Fetal isovolumetric contraction time in a case of fetal tachyarrhythmia.
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Echocardiography, Doppler↗
Biomedical subjects
B Trudinger
Publications and source records attributed to B Trudinger.
Egr-1 transcription activation exists in placental endothelium when vascular disease is present.
OBJECTIVE: To seek evidence of early vascular injury in the placental villous microcirculation in placental insufficiency identified by a high-resistance umbilical Doppler study by examining for expression of fibroblast growth factor receptor-1 (FGFR-1), its transcription factor, early growth response factor-1 (Egr-1) and plasma fibroblast growth factor-2 (FGF-2). DESIGN: Case-control study. SETTING: University teaching hospital. SAMPLE: Placentas and umbilical vein blood were collected at delivery from 12 women with normal pregnancy delivered at term and 14 with placental vascular disease defined by an abnormal umbilical artery Doppler study. METHODS: Microvascular endothelial cells were isolated from fresh human placentas using collagenase digestion and Dynabeads coated with monoclonal antibody against CD31. RNA was extracted from the isolated endothelial cells. The messenger RNA (mRNA) expression of FGFR-1 and Egr-1 production were assessed by reverse transcription polymerase chain reaction and factored relative to 18S ribosomal RNA. To confirm that FGF-2 was playing a significant role in this microvascular endothelial cell injury in the placenta, we also measured the soluble fraction of FGF-2 in fetal plasma from same groups of pregnancies using an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Microvascular endothelial cells expression of Egr-1mRNA, FGFR-1 mRNA and presence of soluble FGF-2 in fetal plasma. RESULTS: The soluble level of FGF-2 in the fetal placental circulation from pregnancy with placental vascular disease was increased when compared with normal pregnancy (median 10.15 pg/ml and interquartile range 5.34-21.83 pg/ml versus 4.46 pg/ml and 3.69-5.66 pg/ml; P < 0.05). Microvascular endothelial cells from the placental villi with placental vascular disease showed upregulation of both FGFR-1 mRNA expression (median 0.72 and interquartile range 0.40-1.64 versus 0.34 and 0.19-0.71; P<0.05) and Egr-1 expression (median 0.79 and interquartile range 0.27-1.86 versus 0.23 and 0.17-0.67; P<0.05) in comparison with normal pregnancy. CONCLUSIONS: Endothelial cells from the placental villi are upregulated for expression of Egr-1 transcription factor gene in placental vascular disease. The FGFR-1 activation and increase in FGF-2 in the fetal circulation are known to be very early features of the response of endothelium to injury. Egr-1 is a promoter of many key pathophysiologically relevant target genes, which influence the development of subsequent vascular lesions. This change may occur before the pathological features recognised on microscopy.
Case-Control Studies↗
Sexual behaviour and social class in Australian women.
Sexual behaviour is determined by social, cultural and personal factors. Sexual behaviour studies have been conducted in many countries. However, information from Australia is limited. This study was conducted in Obstetrics Department, Westmead Hospital, Sydney. Questionnaire-derived demographic and behavioural characteristics for public and private patients were compared using bivariate and logistic regression analyses. Of the patients, 3036 were public, and 595 private. On bivariate analysis some significant differences were private patients more likely to be born in Australia and have a higher education level whereas public patients were more likely to have had a greater number of lifetime sexual partners and younger age at first sex. Public patients were more likely to be herpes simplex virus type 2 (HSV-2) antibody positive (12%) than private patients (6%). On logistic regression significant variables included country of birth, being HSV-2 antibody positive, and age at first sex. A number of sexual and social variables were significantly different, comparing patients in the public and private sectors. Evaluation of interventions to reduce the sexual risk to women in the public sector should be considered, including encouraging young women to delay their sexual debut, and reducing the number of sexual partners.
Adolescent↗
Antenatal prediction of hypertrophic pyloric stenosis.
