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Biomedical subjects

N M Fisk

Publications and source records attributed to N M Fisk.

At least 55 records · Page 3Linked to original sources

Perinatal morbidity and mortality rates in severe twin-twin transfusion syndrome: results of the International Amnioreduction Registry.

OBJECTIVE: Serial aggressive amnioreduction is the most widely used therapy for pregnancies that are complicated by twin-twin transfusion syndrome. Survival rates reported with this therapy are 33% to 83%, the wide range attributable to the small number of patients in these case series. Similarly, data on morbidity in survivors are imprecise. We instituted the international twin-twin transfusion syndrome registry to determine the perinatal survival and morbidity rates and the factors that influence perinatal outcome in patients with twin-twin transfusion syndrome who were treated with serial aggressive amnioreduction from 1990 to 1998. STUDY DESIGN: A total of 223 sets of twins who were diagnosed with twin-twin transfusion syndrome before 28 weeks' gestation from 20 fetal medicine referral centers were analyzed, with follow-up data until 4 weeks after birth. RESULTS: Three hundred forty-six twins (78%; 182 recipients and 164 donors) were born alive. Two hundred sixty-six twins (60%; 144 recipients and 122 donors) were alive 4 weeks after birth. Both fetuses survived to 4 weeks in 108 pregnancies (48.4%), whereas, at least 1 fetus survived in 158 pregnancies (70.8%). The interval between the last amnioreduction and delivery ranged from zero to 138 days (median, 17.5 days). In the infants who survived to 4 weeks after birth, abnormalities on neonatal cranial scan were diagnosed in 24% of recipients and in 25% of donors. Logistic regression analysis indicated that the survival rate was significantly related to gestational age at diagnosis, presence of end-diastolic blood flow in the umbilical artery velocity waveforms, presence of hydrops, mean volume of amniotic fluid removed per week, larger birth weight, and gestational age at delivery. The hemoglobin level difference at birth was the only significant parameter to predict abnormal cranial ultrasonography in newborns. CONCLUSION: These data document perinatal survival and neonatal morbidity rates in severe twin-twin transfusion syndrome that were treated by serial aggressive amnioreduction. Outcome was influenced by several perinatal risk factors, which may be used to counsel patients before and during therapy.

Amnion↗

Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling.

BACKGROUND: Whether the fetus can experience pain remains controversial. During the last half of pregnancy, the neuroanatomic connections for nociception are in place, and the human fetus mounts sizable stress responses to physical insults. Analgesia has been recommended for intrauterine procedures or late termination, but without evidence that it works. The authors investigated whether fentanyl ablates the fetal stress response to needling using the model of delayed interval sampling during intrahepatic vein blood sampling and transfusion in alloimmunized fetuses undergoing intravascular transfusion between 20 and 35 weeks. METHODS: Intravenous fentanyl (10 microg/kg estimated fetal weight x 1.25 placental correction) was given once at intrahepatic vein transfusion in 16 fetuses, and changes (posttransfusion - pretransfusion) in beta endorphin, cortisol, and middle cerebral artery pulsatility index were compared with intrahepatic vein transfusions without fentanyl and with control transfusions at the placental cord insertion. RESULTS: Fentanyl reduced the beta endorphin (mean difference in changes, -70.3 pg/ml; 95% confidence interval, -121 to -19.2; P = 0.02) and middle cerebral artery pulsatility index response (mean difference, 0.65; 95% confidence interval, 0.26-1.04; P = 0.03), but not the cortisol response (mean difference, -10.9 ng/ml, 95% confidence interval, -24.7 to 2.9; P = 0.11) in fetuses who had paired intrahepatic vein transfusions with and without fentanyl. Comparison with control fetuses transfused without fentanyl indicated that the beta endorphin and cerebral Doppler response to intrahepatic vein transfusion with fentanyl approached that of nonstressful placental cord transfusions. CONCLUSIONS: The authors conclude that intravenous fentanyl attenuates the fetal stress response to intrahepatic vein needling.

Adult↗

Interstitial laser: a new surgical technique for twin reversed arterial perfusion sequence in early pregnancy.

