Prenatal diagnosis: the way ahead?
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Biomedical subjects
Publications and source records attributed to M D Kilby.
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Oligohydramnios-polyhydramnios sequence in twin pregnancies may be managed by aggressive amniocentesis and is described in nine consecutive cases. In four of the nine pregnancies both twins survived, one pair died in the neonatal period, and the other four pairs all suffered intrauterine death. The median number of amnioreductions performed was five (range 2-7). In this series the reaccumulation of urine in the bladder of the 'stuck twin' was a predictive prognostic marker of survival in both twins, with a sensitivity and specificity of 100%.
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OBJECTIVES: Analysis of incidence and characteristics of congenital abdominal wall defects, with special reference to the differences between the incidence of gastroschisis and exomphalos (omphalocele). DESIGN: Retrospective analysis using data from the Office of Population Censuses and Surveys (recoded to differentiate exomphalos and gastroschisis) and the National Congenital Malformation Notification Scheme. SETTING: England and Wales, 1987 to 1993. RESULTS: 1043 congenital anterior abdominal wall defects were notified within the seven year study period. Of these, 539 were classified as gastroschisis, 448 as exomphalos, 19 as "prune belly syndrome," and 37 as "unclassified." Gastroschisis doubled in incidence from 0.65 in 1987 to 1.35 per 10,000 total births in 1991, with little further change; the incidence of exomphalos decreased from 1.13 to 0.77 per 10000 births. The overall incidence of notified congenital abdominal wall defects was 2.15 per 10000 total births. Gastroschisis was associated with a lower overall maternal age than exomphalos and with a significantly lower proportion of additional reported congenital malformations (5.0%) than in the cohort with exomphalos (27.4%) (odds ratio 0.14, 95% confidence interval 0.09 to 0.22; P < 0.001). The sex ratio of the two cohorts was the same. The incidence of gastroschisis and exomphalos was higher in the northern regions of England than in the south east of the country. CONCLUSIONS: The national congenital malformation notification system showed an increasing trend in the incidence of fetuses born with gastroschisis and a progressive decreasing incidence of exomphalos in England and Wales between 1987 and 1993. Although the reasons for this are likely to be multifactorial, a true differential change seems likely. The observed increase in incidence of gastroschisis relative to exomphalos and the differentiation in maternal age have implications for resource management within the NHS and warrant further epidemiological monitoring. Regional differences may be due to a dietary or environmental factor, which requires further study.
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In order to determine the outcome and associated chromosomal and structural anomalies in fetuses diagnosed in utero as having a congenital diaphragmatic hernia, we reviewed 48 consecutive cases referred to our regional Fetal Diagnostic Unit between 1988 and 1995. All babies were delivered in units with appropriate neonatal resuscitation facilities. Thirteen babies [34 per cent of those tested, confidence interval (CI) 19-49 per cent] had karyotypic abnormalities. Three had trisomies but the other nine had more complex karyotypic abnormalities including translocations, deletions, and marker chromosomes. Twenty-one fetuses (44 per cent, CI 30-58 per cent) had additional ultrasound abnormalities which affected the heart in ten cases (21 per cent). Overall, 13 babies survived (27 per cent, CI 14-40 per cent). In babies with normal chromosomes and no additional structural abnormalities the survival rate was 50 per cent (CI 25-75 per cent). Poor outcome was not predicted by early gestation at diagnosis, the hernial contents, or the presence of polyhydramnios. We conclude that parents should be counselled about prognosis with information derived from series of prenatally diagnosed diaphragmatic hernias. The investigations offered should include a detailed ultrasound examination, particularly of the heart, and karyotyping by fetal blood sampling.
Successful pregnancy depends upon placental growth and development, which follows a specific spatial and temporal sequence. Hepatocyte Growth Factor (HGF) is a potent mitogen, morphogen and motogen to both endothelial and epithelial cell types and is linked to a tyrosine kinase, proto-oncogene, c-met receptor. In 'normal' third trimester placentae (n = 5) full thickness biopsies (obtained at Caesarean section), immunolocalisation and in situ hybridisation studies were performed for HGF and c-met., respectively. HGF immunoreactive protein was present in mesenchymal core, the vaculosyncytial membrane (syncytotrophoblast) and the vascular endothelial cells of villous trophoblast. The HGF mRNA was present particularly strongly in the perivascular stromal cells surrounding the villous vasculature and the amnion/chorionic membranes. Immunoreactive c-met protein was strongly localised to the endothelial cells lining the villous vasculature and the vasculosyncytial membrane. A relatively weak and diffuse hybridisation signal for c-met mRNA was present throughout the villous trophoblast, most pronounced in the vasculosyncytial membrane. These results indicate that HGF may serve as a paracrine mediator to control placental development and growth.
