Biomedical subjects
Publications and source records attributed to N M Fisk.
The incidence of twin pregnancies continues to rise with increasing use of assisted fertility techniques. The search for accurate methods of chorionicity determination and aneuploidy screening, and the outcome following multi-fetal pregnancy reduction dominate the recent literature. In addition, debate on the aetiology and management of the transfusional complications of monochorionicity continues.
Cleidocranial dysostosis is an autosomal dominant disorder characterized by absence or hypoplasia of the clavicles, skull abnormalities, and abnormal dentition. The prenatal diagnosis of this condition has been reported once previously in a known high-risk pregnancy. In this report we describe the prenatal findings of cleidocranial dysostosis at 19 weeks' gestation in a woman affected with this disorder but undiagnosed before the fetal scan. This report is unique in the sense that an autosomal dominant condition diagnosed in the fetus led to a similar diagnosis in the mother.
Until recently, doctors and patients have been united in wanting lower caesarean section rates. This is changing, and the concept of a more liberal patient-centred choice is gaining credence. Caesarean sections are no longer black and white decisions, but are becoming increasingly discretionary, based on maternal choice, their increasing safety for mother and baby, and recognition of the pelvic damage associated with vaginal birth.
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OBJECTIVE: To determine the prevalence of the most common cystic fibrosis mutations in pregnancies complicated by fetal echogenic bowel by using DNA testing. METHODS: Forty-five pregnancies with fetal echogenic bowel were studied prospectively for cystic fibrosis mutations. Using polymerase chain reaction, DNA from fetal amniocytes (n = 21), fetal blood (n = 5), or parental blood (n = 19) was amplified and tested for delta F508, G551D, G542X, and 621 + 1G-->T cystic fibrosis mutations, which account for about 85% of the mutations in the British population. In selected cases, further mutations were tested according to the parental ethnic background. RESULTS: Only one of the 26 fetuses screened was heterozygous for cystic fibrosis mutations. Among 38 parental samples screened from the remaining 19 pregnancies, cystic fibrosis mutations were detected in two cases, only one of the parents being a carrier in each case. The prevalence of cystic fibrosis carrier status in fetal and parental samples (1:26 and 1:19, respectively) is within the expected prevalence in the British population (1:25). No fetuses were affected by cystic fibrosis in this series, but five were found to have growth restriction, two trisomy 21, two congenital infection, and two bowel obstruction. CONCLUSION: Our results suggest that ultrasonographic detection of fetal echogenic bowel is not associated with an increased prevalence of cystic fibrosis mutations in pregnancies at low risk for this disease.
OBJECTIVE: To determine the failure rate of karyotyping from samples taken after termination of pregnancy for fetal abnormality. METHODS: Perinatal autopsy reports over a 12-month period were reviewed to identify those with cytogenetic studies performed after termination of pregnancy for fetal abnormality. RESULTS: During the audit period, there were 104 terminations for fetal abnormality. In 89 fetuses, fetal skin (n = 85), placenta (n = 62), or other samples (n = 8) were obtained for postmortem cytogenetic analysis. In 24 (27%) fetuses, postmortem tissues did not yield a karyotype result. The failure rate of post-termination karyotyping was significantly influenced by delivery-sampling interval, but not by gestational age, type of tissue sampled, use of potassium chloride, or aneuploidy. Of the 24 cases for which no post-termination karyotype was obtained, 16 had had successful pre-termination karyotyping, resulting in only eight of 89 (9%) cases in the overall series not having a final karyotype. CONCLUSION: The high failure rate for post-termination karyotyping suggests that a pre-termination procedure is necessary if parents wish to have almost 100% certainty that cytogenetic information will be available for later genetic counseling.
OBJECTIVE: We investigated whether reliable prenatal diagnosis is possible from fetal cells harvested transcervically in first-trimester pregnancies. STUDY DESIGN: Fetal cells were obtained transcervically from 87 women undergoing pregnancy termination. Fetal gender was determined in 51 pregnancies with three different polymerase chain reaction techniques and in 36 pregnancies with fluorescent in situ hybridization. In known male pregnancies the number of male fetal cells present was also determined. RESULTS: Polymerase chain reaction detected male deoxyribonucleic acid in up to 79% of cases in male pregnancies and up to 45% of cases in female pregnancies. Fetal gender was correctly predicted in up to 72% of cases with fluorescent in situ hybridization. However, fetal cells were identified in < 40% of informative male pregnancies and were present in low numbers-0.7% to 3.4% in swabs and 4.4% to 24.8% in flushes. CONCLUSION: The use of fetal cells obtained by minimally invasive first-trimester transcervical sampling is unreliable for prenatal diagnosis.
