Cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis.

OBJECTIVE: To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. DESIGN: Model based on a population-based cohort study. SETTING: The Swedish health service. POPULATION: Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010-2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008-2009 when standard care did not include RAADP (n = 7099). METHODS: Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. MAIN OUTCOME MEASURE: Additional cost per RhD immunisation averted. RESULTS: Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. CONCLUSION: Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. TWEETABLE ABSTRACT: Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP.

Simulator training in fetoscopic laser surgery for twin-twin transfusion syndrome: a pilot randomized controlled trial.

OBJECTIVE: To evaluate the effect of a newly developed training curriculum on the performance of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS) using an advanced high-fidelity simulator model. METHODS: Ten novices were randomized to receive verbal instructions and either skills training using the simulator (study group; n = 5) or no training (control group; n = 5). Both groups were evaluated with a pre-training and post-training test on the simulator. Performance was assessed by two independent observers and comprised a 52-item checklist for surgical performance (SP) score, measurement of procedure time and number of anastomoses missed. Eleven experts set the benchmark level of performance. Face validity and educational value of the simulator were assessed using a questionnaire. RESULTS: Both groups showed an improvement in SP score at the post-training test compared with the pre-training test. The simulator-trained group significantly outperformed the control group, with a median SP score of 28 (54%) in the pre-test and 46 (88%) in the post-test vs 25 (48%) and 36 (69%), respectively (P = 0.008). Procedure time decreased by 11 min (from 44 to 33 min) in the study group vs 1 min (from 39 to 38 min) in the control group (P = 0.69). There was no significant difference in the number of missed anastomoses at the post-training test between the two groups (1 vs 0). Subsequent feedback provided by the participants indicated that training on the simulator was perceived as a useful educational activity. CONCLUSIONS: Proficiency-based simulator training improves performance, indicated by SP score, for fetoscopic laser therapy. Despite the small sample size of this study, practice on a simulator is recommended before trainees carry out laser therapy for TTTS in pregnant women.

Routine ultrasound examination at 41 weeks of gestation and risk of post-term severe adverse fetal outcome: a retrospective evaluation of two units, within the same hospital, with different guidelines.

OBJECTIVE: To study whether a routine with a routine ultrasound examination (routine scan) at 41 gestational weeks as compared with ultrasound on clinical indication (indicated scan), lowered the risk of severe adverse fetal outcome in post-term period. DESIGN: A retrospective cohort study. SETTING: Karolinska University Hospital, Stockholm, Sweden. POPULATION: Eight years of deliveries, 2002-2009. METHOD: One of the two delivery units at Karolinska University Hospital used a routine scan at 41 week of gestation and the other unit used an indicated scan. Severe adverse fetal outcome were defined: severe asphyxia, death or cerebral damage. The study was analysed using logistic regression with adjustment for potential confounders. MAIN OUTCOME MEASURES: Differences in post-term severe adverse fetal outcome. RESULTS: No increased risk of post-term severe adverse fetal outcome was seen at the unit using a routine scan; conversely, a 48% significantly increased risk was seen at the unit using an indicated scan (OR 0.89, 95% confidence interval, CI, 0.5-1.5 and OR 1.48, 95% CI 1.06-2.1, respectively). Comparing post-term periods, there was no significantly increased risk at the unit using indicated scans (OR 1.6, 95% CI 0.9-3.0). There was a 60% increased prevalence of small-for-gestational age (SGA) newborns in the post-term period at the unit using indicated scans (OR 1.6, 95% CI 1.1-2.4), but no differences in operative delivery. CONCLUSION: A policy to use routine scans at 41 weeks of gestation seems to normalise an increased post-term risk of severe adverse fetal outcome, possible due to increased awareness of SGA and/or oligohydramniosis.

Effects of isradipine on endothelin-induced constriction of myometrial arteries in normotensive pregnant women.

