First-trimester crown-rump length and embryonic volume of aneuploid fetuses measured in virtual reality.

OBJECTIVES: To examine whether embryonic volume (EV), as measured using three-dimensional (3D) ultrasound and a virtual reality approach, is a better measure of growth restriction than is crown-rump length (CRL) in aneuploid fetuses. METHODS: We retrospectively measured CRL and EV in prospectively collected 3D ultrasound volumes of 55 aneuploid fetuses using the Barco I-Space VR system. The gestational age ranged from 11 + 2 to 14 + 4 weeks. We compared our measured data with previously published reference curves for euploid fetuses. Delta-values were calculated by subtracting the expected mean for euploid fetuses of the same gestational age from observed values. The one-sample t-test was used to test the significance of differences observed. RESULTS: The CRL measurements of fetuses with trisomy 21 (n = 26), trisomy 13 (n = 5) and monosomy X (n = 5) were comparable with those of euploid fetuses, but in fetuses with trisomy 18 (n = 19) the CRL was 14.5% smaller (P < 0.001). The EV in fetuses with trisomies 21, 18 and 13 and monosomy X was smaller than in euploid fetuses (-27.8%, P < 0.001; -39.4%, P < 0.001; -40.9%, P = 0.004; and -27.3%, P = 0.055, respectively). CONCLUSIONS: When relying on CRL measurements alone, first-trimester growth restriction is especially manifest in trisomy 18. Using EV, growth restriction is also evident in trisomies 21 and 13 and monosomy X. EV seems to be a more effective measurement for the assessment of first-trimester growth restriction in aneuploid fetuses.

An urban perinatal health programme of strategies to improve perinatal health.

Promotion of a healthy pregnancy is a top priority of the health care policy in many European countries. Perinatal mortality is an important indicator of the success of this policy. Recently, it was shown that the Netherlands has relatively high perinatal death rates when compared to other European countries. This is in particular true for large cities where perinatal mortality rates are 20-50% higher than elsewhere. Consequently in the Netherlands, there is heated debate on how to tackle these problems. Without the introduction of measures throughout the entire perinatal health care chain, pregnancy outcomes are difficult to improve. With the support of health care professionals, the City of Rotterdam and the Erasmus University Medical Centre have taken the initiative to develop an urban perinatal health programme called 'Ready for a Baby'. The main objective of this municipal 10-year programme is to improve perinatal health and to reduce perinatal mortality in all districts to at least the current national average of l0 per 1000. Key elements are the understanding of the mechanisms of the large health differences between women living in deprived and non-deprived urban areas. Risk guided care, orientation towards shared-care and improvement of collaborations between health care professionals shapes the interventions that are being developed. Major attention is given to the development of methods to improve risk-selection before and during pregnancy and methods to reach low-educated and immigrant groups.

Erroneous production of PAPP-A kits: the impact of a downward shift in PAPP-A concentration on the test performance of first-trimester combined screening for Down syndrome.

OBJECTIVE: To evaluate a 20% downward shift in the pregnancy-associated plasma protein A (PAPP-A) concentration on the test performance of first-trimester combined screening (FTS) for Down syndrome (DS) following a flaw in the production of PAPP-A kits on FTS for DS. METHODS: A retrospective re-evaluation of PAPP-A in stored sera. Inclusion criteria were a maternal weight-corrected PAPP-A multiple of the median value ≥ 0.9 and a biochemical risk of DS ≤ 1:200 at the time of testing. RESULTS: Of the 3100 women, 473 (15%) fulfilled the inclusion criteria. After combining the biochemical risk based on the incorrect PAPP-A values with nuchal translucency findings, an increased risk for DS was initially found in 107 women [false positive rate (FPR): 3.1]. Eighty-two (77%) of the 107 women opted for invasive testing. Following re-analysis of PAPP-A, the biochemical risk and the combined risk were statistically significantly different from the initial risk estimates (p < 0.001.). We noticed that 25 women (30%) had invasive testing, while this was unjustified given the re-analysed PAPP-A. CONCLUSION: Erroneous PAPP-A kits resulted in an increase in the FPR by 1.2%. There were no reports of iatrogenic miscarriage. The occurrence of this problem reaffirms the importance of continuous monitoring of quality in FTS.

The impact of rapid aneuploidy detection (RAD) in addition to karyotyping versus karyotyping on maternal quality of life.

