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Objective To examine the impact of introduction of the mid-trimester scan on pregnancy outcome in cases of open spina bifida in two regions of The Netherlands. Methods This was a retrospective cohort study of 190 cases of open spina bifida diagnosed pre- or postnatally, with an estimated date of delivery between 2003 and 2011. Results With implementation of the mid-trimester scan the percentage of cases of open spina bifida detected before the 24th week of pregnancy increased from 43% to 88%. The rise in prenatal detection rate was associated with a significant increase in the number of terminated pregnancies and a decrease in the rate of perinatal loss; the percentage of children born alive did not change significantly. In the subgroup that underwent a scan between 18 and 24 weeks of pregnancy, cranial signs were present in 94.4% of cases. Conclusion Introduction of the mid-trimester scan has led to an increase in early identification of pregnancies complicated by open spina bifida. Pregnancies previously destined to end in perinatal loss are now terminated whilst pregnancies with a relatively good prognosis are frequently continued; the number of children with open spina bifida who are born alive has not changed significantly. Our study confirms that prenatal diagnosis is usually triggered by visualization of a lemon-shaped skull or a banana-shaped cerebellum. Copyright (C) 2013 ISUOG. Published by John Wiley & Sons Ltd.

Objective To identify short-term factors influencing psychological outcome of termination of pregnancy for fetal anomaly, in order to define those patients most vulnerable to psychopathology.Study Design A prospective cohort of 217 women and 169 men completed standardized questionnaires 4 months after termination. Psychological adjustment was measured by the Inventory of Complicated Grief (ICG), the Impact of Event Scale (IES), the Edinburgh Postnatal Depression Scale (EPDS), and the Symptom Checklist-90 (SCL-90).Results Women and men showed high levels of posttraumatic stress (PTS) symptoms (44 and 22%, respectively) and symptoms of depression (28 and 16%, respectively). Determinants of adverse psychological outcome were the following: high level of doubt in the decision period, inadequate partner support, low selfefficacy, lower parental age, being religious, and advanced gestational age. Whether the condition was Down syndrome or another disability was irrelevant to the outcome. Termination did not have an important effect on future reproductive intentions. Only 2% of women and less than I % of men regretted the decision to terminate.Conclusion Termination of pregnancy (TOP) for fetal anomaly affects parents deeply. Four months after termination a considerable part still suffers from posttraumatic stress symptoms and depressive feelings. Patients who are at high risk could benefit from intensified support. Copyright (c) 2007 John Wiley & Sons, Ltd.

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. Copyright (C) 2000 John Wiley & Sons, Ltd.

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

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. (C) 1998 John Wiley & Sons, Ltd.

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.

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.

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 alphafetoprotein 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 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 of hCG.

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. (C) 1997 by John Wiley & Sons, Ltd.

To examine the impact of introduction of the mid-trimester scan on pregnancy outcome in cases of open spina bifida in two regions of The Netherlands.This was a retrospective cohort study of 190 cases of open spina bifida diagnosed pre- or postnatally, with an estimated date of delivery between 2003 and 2011.With implementation of the mid-trimester scan the percentage of cases of open spina bifida detected before the 24(th) week of pregnancy increased from 43% to 88%. The rise in prenatal detection rate was associated with a significant increase in the number of terminated pregnancies and a decrease in the rate of perinatal loss; the percentage of children born alive did not change significantly. In the subgroup that underwent a scan between 18 and 24 weeks of pregnancy, cranial signs were present in 94.4% of cases.Introduction of the mid-trimester scan has led to an increase in early identification of pregnancies complicated by open spina bifida. Pregnancies previously destined to end in perinatal loss are now terminated whilst pregnancies with a relatively good prognosis are frequently continued; the number of children with open spina bifida who are born alive has not changed significantly. Our study confirms that prenatal diagnosis is usually triggered by visualization of a lemon-shaped skull or a banana-shaped cerebellum.