The results of our previous studies suggested that endothelin-1 (ET-1) might be contributory to the impaired uteroplacental blood flow seen in preeclampsia. The aim of this study was to investigate the in vitro influence of isradipine on ET-1-induced contraction of myometrial resistance arteries from pregnant women, as these vessels are partly responsible for the regulation of uteroplacental blood flow in preeclampsia. Small myometrial arteries were dissected from myometrium obtained from 20 normotensive term pregnant women undergoing elective cesarean section and mounted in a tissue chamber. Tension was recorded isometrically. When ET-1 (10(-8) mol/L)-contracted vessels were exposed to increasing concentrations (10(-6), 10(-5), and 10(-4) mol/L) of isradipine, the myometrial arteries demonstrated essentially no relaxation. A significant mean relaxation of 31% was seen only with the highest isradipine concentration of 10(-3) mol/L. Pretreatment with isradipine attenuated ET-1-induced contraction by 26% at 3 x 10(-4) mol/L and by up to 80% at 10(-3) mol/L. Preincubation with lower concentrations of isradipine did not significantly reduce subsequent ET-1 contraction. The present study has thus shown that isradipine at high concentrations counteracts ET-1-induced constriction of myometrial arteries in term pregnant women. Pretreatment with isradipine at high concentrations attenuates the ET-1 contraction.

Lactate in scalp and cord blood from fetuses with ominous fetal heart rate patterns.

OBJECTIVE: We investigated lactate concentrations in fetal scalp and cord blood to determine the sources of fetal lactacidosis in fetuses with ominous heart rate patterns. METHODS: Cord blood was collected from newly delivered infants who had been monitored by fetal scalp blood sampling during labor. In 250 cases umbilical arterial and venous cord blood lactate levels were measured. We assessed the umbilical arterial lactate concentrations in relation to the venous lactate levels, the arterial pH level, base excess, and arteriovenous lactate differences in cord blood. In 103 cases the levels of lactate in fetal scalp blood, sampled within 60 minutes of delivery, were compared with those in the umbilical artery and vein and the pH level and base excess immediately after birth. RESULTS: Lactate level in the umbilical artery showed a significant correlation to that in umbilical venous blood (r = .84, P < .001), to arteriovenous lactate differences (r = .52, P < .001), as well as to pH (r = -.55, P < .001) and base excess (r = -.63, P < .001) in arterial cord blood. Lactate concentrations in fetal scalp blood shortly before delivery showed a significant correlation to lactate levels in the umbilical arterial (r = .65, P < .001) and venous blood (r = .62, P < .001). CONCLUSION: The study indicates a close correlation between lactate levels in arterial and venous cord blood, as well as between the lactate levels and pH and base excess in cord arterial blood in patients with ominous fetal heart rate patterns. We also found an increased fetal contribution with increasing lactacidemia. Lactate concentrations in fetal scalp blood correlated well with those in cord arterial and venous blood.

Effects of nitroglycerin on the uterine and umbilical circulation in severe preeclampsia.

OBJECTIVE: To determine the effects of nitroglycerin on placental circulation in severe preeclampsia. METHODS: Twelve women with severe preeclampsia were examined. Uterine and umbilical artery pulsatility indices (PI) were assessed by pulsed Doppler ultrasound before and after infusion of nitroglycerin, starting at 0.25 micrograms/kg per minute with stepwise dosage increases until a diastolic blood pressure (BP) of 100 mmHg was achieved. Blood pressure and heart rate were recorded every 5 minutes. Blood was sampled for analysis of the second messenger of nitric oxide, cyclic guanosine monophosphate (cGMP), before and at the end of the infusion. RESULTS: During the infusion, the mean systolic BP decreased from 161 (95% confidence interval [CI] 154-169) to 138 mmHg (95% CI 131-146), and the diastolic pressure decreased from 116 (95% CI 111-122) to 103 (95% CI 96-110) mmHg (P < .01). The PI of the uterine artery did not change significantly (1.23 [95% CI 1.01-1.61]) versus 1.30 [95% CI 1.01-1.88]), whereas umbilical artery PI decreased significantly (P < .01), from 1.35 (95% CI 1.09-1.73) to 1.20 (95% CI 1.05-1.40), with a more pronounced decrease in patients with high basal values. Cyclic GMP remained essentially unchanged (6.4 [95% CI 5.4-7.7] versus 5.5 [4.7-6.6] nmol/L). CONCLUSION: The reduction in the PI of the umbilical artery during nitroglycerin-induced BP reduction implies vasodilation in the umbilical circulation. The absence of an increase in cGMP does not support the view that the nitroglycerin effect is reflected by the plasma concentration of cGMP.

