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PubMed2000

Habituation in fetuses of diabetic mothers.

Fetuses of diabetic mothers exhibit maturational delays in their behaviour and disturbances in behavioural and intellectual functioning in childhood. This suggests an effect of maternal diabetes on the central nervous system of the fetus. The habituation technique enables the functioning of the higher central nervous system to be examined. A normal habituation pattern reflects an intact central nervous system. Previous studies have found abnormalities in the fetal central nervous system are reflected in habituation performance. This paper examined the habituation ability of fetuses of diabetic mothers and of non-diabetic mothers. The fetuses were tested at 28, 32 and 36 weeks of gestation. After 2 min of fetal inactivity a series of vibroacoustic stimuli were presented to the fetus. This continued until no response was observed on five consecutive stimulus presentations. The number of stimulus presentations to habituate at each gestational age was recorded. The results reveal that there was a highly significant main effect of group (F(1,47)=19.65, P<0.001). Fetuses of diabetic pregnancies took longer to habituate. There was a significant effect of gestational age (F(2,94)=44.67, P<0.0001). In both groups the number of trials to habituate decreased with advancing gestation. There was no relationship between random blood glucose levels and habituation performance. The results demonstrate that maternal diabetes affects higher aspects of central nervous system functioning in the fetus.

Adult↗
PubMed2003

Effects of antenatal steroids on ischemic brain injury in near-term ovine fetuses.

BACKGROUND: Hypoxia/ischemia in utero can result in brain damage to the fetus and newborn. Antenatal steroids are a routine part of the management of women who develop premature labor. Pretreatment of young postnatal rats with dexamethasone before hypoxic/ischemic insults has been reported to attenuate brain injury. However, the effects of antenatal steroids on ischemic brain injury in fetuses have not been investigated. OBJECTIVE: We examined the effects of maternally administered antenatal corticosteroids on ischemic brain injury in near-term ovine fetuses. METHODS: Chronically instrumented fetuses at 122 days of gestation were studied 12 h after the last of four 4 mg dexamethasone, or placebo injections were given over 48 h to the ewes. Groups were dexamethasone/ischemic, placebo/ischemic and sham-treated control. Fetuses were exposed to 30 min of carotid occlusion (ischemia) or no occlusion (control) and 72 h of reperfusion. Whole brain coronal sections stained with Luxol fast blue-hematoxylin-eosin were scored for white matter and cerebral cortical lesions. Both areas received pathological scores of 0 to 5 reflecting the degree of injury (0=0%, 1=1-10%, 2=11-50%, 3=51-90%, 4=91-99% and 5=100%). Bilateral carotid blood flow also was measured before, during and after brain ischemia in the dexamethasone/ischemic and placebo/ischemic groups. RESULTS: White matter (WM) and cerebral cortical scores did not differ between the dexamethasone/ischemic and placebo/ischemic (WM: 3.0+/-1.9 and 2.9+/-1.7; cortex: 3.1+/-1.7 and 2.6+/-1.8, mean+/-S.D.) groups. White matter and cerebral cortical scores were higher in the dexamethasone/ischemic (WM: 3.0+/-1.9, P<0.02; cortex: 3.1+/-1.7, P<0.005) and placebo/ischemic (WM: 2.9+/-1.7, P<0.006; cortex: 2.6+/-1.8, P<0.007) than control (WM: 0.2+/-0.4; cortex: 0.2+/-0.4) group. Carotid blood flow was relatively higher (P<0.05) after 24, 48 and 72 h of reperfusion in the dexamethasone/ischemic than placebo/ischemic group. CONCLUSIONS: We conclude that maternal pretreatment with antenatal dexamethasone did not attenuate ischemic brain injury in the fetus, and that carotid blood flow was higher during reperfusion in fetuses of dexamethasone than placebo-treated ewes, most likely secondary to decreases in arterial oxygen tension.

Animals↗
PubMed1986

Brain metabolic correlates of hypoxic-ischemic cerebral necrosis in mid-gestational sheep fetuses: significance of hypotension.

