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Biomedical subjects

J G Aarnoudse

Publications and source records attributed to J G Aarnoudse.

At least 19 recordsLinked to original sources
PubMed2001

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.

Chromosome Mapping↗
PubMed2001

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.

Arteries↗
PubMed2001

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.

Birth Weight↗
PubMed2001

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.

Adolescent↗
PubMed2000

Quantification of the diastolic notch in Doppler ultrasound screening of uterine arteries.

OBJECTIVE: To investigate a new method of quantification of the diastolic notch of the flow velocity waveforms of uterine arteries in the prediction of hypertensive disorders of pregnancy. METHODS: Pulsed-wave Doppler was used to obtain flow velocity waveforms (FVWs) from the uterine arteries at 21-22 weeks of gestation from 531 nulliparous women and 94 multiparous women at high risk. From the FVWs, both the pulsatility index (PI) and the notch index (NI) were calculated and the predictive values for both indices were compared using logistic regression analysis for mild and severe early onset hypertensive pregnancy complications. RESULTS: Both the PI and the NI were poor predictors for mild gestational hypertension and pre-eclampsia; predictive values for severe early onset disease, however, were much better. Logistic regression analysis showed the NI has no additional value compared with the PI in the prediction of either mild or severe disease. CONCLUSIONS: The NI offers the possibility to quantify the diastolic notch in uterine artery analysis. Compared to the PI, this does not lead to better predictive values for hypertensive disorders of pregnancy.

Arteries↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Animals↗
PubMed1999

Delayed neuronal migration of protein kinase Cgamma immunoreactive cells in hippocampal CA1 area after 48 h of moderate hypoxemia in the near term ovine fetus.

The brain is uniquely sensitive to disturbances in energy and oxygen supply, particularly during the early stage of life. Since hypoxemia can indirectly activate the intracellular messenger protein kinase C (PKC), we studied the PKCgamma-immunoreaction in the fetal hippocampal CA1 region of naive (n=4), instrumented control (n=7), and instrumented hypoxemic fetuses (n=14), at a mean gestational age of 127 days. Forty-eight hours of mild to moderate hypoxemia, were followed by a 48-h recovery period. Hypoxemia resulted in an increase in carotid blood flow (137% of control), and a shift towards a higher percentage of high-voltage electrocortical activity. After recovery, the fetal brain was fixated by perfusion of both carotid arteries, sectioned and immunostained for PKCgamma. The distribution of PKCgamma-immunoreactive cells was significantly changed after 48 h of hypoxemia in that the migration of cells (from the ventricular region towards the stratum pyramidale) was delayed (p<0.01) compared to naive and instrumented control animals. In contrast to the distribution, the relative total optical density of PKCgamma-ir cells and fibres in the CA1 hippocampal area was not significant different between the animal groups. We conclude that hypoxemia delayed migration of PKCgamma-ir cells, without neuronal degeneration.

Animals↗
PubMed1999

[Obstetric problems followed by stroke].

Obstetrical problems sometimes portend manifestations of atherosclerosis, as illustrated by two case reports. The first patient had the combination of hyperhomocysteinaemia due to chronic vitamin deficiencies in the diet, and smoking. The second was also a smoker and had a genetically determined mild hyperhomocysteinaemia, aggravated by chronic vitamin deficiencies resulting from poor dietary habits; she also had an increased folic acid requirement because of use of anti-epileptic drugs in combination with a familial predisposition for premature atherosclerotic manifestations. The first patient had four pregnancies, two of which ended in intrauterine foetal death due to placental infarction, and one in the birth of a dysmature boy. The second patient's four pregnancies ended twice in abortion and twice in the birth of a dysmature child; in one of the latter cases placental infarction was observed. Both women subsequently suffered cerebrovascular accidents while in addition, older cerebral infarctions were found to be present. Women with recurrent abortion, pre-eclampsia, placental infarction, placental detachment and foetal growth retardation should be examined, even if other risk factors are also present, for (mild) hyperhomocysteinaemia, and treated for it with vitamin suppletion (folic acid, vitamins B6 and B12), even although admittedly more research is necessary to make certain that such treatment has a preventive effect on the manifestations of this disorder.

Abortion, Habitual↗
PubMed1999

Pre-eclampsia and the HELLP syndrome still cause maternal mortality in The Netherlands and other developed countries; can we reduce it?

Maternal mortality in developed countries does not seem to have decreased during the past decade, despite good prenatal care. Hypertensive disorders of pregnancy are the main cause of maternal mortality in most countries. In more than half of these cases, the HELLP syndrome is involved. In this article attention is drawn again to the life-threatening complications that might occur in cases of pre- eclampsia and the HELLP syndrome. Two case histories with fatal outcomes are described to provide extra emphasis. The literature indicates that some cases of maternal mortality might be avoidable. From a review of the literature, suggestions and recommendations are made about how to achieve a decrease in maternal mortality from pre-eclampsia/the HELLP syndrome. The most important are the making of an early, correct diagnosis, anticipating the possibilities of serious complications, and, if necessary, early referral to a regional centre with special expertise.

Adult↗
PubMed1999

Renal responses to prolonged (48 h) hypoxemia without acidemia in the late-gestation ovine fetus.