Current treatments for twin reversed arterial perfusion sequence are associated with significant morbidity and most are not feasible in early gestation. We report the use of an interstitial laser in two pregnancies complicated by this sequence at 14 and 15 weeks, respectively. A 600 microm laser fibre was introduced via a 17 gauge needle into the abdomen of the perfused twin close to the vitelline artery and umbilical vein, which were occluded by neodymium:yttrium aluminium garnet (Nd:YAG) laser. Both pregnancies continued uneventfully and each resulted in the birth of a healthy baby at term.

Female↗

Fetal hypothalamic-pituitary-adrenal stress responses to invasive procedures are independent of maternal responses.

Paired fetal and maternal samples were obtained, at fetal blood sampling and intrauterine transfusion, to study hypothalamic-pituitary-adrenal stress responses. This confirmed that the fetus mounts an hypothalamic-pituitary-adrenal stress response to transfusion via the intrahepatic vein, which involves piercing the fetal trunk, but not to transfusion via the placental cord insertion [mean cortisol response via intrahepatic vein delta = 52.6 nmol/L, 95% CI (25.3-79.9), P = 0.001; mean beta-endorphin response delta =106 pg/mL, 95% CI (45.3-167), P = 0.002]. Baseline maternal fetal ratios were 13 [95% CI (10.7-15.2)] for cortisol and 0.8 [95% CI (0.5-1.0)] for beta-endorphin. The novel findings were: 1) that the fetal responses were independent of those of the mother, which did not change during transfusion at either site; 2) that there was a correlation between baseline fetal and maternal cortisol levels (r = 0.58, n = 51, P < 0.0001) but not between baseline fetal and maternal ss-endorphin levels, suggesting cortisol transfer across the placenta, rather than joint control by placental CRH; and 3) that fetal beta-endorphin responses were apparent from 18 weeks gestation and independent of gestational age, whereas fetal cortisol responses were apparent from 20 weeks gestation and were dependent on gestational age (y = -91.4 + 5.08x, r = 0.51; n = 16; P = 0.04; CI for slope, 0.16-10.0), consistent with the maturation of the fetal pituitary before the fetal adrenal.

Blood Transfusion↗

Mode of delivery and subsequent stress response.

We have shown that a baby's stress (saliva cortisol) and crying response to inoculation at 8 weeks was related to mode of delivery, with the greatest response shown in those born by assisted delivery and the least response in those born by elective caesarean section.

Cesarean Section↗

Preclinical development of noninvasive vascular occlusion with focused ultrasonic surgery for fetal therapy.

OBJECTIVE: This study was undertaken to investigate the ability of focused ultrasonic surgery to occlude blood flow in vivo. STUDY DESIGN: A 5-mm linear track exposure of 1.7-MHz focused ultrasound was applied across the femoral vessels for 5 seconds. Free field spatial peak intensities in the range of 1,000 to 4,660 W x cm(-2) were used. Vascular occlusion was confirmed after demonstration of an absent distal arterial pulse and an absent flow signal on magnetic resonance angiography and subtracted (after minus before) contrast-enhanced dual-echo steady-state sequences. RESULTS: The minimum intensity for consistent vascular occlusion was 1,690 W x cm(-2) at a focal depth of 5 mm when the transducer was moved at 1 mm x s(-1) orthogonal to the direction of blood flow. CONCLUSIONS: This study demonstrates that focused ultrasonic surgery can achieve reproducible vascular occlusion in vivo. Potential obstetric applications include noninvasive ultrasonographically guided occlusion of placental vessels mediating interfetal transfusion in monochorionic twins.

Animals↗

Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome.

OBJECTIVE: We sought to correlate placental vasculature with fetal growth and outcome in monochorionic twins. STUDY DESIGN: Eighty-two patients with consecutive monochorionic pregnancies underwent biweekly ultrasonography for determination of fetal growth and well-being. After delivery, blinded placental injection studies delineated vascular anastomoses and territory share. Degree of balance in arteriovenous anastomoses equaled the number of arteriovenous anastomoses in one direction minus the number in the other. RESULTS: Pregnancies affected by fetofetal transfusion syndrome (n = 21) had numbers of arteriovenous and venovenous anastomoses that were similar to those in pregnancies without fetofetal transfusion syndrome but fewer arterioarterial anastomoses (P <.0001). Fetofetal transfusion syndrome occurred in 78% of pregnancies with >/=1 arteriovenous and no arterioarterial anastomoses. Birth weight discordancy correlated with placental territory discordancy (P <.0001) and the degree of balance in arteriovenous anastomoses (P =.004). The larger placental share twin had a greater growth velocity than its smaller placental share co-twin (P =.008) for all but one anastomotic pattern. Where arteriovenous anastomoses were aligned with the net venous outflow to the fetus with the smaller territory, co-twins had similar birth weights and growth velocities irrespective of placental share. Fetal survival was higher in pregnancies with an arterioarterial anastomosis (P =.01) but lower with a venovenous anastomosis (P =. 01). Survival of both fetuses was inversely associated with birth weight discordancy (P <.0001). CONCLUSION: Although interrelationships among the various types of anastomoses are complex, our data suggest that the placental territory share and the pattern of arteriovenous anastomoses influence fetal growth, that arterioarterial anastomoses protect against fetofetal transfusion syndrome, and that venovenous anastomoses reduce perinatal survival.

