Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.

Infant outcome after active management of early-onset fetal growth restriction with absent or reversed umbilical artery blood flow.

OBJECTIVE: To describe the short- and long-term outcomes of infants with early-onset fetal growth restriction (FGR) and umbilical artery absent or reversed end-diastolic flow (AREDF), delivered before 30 weeks' gestation and managed proactively. METHODS: This was a retrospective cohort study of fetuses delivered for fetal indication before 30 completed weeks' gestation that had early-onset FGR (defined as estimated fetal weight more than 2 SD below the mean) with AREDF in the umbilical artery (FGR group), at the level-3 perinatal unit in Lund, Sweden, between 1998 and 2015. Perinatal outcome and neurodevelopment at ≥ 2 years of age in surviving infants were compared with those of a group of infants without small-for-gestational-age birth weight or any known fetal Doppler changes delivered before 30 weeks in Lund during the corresponding time period (non-FGR group). In the FGR group, the main indication for delivery was the Doppler finding of AREDF in the umbilical artery. RESULTS: There were 139 fetuses (of which 26% were a twin/triplet) in the FGR group and 946 fetuses (of which 28% were a twin/triplet) in the non-FGR group. The FGR infants had a median birth weight of 630 g (range, 340-1165 g) and gestational age at birth of 187 days (range, 164-209 days), as compared with 950 g (range, 470-2194 g) and 185 days (range, 154-209 days), respectively, in the non-FGR group. The rate of fetal mortality did not differ between the two groups (5.0% and 5.4% in the FGR and non-FGR groups, respectively). All seven intrauterine deaths in the FGR group occurred before 26 weeks' gestation. In the FGR group compared with the non-FGR group, severe intraventricular hemorrhage was less frequent and bronchopulmonary dysplasia and septicemia were more frequent (P = 0.008, P < 0.001 and P = 0.017, respectively). In the FGR group, the survival rate at 2 years (83% of liveborn infants) and the rate of cerebral palsy (7%) did not differ significantly from those in the non-FGR group (82% and 8%, respectively). The rate of survival without neurodevelopmental impairment was higher in the non-FGR group (83%) than in the FGR group (62%) (P < 0.001), as well as in infants in the FGR group delivered at or after 26 weeks (72%) compared with those delivered before 26 weeks (40%) (P = 0.003). Within the FGR group, outcomes were similar between twins and singletons and, in those who survived beyond 2 years, outcomes were similar between fetuses with absent and those with reversed end-diastolic flow in the umbilical artery. CONCLUSIONS: Infants delivered very preterm after severe FGR with AREDF in the umbilical artery had a similar rate of survival as did non-FGR infants of corresponding gestational age; however, they were at higher risk of neurodevelopmental impairment, the risk being most pronounced following birth before 26 weeks. Gestational age remains an important factor associated with the prognosis of early-onset FGR; nevertheless, the present results support the hypothesis, which should be tested prospectively, that fetuses with early-onset FGR and umbilical artery AREDF may benefit from early intervention rather than expectant management, and that umbilical artery Doppler findings could be incorporated into clinical protocols for cases very early in gestation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction: prospective cohort study.

OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. RESULTS: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. CONCLUSION: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Cardiovascular function in adulthood following intrauterine growth restriction with abnormal fetal blood flow.

OBJECTIVES: To examine whether intrauterine growth restriction (IUGR) is associated with increased cardiovascular risk later in life. METHODS: We examined 19 young adults (aged 22-25 years) who were born at term after IUGR, along with 18 controls. All had been examined previously with fetal Doppler, and in the present follow-up with echocardiography, carotid echo-tracking ultrasound, applanation tonometry, blood pressure and laser Doppler, in order to characterize their cardiac and vascular geometry and/or function. RESULTS: The diameter of the ascending aorta and the left ventricular diameter were smaller in the IUGR group, but only ascending aortic diameter remained significantly smaller after adjustment for body surface area (P < 0.05). The aortic pressure augmentation index was higher in the IUGR group (P < 0.05). The common carotid artery diameter, intima-media thickness and distensibility as well as left ventricular mass and function were similar in the two groups. IUGR status was found to be an independent predictor of ascending aortic diameter. CONCLUSIONS: IUGR due to placental dysfunction seems to contribute to the higher systolic blood pressure augmentation and the smaller aortic dimensions that are observed in adults more than 20 years later, with possible negative consequences for future left ventricular performance due to increased aortic impedance.

