. As EPC and FMD did not correlate, mechanisms other than mobilization of EPC to repair endothelial damage must be responsible for the gestational-age-associated increase in EPC.

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.

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.

PP055. Uric acid correlates with uterine artery vascular resistance, but not with uterine artery pulsatility index.

INTRODUCTION: Studies indicate that uric acid is involved in the development of hypertensive diseases of pregnancy, and that uric acid might influence the remodeling of the spiral arteries. OBJECTIVE: To investigate the relationship with uric acid and utero-placental hemodynamics in the second half of pregnancy. METHODS: 53 women with uncomplicated pregnancies were examined longitudinally at 4-weekly intervals from 22 to 40 weeks of gestation. Blood samples for plasma uric acid were analyzed (enzymatic colorimetric method. INSTRUMENT: Modular P, Roche Diagnostic), and blood pressure (BP) was measured. Uterine artery Doppler velocity waveforms were obtained, and vessel diameter was measured bilaterally. Uterine artery volume blood flow (Quta) was calculated as the product of mean velocity and cross-sectional area of the vessel. Mean arterial pressure (MAP) was calculated as: diastolic BP+(systolic BP - diastolic BP)/3. Uterine artery resistance (Rquta) was calculated as: MAP/Quta. Uterine artery pulsatility index (UtaPI) was calculated as: (peak systolic velocity - end-diastolic velocity)/time-averaged maximum velocity. Linear mixed models and linear regression models were used for statistical analysis. RESULTS: 242 blood samples were analyzed. Uric acid increased from 176 to 238µmol/L. Rquta and UtaPI decreased from 0.26 to 0.13mmHg/ml/min and 0.8-0.6 respectively. Uric acid was significantly correlated to Rquta (p=0.005), but not to Uta PI (p=0.178). CONCLUSION: There is a strong association between uric acid and uterine artery vascular resistance during the second half of pregnancy indicating that uric acid might play a role in establishing low resistance blood flow in the uteroplacental compartment.

PP079. Ovarian reserve and function is preserved following severe preeclampsia.

INTRODUCTION: Preeclampsia is a multi-organ disorder that predominantly affects renal, cardiovascular, and endocrine systems with long-term consequences for the women's health. As advanced age and history of subfertility increase the risk of developing preeclampsia, reduced ovarian reserve may be associated with preeclampsia. However, long-term effect of preeclampsia on the ovarian function and reserve is not known. We hypothesized that the ovarian reserve and function are reduced in women with a previous history of severe preeclampsia. OBJECTIVE: To compare the plasma levels of markers of ovarian function (FSH, LH, SHBG, testosterone) and reserve (anti-Müllerian hormone, AMH) in women who previously had preeclampsia with their matched controls. METHOD: Twenty women who had severe preeclampsia (PE group) requiring delivery before 36 weeks of gestation and 20 controls were matched for age, parity, height and weight were included in the study. Women were not breast-feeding, they were having regular menstrual periods and were not using any hormonal contraception. Fasting blood samples were taken during the follicular phase. Plasma was separated and frozen at -70 degrees until analyzed. Comparison between groups was performed using paired sample t-test for parametric and Wilcoxon T-test for nonparametric data. A two-tailed p-value <0.05 was considered significant. RESULTS: The mean age was 36.4 years, height 164cm and weight 72kg in PE group, compared to 37.0 years, 165cm and 69kg, respectively in control group. The mean AMH was 1.34ng/mL in PE group compared to 1.55ng/mL in controls (p=NS). No significant differences were found in the levels of LH (6.72 versus 6.53 IU/L), FSH (5.27 versus 7.16 IU/L), LH/FSH ratio (1.39 versus 1.11), SHBG (63.65 versus 52.90 versus 52.90nmol/L), and testosterone (0.72 versus 1.01nmol/L) between groups. CONCLUSION: Ovarian reserve and function is not altered significantly in women with a previous history of preeclampsia.

Relation between utero-placental and feto-placental circulations: a longitudinal study.

OBJECTIVE: To explore the relation between total utero-placental (TQ(uta)) and feto-placental (Q(uv)) blood flows and establish longitudinal reference ranges for the TQ(uta)/Q(uv) ratio and the mean uterine artery and umbilical artery pulsatility (UtaPI/UAPI) and resistance index (UtaRI/UARI) ratios. DESIGN: Prospective longitudinal observational study. SETTING: University hospital in Norway. POPULATION: Fifty-three low-risk pregnant women. METHODS: Uterine artery and umbilical vein blood flow was measured using Doppler ultrasonography at 4-weekly intervals from 22(+0) to 39(+6) weeks of gestation. MAIN OUTCOME MEASURES: Ratios between utero-placental and feto-placental volume blood flows and between indices of uterine and umbilical artery impedance. RESULTS: The TQ(uta)/Q(uv) ratio had a significant association with the gestational age (p < 0.00001) and decreased with advancing gestation during the second half of pregnancy. The mean UtaPI/UAPI (p = 0.094) and mean UtaRI/UARI (p = 0.323) ratios were not significantly associated with gestational age and remained relatively constant. There was no significant association between TQ(uta) and Q(uv) (p = 0.72), mean UtaPI and UAPI (p = 0.56), or mean UtaRI and UARI (p = 0.57). CONCLUSION: The gestational-age-related changes in the utero-placental and feto-placental circulations do not appear to be affected by each other under physiological conditions. We have established longitudinal reference ranges for the utero-placental and feto-placental blood flow and impedance ratios during the second half of pregnancy.

[Female circumcision--complications and treatment]. / Omskjaering av kvinner--komplikasjoner og behandling.

The majority of women with extensive forms of genital cutting develop one or more chronic complications such as dysmenorrhea, dyspareunia, pain and cysts in the perineum, vaginal obstruction with haematocolpos, relative urine retention and recurrent urinary tract infections. Extensive forms of circumcision also influence childbirths. The severity of the cutting is associated with the probability of developing later complications. The women's clinics at the regional hospital in Norway have established outpatient clinics to receive women with complications after genital cutting. The aim was to develop an adequate health service to the affected. In order to improve the access to care and to ensure anonymity the women may refer themselves. During 2004, a total of 60 women were treated. The majority suffered from poor urinary flow, pain at micturition, dysmenorrhea and dyspareunia. Reconstruction of the vaginal orifice was performed to relieve some of the discomforts. The numbers of women who visit the clinics are increasing. The surgical procedure itself is not technically difficult, but the consultation before and after the surgery require cultural sensitivity. As health care personnel we can influence the affected to realise that genital cutting is an assault against a small girl. Norwegian health care workers need to learn more about how to communicate well about the medical as well as the cultural and mental aspects of genital cutting.