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Biomedical subjects

G Haugen

Publications and source records attributed to G Haugen.

At least 19 recordsLinked to original sources

Prenatal diagnosis of congenital malformations and parental psychological distress--a prospective longitudinal cohort study.

OBJECTIVE: To test whether postnatal psychological distress in parents of babies with congenital malformations is reduced by prenatal diagnosis. METHODS: A prospective observational longitudinal cohort study was conducted at two Norwegian hospitals. We included 293 parents of babies with congenital malformations (prenatal detection rate: 36.5%) referred for neonatal surgery and 249 parents of healthy babies (comparison group). Parental psychological responses were assessed on three postnatal occasions by psychometric instruments (GHQ-28, STAI-X1, and IES). RESULTS: Significantly increased psychological distress (GHQ-28) was reported by parents who received prenatal diagnosis as compared to postnatal diagnosis; acutely 28.9 versus 24.4, P = 0.006 (comparison group: 19.6); at 6 weeks 26.8 versus 21.5, P < 0.001 (comparison group: 17.7); and at 6 months 22.6 versus 18.7, P = 0.015 (comparison group: 16.6). Mothers consistently reported higher levels of distress than fathers. Multiple linear regression analysis showed that prenatal diagnosis and being a mother significantly predicted severity of acute psychological distress. At 6 weeks and 6 months, mortality and associated anomalies were significant independent predictors of psychological distress. CONCLUSION: Controlling for other covariates, we found that prenatal diagnosis of congenital malformations was a significant independent predictor of acute parental psychological distress after birth.

Adult↗

Correlation between prenatal ultrasound and autopsy findings: A study of second-trimester abortions.

OBJECTIVE: To evaluate discrepancies between sonographic and autopsy findings following termination of pregnancy (TOP) in the second trimester. METHODS: This retrospective report is based on 288 consecutive second-trimester abortions carried out because of fetal malformations diagnosed by ultrasound examination at a tertiary referral center. The correlation between the results from the ultrasound and autopsy examinations was evaluated. RESULTS: Autopsy was performed in 274 cases. In 160 of the 274 pregnancies (58.4%) there was full agreement between the two examination methods. Findings detected by autopsy (in addition to those leading to termination) were not observed by ultrasonography in 86 (31.4%) of the pregnancies; of the 64 malformations that occurred, 30 (46.9%) were judged as 'detectable'. In 27 (9.9%) pregnancies, observations made by ultrasound (in addition to those leading to termination) were not confirmed at autopsy. In one pregnancy, postmortem radiology examination-but not autopsy-confirmed the ultrasound observations. No pregnancies were terminated because of false positive ultrasound observations. The correlation between ultrasound and autopsy findings was evaluated by three investigators; the inter-rater agreement was high (kappa = 0.85). CONCLUSION: Discrepancies between ultrasound and autopsy findings were observed in about 40% of the pregnancies. These discrepancies confirm the need for autopsy following TOP.

Abnormalities, Multiple↗

Portal and umbilical venous blood supply to the liver in the human fetus near term.

OBJECTIVES: To determine the contribution of the umbilical (UV) and portal (PV) veins to blood supply to the human fetal liver in a low-risk population near term, and to assess the distribution between the left and right lobes. METHODS: In 91 low-risk pregnancies with normally grown fetuses at 36 weeks of gestation we measured the distribution of blood in the UV and PV to the right and left hepatic lobes using ultrasound imaging and Doppler techniques. RESULTS: The median (10(th), 90(th) centile) total UV return was 205 (127, 294) mL/min, of which 25% (13, 47%) was shunted through the ductus venosus, 55% (35, 66%) was distributed to the left hepatic lobe, and 20% (11, 30%) was distributed to the right hepatic lobe. While the left lobe was supplied exclusively by the UV, the right lobe received 50% (20, 70%; 37 (16, 65) mL/min) of its venous blood supply from the PV. The total venous blood supply to the liver parenchyma was 185 (114, 277) mL/min; 21% (8, 34%) came from the PV supply to the right lobe and the remainder came from the UV supply to both lobes. CONCLUSIONS: The venous supply to the left lobe is from nutrient-rich UV blood; for the right lobe, half is from UV blood and half from nutrient-poor PV blood. This watershed between the portal and umbilical venous flows to the fetal liver suggests a corresponding functional dichotomy; this may be modified by hemodynamic influences, with long-term consequences.