Early intervention in management of very preterm growth-restricted fetuses: 2-year outcome of infants delivered on fetal indication before 30 gestational weeks.

OBJECTIVES: To describe the outcome of growth-restricted fetuses with absent or reversed end-diastolic flow (ARED) in the umbilical artery delivered on fetal indication before 30 gestational weeks. METHODS: Between 1998 and 2004, 42 fetuses with intrauterine growth restriction (IUGR) and ARED in the umbilical artery were delivered liveborn by Cesarean section on fetal indication before 30 gestational weeks. The median gestational age at delivery was 27 + 1 (range, 24 + 4 to 29 + 5) weeks. An additional four fetuses died in utero at a median gestational age of 24 + 2 (range, 23 + 5 to 25 + 4) weeks. Neonatal morbidity, infant mortality and major neurological morbidity of liveborn infants were compared with those in two control groups: all 371 liveborn infants delivered at < 30 weeks during the corresponding time period (Group A) and a subset of these, 42 matched infants without IUGR (Group B). RESULTS: Thirty-two fetuses (76%) [corrected] were delivered within 48 h of the occurrence of ARED (25 absent, seven reversed end-diastolic flow). The remaining 10 fetuses (five absent, five reversed end-diastolic flow) were monitored for a median of 6.5 (range, 3-18) days before delivery. One infant died in the neonatal period and three during the first year of postnatal life (2-year survival 90%). The incidence of chronic lung disease was higher in the ARED Group than in Control Groups A and B (P = 0.001 and P = 0.03, respectively). There were no differences between the groups in the occurrence of necrotizing enterocolitis, cerebral hemorrhage or retinopathy of prematurity. Cerebral palsy was diagnosed in 14% of the index group compared with 11% and 17% of Control Groups A and B (P > 0.05). CONCLUSIONS: Very preterm growth-restricted fetuses with umbilical artery ARED delivered on fetal indication, in most cases before the occurrence of severe changes in the ductus venosus velocity waveforms and/or fetal heart rate tracings, showed high 2-year survival and low morbidity.

Vascular mechanical properties and endothelial function in pre-eclampsia with special reference to bilateral uterine artery notch.

OBJECTIVES: To assess whether women with pre-eclampsia (PE) have different properties of the blood vessel wall compared to healthy pregnant controls. Further, to evaluate endothelial function and vascular mechanical properties in women with PE with special regard to its association with bilateral uterine artery notch and placental histopathology. PARTICIPANTS: Some 57 Caucasian pregnant women: 23 with uncomplicated pregnancies and normal uterine artery Doppler, and 34 with PE, the PE group comprising 2 subgroups according to the presence (n=20) or absence (n=14) of bilateral uterine artery notches. METHODS: Ultrasonic echo-tracking assessed the elastic properties of the common carotid artery, abdominal aorta and popliteal artery. Flow-mediated dilatation (FMD) of the brachial artery was measured by ultrasonography. Histopathological examination of the placenta was carried out in 46 pregnancies: 18 uncomplicated pregnancies, 15 with PE with bilateral notch, and 13 with PE without bilateral notch. RESULTS: There were no significant differences in carotid, aortic or popliteal vessel wall stiffness either between women with PE and controls or within the PE group. FMD was significantly lower in women with PE than in controls (p=0.03). The lowest FMD was observed in pre-eclamptic women with bilateral uterine artery notches 9.5% (SD: 5.3) compared to 11.6% (SD: 5.4) in pre-eclamptic women without bilateral uterine artery notch, and 13.4% (SD: 4.0) in controls (p=0.01). Bilateral uterine artery notching was significantly associated with a lower FMD (OR: 0.87; 95% CI: 0.77-0.98). There were significantly more placentas with high ischaemic score in the bilateral notch group than in the group with PE and normal circulation. CONCLUSIONS: There were no differences in vessel wall stiffness between women with PE and healthy controls. Women with PE showed signs of endothelial dysfunction, significantly more pronounced in women with bilateral uterine artery notch. Bilateral uterine artery notch was associated with ischaemic pathology of the placenta. Notwithstanding, a significant number of placentas in the PE group failed to show noteworthy ischaemic or other morphological changes that could explain the role of the placenta in the development of PE.