This is the first reported case where the diagnosis of hypertrophic pyloric stenosis (HPS) was entertained in the antenatal period and the neonate was followed up in the postnatal period on a prospective basis until the HPS became manifest.
Adult↗
A new and simple Doppler method for measurement of fetal cardiac isovolumetric contraction time.
OBJECTIVES: The fetal cardiac isovolumetric contraction time is defined as the interval between mitral valve closure and aortic valve opening. The objective of this study was to develop a simple and reliable Doppler method for measuring fetal isovolumetric contraction time using a digital filtering and processing system. METHODS: Cardiac Doppler signals were recorded from 40 fetuses at 18-40 weeks' gestation using a continuous-wave ultrasound transducer. The raw signal was digitized, filtered and divided into five different frequency ranges: 250-375, 375-500, 500-750, 750-1000 and 1000-1500 Hz. To determine the most suitable filter setting for detecting mitral valve closure and aortic valve opening signals, we examined whether they were detected clearly in each filter range. RESULTS: Both mitral valve closure and aortic valve opening signals were detected clearly in the 500-1000 Hz range. The atrioventricular flow and outflow noises in the 250-500 and 1000-1500 Hz ranges helped us to identify the signals. It was found that dividing the raw signals into three ranges of 250-500, 500-1000 and 1000-1500 Hz was the most suitable digital-filter setting for measuring isovolumetric contraction time. CONCLUSIONS: We have developed a simple Doppler method for measuring fetal isovolumetric contraction time. The advent of digital processing has simplified the equipment and the simultaneous multidisplay of three different filtered signals enables easy and accurate measurement.
Aortic Valve↗
The fetal cardiac isovolumetric contraction time in normal pregnancy and in pregnancy with placental vascular disease: the first clinical report using a new ultrasound technique.
OBJECTIVE: To study the fetal cardiac isovolumetric contraction time in normal and complicated pregnancies with placental vascular disease using a newly developed digital Doppler cardiography system. DESIGN: A preliminary case-control study. SETTING: Tertiary referral hospital. SAMPLE: One hundred and sixteen normal fetuses (20 to 40 weeks) and 55 complicated pregnancies with placental vascular disease as documented by a high systolic: diastolic ratio in the umbilical artery Doppler flow study. METHOD: A digital Doppler cardiography system with a high sampling rate (4,000 Hz) was used to detect the fetal cardiac valvular movements. The isovolumetric contraction time was measured as the interval between the mitral valve closing and the aortic valve opening with a built-in scale device. RESULTS: In normal pregnancy the isovolumetric contraction time remained remarkably constant with gestation and fetal heart rate. Comparison between clinical outcome and the isovolumetric contraction time of the complicated fetuses who were born within a week after the last determination of the isovolumetric contraction time revealed a strong correlation between prolonged isovolumetric contraction time duration and abnormalities in the perinatal course (non-reactive fetal heart rate pattern, low pulsatility index in the fetal middle cerebral artery Doppler flow and low birthweight infant). CONCLUSIONS: The isovolumetric contraction time is constant with gestation and fetal heart rate in normal pregnancy. In the presence of placental vascular disease a prolonged fetal isovolumetric contraction time predicts adverse outcome.
Case-Control Studies↗
Sexual and demographic risk factors for herpes simplex type 1 and 2 in women attending an antenatal clinic.
