Maternal cardiac function, uteroplacental Doppler flow parameters and pregnancy outcome: a systematic review.

OBJECTIVE: To investigate the existing evidence for a link between maternal cardiac function, abnormal uteroplacental flow and poor perinatal outcome in women with and without known cardiac disease. METHODS: PubMed and EMBASE databases were searched systematically for studies relating cardiac functional parameters and uteroplacental Doppler flow with pregnancy outcome in women with pre-existing congenital cardiac disease and women without known cardiac disease. Only studies based on echocardiography were included. RESULTS: From 1732 citations, 10 articles were included. In women with known congenital heart disease, a relationship was found between abnormal uteroplacental Doppler flow patterns and cardiac function before and during pregnancy. Conversely, women without a history of congenital heart disease, but with abnormal uterine artery resistance and pregnancy complications, more often showed global left ventricular diastolic dysfunction (33%; P = 0.0001), impaired myocardial relaxation (72%; P < 0.0001) and left ventricular systolic dysfunction (17%; P = 0.006), even up to 1 year postpartum. CONCLUSION: There is increasing evidence for an association between pre-existing subclinical cardiac dysfunction, poor placentation (reflected by uteroplacental Doppler flow abnormalities) and poor pregnancy outcome. It may be postulated that pre-existing suboptimal cardiac performance, as a result of either congenital heart disease or a subclinical latent condition, is one of the common denominators of poor placentation, leading to poor pregnancy outcome.

The effect of Porphyromonas gingivalis lipopolysaccharide on pregnancy in the rat.

OBJECTIVE: Periodontitis, mostly associated with Porphyromonas gingivalis, has frequently been related to adverse pregnancy outcomes. We therefore investigated whether lipopolysaccharides of P. gingivalis (Pg-LPS) induced pregnancy complications in the rat. METHODS: Experiment 1: pregnant rats (day 14) received increasing Pg-LPS doses (0.0-50.0 µg kg(-1) bw; n = 2/3 p per dose). Maternal intra-aortic blood pressure, urinary albumin excretion, placental and foetal weight and foetal resorptions were documented. Experiment 2: 10.0 µg kg(-1) bw (which induced the highest blood pressure together with decreased foetal weight in experiment 1) or saline was infused in pregnant and non-pregnant rats (n = 7/9 p per group). Parameters of experiment 1 and numbers of peripheral leucocytes as well as signs of inflammation in the kidney and placenta were evaluated. RESULTS: Pg-LPS infusion in pregnant rats increased maternal systolic blood pressure, reduced placental weight (dose dependently) and decreased foetal weight and induced foetal resorptions. It, however, did not induce proteinuria or a generalised inflammatory response. No effects of Pg-LPS were seen in non-pregnant rats. CONCLUSION: Pg-LPS increased maternal blood pressure, induced placental and foetal growth restriction, and increased foetal resorptions, without inducing proteinuria and inflammation. Pg-LPS may therefore play a role in pregnancy complications induced by periodontitis.

Routine screening for Coxiella burnetii infection during pregnancy: a clustered randomised controlled trial during an outbreak, the Netherlands, 2010.

Between 2007 and 2010, the Netherlands experienced one of the largest outbreaks of Q fever. Since asymptomatic Coxiella burnetii infection has been associated with maternal and obstetric complications, evidence about the effectiveness of routine screening during pregnancy in outbreak areas is needed. We performed a clustered randomised controlled trial during the Dutch outbreak, in which 55 midwife centres were randomised to recruit pregnant women for an intervention or control strategy. In both groups a serum sample was taken between 20 and 32 weeks of gestation. In the intervention group (n=536), the samples were analysed immediately by indirect immunofluorescence assay for the presence of IgM and IgG (phase I/II) and treatment was given during pregnancy in case of an acute or chronic infection. In the control group (n=693), sera were frozen for analysis after delivery. In both groups 15% were seropositive. In the intervention group 2.2% of the women were seropositive and had an obstetric complication, compared with 1.4% in the control group (Odds ratio: 1.54 (95% confidence interval 0.60-3.96)). During a large Q fever outbreak, routine C. burnetii screening starting at 20 weeks of gestation was not associated with a relevant reduction in obstetric complications and should therefore not be recommended.

Long-term cerebral imaging after pre-eclampsia.