Mid-gestational sheep fetuses exposed to marked hypoxia for 2 h remain brain intact if MABP is maintained above 30 mm Hg. On the other hand, similarly hypoxic fetuses, if they experience reductions in MABP below 30 mm Hg, develop foci of necrosis that predominantly affect hemispheric white matter and neostriatum. Cortex damage is more restricted and is usually associated with more massive underlying white matter damage. The present study examines the brain metabolic basis for the important role of hypotension in brain injury development in marked hypoxia. Sheep fetuses rendered hypoxic by respiring their ewes with 11% oxygen (fetal PaO2 = 8-12 mm Hg) in which MABP was maintained above 30 mm Hg showed increases in brain lactic acid concentrations to 7-13 mumol/g but unaltered energy charge. In contrast, fetuses that sustained MABP reductions below 30 mm Hg showed increases in lactic acid concentrations in vulnerable structures to 16-24 mumol/g accompanied by marked decreases in energy charge. The vulnerable structures also showed reductions in fructose concentrations but a variable behavior of other brain metabolites including phosphocreatine, glycogen, and glucose. Thus, the present findings suggest a relation between hypotension during marked hypoxia, low energy charge, lactic acid accumulation in brain at high concentrations, and fetal brain injury. The ewes of hypoxic hypotensive fetuses received pentobarbital at lower doses than did those of fetuses that maintained blood pressure. This suggests that pentobarbital plays an important role in protecting the fetal brain from asphyxia by extending the hypoxic fetus's ability to maintain blood pressure in addition to reducing its brain metabolism.

Animals↗
PubMed2000

Long-term gene transfer to mouse fetuses with recombinant adenovirus and adeno-associated virus (AAV) vectors.

We have developed a micro-injection technique to deliver recombinant adenovirus and AAV to mouse fetuses at day 15 after conception. Several routes of delivery, including injections to the amniotic fluid, the front limb, the placenta, the liver, and the retro-orbital venus plexus, were tested using an E1-deleted recombinant adenovirus (Ad.CBlacZ) or a recombinant adeno-associated virus (AAV.CMVlacZ) carrying a beta-galactosidase (lacZ) gene. Injection of Ad.CBlacZ into the amniotic cavity led to transgene expression in the skin and in the digestive tract of the fetuses. Injection of Ad.CBlacZ in the front limb resulted in LacZ expression in all major muscle groups around the injection site and at low levels in the liver. The other three routes of delivery, ie intra-placental, intra-hepatic and retro-orbital injections of Ad.CBlacZ, all led to lacZ expression predominantly in the liver. Further studies revealed a maximal tolerant dose (defined as the highest viral dose with < or =20% mortality in the injected fetuses) of 1 x 10(9) particles per fetus for intra- hepatic injections, 3 x 10(9) particles per fetus for intra-placental injection, 1 x 1010 particles per fetus for retro-orbital and intra-amniotic injections, and 2 x 10(10) particle per fetus for intra-muscular injection. The adenovirus-mediated lacZ expression in liver and muscle persisted for at least 6 weeks. Intra-muscular injection of AAV.CMVlacZ also resulted in lacZ expression in the muscle up to 3 months after birth with no indication of cellular immune response at the injection site. Taken together, our results demonstrated that prolonged transgene expression can be achieved by in utero gene transfer using either adenoviral or AAV vectors. The distribution of virus-mediated gene transfer appeared to determined mostly by the route of viral administration.

Adenoviridae↗
PubMed1994

Correlations in umbilical blood flow Doppler velocities in the human fetus during breathing.