OBJECTIVE: To establish risk factors for the presence of HSV-2 and HSV-1 infections in pregnant women. DESIGN, POPULATION, AND SETTING: A prospective study of 3306 women attending the antenatal department Westmead Hospital, Sydney, between June 1995 and April 1998. METHODS: Women completed a self administered questionnaire to establish risk factors for the presence of HSV-2 and HSV-1. Sera were tested for antibodies to HSV-2 and HSV-1. Data were analysed using SPSS and SAS. MAIN OUTCOME MEASURES: Seroprevalence of and risk factors for HSV-2 and HSV-1. RESULTS: 375 (11.3% (95% CI 10.3-12.5)) women were HSV-2 antibody positive. Increasing age, Asian country of birth, lower education level, public hospital status, confirmed genital herpes, a partner with genital herpes, early age of first sex, more than one lifetime sexual partner, and previous chlamydia infection were independently associated with HSV-2 seropositivity. Of 408 women tested for HSV-1 antibodies, 323 (79.2% (95% CI 74.9-83.0)) were positive. Oral herpes, oral blisters or sores, and being HSV-2 seropositive were independently associated with HSV-1 seropositive status. When the logistic regression model was rerun without HSV-2 status, parity of two or more and one or more sexual partners in the past 3 months were significant predictors of HSV-1 seropositivity. CONCLUSIONS: The presence of antibodies to HSV-2 and HSV-1 is related to a number of sexual and demographic risk factors. Public health campaigns directed at encouraging young people to delay the onset of sexual activity and reduce the number of sexual partners need to be evaluated. However, the possible availability of an HSV-2 vaccine that is able to protect over 70% of women offers the best hope for control of genital herpes.
Adolescent↗
Genotype dependent and cigarette specific effects on endothelial nitric oxide synthase gene expression and enzyme activity.
We explored the interactive effects of endothelial nitric oxide synthase (eNOS) genotypes and cigarette smoking on protein levels and enzyme activity in 33 postpartum placentas. Whilst the eNOS protein levels were lower in the rare allele (0.48+/-0.11, n=9 vs. 1. 05+/-0.10, n=24, P<0.01), the eNOS enzyme activity was about 7-fold higher in the rare allele (4556.2+/-255.4 vs. 621.8+/-180.5 cpm/mg/min, P<0.01). Smokers had lower eNOS protein levels (1.07+/-0. 09 vs. 0.50+/-0.19, P<0.05) in both alleles. It reduced the eNOS activities only in the rare allele (non-smokers: 6143.8+/-251.2, n=5, smokers: 2968.5+/-259.4, n=4, 52% reduction, P<0.01). We conclude that associations between eNOS polymorphism and protein levels and enzyme activities are modifiable by smoking, the effects of smoking are dependent on the eNOS genotypes.
Female↗
Is an atherogenic lipoprotein profile in the fetus a prerequisite for placental vascular disease?
OBJECTIVE: To measure the blood apolipoprotein A-1 and apolipoprotein B in the fetal circulation in normal pregnancy and in pregnancy with evidence of vascular disease in the fetal umbilical placental circulation defined in the antenatal period by Doppler ultrasound study. DESIGN: An observational study to compare fetal plasma apolipoprotein levels in normal and complicated pregnancy. SETTING: A university hospital tertiary referral obstetric unit. SAMPLES: Umbilical vein blood was collected at delivery from 22 normal fetuses delivered by elective caesarean section for non fetal reasons and 30 fetuses with evidence of umbilical placental vascular disease identified antenatally by Doppler ultrasound study. METHODS: Plasma apolipoprotein A-1 and B were determined using an enzyme-linked immunosorbent assay (ELISA) methods. MAIN OUTCOME MEASURES: Fetal plasma levels of apolipoprotein A-1 and B were measured. RESULTS: There was a significantly lower level of fetal plasma apolipoprotein A-1 in placental insufficiency [placental insufficiency vs normal pregnancy, median 0.30 g/L (interquartile range 0.24, 0.39 g/L) vs 0.35 g/L (0.31, 0.42 g/L), P = 0.045]. In contrast, the levels of fetal plasma apolipoprotein B in placental insufficiency [0.20 g/L (0.17, 0.26 g/L)] were significantly increased compared with normal pregnancy [0.16 g/L (0. 14, 0.20 g/L), P = 0.03]. The ratio of fetal plasma apolipoprotein B to A-1 was also substantially higher in placental insufficiency [0.68 (0.55, 0.83)] than in normal pregnancy [0.45 (0.36, 0.60), P = 0.0003]. CONCLUSIONS: Our study has demonstrated that levels of fetal plasma apolipoprotein A-1, apolipoprotein B and the ratio of apolipoprotein B to A-1 were altered in the fetuses who are victims of umbilical placental insufficiency in the same direction as in adults associated with a high risk of atherogenesis.