OBJECTIVE: Formerly eclamptic women demonstrate cerebral white matter lesions (WMLs) several years following the index pregnancy. The pathophysiology is unclear and may be related to the predisposition for cerebrovascular/cardiovascular disease in such women and/or the occurrence of posterior reversible encephalopathy syndrome whilst pregnant. The aim of this study was to assess the presence and severity of WMLs and their relationship with the severity of the neurological symptoms during the index pregnancy and several current cardiovascular risk factors in formerly pre-eclamptic women. DESIGN: This was a retrospective cohort study. SETTING: The Neuroimaging Centre at the School for Behavioural and Cognitive Neurosciences, Groningen, the Netherlands. POPULATION: Seventy-three formerly pre-eclamptic women were matched for age (37 ± 6 years) and elapsed time since index pregnancy (5.1 ± 3.7 years) with parous control women. METHODS: Cerebral magnetic resonance imaging scans were performed on cases and controls. Scans were rated by a neuroradiologist blind to the patient category. MAIN OUTCOME MEASURES: The presence and severity of cerebral WMLs. RESULTS: Formerly pre-eclamptic women had WMLs significantly more often (37%) and more severely (mean, 0.11; median, 0.00; range, 0-2.34 ml) than controls (21%, P = 0.04; mean, 0.015; median, 0.00; range, 0-0.13 ml; P = 0.02). Current hypertension and a history of early-onset pre-eclampsia (<37 weeks) were independently associated with the presence of WMLs (ß = 1.34, P = 0.02 and ß = 1.73, P = 0.01, respectively). CONCLUSIONS: Our findings indicate that pre-eclampsia might be a risk marker for early cerebrovascular damage. The predisposition of formerly pre-eclamptic women to later cardiovascular and cerebrovascular disease may be an important factor for the development of cerebral WMLs. Whether a history of posterior reversible encephalopathy syndrome may be an additive risk factor for the development of these lesions remains unknown.

Screening for Coxiella burnetii infection during pregnancy: pros and cons according to the Wilson and Jungner criteria.

In Europe the incidence of human Q fever has dramatically increased over the previous years. Untreated infections with Coxiella burnetii, the causal agent of Q fever, have been associated with both obstetric and maternal complications. The majority of pregnant women with a C. burnetii infection remain asymptomatic, hence screening could be of value to prevent unwanted outcomes in this high-risk group. We applied the updated Wilson and Jungner criteria to review the evidence for routine screening for C. burnetii infection during pregnancy. Since much uncertainty remains about the incidence, clinical consequences, diagnostics and treatment of C. burnetii infection during pregnancy, routine screening for C. burnetii infection during pregnancy should not be recommended. Rigorous studies to assess the effectiveness of C. burnetii screening are warranted.

Placental histopathology after Coxiella burnetii infection during pregnancy.

Symptomatic and asymptomatic Coxiella burnetii infection during pregnancy have been associated with obstetric complications. We described placental histopathology and clinical outcome of five cases with asymptomatic C. burnetii infection during pregnancy and compared these cases with four symptomatic cases from the literature. In contrast with the symptomatic cases, we did not observe necrosis or active inflammation in the placentas of the asymptomatic women. Obstetrical outcome was more favourable in the asymptomatic cases than in the symptomatic cases. Asymptomatic and symptomatic C. burnetii infection during pregnancy are different entities with respect to placental histopathology and the risk of obstetric complications.

Posttraumatic stress disorder following preeclampsia and PPROM: a prospective study with 15 months follow-up.

OBJECTIVE: A prospective longitudinal evaluation of the prevalence of and risk factors for posttraumatic stress disorder (PTSD) in women with preeclampsia (PE) or preterm premature rupture of membranes (PPROM) compared to uncomplicated pregnancies. METHODS: Participating women completed PTSD and depression questionnaires during pregnancy, 6 weeks, and 15 months postpartum. Data regarding psychiatric history and indices of obstetric care were collected from patient charts. RESULTS: We included 57 PE, 53 PPROM, and 65 healthy pregnant women, of whom 137 also participated in the 15-month follow-up (PE 70%, PPROM 48%, and controls 95%; P < .001). At 6 weeks postpartum, the prevalence of PTSD, but not depression, following childbirth was significantly higher in patients than in controls (14% vs 3%; P = .023). A history of depression, depressive symptoms during pregnancy, and infant death were significantly associated with symptoms of postpartum PTSD. The maternal condition seems to be of less decisive value, as there was no difference between the prevalence of PTSD after PE and PPROM (11% vs 17%; P = .324). At 15 months postpartum, 11% of women with PE had PTSD, some of which did not have PTSD 6 weeks postpartum. The low response rate in the PPROM group at 15 months postpartum does not allow for definite conclusions. CONCLUSION: Pregnancies complicated by PE or PPROM are associated with PTSD in a substantial number of women. Especially women with proven vulnerability for psychological problems are at risk of developing PTSD postpartum, as are women whose children died in the perinatal period.