The effect of sustained moderate hypoxia on renal blood flow and renal function was studied in the ovine fetus (123-129 days). The experiments consisted of 48 h of isocapnic hypoxia, not resulting in acidemia, but sufficient to produce redistribution of blood flow in favor of the brain at the expense of the carcass. Hypoxemia was induced by maternal nitrogen inhalation. Fetal arterial O(2) saturation and arterial O(2) pressure (Pa(O(2))) decreased from, respectively, 50.6 +/- 3.0% and 17.2 +/- 0.9 mmHg during control to 36.4 +/- 2.7% and 13.4 +/- 0.7 mmHg on the first and to 32.2 +/- 2. 2% and 12.4 +/- 0.7 mmHg on the second day of hypoxemia. Fetal renal blood flow and urine production rate were continuously measured using ultrasonic flow transducers. Fetal renal blood flow increased during hypoxemia from 11.8 +/- 1.6 to 15.6 +/- 1.8 ml/min and remained elevated throughout the 48-h hypoxemia period (P < 0.01). Renal blood flow was inversely correlated with fetal Pa(O(2)) (r is -0.69, P < 0.0001). Fetal urine production rate, glomerular filtration rate, filtration factor, osmotic clearance, and free water clearance did not significantly change from control values during hypoxemia or recovery. We conclude that hypoxemia without acidemia results in an immediate and considerable increase in fetal renal blood flow, which remains elevated for the entire hypoxemic period.

Acids↗
PubMed1998

Perinatal changes in myocardial supply and flux of fatty acids, carbohydrates, and ketone bodies in lambs.

No information is available on perinatal changes in myocardial metabolism in vivo. We measured myocardial supply and flux of fatty acids, carbohydrates, and ketone bodies in chronically instrumented fetal, newborn (1-4 days), and juvenile (7 wk) lambs, by measuring aorta-coronary sinus concentration differences and blood flow. In the fetal lambs, myocardial supply and flux of fatty acids were zero. In the newborn lambs, the supply of fatty acids increased tenfold, but there was no flux of fatty acids. Carbohydrates were the major energy source in fetal and newborn lambs, accounting for 89 and 69% of myocardial oxygen consumption, respectively. In the juvenile lambs, the flux of fatty acids was increased threefold. The supply and flux of carbohydrates were decreased (by 31 and 82%, respectively). The supply and flux of ketone bodies gradually increased with age. We show that the myocardium of the lamb in vivo does not switch immediately after birth from carbohydrates to fatty acids. The mechanisms involved in the development of myocardial fatty acid oxidation remain to be elucidated.

Age Factors↗
PubMed1998

Urine production rate and renal blood flow in the near-term ovine fetus are not related to high and low voltage electrocortical activity.

Studies in both the human and ovine near-term fetus have identified the clustering of physiologic and behavioral parameters into states. In a recent study in the human fetus a considerable decrease was found in fetal urine production during non-rapid eye movement (non-REM) compared with REM sleep. Whether this decrease was caused by decreased renal blood flow or changes in urine concentration is not known. This prompted us to investigate the relation between fetal urine production rate and electrocortical activity in the near-term ovine fetus. We hypothesized that in the ovine fetus urine production and renal blood flow during REM [comparable to low voltage electrocortical activity (LV ECoG)] would be lower than during non-REM [(high voltage (HV) ECoG)]. In eight fetal sheep between 123 and 127 d of gestation (term 147 d), ECoG, renal blood flow, urine flow, and urine osmolality were measured continuously for 6 h on 2 consecutive days. Data were analyzed into HV ECoG and LV ECoG whereafter urine flow, urine osmolality, and renal blood flow data were averaged per state. We found no significant differences in urine flow, urine osmolality, or renal blood flow between the two behavioral states in the ovine fetus. Because these data are in sharp contrast to those found in the human fetus, we conclude that the observed dissimilarities in renal responses between the human and sheep fetus add to the already known differences in behavioral states between the two species.

Animals↗
PubMed1997

Effect of location of the sensor on reflectance pulse oximetry.

OBJECTIVE: The influence of the location of the sensor on reflectance pulse oximetry during fetal monitoring in labour was investigated using the newborn infant as a model. METHODS: Seven healthy infants were studied between 19 and 48 hours after term delivery. Recordings of reflectance pulse oximetry were obtained from eight different sites on the infant's head. The relative changes in red to infrared light (R/IR) were determined. In pulse oximetry R/IR values are converted to arterial oxygen values by means of an empirically derived calibration curve. RESULTS: Significantly lower R/IR values were found at the forehead compared with the fontanelle, the parietal and occipital position, and the temporal area. Conversion to oxygen saturation values revealed a difference of up to 13.4% in oxygen saturation between the forehead and the occipital area. CONCLUSION: Assuming that the arterial blood oxygen saturation did not change substantially, our findings indicate that in reflectance pulse oximetry there is no unique relation between R/IR and arterial oxygen saturation. The differences in reflectance pulse oximetry at the various sites are explained by differences in optical properties (scattering and absorption) of the tissue underneath the sensor. These will affect the red and infrared light reaching the detectors in a different way, and consequently R/IR changes. Because during intrapartum monitoring exact positioning of the sensor on the fetal head is usually impossible, the accuracy of fetal reflectance pulse oximetry is impaired.

Fetal Monitoring↗
PubMed1996

[Liver rupture in pregnancy: a life-threatening complication of the HELLP syndrome].

A 31-year-old primigravida with pre-existent hypertension was admitted at 28.5 weeks gestation with foetal growth retardation. On the third day after admission she developed a 'haemolysis, elevated liver enzymes and low platelets' (HELLP) syndrome with severe pain in the epigastrium. Intrauterine death had occurred and abruptio placentae was suspected. Induction of labour was started with intravenous prostaglandins. The next day the haemoglobin concentration had decreased despite transfusions of red blood cell concentrates. At ultrasound examination, free fluid was detected in the abdomen and at explorative laparotomy a subcapsular liver haematoma appeared to have ruptured. An intrahepatic haematoma does not require operative treatment, unless it has ruptured. Packing of the ruptured liver with gauze and later removal of the gauze is preferable to lobectomy.

Adult↗