We hypothesized that changes in intrathoracic pressure during fetal breathing episodes result in quantifiable variations in umbilical arterial and venous blood flow velocities, and that these variations are related to compliance properties of each system. We further hypothesized that these variations in velocities are different in fetuses with normal and abnormal umbilical arterial Doppler velocities. Umbilical arterial and venous Doppler velocities were measured simultaneously during breathing episodes in 15 normal fetuses and 14 fetuses with elevated systolic-to-diastolic (S/D) umbilical arterial Doppler velocity ratios. Umbilical arterial end-diastolic velocity changes were less than umbilical venous velocity changes in normal fetuses, but were significantly greater in four fetuses with elevated S/D ratios (p < 0.004). Furthermore, umbilical arterial diastolic velocity minima preceded umbilical venous velocity minima by a time lag that was greater in fetuses with elevated S/D ratios (p < 0.002). These results suggest that differences in umbilical arterial and venous velocity variation during fetal breathing episodes may be related in part to vascular compliance, which may be altered in fetuses with abnormal umbilical arterial Doppler velocity.

Journal Article↗
PubMed1996

Doppler indices from inferior vena cava and ductus venosus in predicting pH and oxygen tension in umbilical blood at cordocentesis in growth-retarded fetuses.

The objective of this study was to assess the value of Doppler indices calculated from the inferior vena cava and ductus venosus in the identification of acidemia and hypoxemia as determined by pH and gas analysis of fetal blood obtained by cordocentesis in growth-retarded fetuses. Doppler measurements were performed in the inferior vena cava and ductus venosus in 209 normally grown fetuses and in 89 growth-retarded fetuses. All growth-retarded fetuses were free from structural and chromosomal abnormalities, and uteroplacental insufficiency characterized by Doppler changes in the umbilical and middle cerebral arteries was the most likely etiology of the growth defect. In this group of fetuses, Doppler recordings were performed immediately before cordocentesis. Ten different indices were calculated from venous velocity waveforms, and reference limits for gestation were constructed by the cross-sectional analysis of data from normally grown fetuses. Logistic regression and receiver operator characteristic curve analysis were performed to examine the relationship between Doppler indices and acid-base status. The pre-load index (peak velocity during atrial contraction/peak velocity during systole) in the inferior vena cava was the best explanatory variable for acidemia (chi 2 = 48.33; p < or = 0.001). Hypoxemia was predicted less well by venous indices and the best results were achieved by the S/A ratio in the ductus venosus (chi 2 = 9.46; p < or = 0.005). In conclusion, our data suggest that acidosis in growth-retarded fetuses may be non-invasively identified by Doppler measurements of the inferior vena cava and that a higher efficiency can be achieved by the use of the pre-load index.

Acidosis↗
PubMed1998

Outcome of fetuses with enlarged nuchal translucency and normal karyotype.

The aim of this study was to examine the relationship between nuchal translucency measurements and outcome of pregnancy with special regard to fetuses with an enlarged nuchal translucency and a normal karyotype. Fetal nuchal translucency measurements were performed on consecutive mothers attending the prenatal diagnosis center of our hospital. A complete follow-up was obtained in 88.4% of the cases. Of the 74 fetuses (4.4%) with an enlarged nuchal translucency (> or = 3 mm), 25 (33.8%) had an abnormal karyotype. Two pregnancies ended in a spontaneous abortion before karyotyping was performed. In the remaining 47 eukaryotic fetuses with enlarged nuchal translucency, five (10.6%) had a structural anomaly, two were affected by genetic syndromes (4.2%) and an additional four fetuses (8.5%) were affected by a single-gene disorder. A spontaneous abortion or an intrauterine death occurred in 6.4% and in 2.1% of these fetuses, respectively. The total incidence of an unfavorable outcome in the group of chromosomally normal fetuses with enlarged nuchal translucency was 32%. In contrast, in the group with a normal nuchal translucency (< 3 mm), the incidence of an unfavorable outcome was 7.5%. There is a strong association between enlarged nuchal translucency measurements and congenital (structural and genetic) abnormalities, as assessed by receiver operator characteristic analysis. This may represent, in fetuses with a normal karyotype, a non-specific sign of a disturbance in the developmental process. In these cases, detailed ultrasound surveillance is recommended.

