Low birthweight has been linked to increased cardiovascular risk in adulthood. We evaluated the effect on cardiovascular outcome of intrauterine growth restriction (IUGR) with abnormal fetal blood flow in children born very preterm. Blood pressure, cardiac function and size, diameters, distensibility, and stiffness of the abdominal aorta, carotid, and popliteal arteries, and endothelial function were assessed non-invasively in 7-year-old children (n = 32) born very preterm with IUGR, with birthweight (median, range) 650 g (395–976 g) and gestational age 27 weeks (24–29 weeks). In addition, intima-media thickness was measured in the carotid artery. Controls were matched for gender and age and had birthweight appropriate-for-gestational-age (AGA). The study included 32 preterm-AGA children with birthweight 1010 g (660–1790) g and 32 term-AGA children with birthweight 3530 g (3000–4390) g. Preterm-IUGR children had lower microvascular response to acetylcholine, lower aortic stiffness, and higher distensibility compared with the preterm-AGA group (p = 0.019, p = 0.001, and p < 0.001, respectively) and lower carotid intima-media thickness compared with the term-AGA group (p = 0.047). The highest aortic β and lowest distensibility were found in the preterm-AGA group. Height-adjusted systolic blood pressure was higher in the preterm groups than in the term-AGA group (p = 0.018). Cardiac function and size did not differ between the groups. IUGR and preterm birth appear to be associated with structural changes in the arterial wall, whereas preterm birth seems to be associated with higher blood pressure. Using conventional echocardiography, we observed no effect of IUGR on cardiac size and function.
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.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.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.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.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.
Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.
Fetal experience forms the basis for postnatal life. The nutritional as well as the psychosocial environment during the first postnatal years may add to, but equally compensate for, previous adverse influence during fetal development. Intrauterine growth restriction (IUGR) has been proven in epidemiological studies to have implications for adult life by increasing the risk of developing cardiovascular, endocrine and metabolic diseases. Small-for-gestational date fetuses with abnormal flow velocity waveforms have been shown to have high perinatal mortality and neonatal morbidity. At early school age, IUGR is associated with impairment of intellectual capacity and neurodevelopmental delay. We have performed a longitudinal follow-up study up to 18 years of age of IUGR subjects with abnormal fetal blood flow. At the age of 7 years (n = 148), they had an impaired intellectual outcome and increased frequency of minor neurological deviations. There were no changes in aortic compliance. At 18 years, a subcohort of IUGR individuals (n = 28) was compared with a control group (n = 23) and found to have decreased cognitive capacity and emotional disturbances. Quantitative analysis of ocular fundus photographs showed a reduced axonal area in the optic nerve and deviating central field vision. The growth-restricted young adults also showed a decrease in the number of retinal vascular branching points and smaller vessel diameter of large arteries in proportion to the body size. Male adolescents had a lower aortic compliance coefficient. The flow-mediated vasodilation of brachial artery was sustained in the IUGR group. The above findings indicate that IUGR, i.e. SGA fetus with abnormal fetoplacental circulation, is associated with impaired postnatal neurological, intellectual and vascular development. Possibly, a more active obstetric management of pregnancies with IUGR might decrease the degree of long-term consequences.
To examine whether intrauterine growth restriction (IUGR) is associated with increased cardiovascular risk later in life.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.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.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.
Epidemiological studies indicate that fetal adaptation to hostile intrauterine environment in growth restriction (IUGR) may result in programming of cardiovascular system and disease later in life. Possible mechanisms were investigated by which IUGR may influence later cardiovascular health. In a follow-up study, association was explored between intrauterine circulatory changes and postnatal vascular, neurological and cognitive development. 1. Cardiovascular function in 11 IUGR fetuses and 20 controls was followed longitudinally. Pulse wave velocity, vessel wall pulsations, aortic volume blood flow and cardiac function were examined using automatic echo-tracking system, echocardiography and Doppler ultrasound. 2. A cohort of 21 18-year old subjects IUGR at birth and 23 controls were examined with digital image analysis of the ocular fundus. Retinal vascular morphology and size of the neuroretinal rim area were evaluated. Visual function was examined with Rarebit perimetry and the cognitive development was assessed. 1. Cardiac growth and volume blood flow were appropriate for somatic size in IUGR fetuses, but cardiac wall thickness was increased. IUGR fetuses showed impaired right atrial contractibility. The development with gestational age of arterial wall pulsations did not followed the same pattern of improving cardiovascular coupling as seen in normal fetuses. 2. At 18-years, individuals with IUGR (small size and abnormal fetal blood flow) showed fewer branching points of retinal vessels and decrease in neuroretinal rim area, suggesting either a decrease in axonal growth or lower number of axons in the optical nerve. They had more often impaired visual function and lower IQ than the controls. IUGR is associated with abnormal cardiovascular function that may prejudice later health. In young adults, IUGR is associated with impaired vascular, neurological and cognitive development.
The aim of this retrospective study was to describe the outcome of fetuses with absent or reversed end-diastolic flow (ARED) in the umbilical artery (UA) delivered on fetal indication before 30 gestational weeks. Between 1998 and 2004, 42 fetuses with ARED flow in the UA were actively delivered with Cesarean section at 26.5 (24–29) (median (range)) weeks. Neonatal morbidity, infant mortality and major neurological morbidity of liveborn infants were compared to two control groups: (1), all infants born before 30 weeks during the corresponding time period (n = 371; 27(24–29) weeks); (2), AGA matched infants (n = 42; 27(24–29) weeks). Twenty-six fetuses (62%) were delivered within 24 h after detection of ARED flow in the UA (19 AED, 7 RED). The remaining fetuses were monitored for 2.5 days before delivery (median; range, 1–18 days). Twenty-three fetuses had pulsations in the umbilical vein, 24 abnormal ductus venosus flow, 31 brainsparing and eight abnormal fetal heart rate (decelerations). One infant died during the neonatal period and three during the first year of life (4/42; 10%). Birth weight was lower than in both control groups (P < 0.001 respectively). 17% of index neonates had an Apgar score < 7 at 5 min compared to 33% and 21% of the respective control groups (P = 0.03; P > 0.05). The incidence of bronchopulmonary dysplasia (BPD) was significantly higher in the ARED group (P = 0.001; P = 0.025). There were no differences between the groups in necrotizing enterocolitis, cerebral hemorrhage or retinopathy of prematurity. Cerebral palsy was diagnosed in 14% of infants of the index group compared to 11% and 17% of the control groups (P > 0.05 respectively). An active approach to delivery of fetuses with ARED flow before 30 gestational weeks prevented antenatal death and did not lead to increased infant mortality or severe neurological morbidity as compared to infants born at the same gestational age. Fetuses with ARED flow did however have an increased risk for development of BPD.
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