An economic analysis of induction of labour and expectant monitoring in women with gestational hypertension or pre-eclampsia at term (HYPITAT trial).

OBJECTIVE: To assess the economic consequences of labour induction compared with expectant monitoring in women with gestational hypertension or pre-eclampsia at term. DESIGN: An economic analysis alongside the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT). SETTING: Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands. POPULATION: Women diagnosed with gestational hypertension or pre-eclampsia between 36(+0) and 41(+0) weeks of gestation, randomly allocated to either induction of labour or expectant monitoring. METHODS: A trial-based cost-effectiveness analysis was performed from a societal perspective during a 1-year time horizon. MAIN OUTCOME MEASURES: One-year costs were estimated and health outcomes were expressed as the prevalence of poor maternal outcome defined as either maternal complications or progression to severe disease. RESULTS: The average costs of induction of labour (n = 377) were €7077 versus €7908 for expectant monitoring (n = 379), with an average difference of -€831 (95% CI -€1561 to -€144). This 11% difference predominantly originated from the antepartum period: per woman costs were €1259 for induction versus €2700 for expectant monitoring. During delivery, more costs were generated following induction (€2190) compared with expectant monitoring (€1210). No substantial differences were found in the postpartum, follow-up and for non-medical costs. CONCLUSION: In women with gestational hypertension or mild pre-eclampsia at term, induction of labour is less costly than expectant monitoring because of differences in resource use in the antepartum period. As the trial already demonstrated that induction of labour results in less progression to severe disease without resulting in a higher caesarean section rate, both clinical and economic consequences are in favour of induction of labour in these women. TRIAL REGISTRATION: The trial has been registered in the clinical trial register as ISRCTN08132825.

Plasma of pregnant and preeclamptic women activates monocytes in vitro.

OBJECTIVE: The objective of the study was to test the hypothesis that factors circulating in the plasma of pregnant women and women with preeclampsia activate monocytes. STUDY DESIGN: Blood samples were taken from patients with early-onset severe preeclampsia (n = 9), healthy pregnant women (n = 9), and healthy nonpregnant women (n = 9). A monocytic cell line was incubated with the plasma for 4, 16, and 24 hours. After the incubation, reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM)-1 expression (protein and messenger ribonucleic acid) were measured. RESULTS: Plasma of both pregnant women and women with preeclampsia, as compared with plasma from nonpregnant women, increased the mean channel brightness (MCB) of ROS after 4 hours of incubation, whereas only plasma of pregnant women increased the percentage of cells producing ROS (after 4 and 24 hours of incubation). Plasma of pregnant women and women with preeclampsia up-regulated the percentage of ICAM-1-expressing cells after 4 hours and down-regulated the percentage of ICAM-1-expressing cells and MCB after 24 hours. CONCLUSION: Plasma of both pregnant women and women with preeclampsia activated monocytes in vitro.

Posttraumatic stress disorder following preeclampsia and HELLP syndrome.

Posttraumatic stress disorder (PTSD) in connection with pregnancy was first described in the 1990s--initially in relation to childbirth but later more specifically to the mode of delivery. Instrumental vaginal delivery carries the highest risk of PTSD followed by emergency caesarean section and normal spontaneous delivery. Loss of pregnancy, spontaneous abortion or intrauterine death for example can also lead to PTSD. Little systematic research has been performed regarding the psychological consequences of severe preeclampsia or HELLP syndrome, although it would seem obvious that these conditions may have a great effect The combination of suffering a serious illness combined with an unexpected caesarean section or delivery, often of a premature child, is a heavy burden to bear both physically and psychologically. We describe here three patients who developed PTSD after pregnancies complicated by severe preeclampsia or HELLP syndrome. PTSD can develop after preeclampsia or HELLP syndrome.

