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PubMed1988

The relationship of maternal and fetal glucose concentrations in the human from midgestation until term.

The relationship between maternal and fetal glucose concentrations was investigated in pregnant women at different gestational ages. Maternal and fetal blood samples were obtained during 14 fetoscopies (17 to 21 weeks), four umbilical cord samples (32 to 36 weeks), nine elective cesarean sections with appropriate for gestational age (AGA) fetuses (35 to 39 weeks) and nine elective cesarean sections with small for gestational age (SGA) fetuses (34 to 37 weeks). A significant linear relationship between maternal and fetal glucose concentrations was demonstrated at midgestation (P less than .001) and at late gestation (P less than .001). At equal maternal concentrations there were no significant differences in fetal glucose concentration between the cord samples obtained in late gestation and those obtained at cesarean section. At midgestation fetal glucose concentration is independent of and may exceed maternal concentration at maternal glucose levels less than 4.44 mmol/L. Furthermore, the relationship between maternal and fetal concentrations at maternal glucose concentrations greater than 4.44 mmol/L is significantly different at midgestation from that at late gestation (P less than .01); at equal maternal concentrations there were higher glucose concentrations in the mid trimester fetus. In late gestation as the maternal glucose concentration increases there is an increase in the maternal arterial-umbilical arterial glucose concentration difference and the umbilical glucose/oxygen quotient (P less than .003) reflecting increased glucose utilization by the fetus. There were no significant differences between AGA and SGA babies with respect to these relationships.

Blood Glucose↗
PubMedDate not supplied

Prenatal diagnostic techniques. Chorionic villus sampling.

Chorionic villus sampling (CVS) is a new prenatal diagnostic technique which is performed in the first trimester of pregnancy. Traditional methods of prenatal diagnosis, including amniocentesis and fetoscopy, must be performed in the midtrimester. In concert with the development of DNA methods of fetal cell analysis, first trimester fetal diagnosis utilizing CVS offers many advantages over traditional mid-trimester techniques. In addition, CVS may potentially allow therapeutic intervention to prevent or ameliorate some congenital defects.

Amniocentesis↗
PubMed1985

Fetal blood sampling during pregnancy with use of a needle guided by ultrasound: a study of 606 consecutive cases.

Because of various prenatal diagnoses, 606 fetal blood samplings were carried out in 562 pregnancies from the gestational week 17 to 38 with use of a 20-gauge needle guided by ultrasound. The procedure was performed on outpatients under local anesthesia and without medication before or after the procedure. Pure fetal blood was obtained at the first attempt in 588 cases. A second attempt was necessary in 18 cases. Maternal blood contamination was never present. Amniotic fluid dilution was noted in 15 cases. At the beginning of our experience only three cords could not be punctured. The duration of the procedure was less than 10 minutes in 90% of cases. Fifty-eight pregnancies were terminated after consideration of the results of the diagnosis, and 504 pregnancies were continued. The complications found in these pregnancies were premature delivery (5%), growth retardation (8%), in utero death (1.1%), and spontaneous abortion (0.8%). In the future this new procedure could replace fetoscopy and initiate an important field of new investigations.

Blood Specimen Collection↗
PubMed1979

Plasma assay of fetal factors VIIIC and IX for prenatal diagnosis of haemophilia.

Fetal blood unmixed with maternal blood or amniotic fluid was obtained by direct-vision fetoscopy in 22 consecutive cases at 15--22 weeks' gestation; the investigation was done either for prenatal diagnosis or before therapeutic abortion. Fetal plasma factors VIIIC and IX averaged 50 I.U./dl (S.D. 12.8) and 12.5 I.U./dl (S.D. 2.4), respectively. Two male fetuses at risk of haemophilia had normal factor VIIIC levels by these criteria, and both pregnancies ended in the birth of a normal boy. Five others gave 3 normal and 2 haemophilic results, which were confirmed in two of the three terminated pregnancies.

Amniocentesis↗
PubMed1980

Dual diagnosis of prenatal haemophilia A by measurement of fetal factor VIIIC and VIIIC antigen (VIIICAg).

