[Serum screening in pregnant women for Down syndrome and open neural tube defects; testing of Health Council's criteria for genetic screening].
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Down Syndrome↗
Biomedical subjects
A Mantingh
Publications and source records attributed to A Mantingh.
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↗
The relation between serum markers in the second trimester and placental pathology. A study on extremely small for gestational age fetuses.
OBJECTIVES: To examine whether in women who are delivered of an extremely small for gestational age infant, raised levels of second trimester maternal serum alpha-fetoprotein (MSAFP) or human chorionic gonadotrophin (MShCG) levels are related to the presence of placental pathology detected at birth. DESIGN: Retrospective cross-sectional study. SETTING: Department of Obstetrics and Gynaecology, Antenatal Diagnosis Unit, Groningen University Hospital, The Netherlands. PARTICIPANTS: Eighty-four women who were delivered of an extremely SGA infant (< 2.3rd centile) in whom the MSAFP and the MShCG levels were known and placental pathology reports were available (study group), and 8692 women in whom the MSAFP and MShCG levels were known and the pregnancy outcome was normal (control group). Pregnancies with congenital anomalies were excluded. Analyte levels were expressed in multiples of the median (MoM) for gestational age. Statistical analysis between groups was performed by ANOVA, after logarithmic transformation of the MoMs, to normalise their distribution. MAIN OUTCOME MEASURES: 1. The means of the MSAFP and MShCG concentrations in the study group with and without placental lesions were compared with those in the control population. 2. The means of the MSAFP and MShCG levels in the study group with placental lesions were compared with those in the study group without placental lesions. RESULTS: 1. Comparison of study groups with controls: in the study group without placental lesions, the mean log MSAFP MoM (0.062), as well as the mean log MShCG MoM (-0.033), was not significantly different (P = 0.11 and P = 0.68, respectively) from the mean analyte levels in the control population (0.002 and 0.006, respectively). The mean logs of these analytes in the study group with placental lesions (0.162 and 0.129, respectively) were significantly higher compared with the MSAFP and MShCG levels in the control population (P < 0.001 for both analytes). 2. Comparison of study groups with each other: the mean log of the MSAFP level of 0.162 in the group with placental lesions was significantly different from the mean of 0.062 of the study group without placental lesions (P < 0.025). The higher mean log MShCG MoM of 0.129 in the group with placental lesions was significantly different from the mean log MShCG MoM of -0.033 in the study group without placental lesions (P < 0.025). CONCLUSIONS: Raised levels of second trimester MSAFP and MShCG in women who are subsequently delivered of an extremely small for gestational age infant are related to the presence of pathological changes in the placenta, detectable at birth. It is speculated that these placental pathological changes, which frequently accompany small for gestational age pregnancies, have their origin in the second trimester, when the normal physiological changes of the placenta occur.
Analysis of Variance↗
[Serum screening for fetal Down syndrome in pregnant women with an indication for prenatal diagnosis because of age: fewer amniocenteses].
OBJECTIVE: To examine the influence of maternal serum screening for foetal Down's syndrome (DS) on the number of amniocenteses in women with an indication for prenatal diagnosis because of age > or = 36 years. DESIGN: Longitudinal descriptive study. SETTING: Department of Obstetrics and Gynaecology, University Hospital Groningen. METHOD: Between October 1, 1990 and March 31, 1994, sera from 693 women, 36 years or older with a singleton pregnancy, were tested (alpha-foetoprotein and human chorionic gonadotrophin) to calculate the likelihood of their having a foetus with DS. RESULTS: 195 pregnant women (28%) were screen-positive (risk of having a foetus with DS > or = 1:250); 105 of these (54%) chose to have an amniocentesis. Of the remaining 498 (screen-negative) women, 22 (4%) chose to have an amniocentesis. All 7 cases of DS were in the screen-positive group. CONCLUSION: Maternal serum screening in women aged > or = 36 years can markedly reduce the number of invasive prenatal diagnostic procedures, with a minimal reduction in the detection of DS foetuses. It is advisable to offer this form of screening to all women in this age group.
Adult↗
Abnormal levels of maternal serum human chorionic gonadotropin and alpha-fetoprotein in the second trimester: relation to fetal weight and preterm delivery.
