Prenatal Diagnosis Of Fetus Research Articles

Clinical study and prenatal diagnosis of fetus with shortened long bones

To investigate the manifestations and prenatal diagnosis of the fetus with shortened long bones. Ultrasonography was conducted on 57 fetuses with shortened long bones and 62 normal fetuses. Percutaneous umbilical blood sampling was performed on the 57 cases to undergo examination of karyotype and mutation in exon 10 of fibroblast growth factor receptor (FGFR)3 gene. Fetal radiography and autopsy were performed in 30 abnormal induced fetuses. Among the 57 fetuses of the shortened long bones group 21 (37%) were diagnosed as with specific skeletal dysplasia postnatally, abnormal chromosome were found in 8 (14%), 4 (7%) were with fetal growth restriction, and 24 (42%) were with unknown etiology. Prenatal ultrasonography showed that in the fetuses with skeletal dysplasia the value of standard deviation score (SD) for femur length and/or humerus length fell to -4 SD of the corresponding pregnancy week, and increase of biparietal diameter was often found; in the fetuses with abnormal chromosome and fetal growth restriction (FGR) the degree of bone shortening was between -2 SD to -4 SD; and in the fetuses with lethal skeletal dysplasia the long bones were shortened at the degree more than -8 SD. When the ratio of femur length to abdominal circumference was less than 0.16, the sensitivity and specificity for predicting narrow thorax were 100% and 85.7% respectively. The causes of fetus with shortened long bones include abnormal chromosome, skeletal dysplasia, and FGR. Femur length and/or humerus length falls below -4SD is almost an indication for skeletal abnormality. When the SD is between -2SD and -4SD, chromosome analysis is necessary and regular ultrasonography is recommended. When the femur length and/or humerus length is below -8SD and femur length/abdominal circumference (FL/AC) is less than 0.16, lethal skeletal dysplasia is suspected.

Acute increase in femoral artery resistance in response to direct physical stimuli in the human fetus

Objective To determine whether fetal response to needling resembles the fetal ‘brain sparing’ response seen with hypoxaemia.Design Prospective observational study.Setting Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London.Population Eighty‐five pregnant women undergoing invasive procedures associated with fetal prenatal diagnosis and/or management.Methods The femoral artery and the middle cerebral artery pulsatility index were measured by Doppler ultrasonography before and after 89 invasive procedures (fetal blood sampling, transfusion, bladder or cyst aspiration, shunt insertion and amniocentesis, between 17 and 36 weeks). Cases in which the fetal body was transgressed were compared with ‘control’ fetuses undergoing invasive procedures which did not directly involve needling the fetus (amniocentesis and placental cord insertion procedures).Main outcome measures Femoral artery and middle cerebral artery pulsatility index.Results The femoral artery pulsatility index rose after transgression [median change (Δ) 0.73; 95% confidence interval (CI) 0.51 to 0.98]. In contrast, there was no significant change in femoral artery pulsatility index after non‐transgression procedures (mean Δ 0.28; 95% CI −0.20 to 0.76). Analysis confirmed the fall in middle cerebral artery pulsatility index after transgression procedures (median Δ−0.19; 95% CI −0.07 to −0.35), but there was also a significant fall in middle cerebral artery pulsatility index after non‐transgression procedures (mean Δ−0.47; 95% CI −0.23 to −0.71).Conclusions The human fetus mounts a peripheral haemodynamic response to invasive procedures involving transgression of the fetal body, which is consistent with the brain sparing effect. However, the change in middle cerebral artery pulsatility index in both transgression and control procedures suggests that the changes and mechanisms may be more complex than previously thought.

Acute increase in femoral artery resistance in response to direct physical stimuli in the human fetus