Possible improvement in uteroplacental blood flow during atrial natriuretic peptide infusion in preeclampsia.

OBJECTIVE: To study the effects of low doses of the hormone atrial natriuretic peptide (ANP) on uteroplacental blood flow in patients with preeclampsia. METHODS: Eleven women with preeclampsia were infused intravenously with ANP (10 ng/kg/minute). Uteroplacental blood flow index was measured using dynamic placental scintigraphy with indium-113m. Regional blood flows were assessed by pulsed Doppler ultrasound and expressed as pulsatility index (PI). Hemodynamic measurements and blood sampling for peripheral venous plasma analysis of cyclic guanosine monophosphate (cGMP), an ANP second messenger, were performed before and after 30 minutes of infusion. Nonparametric statistics were used. RESULTS: The uteroplacental blood flow index increased by 28% (-2 to 58%; mean and 95% confidence interval). The Doppler findings were unaffected. Mean arterial blood pressure decreased from 112 (108-117) to 108 (103-114) mmHg (P < .01). Cyclic GMP increased significantly from 9.2 (6.2-12.3) to 17.4 (12.3-22.6) nmol/L (P < .01). Subjects exhibiting a substantial increase in uteroplacental blood flow index (25% or more) demonstrated a significantly greater cGMP response (P < .01) than those who did not (6% or less increase). CONCLUSION: A tendency to an increased uteroplacental blood flow index combined with minor blood pressure reduction after ANP infusion suggest the possibility of uteroplacental vasodilatation.

Role of lactate measurements during labor.

Lactate can safely and easily be determined in fetal scalp and umbilical artery blood with a new microvolume (5 microliters) lactate meter. Comparison between lactate and pH in scalp blood revealed a significant correlation (r = -0.43; P < .001). In a management trial where scalp lactate was compared to scalp pH, the lactate group underwent significantly more successful blood sampling procedures and fewer number of scalp incisions per blood sampling attempt. The mode of delivery and neonatal outcome were similar in patients managed with lactate and those using pH. Lactate concentration in umbilical artery blood had the same predictive properties as pH or base deficit in relation to poor neonatal outcome. Our data suggest that this method for lactate determination is robust and feasible and is suitable as a tool for fetal monitoring. Additional clinical management trials will be required to define the clinical usefulness of this method and how it should be combined with other modalities for fetal monitoring.

[Successively improved prognosis in erythrocyte immunization]. / Successivt förbättrad prognos vid erytrocytimmunisering.

Prognosis in cases of erythrocyte immunisation has improved continuously over the past decades. Morbidity and mortality have been reduced by improvements in management, including screening programmes, non-invasive ultrasound evaluation and invasive procedures. The article provides an outline of the latest developments in the management of erythrocyte immunisation, and several controversial issues are discussed, such as antibody screening, strategies for the reduction of antibody titres, and the organisation of care.

Detection of malformations in chromosomally normal fetuses by routine ultrasound at 12 or 18 weeks of gestation-a randomised controlled trial in 39,572 pregnancies.

OBJECTIVE: To compare the antenatal detection rate of malformations in chromosomally normal fetuses between a strategy of offering one routine ultrasound examination at 12 gestational weeks (gws) and a strategy of offering one routine examination at 18 gws. DESIGN: Randomised controlled trial. SETTING: Multicentre trial including eight hospitals. POPULATION: A total of 39,572 unselected pregnant women. METHODS: Women were randomised either to one routine ultrasound scan at 12 (12-14) gws including nuchal translucency (NT) measurement or to one routine scan at 18 (15-22) gws. Anomaly screening was performed in both groups following a check-list. A repeat scan was offered in the 12-week scan group if the fetal anatomy could not be adequately seen at 12-14 gws or if NT was >or=3.5 mm in a fetus with normal or unknown chromosomes. MAIN OUTCOME MEASURES: Antenatal detection rate of malformed fetuses. RESULTS: The antenatal detection rate of fetuses with a major malformation was 38% (66/176) in the 12-week scan group and 47% (72/152) in the 18-week scan group (P= 0.06). The corresponding figures for detection at <22 gws were 30% (53/176) and 40% (61/152) (P= 0.07). In the 12-week scan group, 69% of fetuses with a lethal anomaly were detected at a scan at 12-14 gws. CONCLUSIONS: None of the two strategies for prenatal diagnosis is clearly superior to the other. The 12-week strategy has the advantage that most lethal malformations will be detected at <15 gws, enabling earlier pregnancy termination. The 18-week strategy seems to be associated with a slightly higher detection rate of major malformations, although the difference was not statistically significant.

