Fetal hypoxia is one of the leading causes of perinatal morbidity and mortality. One of the most severe sequels of fetal hypoxic insult is the development of perinatal brain lesions resulting in a ...spectrum of neurological disabilities, from minor cerebral disorders to cerebral palsy. One of the most important fetal adaptive responses to hypoxia is redistribution of blood flow towards the fetal brain, known as the 'brain sparing effect'. The fetal blood flow redistribution in favor of the fetal brain can be detected and quantified by the Doppler cerebral umbilical ratio (C U ratio = cerebral resistance index (CRI) umbilical resistance index (URI)). Our studies on animal models and human fetuses have demonstrated clearly that this phenomenon cannot prevent the development of perinatal brain lesions in the case of severe or prolonged hypoxia. Fetal deterioration in chronic and severe hypoxia is characterized by the disappearance of the physiological cerebral vascular variability (vasoconstriction and vasodilatation), followed by an increase in cerebral vascular resistance. However, our latest study on growth-restricted and hypoxic human fetuses has shown that perinatal brain lesions can develop even before the loss of cerebrovascular variability. The fetal exposure to hypoxia can be quantified by using a new vascular score, the hypoxia index. This parameter, which takes into account the degree as well as duration of fetal hypoxia, can be calculated by summing the daily % C U ratio reduction from the cut-off value 1 over the period of observation. According to our results, the use of this parameter, which calculates the cumulative, relative oxygen deficit, could allow for the first time the sensitive and reliable prediction and even prevention of adverse neurological outcome in pregnancies complicated by fetal hypoxia.
To evaluate the impact of smoking and number of previous births on maternal serum levels of alpha-fetoprotein and free beta-subunit of human chorionic gonadotropin (free beta-hCG).
The study included ...3,252 completed unaffected singleton pregnancies that proceeded beyond 37 weeks' gestation and resulted with a birth of healthy child. Smoking status of mothers and data concerning gravidity and parity were collected at the sampling date. Serum markers were measured between 13 and 22 gestational weeks, corrected for maternal weight, and converted to multiples of median (MoM) for unaffected pregnancy of the corresponding gestational age. Median MoM values for both markers were examined in relation to both: smoking habits and number of previous births.
Smokers had significantly decreased free beta-hCG MoM values compared to nonsmokers (p < 0.001). The median levels showed a negative relationship with the number of previous births. The significance of a decreasing trend was proved, both in smokers (p < 0.001) and nonsmokers (p < 0.001). The median maternal serum alpha-fetoprotein MoM values did not show any significant dependence, neither with regard to smoking (p = 0.65) nor with regard to parity (p = 0.07).
The recommendable adjustment of serum markers to smoking habits, especially concerning the free beta-hCG levels, would be worthwhile. The evidence of the coexisting influence of parity on serum levels of free beta-hCG, both in smokers and nonsmokers, should perhaps be a stimulus for reconsideration of which corrections the screening performance is dependent on.
Contemporary understanding of missed abortion, as the case of spontaneous abortion where embryo is retained in uterus for four-weeks or more after its death, is very poor. Aiming to improve the level ...of knowledge about this process, we have compared glycosylation patterns of placental proteins in normal pregnancy and missed abortion. Oligosaccharide branches were detected by Western-blot using SNA, DBA and PHA-E lectins. The comparison of samples of the same gestational age enabled identification of changes in protein glycosylation between normal and pathological placentas. Lectin DBA detects in normal placenta the glycoprotein GP 105 during the eleventh week, which is absent in missed abortion. PHA-E identifies GP 71 during fourteenth week only in normal placenta. However GP 25 recognized by SNA in missed abortion was not found in normal pregnancy at tenth week. These results indicate that abnormal placental development is associated with changes in glycoprotein structures, and that glycoconjugates might have an important role in placental development.
Ultrasonic markers of fetal chromosomal abnormalities Kurjak, Asim; Kos, Milan; Stipoljev, Feodora ...
European journal of obstetrics & gynecology and reproductive biology,
07/1999, Letnik:
85, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Objective: The aim of this brief investigation was to correlate the most common sonographically detectable markers with certain type of chromosomal disorder diagnosed by available karyotyping ...procedures.
Study design: During the 3 year study period fetal karyotyping was performed in 1055 patients for a variety of clinical indication. Twenty one percent (21%; 222/1055) of procedures were done because of sonographically detectable structural disorders related to phenotype expression of chromosomopathies. Sonographic examinations and karyotyping procedures were performed between the 10th and 36th week. The average maternal age was 27 years, unselected.