Second trimester Doppler ultrasound screening of the uterine arteries differentiates between subsequent normal and poor outcomes of hypertensive pregnancy: two different pathophysiological entities?

The 'classical' concept that pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) primarily originate from defective placentation in early pregnancy has been challenged recently. There is growing evidence that other factors, including maternal predisposing conditions, also play a significant role in the pathophysiology of PIH and PE. The aim of the present study was to test the hypothesis that PIH and PE with an early onset and poor pregnancy outcome is associated with defective placentation, e.g. inadequate spiral artery dilatation and subsequent reduced uteroplacental perfusion, whereas PIH and PE with normal pregnancy outcome is not. Using Doppler ultrasound, we measured the uterine artery pulsatility index (PI) in a population of 531 nulliparous women in the 22nd week of gestation. Uterine artery PI was used as an index of resistance to blood flow in the uteroplacental circulation. Outcome measures were PIH/PE with or without poor pregnancy outcome, preterm birth and intra-uterine growth restriction (IUGR). The results revealed a striking difference between PI values for PIH/PE with and without poor pregnancy outcome. Uterine artery PI in the 22nd week was increased significantly in pregnancies which developed early-onset (before 35 weeks) PIH/PE with a poor pregnancy outcome. In contrast, uterine artery PI values were normal in women who developed PIH/PE, but had a good pregnancy outcome. There was a significant correlation between 22nd week uterine artery PI and subsequent preterm birth or IUGR. Our results indicate that only PIH/PE with poor pregnancy outcome is associated with defective placentation, whereas PIH/PE with good outcome is not. These findings support the concept of heterogeneous causes of hypertensive disorders of pregnancy.

Anatomical and functional changes in the lower urinary tract during pregnancy.

OBJECTIVE: To assess the prevalence and the development of urinary incontinence in nulliparous pregnant women, both subjectively and objectively, and to investigate the relation of incontinence with the mobility of the urethro-vesical junction measured by perineal ultrasound. DESIGN: A prospective longitudinal study. SETTING: University Hospital and Martini Hospital Groningen, the Netherlands. POPULATION: A cohort of 117 nulliparous pregnant women and 27 nulliparous non-pregnant controls. METHODS: Urinary incontinence was measured by a questionnaire and by a 24-hour pad test. The position of the urethro-vesical junction and its mobility were measured by perineal ultrasound. MAIN OUTCOME MEASURE: Prevalence of urinary incontinence; mobility of the urethro-vesical junction, indicated by the displacement/pressure coefficient. RESULTS: Up to 35% of the women reported urinary incontinence in pregnancy, and 20% of the women had a positive pad test. The angle of the urethro-vesical junction angle at rest and the displacement/pressure coefficient during coughing showed a significant increasing trend during pregnancy, but no changes were seen during the Valsalva manoeuvre. No relationship was found between subjective and objective incontinence data and the position and mobility of the urethro-vesical junction. CONCLUSION: The prevalence of incontinence in nulliparous women as found by the pad test was significantly higher in pregnancy (20%) than in the non-pregnant control group (4%). Perineal ultrasound of the urethrovesical junction showed lowering of the pelvic floor occurring as early as 12-16 weeks of pregnancy. Serial measurements of the displacement/pressure coefficient suggest that the dynamic characteristics of the connective tissues of the pelvic floor remain unaltered,whereas a significant decrease in pelvic floor muscle contraction occurs. Since no relation was found between measurements of the urethro-vesical junction and incontinence, urinary incontinence in pregnancy is most likely explained by other factors.

Uterine artery Doppler flow and uteroplacental vascular pathology in normal pregnancies and pregnancies complicated by pre-eclampsia and small for gestational age fetuses.