Routine ultrasound examination at 12 or 18 gestational weeks for prenatal detection of major congenital heart malformations? A randomised controlled trial comprising 36,299 fetuses.

OBJECTIVE: To compare the rate of prenatal diagnosis of heart malformations between two policies of screening for heart malformations. DESIGN: Randomised controlled trial. SETTING: Six university hospitals, two district general hospitals. SAMPLE: A total of 39 572 unselected pregnancies randomised to either policy. METHODS: The 12-week policy implied one routine scan at 12 weeks including measurement of nuchal translucency (NT), and the 18-week policy implied one routine scan at 18 weeks. Fetal anatomy was scrutinised using the same check-list in both groups, and in both groups, indications for fetal echocardiography were ultrasound findings of any fetal anomaly, including abnormal four-chamber view, or other risk factors for heart malformation. In the 12-week scan group, NT >or=3.5 mm was also an indication for fetal echocardiography. MAIN OUTCOME MEASURE: Prenatal diagnosis of major congenital heart malformation. RESULTS: In the 12-week scan group, 7 (11%) of 61 major heart malformations were prenatally diagnosed versus 9 (15%) of 60 in the 18-week scan group (P= 0.60). In four (6.6%) women in the 12-week scan group, the routine scan was the starting point for investigations resulting in a prenatal diagnosis versus in 9 (15%) women in the 18-week scan group (P=0.15). The diagnosis was made

Ultrasound dating at 12-14 weeks of gestation. A prospective cross-validation of established dating formulae in in-vitro fertilized pregnancies.

OBJECTIVES: To determine the accuracy of established ultrasound dating formulae when used at 12-14 weeks of gestation. METHODS: One-hundred and sixty-seven singleton pregnancies conceived after in-vitro fertilization (IVF) underwent a dating scan at 12-14 weeks of gestation. Gestational age at the dating scan was calculated by adding 14 days to the number of days between the date of oocyte retrieval and the date of the ultrasound scan. Gestational age according to oocyte retrieval was regarded as the true gestational age. True gestational age was compared to gestational age calculated on the basis of 21 dating formulae based on fetal crown-rump length (CRL) measurements and to three dating formulae based on fetal biparietal diameter (BPD) measurements. In a previous study the three BPD formulae tested here had been shown to be superior to four other BPD formulae when used at 12-14 weeks of gestation. The mean of the differences between estimated and true gestational age and their standard deviation (SD) were calculated for each formula. The SD of the differences was assumed to reflect random measurement error. Systematic measurement error was assumed to exist if zero lay outside the mean difference+/-2SE (SE: standard error of the mean). RESULTS: The three best CRL formulae were associated with mean (non-systematic) measurement errors of -0.0, -0.1 and -0.3 days, and the SD of the measurement errors of these formulae varied from 2.37 to 2.45. All but two of the remaining CRL formulae were associated with systematic over- or under-estimation of gestational age, and the SDs of their measurement error varied between 2.25 and 4.86 days. Dating formulae using BPD systematically underestimated gestational age by -0.4 to -0.7 days, and the SDs of their measurement errors varied from 1.86 to 2.09. CONCLUSIONS: We have identified three BPD formulae that are suitable for dating at 12-14 weeks of gestation. They are superior to all 21 CRL formulae tested here, because their random measurement errors were much smaller than those of the three best CRL formulae. The small systematic negative measurement errors associated with the BPD formulae are likely to be clinically unimportant.

