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ORIGINAL RESEARCH |
From the Department of Obstetrics and Gynecology, Prenatal and Preimplantation Genetic Diagnosis, Fetal Therapy, Ospedale Microcitemico, Cagliari, Italy.
Address reprint requests to: Giovanni Monni, MD Ospedale Microcitemico Department of Obstetrics and Gynecology Prenatal and Preimplantation Genetic Diagnosis Fetal Therapy via Jenner 09121 Cagliari Italy E-mail: prenatalmonni{at}tiscalinet.it
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Abstract |
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Methods: Two groups of women, referred to our center for prenatal karyotype diagnosis because of maternal age, were compared: one in 1995 and the other in 1999 after the introduction of nuchal translucency measurement. Each woman received nondirective genetic counseling, and for the 1999 group, nuchal translucency results were also discussed. Risks of transabdominal chorionic villi sampling (CVS) and amniocentesis, laboratory techniques, genetic results, and local experiences were discussed. Patient’s decision to undergo prenatal diagnosis, acceptance of the nuchal translucency test (in the 1999 group), and the rate of chromosomal abnormalities diagnosed by transabdominal CVS and amniocentesis, were considered.
Results: Two hundred twenty-one of 982 (22%) women in the 1995 group and 421 of 1386 (30%) in the 1999 group, after nondirective genetic counseling declined invasive diagnosis (P < .05). In the 1999 cohort, 1088 of 1089 (99.9%) women of appropriate gestational age had nuchal translucency measurement. Among women seen in 1995, 214 opted for transabdominal CVS (31%) and 476 (69%) for amniocentesis. Nineteen abnormal karyotypes were detected, six by transabdominal CVS and 13 (68.5%) by amniocentesis. In 1999, 266 women (29%) opted for transabdominal CVS and 650 (71%) for amniocentesis. Twenty abnormal karyotypes were detected, 13 (65%) by transabdominal CVS and seven (35%) by amniocentesis (P < .05).
Conclusion: Knowledge of nuchal translucency could lead to a decrease in the demand for invasive diagnosis and to a more frequent diagnosis by first-trimester transabdominal CVS.
In most nations, the standard care in prenatal diagnosis is to offer invasive genetic diagnosis to determine fetal karyotype in pregnant women 35 years and older, whereas resources for noninvasive screening tests (such as ultrasound or maternal serum biochemistry) are usually used in younger women.1,2 The procedures commonly offered to pregnant women in early pregnancy to obtain fetal karyotype are chorionic villi sampling (CVS) and amniocentesis.3 Apart from transvaginal or transcervical CVS and first-trimester amniocentesis, whose use is rarer,4,5 first-trimester transabdominal CVS and second-trimester amniocentesis are the most used.3 Various and comparable are the advantages presented by these techniques (at parity of procedure-related fetal losses). Transabdominal CVS could be performed from 10 weeks, allowing for an earlier reassurance on the healthy state of the fetus, or earlier termination in those affected; on the other hand, amniocentesis is performed at 15 weeks and after, carries a lower number of mosaicism, and is easier to learn by operators.3,6,7 Therefore, the choice to undergo prenatal diagnosis or not, and if so, which of these two procedures to choose, is up to the woman herself, who realizes this right with responsibility after the informative nondirective genetic counseling.
Enlarged fetal nuchal translucency thickness has been proposed as an ultrasound marker to identify fetuses at high risk of chromosomal abnormalities in first trimester, and its efficacy has been confirmed by different groups using the same standard techniques.8–12 Pregnant women could find nuchal translucency test acceptable at all ages, and therefore those already at high risk for chromosomal abnormalities because of age might choose the nuchal translucency test before prenatal diagnosis.13 Whether the benefit of such a policy outweighs the costs and disadvantages is questionable.14 It may be expected that a more accurate knowledge of a woman’s individual risk for aneuploidies, as obtained by nuchal translucency screening, could have some effects on the process of the nondirective genetic counseling and on the woman’s decision about prenatal diagnosis.15,16 In this study, we investigated the effect of nuchal translucency screening on prenatal diagnosis for chromosomal abnormalities in women aged 35 years and older.
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Patients and Methods |
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Both groups underwent nondirective genetic counseling with the same team of genetists, and for the 1999 cohort, when available, the nuchal translucency results were taken into consideration. The following issues were discussed, using figures as quoted by the literature currently available: maternal and fetal risks for invasive diagnostic procedures (first-trimester transabdominal CVS since 10 weeks, and second-trimester amniocentesis since 15 weeks),7,18–20 laboratory techniques and genetic results,7 and local experiences and resources.21,22 The timetable of procedures was arranged on a weekly basis according to patient choice and availability of resources at the two local genetic laboratories, one performing both transabdominal CVS and amniocentesis analysis and the other only amniocentesis analysis. These laboratories were normally able to fulfill the needs of the local district (Cagliari and surroundings, which has about 15,000 births per year, 12% of these being to women of 35 years or older). They provide prenatal invasive diagnosis in cases who fall within those categories eligible under the Italian Ministry of Health’s decrees (maternal age 35 and over; one parent a carrier of chromosomal abnormalities and fetal risks evidentiated by ultrasound or biochemical screening during the pregnancy). Each woman was given a form to fill in and return about the outcome of the pregnancy.
Acceptance of the nuchal translucency test (for the1999 group), maternal choice of invasive prenatal diagnosis, chromosomal abnormalities and rate of diagnosis by transabdominal CVS, and amniocentesis among the two groups were compared. 
