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Biomedical subjects

A Mantingh

Publications and source records attributed to A Mantingh.

At least 19 recordsLinked to original sources

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies.

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down syndrome pregnancies and 115 unaffected pregnancies before chorionic villus sampling (CVS), between 9 and 11 completed weeks of pregnancy. The samples were matched for gestational age, maternal age, maternal weight and duration of storage of the serum sample. Maternal TSH concentration was slightly decreased in Down syndrome pregnancies, with a median of 0.84 multiples of the median (MoM). Maternal serum human chorionic gonadotropin (hCG) concentration was slightly elevated in Down syndrome pregnancies, with a median of 1.03 MoM. Both differences were not significant applying matched rank analysis (p=0.50 for TSH and p=0.43 for hCG). The association between TSH and hCG in unaffected pregnancies was also measured. The Spearman correlation coefficient between TSH and hCG was -0.21 which was statistically significant (p=0.02, 95% confidence interval -0.38 to -0.03). However, it was concluded that TSH is not a useful marker for distinguishing Down syndrome-affected pregnancies from normal pregnancies in the first trimester.

Adult↗

How women deal with the results of serum screening for Down syndrome in the second trimester of pregnancy.

To gain insight into how pregnant women experience serum screening for Down syndrome, we sent questionnaires to two groups of relevant subjects in the north of the Netherlands. The questionnaires addressed the following issues: decision-making process, knowledge and opinions. Questionnaire A was sent to women of 36 years of age and older (n=99) (group A) who were all 20 to 36 weeks pregnant at that time. In the Netherlands prenatal diagnosis is routinely available to these women. Questionnaire B was sent to women of younger than 36 years (n=69) (group B) who had received a screen-positive result and had subsequently undergone amniocentesis. About half of these women were still pregnant at that time. For these women, serum screening is only available on the basis of opting-in. The two questionnaires were largely identical. The response rates to questionnaires A and B were 82% and 91%, respectively. Group A (women of 36 years and older) considered that second trimester serum screening made a welcome contribution to the decision-making process about whether to undergo amniocentesis. Moreover, it reduced the amniocentesis rate considerably. The vast majority said they would apply for serum screening in a following pregnancy, but favoured the idea of first trimester screening. In group B (women of younger than 36 years), reassurance was the most commonly mentioned reason for undergoing serum screening. Almost all the women experienced some degree of anxiety when they were informed about the screen-positive result and 13% continued to be anxious, even after the favourable result of the amniocentesis. The majority of the respondents would also apply for serum screening in a following pregnancy and were of the opinion that this screening should be offered to all pregnant women in the Netherlands.

Adult↗

Trends in live birth prevalence of down syndrome in the Northern Netherlands 1987-96: the impact of screening and prenatal diagnosis.

In the Northern Netherlands, we examined the live birth prevalence of Down syndrome (DS) and the impact of maternal serum screening (MSS) and prenatal cytogenetic diagnosis (PCD) during the period 1987-96. In this period the live birth prevalence, based on the maternal age distribution and the age specific risk of delivering a child with DS was expected to increase from 1.26 in 1987 to 1.62 in 1996. The introduction of MSS in 1991 made PCD available to women of all ages. Nevertheless, the utilization of PCD remained very stable. In 1991, 4.7% of pregnant women underwent a diagnostic test. In 1996 this percentage was 6.4%. As a result of MSS and PCD, the live birth prevalence of DS was 19% lower than expected (p<0.01). Despite utilization of PCD based on opting-in and a discouraging government policy regarding the offer of MSS, the percentage of DS cases detected by PCD increased from of 17% during the period 1987-90 to 27% in the period 1991-96 when MSS was available. The percentages have been corrected for spontaneous pregnancy loss. From a medical and financial point of view, MSS was the most cost-effective indication for PCD. However, the potential of reducing the birth prevalence of DS is limited by the low utilization of MSS and PCD by pregnant women.

Adult↗

Urinary hyperglycosylated hCG in first trimester screening for chromosomal abnormalities.