Adult↗
Administration of low-dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double-blind controlled trial.
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Aspirin↗
Neonatal herpes prevention: a minor public health problem in some communities.
BACKGROUND: Neonatal herpes is a condition with high morbidity and mortality. The greatest risk occurs when the mother acquires herpes simplex virus (HSV) towards the end of pregnancy. A study from Seattle has suggested that the risk of acquisition of HSV during pregnancy was 3.7%. In Australia, HSV-2 infection is less common in pregnant women than in the United States. Consequently we conducted a study to establish HSV seroprevalence and the rate of HSV seroconversion in this population. METHODS: The study was conducted at Westmead Hospital, Sydney, between June 1995 and April 1998. Women completed a questionnaire covering risk factors for the acquisition of genital herpes. A serum sample during pregnancy and a specimen of cord blood were obtained and tested for antibodies to HSV-2 using a type specific indirect enzyme linked immunosorbent assay (ELISA). Equivocal results were resolved by western blot. A subset of the paired sera was tested for antibodies to HSV-1. The data were analysed using SPSS. RESULTS: 326 of the 2616 (12.5%) women were HSV-2 seropositive. Three women (0.15%) acquired HSV-2 infection during pregnancy. None of the three babies of these mothers developed neonatal herpes. 416 maternal cord pairs were tested for HSV-1 antibodies and 330 (79.3%) were positive. No HSV-1 seroconversions occurred. CONCLUSIONS: In this population, HSV acquisition was uncommon (0.34% per year) and neonatal herpes was rare. A cost effective analysis suggested that type specific serology to screen pregnant women and their partners in low prevalence communities was not cost effective.
Adult↗
Elevated levels of lipoprotein(a) in women with preeclampsia.
OBJECTIVE: We examined the hypothesis that lipoprotein(a) levels are elevated in preeclampsia and associated with severity of the disease. STUDY DESIGN: Plasma lipoprotein(a) levels were measured in 24 normal pregnant women, 18 mild, and 8 severe preeclamptic women using an enzyme-linked immunosorbent assay method. Kruskall-Wallis one-way analysis of variance was used to evaluate the difference in plasma lipoprotein(a) among different groups. The Mann-Whitney U test was used to compare the differences between two groups. RESULTS: The plasma lipoprotein(a) levels were increased in pregnant women with both severe preeclampsia (median 826.9 mg/L [interquartile range 590.7, 986.9 mg/L], n = 8, p < 0.0001) and mild preeclampsia (median 357.7 mg/L [interquartile range 208.0, 477.1 mg/L], n = 18, p < 0.0001) compared with normal pregnancy (median 78.5 mg/L [interquartile range 45.2, 127.9 mg/L], n = 24). The lipoprotein(a) level was significantly higher in severe than in mild preeclampsia (p < 0.001). CONCLUSION: This study has demonstrated that lipoprotein(a) levels are elevated in preeclampsia and associated with severity of the disease. It may serve as a marker of the pathogenic process.
Adult↗
Changes of resistance to activated protein C in the course of pregnancy and prevalence of factor V mutation.