2 was used for comparison. P < .05 was considered statistically significant.
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Results |
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). Nineteen chromosomal abnormalities were diagnosed by prenatal diagnosis, six (31.5%) by transabdominal CVS and 13 (68.5%) by amniocentesis (Table 2). Of 221 cases who refused prenatal diagnosis, 15 cases were lost at follow-up (6.7%) and 206 women who returned the form, had no obvious signs of chromosomal abnormalities.
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), in 1089 cases the gestational age was appropriate to nuchal translucency measurement (range 10.3–13.6 weeks), and in 1088 nuchal translucency measurement was carried out and obtained. One patient refused nuchal translucency measurement. In 297 of 1386 cases, gestational age was over 13.6 weeks, thus nuchal translucency was not measured. Nuchal translucency was above the 95th centile for gestational age19 in 39 of 1088 cases (3.5%). After nondirective genetic counseling, 421 (30%) patients decided against invasive prenatal diagnosis; among these patients, 352 had nuchal translucency measurement with a result below the 95th centile, one case was that where the nuchal translucency measurement had been refused, and 68 were among the 297 cases where nuchal translucency measurement was not taken because gestational age was over 13.6 weeks. Forty-seven women had spontaneous miscarriages (one of them had an enlarged nuchal translucency), and two had voluntary abortions for socioeconomic reasons. Karyotype analysis was not performed on these fetuses. Nine hundred sixteen patients (median 37 years, range 35–48) underwent an invasive prenatal diagnosis, 266 (29%) by transabdominal CVS and 650 (71%) by amniocentesis. Of 421 cases that refused prenatal diagnosis, although 25 cases were lost at follow-up (6%), 396 women returned the form, and no obvious signs of chromosomal abnormalities were referred. Twenty chromosomal abnormalities were diagnosed by invasive prenatal diagnosis, 13 (65%) by transabdominal CVS and seven (35%) by amniocentesis (Table 3). Twelve of 13 chromosomal abnormalities diagnosed by transabdominal CVS presented a nuchal translucency above the 95th centile; three of seven fetuses with chromosomal abnormalities diagnosed by amniocentesis had a nuchal translucency above the 95th centile for gestational age, whereas in three cases the nuchal translucency was not measured. The 39 cases with enlarged fetal nuchal translucency opted for invasive prenatal diagnosis, amniocentesis in four cases, transabdominal CVS in 35. One spontaneous miscarriage after transabdominal CVS procedure, one intrauterine death at 38 weeks without apparent malformations (after transabdominal CVS), and one encephalocele in three normal karyotype fetuses occurred.
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), and significantly higher rate of chromosomal abnormalities diagnosed by means of transabdominal CVS was also evident in 1999 (six, 31.5%, in 1995 compared with 13, 65%, in 1999, P < .05) (Table 1). |
Discussion |
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Our study confirms that nuchal translucency testing is well accepted and requested by pregnant women whose age makes them at high risk for chromosomal abnormalities (in the 1999 group, 1088 of 1089 women requested a nuchal translucency test). We observed a significant reduction in demand for prenatal invasive diagnosis with nuchal translucency screening (30% of patients declined invasive prenatal diagnosis in 1999, whereas 22% declined in 1995). The policy to offer a screening test (by ultrasound or biochemistry) for chromosomopathies to all pregnant women could be able to save money for the health system, and to spare a lot of fetal lives, if invasive prenatal diagnosis were reserved only for test-positive patients, whether younger or older than 35 years.24,25
Another evident finding is that in the 1999 group, the proportion of chromosomal abnormalities diagnosed by transabdominal CVS was significantly greater than in 1995 (65% compared with 31.5%). We could not prove if the wide experience of our center in transabdominal CVS (over 4500 cases due to our work diagnosing beta-halassemia and other mendelian disorders)26 could create a sort of bias in this study in one direction or if, because amniocentesis analysis was available in both laboratories, whereas transabdominal CVS analysis was available only in one, it could affect the results in the opposite direction, making it difficult to reproduce the same results in other places. Nevertheless, we do not think that these things should invalidate the finding that in the 1999 group, despite the rate of transabdominal CVS performed not being increased (29% and 31% of procedures) from the 1995 group, the diagnosis of most of the chromosomal abnormalities, which resulted positive to nuchal translucency test, was performed by transabdominal CVS. This means that, in our experience, after genetic counseling, with a more accurate knowledge of the individual maternal risk of chromosomal abnormalities adjusted by nuchal translucency, in cases most at risk, the choice might be frequently for a first-trimester prenatal diagnosis by transabdominal CVS, and in cases at lower risk, for a later amniocentesis. In prenatal care, for serious fetal abnormalities, such as chromosomal abnormalities or single-gene defects, an early diagnosis is desirable.27,28 In the evaluation of first-trimester screening tests, there is still a major debate over the concern about a possible bias towards detection of cases that are destined to miscarry.29,30 Nonetheless, an early knowledge of fetal disease has been proved to be better for the preparation of parents, and an early gestational age reduces the physical and psychological trauma in cases of termination of pregnancy.31–33
We conclude that if nuchal translucency screening is performed in women 35 years or older, it could have some influence on the decision about invasive prenatal diagnosis, leading to a reduction of demand for invasive procedures and to an anticipation of diagnosis of most chromosomal abnormalities by CVS, which could represent in certain circumstances a real and quantifiable benefit.
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Footnotes |
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Received November 6, 2000. Received in revised form February 22, 2001. Accepted March 1, 2001.
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