Screening for Down syndrome based on maternal age or fetal nuchal translucency: a randomized controlled trial in 39,572 pregnancies.

OBJECTIVES: Nuchal translucency (NT) screening increases antenatal detection of Down syndrome (DS) compared to maternal age-based screening. We wanted to determine if a change in policy for prenatal diagnosis would result in fewer babies born with DS. METHODS: A total of 39,572 pregnant women were randomized to a scan at 12-14 gestational weeks including NT screening for DS (12-week group) or to a scan at 15-20 weeks with screening for DS based on maternal age (18-week group). Fetal karyotyping was offered if risk according to NT was > or = 1:250 in the 12-week group and if maternal age was > or = 35 years in the 18-week group. Both policies included the offer of karyotyping in cases of fetal anomaly detected at any scan during pregnancy or when there was a history of fetal chromosomal anomaly. The number of babies born with DS and the number of invasive tests for fetal karyotyping were compared. RESULTS: Ten babies with DS were born alive with the 12-week policy vs. 16 with the 18-week policy (P = 0.25). More fetuses with DS were spontaneously lost or terminated in the 12-week group (45/19,796) than in the 18-week group (27/19 776; P = 0.04). All women except one with an antenatal diagnosis of DS at < 22 weeks terminated the pregnancy. For each case of DS detected at < 22 weeks in a living fetus there were 16 invasive tests in the 12-week group vs. 89 in the 18-week group. NT screening detected 71% of cases of DS for a 3.5% test-positive rate whereas maternal age had the potential of detecting 58% for a test-positive rate of 18%. CONCLUSIONS: The number of newborns with DS differed less than expected between pregnancies that had been screened at 12-14 weeks' gestation by NT compared with those screened at 15-20 weeks by maternal age. One explanation could be that NT screening--because it is performed early in pregnancy--results in the detection and termination of many pregnancies with a fetus with DS that would have resulted in miscarriage without intervention, and also by many cases of DS being detected because of a fetal anomaly seen on an 18-week scan. The major advantage of the 12-week scan policy is that many fewer invasive tests for fetal karyotyping are needed per antenatally detected case of DS.

Effect of variations of heart rate within the normal range on renal artery Doppler indices in nonpregnant and pregnant women.

The effect of heart rate on Doppler indices in the renal artery was studied in 21 nonpregnant, 17 normal and 27 preeclamptic pregnant patients. The central hemodynamics was evaluated by Doppler ultrasound in all pregnant women. The study demonstrated no influence of heart rate on renal artery Doppler indices. Central hemodynamic parameters, such as cardiac output, stroke volume, mean arterial pressure and total systemic resistance did not change with increasing heart rate. We do not recommend any correction of the renal artery Doppler indices for heart rate in the range considered clinically normal (60 to 95 beats/min). Above or below this range further investigations are required to determine if corrections would be necessary.

The minimum number of cardiac cycles necessary for calculation of renal blood flow velocity indices in pregnant and non-pregnant women.

In this study Doppler ultrasound was used to measure the blood flow velocity in the main and segmental renal arteries in 16 healthy non-pregnant women. There were no differences in blood flow indices between the right and left kidneys as well as between the main and segmental arteries. The variability of the indices in the main and segmental renal arteries in healthy non-pregnant and in the segmental renal artery in normal pregnant women (32-37 weeks of gestation) was investigated. The within-patient error standard deviations of ten cycles and two, and three to nine averaged cycles were compared. In non-pregnant women, values for the error standard deviation comparable with those obtained from ten cycles for the systolic/diastolic ratio and pulsatility index from both main and segmental arteries were obtained by averaging from five to six consecutive cycles, while the error standard deviation for the resistance index stabilized when averaging only two to four cycles. In pregnant women, the error standard deviations for both the systolic/diastolic ratio and pulsatility index reached quite stable values after three cycle had been averaged as did the error standard deviation for the resistance index. We speculate that this difference between non-pregnant and pregnant women is due to more favorable conditions for renal visualization and consequently higher quality Doppler signals during pregnancy. A knowledge about the number of cardiac cycles required for an accurate calculation of renal blood flow velocity indices may prevent time-consuming calculations and inaccurate conclusions.