OBJECTIVE: Our purpose was to determine whether the presence of heme pigments in amniotic fluid is associated with the ultrasonographic findings of increased fetal bowel echogenicity in the second trimester. STUDY DESIGN: Spectrophotometric analysis of amniotic fluid for optical density at 410 nm was prospectively performed to study the presence of heme pigments in (1) 104 pregnancies undergoing second-trimester amniocentesis for routine cytogenetic indications and (2) in 14 pregnancies undergoing amniocentesis for prenatal karyotyping because of fetal strongly echogenic bowel. In the routine amniocentesis group the fetal small bowel echogenicity was assessed immediately before amniocentesis and classified as nonechogenic (n = 64), mildly echogenic (n = 36), or hyperechogenic (n = 4) with the fetal iliac wing and liver used as references. Only amniotic fluid specimens that were obtained at the first attempt and that were not blood-stained were included in this study, with the first milliliter being discarded in all samples. RESULTS: In the routine amniocentesis group abnormal amniotic fluid optical density readings were significantly more frequent in fetuses with increased bowel echogenicity compared with those with nonechogenic bowel (8/40 [20%] vs 3/64 [5%], respectively; p < 0.001). In the hyperchogenic bowel group abnormal amniotic fluid optical density readings were found in four samples (29%). Overall, 12 of 54 fetuses (22%) with increased bowel echogenicity had a detectable peak at 410 nm. Three of the 12 (25%) fetuses with echogenic bowel and positive readings for hemoglobin were chromosomally abnormal. CONCLUSIONS: Fetal small bowel echogenicity is associated with the presence of heme pigments in amniotic fluid as determined by amniotic fluid optical density at 410 nm. Swallowing of amniotic fluid after intraamniotic bleeding seems implicated in the etiology of second-trimester echogenic bowel in both euploid and aneuploid fetuses.
OBJECTIVE: Our purpose was to determine whether the twin reversed arterial perfusion sequence (acardiac anomaly) results from fertilization of the first or second polar body. STUDY DESIGN: Placental or fetal tissue was obtained from nine twin sets discordant for twin reversed arterial perfusion. After deoxyribonucleic acid extraction, the polymerase chain reaction was used to amplify five polymorphic microsatellite repeats. The products were differentiated by polyacrylamide gel electrophoresis, and patterns were compared within twin sets. RESULTS: Deoxyribonucleic acid fingerprinting patterns were identical in all twin sets for all primer pairs. It is calculated that the chance that any of the acardiac twins resulted from fertilization of either the first or second polar body is <4% and the chance that they all resulted from polar body fertilization is <0.001%. CONCLUSION: Twins discordant for the twin reversed arterial perfusion sequence anomaly are monozygous. Our results exclude polar body fertilization as a likely cause of this condition.
OBJECTIVE: In spite of recent advances in the assessment and treatment of fetofetal transfusion syndrome, its underlying mechanism remains controversial. We aimed to determine whether the clinical features of fetofetal transfusion syndrome could be explained by unidirectional or bidirectional intertwin transfusion along placental vascular anastomoses. STUDY DESIGN: We constructed a dynamic computerized model of monochorial twin fetoplacental units on the basis of numerous interrelated hemodynamic, osmotic, and metabolic physiologic variables. The circulations were then linked by various combinations of direction and number of arteriovenous anastomoses. RESULTS: With unidirectional anastomoses disease severity, characterized by disparity in blood solids, depended on donor arterial pressure but not on the number of anastomoses. In the chronic state water movement resulting from raised osmotic pressure in the recipient and reduction in the donor produced hydroosmotic pressure equilibrium, reducing anastomotic flow to near zero. Atrial natriuretic peptide-driven urine production was markedly increased in the recipient because of the raised vascular hydrostatic pressure component. With bidirectional anastomoses recirculation between twins reduced discordancy in colloids and hematocrit, and the clinical picture was determined by the degree of asymmetry in the number of connections. CONCLUSIONS: Severe manifestations of fetofetal transfusion syndrome can be explained by unidirectional intertwin transfusion and lesser degrees by asymmetric bidirectional transfusion.