Adult↗
PubMed2001

Fetal hydrops and hepatosplenomegaly in the second half of pregnancy: a sign of myeloproliferative disorder in fetuses with trisomy 21.

OBJECTIVE: To demonstrate the relationship between fetal hydrops and/or hepatosplenomegaly in the second half of pregnancy with a myeloproliferative disorder in fetuses with trisomy 21 or mosaic trisomy 21. DESIGN: A retrospective case series. SUBJECTS: Cases were selected from 79 cases of trisomy 21 diagnosed in our prenatal unit between 1993 and 1999. METHODS: All fetuses had a detailed sonographic anatomic survey and biometry. Doppler of the umbilical and middle cerebral arteries, ductus venosus, inferior vena cava and umbilical vein was performed whenever possible. Two-dimensional echocardiography supplemented by color Doppler flow mapping and spectral pulsed wave Doppler was performed in all cases of fetal hydrops. Fetal karyotyping was obtained by amniocentesis, chorionic villus sampling or fetal blood sampling. In the presence of fetal hydrops a cordocentesis was performed for fetal hematology, biochemistry and TORCH serology. In cases with diagnosis of myeloproliferative disorder, peripheral blast cells were characterized by microscopy, cytochemistry and determination of surface markers. All cases with myeloproliferative disorder were stillborn and subsequently had a postmortem examination performed. RESULTS: During the study period 79 cases of trisomy 21 were diagnosed. Eleven of these had fetal hydrops. Three of these fetuses presented with hepatosplenomegaly and myeloproliferative disorder in the second and third trimesters. In addition, one fetus with sonographic markers of trisomy 21, where karyotyping was unfortunately unsuccessful, presented with hepatosplenomegaly, hydrops and myeloproliferative disorder. In the four fetuses with hepatosplenomegaly and hydrops, serology was negative for congenital infection. The characteristics of blast cells in the peripheral blood smear revealed a myeloproliferative disorder. CONCLUSION: Fetal hydrops and/or hepatosplenomegaly in the second half of pregnancy, although suggestive of infectious etiology, may be a sign of myeloproliferative disorder in fetuses with trisomy 21 or mosaic trisomy 21. There is a possibility that a transient myeloproliferative disorder is a more common cause of mid or late-trimester hydrops in cases of trisomy 21 than previously thought. In these hydropic fetuses the prognosis seems to be poor. On the other hand we can speculate that a myeloproliferative disorder and the associated hepatosplenomegaly and/or hydrops may show spontaneous remission or that the transient myeloproliferative disorder may be without any detectable ultrasonographic signs and therefore may be more frequent in utero than realized.

Adult↗
PubMed2001

Ductus venosus studies in fetuses at high risk for chromosomal or heart abnormalities: relationship with nuchal translucency measurement and fetal outcome.

OBJECTIVE: To investigate, in a high-risk group of fetuses, the role of ductus venosus Doppler velocimetry as a prognostic factor, in addition to nuchal translucency measurement, for predicting chromosomal anomalies and, where the karyotype was normal, for predicting fetal outcome. METHODS: Nuchal translucency was measured and ductus venosus pulsatility index and late diastolic flow (a-wave) were recorded in 186 fetuses at a median gestational age of 12.6 weeks (range, 10-17). Fetal karyotype, the presence of structural anomalies, pregnancy outcome, neonatal examination at birth and postnatal follow up were the outcome values. RESULTS: Nuchal translucency measurement was increased in 112 fetuses. The outcome of pregnancy was normal in 130 fetuses. Fifty-six fetuses had an adverse outcome (46 chromosomal anomalies, three intrauterine deaths, six structural anomalies and one developmental disorder). The sensitivity of an abnormal ductus venosus pulsatility index or of absent or reversed flow during the a-wave was 65% for chromosomal anomalies and 68% for an adverse outcome. The specificity was 79%. There was a significant correlation between nuchal translucency and ductus venosus pulsatility index. In chromosomally normal fetuses with an enlarged nuchal translucency an abnormal ductus venosus flow was associated with a nearly nine-fold increase in adverse outcome (odds ratio 11.7). CONCLUSION: Ductus venosus Doppler velocimetry can be used in addition to nuchal translucency measurement as a predictor of chromosomal anomalies. However, as the ductus venosus blood flow pattern is correlated with nuchal translucency measurement it cannot be used as an independent variable to reduce the indication for fetal karyotyping. Ductus venosus Doppler velocimetry may have a role in the counseling of parents in the case of an enlarged nuchal translucency and normal karyotype by identifying those fetuses in need of an intensive follow up due to an increased risk of adverse outcome.