The aim of this prospective descriptive cross-sectional study was to examine the clinical significance of abnormal maternal serum human chorionic gonadotropin (MShCG) and alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. The study group comprised 8892 women with a singleton pregnancy, who were screened for a neural tube defect and Down's syndrome. Exclusion criteria were unknown pregnancy outcome, a congenital anomaly, delivery before 25 weeks of amenorrhoea, or known insulin-dependent diabetes. MSAFP and MShCG were determined between 15 and 20 weeks' amenorrhoea. An abnormal result was defined as (a) MSAFP or MShCG > or = 2.5 MOM, (b) MSAFP or MShCG < or = 0.5 MOM, and (c) MSAFP and MShCG > or = 2.5 MOM. Birth weight percentiles and the duration of amenorrhoea at the time of delivery were employed as outcome parameters. Of the women with an abnormally elevated MSAFP, 9.4 per cent had an extremely small-for-gestational age (SGA) infant (< 2.3rd percentile; P < 0.01, relative risk 4.5), 27.1 per cent had an SGA infant (< tenth percentile; P < 0.01, relative risk 2.7), and 14.3 per cent had an appropriate-for-gestational age (AGA) infant that was delivered preterm (< 259 days; P < 0.01, relative risk 2.4). In the cases where the MShCG level was elevated, 4.4 per cent had an extremely SGA infant (P < 0.01, relative risk 2.1) and 15.5 per cent had an SGA infant (P < 0.01, relative risk 1.5). No significant association was found between an elevated MShCG level and preterm delivery. Low MShCG was significantly associated with SGA infants (P < 0.01, relative risk 1.2) but not with extremely SGA or preterm deliveries. In the group whose MSAFP and MShCG levels were both elevated, 23.8 per cent delivered an extremely SGA infant (P < 0.01, relative risk 10.9), 38.1 per cent an SGA infant (P < 0.01, relative risk 3.7) and 47.6 per cent had a preterm delivery or an SGA infant (P < 0.01, relative risk 3.0). Isolated or combined elevation of the MSAFP and MShCG levels in the second trimester of pregnancy is an indication for extra vigilance during further prenatal care. This applies to a lesser extent to a low MShCG level.
Birth Weight↗
[Legislation on Mass Screening].
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Down Syndrome↗
The influence of serum screening on the amniocentesis rate in women of advanced maternal age.
We investigated the effect of maternal serum screening on the amniocentesis (AC) rate in women of advanced maternal age. The AC rate after maternal serum screening was compared in two groups of women with a singleton pregnancy, 855 women of 30-35 years and 98 of 36 years and older. In our population, 34.1 per cent of the women of 36 years or older were 'screen-positive' for Down syndrome. Only 41.2 per cent of these women chose to undergo AC as opposed to 88.2 per cent in the younger age group. Within the older age group, the tendency to avoid AC increased with increasing age. Maternal serum screening led to a significant decrease in the AC rate in the older women. In this group, a comparison between the 'a priori' and the calculated risk might have had more influence on the decision to undergo AC than being screen-positive or screen-negative as such. We conclude that maternal serum screening had a major effect on the AC rate in women of advanced maternal age. This is of importance in a society in which the average maternal age is steadily increasing.
Adult↗
First-trimester maternal serum immunoreactive inhibin in chromosomally normal and abnormal pregnancies. Dutch Working Party on Prenatal Diagnosis.
OBJECTIVE: To investigate the maternal serum immunoreactive inhibin level in chromosomally normal and abnormal pregnancies in the first trimester. METHODS: This was a retrospective study under the auspices of the Dutch Working Party on Prenatal Diagnosis. Maternal serum samples were taken before prenatal diagnosis. Forty-eight maternal serum samples from chromosomally abnormal pregnancies, including 23 with Down syndrome, were available for analysis; 284 samples from chromosomally normal pregnancies were used to establish reference ranges. RESULTS: The median value of maternal serum immunoreactive inhibin in the 23 Down syndrome pregnancies was 1.3 multiples of the normal median (95% confidence interval 0.8-2.1). No significant difference was found between the distributions of the inhibin concentrations in the normal and the Down syndrome pregnancies or in the normal and the other chromosomally abnormal pregnancies. CONCLUSION: In contrast to the second trimester of pregnancy, the level of maternal serum immunoreactive inhibin in the first trimester is not related to fetal chromosomal abnormalities and therefore is not useful as a biochemical screening index.