Hyperglycosylated human chorionic gonadotrophin (H-hCG), also known as Invasive Trophoblast Antigen or ITA, is a unique metabolic variant of hCG with more complex oligosaccharide side chains. Concentrations are independent of regular hCG. Urine H-hCG has recently proved to be a highly sensitive marker for Down syndrome screening in the second trimester of pregnancy. We evaluated H-hCG as a potential marker in the first trimester of pregnancy. Maternal urine samples were collected from 10(+0) to 11(+6) weeks of gestation prior to genetic analysis and stored in frozen form. Samples from eight cases of Down syndrome, two cases of trisomy 13, one case of trisomy 18, and 55 control pregnancies were hand-carried frozen to the USA and tested blindly. Samples were tested in a specific H-hCG immunoassay and values were normalized to creatinine concentration. Values were plotted against gestational age, and multiples of control pregnancy median (MoM) calculated. The median level of the MoMs of the eight Down syndrome cases was 3.6 MoM. Five of the eight Down syndrome cases exceeded the 90th centile of the 55 unaffected cases. The MoMs of the trisomy 13 and 18 pregnancies were 0.2, 0.2 and 0.3. All three cases were under the 10th centile of unaffected pregnancies. The results of this study indicate that H-hCG testing may be useful in screening for Down syndrome in the first trimester of pregnancy. Further studies are needed to assess the potential screening values of urine H-hCG and the combination of this test with free beta-subunit, PAPP-A and other markers for Down syndrome in the first trimester of pregnancy.

Biomarkers↗

Four years' cytogenetic experience with the culture of chorionic villi.

In 1958 chorionic villus samples, investigated by culture method, we found 137 (7%) abnormalities. The abnormal results were classified in certain abnormal (generalised abnormal at high probability) and uncertain abnormal (potentially confined to the placenta) results. Certain abnormal were 73 cases (3.7%). Uncertain abnormal were 64 cases (3.3%), in which confirmation studies were done in 47 cases. In 12 cases of these 47, the abnormality was confirmed and in 35 cases (1.8%) the abnormality was confined to the placenta. Among the latter cases, poor pregnancy outcome [16% intrauterine death (IUD), 6% intrauterine growth retardation (IUGR)] was increased. Total maternal cell contamination was not seen. The positive predictive value of all confirmed abnormal cases was 66%. The positive predictive value was 100% for indications 'ultrasound abnormalities' and 'carrier' and between 50 and 60% for all other indications. Predictive value among uncertain abnormal cases was low (26%). However, the positive predictive value depends of the type of abnormality. Therefore we conclude that the culture method for chorionic villi is a good test for indications 'ultrasound abnormalities' and 'carrier' and reliable for all other indications. Whether or not follow-up investigations should be offered to the parents depends of the type of abnormality. We conclude that the culture method is reliable for prenatal diagnosis and can be used as the sole investigative method.

Chorionic Villi Sampling↗

Maternal serum levels of free beta-hCG and PAPP-A in the first trimester of pregnancy are not associated with subsequent fetal growth retardation or preterm delivery.

The purpose of this case-control study was to examine the association of first-trimester concentrations of free beta-human chorionic gonadotropin (free beta-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum with subsequent preterm delivery or small-for-gestational age (SGA) fetuses. We collected all the blood samples before chorionic villus sampling in the first trimester. Concentrations of free beta-hCG and PAPP-A were expressed in multiples of the median (MOM) for gestational age. We compared the levels of both analytes in 73 SGA pregnancies (birth weight below the fifth percentile) with those in 292 normal controls, who were matched for gestational age, maternal age, parity, maternal weight, and smoking habits. We also compared the levels in 87 pregnancies with a preterm delivery (delivery before 37 completed weeks) with those in 348 matched controls. The median concentrations of PAPP-A and free beta-hCG, expressed in MOMs, in the 73 SGA pregnancies were 0.83 and 0.95, respectively, compared with 0.98 and 1.01, respectively, in the 292 matched controls (P=0.08 and 0.19, respectively). In the 87 pregnancies with a preterm delivery, the median concentrations of PAPP-A and free beta-hCG were 0.98 and 0.94, respectively, compared with 0.99 and 0.99, respectively, in the 348 matched controls (P=0.82 and 0.10, respectively). In contrast with the maternal serum analytes used in second-trimester screening--alpha-fetoprotein and human chorionic gonadotropin--this study showed that concentrations of PAPP-A and free beta-hCG in the first trimester were not associated with subsequent fetal growth retardation or preterm delivery.