In this patient-control study, we examined the impact of placental mosaicism on the concentrations of maternal serum human chorionic gonadotropin (MShCG) and maternal serum alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. Patient and control groups were selected from 2347 women with a singleton pregnancy, who underwent chorionic villous sampling in the first trimester and from whom second-trimester serum samples had been collected. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 35 women with confined placental mosaicism (CPM) were compared with those in 70 controls with uncomplicated pregnancies. Elevated MSAFP or MShCG was defined as a concentration of > or = 2.0 MOM. Of the 35 pregnancies with CPM, none had an elevated MSAFP level, as opposed to two out of the 70 women (2.9 per cent) in the control group (P = NS). Nine women in the placental mosaicism group (26 per cent) had an MShCG level of > or = 2.0 MOM, compared with five in the control group (7.1 per cent; P = 0.0135). Nineteen women in the placental mosaicism group (54 per cent) were screen-positive for Down's syndrome (cut-off 1:250), compared with 17 women (24 per cent) in the control group (P = 0.0042; relative risk = 2.3). The three highest MShCG levels were found in pregnancies with CPM that involved trisomy 16; all these women delivered a small-for-gestational age (SGA) infant. CPM, especially with trisomy 16, is associated with elevated levels of MShCG, but not with elevated levels of MSAFP. It is an important cause of false-positive results in serum screening programmes for fetal Down's syndrome. It is possible that abnormal MShCG levels in pregnancies with CPM result from dysfunctional placenta, caused by chromosomally abnormal areas. We therefore recommend increased surveillance of pregnancies with unexplained elevated MShCG levels.

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.

A case is reported in which enlarged, hyperechogenic lungs, ascites and polyhydramnios on prenatal ultrasound were indications of a partial tracheal agenesis and tracheoesophageal fistula. A review of the literature is given to assist clinicians in effectively counselling women in whom this ultrasound abnormality is detected.

We report two cases of apparently balanced complex de novo chromosomal rearrangements (BCCR) detected prenatally at 17 weeks and 10 weeks of gestation, respectively. Chromosomes were studied using GTG‐banding and fluorescent in situ hybridization (FISH). In one case four chromosomes and in the other case three chromosomes were involved in the rearrangements. One of the pregnancies was terminated and no external or internal abnormalities were detected at autopsy. The other pregnancy continued to term. Level III ultrasound examination showed no abnormalities. The child is now 3 years old and has neither congenital anomalies nor evidence of delayed psychomotor development.

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.

Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with second-trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a normal amniotic fluid volume. This suggests that in oligohydramnios the origin of excess AFP in the maternal compartment is amniotic fluid. It is proposed that oligohydramnios and the associated raised maternal serum AFP levels are caused by damage of the fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic fluid to the decidual tissue and resorption in the maternal circulation.

We have studied the opinions and attitudes of women towards prenatal diagnosis (amniocentesis/chorionic villus sampling/ultrasound/serum AFP testing). A questionnaire was sent to 185 women who had had their first baby a few months before. The respondents have a strong positive attitude towards the diagnostic procedures, especially if treatable abnormalities can be detected. Younger women and women with a high level of education were less inclined to make use of prenatal diagnosis. If tests were made more widely available, this might lead to a significant increase in the use of prenatal diagnosis.

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.

Three women, aged 30, 18 and 37 years respectively, were diagnosed during the course of their pregnancies with congenital anomalies that carry a high risk of mortality and morbidity, namely a neural tube defect, gastroschisis and trisomy 22. All 3 women chose to continue their pregnancy and received various forms of counselling concerning the differences between the estimated prognoses. For the first patient, the emphasis was explaining the consequences of the disease for the unborn child and the parents and how the resulting handicaps could be minimised by medical treatment. For the second patient, the treatment plan was deliberately curative, and regrettably this failed. For the third patient, the attending physician guided the parents through their future loss and supported them during their period of mourning.

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.

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. Copyright (C) 2000 John Wiley & Sons, Ltd.

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 (p0.01). 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.