Adult↗
PubMed2002

Middle cerebral artery Doppler in fetuses with transposition of the great arteries.

OBJECTIVE: A previous anthropometric study has shown that neonates with transposition of the great arteries have a smaller head circumference and intracranial volume, which may be related to a lower oxygen content of blood delivered to the head and upper extremities. The aim of this study was to compare Doppler blood flow velocity waveforms in fetuses with transposition of the great arteries with those in healthy fetuses. METHODS: Doppler blood flow velocimetry was performed in the middle cerebral artery, the umbilical artery, the aorta and the ductus venosus in a consecutive series of 23 fetuses with transposition of the great arteries between 36 and 38 weeks' gestation. The control group consisted of 40 healthy fetuses matched for gestational age. RESULTS: There was no significant difference in pulsatility indices in the umbilical artery, the aorta and the ductus venosus between fetuses with transposition of the great arteries and controls. The median middle cerebral artery pulsatility index in the group with transposition of the great arteries was 1.37 (range, 1.10-2.02) and was significantly lower than that in the control group (median, 1.68; range, 1.46-2.04) (P < 0.001, Mann-Whitney test). CONCLUSIONS: The lower pulsatility indices observed in the middle cerebral artery of fetuses with transposition of the great arteries may reflect a trend towards cerebral vasodilation. This phenomenon could be an indicator of hypoxemia and/or hypercapnia restricted to areas perfused by the preisthmus aorta and be related to the characteristics of the circulation in fetuses with transposition of the great arteries.

Blood Flow Velocity↗
PubMed2002

Venous Doppler velocimetry in the surveillance of severely compromised fetuses.

OBJECTIVE: To investigate whether venous Doppler velocimetric signs of cardiac decompensation might predict fetal demise in severely compromised fetuses. MATERIAL AND METHODS: This was a prospective study involving 154 growth-restricted fetuses, 37 of which were found to have reversed flow in the umbilical artery (BFC III). Doppler velocimetry of the right hepatic vein and ductus venosus were investigated serially and the presence of umbilical venous pulsations also registered. Only the final examination prior to birth or fetal demise was accepted for analysis and related to obstetric outcome defined as gestational age at birth, birth weight and perinatal mortality. In cases of BFC III the venous velocimetry of 15 nonsurviving fetuses was compared to that of the 22 survivors. RESULTS: There was a significant correlation between venous blood velocity and placental vascular resistance. In the right hepatic vein there was a significant decrease in peak systolic and end-systolic velocities and an increase of maximum velocity during atrial contraction and pulsatility (P < 0.05). A decrease of all velocities and increase of pulsatility were noted in the ductus venosus (P < 0.05). A reversed flow in the ductus venosus was found in 9/37 fetuses and double umbilical venous pulsations in 16/37 fetuses. However, the hepatic vein seemed to be a better predictor of impending mortality than the ductus venosus. Changes in diastolic venous blood velocity and a double pulsation in the umbilical vein were closely related to perinatal mortality, although these parameters did not provide a useful threshold to optimize the timing of delivery. CONCLUSION: Diastolic venous velocimetry changes significantly in severely compromised fetuses. These changes might be of great clinical value in deciding on the timing of delivery to minimize damage to the fetus and newborn.

