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Biomedical subjects

N M Fisk

Publications and source records attributed to N M Fisk.

At least 73 records · Page 4Linked to original sources

Association between maternal anxiety in pregnancy and increased uterine artery resistance index: cohort based study.

OBJECTIVE: To investigate whether maternal anxiety in the third trimester is associated with an increased uterine artery resistance index. DESIGN: Cohort based study. SUBJECTS: 100 pregnant women, with a mean gestation of 32 weeks. OUTCOME MEASURES: Self rating Spielberger questionnaire for state anxiety and trait anxiety, and uterine blood flow waveform patterns as assessed by colour Doppler ultrasound. RESULTS: A significant association was found between uterine artery resistance index and scores for both Spielberger state anxiety and trait anxiety (rs=0.31, P<0.002 and 0.28 P<0.005 respectively). Women with state anxiety scores >40 (n=15) had a higher mean uterine resistance index than those with scores </= 40 (mean difference with mean resistance index 24%, 95% confidence interval 12% to 38%; P<0.0001). Similarly, women with trait anxiety scores >40 (n=32) had a higher mean resistance index than those with scores </= 40, although to a lesser extent. The presence of notches in the waveform pattern produced by uterine artery blood flow was found in 4/15 (27%) women with high state anxiety scores compared with 4/85 (5%) with low anxiety scores (P<0.02). CONCLUSIONS: This study shows an association between maternal anxiety in pregnancy and increased uterine artery resistance index. It suggests a mechanism by which the psychological state of the mother may affect fetal development, and may explain epidemiological associations between maternal anxiety and low birth weight. The influence of maternal anxiety may be one mechanism by which the intrauterine environment contributes to later disease in offspring.

Anxiety↗

High failure rate of umbilical vessel occlusion by ultrasound-guided injection of absolute alcohol or enbucrilate gel.

The success rate for injected umbilical vascular occlusion in the published literature exceeds 85 per cent. In this study we assessed the efficacy of two forms of injected sclerosants in achieving umbilical vessel occlusion. 12 cases of attempted ultrasound-guided occlusion over a 2 1/2 year period were reviewed. These were monochorionic (MC) twins (n=6), dichorionic twins (n=3) and singletons (n=3) undergoing fetocide for severe anomalies, or impending fetal demise. Absolute alcohol (n=6), enbucrilate gel (n=5) or both (n=1) were used in an attempt to achieve vascular occlusion. Complete vessel occlusion was achieved in only a third of cases (4/12), three with absolute alcohol and one with enbucrilate gel. In MC twins occlusion was successful in two of six cases. In contrast to previously published data, this large series, containing more cases than the total previously reported, shows considerably poorer success rates for injected umbilical vascular occlusion. Injection of currently available sclerosants can no longer be recommended for umbilical vascular occlusion in human fetuses.

Enbucrilate↗

Acute cerebral redistribution in response to invasive procedures in the human fetus.

OBJECTIVES: We sought to investigate the fetal hemodynamic response to the acute stress of invasive procedures. STUDY DESIGN: The middle cerebral artery pulsatility index was measured by Doppler ultrasonography before and after 136 invasive procedures (fetal blood sampling, transfusion, shunt insertion, tissue biopsy, and ovarian cyst aspiration). The response of fetuses submitted to invasive procedures involving transgression of the fetal body, such as intrahepatic vein blood sampling, was compared with that of control procedures at the placental cord insertion. RESULTS: The middle cerebral artery pulsatility index value fell with fetal blood sampling performed at the intrahepatic vein (median, -0.26; 95% confidence interval, -0.35 to -0.15) but not at the placental cord insertion (median, 0.05; 95% confidence interval, -0.04 to 0.19). With transfusions, the middle cerebral artery pulsatility index also fell with procedures at the intrahepatic vein (mean, -0.51; 95% confidence interval, -0.66 to -0.35) but not at the placental cord insertion (mean, -0.04; 95% confidence interval, -0.23 to 0.14). The magnitude of the response was greater with transfusions than with blood sampling alone. The middle cerebral artery pulsatility index value also fell with non-fetal blood sampling procedures involving transgression of the fetal body (mean, -0.32; 95% confidence interval, -0.56 to -0.09) but not with control non-fetal blood sampling procedures. The change in the middle cerebral artery pulsatility index was not related to gestational age, with the youngest fetus showing a fall in the middle cerebral artery pulsatility index value being at 16 weeks' gestation. Although the degree of response was weakly correlated with the duration of needling (y = -0.21 - 0.00014x; R (2) = 0.08; P =.02), multiple logistic regression demonstrated that this was instead a function of the type of the procedure. A response was seen within 70 seconds of fetal puncture. The fetal heart rate did not change significantly with procedures in any of the above-mentioned groups. CONCLUSIONS: The human fetus mounts a cerebral hemodynamic response to invasive procedures involving transgression of the fetal body, which is consistent with the brain-sparing effect.