Maternal renal artery blood flow velocimetry in normal and hypertensive pregnancies.

OBJECTIVE: To investigate the effect of normal pregnancy and hypertensive disorders of pregnancy on the maternal renal artery Doppler blood flow velocity indices. METHODS: The patient material consisted of 30 normal pregnant women, 29 women with pregnancy induced hypertension, 43 women with preeclampsia and 22 pregnant women with chronic hypertension. Blood flow velocities in the segmental renal arteries from the right kidney were analysed by pulsed and color Doppler. The systolic/diastolic (s.d.) ratio, resistance index (RI) and pulsatility index (PI) were used for Doppler waveform analysis. RESULTS: In all of the groups of hypertensive pregnant women renal artery Doppler indices were significantly lower compared to the normal pregnant women group. There was a significant negative relationship between renal artery PI and mean arterial pressure in the preeclampsia group and in the chronic hypertension group. CONCLUSION: The present results demonstrate that the mechanism of renal autoregulation in preeclampsia might be altered, leaving glomerulus unprotected from increased blood pressure. It seems that the concept of renal vasoconstriction in preeclampsia might be disputed and needs further investigation.

Ultrasound dating at 12-14 or 15-20 weeks of gestation? A prospective cross-validation of established dating formulae in a population of in-vitro fertilized pregnancies randomized to early or late dating scan.

OBJECTIVES: To determine the accuracy of established ultrasound dating formulae when used at 12-14 and 15-20 gestational weeks. METHODS: A total of 363 singleton pregnancies conceived after in-vitro fertilization (IVF) and randomized to a dating scan at 12-14 or 15-20 gestational weeks were studied. 'True' gestational age was calculated on the basis of the day of oocyte retrieval and was compared to gestational age calculated on the basis of seven dating formulae including the fetal biparietal diameter (BPD) and three dating formulae including BPD and fetal femur length (FL). The mean of the differences between estimated and true gestational age (systematic measurement error) and their SD (random measurement error) were calculated for each formula. RESULTS: Three formulae showed systematic errors of less than -0.7 days at both early and late scanning. Two formulae overestimated gestational age at both early and late scanning by 5.7 and 3.1 vs. 2.3 and 2.8 days, respectively, while five formulae manifested very different systematic errors at early and late scanning. The formulae used for clinical management underestimated gestational age by a mean of 3 days when dating was performed at 12-14 weeks, and by a mean of 0.8 days when dating was done at 15-20 weeks. The random error was on average 1 day less when the scan was carried out early (2 vs. 3 days; P < 0.0005). Mean true gestational age at delivery in IVF pregnancies with spontaneous start of labor was 279 days (SD 12.9); excluding preterm deliveries it was 281 days (SD 8.1). CONCLUSIONS: Ultrasound dating formulae originally intended for use in the middle of the second trimester do not necessarily perform well when used for dating earlier in gestation. The systematic and random error of any dating formula must be assessed for the gestational age interval in which the formula is intended to be used.

A comparison of myogenic and endothelial properties of myometrial and omental resistance vessels in late pregnancy.

OBJECTIVE: Our purpose was to compare myometrial and omental resistance arteries from term pregnant women with respect to myogenic behavior in the presence or absence of a nitric oxide synthase inhibitor and to compare distensibility and acetylcholine-mediated dilatation in these vessels. STUDY DESIGN: Intramyometrial (n = 17) and omental (n = 14) resistance arteries from term normal pregnant women were studied in a pressurized arteriograph system. Myogenic tone was evaluated during increments in intraluminal pressure from 20 to 120 mm Hg with and without inhibition of nitric oxide synthase. Endothelium-dependent relaxation was assessed by evaluating the response to acetylcholine (10(-6) mol/L) in arteries pressurized at 70 mm Hg. RESULTS: Myogenic tone was greater at all pressure steps in the myometrial than in the omental arteries (p < 0.05). Inhibition of nitric oxide synthase with N(omega)-nitro-L-arginine had no influence on myogenic tone in either group. Relaxation to acetylcholine was greater in myometrial (18% +/- 4%) compared with omental vessels (7% +/- 2%, p < 0.05). The passive distensibility (Ca++-free solution and in the presence of papaverine) of arteries from the myometrium and the omentum was similar. CONCLUSION: Normal pregnancy is associated with different mechanical properties of resistance vessels from the two vascular beds studied. Basal nitric oxide release does not modify myogenic tone, at least under no-flow conditions. Acetylcholine-induced relaxation is greater in myometrial than in omental arteries.