This study was conducted to investigate the association between uterine artery Doppler flow patterns and uteroplacental vascular pathology in normal and complicated pregnancies in view of the recently described concept of heterogeneous causes of hypertensive pregnancy complications. Forty-three women whose pregnancies were complicated by pre-eclampsia, the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and/or small for gestational age (SGA) fetuses and 27 women with normal pregnancies undergoing elective caesarean section were included. We obtained uterine artery Doppler waveforms at a mean of 4 days before delivery. Placental bed biopsies were obtained at caesarean section and analysed for physiological changes and pathological changes. We found that abnormal uterine artery Doppler flow was strongly associated with pregnancy complications. Absence of physiological changes was seen in 58 per cent of complicated pregnancies and 40 per cent of normal pregnancies. Pathological changes were seen in 58 per cent of complicated pregnancies and 53 per cent of normal pregnancies; they occurred in spiral arteries with and without physiological changes, and there was no significant correlation to Doppler results. In conclusion, absence of physiological changes is associated with abnormal uterine artery Doppler flow and pregnancy complications. However, there is a gradient in the severity of uteroplacental vascular pathology and the correlation with pregnancy complications is not as strong as previously thought. There is also a significant degree of uteroplacental vascular pathology in normal pregnancies with normal uterine artery Doppler flow. This variation may be partly due to sampling error, as a typical biopsy contains only one or two spiral arteries. We hypothesize that additional factors might be necessary to induce the clinical syndrome of pre-eclampsia.

Mutations in the gene for methylenetetrahydrofolate reductase, homocysteine levels, and vitamin status in women with a history of preeclampsia.

OBJECTIVE: This study was undertaken to assess frequencies of the methylenetetrahydrofolate reductase gene mutations cytosine-to-thymine substitution at base 677 (C677T) and adenine-to-cytosine substitution at base 1298 (A1298C) and their interactions with homocysteine and vitamin levels among Dutch women with preeclampsia. STUDY DESIGN: Mutations were studied in the following 5 groups: 47 consecutive women with preeclampsia, 49 women with preeclampsia and with hyperhomocysteinemia, 36 women with preeclampsia but without hyperhomocysteinemia, 127 women with familial preeclampsia (typed for C677T mutations only), and 120 control subjects. Plasma levels of homocysteine, folate, and vitamin B12 were measured. RESULTS: Although 10.6% of the consecutive women with preeclampsia had strictly defined hyperhomocysteinemia (values >97.5th percentile), neither mutation was found in excess relative to the control group. Women with preeclampsia who had mild hyperhomocysteinemia (values >75th percentile) had a significant excess of the TT genotype (homozygosity for C677T mutation) relative to the women with preeclampsia who did not have hyperhomocysteinemia (odds ratio, 8.2; 95% confidence interval, 1.8-39). They also had significantly lower vitamin levels. CONCLUSION: Hyperhomocysteinemia in women with preeclampsia was associated with mutations in the gene for methylenetetrahydrofolate reductase, but the high frequency of hyperhomocysteinemia itself cannot be explained by these mutations alone.

A genome-wide scan for preeclampsia in the Netherlands.

Preeclampsia, hallmarked by de novo hypertension and proteinuria in pregnancy, has a familial tendency. Recently, a large Icelandic genome-wide scan provided evidence for a maternal susceptibility locus for preeclampsia on chromosome 2p13 which was confirmed by a genome scan from Australia and New Zealand (NZ). The current study reports on a genome-wide scan of Dutch affected sib-pair families. In total 67 Dutch affected sib-pair families, comprising at least two siblings with proteinuric preeclampsia, eclampsia or HELLP-syndrome, were typed for 293 polymorphic markers throughout the genome and linkage analysis was performed. The highest allele sharing lod score of 1.99 was seen on chromosome 12q at 109.5 cM. Two peaks overlapped in the same regions between the Dutch and Icelandic genome-wide scan at chromosome 3p and chromosome 15q. No overlap was seen on 2p. Re-analysis in 38 families without HELLP-syndrome (preeclampsia families) and 34 families with at least one sibling with HELLP syndrome (HELLP families), revealed two peaks with suggestive evidence for linkage in the non-HELLP families on chromosome 10q (lod score 2.38, D10S1432, 93.9 cM) and 22q (lod score 2.41, D22S685, 32.4 cM). The peak on 12q appeared to be associated with HELLP syndrome; it increased to a lod score of 2.1 in the HELLP families and almost disappeared in the preeclampsia families. A nominal peak on chromosome 11 in the preeclampsia families showed overlap with the second highest peak in the Australian/NZ study. Results from our Dutch genome-wide scan indicate that HELLP syndrome might have a different genetic background than preeclampsia.