Hyperechogenic bowel has been described as a normal variant in second-trimester fetuses, but also in association with cystic fibrosis, chromosomal abnormalities, congenital infection, intestinal obstruction and intra-amniotic bleeding. These fetuses are also at risk for poor perinatal outcome, mainly due to intrauterine growth retardation. In this report we examine the potential of ultrasonographic detection of isolated fetal hyperechogenic bowel in the second trimester as a marker of subsequent suboptimal fetal growth. Second-trimester fetuses with hyperechogenic bowel in comparison to controls had a greater incidence of birth weight below the 10th centile (6/48, 12.5% vs. 4/149, 2.7%, respectively; p = 0.01) and lower mean birth weight (3176 g (SD 741 vs. 3499 g (SD 493)), respectively; p = 0.001). There was no difference in the prevalence of preterm delivery in both groups (3/48, 6.3% vs. 8/149, 5.4%, respectively; p = 0.7). This study suggests that second-trimester fetuses normally-grown with isolated hyperechogenic bowel are at risk for suboptimal fetal growth.
DESIGN: Prospective audit of first six months. SETTING: Referral from a district general hospital on the Isle of Wight to a comprehensive tertiary referral service, the Centre for Fetal Care at Queen Charlotte's Hospital 120 km away in London. PARTICIPANTS: Women whose pregnancy was suspected, or at risk, of fetal abnormality. INTERVENTIONS: Remote consultation by transmitting ultrasound and video in real-time over ISDN 30 telephone lines. Contemporaneous questionnaire to referring practitioner and patient. MAIN OUTCOME MEASURES: Frequency, indication, technical success and duration of consultation. Qualitative and semi-quantitative image quality. Effect of teleconsultation on need for physical referral. RESULTS: Twenty-nine women underwent 39 teleconsultations, and image quality was sufficient for diagnosis in all but one. Fetal abnormalities were present in 76%. Referral in person was required for only four women, significantly fewer than the 13 the referring hospital indicated would have been physically referred in the absence of this service (P < 0.001). Most mothers were counselled by the specialist "face-to-face' over the link, and 80% felt teleconsultation reduced their anxiety. CONCLUSIONS: A fetal telemedicine service is technically and clinically feasible. This demonstration suggests that such a service reduces the need for physical referral while increasing the rate of consultation, allowing better selection of patients who might benefit from referral. Further evaluation in a variety of clinical settings is now indicated, along with cost-benefit analysis.
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OBJECTIVES: In fetuses with a single umbilical artery the entire blood flow to the placenta is transported through the common and internal iliac arteries from the side of the single artery, whereas the pelvic vessels from the side of the missing artery do not participate in the fetoplacental circulation. The aim of this study was to investigate the effect of gestational age on pelvic arterial blood flow in fetuses with single umbilical artery. DESIGN: In 15 fetuses with a single umbilical artery (SUA), common iliac artery flow velocity waveforms were studied longitudinally using high resolution colour Doppler ultrasonography at three gestational ages: 18 to 20 weeks, 28 to 30 weeks, and 35 to 37 weeks. The pulsatility index was measured in each common iliac artery and mixed model analysis of variance was used to examine the effect of gestational age and side. RESULTS: There was a highly significant difference in pulsatility index between common iliac arteries at all gestational ages, the values always being higher on the side that did not participate in the fetoplacental circulation (P < 0.001). For increasing gestation, the pulsatility index fell significantly in the SUA side but remained high in the non-SUA side (P < 0.001). CONCLUSIONS: This study shows that the asymmetry in the pelvic arterial blood flow in fetuses with SUA increases as pregnancy progresses, consistent with decreasing vascular resistance in the placenta and increasing resistance in the lower extremities.
The transport and uptake of TRH was investigated in the maternal-fetal-placental unit of perfused human term placenta. The degradation of TRH in biological fluid was first determined by incubating [125I]TRH with 100 microL 50% maternal or cord sera with or without pretreatment with 200 microM of p-hydroxymercuriphenyl sulfonic acid (p-HMSA), a proline dipeptidase inhibitor. Transplacental transfer of TRH was then studied by adding 10 microCi of [125I]- or [3H]TRH to the maternal circulation of dually perfused isolated lobule of human term placenta with or without 200 microM p-HMSA. Creatinine was used as an internal marker. The rate of degradation of TRH (P < 0.001) and inhibition by p-HMSA were significantly higher in maternal than cord sera (P < 0.05). In the maternal circulation, TRH concentration declined rapidly from 100% at time 0 to 33.5 +/- 1.2% at 120 min. The fetal concentration increased from undetectable levels to a maximum of 1.8 +/- 0.3% at 120 min with a low feto-maternal ratio (0.08 +/- 0.02). Perfusion in the presence of p-HMSA, however, did not significantly change fetal concentration, or the maternal and fetal concentration-time integral levels of TRH. Chromatography of maternal, fetal, and placental homogenates showed that TRH was metabolized by the placenta into small molecular weight fragments predominantly released in the maternal circulation. These results suggest that human placenta acts as an enzymatic barrier to the free passage of TRH.
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