Acute volume expansion in normal pregnancy and preeclampsia. Effects on plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) concentrations and feto-maternal circulation.

OBJECTIVE: To compare normal pregnancy with pregnancy-induced hypertension (PIH)/preeclampsia with respect to the effects of acute volume expansion on plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP) and fetal-maternal circulation. DESIGN: Observational study. SETTING: University hospital. SUBJECTS: Fifteen women with PIH/preeclampsia and 15 healthy pregnant controls. INTERVENTIONS: Before and after 30 minutes' infusion of a crystalloid solution (15 ml/kg), maternal venous blood was sampled for ANP and cGMP analysis and echocardiographic and Doppler investigations were performed. RESULTS: Basal median (range) ANP and cGMP levels were significantly higher in the PIH/preeclampsia group compared to the controls: 6.5 (3.8-30.4) compared to 3.9 (2.0-6.7) pmol/l, p < 0.01 and 5.8 (2.4-11.6) compared to 4.0 (2.3-10.8) nmol/l, p < 0.05. The response to volume load was enhanced: 4.6 (-4.5-21.8) compared to 0.7 (-4.1-8.8), p < 0.05 and 2.9 (0.1-10.9) compared to 1.2 (-5.0-6.0), p < 0.05, respectively. Systemic vascular resistance was initially higher in the patient group, 22.3 (14.1-36.7) compared to 15.6 (10.0-25.5) peripheral resistance units, p < 0.01 but the response to volume load was similar in both groups (12-13% decrease). The pulsatility index of the uterine artery, 0.85 (0.46-1.38) compared to 0.72 (0.49-1.26) and umbilical artery 0.89 (0.66-1.57) compared to 0.97 (0.74-1.31) did not differ between the groups. Volume expansion did not affect any of these variables. CONCLUSIONS: The pulsatility index of the uterine artery remained unaffected in both preeclamptic patients and healthy controls despite an increase of ANP and cGMP concentration and a systemic vasodilatation during acute volume expansion. This finding may indicate the absence of a vasodilation of the uteroplacental vascular bed.

The interpretation of uterine artery pulsatility index in normal and hypertensive pregnancy.

The Doppler flow velocity pulsatility index (PI) of the uteroplacental vascular bed is of debatable value for the interpretation of hemodynamic changes, when these are due both to pathological alterations in the vasculature, as in mild pre-eclampsia, and to physiological adjustments to vasoactive substances. The aim of this study was to apply a mathematical model, which includes maternal pulse pressure and mean arterial pressure, to the PI and to investigate whether this formula would add information with respect to discrimination between normal women and those with mild or severe pre-eclampsia. The subjects were patients with mild (n = 41) and severe (n = 34) pre-eclampsia and, as a control group, healthy pregnant women (n = 46). The uterine artery PI was studied by spectral Doppler analyses and compared to a P(z) value, theoretically representing a 'back pressure' in the uteroplacental circulation. Additionally, P(z) values were computed from earlier data concerning the dynamic circulatory effects of dihydralazine and acute volume expansion. The basal PI was significantly higher in the severely pre-eclamptic patients but not in the mildly pre-eclamptic patients compared to the controls. However, the P(z) was significantly higher in patients with both mild (p < 0.001) and severe pre-eclampsia (p < 0.0001) compared to the normal group. In the severely pre-eclamptic patients receiving dihydralazine, the P(z) tended to decrease (p = 0.07), in contrast to the volume-expansion group where P(z) was unaffected by the procedure. In conclusion, it seems that including measurement of the mean arterial pressure and pulse pressure with the PI adds valuable information about the circulatory status in this particular vasculature, regarding both 'basal' values and hemodynamic changes.