Blood Flow Velocity↗
PubMed1997

Antenatally detectable markers for the diagnosis of autosomally trisomic fetuses in at-risk pregnancies.

Our aim was to investigate the contribution of certain antenatally detectable markers leading to the diagnosis of trisomic fetuses we observed over a period of 6 years. In our study, we specifically analyzed the role played by advanced maternal age and sonographically discovered abnormalities in the detection of autosomal trisomies. All together, 27 fetuses had this disorder, representing 28.7% (27 of 94) of all cytogenetic aberrations detected at our center over the same period. Down syndrome (12 cases) and Edward syndrome (11 cases) were the most common trisomies, while 4 cases of Patau syndrome were also diagnosed. The most common indication leading to diagnosis was abnormal ultrasound finding (48.2%), followed by advanced maternal age (44.4%). However, 63% of the trisomic fetuses belonged to mothers aged 35 years and above. Down syndrome fetuses (41.7%) had prenatally detected sonographic anomalies, 63.6% for Edward syndrome, and all fetuses with Patau syndrome (4 of 4) showed abnormal sonographic signs. Trisomy 21 presented with the following features: hydramnios, complex malformations, pyelectasis, and duodenal atresia. Trisomy 18 fetuses showed hydramnios, intrauterine growth retardation, microcephaly, spina bifida, and nonimmune hydrops fetalis. Signs observed in fetuses with trisomy 13 were: hydrocephalus, intrauterine growth retardation, oligoanhydramnios, complex malformations, severe fetal bradycardia and hydronephrosis.

Adult↗
PubMed1992

Significance of antenatal detection and the choice of the delivery place of severely small for gestational age fetuses.

The outcome of 72 severely small for gestational age (SGA) fetuses (birthweight below the 2.5 percentile) was compared with the outcome of 144 next-born average for gestational age (AGA) fetuses (birthweight between the 10th and the 90th percentile). Both these groups were matched for gestational age, sex, and maternal parity. The purpose of SGA versus AGA comparison was to allow for discussion on the significance of prenatal diagnosis of severely SGA fetuses in planning an appropriate delivery setting. In this study, SGA fetuses were more often delivered abdominally because of suspected fetal distress; this was especially true of practically all the pre-term SGA fetuses. Severely SGA newborns had more acidosis and they more often needed neonatal intensive care unit (NICU) placement than their AGA counterparts. From these observations, it can be concluded that antenatal detection of severely SGA fetuses seems to be important. Delivery of the severely SGA fetus, moreover, should be scheduled in the hospital setting, where NICU facilities are readily available.

Acidosis↗
PubMed2000

Cardiac structure and function in fetuses of mothers infected with HIV: the prospective PCHIV multicenter study.

BACKGROUND: This study was designed to determine if vertically transmitted HIV infection and maternal infection with HIV are associated with altered cardiovascular structure and function in utero. METHODS: Fetal echocardiography was performed in 173 fetuses of 169 HIV-infected mothers (mean gestational age, 33.0 weeks; SD = 3.7 weeks) at 5 centers. Biparietal diameter, femur length, cardiovascular dimensions, and Doppler velocities through atrioventricular and semilunar valves and the umbilical artery were measured. Measurements were converted to z scores based on published normal data. RESULTS: Fetuses determined after birth to be HIV-infected had similar echocardiographic findings as fetuses later determined to be HIV-uninfected except for slightly smaller left ventricular diastolic dimensions (P =.01). The femur length (P =.03) was also smaller in the fetuses postnatally identified as HIV-infected. Differences in cardiovascular dimensions and Doppler velocities were identified between fetuses of HIV-infected women and previously published normal fetal data. The reason for the differences may be a result of maternal HIV infection, maternal risk factors, or selection bias in the external control data. CONCLUSIONS: Vertically transmitted HIV infection may be associated with reduced left ventricular size but not with altered cardiac function in utero. Fetuses of HIV-infected mothers may have abnormal cardiovascular structure and function and increased placental vascular resistance, regardless of whether the fetuses are subsequently found to be infected with HIV.