Adult↗

Doppler blood flow velocity waveforms in the fetal renal arteries: variability at proximal and distal sites in the right and left arteries.

OBJECTIVE: To investigate variability in pulsatility/resistance indices and absolute velocities of blood flow in fetal renal arteries dependent on side and sampling site within each vessel. METHODS: Doppler blood flow measurements of pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV) and end-diastolic velocity (EDV) were performed in the renal arteries of 27 fetuses between 236 and 247 days of gestation. Velocity waveforms were sampled in both the right and left renal arteries at two different sites: proximally, close to the aorta, and distally, before any major visible bifurcation of the vessels. The intraobserver variation was measured in 15 additional fetuses. RESULTS: Mean values of PI and RI were similar in the right and left renal arteries and at the proximal and distal sampling sites of these arteries. Mean PSV and EDV were higher at the proximal compared to the distal site on both sides. For all parameters the 95% limits of agreement between measurements made in the right and left arteries and at proximal and distal sites were wide but tended to be narrower for the left renal artery and at the distal site. Intraclass correlation coefficients for intraobserver variability were 0.88, 0.89, 0.83 and 0.81 for PI, RI, PSV and EDV, respectively. CONCLUSIONS: It is important to standardize the precise site at which Doppler blood flow velocity waveform measurements are made in the renal arteries of the fetus. On the basis of our observations, we suggest that the left renal artery is the preferred vessel for sampling and that measurements should be made in the renal arterial trunk away from the aorta and before any visible branches.

Blood Flow Velocity↗

Doppler flow velocity waveforms and vasoactive effects of serotonin in human umbilical arteries.

The vasoactive effect of serotonin was investigated by in vitro perfusion in human umbilical arteries in which antenatal Doppler ultrasound examination revealed abnormal velocity waveforms. The results were compared to those obtained in preparations from normotensive uncomplicated term pregnancies as well as from preterm deliveries in which antenatal Doppler ultrasound examination showed normal velocity waveforms related to gestational age. Serotonin induced a monophasic vasoconstriction or a biphasic pressure response with a transient pressure decrease succeeded by a constrictory response. In all groups serotonin induced a significant (p < 0.001) constrictory response, whereas no significant differences were observed between the groups. At a serotonin dose of 10(-7) mol/l, the frequency of preparations with a biphasic pressure response was significantly smaller in the preparations with abnormal diastolic flow as compared to the term control group (5/18 vs. 13/19, p = 0.02), but not significantly different from that of the preterm control group (3/9). The umbilical arterial responsiveness to serotonin does not seem to be dependent on antenatal Doppler velocity waveforms.

Adult↗

Influence of preeclampsia or maternal intake of omega-3 fatty acids on the vasoactive effect of prostaglandin F-two-alpha in human umbilical arteries.

The vasoactive effect of prostaglandin F(2alpha) (PGF(2alpha)) was studied in in vitro perfused human umbilical arteries following maternal dietary supplementation with omega-3 fatty acids or in pregnancies complicated by a moderate degree of preeclampsia. In most preparations PGF(2alpha) induced a biphasic pressure response with a transient dilatation followed by a constrictory response. The pressure increase was significant in both groups, but no significant differences in the constrictory response or in the proportions of preparations displaying dilatatory responses were observed when compared to appropriate control groups. In conclusion, neither preeclampsia nor dietary supplementation with cod-liver oil had any significant effect on the vasoactive response to PGF(2alpha) in umbilical cord arteries.

