First-trimester serum PAPP-A and fß-hCG concentrations and other maternal characteristics to establish logistic regression-based predictive rules for adverse pregnancy outcome.

OBJECTIVE: To determine the clinical relevance of maternal characteristics and first-trimester serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotrophin (fß-hCG) in predicting placenta-related complications, miscarriage and preterm delivery. DESIGN, SETTING AND POPULATION: A historical cohort study of data of the National Institute for Public Health and the Environment of first-trimester screening tests performed between July 2002 and May 2006 was done. Data from 28 566 (64.1%) tests were eligible for analysis. METHODS: By logistic regression, predictive rules were made based on PAPP-A and fß-hCG concentrations, maternal smoking, maternal weight and age, low birth weight, stillbirth and hypertensive disorders, miscarriage and preterm birth. Predictive values were analysed with the area under the curve (AUC) of receiver operating curves (ROC). RESULTS: Predictive for placenta-related complications were low PAPP-A, low fß-hCG, smoking and weight (AUC 54%). For miscarriage low PAPP-A, low fß-hCG and maternal age (MA) were predictive (AUC 78%) and for preterm delivery low PAPP-A, smoking, MA and maternal weight (AUC 55%). CONCLUSION: Only the predictive model for miscarriage had a clinically relevant predictive value of 28%. Results together do not justify closer surveillance of chromosomally normal pregnancies with PAPP-A or fß-hCG levels below the fifth percentile.

Lack of standardization in determining gestational age for prenatal screening.

OBJECTIVES: To determine whether estimation of gestational age (GA) in the context of first-trimester Down syndrome screening is standardized in the Netherlands. METHODS: This was a retrospective study, carried out between January 2005 and December 2006, of women who underwent first-trimester Down syndrome screening (n = 40,730) based on GA, maternal serum analysis and nuchal translucency (NT) measurement. Date of the last menstrual period (LMP), dating scan information including measurement of crown-rump length (CRL), NT thickness and name of the sonographer were recorded for all pregnancies. The accuracy of estimation of GA was evaluated by comparing the GA based on the LMP with that estimated from the CRL, using relevant subsets of the database. A survey of 104 sonographers was performed to further investigate the findings of the preceding analysis. RESULTS: In 44% of all first-trimester combined tests the estimation of GA was based on the dating scan; the method of determination of GA was unknown in 23%. In 15% of all cases a dating scan was recorded but was not used to provide the estimation of GA at blood sampling. Detailed analysis showed that a consistent methodology for the estimation of GA from CRL was not maintained within hospitals and obstetric practices. For a single CRL, the reported GA differed by up to 10 days. Finally, it was demonstrated that individual sonographers reported different GAs for a given CRL. CONCLUSIONS: Currently, estimation of GA in the first trimester in the Netherlands is not standardized. To improve the performance of prenatal screening for Down syndrome, estimation of GA should be based on ultrasound examination, with one nationally accepted CRL curve.

Multi-centre first-trimester screening for Down syndrome in the Netherlands in routine clinical practice.

OBJECTIVES: This is the first report on the results of a first-trimester combined-test screening programme in the Netherlands in a multi-centre routine clinical setting. METHODS: Between July 2002 and May 2004, blood samples were taken from subjects in 44 centres in the Netherlands and sent to our laboratory to assay for maternal serum concentrations of fbeta-hCG and PAPP-A. Fetal nuchal translucency (NT) was measured in the participating centres at a gestational age (GA) of 10-14 weeks. Results of those pregnancies for which a combined biochemical and NT risk was calculated were included in the epidemiological analysis of this study. RESULTS: A total of 4033 singleton pregnancies were included in the analysis. The median maternal age of the analysed group was 36.5 years. The distribution of GA was biphasic, with median GA of 10.3 and 12.1 weeks, respectively. The detection rate using the combined ultrasound and serum screening at a cut-off level of 1 in 250 was 71% (15/21), with a screen-positive rate of 4.7%. CONCLUSION: The results of this study show that the first-trimester combined test is suitable as a prenatal screening test in a multi-centre routine clinical setting in the Netherlands. Strict performance evaluation should identify weaknesses in the organisation that impair the performance of the test. Here, the performance of NT was especially identified as a candidate for improvement.