Adult↗
PubMed1996

Catecholamine and serotonin concentrations in fetal guinea-pig brain: relation to regional cerebral blood flow and oxygen delivery in the growth-restricted fetus.

To test the hypothesis that intrauterine growth restriction (IUGR) would lead to altered neurotransmitter metabolism in the brain because of poorer oxygenation, blood flows and tissue concentrations of noradrenaline, dopamine, serotonin and their metabolites were measured in 14 parts of the brain of guinea-pig fetuses at 61-64 days' gestation. Eight fetuses with IUGR induced by uterine artery ligation were compared with 8 controls. Regional brain blood flows were determined by the microsphere method and tissue concentrations of monoamines by HPLC with electrochemical detection. The oxygen content of preductal arterial blood was significantly lower in IUGR fetuses than in controls (2.3 +/- 0.6 v. 3.5 +/- 0.5 mM; P < 0.001). Although this was compensated by increases in blood flow to many areas of the brain, significant decreases occurred in oxygen delivery to the temporal and occipital cortex, hippocampus and cerebellum of IUGR fetuses. In contrast, oxygen delivery to brainstem areas was maintained. Noradrenaline concentrations were closely similar in brains from the two groups, except for an increase in the caudate nucleus of IUGR fetuses. Dopamine concentrations were significantly elevated in brainstem areas. Concentrations of 3,4-dihydroxyphenylglycol (DOPEG), a noradrenaline metabolite, and 3,4-dihydroxyphenylacetic acid (DOPAC), a dopamine metabolite, showed a similar pattern of increase in brains of IUGR fetuses, possibly resulting from increased synthesis of noradrenaline and dopamine rather than from decreased degradation. Concentrations of serotonin were significantly higher in frontal and temporal cortex of IUGR fetuses, and the serotonin metabolite 5-HIAA increased significantly in cortical areas. Changes in neurotransmitter metabolism could not be related to oxygen supply, since serotonin concentrations increased in the forebrain, despite reduced oxygen delivery and the known dependence of tryptophan-5-hydroxylase on tissue PO2, and dopamine levels were elevated in the brainstem, where the oxygen supply was maintained.

Animals↗
PubMed2002

Prognostic role of umbilical artery Doppler velocimetry in growth-restricted fetuses.

OBJECTIVE: To correlate umbilical artery Doppler velocimetry with perinatal outcome in a group of growth-restricted fetuses. DESIGN: The study was a retrospective analysis of 578 singleton pregnancies with diagnosis of intrauterine growth restriction (IUGR), delivered in a single obstetric unit, at the Spedali Civili, Brescia, Italy, a university and teaching hospital with 3500 deliveries a year and neonatal intensive care unit (NICU). METHODS: During 1991-99 we studied 578 pregnancies with a diagnosis of IUGR referred for Doppler velocimetry. From this population, four subsets were formed: normal umbilical artery pulsatility index (NUAPI; 334 fetuses); increased pulsatility index but with telediastolic flow (abnormal umbilical artery pulsatility index AUAPI; 137 fetuses); absent end-diastolic flow (AEDF; 70 fetuses); reverse telediastolic flow (RF; 37 fetuses). Fetal biometry, amniotic fluid and fetal-maternal Doppler velocimetry were evaluated in all patients, with biophysical profile and routine non-stress test, when indicated. The following outcomes were examined: mean gestational age at delivery, number of preterm deliveries (< 34 weeks), mean neonatal weight, Apgar score at 5 min < 7, prenatal and neonatal deaths (within the first 28 days of life), admission to the NICU and number of days spent after birth in hospital. Neonatal morbidity was analyzed, including respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH, grade 2-3), necrotizing enterocolitis (NEC) and retinopathy of prematurity. Long-term neurological follow-up is still ongoing and will not be presented in this paper. RESULTS: Out of 578 fetuses with IUGR, 547 were born alive. There were 26 neonatal deaths. The mean gestational age at delivery was 35.6 +/- 4 weeks and mean birth weight 1844 +/- 612 g. There were 28 intrauterine deaths and three elective terminations of pregnancy. A total of 60 cases (11%) were complicated by RDS, 13 cases (2.4%) by retinopathy of prematurity, IVH was present in nine cases (1.6%) and NEC in seven cases (1.3%). Total perinatal mortality was 9.8%; in the 26 cases of neonatal death, the mean week at delivery was 29.6 +/- 4 with a mean weight of 840 +/- 425 g. Patients with NUAPI had a mean week at delivery of 37 +/- 3, those with AUAPI delivered at 34 +/- 3.2, those with AEDF delivered at 31 +/- 3 and those with RF delivered at 29 +/- 2 weeks. In progressively worsening umbilical velocimetry, we observed an increase of incidence of low Apgar score. Days of admission to the NICU and incidence of perinatal mortality increased with the worsening of Doppler velocimetry. CONCLUSIONS: Our study underlines the existence of a strict correlation between umbilical Doppler velocimetry and an increased incidence of perinatal complications in IUGR fetuses.