Procoagulant factor VIII (VIIIC) and procoagulant factor VIII antigen (VIIICAg) were measured in 20 samples of pure fetal blood obtained by fetoscopy at mid-term from non-haemophilic fetuses. VIIIC levels ranged from 25 to 89 U/dl (mean 43.5) and VIIICAg from 11 to 43 U/dl (mean 22.3). Samples from 39 consecutive fetuses at risk of haemophilia A gave results indicating haemophilia in 11, and these pregnancies were terminated at the parents' request. Of the remaining 28, 18 have resulted in normal births, 8 still await delivery, and 2 pregnancies were terminated for non-haematological reasons. The results confirm that pure fetal blood can be aspirated fetoscopically for plasma assays of both VIIIC and VIIICAg. Dual measurement enhances the reliability of predicting or excluding haemophilia A, and makes prenatal diagnosis a dependable option for known or potential carriers seeking this information.

Antigens↗
PubMed1989

Diagnosis of congenital toxoplasmosis in Scotland.

During a period of 10 years (1976-1986) 853 cases of toxoplasmosis were identified serologically in the Toxoplasma Reference Laboratory in Scotland. Suspected cases of infection in pregnancy (29 cases) and of congenital infection (27 cases) were rare but ophthalmic disease was common (224 cases). In two of the congenital cases, maternal infection was identified during pregnancy. The other 25 babies were investigated because of suspected congenital infection. Toxoplasmosis was confirmed retrospectively in 11/25 babies and excluded in two of them. The other 12 cases remain unclassified. Diagnosis of infection in babies was difficult although the introduction of an IgM capture ELISA was of some help. IgM was detected by ELISA in 3/13 congenitally infected babies but by immunofluorescence tests in only one of these. In two antenatal studies, involving 16,000 women, an additional 32 women were identified whose babies might have benefited from treatment or the availability of fetoscopy for early detection of congenital infection.

Animals↗
PubMed2001

Doppler ultrasound measurements in the central circulation of anesthetized fetal sheep during obstruction of umbilical-placental blood flow.

OBJECTIVE: To establish by Doppler ultrasound the effects of acute blockage of umbilical cord vessels on the fetal central circulation. DESIGN: Experimental study in anesthetized pregnant sheep. METHODS: In 11 anesthetized pregnant sheep (0.66 of gestation), Doppler velocity profiles and/or venous flow rates were recorded in the ductus venosus, the fetal aorta, the umbilical arteries and the umbilical vein. This involved three phases. In Phase 1, the abdominal wall was closed (n = 9); Phase 2 was during fetoscopy after laparotomy (n = 8); Phase 3 was after coagulation of one of the umbilical arteries (n = 10). As an additional intervention in six fetuses, the umbilical cord was clamped for 5-15 s while blood flow velocity changes in the ductus venosus were observed. RESULTS: There were no significant differences between Doppler recordings in Phases 1 and 2. During Phase 3, the pulsatility index of the aorta and of the coagulated umbilical artery increased significantly. The umbilical vein blood flow rate was significantly reduced from a median of 408 (range, 243-575) mL/min/kg in Phase 1 to a median of 173 (range, 107-426) mL/min/kg in Phase 3, but the blood flow rate in the ductus venosus (median, 94; range, 56-148 mL/min/kg vs. median, 92; range, 33-237 mL/min/kg) remained unchanged. The ductus venosus/umbilical vein ratio increased from a median of 0.22 (range, 0.13-0.41) to 0.56 (range, 0.17-0.97) (P < 0.05). Compression of the cord (5-15 s) immediately reduced the time averaged maximum velocity in the ductus venosus from a mean of 51 (standard deviation, 11) cm/s to 20 (standard deviation, 6) cm/s (P < 0.001) without significant changes of the velocity profile. However, the pulsatility index increased from a mean of 0.55 (standard deviation, 0.19) to 1.89 (standard deviation, 0.73) (P < 0.001). CONCLUSION: Central venous flows in anesthetized fetal sheep are unaffected by laparotomy and hysterotomy. Obliteration of one umbilical artery increases the ductus venosus/umbilical vein volume flow (mL/min/kg) ratio. Compression of the umbilical cord shifts down blood flow velocity profiles in the ductus venosus, and the pulsatility index thus increases.

Animals↗
PubMed1983

Prenatal diagnosis using DNA polymorphisms. Report on 95 pregnancies at risk for sickle-cell disease or beta-thalassemia.