Arteriovenous Anastomosis↗

Ex vivo delineation of placental angioarchitecture with the microbubble contrast agent Levovist.

OBJECTIVE: The aim of this study was to delineate placental vasculature with the microbubble contrast agent Levovist (99.9% galactose and 0.1% palmitic acid; Schering AG, Berlin, Germany), with the ultimate goal of delineating placental vascular anatomy in utero. STUDY DESIGN: A placental lobule from each of 11 term human placentas was perfused on the fetal side of the circulation under physiologic conditions. Randomly assigned dose-concentration combinations of Levovist were administered through a chorionic artery into the corresponding placental lobule, and the resultant echoenhancement with power Doppler imaging was recorded for digital analysis. Interplacental variability was corrected for by averaging the results of three injections at each dose-concentration combination. RESULTS: Echoenhancement was seen at all dose-concentration combinations in the injected lobule but not in adjacent control lobules. The three dose-concentration combinations that achieved optimal maximal integrated intensity and duration of action for both chorionic vessel and villus enhancement were 100 microL/kg of 400-mg/mL Levovist, 200 microL/kg of 400-mg/mL Levovist, and 400 microL/kg of 200-mg/mL Levovist. CONCLUSION: Microbubble contrast injection into the fetal vasculature enabled power Doppler imaging echoenhancement both in chorionic vessels and within the villus tree. We speculate that fetal injection of contrast agent may be applied to the delineation of placental lesions or areas of interfetal transfusion, although its applicability will be hindered by the need for fetal blood sampling.

Blood Vessels↗

Pain and stress in the human fetus.

Invasive diagnostic and therapeutic techniques are increasingly applied to the fetus. It is not known if the fetus feels pain during such procedures, but the fetus does mount significant stress hormonal and circulatory changes in response to these from 18-20 weeks. Perinatal stress may have long-term neurodevelopmental implications. During open fetal surgery, maternal general anaesthesia provides fetal anaesthesia. However, in closed procedures, fetal analgesia presents difficulties. The optimal drug, dose, and route of administration remain to be determined.

Analgesia↗

Middle cerebral artery peak systolic velocity in the prediction of fetal anemia.

OBJECTIVE: The fetal middle cerebral artery peak systolic velocity (MCA PSV) has been suggested as a potential test to predict the fetal hematocrit level. We tested the hypothesis that a low fetal hematocrit is associated with an increase in MCA PSV in a prospective study of normal and alloimmunized pregnancies. METHODS: Fetal hematocrit and MCA PSV were obtained in 26 alloimmunized fetuses, immediately before their first fetal blood transfusions between 15 and 35 weeks. Results were compared with the MCA PSVs from 170 control fetuses not at risk of alloimmune anemia between 13 and 37 weeks. RESULTS: In control fetuses, PSV varied with gestation (PSV = 0.56 - 0.032 GA + 0.00086 GA2, where GA is gestational age; R2 = 0.41). The correlation between PSV and hematocrit Z scores (Pearson correlation coefficient r = -0.69) was highly significant (P = 0.0001). Using a PSV > 1 SD, the sensitivity of the test in predicting a fetal hematocrit < 2 SD below the mean was only 64% but the specificity was 100%. However, the sensitivity of the test in predicting a fetal hematocrit < 3 SD and < 4 SD rose to 73% and 83%, while the specificity was still good (93% and 80% respectively). CONCLUSIONS: MCA PSV and fetal hematocrit are highly significantly correlated. The sensitivity of the test was good and the high positive predictive value indicates that the presence of a raised PSV (defined as > 1 SD) is a strong indicator of fetal anemia. In conclusion, MCA PSV is a useful test in clinical practice for the detection of fetal anemia.