Adult↗

First trimester maternal serum concentrations of fetal antigen 2 in normal pregnancies and those affected by trisomy 21.

Serum concentrations of fetal antigen 2 (FA-2), the amino-propeptide of the alpha1 chain of collagen type I, were measured in peripheral blood from women with normal (n = 234) and trisomy 21 affected (n = 14) pregnancies between 9 and 11 weeks gestation. Serum FA-2 concentrations were seen to be stable throughout this period, and though raised FA-2 concentrations were seen at the 10th week of gestation, a statistically significant difference between normal and trisomy 21 affected pregnancies was not found overall. Therefore it seems unlikely that FA-2 has a role in first trimester screening for trisomy 21, despite the fact that significantly higher FA-2 concentrations in trisomy 21 and significantly lower concentrations in trisomy 18 had been previously demonstrated in amniotic fluid in the second trimester.

Biological Assay↗

Schwangerschafts protein 1 (SP1) adds little to the age-related detection of fetal Down syndrome in the first trimester of pregnancy.

Schwangerschafts Protein 1 (SP1), being a placental protein appearing in the maternal circulation early in pregnancy, has been investigated as a potential marker for Down syndrome in the first trimester. Our study compared SP1 levels in 15 pregnancies with a Down syndrome fetus and 97 matched controls. Although the median MoM in Down syndrome pregnancies (0.49) was lower than in controls, its use as a marker added very little to the detection rate above the maternal age alone.

Biomarkers↗

Maternal urinary beta-core hCG in chromosomally abnormal pregnancies in the first trimester.

We evaluated urinary beta-core human chorionic gonadotropin (beta-core hCG) in the detection of fetal Down's syndrome (DS) in the first trimester of pregnancy. Urine was collected prior to performing chorionic villous sampling (CVS) between 10 and 12 completed weeks from the last menstrual period. In the 9 months of the study, there were 15 chromosomal abnormalities detected by CVS: five trisomy 21, four monosomy X, two trisomy 18, and four cases of confined placental mosaicism (CPM). In these 15 aneuploid pregnancies, the levels of urinary beta-core hCG were expressed as multiples of the median (MOM) of the ratio of beta-core hCG/creatinine for gestational age. The MOMs of this ratio in each of the five DS pregnancies were 0.2, 0.5, 1.3, 1.4, and 1.7. No difference was found between fetuses with DS or any of the other chromosomal abnormalities tested and normal fetuses. Contrary to optimistic reports of urinary beta-core hCG in the second-trimester detection of fetal DS, our data suggest that this is not a useful screening test for DS in the first trimester of pregnancy.

Aneuploidy↗

Women's opinions and the implications of first- versus second-trimester screening for fetal Down's syndrome.

Two groups of pregnant women were questioned regarding their opinions on serum screening for Down's syndrome in the first trimester of pregnancy. One group comprised 83 women attending our antenatal clinic who were questioned at the time of the existing second-trimester screening test. Seventy-six per cent of those who participated in the second-trimester screening programme would have preferred the test to have been in the first trimester, mainly because of the easier termination of pregnancy and/or the earlier reassurance provided. The remaining 24 per cent could see no advantage in the earlier time frame. Of the 49 women who had declined second-trimester screening, only two would have participated in screening had it been in the first trimester. The other group comprised those women attending our antenatal diagnosis clinic who were considering chorionic villus sampling (CVS). Forty-four per cent of these women would have allowed serum screening in the first trimester to influence their decision as to whether to undergo definitive prenatal diagnostic testing. In general, those women who made use of second-trimester serum screening would also do so in the first trimester. Those who declined the existing screening programme would also decline first-trimester screening. Many women currently deciding to undergo CVS would allow a first-trimester screening test to influence their decision.

Adult↗

The association between hypertensive disorders of pregnancy and abnormal second-trimester maternal serum levels of hCG and alpha-fetoprotein.

