Indications of invasive genetic study in a selected population: August 2005 to December 2007

Indicaciones de estudio genético invasivo en una población seleccionada: Agosto de 2005 a diciembre de 2007

Background: the greater use of prenatal ultrasound and invasive diagnostic procedures has made it possible to improve the identification of fetal malformations at birth. The dilemma involves a risk related to the procedure, so physicians continue to grapple with how to identify high-risk patients so as not to subject those at low risk to unnecessary diagnostic procedures. In the present study we have set out to describe the different indications for the invasive genetic diagnosis of chromosomal alterations in a selected population of Bogotá D.C. PATIENTS AND METHODS: A cross-sectional descriptive study was conducted between August 1, 2005 and December 31, 2007. The medical records of pregnant women referred with an indication of invasive genetic study due to chromosomal abnormalities were reviewed. Results: 374 pregnancies were analyzed, of which 98.9% (n = 370) were simple and 1.1% (n = 4) corresponded to twins, for a total of 378 analyzes of the fetal karyotype. The average maternal age was 35 years and the average gestational age was 17.4 weeks. 366 amniocentesis (96.8%) and 12 chorionic villus biopsies (3.2%) were performed. The most requested cytogenetic study was the 64.8% karyotype (n = 245) and 33.6% (n = 127) of the cases were analyzed by FISH and karyotype. Among the indications for requesting an invasive genetic study, maternal age stands out with 35.7% (n = 135), followed by minor sonographic malformations 14.8% (n = 56), second trimester screening 9.3% (n = 35). ), increased nuchal sonography 6.9% (n = 26) and major sonographic malformations 6.3% (n = 24). 54 altered cytogenetic studies (14.3%) were reported; Of these, 36 corresponded to aneuploidies (66.67%) and eighteen to structural variations (33.33%). When maternal age was the only indication of an invasive procedure, only 6.66% of altered karyotypes were detected, while in the group where the indication was due to minor malformations, major malformations and nuchal sonolysis, the diagnosis of aneuploidy was made in 25%, 29% and 26% respectively. Conclusions: the decision to offer invasive tests should not be based only on maternal age. The differences between screening and diagnostic tests should be discussed with all patients. Thus, the maternal age of 35 years should no longer be considered as an independent cut-off point to determine who is offered screening or invasive tests. Although precise non-invasive prenatal diagnosis has not been achieved, technological advances continue to focus on improving individual risk assessment, so that the number of invasive diagnostic procedures and gestational losses associated with the procedure can be minimized. Abbreviations: ECO, ultrasound, ultrasound; RN, newborn (s).

1. Alfirevic Z, Sundberg K, Brigham S. Amniocentesis and chorionic villus sampling for prenatal diagnosis. Cochrane Database Syst Rev. 2003; (3):CD003252.

2. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 88. Invasive Prenatal testing for aneuploidy. Obstet Gynecol. 2007; 110 (6): 1459-67. 3. Cuckle HS, Wald NJ. Principles of screening. In: Wald NJ, editor. Antenatal and neonatal screening. Oxford: Oxford University Press; 2008. p 1–22.

4. Gardner RJ, Sutherland GR. Chromosome abnormalities and genetic counseling. 3rd ed. New York : Oxford University Press; 2004.

5. Milunsky A, Milunsky JM. Genetic counseling: preconception, prenatal, and perinatal. In: Milunsky A, editor. Genetic disorders and the fetus: diagnosis, prevention, and treatment. 5th ed. Baltimore (MD): Johns Hopkins University Press; 2004. p. 1–65.

6. Reddy UM, Wapner RJ. Comparison of first and second trimester aneuploidy risk assessment. Clin Obstet Gynecol. 2007; 50(2): 442-53.

7. Egan JF, Benn PA, Zelop CM, et al. Down syndrome births in the United States from 1989 to 2001. Am J Obstet Gynecol. 2004; 191 (3):1044–48.

8. Nicolaides KH. Screening for chromosomal defects. Ultrasound Obstet Gynecol. 2003; 21 (4): 313-21.

9. Verdin SM, Whitlow BJ, Lazanakis M, Kadir RA, Chatzipapas I, Economides DL. Ultrasonographic markers for chromosomal abnormalities in women with negative nuchal translucency and second trimester maternal serum biochemistry. Ultrasound Obstet Gynecol. 2000; 16 (5): 402-6.

10. Shipp TD, Benacerraf BR. Second trimester ultrasound screening for chromosomal abnormalities. Prenat Diagn. 2002; 22 (4): 296–307.

11. Simpson JL. Prenatal cytogenetic screening. Ultrasound Obstet Gynecol. 1995; 5 (1): 3-5

12. Saller DN, Canick JA. Current methods of prenatal screening for Down syndrome and other fetal abnormalities. Clin Obstet Gynecol. 2008; 51(1): 24-36

13. Resta RG. Changing demographics of advanced maternal age (AMA) and the impact on the predicted incidence of Down syndrome in the United States: implications for prenatal screening and genetic counseling. Am J Med Genet. 2005; 133A (1):31-6.

14. Chorionic villus sampling and amniocentesis: recommendations for prenatal counseling. Centers for Disease Control and Prevention. MMWR Recomm Rep. 1995; 44 (RR-9):1–12.

15. Seeds W. Diagnostic mid trimester amniocentesis: how safe?. Am J Obstet Gynecol. 2004; 191(2): 607–15.

16. Caughey AB, Hopkins LM, Norton ME. Chorionic villus sampling compared with amniocentesis and the difference in the rate of pregnancy loss. Obstet Gynecol. 2006; 108 (3 pt 1):612–16.

17. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 77. Screening for fetal chromosomal abnormalities. Obstet Gynecol. 2007; 109 (1): 217–28.

18. Nicolaides KH, Spencer K, Avgidou K, Faiola S, Falcon O. Multicenter study of first-trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk-orientated twostage first-trimester screening. Ultrasound Obstet Gynecol. 2005; 25 (3): 221–26.

19. Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM. First and second trimester antenatal screening for Down’s syndrome: the results of the serum, urine and ultrasound screening study (SURUSS). Health Technol Assess. 2003; 7 (11): 1-77.

20. Borgida AF, Mills AA, Feldman DM, Rodis JF, Egan JF. Outcome of pregnancies complicated by ruptured membranes after genetic amniocentesis. Am J Obstet Gynecol. 2000; 183(4): 937–9.

21. Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides KH. Absence of nasal bone in fetuseswith trisomy 21 at 11–14 weeks of gestation: an observational study. Lancet. 2001; 358 (9294):1665–67.

22. Matias A, Gomes C, Flack N, Montenegro N, Nicolaides KH. Screening for chromosomal abnormalities at 11–14 weeks: the role of ductus venosus blood flow. Ultrasound Obstet Gynecol.1998; 12 (6): 380–84.

23. Huggon IC, DeFigueiredo DB, Allan LD. Tricuspid regurgitation in the diagnosis of chromosomal anomalies in the fetus at 11–14 weeks of gestation. Heart. 2003; 89 (9): 1071–73.

24. Tabor A, Philip J, Madsen M, et al. Randomised controlled trial of genetic amniocentesis in 4606 lowrisk women. Lancet. 1986; 1 (8493):1287–93.

25. Ralston SJ, Craigo SD. Ultrasound-guided procedures for prenatal diagnosis and therapy. Obstet Gynecol Clin N Am. 2004; 31 (1) 101–23.