Adult↗

Identification of arterio-venous anastomoses in vivo in monochorionic twin pregnancies: preliminary report.

OBJECTIVE: To determine whether it is possible to identify in vivo placental arterio-venous anastomoses (AVAs) by color Doppler flow mapping. METHODS: Three monochorionic twin pregnancies (one with and two without twin-to-twin transfusion syndrome) underwent placental mapping by color Doppler ultrasound. Placental vessels along the chorionic plate were recorded together with the direction of blood flow and their location in relation to the cord insertions and to superficial arterio-arterial anastomoses. Suggestive AVAs were mapped topographically and results were compared with the findings of formal postnatal placental injection studies. RESULTS: An AVA was identified in each of the three cases. Injection studies showed multiple AVAs. Each antenatally identified AVA was confirmed at placental injection study. Their placental location correlated to other landmarks as predicted by ultrasound. CONCLUSIONS: This preliminary report demonstrates that AVAs can be identified using color Doppler ultrasound. This may facilitate planning for highly selective ablation of AVAs, and shorter procedure times. Formal studies are now indicated to determine the accuracy of this technique.

Arteriovenous Anastomosis↗

Prenatal diagnosis in multiple pregnancy.

Fetal abnormality is more common in multiple than in singleton pregnancies. This, together with the requirement to consider the risks with at least two babies to sample correctly each fetus and to undertake accurately-targeted selective termination, amounts to a major challenge for obstetricians involved in prenatal diagnosis. Early determination of chorionicity should be routine, since this influences not only the genetic risks but also the invasive procedure chosen for karyotyping or genotyping. Assessment of nuchal translucency identifies individual fetuses at risk of trisomy. Contrary to expectation, invasive procedures in twins appear to have procedure-related miscarriage rates that are similar to those in singletons. Instead, contamination remains a concern at chorionic villus sampling. Elective late karyotyping of fetuses may have a role in some countries. Whereas management options for discordant fetal abnormality are relatively straightforward in dichorionic pregnancies, monochorionic pregnancies are at risk of co-twin sequelae after any single intrauterine death. Techniques have now been developed to occlude completely the cord vasculature by laser and/or ultrasound guided bipolar diathermy. Given the complexities associated with prenatal diagnosis, all invasive procedures in multiple pregnancies should be performed in tertiary referral centres.

Amniocentesis↗

Antenatal factors at diagnosis that predict outcome in twin-twin transfusion syndrome.

OBJECTIVE: We sought to identify clinical factors at diagnosis that predict outcome in twin-twin transfusion syndrome. STUDY DESIGN: In this retrospective series 23 patients with twin-twin transfusion syndrome were seen in a tertiary referral fetal medicine center over a 3-year period. Ten antenatal factors were assessed to determine their ability to predict outcome by use of ordered logistic regression. These factors were the following: (1) absent or reversed end-diastolic flow in the umbilical artery, nonvisible bladder, anhydramnios, and estimated fetal weight of <3rd percentile in the donor; (2) pulsatile umbilical vein, either absent or reversed end-diastolic flow in the ductus venosus, or both, and tricuspid-mitral valve regurgitation in the recipient; and (3) gestational age at presentation, estimated fetal weight discordancy, absent arterioarterial anastomosis, and spontaneous rupture of the membranes or cervical change as pregnancy factors. Management comprised serial amnioreduction (n = 10), selective feticide (n = 5; 4 also had amnioreduction), septostomy (n = 4; 1 also had amnioreduction), and delivery (n = 2). Two patients miscarried before treatment. RESULTS: The chance of survival of both twins fell and double deaths increased linearly with increasing number of adverse factors (P =.026). A low chance of survival was independently associated with absent or reversed end-diastolic flow in the donor umbilical artery (P =.02) and with a pulsatile umbilical vein or absent or reversed end-diastolic flow in the ductus venosus (P =.03) of the recipient. The probability of at least one twin surviving was only 33% if there was absent or reversed end-diastolic flow in the donor umbilical artery or 37% when abnormal venous recordings were seen in the recipient. An arterioarterial anastomosis detected at diagnosis also influenced prognosis, with all twins surviving when an arterioarterial anastomosis was identified (P =.04). CONCLUSIONS: Three factors identified at diagnosis independently predict poor survival in twin-twin transfusion syndrome-absent or reversed end-diastolic flow in the donor umbilical artery, abnormal pulsatility of the venous system in the recipient, and absence of an arterioarterial anastomosis. These may have a role in the counseling of parents and in selecting the appropriate treatment strategy.

