Hintergrund: Häufigkeiten und Ursachen angeborener Fehlbildungen sind in mehr als der Hälfte der Fälle unbekannt und somit Inhalt wissenschaftlicher Forschungsprojekte. Ziele: Die Aufgaben der Geburtenregister liegen einerseits in der Ermittlung populationsbezogener Fehlbildungsprävalenzen und gegebenenfalls zeitlicher/räumlicher Trends als auch in der Ursachenforschung zur Entstehung angeborener Malformationen. Weitere Zielsetzungen sind die Ermittlung von Ansatzpunkten für Präventionsmaßnahmen sowie deren Überprüfung und die Wirkungsweise als Instrument der Qualitätskontrolle. Methode: Seit der Etablierung (1990) des Geburtenregisters Mainzer Modell wurden bis 2004, 51.345 Neugeborene und Feten innerhalb der ersten Lebenswoche standardisiert untersucht. Bei allen induzierten Aborten, Totgeburten und Spontanaborten wurden die Befunde des pathologischen Instituts herangezogen. Die Erhebung der anamnestischen Daten erfolgt etwa sechs Wochen vor dem Geburtstermin. Risikofaktoren werden in Fall-Kontroll-Analysen der Geburtenkohorte ermittelt. Als Maßzahl dient das Odds Ratio (OR) mit 95-%-Konfidenzintervall. Ergebnisse: Große Fehlbildungen wurden populationsbezogen bei 6,7% aller Kinder diagnostiziert. Die am häufigsten betroffenen Organkategorien sind Skelettsystem (2,2%), kardiovaskuläres System (1,1%) und internes Urogenitalsystem (1,5%). Als mögliche Ursachen sind künstliche Befruchtung (ICSI-Methode OR 2,7, 1,8–3,9), mütterliches Alter OR 1,1, 1,01–1,2, Medikamente (β2-Sympathomimetika OR 1,9, 1,1–3,0), etc. zu diskutieren. Die pränatale sonographische Erkennungsrate wurde ermittelt und im Rahmen einer europäischen Zusammenarbeit bewertet. Schlussfolgerung: Das Geburtenregister Mainzer Modell ermittelt populationsbezogene epidemiologische Daten zur perinatalen Gesundheit. Ein Follow-up der Patienten dieser Geburtenkohorte ist geplant.

Hintergrund: Folsäure und ihre gesundheitsprotektiven Wirkungen, insbesondere bei Schwangeren zur Prävention von Neuralrohrdefekten (NRD), sind unumstritten u. wissenschaftlich belegt. In anderen Ländern, wie z.B. den USA, wurde durch eine Anreicherung von Mehl die gesundheitspolitische Konsequenz gezogen. Ziele: Der Bekanntheitsgrad und das Wissen über Folsäure in der Allgemeinbevölkerung sollte für Rheinland-Pfalz überprüft werden. Der Anteil der werdenden Mütter, die über den positiven Effekt der perikonzeptionellen Folsäureprophylaxe informiert sind und sie durchführen, sollte ermittelt werden. Methode: In einer Stichprobe wurden 5.366 Mütter neugeborener Kinder in Rheinland-Pfalz (23% aller Geburten des Studienzeitraumes 2003/2004) zum Kenntnisstand über Folsäure und deren Substitution befragt, 2.346 (44%) Fragebögen wurden ausgewertet. Ende 2005 wurde in Rheinland-Pfalz eine repräsentative Telefonumfrage mit 1.076 deutschsprachigen Einwohnern zum Wissen über Folsäure durchgeführt. Die deskriptive Analyse erfolgte mittels SPSS. Ergebnisse: 2/3 der Schwangeren kannten den Sinn einer perikonzeptionellen Folsäuresubstitution, jedoch nur jede elfte Mutter hat zum richtigen Zeitpunkt in ausreichender Dosis eine Prophylaxe durchgeführt. Der Anteil der Kinder mit NRD liegt seit mehr als 10 Jahren unverändert bei ca. 2 Kindern pro 1.000 Geburten. Der Bekanntheitsgrad der Folsäure lag bei den Teilnehmern der Telefonumfrage bei ca. 60%, wobei Frauen (w:56% vs. m:44%) und höhere soziale Schichten (40% vs. 71%) besser informiert waren, ein Stadt-Land-Unterschied nicht erkennbar war und jüngere Teilnehmer (16–19 Jahre; 31%) gegenüber älteren (30–39J.; 70%) schlechter abschnitten. Schlussfolgerung: Trotz des Wissens einer Mehrheit der Bevölkerung über Folsäure und deren Nutzen ist von einer Unterversorgung – insbesondere von Schwangeren – auszugehen. Eine Verminderung des Auftretens von Neuralrohrdefekten ist nicht festzustellen. Deutschland kann als „Folsäure-Entwicklungsland“ bezeichnet werden. Die bisherige Aufklärung ist als unzureichend anzusehen. Eine Anreicherung von Grundnahrungsmitteln muss diskutiert werden.

