Determination of maternal serum acetylcholinesterase in pregnancies with fetal neural tube defects

We have investigated the occurrence of acetylcholinesterase (AChE) (E.C.3.1.1.7) in fetal serum, amniotic fluid and maternal serum using an immuno-chemical assay-technique employing both polyclonal and monoclonal antibodies. Fetal serum had increased amounts of AChE, which is due to an increase in the 10.5S form of the enzyme. This form was also found in amniotic fluids of pregnancies with a fetal neural tube defect (NTD), but not in normal amniotic fluid. The increase in amniotic fluid AChE was however, not reflected in the maternal serum.     

Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities

The alpha subunit of human chorionic gonadotropin (alpha-hCG), human chorionic gonadotropin (hCG) and alpha fetoprotein (AFP) were measured in the serum of 25 women with chromosomally abnormal fetuses between 18 and 25 weeks of gestation and in 74 normal pregnancies. AFP levels less than 0.5 multiples of the median (MoM) or greater than 2.5 MoM were observed in 24 per cent of the abnormal pregnancies and in 6.76 per cent of the normal pregnancies. A low concentration of hCG (< 0.25 MoM) was observed in 8 per cent of abnormals and in 2.7 per cent of normals while an elevated concentration of hCG (>2.5 MoM) was observed in 56 per cent of abnormals and in 1.35 per cent of normals. Elevated hCG-alpha (>2.5 MoM) was observed in 28 per cent of abnormals and in none of the normals. Determination of elevated levels of hCG-alpha or hCG resulted in detection of 68 per cent of pregnancies with chromosomally abnormal fetuses with a false positive rate of 1.35 per cent. Determination of both elevated and depressed gonadotropin levels resulted in detection of 76 per cent of abnormal pregnancies with a false positive rate of 4.05 per cent. Measurement of hCG and hCG-alpha in maternal serum samples can be used as a screening procedure for detecting pregnancies at risk for fetal chromosome abnormalities.     

First-trimester maternal serum schwangerschafts protein 1 (SP1) in pregnancies associated with chromosomal anomalies

The relationship between first-trimester maternal serum Schwangerschafts protein 1 (SP1) and the karyotype of the pregnancy was examined in 692 women who underwent chorionic villus biopsy at 6–12 weeks. There were 30 pregnancies with abnormal karyotypes, consisting of 14 Down's syndrome (DS), eight trisomy 18, and eight other anomalies, two of which were mosaics. The normal ranges and medians for gestation were defined from the 662 cases in which the karyotype was normal. The median SP1 (0·5 MOM) of the abnormal group was significantly lower than that of the normal group (10 MOM). This relationship was maintained for the DS pregnancies (0·4 MOM) and for anomalies other than trisomy 18 (0·43 MOM) but not trisomy 18 (1·1 MOM). It is possible that the use of SP1 as a screening test for chromosome anomalies in the first trimester could have a 43 per cent detection rate for a 5 per cent false-positive rate.     

First trimester maternal serum placenta growth factor (PIGF)concentrations in pregnancies with fetal trisomy 21 or trisomy 18

Placenta growth factor (PIGF), an angiogenic factor belonging to the vascular endothelial growth factor family, pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (β-hCG) were measured in maternal serum from 45 pregnancies with trisomy 21, 45 with trisomy 18 and 493 normal controls at 10–13 completed weeks of gestation. In the normal pregnancies maternal serum PIGF levels increased exponentially with gestation. The median multiple of the median (MoM) PIGF concentration in the trisomy 21 group (1.26 MoM) was significantly higher (p<0.0001) than in the control group (1.00 MoM). In the trisomy 18 group the median PIGF was lower (0.889 MoM) but this did not quite reach significance (p=0.064). The corresponding median MoM values for PAPP-A were 1.00 MoM for the controls, 0.49 MoM for trisomy 21 and 0.16 MoM for trisomy 18. The median MoM values for free β-hCG were 1.00 MoM for the controls, 2.05 MoM for trisomy 21 and 0.38 MoM for trisomy 18. In the control group there was a small but significant correlation of PIGF with free β-hCG (r=+0.1024) and PAPP-A (r=+0.2288). In the trisomy 18 group there was a significant association between PIGF and free β-hCG (r=+0.2629) but not with PAPP-A (r=+0.0038). In the trisomy 21 group there was a small but significant association with PAPP-A (r=+0.1028) but not with free β-hCG (r=+0.0339). The separation of affected and unaffected pregnancies in maternal serum PIGF is small, and therefore it is unlikely that measurement of PIGF would improve screening for these abnormalities provided by the combination of fetal nuchal translucency and maternal serum PAPP-A and free β-hCG. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal detection of fetal hemoglobin E gene from maternal plasma