Analysis of Variance↗

Haplotype association and mutation analysis of the transglutaminase 1 gene for prenatal exclusion of lamellar ichthyosis.

Lamellar ichthyosis (LI) is an autosomal recessive keratinization disorder of the skin. Genetic heterogeneity has been shown for the disease and there is evidence for the involvement of the transglutaminase 1 (TGM1) gene on chromosome 14q11. We have previously identified chromosome 14q11 haplotypes associated with ichthyosis in the Norwegian population. In this paper we describe antenatal exclusion of ichthyosis in two Norwegian families by chromosome 14q11 haplotype association and direct mutation analysis. In one pregnancy, the 11-week old fetus at risk for LI was found to share only one disease-associated haplotype. A subsequent mutation analysis of the TGM1 gene in fetal DNA revealed that the fetus carried a novel 3795A-->T transversion. The affected proband was compound heterozygous for the mutations 3795A-->T and 3239G-->C resulting in an Asp430Val and a Val379Leu, respectively. In another LI family, the 11-week old fetus was found to be heterozygous for the 14q11 haplotype associated with the disease. Subsequent mutation analysis revealed that the fetus was heterozygous for the 2526A-->G transition in the splice site of intron 5 whereas the proband was homozygous for the same mutation. Our results show that haplotyping can be a useful tool for prenatal diagnosis in diseases with genetic heterogeneity.

Chromosomes, Human, Pair 14↗

Prenatal diagnosis of tracheal obstruction: possible association with maternal pertussis infection.

A fetus with the sonographic appearance of echogenic and enlarged lungs and dilated trachea and bronchi, indicating laryngotracheal obstruction, is reported. Additionally, the fetus had ascites and subcutaneous edema and the amniotic fluid volume was reduced. Doppler flow investigation of the systemic venous circulation revealed signs of heart failure, and color Doppler visualized possible increased pulmonary flow. Following termination of pregnancy, autopsy confirmed the sonographic observations and revealed a hypoplastic thymus. During the present pregnancy the mother suffered from sustained cough, and serological tests revealed acute pertussis infection. Polymerase chain reaction investigation for Bordetella pertussis in the amniotic fluid was negative. The possibilities of pertussis toxins as noxious factors and of an atypical presentation of DiGeorge anomaly are discussed.

Abortion, Therapeutic↗

Congenital diaphragmatic hernia: a meta-analysis of mortality factors.

PURPOSE: The aim of this study was to review all available studies reported in the English-language literature from 1975 through 1998, and by meta-analysis assess the importance of prenatal diagnosis, associated malformations, side of hernia, timing of surgery, and study population on mortality rates in patients with congenital diaphragmatic hernia (CDH). METHODS: One-hundred-two studies were identified, and 51 studies (2,980 patients) fulfilled the prespecified inclusion criteria. Studies were grouped according to study population into: (I) fetuses diagnosed prenatally; (II) neonates admitted to a treatment center; and (III) population-based studies. RESULTS: Pooled total mortality rate was significantly higher in category I than in category III (75.6% v 58.2%, P < .001). Pooled hidden postnatal mortality rate (deaths before admittance to a treatment center) in population-based studies was 34.9%. Prenatally diagnosed patients in both category II and III had significantly higher mortality rates than those diagnosed postnatally. Mortality rates were significantly higher among CDH infants with associated major malformations compared with isolated CDH in all 3 categories. An increased mortality rate in right-sided CDH was found in category II and III. CONCLUSIONS: Prenatal diagnosis of CDH, presence of associated major malformations, and the study population have a major influence on mortality rate. The very high mortality rate in studies of fetuses with a prenatal diagnosis of CDH should be taken into account in prenatal counselling.

Abnormalities, Multiple↗

Hemostatic variables as independent predictors for fetal growth retardation in preeclampsia.