To assess at a population‐based level the frequency with which severe structural congenital malformations are detected prenatally in Europe and the gestational age at detection, and to describe regional variation in these indicators.

The study was performed to evaluate the prevalence of prenatal ultrasound diagnoses for renal anomalies in 20 registries of 12 European countries, and to compare the different prenatal scanning policies. Standardized data were acquired from 709,030 livebirths, stillbirths, and induced abortions during the study period of 2.5 years and transmitted for central analysis. At least one renal malformation was diagnosed in 1130 infants and fetuses. Prenatal diagnosis (PD) was given in 81.8% of all cases, 29% of these pregnancies were terminated. The highest detection rate was reported for unilateral multicystic dysplastic kidneys with 97% (102/105). An early diagnosis was documented for exstrophy of bladder at a mean gestational age of 18.5 weeks. Dilatations of the upper urinary tract were seen late in pregnancy at 28.3 weeks. Terminations of pregnancies (TOP) were performed in 67% (58/86) of the detected bilateral renal agenesis/dysgenesis, but only 4% of the unilateral multicystic dysplastic renal malformations (4/102). In about 1/3 of the cases, renal malformations are within the category of associated malformations, which include multiple non-syndromal malformations, chromosomal aberrations, and non-chromosomal syndromes. Renal malformations were detected in 2/3 of the associated category by the first prenatal ultrasound scan. Detection rates vary in the different countries of the European community due to diverse policies, ethical, and religious background. Countries with no routine ultrasound show the lowest rates in detection, and termination of pregnancy. Prenatally detected renal malformations should result in a careful examination for further anomalies. Prenatal ultrasound fulfills the needs of screening examinations and is a good tool in detecting lethal and severe renal malformations.

Background: EUROCAT is a network of population-based registries for the epidemiologic surveillance of congenital anomalies covering approximately one quarter of births in the European Union. Down syndrome constitutes approximately 8% of cases of registered congenital anomaly in Europe, with over 7000 affected pregnancies in the 15 current member states of the European Union each year. In this paper, we aim to examine trends in the live birth prevalence of Down syndrome in Europe in the light of trends in maternal age and in prenatal diagnosis.Methods: Descriptive analysis of data from 24 EUROCAT registries, covering 8.3 million births 1980-99. Cases include live births, stillbirths and terminations of pregnancy following prenatal diagnosis.Results: Since 1980, the proportion of births to mothers of 35 years of age and over has risen quite dramatically from 8 to 14% for the European Union as a whole, with steeper rises in some regions. By 1995-1999, the proportion of "older" mothers varied between regions from 10% to 25%, and the total prevalence (including terminations of pregnancy) of Down syndrome varied from 1 to 3 per 1000 births. Some European regions have shown a more than twofold increase in total prevalence of Down syndrome since 1980. The proportion of cases of Down syndrome which were prenatally diagnosed followed by termination of pregnancy in 1995-1999 varied from 0% in the three regions of Ireland and Malta where termination of pregnancy is illegal, to less than 50% in 14 further regions, to 77% in Paris. The extent to which terminations of pregnancy were concentrated among older mothers varied between regions. The live birth prevalence has since 1980 increasingly diverged from the rising total prevalence, in some areas remaining approximately stable, in others decreasing over time.Conclusion: The rise in average maternal age in Europe has brought with it an increase in the number of pregnancies affected by Down syndrome. The widespread practice of prenatal screening and termination of pregnancy has in most of the regions covered by EUROCAT counteracted the effect of maternal age in its effect on live birth prevalence. Under the joint influences of maternal age and prenatal screening the pattern of geographic inequalities in Down syndrome live birth prevalence in Europe has also been changed.