DNA polymorphisms are normal inherited variations in DNA that can often be used to document the inheritance of genes that produce disease. In this report we summarize our experience with prenatal diagnosis in 95 pregnancies in which the fetus was at risk for a hemoglobinopathy; the diagnosis was performed with use of DNA polymorphisms located so near the beta-globin gene that they are inherited along with that gene. Of the 95 pregnancies, 57 involved fetuses at risk for sickle-cell anemia, 32 fetuses at risk for beta-thalassemia, and 6 fetuses at risk for other beta-chain hemoglobinopathies. Diagnosis was achieved solely by analysis of DNA polymorphisms in cells recovered by amniocentesis in 82 cases (86 per cent) and was completed by fetoscopy and fetal-blood study in an additional 6 cases (6 per cent). Prenatal diagnosis was proved correct in all 78 cases that have been available for confirmation to date. Our experience demonstrates that DNA polymorphisms can be useful for the prenatal diagnosis of genetic diseases in which the basic defect cannot be directly detected.

Amniocentesis↗
PubMed1980

Prenatal diagnosis of sickle cell anemia by restriction and endonuclease analysis: HindIII polymorphisms in gamma-globin genes extend test applicability.

Polymorphism for a Hpa I restriction endonuclease site associated with about 60% of beta S genes in American Blacks allows exact prenatal diagnosis of sickle cell anemia by amniocentesis in 36% of couples at risk. In three families in whom exact diagnosis by Hpa I sites was impossible, we found analysis for the presence of polymorphic HindIII sites in the G gamma and A gamma intervening sequences would allow an exact prenatal diagnosis of sickle cell status in all three. In one of these families, the presence of an A gamma HindIII site in amniocyte DNA confirmed the diagnosis (sickle cell trait) made by synthetic studies using fetal erythrocytes obtained at fetoscopy. Studies of other Black families and individuals provide evidence for linkage disequilibrium in the G gamma-A gamma-delta-beta gene complex involving the four sites, G gamma HindIII, A gamma HindIII, beta S, and Hpa I, which span 33 kilobases (kb). Ten of 14 chromosomes bearing a beta S gene in a 7.6-kb Hpa I fragment contained a G gamma but not an A gamma HindIII site, whereas 16 of 16 chromosomes bearing a beta S gene in a 13-kb Hpa I fragment lacked both the G gamma and A gamma HindIII sites. Two-thirds of beta A-bearing chromosomes lacked both G gamma and A gamma sites, whereas one-third contained either the G gamma or both G gamma and A gamma sites. These data demonstrate that combined analysis of both Hpa I and HindIII polymorphisms and verification of their linkage phase should increase the fraction of couples for whom amniocentesis can provide an exact diagnosis of sickle cell status from 36% to greater than 80%.

Anemia, Sickle Cell↗
PubMed2004

Fetoscopic surgery: where are we today?

PURPOSE OF REVIEW: Since the early 1990s, advances in endoscopic equipment and the commercial availability of micro-catheters, mini-balloons, tiny laser fibers and other ingenious tools have set the trend toward the development of minimally invasive fetoscopic surgical techniques for the treatment of some congenital malformations that progress in severity over the course of gestation and may destroy entire organ systems of the unborn. The purpose of this review is to provide a state-of-the-art overview of these new procedures for the anesthesiologist. RECENT FINDINGS: Procedures like diagnostic fetoscopies, laser coagulation of inter-twin placental vascular connections in twin-twin transfusion syndrome, fetal tracheal balloon occlusion in diaphragmatic hernia, laser perforation of posterior urethral valves, vocal cord division in congenital high-airway obstruction syndrome and most recently even coverage of spina bifida aperta can be performed entirely percutaneously using minimally invasive fetoscopic techniques. Careful selection of anesthetic methods and intensive maternal monitoring by the anesthesiology team are paramount to the success of these procedures, particularly in hemodynamically unstable fetuses or procedures that employ gas insufflation of the amniotic cavity. SUMMARY: An increasing spectrum of congenital malformations can be treated by fetoscopic surgery. Compared to open fetal surgery, fetoscopic surgery results in significantly less maternal trauma. Like the open procedures, the efficacy of the fetoscopic procedures to improve fetal outcome over postnatal treatment strategies will have to be assessed in further studies under close supervision of committees for human research.