BACKGROUND: Preeclampsia is a major contributor to perinatal disease and fetal growth retardation (FGR). It has been suggested that increased intravascular coagulation, fibrin deposition in spiral arteries and hypoperfusion of the placenta are involved in these pregnancy complications. METHODS: Multiple variables of the hemostatic system and lipid metabolism, as well as clinical features, were entered into univariate and multivariate models in order to examine the association with preeclampsia and FGR. RESULTS: Two hundred women with preeclampsia and 97 normotensive pregnant women were examined. Plasma levels of the thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor free antigen (TFPI-Fag), protein S free antigen, plasminogen activator inhibitor type-1 (PAI-1) activity and serum levels of triglycerides were significantly increased, whereas plasma levels of antithrombin (AT), fibrinogen, C4b-binding protein (C4b-BP), PAI-2 antigen and serum HDL-cholesterol levels were decreased in the presence of preeclampsia. In the multivariate regression analysis, high TFPI-Fag plasma levels were associated with the presence of preeclampsia. The presence of FGR was in the univariate analysis associated with decreased PAI-1 activity and lower concentrations of fibrin, fibrinogen, factor VII antigen and PAI-2 antigen, as well as with evidence of macroscopic placental infarction. In a multivariate regression model, low maternal weight, placental infarction and low PAI-2 levels were predictors for low birth weight. In a logistic regression model, with the presence or absence of FGR as the dependent variable, male sex of the infant, placental infarction, low PAI-1 activity and factor VII antigen or PAI-2 antigen levels were independent predictors. CONCLUSIONS: Our results are consistent with activated coagulation in the placental vessels in preeclampsia. A low concentration of PAI-2 antigen in plasma emerged as the most consistent risk factor for preeclampsia and FGR.

Adolescent↗

In vitro perfusion studies of single umbilical artery cords: the vasoactive effects of serotonin.

BACKGROUND: To investigate the vascular resistance and the vasoactive effects of serotonin in arteries from single umbilical artery (SUA) cords. METHODS: The preparations were sampled from 10 patients with SUA cords. The control group (n=20) was matched according to gestational age, birth weight percentile, blood pressure and proteinuria. The arterial segments were perfused in vitro employing a constant perfusion rate and measuring alterations in perfusion pressure. Following an initial test with serotonin 10(-7) M the drug was administrated in stepwise increasing concentrations from 10(-10) to 10(-5) M. RESULTS: The vascular resistance was significantly reduced in the SUA group compared to the control group (p<0.01). In about half of the preparations in both groups serotonin 10(-7) M induced a transient pressure decrease followed by a larger pressure increase. The remaining arteries showed a monophasic pressure increase. The maximum constrictory response calculated in percent of the prestimulatory perfusion pressure was significantly increased (p<0.01) in the SUA compared to the control group, but non-significantly increased (p=0.073) when calculated in absolute values (mmHg). CONCLUSIONS: Arteries in SUA cords display reduced vascular resistance compared to arteries from normal cords in in vitro perfused preparations. The response pattern to serotonin was not altered, but the constrictory response might be increased in arteries from SUA cords.

Adult↗

Consequences of prenatal ultrasound diagnosis: a preliminary report on neonates with congenital malformations.

OBJECTIVE: The aim of the present study was to examine the sensitivity of prenatal ultrasound diagnosis in neonates referred for surgery, and to test whether a prenatal versus postnatal diagnosis influenced mode of delivery and neonatal outcome of these infants. PATIENTS: Thirty-six consecutive neonates with congenital diaphragmatic hernia, abdominal wall defects, bladder exstrophy and meningomyelocele were included. RESULTS: The sensitivity of prenatal ultrasound for diagnosis of the congenital malformations was 7/36 (19%) at 17-18th week of gestation, and overall 13/36 (36%). Overall sensitivity was 2/8 in neonates with congenital diaphragmatic hernia, 6/12 in neonates with abdominal wall defects, 5/13 in neonates with meningomyelocele, whereas none of three cases with bladder exstrophy were detected prenatally. No significant improvement in neonatal morbidity was found comparing the prenatally and postnatally diagnosed groups. The neonatal survival rate was 10/13 (77%) in the prenatally diagnosed group and 22/23 (96%) in the postnatally diagnosed group (p=0.12). CONCLUSIONS: The sensitivity of prenatal ultrasound in diagnosing the congenital malformations under study in a low risk population was 19% at 17-18th week of gestation and 36% throughout the pregnancy. Prenatal diagnosis altered management of labor, but caused no improvement in neonatal outcome.

