engleski

Optimization of the Methodology and Effectiveness of the First-trimester Combined Screening for Down Syndrome through Three-years’ Experience in Croatia

AIM OF THE STUDY: This study has been created with the aim of the best evidence for the accuracy of the first-trimester biochemical markers. The main interest was to evaluate their specificity through particular gestational weeks. We have assessed the magnitude of variability of maternal serum free &#946; -hCG and PAPP-A concentrations between the 10+0 and 13+6 week of gestation. In order to minimise the potential influence of co-variables on the serum markers&#8217; concentrations, this study comprised only of unaffected, singleton, non-diabetic and spontaneously conceived pregnancies in Croatian women, who underwent the routine first-trimester combined screening for chromosomal abnormalities. MATERIALS AND METHODS: Patients: The study group comprised of 2883 unaffected, spontaneously conceived, non-diabetic, singleton pregnancies, detached retrospectively from the population who underwent the first-trimester screening for chromosomal abnormalities and whose pregnancies reached the term before starting this investigation. Follow-up of the courses of the pregnancies and the income data were completed for the comparison with the selection criteria. All pregnant women had an ultrasound examination between 10 and 14 weeks&#8217; pregnancy, which included a crown-rump measurement for pregnancy dating, a nuchal translucency (NT) measurement and maternal serum biochemical markers for the calculation of the combined risk for trisomies 21, 18 and 13. The obstetricians filled the form for the test with a patient&#8217; s personal and pregnancy data: maternal birth date, weight, gravidity/parity, ethnicity, mode of conception, cigarette-smoking habits, medications, insulin-dependent diabetes mellitus and previous medical history, respectively. The blood sample was taken by venipuncture on the same day of the ultrasound or, alternatively, within 48 hour period after the ultrasound examination. The Hospital Ethics Committee approved the accessibility of the first-trimester screening to all pregnant women. Methods: The concentrations of free free &#946; -hCG and PAPP-A in maternal serum were determined by solid-phase, enzyme-labelled chemiluminiscent immunometric assay (DPC-IMMULITE, Siemens Medical Solution Diagnostics ; Gwynedd-UK, Los Angeles-USA). Concentrations of biochemical markers were interpreted in terms of the WHO-standards, for free &#946; -hCG to IRP 75/551, and for PAPP-A to IRP 78/610, respectively. Measured concentrations were converted to MoM values, according to centre-specific weighted regression median curves for free &#946; -hCG and PAPP-A, obtained on daily median values for unaffected pregnancies. Those raw values were corrected for maternal weight and smoking status when used for the calculation of risks for trisomies. The final risk for trisomies 21, 18 and 13 was computed by Prisca 4.0 software (Typolog) and by FMF First-trimester software (v. 2.2.0_68). Statistics: Statistical analyses were performed using MedCalc for Windows and descriptive statistics using Excel 7.0, respectively. The normality of distributions of biochemical markers was ascertained using log10 MoM values, according to Kolgomorov-Smirnov test. Data concerning proportions of smokers and the false-positive rates in particular weeks were analyzed by &#967; 2 test. The differences in maternal ages and maternal weight, between particular weeks, were assessed by one-way ANOVA. The level of p<0.05 was considered statistically significant. CONCLUSIONS: 1. In total number of 2883 studied pregnancies (unaffected, singleton, spontaneously conceived, non-diabetic) there were no statistical differences according to maternal age, maternal weight and smoking women, when distributed in separated weeks of the first-trimester. 2. The normality of the distribution log10 MoM of free &#946; -hCG and PAPP-A was assessed by Kolgomorov-Smirnov test. 3. The differences in false-positive rates for trisomy 21 between particular weeks, on the basis of biochemistry alone, were not statistically significant. 4. There was significantly higher false-positive rate for combined risk of trisomy 21 in week 10th, compared to week 11th and 12th, respectively. 5. For log10 MoM PAPP-A, significant variations were found in the gestational period from week 11+0 to13+6. 6. For log10 MoM free &#946; -hCG, significant variations were found in the gestational period from week 10+0 to 11+6.

Down syndrome; first-trimester screening; PAPP-A; free &#946; -hCG

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