Fehlbildungsregister/Geburtenregister sind die epidemiologische Grundlage, Häufigkeiten angeborener morphologischer Defekte zu erfassen und somit das Basisrisiko angeborener Fehlbildungen für Neugeborene zu ermitteln. Das Risiko, mit einer großen Fehlbildung geborenen zu werden, liegt derzeit in Deutschland bei 5–7%. Die in den Fehlbildungsregistern erhobenen Basisdaten dienen dazu, zeitliche und regionale Trends von Fehlbildungsprävalenzen zu erfassen, Risikofaktoren und damit Ansatzpunkte für Präventionsmaßnahmen zu ermitteln, Präventionsmaßnahmen zu veranlassen bzw. zu überprüfen sowie Forschungsprojekte zu initiieren. Zur Erfassung valider Prävalenzen und Daten sowie zur Vermeidung von Beobachter-, Definitions-, und Selektionsverzerrungen ist die Verwendung aktiver Erfassungssysteme erforderlich. Das wesentliche epidemiologische Basiswissen für die Fehlbildungsforschung wird dargestellt.

Biometrical JournalVolume 46, Issue S1 p. 7-7 Oral Sessions Abstracts S03.4: Associations between childhood cancer and major malformations: Analysis of 36.874 newborns of the birth registry Mainz Model Gabriela Stolz, Gabriela StolzSearch for more papers by this authorA. Wiesel, A. WieselSearch for more papers by this authorK. Schlaefer, K. SchlaeferSearch for more papers by this authorM. Dittrich, M. DittrichSearch for more papers by this authorC. Spix, C. SpixSearch for more papers by this authorJ. Wahrendorf, J. WahrendorfSearch for more papers by this authorA. Queisser-Luft, A. Queisser-Luft queisser@kinder.klinik.uni-mainz.de Universitätskinderklinik, Mainzer ModellSearch for more papers by this author Gabriela Stolz, Gabriela StolzSearch for more papers by this authorA. Wiesel, A. WieselSearch for more papers by this authorK. Schlaefer, K. SchlaeferSearch for more papers by this authorM. Dittrich, M. DittrichSearch for more papers by this authorC. Spix, C. SpixSearch for more papers by this authorJ. Wahrendorf, J. WahrendorfSearch for more papers by this authorA. Queisser-Luft, A. Queisser-Luft queisser@kinder.klinik.uni-mainz.de Universitätskinderklinik, Mainzer ModellSearch for more papers by this author First published: 17 March 2004 https://doi.org/10.1002/bimj.200490275AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, IssueS1Supplement: Abstracts of the Joint Meeting of the IBS-DR and the DAEMarch 2004Pages 7-7 RelatedInformation

Objective To investigate outcomes of ultrasound investigations (US) and invasive diagnostic procedures in cases of congenital malformations (CM), and to compare the use of invasive prenatal test techniques (amniocentesis (AC) versus chorionic villus sampling (CVS)) among European populations.Design Analysis of data from population-based registries of CM.Subjects 25 400 cases of CM recorded by 14 EUROCAT registries covering a total population of 1013 352 births 1995-99.Results US were performed in 91% of cases, and positively detected CM in 35% of cases. AC was performed in 24% of the cases and CVS in 3% of cases. Thirty-eight percent of invasive tests gave positive results. Fifty-two percent of cases with maternal age greater than or equal to35 years had an invasive test performed compared to 20% of cases with younger mothers.Considerable variation was found between registries in the uptake rate of invasive tests in cases with older maternal age and on the use of invasive tests with only four regions employing CVS techniques in at least a third of the cases having invasive tests. For chromosomal anomalies US gave positive results in 46% of cases with maternal age <35 years with US performed and in 36% of cases with maternal age greater than or equal to35 years with US performed.Conclusion Prenatal US was performed in 91% of all pregnancies with CM but the test was only positive in a third of the cases. There was large regional variation in the uptake rate of invasive tests with maternal age of 35 years or more. For every CVS carried out there were nine AC tests. US is an important tool in the prenatal diagnosis of chromosomal anomalies in Europe. Copyright (C) 2004 John Wiley Sons, Ltd.