Journal Article↗
PubMed2006

Recent findings on laser treatment of twin-to-twin transfusion syndrome.

PURPOSE OF REVIEW: Despite the recent demonstration of the benefit of the primary laser over amnioreduction, overall survival is far from optimal (70-80%), and therefore diagnosis and management of early and late complications following placental surgery became of great importance. RECENT FINDINGS: Laser therapy has proven to be better than amnioreduction in treating twin-to-twin transfusion syndrome. Miscarriage, preterm premature rupture of the membranes and preterm delivery account for more than 20% of perinatal mortality after treatment. In those who die despite treatment, recurrence of twin-to-twin transfusion syndrome, placental insufficiency or feto-fetal hemorrhage with anemia/polycythemia are complications that have to be managed with different secondary therapeutic options, such as amnioreduction, cord coagulation, intrauterine transfusion or repeat fetoscopy-guided laser. Ex-vivo placental angiography has confirmed that these complications occur when anastomoses are missed. Early predictors of laser efficacy in twin-to-twin transfusion syndrome treatment, such as improvement in the umbilical vein flow imbalance and urine production, are being evaluated, because they are earlier predictors of outcome than amniotic fluid discordance. SUMMARY: Optimization of laser treatment of twin-to-twin transfusion syndrome and new insight into the follow-up are likely to become the key to a better prognosis, and they are therefore important issues that have to be addressed in forthcoming studies.

Female↗
PubMed1982

Normal activities of glycolytic enzymes in the fetal erythrocytes.

Pure fetal blood was obtained by direct-vision fetoscopy from 24 fetuses at 17-24 weeks' gestation. The activities of 14 glycolytic enzymes in the erythrocytes were analysed by established techniques to find the normal ranges of activity for this gestational age. The results were compared with those obtained from 24 normal adults and with published values on neonatal blood. The activities of most enzymes in fetal erythrocytes were found to be higher and the relative pattern of activity different from those of adult or neonatal blood. The ranges were relatively narrow and can serve as reference values for the prenatal diagnosis of erythrocytic enzymopathies. Also, the activities of the glycolytic enzymes will provide a basis for the understanding of erythrocyte metabolism in the fetus.

Adult↗
PubMed1984

Normal glutathione content and some related enzyme activities in the fetal erythrocytes.

Pure fetal blood was obtained by direct-vision fetoscopy from 66 fetuses at 17-24 weeks gestation. The concentration of GSH and the activities of the enzymes gamma-glutamylcysteine synthetase (GCS), glutathione synthetase (GS), glutathione reductase (GR) and glutathione peroxidase (GPx) were analysed by established techniques to find the normal ranges for this gestational age. The ranges were relatively narrow and could serve as reference values for the prenatal diagnosis of defects in the GSH metabolism of erythrocytes. The results were compared with those obtained from 38 normal adults and with published values on neonatal blood. In the case of GR a comparison was also made with maternal blood. In comparison with adults, fetal erythrocytes showed higher GSH concentration and GCS activity and lower GS and GPx activities. This pattern resembled that found in neonatal erythrocytes except for the GCS activity, which was higher in the fetal cells. Furthermore the differences between fetal and adult erythrocytes were more pronounced than those between neonatal and adult cells. The GR activity of fetal erythrocytes was also higher than that of either normal adult or maternal blood. This difference, however, was reduced to an insignificant level when the enzyme was activated in vitro by flavin adenine dinucleotide (FAD) because of a relatively low per cent activation of the GR in the fetal erythrocytes.

Enzyme Activation↗
PubMed1986

Normal levels of ATP, total nucleotides and activities of three enzymes related to nucleotide metabolism in fetal erythrocytes.

Pure fetal blood was obtained by direct-vision fetoscopy from 30 fetuses at 17-23 weeks gestation. The erythrocyte concentrations of ATP and total nucleotides and the activities of the enzymes pyrimidine-5'-nucleotide nucleosidase (Pyr5N), phosphoribosylpyrophosphate (PRPP) synthetase and adenylate kinase (AK) were analysed by established techniques to find the normal ranges for this gestational age. The ranges were relatively narrow and could serve as reference values for the prenatal diagnosis of defects in nucleotide metabolism. The results from the fetal erythrocytes were compared with the corresponding values from the maternal blood collected and analysed concurrently. The ATP and total nucleotide concentrations and the activity of Pyr5N in the fetal cells were substantially higher than those of the maternal blood. The activities of PRPP synthetase and AK were much lower. The significance of these findings is discussed.