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.

To describe the epidemiological impact of prenatal diagnosis and selective abortion on the frequency of neural tube defects (NTD) in the period 1980-1992 in the Northern Netherlands in comparison with data from other European regions.Descriptive.17 'European registration of congenital anomalies' (EUROCAT) registrations, localized in 10 European countries.Data were collected actively and retrospectively from multiple sources fed by voluntary registration of congenital anomalies in live births, stillbirths and pregnancies terminated because of congenital anomalies.In Europe the total birth prevalence of NTD in the period 1980-1992 ranged from 5.3 per 10,000 in Switzerland to 29.0 per 10,000 in Glasgow, a difference of a factor 5.5. In live births the difference was ninefold: ranging from 2.0 per 10,000 in Paris to 18.8 per 10,000 in Dublin. The Netherlands had a conspicuously high prevalence among live births, higher than in other regions in continental Europe. For spina bifida the live birth prevalence both in other continental regions and in Glasgow was also lower than in the Netherlands. In Glasgow serum alpha-foetoprotein screening apparently led to frequent early prenatal diagnosis of NTD and to frequent termination of pregnancy. In Paris the use of ultrasound screening appears to lead to frequent later prenatal diagnosis, as well as frequent termination of pregnancy.In the Netherlands the impact of prenatal diagnosis and selective abortion is limited, so that primary prevention (periconceptional use of folic acid) is more important than in some other European countries.

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.

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.

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. (C) 1997 by John Wiley & Sons, Ltd.

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.

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.

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 (P0.0001). 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 (P0.025). 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 (P0.01). 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.

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.

We decided to assess the practicability of introducing nuchal translucency (NT) measurements as a screening programme for fetal Down's syndrome in the first trimester of pregnancy, within the population of women who receive ultrasound examinations in our department. Over a 1-year period, measurements were made in 923 fetuses ator = 13 weeks' gestation. Fifty-two per cent of the mothers were 36 years or older or had a past history of a chromosomally abnormal fetus or child. Measurements were only successful 58 per cent of the time; this improved to 74 per cent if the fetus wasor = 10 weeks' gestation. Inter-observer variability did not cause a major problem. There were 36 fetuses with an NTor = 3 mm. Two of these fetuses had a chromosomal abnormality (both trisomy 21). The translucency in these two cases was so large that they would have been detected and offered prenatal diagnosis even prior to this study. There was a total of ten aneuploidies in the study group. Only two of these fetuses were detected by this screening method; five had an NT measurement3 mm and in three fetuses (all trisomy 21), measurements were not successful. We outline the practical problems that could be expected by introducing ultrasound screening in a routine setting. Although the efficacy of the test in a research setting may seem good, the effectiveness in everyday usage appears much less impressive, making its uptake as a screening technique in a general ultrasound practice at this stage imprudent.

We decided to asses the practicability of introducing nuchal translucency (NT) measurements as a screening programme for fetal Down's syndrome in the first trimester of pregnancy, within the population of women who receive ultrasound examinations in our department. Over a 1-year period, measurements were made in 923 fetuses at less than or equal to 13 weeks' gestation. Fifty-two per cent of the mothers were 36 years or older or had a past history of a chromosomally abnormal fetus or child. Measurements were only successful 58 per cent of the time; this improved to 74 per cent if the fetus was greater than or equal to 10 weeks' gestation. Inter-observer variability did not cause a major problem. There were 36 fetuses with an NT greater than or equal to 3 mm. Two of these fetuses had a chromosomal abnormality (both trisomy 21). The translucency in these two cases was so large that they would have been detected and offered prenatal diagnosis even prior to this study. There was a total of ten aneuploidies in the study group. Only two of these fetuses were detected by this screening method; five had an NT measurement