Biopsy↗

Vascular occlusion using focused ultrasound surgery for use in fetal medicine.

OBJECTIVE: Focused ultrasound surgery (FUS) is being developed clinically for the non-invasive treatment of soft tissue tumours of the prostate, bladder, liver, kidney, muscle and breast. In the work described in this paper, the application of FUS is extended to investigate the potential to induce vascular occlusion, with the aim of applying the technique to problems in fetal medicine and oncology. METHODS: In this feasibility study the occlusion of femoral blood flow in vivo is demonstrated using an array of multiple single exposures of 1.7 MHz focused ultrasound. These were placed in two rows of four lesions at a focal depth of 5 mm. The 4660-W cm-2 (free field spatial peak intensity) 2-s exposures were placed 2 mm apart. Vascular patency was assessed using a Siemens Vision (1.5T) magnetic resonance (MR) imaging scanner with an extremity coil, and intravenous gadolinium contrast agent. FLASH and FISP MR sequences were used to obtain full 3D data sets providing information on soft tissue damage and perfusion. RESULTS AND CONCLUSION: Total vascular occlusion was achieved in four of nine cases and significant vascular disruption in five of nine cases. Refinement of the FUS technique and long-term studies are now indicated prior to initial clinical application in fetal medicine.

Animals↗

First-trimester cord entanglement in monoamniotic twins.

OBJECTIVE: Monoamniotic twinning occurs in only 1% of twin pregnancies, but carries a high perinatal mortality rate. Early and reliable diagnosis is essential if attempts are to be made to reduce the complication rate. We report color Doppler demonstration of cord entanglement in the first trimester, which is diagnostic of monoamnionicity. METHODS: Two patients with twin pregnancies were examined in the first trimester with pulsed and color Doppler insonation of their umbilical arteries. RESULTS: Cord entanglement was suspected and proved by demonstrating differing fetal heart rate patterns in the same direction on umbilical artery Doppler analysis of a common mass of cord vessels. Following appropriate counselling, medical amnioreduction was induced at 20 weeks of gestation to reduce fetal movements and worsening cord entanglement. Delivery was by elective Cesarean section at 32 weeks' gestation and monoamnionicity was confirmed. CONCLUSION: We report a new sign for the demonstration of monoamnionicity in twin pregnancies in the first trimester. This should improve the reliability of early diagnosis, but further studies are required to confirm that, if cord entanglement occurs, it is usually present by the end of the first trimester.

Amnion↗

Endothelin concentrations in monochorionic twins with severe twin-twin transfusion syndrome.

The objective of this study was to determine endothelin (ET-1) concentrations in monochorionic twin fetuses with and without twin-twin transfusion syndrome (TTTS). Fourteen monochorionic twin pregnancies complicated by TTTS and six without TTTS were studied. Matched maternal and fetal blood samples were obtained both in utero and at birth. Amniotic fluid samples were also collected from twin pairs. ET-1 concentrations were measured by radio-immunoassay. ET-1 concentrations in recipient fetuses were higher than in the donors both in utero(P < 0.001) and at birth (P < 0.01). Fetal concentrations of ET-1 in donors were similar to non-TTTS twins. Plasma ET-1 concentrations were significantly higher (P < 0.01) in recipient fetuses with severe hydrops than those with mild/no hydrops. Maternal concentrations of ET-1 were comparable in the two groups. Endothelin concentrations in recipient twins were 2(1/2) times higher than in their co-twins and this was related to the severity of hydrops.

Amniotic Fluid↗

X-chromosome inactivation patterns do not implicate asymmetric splitting of the inner cell mass in the aetiology of twin-twin transfusion syndrome.