OBJECTIVE: To assess the impact of rapid aneuploidy detection (RAD) combined with fetal karyotyping versus karyotyping only on maternal anxiety and health-related quality of life. METHODS: Women choosing to undergo amniocentesis were selected into group 1, i.e. receiving a karyotype result only (n = 132) or to group 2, i.e. receiving both the result of RAD and karyotyping (n = 181). RESULTS: There were no systematic differences in time of RAD combined with karyotyping versus karyotyping only in terms of anxiety (P = 0.91), generic physical health (P = 0.76, P = 0.46), generic mental health (P = 0.52, P = 0.72), personal perceived control (P = 0.91) and stress (P = 0.13). RAD combined with karyotyping reduced anxiety and stress two weeks earlier compared to karyotyping only. CONCLUSION: RAD as add-on to karyotyping reduces anxiety and stress in the short term but it does not influence overall anxiety, stress, personal perceived control, and generic mental and physical health when compared to a karyotype-only strategy.

[Termination of pregnancy after the 20-week ultrasonographic examination: haste and caution]. / Zwangerschapsafbreking na de 20-wekenecho: haast en zorgvuldigheid.

The recently introduced ultrasonographic screening programme for the detection of fetal structural anomalies at 20 weeks' gestation is leading to a growing number of cases with an unclear prognosis. This article presents the decision-making process which followed the screening of two women: one aged 36 years, where a post-screening work-up was conducted and swiftly led to well-balanced decision making to abort a fetus with trisomy 21, and one woman aged 30 years, in whom repeated non-decisive results of further diagnostic tests ultimately led to a hasty decision to abort the pregnancy. Up to 24 weeks, current Dutch law allows the couple to decide to have a termination of pregnancy; thereafter the legal possibility of having a termination is very limited. This may lead to rushed decision-making. It is argued that careful decisions in these matters are more important than staying within the 24-week limit. The national central committee ofexperts which is responsible for the evaluation of all abortions after 24 weeks gestation in the so-called category 2 cases (conditions which will lead to serious and irreparable functional disorders, such as severe spina bifida and hydrocephalus, but which are compatible with life) should take account of this dilemma ofhaste and caution.

[Assessment of late pregnancy terminations, 2004-2007]. / Toetsing van late zwangerschapsafbreking, 2004-2007.

OBJECTIVE: To provide an inventory of the reported late terminations of pregnancy because ofa severe anomaly of the unborn child, i.e. termination after 24 weeks of pregnancy, in The Netherlands for the period 2004-2007. DESIGN: Inventory and descriptive. METHOD: A description is given of the various assessment procedures for the termination of pregnancy after 24 weeks. A distinction is made between abortion for lethal foetal abnormalities (category 1) and severe functional impairments with a limited chance for survival of the unborn (category 2). The level of caution exercised in decision making and performing category 1 terminations is assessed by the professional group, namely by the assessment committee for Late Pregnancy Termination of the Dutch Association for Gynaecology and Obstetrics. Since 15 March 2007, late pregnancy terminations that fall under category 2 have by law been assessed by a national central committee of experts. An overview of the reported cases of late terminations of pregnancy in the Netherlands for the period 2004-2007 is given. RESULTS AND CONCLUSION: The number of reported terminations of pregnancy after 24 weeks (n = 72) has declined considerably since the early 1990s. A possible explanation is that due to increasing technological improvements and the implementation of prenatal screening in early preg-nancy, an abortion can be performed before the 24th week of pregnancy if any severe abnormalities are observed.

[Sonomarkers: subtle ultrasound findings in the 20-week ultrasound examination, which have a low association with some chromosomal and non-chromosomal abnormalities in the fetus]. / Sonomarkers: subtiele echoscopische bevindingen op de 20-wekenecho, die zwak correleren met enkele chromosomale en niet-chromosomale afwijkingen bij de foetus.

Currently all pregnant women residing in the Netherlands are offered second trimester ultrasound screening for the detection of fetal congenital structural abnormalities. This routine ultrasound examination takes place at 18 to 22 weeks' gestation. The ultrasound examination may yield soft markers, which are characterized by subtle morphological changes that are often transient and have little or no pathological significance. Soft markers are of interest because of their association with fetal congenital anomalies, in particular aneuploidy. This may create uncertainty for the pregnant woman and the care provider. Information can be found in the literature about the strength of the association of soft markers, when detected as an isolated finding, and the presence of fetal abnormalities. One or more soft markers are detected during routine ultrasound in approximately 5% of pregnant women. 4 markers (echogenic intracardiac focus, echogenic bowel, mild ventriculomegaly and shortened femur) are associated with Down syndrome. Given the low prevalence of Down syndrome in the general population and the relatively low strength of association with the syndrome, the positive predictive value of these markers is very low. The same is true for choroid plexus cysts, which are associated with trisomy 18. Apart from chromosomal abnormalities, some soft markers (echogenic bowel, mild ventriculomegaly and shortened femur) are also associated with non-chromosomal fetal abnormalities. Renal pyelectasis and the 2-vessel (instead of 3-vessel) umbilical cord are associated with non-chromosomal abnormalities only. It is recommended that pregnant women be informed about the nature and implications of these findings before the examination.