Adult↗
[The triple serum test for the diagnosis of Down syndrome and neural tube defects; the problem of a risk assessment test].
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Amniotic Fluid↗
[Serum screening of pregnant women for fetal neural tube defects and Down syndrome; initial experiences in The Netherlands].
OBJECTIVE: To examine if, and if so, in what way, the maternal serum screening for fetal neural tube defects (NTD) and Down's syndrome (DS) in the Dutch decentralized obstetrical organization would be feasible and effective. DESIGN: Prospective. SETTING: University Hospital Groningen. METHOD: Between October 1st 1990 and December 1st 1991 we determined the likelihood of a baby with a NTD and/or DS in 2580 pregnant women, at 15 to 20 weeks gestation, by serum screening. RESULTS: Five foetuses with DS were detected, as well as two with a NTD, one foetus with an omphalocele, and one with Turner's syndrome. One infant with a NTD and one with DS were not found prenatally. Of all 98 women of 36 years or older, 68 declined amniocentesis because their risk was lower than the age related risk. CONCLUSIONS: Maternal serum screening for NTD and DS is feasible and effective in principle. In a decentralized prenatal care system, special attention has to be paid to the time needed to report the results and to the completion of the follow-up. The detection rate of DS in pregnant women of 36 years or older remains almost the same, but a significant number of them decline prenatal diagnosis. An increased risk of foetal DS, determined by serum screening, should be added to the official list of indications for prenatal diagnosis in the Netherlands.
Adolescent↗
[How women cope with the results of maternal serum screening for fetal neural tube defects and Down syndrome].
At the University Hospital of Groningen maternal serum screening for fetal neural tube defects and Down's syndrome is available to pregnant women on their request. We have inquired into the reasons why women apply for serum screening and how this affects them. We did so by means of questionnaires sent to 200 women and by interviewing 20 women whose screening result indicated an increased chance of giving birth to a Down's syndrome child. The response percentage was 52.5. It appeared that opting for serum screening is seen as a self evident choice rather than a conscious one. In general, at the time of the decision, the women only saw the advantages of the test while possible consequences were often not taken into account. More than 70% of the women said they would apply for amniocentesis if they were told that they had an increased risk of having a baby with Down's syndrome. The confrontation with an increased risk of Down's syndrome then came unexpectedly and caused much distress. How to deal with the risk assessment results proved to be very difficult for these women. The difference in scale of the risk factor as established by the screening test compared with the original risk factor based on maternal age was interpreted by them as being of more significance than the statistical implication of the factor itself.
Adaptation, Psychological↗
Women's opinions on the offer and use of maternal serum screening.
We studied the opinions and experiences concerning maternal serum screening of two groups of women: (A) women who were not eligible for prenatal diagnosis; and (B) women for whom prenatal diagnosis was available because of advanced maternal age, and who either underwent chorionic villus sampling or amniocentesis. Many of the women were in favour of the availability of serum screening and would apply for this test in a future pregnancy. This applied also to many respondents who had previously undergone prenatal diagnosis. Most of these women, however, did not intend to decline diagnostic amniocentesis if the screening results did not indicate an increased risk. The majority of the group of respondents of 36 years and over did not consider it acceptable if age indication was dropped altogether. A system based on serum screening will have other implications than a policy based on age indication, since specific individual risk assessment is perceived as being of more significance than a risk statistically derived from age alone. Serum screening is often seen as a means of reassurance and many women are not aware of the possible drawbacks. As technology becomes increasingly complicated, counselling has to be adjusted correspondingly. Further research is needed to establish whether and how distress can be minimized and well-considered individual choice can be achieved.
Decision Making↗
Maternal serum CA 125 levels in pregnancies with chromosomally-normal and -abnormal fetuses. Dutch Working Party on Prenatal Diagnosis.
We measured the maternal serum cancer antigen 125 (MS-CA 125) levels in 98 nonpregnant women, 765 first- and second-trimester pregnancies with chromosomally-normal fetuses, and 54 chromosomally-abnormal pregnancies. To determine the MS-CA 125 concentration, we used a new automated microparticle enzyme immunoassay with low inter-assay variability. The median MS-CA 125 level decreased from the first to the second trimester of pregnancy and was higher than that in non-pregnant women. We found no difference between normal and Down's syndrome (n = 29) pregnancies (t-test: t = 0.57, p > 0.5). The MS-CA 125 levels in pregnancies with other chromosomal abnormalities showed no difference either, compared with the normals. We conclude that MS-CA 125 is not a useful marker for fetal Down's syndrome, nor for other chromosomal disorders in pregnancy.