The aetiology of twin-twin transfusion syndrome (TTTS) is unclear. We investigated the hypothesis that monochorionic (MC) pregnancies with TTTS are associated with differences in the timing and symmetry of twinning compared to MC twin pregnancies without TTTS. DNA was extracted from the umbilical cord vessels of 26 female MC twins, 14 with and 12 without TTTS on serial antenatal ultrasound. X-inactivation patterns were determined by DNA digestion with Hhal and Hpall followed by polymerase chain reaction for a polymorphic trinucleotide repeat in the androgen receptor gene. Products were quantified by densitometry and results compared to those in peripheral blood samples of adult female controls. The median degree of non-random inactivation was similar in MC twins with TTTS, in MC twins without TTTS, and in adult controls. The percentage of individuals with skewed (> or =30/70%) inactivation patterns was no different in MC twins with TTTS compared to those without TTTS, and was similar to adult controls using either enzyme technique. In conclusion we found no difference in the degree or frequency of non-random X-inactivation patterns in TTTS. X-inactivation patterns do not appear to be a useful tool for studying the symmetry of inner cell mass splitting in monochorionic twins.

Adult↗

Randomised trial of educational visits to enhance use of systematic reviews in 25 obstetric units.

OBJECTIVE: To evaluate the effectiveness of an educational visit to help obstetricians and midwives select and use evidence from a Cochrane database containing 600 systematic reviews. DESIGN: Randomised single blind controlled trial with obstetric units allocated to an educational visit or control group. SETTING: 25 of the 26 district general obstetric units in two former NHS regions. SUBJECTS: The senior obstetrician and midwife from each intervention unit participated in educational visits. Clinical practices of all staff were assessed in 4508 pregnancies. INTERVENTION: Single informal educational visit by a respected obstetrician including discussion of evidence based obstetrics, guidance on implementation, and donation of Cochrane database and other materials. MAIN OUTCOME MEASURES: Rates of perineal suturing with polyglycolic acid, ventouse delivery, prophylactic antibiotics in caesarean section, and steroids in preterm delivery, before and 9 months after visits, and concordance of guidelines with review evidence for same marker practices before and after visits. RESULTS: Rates varied greatly, but the overall baseline mean of 43% (986/2312) increased to 54% (1189/2196) 9 months later. Rates of ventouse delivery increased significantly in intervention units but not in control units; there was no difference between the two types of units in uptake of other practices. Pooling rates from all 25 units, use of antibiotics in caesarean section and use of polyglycolic acid sutures increased significantly over the period, but use of steroids in preterm delivery was unchanged. Labour ward guidelines seldom agreed with evidence at baseline; this hardly improved after visits. Educational visits cost pound860 each (at 1995 prices). CONCLUSIONS: There was considerable uptake of evidence into practice in both control and intervention units between 1994 and 1995. Our educational visits added little to this, despite the informal setting, targeting of senior staff from two disciplines, and donation of educational materials. Further work is needed to define cost effective methods to enhance the uptake of evidence from systematic reviews and to clarify leadership and roles of senior obstetric staff in implementing the evidence.

Costs and Cost Analysis↗

Detection of fetal messenger ribonucleic acid in maternal blood to determine fetal RhD status as a strategy for noninvasive prenatal diagnosis.

OBJECTIVES: Our purpose was to test the hypothesis that reverse transcriptase-polymerase chain reaction for fetal messenger ribonucleic acid in maternal blood is more sensitive than polymerase chain reaction from genomic deoxyribonucleic acid in prenatal determination of fetal RhD blood type. STUDY DESIGN: Fetal nucleated erythrocytes in peripheral blood from 35 RhD-negative women were enriched by triple-density gradient centrifugation, anti-CD71 magnetic sorted, and deoxyribonucleic acid and ribonucleic acid extracted. Sensitivities of reverse transcriptase-polymerase chain reaction and polymerase chain reaction were compared to predict definitive fetal RhD blood type determined in fetal tissues. RESULTS: Reverse transcriptase-polymerase chain reaction was significantly more accurate (P = .03) than genomic-polymerase chain reaction in predicting fetal RhD blood type, both overall (28 of 35 vs 22 of 35) and when the fetus was RhD-positive (12 of 19 vs 6 of 19). CONCLUSIONS: Reverse transcriptase-polymerase chain reaction is more sensitive than genomic-polymerase chain reaction in detection of fetal RhD sequences in maternal blood.

Female↗

Neonatal cranial ultrasonographic findings in preterm twins complicated by severe fetofetal transfusion syndrome.