Results: The fetal karyotype was abnormal in 13.5% of cases (30/222). Within the group of single marker, 11.6% (7/60) of karyotypes were abnormal. Multiple markers of chromosomal abnormalities resulted in 14.2% (23/162) of abnormal karyotypes. The most frequent chromosomal disorder detected in sonographic screening is trisomy 18 (50%; 15/30). The data on the frequency of different types of chromosomal abnormalities are given.
Conclusions: The incidence of chromosomal abnormalities for ultrasonographically detectable malformations is much higher than the incidence reported in screening studies based on maternal age or biochemical screening. Trisomy 21 showed the relative lack of variety in phenotypic expression, and nuchal translucency screening has to be accepted rationally. Associated numerous major and minor malformations were the most prominent factors leading to the diagnosis of chromosomopathies, particularly trisomy 18.
Presentation of a prenatally diagnosed case of Werdnig-Hoffmann disease, the most severe type of spinal muscular atrophy.
DNA obtained from cultivated amniocytes was analyzed for deletions in the ...survival motor neuron gene and neuronal apoptosis inhibitory protein gene.
The fetus was diagnosed as an affected homozygote for deletions in exon 7 and exon 8 of the survival motor neuron gene. No deletions of exon 5 in the neuronal apoptosis inhibitory protein gene were found.
Direct DNA deletion analysis of the survival motor neuron gene and neuronal apoptosis inhibitory protein gene in affected families represents a highly reliable and fast method for prenatal diagnosis of Werdnig-Hoffmann disease.
Changes in glycoprotein and ganglioside composition in human trophoblasts (eighth week of gestation) after
in vitro exposure to pulsed Doppler ultrasound (pulse duration 1.22 μs; repetition frequency ...11.1 kHz; center frequency 4 MHz; ISPPA = 175.5 W/cm
2; ISPTA = 0.59 W/cm
2) were investigated. Evacuated trophoblasts were divided in two halves and insonated for 10 min on top of a 6-cm layer of 5% gelatin in 50-mL tubes (Falcon) at 37°C. One half of each trophoblast was sham insonated and served as an internal control. After insonation trophoblasts were maintained at 37°C for 24 h. Glycoproteins were detected using α-
d-mannose specific lectins from
Galanthus nivalis and
Narcissus pseudonarcissus. A decrease in the expression of mannose containing glycoprotein mgp47 and an increase in expression of mgp54 were observed. Ganglioside composition was also significantly altered. Concentrations of two gangliosides migrating similarly to GM2, and one similarly to GQ1, decreased by more than 75%. At the same time, concentrations of one ganglioside migrating similarly to GM3, and two other unidetified gangliosides increased two- to fourfold.
Osteogenic protein-1 (OP-1) is a member of the bone morphogenetic protein subfamily of the transforming growth factor-beta (TGF-beta) superfamily. Since members of the TGF-beta superfamily have a ...role in tissue development the distribution of OP-1 in developing human embryos (gestational age 5-14 weeks) was examined by immunohistochemical methods. Positive staining for OP-1 was observed in: sclerotome, hypertrophied chondrocytes, osteoblasts, periosteum, epithelial cells of the adrenal "provisional cortex" and the convoluted tubules of developing kidneys. In the developing lungs, pancreas and skin, OP-1 was localized in basement membranes underlying the epithelium. In vitro binding studies of 125I-OP-1 to various extracellular matrix components revealed high affinity of OP-1 for type IV collagen and less for heparin, collagen types I and VI. Present findings suggest that, in addition to bone formation, OP-1 could have other important regulatory roles in human embryogenesis with high binding affinity to a basement membrane component.
Analysis of the color Doppler features of intervillous flow in cases of missed abortion, and their comparison with the findings in normal pregnancy.
Transvaginal color and pulsed Doppler was used in ...the analysis of 38 patients with missed abortion and 40 patients with normal pregnancy. The gestational age ranged from 6 to 11 weeks. Repeated analysis of variance was used to compare the groups.
Two types of Doppler signals were detected in the intervillous space: pulsatile and continuous. Impedance in the intervillous space of both groups did not change significantly with the gestational age. For the group with missed abortion, the mean resistance index (RI) was 0.37 +/- 0.03 and pulsatility index (PI) 0.75 +/- 0.07. For the control group, the mean RI was 0.36 +/- 0.02 and PI 0. 72 +/- 0.04. The differences in RI and PI for all gestational age groups and between the two patient groups were not statistically significant. With advancing gestation, continuous, venous-like signal became stronger and randomly dispersed throughout the placenta. Peak flow velocity values obtained from both groups did not change significantly with gestational age, nor between the two groups. Conclusion. The new generation of sensitive Doppler units can detect the intervillous flow as a continuous progressive process at 6-11 weeks of gestation. The vascular resistance in the intervillous space does not change in cases of missed abortion.