Increased aortic pulse wave velocity in middle aged women with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a connective tissue disease where inflammatory activity affects several organ systems. An increased risk of cardiovascular disease has been identified in these patients, even after correction for traditional risk factors. The aim of the present study was to evaluate arterial stiffness and central hemodynamics in women with SLE in comparison to controls. Arterial tonometry was used to measure aortic (carotid-femoral) and arm (carotid-radial) pulse wave velocity (PWV), reflected pressure waves, and aortic augmentation index (AIx) in 27 women with SLE (52 to 68 years) and 27 controls. Aortic PWV was higher in women with SLE than controls, 9.8 m/s versus 8.2 m/s (P < 0.01), after correction for mean arterial pressure and body mass index, 9.5 m/s versus 8.5 m/s (P < 0.05). Other parameters were similar, arm PWV, 8.4 versus 8.5 m/s, AIx 34 versus 33% and calculated central aortic pulse pressure 48 versus 43 mmHg, in SLE and controls, respectively (NS). Aortic PWV was positively associated to C-reactive protein (CRP) and complement factor 3 (C3). Women with SLE have increased stiffness of their elastic central arteries. This may be one factor contributing to the increased cardiovascular risk seen in this cohort.

Gene expression profiling of human placentas from preeclamptic and normotensive pregnancies.

The aim of this study was to investigate patterns of gene expression in placental samples from patients with preeclampsia (PE), persistent bilateral uterine artery notching (without PE), and normal controls. This study included placental tissue from nine women with PE, seven with uncomplicated pregnancies and five with bilateral uterine artery notching in Doppler velocimetry tracings. Human cDNA microarrays with 6500 transcripts/genes were used and the results verified with real-time PCR and in-situ hybridization. Multidimensional scaling method and random permutation technique demonstrated significant differences among the three groups examined. Within the 6.5K arrays, 6198 elements were unique cDNA clones representing 5952 unique UniGenes and 5695 unique LocusLinks. Multidimensional scaling plots showed 5000 genes that met our quality criteria; among these, 366 genes were significantly different in at least one comparison. Differences in three genes of interest were confirmed with real-time PCR and in-situ hybridization; acid phosphatase 5 was shown to be overexpressed in PE samples and calmodulin 2 and v-rel reticuloendotheliosis viral oncogene homolog A (RELA) were downregulated in PE and uterine artery notch placentas. In conclusion downregulation of RELA and calmodulin 2 might represent an attempt by the placenta to compensate for elevations in intracellular calcium, possibly caused by hypoxia and/or apoptosis, in both pregnancies with uterine artery notching and preeclampsia.

Impaired vascular growth in late adolescence after intrauterine growth restriction.

BACKGROUND: Abnormal blood flow in a fetus small for gestational age indicates true fetal intrauterine growth restriction (IUGR). We tested the hypothesis that IUGR with abnormal fetal blood flow is associated with long-term abnormal vascular morphology and function in adolescence. METHODS AND RESULTS: In a prospective study, vascular mechanical properties of the common carotid artery (CCA), abdominal aorta, and popliteal artery (PA) were assessed by echo-tracking sonography in 21 adolescents with IUGR and abnormal fetal aortic blood flow and in 23 adolescents with normal fetal growth and normal fetal aortic blood flow. Endothelium-dependent and -independent vasodilatation of the brachial artery was measured by high-resolution ultrasound. After adjustment for body surface area and sex, the IUGR group had significantly smaller end-diastolic vessel diameters than the referents in the abdominal aorta and PA (mean difference, 1.7 mm [95% CI, 0.62 to 2.74] and 0.6 mm [95% CI, 0.25 to 1.02], respectively) (P=0.003 and P=0.002, respectively), with a similar trend in the CCA (P=0.09). A higher resting heart rate was observed in the IUGR group (P=0.01). No differences were found in stiffness or in endothelium-dependent and -independent vasodilatation between the 2 groups. CONCLUSIONS: IUGR caused by placental insufficiency appears to be associated with impaired vascular growth persisting into young adulthood in both men and women. The smaller aortic dimensions and the higher resting heart rate seen in adolescents with previous IUGR may be of importance for future cardiovascular health.

Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies.