[Perinatal outcomes in the four largest cities and in deprived neighbourhoods in The Netherlands]. / Perinatale uitkomsten in de vier grote steden en de prachtwijken in Nederland.

OBJECTIVE: To analyse the association between neighbourhood, ethnicity and adverse perinatal outcome in pregnant women from the 4 largest cities (Amsterdam, Rotterdam, The Hague and Utrecht; G4) and elsewhere in The Netherlands. DESIGN: Descriptive, retrospective. METHOD: The perinatal outcome of 877,816 single pregnancies during the years 2002-2006, derived from The Netherlands Perinatal Registry, was analysed for the ethnicity (Western or non-Western) and the neighbourhood (deprived or not) of the pregnant women in the G4 and elsewhere in The Netherlands. Adverse perinatal outcome was defined as perinatal mortality, congenital abnormalities, intra-uterine growth restriction, preterm birth, Apgar score after 5 minutes < 7 and/or admission to a neonatal intensive-care unit. RESULTS: The overall perinatal mortality rate was higher in the G4 than elsewhere in The Netherlands (11.1 per thousand versus 9.3 per thousand; p < 0.001; 95% confidence interval of the difference: 1.2-2.4 per thousand). The same was true for the sum of adverse perinatal outcomes (154.9 per thousand versus 138.9 per thousand). In the G4 the perinatal mortality among non-Western women was higher than among Western women (13.2 per thousand versus 9.5 per thousand). Residing in Dutch deprived neighbourhoods was associated with a higher perinatal mortality than outside deprived neighbourhoods (13.5 per thousand versus 9.3 per thousand). The relative risks of living in deprived neighbourhoods for adverse pregnancy outcomes are higher among Western than among non-Western women. CONCLUSION: Pregnant women in the G4 have an increased risk ofadverse perinatal outcomes. The risks of residing in a deprived neighbourhood are even higher, especially among Western women. The findings are important for new strategies to improve perinatal outcomes.

[Preconception care: an essential part of the care for mother and child]. / Preconceptiezorg: een onlosmakelijk onderdeel van de zorg voor moeder en kind.

Despite the modernisation of antenatal care in the Western world, the incidence of a number of adverse pregnancy outcomes, such as birth defects, low birth weight and preterm birth, has not decreased over the past few decades. Since its inception at the beginning of the last century, the concept of antenatal care has not changed. The first antenatal visit typically starts at the end of the first trimester. By this stage of pregnancy organogenesis and early placentation have been completed making it almost impossible to reverse any unfavourable exposure on the foetus. Preconception care addresses risk factors that are present prior to pregnancy. By either eliminating or altering risk factors during this period, pregnancy outcome may improve. The goal of preconception care is to optimise the quality of foetal, newborn and infant life through primary prevention. With regard to genetic conditions the aims of preconception care are more nuanced. The principle components of preconception care include (a) risk assessment, (b) information and advice on health promotion, (c) specific counselling and (d) intervention. The effectiveness of preconception care has been demonstrated in women who are at increased risk of adverse pregnancy outcome. In women at low-risk, however, the usefulness of preconception care has yet to be established. The concept of preconception care is relatively simple, logical and promises much. For preconception care to be a success, it is crucial to make this form of preventive care available to all prospective parents. The Internet could play a major part in the dissemination of information that is relevant to a successful outcome of pregnancy.

[Radioiodine therapy for women with Graves' disease and the risk of foetal hypothyroidism if they are later found to be pregnant]. / Behandeling van een vrouw met de ziekte van graves door middel van radioactief jodium en het risico op foetale hypothyreoïdie als zij later zwanger blijkt te zijn.

Three fertile female patients aged 33, 29 and 38 years, respectively, were treated with radioiodine 1-131 for Graves' disease. In retrospect, the first woman was 14 weeks pregnant at the time of treatment, and the other 2 women were treated around the time of conception. All 3 women decided to continue their pregnancies after being counselled about the potential adverse health risks of radioiodine therapy for the infant. The first woman was delivered at term of an infant diagnosed with hypothyroidism that was ascribed to radioiodine. The other 2 women delivered euthyroid infants. According to international standards, radioiodine should not be given during pregnancy because of its toxic effects. An interval of at least 4 months is advised between maternal radioiodine therapy and conception. This should be discussed with the patient. Prior to the initiation of radioiodine therapy, menstrual and contraceptive history should be ascertained in fertile female patients. Pregnancy testing should be performed where indicated, and the result should be verified before radioiodine therapy is initiated.

[Towards a national programme for prenatal screening for Down's syndrome]. / Naar een landelijk programma voor prenatale screening op downsyndroom.