The purpose of this study was to examine the changes in activated protein C (APC) anticoagulant activity during pregnancy and determine whether changes in APC could contribute to thrombosis in the placental bed in preeclampsia. We measured APC anticoagulant activity in 150 women with a normal pregnancy and 50 women with preeclampsia. There was a significant reduction in the mean APC sensitivity ratio (APC-SR) during pregnancy (p<0.001). APC resistance in preeclampsia was significantly higher than in normal pregnancy (p<0.01). Amongst women with APC resistance the presence of the factor V Leiden mutation was significantly higher in the preeclampsia group than in the normal pregnancy group (p<0.01). It seems that both factor V Leiden mutation and APC resistance may be associated with the development of preeclampsia. These results suggest that APC resistance may be an important mechanism underlying placental bed pathology in pregnancy and may be associated with an increased tendency to develop preeclampsia in some women. Assay of APC resistance and factor V Leiden mutation should be performed in women with preeclampsia.
Adult↗
The fetal aortic pressure pulse waveform in normal and compromised pregnancy.
OBJECTIVE: To study the arterial pressure waveform in the descending thoracic aorta during pregnancy in both normal and compromised fetuses. DESIGN: The pressure pulsation waveform propagated along the vascular tree, and acting laterally on the arterial wall, produces a corresponding change in the vessel diameter. The distance between diametrically opposite points of the aortic lumen was followed using a phase locked loop echo tracking system coupled to a B-mode ultrasonic imager (central frequency 3.5 MHz). SETTING: Tertiary referral unit, teaching hospital. PARTICIPANTS: A cross-sectional study of 80 normal fetuses between 20 and 40 weeks yielded normal data. We studied 58 women with evidence of potential fetal compromise (high umbilical artery systolic: diastolic ratio). MAIN OUTCOME MEASURES: From the aortic diameter waveform we measured the maximum systolic and minimum diastolic dimension and calculated pulse amplitude. The first derivative of the aortic diameter waveform identified the incisura of aortic and pulmonary valve closure and was used to time the end of ventricular ejection and systole. RESULTS: In normal pregnancy there was an increase in systolic and diastolic diameter and pulse amplitude with advancing gestation. Ventricular ejection time was constant. In the fetal compromised group the absolute systolic and diastolic diameters were within the normal range, but diastolic diameter per unit fetal weight was increased. There was a decrease in pulse amplitude as a percentage of diastolic diameter and an increase in the diastolic systolic diameter ratio. Fetal outcome was examined in relation to the diastolic systolic diameter ratio. Those with a high ratio (above 90th centile of normal group) exhibited significantly more adverse indices of fetal outcome. CONCLUSIONS: The fetal aortic pressure pulse waveform was represented by the vessel diameter waveform. In fetal compromise reduced pulse amplitude and increased diastolic to systolic diameter ratio suggest corresponding changes in arterial pressure pulse. We suggest these are the response of the cardiac pump to increased afterload imposed by the high umbilical placental vascular resistance.
Aorta, Thoracic↗
Treatment of preterm cervical dilatation with glyceryl trinitrate, a nitric oxide donor.
We report an observational study on the use of transdermal glyceryl trinitrate as a treatment to delay delivery of women presenting in pregnancy with dilatation of the cervix. Ten women found to have cervical dilatation more than 2 cm (range 2 to 8 cm) at gestations between 16 and 32 weeks were studied. These women were treated with 50 mg glyceryl trinitrate patches. The mean prolongation of gestation from the time of admission was 46.2 days (range 1 to 130 days). There was 1 stillbirth in a 22.6-week fetus and 1 neonatal death secondary to prematurity. Vaginal delivery occurred in all but 3 cases. All babies were of size appropriate for gestational age at delivery. The only reported maternal side-effect was headache. No adverse fetal effects were noted. We conclude that glyceryl trinitrate may provide an effective and safe method of tocolysis, well suited for long-term use. The purpose of reporting this study is to highlight the mounting accumulation of data on glyceryl trinitrate and reinforce the need to evaluate its use in randomized controlled trials.
Administration, Cutaneous↗
The fetal central venous pressure waveform in normal pregnancy and in umbilical placental insufficiency.