1. Lipid, apolipoprotein concentration and composition were determined in maternal venous and umbilical arterial and venous blood at delivery by elective Caesarean section in 13 full-term pregnancies and in 25 healthy non-pregnant females. The indications of Caesarean section were a previous Caesarean section or breech presentation. None of the women was in labour and there were no other complications of pregnancy or fetal distress. 2. The objectives of the study were to establish whether the placenta has a role in feto-maternal cholesterol metabolism through either synthesis or transplacental cholesterol flux. The potential for free cholesterol diffusion between mother and fetus and rates of cholesterol esterification and transfer between lipoproteins were determined and related to the differences in composition between fetal and maternal lipoproteins. 3. Pregnant women had raised levels of all lipid and lipoprotein fractions compared with control subjects. The greatest increases were in free cholesterol and triacylglycerol (P < 0.0001). Lipoprotein (a) levels were significantly greater in the pregnant women [112 (12.2) mg/l] than in the control women [50 (10.0) mg/l]. 4. The only significant correlation between maternal and fetal lipoprotein concentrations was in lipoprotein (a) levels (r = 0.791, P = 0.002). In both umbilical venous and arterial blood, concentrations of very-low- and low-density lipoproteins, particularly apolipoprotein B, cholesteryl ester and triacylglycerol, were lower than in maternal blood (P < 0.0001), but high-density lipoprotein levels were similar. 5. There was no umbilical arteriovenous differences in lipoprotein concentration or composition. This suggests that cholesterol synthesis or free cholesterol diffusion does not occur in the placenta.(ABSTRACT TRUNCATED AT 250 WORDS)
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A prospective study investigated platelet cytosolic calcium in non-pregnant volunteers (n = 30) and samples from the umbilical veins of babies from both normotensive (n = 18) and hypertensive (n = 15) primigravidae, and their mothers. There was no significant difference between the neonatal umbilical venous platelet cytosolic calcium concentration (p[Ca2+]i) in babies born to normotensive primigravidae or to those whose pregnancies were complicated by gestational hypertension (88 x 9 (SE) 2 x 5) in normotensive primagravidae, 80 x 6 (2 x 8) in pregnancy induced hypertension without proteinuria, and 89 x 3 (3 x 2) nmol/l in pre-eclampsia. There was also no significant difference in the p[Ca2+]i from the umbilical veins of the pregnancies studied and those of non-pregnant female volunteers in the follicular phase of their menstrual cycle. This was despite a gradual and significant rise in p[Ca2+]i with increasing severity of disease in the mothers of the babies studied (119 x 9 (4 x 1) in normotensive primagravidae, 130 x 8 (7 x 3) in pregnancy induced hypertension without proteinuria, and 148 x 2 (4 x 5 ) nmol/l in pre-eclampsia). The mean maternal p[Ca2+]i in the three samples returned to concentrations comparable with those in non-pregnant subjects by 12 weeks after birth. These data demonstrate no significant difference between the mean p[Ca2+]i in non-pregnant women and those obtained from the umbilical venous blood of normotensive or hypertensive primigravidae. They suggest that the functional hypoactivity of neonatal platelets is probably not secondary to a decrease in basal p[Ca2+]i. They also suggest that the progressively raised p[Ca2+]i in normal and hypertensive pregnancies might be due to a pregnancy specific factor that does not cross the placenta,
OBJECTIVE: To examine the perinatal and maternal outcomes in twin pregnancies when a single intrauterine death occurs. METHODS: This was a retrospective, observational study. Comparison was made to viable twin pregnancies. RESULTS: Of a total 34,804 live deliveries, 342 were documented as twin births at a gestation of greater than 20 weeks (incidence 0.98%). Of the twin pregnancies over this period, 20 (5.85%) were complicated by a single intrauterine death. There was an increase in the incidence of congenital structural abnormalities among those twins dying in utero as compared to uneventful twin pregnancies (25 versus 0.3%; P < .001). A significant proportion of these twin pregnancies had monochorionic placentas (35 versus 9%; P < .001) and were admitted to special care units (70 versus 5.6%; P < .001) as compared to the normal twin sample. Maternal morbidity has previously been described as being increased. Although there was an increased risk of nonproteinuric and mild pregnancy-induced hypertension, no adverse maternal effects of conservative management were noted in this study. CONCLUSION: The risk of a single fetal death in twin pregnancies is increased with a monochorionic placenta or a structural abnormality. Conservative management and regular surveillance seem advisable.
Five pregnant women whose pregnancies were complicated only by essential hypertension had significantly elevated platelet cytosolic calcium levels as compared with those of their normotensive counterparts. There seems to be an association between platelet cytosolic calcium level and arterial blood pressure that has previously been described in both nonpregnant and preeclamptic women.
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OBJECTIVE: To determine if platelet intracellular free calcium concentration (p.(Ca2+)i) changes with gestation in normotensive, uncomplicated pregnancy. DESIGN: A prospective, longitudinal study of primigravid pregnant women compared to a large control group consisting of nulliparous nonpregnant volunteers. SETTING: The antenatal clinic at University Hospital, Queen's Medical Centre, Nottingham. SUBJECTS: Two groups of women were studied. Thirty-one nulliparous, nonpregnant women not using oral contraception were investigated in the early follicular phase of their menstrual cycles. Also, 24 primigravid women with normotensive, uncomplicated pregnancies were investigated on eight separate occasions during their pregnancies. RESULTS: A significant increase in mean p.(Ca2+)i was demonstrated by 28 weeks gestation in the pregnant women as compared to the nonpregnant control group and the same individuals when investigated at 12 weeks postpartum (P < 0.05; ANOVA). This change was maximal at 36 weeks gestation (P < 0.001; ANOVA); concentrations had returned to those not significantly different from nonpregnant women by six weeks postpartum. CONCLUSIONS: Basal platelet (Ca2+)i increases significantly by the third trimester of normal, primigravid pregnancy as compared to pregnancy values and postnatal values. These data mirror the previously described observations of platelet behaviour noting increased activity at this gestation of pregnancy. It may be that the increased basal p.(Ca2+)i indicates that smaller transient signals have to be generated to induce platelet activity, such as shape change, aggregation and exocytosis.
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