Pre-eclampsia is one of the most common causes of perinatal and maternal morbidity and mortality. High blood pressure and proteinuria are important clinical signs of pre-eclampsia. Sympathetic overactivity and elevated level of circulating vaso active substances, such as monoamines has been shown. Extracellular concentrations of monoamines are normally kept low by specific transporter proteins of which many are expressed in the placenta. In this study we used in situ hybridization and real-time PCR to study the gene expression of monoamine transporters, such as NET, SERT, VMAT2, EMT and OCT1/2, in normal as well as in pre-eclamptic placentae. We demonstrated high expression of NET mRNA in the trophoblast cells of the anchoring villi and a lower expression intensity in the chorionic villi. SERT mRNA was mainly detected in chorionic villi. VMAT2 mRNA was not detected in the central part of the placenta but was present in the spiral arteries of placenta bed biopsies, in cytokeratin positive cells. EMT mRNA was mainly detected in the intra lobular septa and together with OCT1 and OCT2 mRNAs also expressed in scattered cells of placental vessel adventitias. Moreover, quantitative analysis showed a significant lower expression of NET and EMT mRNAs in pre-eclamptic placentae as compared to the control group. A defective gene expression or function of these monoamines transporters might explain the elevated concentrations of monoamines in pre-eclamptic patients. Monoamine transporters may serve as a protective mechanism preventing vasoconstriction in the placental vascular bed and thereby securing a stable blood flow to the fetus.

Abnormal mechanical properties of larger arteries in postmenopausal women with systemic lupus erythematosus.

There is limited knowledge of potential defects in arterial wall properties in female systemic lupus erythematosus (SLE) patients without manifest cardiovascular disease (CVD) and significant atherosclerotic lesions. The aim of the present study was to investigate the mechanical properties of larger vessels in these patients and to compare them with healthy controls. B-mode ultrasound was used to assess vessel wall structure and to exclude presence of plaque. The ankle/brachial pressure index was measured to exclude occlusive arterial disease. An ultrasound echo-tracking system was used to determine stiffness of the abdominal aorta, common carotid artery (CCA) and popliteal artery (PA) in 39 female patients with SLE and 55 female, healthy controls. SLE had an independent effect on stiffening of the CCA (P = 0.01) and PA (P = 0.005). In addition, larger vessel diameters were observed in the CCA (P = 0.002) after adjustments for the effects of mean arterial pressure and age. Thus, this investigation demonstrated an increased arterial stiffness and signs of premature vascular ageing in the SLE patients without manifest cardiovascular disease and without significant atherosclerotic lesions. The results of this study indicate that other mechanisms besides atherosclerosis might be involved in the pathogenesis of arterial stiffening in SLE patients.

Altered vascular function in healthy normotensive pregnant women with bilateral uterine artery notches.

OBJECTIVES: To assess endothelial function and vascular mechanical properties in normotensive pregnant women with high resistance in the uteroplacental circulation. DESIGN: Cross-sectional prospective study. SETTING: Doppler ultrasound laboratory at university department of obstetrics and gynaecology referral centre for high risk pregnancies. PARTICIPANTS: Forty-two caucasian normotensive pregnant women: 23 with uncomplicated pregnancies and 19 with bilateral uterine artery notches. METHODS: Flow-mediated dilatation of the brachial artery was measured by ultrasonography at 25 gestational weeks. Concentrations of nitrite and nitrate in the plasma were established at 25 and 32 gestational weeks. The elastic properties of the common carotid artery, abdominal aorta and popliteal artery were measured with an ultrasonic echo-tracking system. RESULTS: Flow-mediated dilatation at two minutes after cuff deflation was significantly lower in the bilateral notch group compared with the control group, 8.3% and 13.7%, respectively (P = 0.0007). The ability to sustain vasodilatation was reduced in the bilateral notch group (P = 0.02). Lower values of nitrite and nitrate in the plasma were found at 32 gestational weeks in the bilateral notch group than in the control group (mean 24.76 microM/L (SD 5.6) and 30.93 microM/L (8.2), respectively; P = 0.008). Nitrite and nitrate levels tended to be lower in the bilateral notch group even at 25 gestational weeks (29.45 microM/L (8.3) and 35.73 microM/L (11.0) in the bilateral notch and control group, respectively; P = 0.09). There was no difference in aortic, carotid or popliteal elasticity between the two groups. CONCLUSIONS: Healthy normotensive pregnant women with bilateral uterine artery notches show impaired endothelial function, but no differences in vascular mechanical properties.

Uterine artery score and perinatal outcome.

