Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome.

BACKGROUND: First trimester screening (FTS) for Down syndrome combines measurement of nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A (PAPP-A). The aim of this study was to undertake a detailed analysis of FTS results in singleton pregnancies conceived using assisted reproductive technologies (ART) and non-ART pregnancies. METHODS: A record linkage study compared outcomes in 1739 ART-conceived and 50 253 naturally conceived pregnancies. RESULTS: Overall, significantly lower PAPP-A levels were detected in ART pregnancies (0.83 multiples of median, MoM) than in controls (1.00 MoM) (t-test P < 0.001). This difference remained after excluding complicated pregnancies. Analysis of factors affecting PAPP-A levels suggested fresh compared with frozen embryo transfers and use of artificial cycles compared with natural cycles for frozen transfers were associated with lower values. The adjusted odds ratio (AdjOR) for receiving a false-positive result was 1.71 (95% CI 1.44-2.04; P < 0.001) for ART pregnancies compared with non-ART pregnancies, and this leads to a higher AdjOR (1.24, 95% CI 1.03-1.49; P = 0.02) for having a chorionic villous sampling (CVS) or amniocentesis. CONCLUSIONS: ART pregnancies have reduced FTS PAPP-A levels leading to an increased likelihood of receiving a false-positive result and having a CVS/amniocentesis. Lower PAPP-A may reflect impairment of early implantation with some forms of ART.

Follow up and evaluation of the Victorian first-trimester combined screening programme for Down syndrome and trisomy 18.

OBJECTIVE: The objective of this study was to follow up and evaluate the statewide first-trimester combined screening programme for Down syndrome and trisomy 18 at Genetic Health Services Victoria, Australia. DESIGN: Retrospective population cohort. SETTING: Maternal Serum Screening Laboratory records. SAMPLE: All women screened between February 2000 and June 2002 (16,153 pregnancies). METHODS: Screening results were matched to Victorian perinatal and birth defect data via record linkage, with an ascertainment of 96.8% of pregnancy outcomes. Manual follow up with health professionals increased ascertainment to more than 99%. MAIN OUTCOME MEASURES: Fetal Down syndrome or trisomy 18, and combined screen results, to calculate test characteristics. RESULTS: Using a risk threshold of 1 in 300 at time of ultrasound, the sensitivities for standard first-trimester combined screening and augmented 13-week combined screening for Down syndrome were 87.3 and 90.5% and the false-positive rates (FPR) were 4.1 and 3.9%, respectively. The sensitivity for trisomy 18 was 66.7% (10/15, 95% CI 42.8-90.5%) with a 0.4% FPR and 15.2% positive predictive value (1 in 250 risk threshold). CONCLUSIONS: The combined use of record linkage and manual follow-up techniques was effective in ascertaining more than 99% of pregnancy outcomes for calculations of accurate test characteristics of the combined screen. The sensitivity for Down syndrome at Genetic Health is comparable to similar populations. However, the sensitivity for trisomy 18 is lower than that elsewhere, which may reflect the overall low birth prevalence of trisomy 18 and associated small numbers in this particular cohort.

Do women know that prenatal testing detects fetuses with Down syndrome?

This questionnaire-based study in Victoria, Australia, examined the responses of pregnant women, aged 37 years and over, to a question about what they expected prenatal testing (screening and/or diagnosis) for birth defects to tell them about their pregnancy. Content analysis showed that, of the 432 tested women, 61.3% mentioned Down syndrome, chromosomal abnormalities or trisomies. Women undergoing both screening and diagnosis were more likely than those having one or other test to mention Down syndrome (adjusted OR = 1.6, P = 0.06), having adjusted for age, marital status, education, residence and parity. Similarly, those from an English-speaking background were more likely to mention Down syndrome, etc. compared to women from a non-English-speaking background (adjusted OR = 3.5, P < 0.001). Down syndrome, a fundamental piece of information about prenatal tests, was not mentioned in nearly 40% of women's responses. This suggests that pregnant women need clearer information about prenatal testing, including the conditions that might be detected.