Abortion, Spontaneous↗
Increased maternal serum alpha-fetoprotein and human chorionic gonadotropin in compromised pregnancies other than for neural tube defects or Down syndrome.
Intrauterine fetal death occurred in four women who were 'screen-positive' in a screening programme for neural tube defects (NTDs) and Down syndrome (DS). These women had very high levels of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG). Therefore, we evaluated all 'screen-positive' women in whom both of these markers were greater than or equal to 2.0 multiples of the median. The cases fulfilling these criteria totalled 11, and only one of them had no complications. High concentrations of both MSAFP and MShCG in a number of these cases might have been caused by an increased placental volume, which, in turn, might have been induced by decreased perfusion of the placenta. We conclude that screening programmes wrongly determine a high risk of fetal NTD or DS if the concentrations of both these parameters are very high. Invasive diagnostic procedures should be avoided in these cases, particularly in view of the increased risk of an adverse pregnancy outcome.
Adult↗
Second-trimester maternal serum immunoreactive inhibin as a marker for fetal Down's syndrome.
We measured immunoreactive inhibin in the maternal serum of 80 pregnancies with a chromosomally normal fetus and ten Down's syndrome pregnancies in the second trimester. The inhibin level in all Down's syndrome pregnancies was above the normal median; the multiple of the normal median (MoM) was 1.9. We found a statistically significant difference between the levels of inhibin in unaffected and affected pregnancies (Kolmogorov-Smirnov test: p < 0.002). Using an arbitrarily chosen cut-off of 2.4 MoM, 40 per cent of Down's syndrome and 5 per cent of the normal pregnancies were found. We conclude that immunoreactive inhibin may be useful as a marker for fetal Down's syndrome.
Biomarkers↗
Fetal heart rate in early pregnancy and chromosomal disorders.
OBJECTIVE: To investigate normal fetal heart rate in early pregnancy and assess the hypothesis that abnormal fetal heart rate is associated with fetal chromosomal abnormalities. DESIGN: Prospective descriptive cross-sectional study. SETTING: Antenatal clinic associated to the University Clinic of Obstetrics, University Hospital Groningen, The Netherlands. SUBJECTS: 424 pregnant women who attended for prenatal counselling. INTERVENTIONS: Measurements of fetal heart rate from 6-16 weeks gestation, cross-sectional study. MAIN OUTCOME MEASURES: Fetal heart rate expressed as beats/min. RESULTS: Karyotyping showed a normal chromosomal pattern in 414 fetuses. The median fetal heart rate increased from 138 beats/min at 6 weeks to 177 beats/min at 9 weeks, thereafter, fetal heart rate gradually decreased to 150 beats/min at 16 weeks. Karyotyping showed 10 abnormalities: five trisomies 21, three trisomies 18, and two mosaic patterns in chorionic villi. Fetal heart rate of the trisomic fetuses was distributed around the median with that of all Down's syndrome fetuses within the normal range. In one fetus with trisomy 18, the heart rate exceeded the 90th centile, in another it fell under the 10th centile. The two fetuses with a mosaic pattern in chorionic villi had heart rates outside the normal range. CONCLUSION: Fetal heart rate in chromosomally abnormal fetuses in early pregnancy do not appear to be consistently different from that in normal fetuses. The use of a single measurement of fetal heart rate is not valuable for screening purposes. Chromosomal mosaicism in chorionic villi may be associated with abnormal fetal heart rate.
Chromosome Aberrations↗
[Opinion of primiparae on the possibility of sex selection].
Recent medical-technological developments such as chorionic villi sampling and in vitro fertilization make sex selection in principle possible. The literature and our own experiences suggest an increasing demand for it. We interviewed a selected group of 180 women regarding sex selection, of whom 127 responded. More than 80% of these rejected a selection based on sex. The legitimacy of withholding information about the sex of the foetus is questionable. The existence of a demand, however small, should prompt professionals to take a stand about its acceptability.
Abortion, Induced↗
[Fetal echography and neural tube defects: morphological diagnosis without clinical certainty].
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Amniocentesis↗