OBJECTIVE: To evaluate a modified uterine artery score based on the pulsatility index and presence or absence of notching in the Doppler velocity waveform recorded from both uterine arteries in relation to the perinatal outcome. METHODS: A retrospective analysis was performed in 741 third-trimester high-risk pregnancies. The uterine artery score was constructed assigning one point to each abnormal parameter-high pulsatility index and presence of notch-thus ranging from 0 (normal findings in both uterine arteries) to 4 (notch and high pulsatility index in both uterine arteries). In a subgroup with lateral placenta (n = 359), two definitions of abnormal pulsatility index were compared. In the uniform uterine artery score, a pulsatility index > 1.20 in both uterine arteries was considered abnormal, disregarding the placental location; in the subgroup with lateral placenta, the high pulsatility index was defined as > 1.00 on the placental side and > 1.40 on the non-placental side. RESULTS: Receiver-operating characteristic curves did not reveal any difference in the diagnostic capacity between the group with a uniform uterine artery score and the subgroup with lateral placenta (P = 0.54). In the total material, the odds ratios and linear regression analysis showed an increased risk for an adverse perinatal outcome with increasing uterine artery score (P < 0.01). At a uterine artery score > 2, there was a significantly increased risk for operative delivery for fetal distress, neonatal intensive care unit admission, 5-min Apgar score < 7, preterm delivery and delivery of a small-for-gestational age fetus. CONCLUSION: In high-risk third-trimester pregnancies, Doppler velocity waveforms of the uterine arteries can be evaluated using the uterine artery score disregarding the placental location. The uterine artery score possesses a high predictive value regarding adverse perinatal outcome.

Can the degree of retrograde diastolic flow in abnormal umbilical artery flow velocity waveforms predict pregnancy outcome?

OBJECTIVE: Reverse end-diastolic flow is the most pathological type of the umbilical artery flow velocity waveform. We aimed to investigate whether additional prognostic information can be obtained from umbilical artery waveforms in cases with reverse end-diastolic flow. SUBJECTS AND METHODS: Umbilical artery Doppler velocity waveforms from 44 fetuses with reverse end-diastolic flow were analyzed and the following parameters measured: the highest amplitude and the area below the maximum velocity curve of forward and reverse flow (A, B and C, D, respectively) and the duration of forward and reverse flow (Tc and Td, respectively). Ratios A/B, C/D and Tc/Td were calculated. The cut-off values for A/B, C/D and Tc/Td with the best predictive values for perinatal death were established with the help of receiver operating characteristics curves. The three curves were compared with each other. RESULTS: Of the three ratios, A/B and C/D had the best capacity to predict perinatal death. Both ratios had acceptable sensitivities, specificities and positive predictive values. In this regard, A/B and C/D were comparable. The cut-off values for A/B and C/D were 4.3 and 4.52, respectively. Survivors had I significantly higher A/B and C/D ratios than non-survivors (P = 0.0001 and 0.0003, respectively). Significantly more fetuses with A/B or C/D below the established cut-off values had pulsations in the venous system (P < 0.05). In fetuses with a gestational age < =210 gestational days the survival rate was significantly higher in those with A/B or C/D above the cut-off values (P = 0.03 and 0.003, respectively). CONCLUSIONS: The A/B or C/D ratio can be used for quantification of the reverse end-diastolic flow waveforms in the umbilical artery and may offer additional information to the evaluation of fetal condition.

Ventriculo-vascular interaction in the normal development of the fetal circulation.

OBJECTIVES: To examine cardiovascular physiology in the healthy fetus during normal development. DESIGN: Twenty normal fetuses were studied longitudinally from 20 weeks to term. Serial echocardiography was performed, and arterial and venous diameter pulse wave characteristics and aortic pulse wave propagation velocity (PWV) were examined in the thoracic descending aorta (AoD) and inferior caval vein (IVC) using an ultrasonic phase-locked echo-tracking system. Statistical analyses included ANOVA, paired t-test and logistic regression where appropriate. RESULTS: Aortic PWV, maximum incremental and late decremental velocities increased with gestation while the relative pulse amplitude decreased, reflecting falling distal impedance. There was a linear increase in cardiac preload and relative pulse amplitude in the IVC with gestation that correlated significantly with the presence of end-diastolic flow in the pulmonary artery and improvement in right ventricular diastolic function. CONCLUSIONS: Non-invasive concurrent assessment of preload, ventricular function and impedance are possible in the fetus and may prove useful in the longitudinal study of fetal adaptation to pathophysiological changes.

Ventriculovascular physiology of the growth-restricted fetus.