Congenital Abnormalities↗

Characterization of the vasodilatatory response to serotonin in human umbilical arteries perfused in vitro. The influence of the endothelium.

In most preparations of human cord arteries perfused in vitro, infusion of 10(-7) M of serotonin leads to a biphasic pressure response starting with a transient minor vasodilatation followed by a dominant vasoconstriction. In some preparations, however, the vasoconstrictive part of the response with this dose of serotonin is less pronounced or completely absent, whereas the dilatation is stronger and more prominent. The present study deals exclusively with experiments on cord arteries displaying the latter type of serotonin reactivity, and was undertaken in order to characterize the relaxing effect of serotonin, and in particular, the role of the endothelial layer. This was accomplished by studying the response pattern before and after treatment with different drugs or removal of the endothelium. The vasodilatatory action of serotonin was found to be abolished following treatment with methysergide, significantly reduced after denudation (P <0.05), slightly reduced after exposure to methylene blue or N omega-nitro-L-arginine methyl ester (L-NAME) (non-significantly), but not affected by indomethacin. The results suggest that the relaxing effect is mediated by specific serotonin receptors and that endothelium-derived substances, possibly including nitric oxide, are involved.

Dose-Response Relationship, Drug↗

Plasma concentrations of Lp(a) lipoprotein and TGF-beta1 are altered in preeclampsia.

This study was performed to investigate the possible association between preeclampsia and the plasma concentrations of Lp(a) lipoprotein and TGF-beta1 in a large series of patients. Additionally, correlation between the concentrations of these molecules and the severity of preeclampsia or fetal growth retardation was evaluated. Following clinical examination and biochemical analyses, both electroimmunoassay and RIA technique were used for quantitative determinations of plasma Lp(a) lipoprotein. ELISA technique was used to measure the active form of TGF-beta1 in plasma of pregnant normotensive and preeclamptic women. We examined 154 women with preeclampsia (preeclampsia group) and 76 healthy, pregnant normotensive women (control group). The preeclampsia group was further divided into the following subgroups: mild preeclampsia, severe preeclampsia and preeclampsia with fetal growth retardation. Plasma levels of Lp(a) lipoprotein were lower in the total preeclampsia group as well as in all preeclampsia subgroups (5.45+/-7.41, 5.58+/-8.02, 5.08+/-5.38, and 4.32+/-5.28 mg/dl in the total preeclampsia group, and in subgroups with mild preeclampsia, severe preeclampsia, and preeclampsia with fetal growth retardation, respectively) than in the control group (7.84+/-9.26 mg/dl) as determined by quantitative electroimmunoassay. Corresponding results were obtained with a radioimmunoassay (166.03+/-200.2 U/l in the total preeclampsia group vs. 229.18+/-257.7 U/l in controls). There was good correlation between the two methods used for Lp(a) lipoprotein measurement. The differences between controls and the total preeclampsia group as well as each preeclampsia subgroup were statistically significant by a non-parametric test (one-way Kruskal-Wallis test). Plasma concentrations of the active form of TGF-beta1 were increased in all preeclampsia subgroups as well as in the total group (5.63+/-1.68 ng/ml) compared to controls (4.67+/-1.33 ng/ml). This increase in TGF-beta1 was statistically highly significant. Plasma concentrations of Lp(a) lipoprotein and the active form of TGF-beta1 did not differ significantly between the preeclampsia subgroups. The outcome of this study may suggest involvement of both parameters in the pathophysiology of preeclampsia and may substantiate the notion of a multifactorial etiology of the disease.

Adult↗