Arteries↗

Doppler detection of arterio-arterial anastomoses in monochorionic twins: feasibility and clinical application.

The accuracy of in-vivo detection of arterio-arterial anastomoses (AAA) in monochorionic (MC) twins and its predictive value for twin-twin transfusion syndrome (TTTS) was assessed in 105 consecutive MC twins scanned at fortnightly intervals. AAA were sought using spectral and colour energy Doppler and ultrasound findings were compared with placental injection studies. AAA were identified in vivo in 59 (56%) pregnancies and at injection study in 68 (65%). The overall sensitivity and specificity was 85 and 97.3% respectively for the detection of AAA. Detection rates were higher at later gestations, with anterior placentae and with larger diameter AAA. The median insonation time to detect an AAA was 10 min (range 1-30). Where an AAA was identified, 15% of pregnancies (nine of 59) developed TTTS compared to 61% (28 of 46) when no AAA was seen (odds ratio 8.6). We conclude that AAA can be detected in vivo with high sensitivity and specificity without undue prolongation of scanning times and have a role in risk stratification in the antenatal assessment of MC twins.

Arterio-Arterial Fistula↗

Twin fetuses: intravascular microbubble US contrast agent administration--early experience.

PURPOSE: To explore the feasibility of administering SH U 508A by using a single-needle procedure at ultrasonography (US) in twin pregnancies to confirm interfetal transfusion in monochorionic twins and delineate placental angioarchitecture in pregnancies with twin-twin transfusion syndrome. MATERIALS AND METHODS: Fourteen twin pregnancies were studied over 12 months: seven with monochorionic twins, including six with twin-twin transfusion syndrome; two of unknown chorionicity; and five with known dichorionic twins discordant for fetal karyotype or anomaly and undergoing selective feticide in the third trimester. Bolus injection of 100 microL/kg of estimated fetoplacental weight of 400 mg/mL of SH U 508A was performed in the intrahepatic vein of one twin, and evidence of interfetal transfusion was sought by means of digital analysis of power Doppler signals in the contralateral twin. RESULTS: Contralateral twin echo enhancement was seen in four of the nine ultimately histopathologically proved monochorionic twins. As expected, no evidence of echo enhancement in the contralateral twin was seen in any of the five dichorionic twin pregnancies. There was no evidence of fetal compromise associated with the procedure. CONCLUSION: These pilot results suggest that microbubbles can be used to demonstrate interfetal transfusion but not to delineate placental vascular anatomy.

Adult↗

Clinical outcome of congenital talipes equinovarus diagnosed antenatally by ultrasound.

Congenital talipes equinovarus is a common anomaly which can now be diagnosed prenatally on a routine ultrasound scan at 20 weeks of gestation. Prenatal counselling is increasingly offered to parents with affected fetuses, but it is difficult to counsel parents if there is a chance that the fetus may not have talipes. Our study correlates the prenatal ultrasound findings of 14 infants diagnosed as having unilateral or bilateral talipes during their routine 20-week ultrasound scan with their clinical findings at birth and the treatment received. No feet diagnosed as talipes on the ultrasound scan were completely normal at birth and therefore there were no true false-positive results. One foot graded as normal at 20 weeks was found to have a mild grade-1 talipes at birth, but did not require treatment other than simple stretches. A total of 32% of feet required no treatment and so could be considered functional false-positive results on the scan. Serial casting was required by 13% of feet and surgical treatment by 55%. The severity of the talipes is difficult to establish before birth. A number of patients are likely to need surgical treatment, but a proportion will have talipes so mildly that no treatment will be required. In counselling parents at 20 weeks, orthopaedic surgeons need to know whether or not there is a small chance that the ultrasound diagnosis could be wrong and also that the talipes may be so mild that the foot will not require treatment.

Casts, Surgical↗