In this patient-control study, we examined the impact of placental mosaicism on the concentrations of maternal serum human chorionic gonadotropin (MShCG) and maternal serum alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. Patient and control groups were selected from 2347 women with a singleton pregnancy, who underwent chorionic villous sampling in the first trimester and from whom second-trimester serum samples had been collected. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 35 women with confined placental mosaicism (CPM) were compared with those in 70 controls with uncomplicated pregnancies. Elevated MSAFP or MShCG was defined as a concentration ofor = 2.0 MOM. Of the 35 pregnancies with CPM, none had an elevated MSAFP level, as opposed to two out of the 70 women (2.9 per cent) in the control group (P = NS). Nine women in the placental mosaicism group (26 per cent) had an MShCG level ofor = 2.0 MOM, compared with five in the control group (7.1 per cent; P = 0.0135). Nineteen women in the placental mosaicism group (54 per cent) were screen-positive for Down's syndrome (cut-off 1:250), compared with 17 women (24 per cent) in the control group (P = 0.0042; relative risk = 2.3). The three highest MShCG levels were found in pregnancies with CPM that involved trisomy 16; all these women delivered a small-for-gestational age (SGA) infant. CPM, especially with trisomy 16, is associated with elevated levels of MShCG, but not with elevated levels of MSAFP. It is an important cause of false-positive results in serum screening programmes for fetal Down's syndrome. It is possible that abnormal MShCG levels in pregnancies with CPM result from dysfunctional placenta, caused by chromosomally abnormal areas. We therefore recommend increased surveillance of pregnancies with unexplained elevated MShCG levels.

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 (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 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.

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.

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 MShCGor = 2.5 MOM, (b) MSAFP or MShCGor = 0.5 MOM, and (c) MSAFP and MShCGor = 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; P0.01, relative risk 4.5), 27.1 per cent had an SGA infant (tenth percentile; P0.01, relative risk 2.7), and 14.3 per cent had an appropriate-for-gestational age (AGA) infant that was delivered preterm (259 days; P0.01, relative risk 2.4). In the cases where the MShCG level was elevated, 4.4 per cent had an extremely SGA infant (P0.01, relative risk 2.1) and 15.5 per cent had an SGA infant (P0.01, 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 (P0.01, 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 (P0.01, relative risk 10.9), 38.1 per cent an SGA infant (P0.01, relative risk 3.7) and 47.6 per cent had a preterm delivery or an SGA infant (P0.01, 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.

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 ageor = 36 years.Longitudinal descriptive study.Department of Obstetrics and Gynaecology, University Hospital Groningen.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.195 pregnant women (28%) were screen-positive (risk of having a foetus with DSor = 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.Maternal serum screening in women agedor = 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.

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 n-tight 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.

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.

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.Prospective.University Hospital Groningen.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.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.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.

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.

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 pattern 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.

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.

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.

The cytogenetic results of 1500 chorionic villus samples (CVS) are presented. In these 1500 samples, 23 samples (1.5 per cent) could not be provided with a diagnosis because of laboratory failure. This failure rate dropped from 3 per cent in the first 500 samples to 0.2 per cent in the last 500. In the remaining 1477 samples, 58 (3.9 per cent) chromosomal aberrations were found. Of these, 21 (36 per cent) proved not to represent the karyotype of the fetus proper. Predictive values of (different groups of) chromosomal aberrations in CVS are calculated. The impact of (differences between) the predictive value for some major chromosomal aberrations is discussed. A tissue- and chromosome-specific selection mechanism is postulated.

Objective To review the use of a membrane-free haemolysate prepared from maternal blood to distinguish the amniotic sacs at amniocentesis in twin gestation.Setting University Hospital, Groningen.Method Haemoglobin solution prepared from maternal blood.Subjects 63 twin pregnancies having amniocentesis.Results The fetal loss before 28 weeks was 4%. There was no perinatal mortality. Dye was detected in the second sac in 9 of 24 women tested before 1985 and none of the 39 women since, no malformations could be ascribed to the use of the haemolysate.Conclusion The use of the membrane-free haemolysate is safe, but the technique will probably gradually become redundant because of improved ultrasound.