Objective To determine whether fetal response to needling resembles the fetal ‘brain sparing’ response seen with hypoxaemia. Design Prospective observational study. Setting Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London. Population Eighty-five pregnant women undergoing invasive procedures associated with fetal prenatal diagnosis and/or management. Methods The femoral artery and the middle cerebral artery pulsatility index were measured by Doppler ultrasonography before and after 89 invasive procedures (fetal blood sampling, transfusion, bladder or cyst aspiration, shunt insertion and amniocentesis, between 17 and 36 weeks). Cases in which the fetal body was transgressed were compared with ‘control’ fetuses undergoing invasive procedures which did not directly involve needling the fetus (amniocentesis and placental cord insertion procedures). Main outcome measures Femoral artery and middle cerebral artery pulsatility index. Results The femoral artery pulsatility index rose after transgression [median change (Δ) 0.73; 95% confidence interval (CI) 0.51 to 0.98]. In contrast, there was no significant change in femoral artery pulsatility index after non-transgression procedures (mean Δ 0.28; 95% CI −0.20 to 0.76). Analysis confirmed the fall in middle cerebral artery pulsatility index after transgression procedures (median Δ −0.19; 95% CI −0.07 to −0.35), but there was also a significant fall in middle cerebral artery pulsatility index after non-transgression procedures (mean Δ −0.47; 95% CI −0.23 to −0.71). Conclusions The human fetus mounts a peripheral haemodynamic response to invasive procedures involving transgression of the fetal body, which is consistent with the brain sparing effect. However, the change in middle cerebral artery pulsatility index in both transgression and control procedures suggests that the changes and mechanisms may be more complex than previously thought.

Deletion patterns of the STS gene and flanking sequences in Israeli X-linked ichthyosis patients and carriers: analysis by polymerase chain reaction and fluorescence in situ hybridization techniques.

Deletion of the entire steroid sulfatase (STS) gene is the most common molecular defect in X-linked ichthyosis (XLI) patients. Usually, additional flanking sequences are also missing. The aim of this study was to estimate the extent of deletions in an ethnically heterogeneous population of Israeli XLI patients. Multiplex polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques were applied in the analysis of blood samples of 24 patients and amniotic cells of seven affected fetuses from 22 unrelated families. In 19 families, a large deletion of the 2-3 megabase was found. It included the whole STS gene and spanned adjacent areas up- and downstream between the loci DXS 1139 and DXS 1132. Two unrelated families of Iraqi ancestry had a partial deletion of the gene and its centromeric adjacent sequence. In another family, the telomeric end of the extragenic segment was only partially missing. Application of FISH on metaphase blood cells and interphase amniotic cells confirmed the diagnosis of XLI in all patients, except the three with partial intragenic deletion. In those cases, the remaining fraction of the gene was sufficient to provide a false negative result. Diagnosis of carriers and prenatal diagnosis in uncultured cells was applicable only by FISH. Our study revealed a remarkable heterogeneity in the deletion pattern among Israeli patients with XLI. This heterogeneity could not be attributed to specific ethnic groups because of the small size of the study group. More studies involving patients of various ancestries should be carried out. In addition, this study demonstrated the usefulness of the FISH technique in the prenatal diagnosis of fetuses with suspected XLI.

Characterization of EcoRI mutation in fucosidosis patients: a stop codon in the open reading frame.

Recently, a subset of fucosidosis patients was identified in which the single EcoRI site in the open reading frame of the human cDNA encoding alpha-L-fucosidase was obliterated. We have employed the polymerase chain reaction technique to amplify alpha-L-fucosidase DNA from the five patients known to carry the EcoRI abnormality as well as four patients and two additional fucosidosis patients who do not carry the EcoRI abnormality. Sequence analysis of the amplified DNA has determined that the EcoRI site was destroyed by a C-T transition in the last position of the EcoRI site. This single base change results in the generation of a stop codon 120 base pairs upstream of the normal stop codon. In addition, we have determined that EcoRI cleavage of amplified DNA may be a useful diagnostic tool in the diagnosis of heterozygotes and in prenatal diagnosis of fetuses at risk for this disease.

Prenatal diagnosis of homozygous alpha 0-thalassaemia by direct DNA analysis of chorionic villi in Singapore.

First-trimester prenatal diagnosis by DNA analysis was carried out for seven pregnancies at risk for homozygous alpha 0-thalassaemia. Transabdominal placental biopsy was carried out at 10-12 weeks' gestation. The presence of alpha-globin genes in the fetal DNA was determined by restriction endonuclease mapping and hybridization with cloned alpha-globin probe. Homozygous alpha 0-thalassaemia was detected in two fetuses and the pregnancies were interrupted. Alpha 0-thalassaemia in both cases was confirmed by electrophoresis of the umbilical cord blood where only haemoglobin Bart's was detected. The remaining five fetuses were diagnosed as normal or as possessing alpha-thalassaemia-1 trait and the pregnancies are being carried to term. The use of DNA analysis in prenatal diagnosis of fetuses at risk for homozygous alpha 0-thalassaemia enables detection of the haemoglobinopathy at 10 weeks' gestation.

