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Ultraschall Med 2017; 38(02): 126-128
DOI: 10.1055/s-0043-102832
Editorial
© Georg Thieme Verlag KG Stuttgart · New York

Can Prenatal Testing in the First Trimester be Performed without Ultrasound?

Pränatale Diagnostik im I. Trimenon – ohne Ultraschall?
E. Merz
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Publication Date:
04 April 2017 (online)

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The introduction of NIPT (noninvasive prenatal testing) [1] [2] [3] [4] [5], i. e., the analysis of cell-free fetal DNA from the maternal blood to diagnose fetal chromosomal abnormalities, has resulted in a rapid change in prenatal testing around the world and a significant reduction is invasive procedures. The ease of the procedure (simple blood withdrawal from the mother), the relatively high detection rate for the most common chromosomal abnormalities (trisomy 21: 99.3 [5]-99.4 % [6], trisomy 18: 97.4 % [5] – 97.7 % [6], trisomy 13: 90.6 % [6] – 97.4 % [5], monosomy X: 90.3 [7] – 92.9 % [6], other anomalies of the sex chromosomes (without monosomy X): 93.0 % [7] and also some individual deletions [8] [9]), and the demand for increasingly early diagnosis have resulted in some patients being offered such a blood test as early as the 7th week of gestation [10], i. e., 4 – 5 weeks before first-trimester screening [11] [12] [13] with qualified ultrasound examination [14] is possible.

NIPT continues to be merely a supplementary, not a diagnostic, screening method that can yield false-positive [5] [15] [16] as well as false-negative results [17], albeit in a limited number of cases. Moreover, a result cannot be reached in the case of a low fetal DNA rate of less than 4 % as seen, for example, in very obese patients [18]. Depending of the sequencing method, a failure rate of between 1.58 % (massive parallel sequencing) and 6.39 % (SNP analysis) has been described [19]. NIPT cannot be used in the case of a high-grade multiple pregnancy, a vanishing twin, chromosomal mosaicism, and, depending on the sequencing method that is used, can only be used on a limited basis in the case of egg donation (the SNP method does not yield a result in this case).

If patients are not properly counceled, a negative NIPT result, i. e., no indication of the chromosomal abnormalities included in this testing, often results in patients believing that all chromosomal abnormalities as well as other malformations of the embryo/fetus can be ruled out. Chromosomal abnormalities account for only approximately 8.5 % of the total spectrum of anomalies [20]. The large majority of abnormalities are structural and can only be detected in the first trimester by a qualified ultrasound examination [14]. This includes severe CNS and facial deformities, spinal defects, thoracic, cardiac, and abdominal defects, severe urogenital defects, extremity defects, and twin deformities. A negative NIPT result therefore does not rule out severe defects, such as anencephaly.

Every positive NIPT result must be confirmed by invasive testing (CVS, amniocentesis) [3] [21]. This is performed under ultrasound guidance. In the case of a very early positive NIPT result, i. e., at 8 or 9 gestational weeks, the waiting time of 3 – 4 weeks until a diagnosis can be made via chorionic villus sampling puts an enormous psychological strain on the patient.

NIPT is not a replacement for first-trimester screening that includes sonographic examination of the fetus and can detect an abnormal nuchal translucency as well as other structural abnormalities [22] [23]. Therefore, NIPT can only be viewed as a supplementary screening method for detecting the most common chromosomal abnormalities and not as a replacement for ultrasound examination. If a missed abortion or a vanishing twin is detected by the ultrasound examination in the first trimester [24], NIPT is unnecessary. In the case of sonographic detection of a fetal malformation, NIPT is also no longer advisable. Chromosomal diagnosis via invasive testing and, if necessary, additional diagnosis via array CGH should be performed in this case.

However, care should also be taken in the case of ultrasound examinations in the first trimester. Some fetal anomalies are not yet able to be detected even by the most thorough ultrasound examination in the first trimester [22]. However, these are usually detected in the second trimester. Therefore, a follow-up ultrasound examination between gestational weeks 18 + 0 and 21 + 6 [25] continues to be an absolute requirement in prenatal testing.

Conclusion

  1. NIPT should never be performed in the first trimester without a prior ultrasound examination.

  2. NIPT is currently limited to the detection of trisomy 21, 18, 13, aberrations of sex chromosomes, and individual deletions.

  3. First-trimester screening between gestational weeks 11 + 0 and 13 + 6 continues to be valid since ultrasound examination makes it possible to detect not only chromosomal but also structural abnormalities.

  4. In the case of sonographic detection of a fetal abnormality, direct diagnosis via invasive testing without NIPT should be performed.

  5. In Germany, both NIPT and first-trimester screening are subject to the Genetic Diagnosis Act, i. e., patients must be counseled prior to examination as well as once results are available.

  6. A normal ultrasound examination in the first trimester does not necessarily rule out fetal anomalies. Therefore, organ screening between gestational weeks 18 + 0 and 21 + 6 continues to be a standard part of prenatal testing.