OBJECTIVE: To examine the association between hypertensive disorders of pregnancy and second-trimester maternal serum alpha-fetoprotein (MSAFP) and hCG levels. METHODS: The proportions of abnormal second-trimester MSAFP and hCG levels in the serum samples from 65 women with true pregnancy-induced hypertension or preeclampsia (cases) were compared to the proportions of abnormal levels in all 1943 women without this disorder in the same cohort in a hospital setting. Maternal serum alpha-fetoprotein and hCG levels of the 65 cases also were compared to those of 325 completely uncomplicated matched control pregnancies, selected from the same cohort. Fisher exact test and Student t test were used for statistical analysis and P < .05 was considered statistically significant. RESULTS: An MSAFP level at least 2.5 multiples of the median (MoM) was found in two of 65 cases (3.1%) and in 27 of 1943 women (1.4%) in the rest of the cohort, a nonsignificant difference (relative risk [RR] = 2.2; P = .24). The statistical power to identify a significant difference for this RR was .27. An hCG level of at least 2.5 MoM was found in six cases (9.2%) and in 89 (4.6%) of women in the rest of the cohort, also a nonsignificant difference (RR = 2.0; P = .12). The statistical power to identify a significant difference for this RR was .38. The mean (+/-standard deviation) logarithms of the MSAFP and hCG MoMs in the 65 cases (0.039 +/- 0.191 and 0.048 +/- 0.265, respectively) were not significantly different from those in the 325 matched controls (0.006 +/- 0.148 and -0.010 +/- 0.244, respectively; P = .12 and .08, respectively). CONCLUSION: Although a weak association cannot be excluded, this study found no clinically important increase in risk of developing subsequent hypertensive disorders of pregnancy among women with abnormal second-trimester levels of MSAFP or hCG.

Adult↗

The HELLP syndrome: its association with unexplained elevation of MSAFP and MShCG in the second trimester.

In this study, we examined the relationship between concentrations of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG) in the second trimester and the haemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 16 women with the HELLP syndrome were compared with those in 10443 women without this syndrome who were screened for Down's syndrome and neural tube defects. All the women with a singleton pregnancy and a known pregnancy outcome were included in this study. At a cut-off level of 2.5 MOM, 37.5 per cent of the pregnancies with the HELLP syndrome had an elevated MShCG level, compared with 4.8 per cent in the whole population (P < 0.0001). 12.5 per cent of the women with the HELLP syndrome had an elevated MSAFP level, compared with 1.3 per cent in the whole population (P < 0.025). Women with a combined elevation of MSAFP and MShCG levels (0.3 per cent of the screened population) had a 47 time greater risk of developing the HELLP syndrome than the others (P < 0.01). The HELLP syndrome should be taken into account in the case of unexplained elevated levels of MShCG and MSAFP, especially in the rare event of combined elevation of both markers.

Chorionic Gonadotropin↗

A demographic approach to the assessment of Down syndrome screening performance.

The aim of this article is to examine the performance of screening for fetal Down syndrome (DS) in the context of demographic variation in time and place, using population and fertility data for several European countries. Two screening approaches are distinguished: one on the basis of maternal serum screening with human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) in combination with maternal age, and one on the basis of maternal age only. Screening performance, as measured by detection and false-positive ratios, is shown to be the result of the screening approach chosen and of the demographic characteristics of the population under consideration. A proper distinction between these two determinants of DS screening performance should be made, in order to distinguish between an improvement in screening performance that is brought about by a new screening approach and an improvement that is brought about by demographic change. We recommend that measures of DS screening performance be standardized for demographic variation. The methodology and demographic data presented in this article can be used for this purpose.

Adolescent↗

Maternal serum screening for fetal Down syndrome in IVF pregnancies.

To assess the influence of in vitro fertilization (IVF) on maternal serum human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP), the maternal serum hCG and AFP values were studied in 67 IVF pregnancies and compared with the results of a control group of 4732 spontaneously conceiving patients. Maternal serum hCG was significantly higher and AFP significantly lower in the IVF group. Possible explanations and implications for prenatal diagnosis in IVF pregnancies are discussed.

Chorionic Gonadotropin↗