OBJECTIVE: To investigate cranial ultrasonographic findings in survivors of monochorionic pregnancies complicated by fetofetal transfusion syndrome. STUDY DESIGN: Case details of all monochorionic twin pregnancies complicated by fetofetal transfusion syndrome were obtained from the Centre for Fetal Care database for a 3-year period. Fetofetal transfusion syndrome was diagnosed according to ultrasonographic criteria. Eligible for entry were twin pregnancies resulting in live-born preterm infants and complicated by fetofetal transfusion syndrome severe enough to require amnioreduction. Cranial ultrasonographic scans performed within 48 hours of birth were reviewed for evidence of abnormality. RESULTS: Seventeen pregnancies were eligible for inclusion in the study. Median gestational age was 25 weeks (between 17 and 29 weeks) at diagnosis and 30 weeks (between 25 and 35 weeks) at delivery. Three infants died before ultrasonography could be performed. The remaining 31 twin infants received an early cranial ultrasonographic scan. One of the 31 had a major cerebral infarct; 10 others had evidence of other, more minor, antenatally acquired lesions. CONCLUSIONS: Both donor and recipient survivors from pregnancies complicated by fetofetal transfusion syndrome are at significant risk for antenatally acquired cerebral lesions. Long-term neurologic follow-up studies are indicated to determine the clinical significance of these lesions.

Brain↗

Maternal-to-fetal transfer of thyrotropin-releasing hormone in vivo.

OBJECTIVE: Our purpose was to determine the transplacental transfer of thyrotropin-releasing hormone at the time of fetal blood sampling. STUDY DESIGN: Four hundred micrograms of thyrotropin-releasing hormone was given intravenously to 13 pregnant women between 24 and 35 weeks' gestation and maternal-to-fetal transfer of thyrotropin-releasing hormone was determined at fetal blood sampling 1 to 93 minutes later. The fetal thyrotropic response to thyrotropin-releasing hormone was determined by measuring thyroid-stimulating hormone, thyroxine, and prolactin. For comparison, endogenous fetal and maternal levels of thyrotropin-releasing hormone, thyroid-stimulating hormone, thyroxine, and prolactin levels were determined in a further 20 patients undergoing fetal blood sampling between 19 and 35 weeks' gestation. The concentration of thyrotrophin-releasing hormone was measured by radioimmunoassay and thyroid-stimulating hormone, thyroxine, and prolactin by chemiluminescence assay. RESULTS: Thyrotropin-releasing hormone was undetectable in the maternal circulation, whereas endogenous levels were detectable in the fetus from 19 weeks' gestation (median 150; range 50 to 276 pmol/L) and did not correlate with gestational age. After thyrotropin-releasing hormone injection as an intravenous bolus, peak levels in the mother were attained at 3 minutes (50,000 pmol/L). Maximal transplacental transfer of thyrotropin-releasing hormone occurred within 5 minutes of maternal administration but accounted in fetal blood for only 0.01% of initial dose administered (median 250; 30 to 550 pmol/L). Thyrotropin-releasing hormone-stimulated fetal peak thyroid-stimulating hormone levels occurred within 13 minutes and were higher than maternal values (p < 0.001). There was no change in fetal prolactin level with thyrotropin-releasing hormone therapy. CONCLUSION: Although maternally administered thyrotropin-releasing hormone crosses the placenta sparingly, it still elicits a thyroid-stimulating hormone but not a prolactin response in the human fetus.

Adult↗

Absence of expression of RhD by human trophoblast cells.

OBJECTIVE: Our purpose was to determine whether the RhD gene is expressed in trophoblast at any stage of gestation. STUDY DESIGN: Trophoblast and fetal tissue were obtained from 18 pregnancies at 8 to 40 weeks' gestation. Deoxyribonucleic acid and ribonucleic acid were extracted from trophoblast. Complementary deoxyribonucleic acid was synthesized from ribonucleic acid, and reverse transcriptase-polymerase chain reaction was performed using primers specific for the RhD gene. Deoxyribonucleic acid was extracted from fetal tissue to determine the fetal RhD status by means of polymerase chain reaction. Antigen expression was also sought by analytic cytometric analysis (flow cytometry and immunocytochemistry) using a monoclonal anti-D antibody. RESULTS: Trophoblast was studied from various combinations of RhD-positive and RhD-negative fetuses (on deoxyribonucleic acid) from mothers to find no RhD gene expression in any sample. Flow cytometry and immunocytochemistry confirmed this by demonstrating no RhD antigen sites on trophoblast cells. CONCLUSION: Contrary to a previous report, we conclude that the RhD gene is not expressed in human trophoblast in any trimester.

DNA↗