Doppler ultrasound screening predicts recurrence of poor pregnancy outcome in subsequent pregnancies, but not the recurrence of PIH or preeclampsia.

OBJECTIVE: To assess the role of Doppler uterine artery screening in the prediction of recurring hypertensive disorders in a high-risk population. METHODS: Ninety-four women with a history of hypertensive disorders in previous pregnancies underwent ultrasound color Doppler to analyze blood flow in the uterine arteries at 21-22 weeks of gestation. We evaluated the performance of the Pulsatility Index (PI) as well as the diastolic notch to predict recurring hypertensive disorders. Outcome measures were the recurrence of hypertensive disorders, and poor pregnancy outcome due to intrauterine death growth retardation, intrauterine death, placental abruption, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, eclampsia, or premature birth. Onset of symptoms was before 35 weeks in all cases of poor pregnancy outcome. RESULTS: Doppler flow recordings were obtained from a well-defined location in both uterine arteries. The predictive value of the uterine artery PI for recurring hypertensive disease was poor and not significant; interestingly, however, the predictive values for poor pregnancy outcome were good (sensitivity 83%, specificity 71%, p < 0.001). The PI also provides a good test for intrauterine growth retardation (sensitivity 80%, specificity 69%, p < 0.01). The "diastolic notch" did not perform as well as the PI. CONCLUSIONS: Uterine artery screening did significantly predict the recurrence of poor pregnancy outcome due to hypertensive complications in this high-risk group. In contrast, gestational hypertension and preeclampsia with normal pregnancy outcome were not significantly predicted by uterine artery screening.

Acute maternal rehydration increases the urine production rate in the near-term human fetus.

OBJECTIVE: We sought to investigate the effect of a decrease of maternal plasma osmolality produced by hypotonic rehydration on the fetal urine production rate in normal near-term human fetuses. STUDY DESIGN: Twenty-one healthy pregnant women attending the clinic for antenatal care were studied between 37 and 40 weeks' gestation. The fetal urine production rate was assessed by serial measurements of 3 diameters of the fetal bladder. The hourly fetal urine production rate was determined by linear regression analysis of the calculated bladder volumes versus time and was initially determined after a period of 4 hours of fluid deprivation. Thereafter, the women were asked to drink 1 L of water, and the hourly fetal urine production rate was assessed again. The hourly fetal urine production rate was only studied during behavioral state 1F because it is dependent on the behavioral state. The fetal behavioral state was determined by assessment of fetal heart rate, fetal eye movements, and fetal body movements. RESULTS: Successful recordings were obtained in 10 of the 21 women. The hourly fetal urine production rate increased significantly after hypotonic rehydration (P <.02). Compared with the initial hourly fetal urine production rate after 4 hours of fluid deprivation, the hourly fetal urine production rate showed an increase of 63.2% after hypotonic rehydration, from 38.2 +/- 16.3 mL/h to 62.4 +/- 34.6 mL/h (mean +/- SD). After rehydration, the baseline fetal heart rate fell significantly, from 141 +/- 6 to 132 +/- 8 beats/min (mean +/- SD; P =.005). CONCLUSION: The fetal urine production rate is augmented after acute maternal oral hypotonic rehydration after 4 hours of fluid deprivation. The current findings demonstrate that the near-term human fetus can handle such acute changes in fluid osmolality by increasing the urine production rate to maintain its fluid homeostasis. This mechanism implies that changes in maternal plasma osmolality and volume probably play an important role in determining amniotic fluid volume. Therefore the application of maternal hydration for the treatment of oligohydramnios should be further investigated.

Daily rhythms in renal blood flow and urine production rate in the near-term sheep fetus.

Daily rhythmicity of renal blood flow (RBF) and urine flow (UF) was studied in fetal sheep between 121-125 d of gestation. Fetal arterial blood pressure, heart rate, UF, and right RBF were measured continuously for 24-h periods in 10 sheep. Rhythmic variations during a 24-h period were found for all variables studied. The rhythms of arterial blood pressure and heart rate were highly correlated, whereas an inverse correlation was found between arterial blood pressure with RBF and between arterial blood pressure with UF. These findings indicate that fetal RBF is not blood pressure dependent. Furthermore, fetal UF appears not to be mediated by pressure-dependent diuresis.