UNLABELLED:Malformations of the internal urogenital system are common. The birth registry "Mainz Model" reflects population-based prevalence of renal malformations, calculates sensitivity rates of the prenatal ultrasonographic findings and demonstrates rates of surgery needed.METHOD AND MATERIAL:During the study period (1990-2001) all newborns of the area of Mainz were examined according to a standardized procedure including ultrasonography of the kidneys. Pathology reports were reviewed for stillbirth, abortions (> 15.SSW) and induced abortions. Beside these clinical findings, since 1996 (after implementation of a special ultrasonographic malformation screening according to the german maternity guidelines) the results of prenatal as well as postnatal ultrasonographic examinations of the kidney were recorded. All children with pathologic diagnoses of the kidneys were retrospectively analysed. Data about the follow up and surgery if needed, were collected.RESULTS:During the study period from 1990-2001 34.450 newborns were examined. 407 of the neonates (1.2%) had a malformation of the kidney. During the study period from 1996-2001 13.162 neonates were examined. 194 neonates (1.5%) had pathologic and 225 neonates (2.07%) had controllable findings. The most common diagnoses were supernumerary kidney, hydronephroses und megaureter. 22 neonates (12.8%) underwent surgery. The sensitivity of the prenatal ultrasonography was 36% and the specificity was 99%.CONCLUSION:Both, the prenatal as well as the postnatal ultrasonographic screening of the kidneys are ingenious examinations. The prenatal examination detects life threatening malformations of the kidneys. The postnatal examination completes early diagnosis of renal defects by uncovering the malformations, which have been missed prenatally. The prevalence of malformations of the kidney is comparable to the one of hip dislocation. We therefore conclude, that ultrasonographic screening of the kidneys is needed.

Prevalence rates of birth defects in the Federal Republic of Germany are informative to assess the general background risk of having a child with a birth defect. They provide basic figures to determine temporal and regional prevalence trends, to evaluate and initiate preventive measures and to initiate research projects. To avoid observer, definition and collection bias, active monitoring systems are required. Data collected in the active monitoring system of the Mainz Birth Defects Registry are presented. From 1990–1998, 30940 livebirths, stillbirths and abortions underwent standardized physical and sonographic examinations. Anamnestic data were collected from prenatal care records, maternity files and hospital records. Major malformations were diagnosed in 2144 (6.9%) and mild errors of morphogenesis in 11104 (35.8%) of all infants. Risk factors associated with the occurrence of major malformations were identified by comparing anamnestic data from infants with and without major malformations. Using multivariate regression models, statistically significant associations were established for 9 risk factors. Causally related risk factors were parents or siblings with malformations, parental consanguinity, more than 3 minor errors of morphogenesis in the proband, maternal diabetes mellitus and ingestion of antiallergic drugs in the first trimester of pregnancy. Conjunctional risk factors were polyhydramnios, oligohydramnios and gestational age <32 weeks at birth. Using these risk factors, populations at risk for the occurrence of major malformation can be identified.

Zusammenfassung Epidemiologische Daten eines klinischen Neugeborenenscreenings sind die Grundlage, zeitliche und regionale Trends von Fehlbildungsprävalenzen zu erfassen, Risikofaktoren und damit Ansatzpunkte für Präventionsmaßnahmen zu ermitteln, Präventionsmaßnahmen zu veranlassen bzw. zu überprüfen sowie Forschungsprojekte zu initiieren. Zur Erfassung valider Daten und zur Vermeidung von Beobachter-, Definitions- und Selektionsverzerrungen sollten aktive Erfassungssysteme verwendet werden. 34.211 Lebendgeborene, Totgeborene und Aborte der populationsbezogenen Geburtenkohorte des aktiven Mainzer Geburtenregisters wurden nach einem standardisierten Schema klinisch und sonographisch untersucht und anamnestische Daten erhoben. Prävalenzen großer und kleiner Fehlbildungen wurden erfasst und frühzeitig therapeutische Maßnahmen eingeleitet. Dies ermöglicht eine optimale, problemangepasste Therapie sowie eine Beratung und Begleitung der betroffenen Familien. Prävalenz-Odds-Ratios wurden berechnet, um Risikofaktoren für angeborene Fehlbildungen zu ermitteln. Dies erlaubt die Identifikation eines Risikokollektivs, bei dem das Vorliegen großer Fehlbildungen ausgeschlossen werden sollte. Die für Screeninguntersuchungen geforderten Voraussetzungen – Existenz therapeutischer Maßnahmen, Verschlechterung der Prognose bei Ausbleiben einer Behandlung und Gesundheitsgewinn bei Durchführung einer Therapie – erfüllt ein strukturiertes klinisch-morphologisches Neugeborenenscreening zur Fehlbildungserfassung vollständig.