During the first trimester of pregnancy, the combination test is used for an assessment of the individual risk of Down's syndrome. Several factors have an effect on the variance of the risk estimates. In this context, special attention is given to the interpretation of test results based on centre-specific medians for gestation and those based on published normal medians that are derived from large databases that have a proven track record in terms of detection rates. Centre-specific medians could be used, provided test performance is closely monitored and stays within acceptable limits. In order to reduce undue anxiety from conflicting false-positive test results, all components that yield the risk estimates should be standardised. To achieve this goal, the government should no longer delay the implementation of a national, first trimester, prenatal screening programme for Down's syndrome as was recommended by the Health Council of The Netherlands. Such a programme should incorporate strict guidelines for information, risk communication, quality assurance and feedback.

[Prenatal investigations for Down's syndrome: medical-technical considerations and dilemmas arising from current screening methods]. / Prenataal onderzoek naar downsyndroom: medisch-technische overwegingen en dilemma's voortkomend uit de huidige toepassingsmogelijkheden.

Prenatal investigations can be divided into specific diagnostic investigations i.e. chorionic villus sampling, amniocentesis and selective ultrasonography for the detection of fetal abnormality, and screening tests which estimate the chances of the condition being present. These include routine ultrasonography and tests based on biochemical and echoscopic markers. Amniocentesis is the most reliable test to detect chromosomal anomalies, but is associated with a low risk of miscarriage and the results are known only relatively late in pregnancy. Implementing the prenatal screening tests will enable the better identification of those women with an increased risk of chromosomal anomalies, and consequently to fewer invasive diagnostic procedures. The choice whether to have prenatal screening should always be made by the parents after they have been told of the advantages and disadvantages of these investigations.

[Invasive prenatal diagnosis in the Netherlands, 1991-2000: number of procedures, indications and abnormal results detected]. / Invasieve prenatale diagnostiek in Nederland, 1991-2000: aantallen ingrepen, indicaties, en gevonden afwijkingen.

OBJECTIVE: To provide an overview of invasive prenatal diagnosis in the Netherlands during the period 1991-2000 and to analyse potential trends. DESIGN: Retrospective. METHOD: The annual results from all 13 Dutch centres for invasive prenatal diagnosis over the period 1991-2000 were combined and described, with particular emphasis on indications, number and type of invasive procedures, and number and type of abnormal results. RESULTS: The percentage of pregnancies in which invasive prenatal diagnostics were carried out increased from 5% in 1991 to 6% in 1996 and remained at the same level until 2000. 'Maternal age' was the main reason for prenatal testing (69.2-73.3% of procedures). However, the number of pregnant women aged 36 or over increased by 69.9%. An abnormal result was found in an average of 4.7% of procedures, rising from 3.6% in 1991 to 5.4% in 2000. In 70.8% of cases with abnormal results, the pregnancy was terminated. Important trends were the relative decrease of cordocentesis (-82%) and chorionic villi biopsy (-18%) in favour of amniocentesis (+48%), and a strong decrease in the number of amniocentesis procedures on indication of increased risk of neural tube defect. CONCLUSION: The total number of invasive prenatal diagnostic procedures remained stable. However, there was an important decrease in the percentage of pregnant women aged 36 or over who underwent invasive prenatal diagnosis without previous prenatal screening.

[Pregnancy termination in the second trimester with vaginally administered dinoprostone followed by intravenous sulprostone, for the indication 'foetal congenital defects'; results of a retrospective study]. / Zwangerschapsafbreking in het tweede trimester met dinoproston vaginaal gevolgd door sulproston intraveneus, op de indicatie 'foetale congenitale afwijkingen'; resultaten van een retrospectieve studie.

OBJECTIVE: To obtain insight into treatment duration and complications of the currently accepted method for pregnancy termination in the second trimester using a combination of prostaglandine-E2 medications. DESIGN: Retrospective study of medical records. METHOD: Data were collected for all second trimester pregnancy terminations performed on foetal indication in the Erasmus Medical Center in Rotterdam, The Netherlands, in the years 1998-2001. The treatment consisted of vaginal administration of dinoprostone, followed by intravenous administration of sulprostone. RESULTS: A total of 134 pregnant women were involved in the analysis. The median age was 33 years and the median pregnancy duration 19 weeks. The median duration of hospital stay was 3 days (range: 2-11 days). The median duration of treatment for the total study population was 19 hours (4-172). For nulliparae this was 23 hours, and for multiparae 17 hours (p < 0.05). Of the total study population, 91 women (68%) delivered within 24 hours. The percentage of multiparae that delivered within 24 hours was higher than the percentage of nulliparae that delivered in this time (76% compared to 53%: p < 0.05). Operative removal of a--partially--retained placenta was conducted in 51 women (38%). This percentage was higher among women with treatment duration longer than 24 hours than among women who delivered within 24 hours (51% versus 32%; p < 0.05). The treatment duration and the complication percentage were less favourable than those described in a number of publications relating to the combination mifepristone and misoprostol.