Blood Flow Velocity↗
PubMed1995

Behavioral state organization in normal human term fetuses: the relationship between periods of undefined state and other characteristics of state control.

Repeated alteration in episodes of quiet sleep and active sleep is a basic feature of behavioral state organization in human fetuses. When compared to normal fetuses, at-risk fetuses generally exhibit extended periods of no coincidence (PsNC), that is, associations between state variables that cannot be classified as a sleep state. The purpose of this study was to determine if fetuses with extended PsNC differ in other state measures from fetuses with short PsNC. Fetal heart rate and fetal eye and gross body movements were collected simultaneously on 85 normal human fetuses between 37 and 41 weeks gestation for a total of 9,135 minutes (mean 108.8 +/- 12.7 minutes, range 85-130 minutes). We found that as percent PsNC increased, the frequency (r = 0.464, p < 0.0001) of state changes increased and the time spent in active sleep (r = -0.456, p < 0.0001) and the number of fetuses entering an awake state (chi 2 = 4.26, p < 0.039) decreased. In contrast, percent PsNC was independent of the length of time spent in quiet sleep (r = 0.070, p > 0.05). We interpret these findings as an indication that extended PsNC may be the result of disruption of homeostatic control mechanisms during active sleep.

Behavior↗
PubMed2001

Maternal endothelial soluble cell adhesion molecules with isolated small for gestational age fetuses: comparison with pre-eclampsia.

OBJECTIVE: 1. To evaluate the activation profile of the endothelium in pregnancies complicated by small for gestational age fetuses compared with pre-eclampsia and normal pregnancy, by measuring the plasma levels of soluble adhesion molecules soluble E-selectin, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1. 2. To determine whether soluble adhesion molecules were related to the severity of small for gestational age fetuses and pre-eclampsia. DESIGN: Observational study. PARTICIPANTS: Sixteen women with small for gestational age fetuses; 15 women with pre-eclampsia and 15 healthy primigravidae were recruited as controls. METHODS: Plasma levels of soluble E-selectin, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 were measured by ELISA. RESULTS: Compared with the healthy controls, soluble E-selectin was significantly increased in both small for gestational age fetuses and pre-eclampsia, whereas intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 were increased only in pre-eclampsia. In the small for gestational age fetuses group, soluble E-selectin correlated inversely with the ratio between birthweight and the expected normal birthweight (r = -0.4, P = 0.007). In the pre-eclampsia group, a significant correlation was observed between vascular cell adhesion molecule-1 and blood pressure (r = 0.54, P = 0.039). CONCLUSIONS: Endothelial activation, reflected by raised levels of soluble E-selectin, is a feature of small for gestational age fetuses and is correlated with the severity of the disease. Differences in the profile of soluble cell adhesion molecules suggest variations in the degrees of endothelial activation between pre-eclampsia and small for gestational age fetuses.

Adult↗