Congenital atresia and stenosis of the duodenum: The impact of a prenatal diagnosis

This review was undertaken to determine the effects of prenatal diagnosis, on the basis of ultrasonographic evidence, of a duodenal obstruction on the care and morbidity of the newborn infant. The records of 46 cases of either atresia or stenosis of the small bowel in infants treated during the last six years in a tertiary perinatal center were reviewed retrospectively. A prenatal fetal diagnosis of obstruction was made in 13 patients (12 obstructions located in the duodenum and one in the jejunum). The mean gestational age at prenatal diagnosis was 33.7 weeks (range 27 to 37 weeks). The course of those infants with the prenatal diagnosis made by ultrasound was compared with that of those infants in whom the diagnosis was established after the onset of symptoms of obstruction appeared. Such a prenatal diagnosis resulted in earlier surgical intervention (1.8 versus 3.9 days). Metabolic complications secondary to repeated vomiting were found to be less frequent. The expectant mother in whom such a fetal prenatal diagnosis has been made can be transported to a tertiary level perinatal center where neonatal and specialized surgical expertise are available. After birth, the infant can undergo immediate operation without being separated from its mother.

Diagnosis of arylsulfatase A deficiency in intact cultured cells using a fluorescent derivative of cerebroside sulfate

A fluorescent derivative of cerebroside sulfate (12-(1-pyrene)dodecanoyl-sphingosylgalactosyl-0-3-sulfate (P12-sulfatide) has been synthesized as a potential substrate for the determination of cerebroside sulfatidase (or arylsulfatase A) activity. It was administered into cultured human skin fibroblasts and thereby utilized for the diagnosis of arylsulfatase A deficiency. Cultured skin fibroblasts from normal individuals and healthy persons suffering from a pseudoarylsulfatase A deficiency (PD) degraded the P12-sulfatide, while in cells derived from a metachromatic leukodystrophy (MLD) patient it remained essentially intact. This contrasts with in vitro determinations of enzymatic activity, where the MLD or PD-derived arylsulfatase A exhibit similar deficiency, in spite of a profoundly different clinical course. Administration of the fluorescent sulfatide into the intact cells permitted a sensitive and rapid diagnosis of MLD and its distinction from the PD-phenomenon. This might be of particular importance for cases in which a rapid diagnosis is required and for prenatal diagnosis of fetuses from families afflicted with both MLD and pseudo-deficiency mutant genes.

Fanconi Anemia: Prenatal Diagnosis in 30 Fetuses at Risk

We report our experience, since 1978, with prenatal diagnosis in fetuses at risk for Fanconi anemia. Amniotic fluid cells from 30 fetuses from 24 families were monitored for baseline and diepoxybutane-induced chromosomal breakage. Seven of the fetuses at risk were diagnosed as affected; baseline and diepoxybutane-induced breakage ranged from 0.18 to 0.45 and 0.69 to 0.96 breaks per cell, respectively. The range of baseline and diepoxybutane-induced chromosomal breakage in amniocytes from the 23 pregnancies at risk that were diagnosed prenatally as unaffected ranged from 0 to 0.08 and 0 to 0.13 breaks per cell, respectively. Four of these cases were also diagnosed as normal on the basis of chromosomal breakage studies in cells obtained by chorionic villus sampling. The range of baseline and diepoxybutane-induced breakage in cells from five control fetuses was 0 to 0.05 and 0 to 0.10 breaks per cell, respectively. Of the pregnancies diagnosed as affected, two were carried to term, whereas five were terminated. One newborn and two abortuses had congenital malformations including abnormalities of the thumb and radius. The other affected live-born infant, now 5 1/2 years old, has severe growth retardation and pancytopenia. No Fanconi anemia-associated malformations were found in any of the other fetuses or newborns studied. In all cases in which tissue was available for study, diagnoses were confirmed by chromosome breakage studies. This method thus permits reliable detection of Fanconi anemia.

Prenatal testing for inherited immune deficiencies by fetal blood sampling.

We attempted to develop a prenatal diagnosis in fetuses at risk for immunodeficiency by fetal blood sampling performed under fetoscopy at 18-22 weeks of gestation. In order to obtain normal values, we first investigated thirty-five control fetuses whose blood punctures were undertaken for the diagnosis of haemoglobinopathies. Surface markers and in vitro mitogen-induced proliferation of the fetal lymphocytes were studied using micromethods. We then examined two fetuses at risk for two different types of severe combined immunodeficiency and established their immunological integrity, hence avoiding an unjustified termination of pregnancy. This immunological integrity was confirmed after birth.