Epidemiological data of clinical screening examinations in newborns represent the basis to determine temporal and regional prevalence trends for malformations, to evaluate and initiate preventive measures, and to initiate research projects. Active monitoring systems should be required to avoid collection, observer and definition bias. 34,211 livebirths, stillbirths and abortions of the population based Mainz birth registry underwent standardized physical and sonographic examinations and anamnestic data were collected. Prevalence rates of major malformations and mild errors of morphogenesis were calculated and early treatment was initiated. This enables optimal care of these infants and adequate counseling of their families. In addition, prevalence odds ratios were established to determine risk factors for congenital malformations, allowing the identification of populations at risk for birth defects where major malformations should be ruled out. The important criteria for screening programs - the existence of preventive or therapeutic interventions, aggravation of the prognosis due to the lack of adequate measures, and health benefit from therapy - are completely fulfilled by clinical screening examinations in newborns.

Objective: Up to now, no prospective, controlled study has been published, which had enough statistical power to evaluate the malformation risk following an ICSI treatment. Design: Prospective, multicentric and controlled trial of German IVF centers. Materials/Methods: 2,809 pregnancies following ICSI have been recruited by 59 German IVF centers. All pregnancies were conceived after a fresh embryo transfer after ICSI, went on more than 16 weeks of gestation (WOG) and were registered for the study after patients informed consent before 16 WOG. Patients were monitored by regular telephone interviews according to a standardized questionnaire. All data related to the fetuses of induced abortions, spontaneous abortions, stillbirths and live births above 16 WOG were recorded. All fetuses and children born were examined according to the standardized scheme of the Mainzer Birth Registry by 25 examiners (specialized in pediatrics and/or medical genetics). All malformations were classified as major or minor according to the EUROCAT (European registry of congenital anomalies and twins). A control group of 2889 children was prospectively recruited from spontaneous conceived pregnancies during the same time period and was evaluated regarding to the same data as the study group. Results: 2,648 fetuses and children after ICSI were examined up to January 2001. 2596 live born and 8 stillborn children, as well as 44 aborted fetuses and 14 fetuses after induced abortions were included. There were 1580 singleton, 922 twin and 141 triplet children. Multiple births were more common in the study group (26% vs 3%). No significant difference in malformation rates between the three cohorts could be found (9.9%, 9.0%, 7.1%, respectively). Mean birth weight and gestational age at birth was the same in the control as in the ICSI cohort, when controlled for multiples. The malformation rate in the ICSI cohort was in the same range as it was in the control cohort of spontaneously conceived children, if certain risk factors were taken into account. Overall 25 of 644 (3.9%) karyotypes in prenatal diagnosis were abnormal, which was higher compared to the control population. It has to be considered, that certain risk factors for the development of malformations were more prevalent in the ICSI cohort. Maternal age was significantly higher (32.8 ± 3.8 vs. 30.1 ± 5.2, p < 0.01), as was the mean number of previous abortions (46% vs. 25%, p < 0.05), and induced abortions (10% vs. 6%, p < 0.05). The prevalence of diabetes mellitus was higher (3.5% vs. 1.9%, p < 0.05). Conclusions: If certain risk factors were taken into account, the malformation risk following an ICSI procedure was not different from that of the cohort of spontaneously conceived children. Supported By: unconditional grant of Serono GmbH, Organon GmbH, ASTA Medica AG, Ferring Arzneimittel GmbH, Firma Gück, and the German IVF Centers.