Background This report presents the scientific evidence for the methods currently used, or in the process of being adopted, to detect fetal chromosomal and structural abnormalities during early pregnancy. Medical, social, psychological, ethical, health economic, quality assurance and safety aspects of early prenatal diagnosis were analysed.

This summary reviews the questions addressed and the most important conclusions reached in each chapter of the report.

In the first section SBU’s main conclusions are presented.

Conclusions

• A combined test of ultrasound nuchal translucency measurement and maternal serum biochemistry (biochemical screening) in early pregnancy (10–14 gestational weeks), along with maternal age, is the clinically evaluated method of assessing the probability of fetal Down syndrome that gives the best balance between the percentage of detected cases and false-positive results (strong scientific evidence).
• Maternal serum biochemistry with four markers (quadruple test) is the clinically evaluated method of assessing the probability of fetal Down syndrome that in the second trimester gives the best balance between the percentage of detected cases and false-positive results (strong scientific evidence).
• All the methods (nuchal translucency measurement, maternal serum biochemistry in the second trimester and the combined test) for assessing the probability of fetal Down syndrome examined by this report and evaluated in clinical practice gives a better balance between the percentage of detected cases and false-positive results than maternal age alone. Thus, the use of these methods requires fewer amniocenteses and chorionic villus samplings per detected cases of Down syndrome than maternal age alone (strong scientific evidence).
• Use of the interphase fluorescence in situ hybridization (FISH) test or quantitative fluorescent polymerase chain reaction (QF- PCR) is essentially as accurate as full karyotyping for detecting aneuploidies in chromosomes 13, 18, 21, x and y (strong scientific evidence).
• Normal results on the rapid FISH test or QF-PCR in prenatal diagnosis leave a residual possibility of fetal chromosomal abnormalities. In approximately 0.9% of all amniocenteses and chorionic villus samplings a full karyotype analysis will detect a chromosomal abnormality missed by the rapid FISH test or QF-PCR. For chromosomal abnormalities of clinical significance, the figure is 0.4% (strong scientific evidence).
• Fewer congenital abnormalities, including heart defects, appear to be detected when a routine ultrasound examination is performed at 12 instead of 18 gestational weeks. That is the case even if the 12-week examination includes nuchal translucency measurement and if increased nuchal translucency or greater probability of chromosomal abnormalities according to nuchal translucency is an indication for a comprehensive fetal anatomy at 18–22 gestational weeks. However, the scientific evidence is insufficient to draw a reliable conclusion in this regard.
• No detrimental impact of ultrasound exposure during the second trimester has been demonstrated on children’s growth, vision or hearing – or their neurological, cognitive or speech development. No correlation has been demonstrated between prenatal ultrasound exposure and childhood malignancies (strong scientific evidence).
• A meta-analysis of randomized trials have not shown any difference with respect to the frequency of non-right handedness (left handedness or no clear preference) between controls and groups assigned to in utero exposure to ultrasound. Analyses of subpopulations and two Swedish registry studies have found a correlation between such exposure and non-right handedness in boys. However, the scientific evidence is insufficient to draw a reliable conclusion.
• Invasive tests (amniocentesis and chorionic villus sampling) increase the risk of fetal loss. The best available estimate, which concerns fetal loss after late amniocentesis (15 or more completed gestational weeks), indicates a 1 percentage point increase in the risk. Most of these losses are miscarriages (moderately strong scientific evidence).
• Pregnant women prefer individual to group information. Audio or video information appears to improve their knowledge and understanding somewhat more effectively than letters and brochures. However, most studies reveal inadequacies when it comes to providing information to women prior to prenatal diagnosis. The women are not sufficiently knowledgeable, particularly with respect to the purpose and the potential implications of the results, to make a well-founded decision about whether or not to undergo testing. It is especially difficult for them to understand that nuchal translucency measurement with ultrasound and an evaluation of markers is part of a probability assessment rather than a final diagnosis (strong scientific evidence).
• Most pregnant women want to obtain early information and prefer screening in the first trimester (strong scientific evidence).
• Greater knowledge does not make pregnant women more anxious. The information required to minimize their stress and anxiety levels should be communicated in the same way as that which is provided prior to other medical interventions. Increased anxiety prior to prenatal diagnosis, while waiting for the results or after obtaining notification of detected (or of increased probability of) abnormalities is a natural reaction on the part of the woman and/or her partner (strong scientific evidence).