In order to provide a noninvasive prenatal diagnosis of the hemoglobin E (Hb E) related disorder, we have evaluated the possibility of identifying the fetal β^E-globin gene in maternal plasma. The analysis was performed during 8 to 18 weeks of gestation using DNA extracted from 200 µL of plasma from pregnant women whose husbands carried Hb E. The β^E-globin mutation in maternal plasma was detected by a nested PCR amplification followed by the Mnl I restriction analysis. The result was compared with that of routine analysis of the CVS specimens. Among the five pregnant women examined, the fetal β^E-globin gene was identified in maternal plasma in three of them and the result was completely concordant with the conventional CVS analysis. This simple noninvasive prenatal detection of the fetal β^E-globin gene should prove useful in a prevention and control program of Hb E/β-thalassemia in countries where the β^E-globin gene is prevalent. Copyright © 2003 John Wiley & Sons, Ltd.     

First-trimester maternal serum alphafetoprotein and chorionic gonadotropin in aneuploid pregnancies

First-trimester maternal serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels were measured in samples from 29 women with cytogenetically abnormal pregnancies and 145 women with cytogenetically normal pregnancies matched for gestational age, race, and sample storage time. All patients had a risk of fetal aneuploidy greater than or equal to that of a mother 35 years of age. AFP was significantly lower in samples from pregnancies affected with trisomy 21 (0.67 MoM;p <0.05), while HCG values were no different from those of matched controls. Trisomies 13 and 18 could not be distinguished from matched controls by AFP. However, levels of HCG were significantly lower in such pregnancy samples, with median values of 0.65 MoM in trisomy 13 and 0.32 MoM in trisomy 18 (p<0.05). Variations in AFP and HCG levels suggest that expressed differences between autosomal aneuploidies include differences in fetal and placenta! protein production in the first trimester.     

Alpha-fetoprotein in fetal serum,amniotic fluid,and maternal serum

In order to gain more insight into the association between alpha-fetoprotein (AFP) and fetal chromosomal disorders, especially Down's syndrome, we measured AFP in fetal serum, amniotic fluid, and maternal serum at cordocentesis. We compared the concentration and gradient of AFP in these three compartments. Our data confirm earlier findings on second-trimester fetal serum AFP concentration. The results indicate that low maternal serum AFP in pregnancies with fetal chromosomal disorders could result from an impaired fetal kidney function as well as from impaired membrane or placental passage of AFP, rather than from reduced fetal AFP production.     

Maternal serum biochemical markers in pregnancies with fetal parvovirus B19 infection

Hydrops fetalis and fetal death caused by fetal parovirus B19 infection have been reported to be associated with elevated maternal serum alpha-fetoprotein (AFP), based on a total of six cases. It has been suggested that the absence of AFP elevation may be reassuring. Maternal serum levels of the Down syndrome screening markers unconjugated oestriol and human chorionic gonadotropin in cases of fetal parvovirus infection have not been previously reported. We report four cases of hydrops fetalis and fetal death caused by fetal parvovirus infection, each with unremarkable second-trimester levels of AFP, unconjugated oestriol, and human chorionic gonadotropin.     

Second-trimester levels of maternal serum unconjugated oestriol and human chorionic gonadotropin in pregnancies affected by fetal anencephaly and open spina bifida

Unconjugated oestriol (uE3) and human chorionic gonadotropin (hCG) levels were determined in second-trimester maternal serum (MS) samples from 21 pregnancies associated with fetal anencephaly and 15 pregnancies associated with fetal open spina bifida. Each measurement was expressed as a multiple of the median (MoM) for unaffected pregnancies for each completed week of gestation. In pregnancies associated with anencephaly, the median value for MSuE3 was very low (0–17 MoM, range <0·12–0·33 MoM), suggesting a functional defect in the fetal adrenal prior to 20 weeks' gestation; the median value for MShCG was also low (0–73 MoM), although not to the same extent as for MSuE3. A biological explanation for the hCG result is not apparent. In pregnancies associated with open spina bifida, the MSuE3 and MShCG values were unremarkable, consistent with a lack of involvement of these open fetal defects in the synthesis and secretion of uE3 and hCG.