OBJECTIVE: Our purpose was to study the fetal central venous pressure waveform recorded noninvasively from the inferior vena cava in normal and complicated pregnancies by means of newly developed equipment to follow the vessel lumen diameter. STUDY DESIGN: A paired ultrasonic phase-locked loop echo tracking system with a high sampling frequency (3000 Hz) was used to follow the movement (point displacement) of diametrically opposite points of the vessel wall. The lumen was measured as the interval between these points. We studied 70 normal fetuses (20 to 40 weeks) and 54 complicated pregnancies with increased umbilical placental resistance. RESULTS: The four component waves of the central venous pressure waveform (A, X, V, Y) were identified and measured in the fetal recording. The crests of the A and V waves were of approximately equal height. An increase in the descent of the Y trough was observed with advancing gestation. By means of data from the normal group, the complicated group was divided into three subgroups. In 10 fetuses the waveform was normal. In 31 there was a high pulsatile pattern with deep descent from the A crest to X trough so that the pulsatility of the waveform appeared increased. In 13 this was shallow and the pulsatility appeared reduced. Clinical outcome (nonreactive fetal heart rate, percentile birth weight, days in neonatal intensive care unit) was significantly worse in both these latter two subgroups in comparison with normal and in the low compared with the high-pulsatile group. CONCLUSIONS: Human fetal central venous pressure waveforms can be simply recorded and represented by the transluminal diameter waveform. In fetal compromise the high pulsatility waveform may result from a reduced ventricular ejection and increased end-diastolic pressure in response to the increase in ventricular afterload caused by the placental vessel obliteration. In the most profoundly compromised fetuses the low pulsatility waveform may indicate depressed myocardial function and output.
Central Venous Pressure↗
A New South Wales population-based study of stillbirths weighing 2,500 g or more.
This paper describes factors associated with singleton stillbirths weighing 2,500 g or more, born in 1987 and reported to the NSW Midwives' Data Collection (MDC), a statewide perinatal data collection system. A total of 136 singleton stillbirths in this weight range were notified to the MDC, representing one-quarter of all singleton stillbirths in NSW. MDC records on these stillbirths were linked with perinatal death registrations for 125 of the 136. The death registrations indicated that fetal death occurred during labour in 20 cases, prior to the onset of labour in 98, and at an unknown time in the remaining 7 cases. Placental complications, including haemorrhage and functional abnormalities of the placenta, were the most frequent group of conditions associated with the stillbirths, being recorded as the underlying cause of death in 42 (34%) of the 125 cases. Cord complications (such as cord compression or cord around the neck) were given as the underlying cause of death in 30 cases (24%). The death certificate diagnosis was confirmed by autopsy in only 27 of the 125 cases (22%), although autopsies may have been done on a further 45 cases (36%). An adequate explanation of the cause appeared to be lacking for many of the fetal deaths. This highlights the importance of a thorough and systematic investigation of stillbirths. A list of standard investigations to be carried out following a stillbirth is proposed.
Birth Weight↗
Placental microvascular changes in twin pregnancies with abnormal umbilical artery waveforms.
OBJECTIVE: To determine whether there is a relationship between umbilical artery Doppler waveforms and placental histology in twin pregnancies. METHODS: The placental vasculature was examined histologically in 41 cases of twin pregnancy in women who had undergone antenatal Doppler umbilical artery waveform analysis. RESULTS: Those fetuses with abnormal systolic-diastolic ratios (S/Ds) showed a reduction in the placental tertiary stem villi arterial vessels compared with fetuses with normal S/Ds. The mean count of small arterial vessels (diameter less than 90 mu) in the placentas from cases with normal S/Ds (below the 95th percentile) was 5.6, whereas the mean arterial count for those with high S/Ds (above the 99th percentile) was 3.9 (P = .039). CONCLUSIONS: In twin pregnancies complicated by placental insufficiency, there is microvascular disease restricted to the placenta of the affected fetus. This suggests that the placental vascular lesion originates in the fetal circulation rather than in the uteroplacental vasculature.
Birth Weight↗