OBJECTIVES: To examine the mechanisms by which intrauterine growth restriction may influence later cardiovascular risk by comparing the ventriculovascular physiology of gestational age- and weight-matched growth-restricted and normal fetuses. DESIGN: A prospective longitudinal observational study of 20 normal fetuses studied from 20 weeks to term at monthly intervals was compared with a growth-restricted cohort examined in the interval between diagnosis and delivery. The last values before delivery of the growth-restricted cohort were compared with the normal cohort in two analyses matched for weight and for gestation. Arterial and venous vessel wall physiology and aortic pulse wave velocity were examined longitudinally in the thoracic descending aorta and inferior vena cava using an ultrasonic phase-locked echo-tracking system. Serial echocardiographic examinations were performed assessing structure, ventricular dimensions, function and Doppler flows. RESULTS: There was a linear increase in cardiac preload and relative pulse amplitude in the inferior vena cava with gestation. In normal fetuses, the aortic pulse wave velocity, maximum incremental and late decremental velocities increased with gestation whilst the relative pulse amplitude decreased reflecting falling distal impedance. In both age- and weight-matched analyses, the growth-restricted fetuses showed significantly reduced values reflecting the chronic fetal ventriculovascular responses to increased placental impedance. Pulse wave velocity increased with gestation and was significantly less in the growth-restricted cohort. CONCLUSIONS: Growth restriction is associated with abnormal ventriculovascular physiology that represents a successful adaptive response to raised placental impedance and reduction in wall stress as evidenced by the lower fetal pulse wave velocity in growth-restricted fetuses. However, whilst fetal adaptive mechanisms may aid survival they may result in cerebral and vascular abnormalities that prejudice later cardiovascular health.

Management of pregnancies with suspected intrauterine growth retardation in Sweden. Results of a questionnaire.

BACKGROUND: Diagnosis and management of intrauterine growth retardation during pregnancy remain a major challenge in obstetric care. The objective of this survey was to evaluate the routine clinical management of pregnancies with suspected intrauterine growth retardation at obstetric departments in Sweden. METHODS: In 1997, a questionnaire was sent to all 59 obstetric departments in Sweden. Forty-two departments, caring for 83% of all deliveries in Sweden, replied. Four major topics were addressed: definition and diagnosis of intrauterine growth retardation; magnitude of the problem; clinical management; use of Doppler ultrasound in clinical decision-making. RESULTS: Intrauterine growth retardation is diagnosed by a combination of serial fundal height measurements and ultrasonic fetal biometry at 40 departments, two departments perform routine fetal biometry at 32 weeks. The diagnosis is most often made at 32-36 gestational weeks. Five departments use 1.5 s.d. below the mean as cut-off point for diagnosis of small for gestational age fetuses; 35 departments use mean - 2 s.d. and two departments mean - 2.5 s.d. Intrauterine growth retardation is suspected in 1.6-6.3% pregnancies. About 19% of patients with suspected intrauterine growth retardation are hospitalized. On average, 63% of all small-for-gestational age babies are diagnosed prenatally. Thirty-nine out of 42 obstetric departments use formalized management protocols. All departments use cardiotocography, repeat ultrasound scans and Doppler ultrasound for antenatal surveillance. CONCLUSIONS: In Swedish obstetric units, the diagnostic procedures and methods of fetal surveillance in pregnancies suspected of intrauterine growth retardation are more or less uniform. Doppler examination of umbilical artery is used at all responding departments and is considered a valuable asset in clinical decision-making.

Reproducibility of ultrasonic fetal volume blood flow measurements.

The intraobserver reproducibility of ultrasonic volume blood flow measurements in the human fetus was evaluated in this study. A new approach, simultaneous measurement of the vessel diameter and the flow velocity with a pulsed-wave Doppler ultrasound synchronized with a real-time ultrasound phase-locked echo-tracking system, was used to estimate volume blood flow (VBF) in the fetal descending aorta. Measurements were performed in a longitudinal study on 20 normally grown fetuses. Intraobserver reproducibility of repeated estimations of mean blood flow velocities throughout gestation was very good, with high values of intraclass correlation coefficient (IntraCC 0.80-0.91) and low values of coefficient of variation (CV 4-11%). The IntraCC of repeated vessel diameter measurements throughout gestation was low (0.30-0.68), whereas the values of CV were acceptable (< 12%), with the exception of the period between 140 and 167 gestational days (CV > 12%). The lower reproducibility of vessel diameter measurement contributed directly to the relatively low reproducibility of VBF estimations overall (IntraCC 0.25-0.70; CV 17-28%), as these are calculated from a formula using both flow velocity and vessel diameter. Nevertheless, the synchronized approach gives absolute values of vessel diameter, flow velocity and VBF comparable with values reported in the human fetus previously. The new method provides, by taking the vessel wall pulsations into consideration and by measuring diameter and velocity simultaneously, a more complete information on fetal haemodynamics and fetal physiology.