5'-Nucleotidase↗
PubMed1987

The use of monoclonal antibodies UCH beta and UCH gamma for the antenatal diagnosis of beta-thalassaemia.

Monoclonal antibodies for the beta-globin chain of human HbA (UCH beta) and the gamma-globin chain of human HbF (UCH gamma) have been made. UCH beta indirectly labelled with rhodamine-labelled goat anti-mouse Ig and directly flouresceinated UCH gamma have been used, via double labelling immunofluorescence microscopy, to assay for the presence of beta-chains in fetal erythrocytes obtained at fetoscopy from fetuses at risk for beta-thalassaemia major. The results from 111 cases demonstrate that beta-chain synthesis of as low as 1.8% can be detected in fetal erythrocytes. The immunochemical labelling can be rendered more sensitive by the use of biotinylated UCH beta and avidin-FITC conjugates. This method is rapid and can be used for a sample that is highly contaminated with maternal erythrocytes.

Antibodies, Monoclonal↗
PubMed1988

Carrier detection in 50 haemophilia A kindred by means of three intragenic and two extragenic restriction fragment length polymorphisms.

Carrier detection was attempted in 50 haemophilia A kindred by means of restriction fragment length polymorphism (RFLP) analysis using two linked and three intragenic probes. The sample comprised 330 individuals including 70 haemophiliacs, 45 obligate carriers and 100 possible carriers. Non-related haplotypes contained within the sample group were used to tabulate the intragenic RFLP allele frequencies. The linkage disequilibrium existing between the XbaI and Bc1I RFLP was shown to be less than previously reported, such that 69% of women are informative for at least one of these two polymorphisms. 36 women were subsequently diagnosed as carriers and 37 as being normal: in 52 of these, diagnosis was based either on intragenic RFLPs or linked RFLP plus strong phenotypic data, and was considered to be unequivocal; in the remaining 21, diagnosis was based on linked RFLPs alone and was considered to be probabilistic, with a 5-10% possible error rate. 27 of the possible carriers, either from families with sporadic haemophilia or from families where missing members precluded haplotype analysis, remained unassigned. 72% of the obligate carriers and firmly diagnosed carriers were heterozygous and phase known for at least one intragenic RFLP, whereas 6% were uninformative for the RFLPs for which they were examined. In 54 informative meioses, three recombinations between the factor VIII locus and the DX13 and/or ST14 loci were observed, giving a recombination rate of 5.5%. 15 prenatal diagnoses were carried out. Of the 11 male fetuses, six were shown to be affected and five to be normal. In three of four prenatal diagnoses where only a linked RFLP was informative, the result was confirmed by fetoscopy, fetal blood sampling, and factor VIII assay.

Alleles↗
PubMed1979

Prenatal testing for birth defects and nursing practice.

Recent advances in the prenatal diagnosis of birth defects including amniocentesis, ultrasound and fetoscopy are discussed. Indications, technical considerations and limitations are presented. Parental reactions to the stresses encountered during the process of prenatal diagnosis are related. Implications are identified for nursing care practice in different clinical settings including prenatal diagnostic units, paediatric services, obstetrical services and in the community.

Chromosome Aberrations↗
PubMed1982

Amniotic fluid acetylcholinesterase: a retrospective and prospective study of the qualitative method.

After retrospective evaluation with stored samples, the qualitative acetylcholinesterase (AChE) test has been used prospectively in conjunction with alpha-fetoprotein (AFP) assay on 986 amniotic fluid specimens received in this laboratory during 1980. The main value of AChE is in classifying fluids in which the AFP level is near the threshold between normal and abnormal. Among abnormal pregnancies with raised AFP levels, neural-tube defects can generally be distinguished from other abnormalities by careful appraisal of the AChE gel pattern, but confirmation of these other fetal abnormalities may require high resolution diagnostic ultrasonography and perhaps fetoscopy. Neural-tube defects with false negative AFP levels can be detected by AChE, but AChE gives occasional false positives so that it cannot be relied on in isolation for the diagnosis of neural-tube defects.

Acetylcholinesterase↗