Guideline sources The following summarized guidelines for the evaluation and management of prenatal screening for chromosomal abnormalities are prepared by our editorial team based on guidelines from the American College of Medical Genetics (ACMG 2022), the American College of Obstetricians and Gynecologists (ACOG/SMFM 2020), the Society of Obstetricians and Gynaecologists of Canada (SOGC 2020; 2017), and the National Society of Genetic Counselors (NSGC 2013). 1 2 3 4 6 Guidelines 1. Screening and diagnosis Indications for screening, general principles: As per SMFM/ACOG 2020 guidelines, discuss and offer prenatal genetic screening (serum screening with or without nuchal translucency ultrasound or cell-free deoxyRNA screening) and diagnostic testing (chorionic villus sampling or amniocentesis) in all pregnant individuals regardless of maternal age or risk of chromosomal abnormality. Allow patients to pursue or decline prenatal genetic screening and diagnostic testing after review and discussion. A As per NSGC 2013 guidelines, consider offering noninvasive prenatal testing to patients desiring screening information due to the high detection rates and low false positive rates. Offer noninvasive prenatal testing only in the context of informed consent, education, and counseling by a qualified provider, such as a genetic counselor. Obtain standard confirmatory diagnostic testing as a follow-up to positive noninvasive prenatal testing results. Inform of alternate screening options as appropriate based on gestational age and screening https://web.pathway.md/diseases/recegSiinBdaNyiEA 1/4 6/29/23, 11:26 PM Prenatal screening for chromosomal abnormalities Pathway availability in high-risk patients declining noninvasive prenatal testing but remaining interested in screening. Indications for screening (trisomies): Obtain noninvasive prenatal screening for fetal trisomies 21, 18, and 13 in all pregnant individuals with a singleton gestation. A Insufficient evidence to recommend for or against noninvasive prenatal screening for the identification of rare autosomal trisomies. I Indications for screening (deletions): Consider obtaining noninvasive prenatal screening for 22q11.2 deletion syndrome in all pregnant individuals. C Insufficient evidence to recommend routine screening for copy number variations other than 22q11.2 deletions. I Indications for screening (sex chromosome aneuploidies): obtain noninvasive prenatal screening for fetal sex chromosome aneuploidies in pregnant individuals with a singleton gestation. A Choice of screening test (general principles): Obtain one prenatal screening approach rather than multiple screening tests simultaneously for screening. A Do not obtain multiple serum screening approaches independently (for example, a first- trimester screening test followed by a quad screen as an unlinked test) because it will result in an unacceptably high positive screening rate and could deliver contradictory risk estimates. D Choice of screening test, ultrasound: As per SMFM/ACOG 2020 guidelines, obtain a second-trimester ultrasound (with or without second-trimester maternal serum AFP), ideally at 18-22 weeks of gestation, for fetal structural defects in all pregnant individuals. A As per NSGC 2013 guidelines, consider obtaining an ultrasound to assess the fetal anatomy at approximately 18-20 weeks of gestation in all pregnant individuals regardless of whether or not they choose to have screening or diagnostic testing. E Choice of screening test (maternal serum screening): Offer maternal serum screening and diagnostic testing for chromosome aneuploidy in all pregnant individuals. E Do not obtain a separate second-trimester maternal serum screening for chromosome aneuploidy if a patient completes combined first-trimester screening. Obtain screening for chromosome aneuploidy in the second trimester in patients presenting before 14 weeks only as a part of integrated, serum-integrated, stepwise-sequential, or contingency screening. Recognize that independent screening in the first and second trimesters increases the false positive rate of screening. D Choice of screening test (cell-free DNA): recognize that cell-free deoxyRNA is the most sensitive and specific screening test for common fetal aneuploidies, however, it has the potential for false-positive and false-negative results and is not equivalent to diagnostic testing. A https://web.pathway.md/diseases/recegSiinBdaNyiEA 2/4 6/29/23, 11:26 PM Prenatal screening for chromosomal abnormalities Pathway Choice of screening test (amniocentesis, general population): Obtain stepwise sequential screening or combined first-trimester screening in patients opting for chorionic villus sampling or amniocentesis because: both are tailored to fit the needs of patients desiring early detection of chromosome aneuploidy but wishing to employ a screening method before making a decision about diagnostic testing both allow for the option of chorionic villus sampling in higher-risk pregnancies while deferring testing of lower-risk pregnancies to the second trimester without causing increased anxiety of the screening options providing risk information in the first trimester, stepwise sequential screening has the highest detection rates for Down syndrome and trisomy 18. E Show 5 more Choice of screening test (amniocentesis, at-risk population): Offer chorionic villus sampling and amniocentesis as diagnostic testing options in patients at increased risk for chromosome aneuploidy when presenting before 14 weeks of gestation. E Offer amniocentesis as the diagnostic testing option in patients at increased risk for chromosome aneuploidy when presenting after 14 weeks of gestation. E 2. Diagnostic investigations Further evaluation: provide genetic counseling and obtain a comprehensive ultrasound evaluation with an opportunity for diagnostic testing to confirm results in patients with a positive screening test result for fetal aneuploidy. A Show 6 more 3. Specific circumstances Patients undergoing assisted reproductive technologies: As per ACOG 2020 guidelines, offer prenatal screening and prenatal diagnosis in all patients undergoing assisted reproductive technologies regardless of previous preimplantation genetic testing because preimplantation genetic testing is not uniformly accurate. B As per SOGC 2020 guidelines, do not use traditional prenatal genetic screening algorithms for trisomies 21 and 18 for pregnancies conceived after preimplantation genetic testing for aneuploidy and euploid embryo transfer. D Show 11 more Patients with twin pregnancies: as per ACOG 2020 guidelines, recognize that no method of aneuploidy screening including a serum sample is as accurate in twin gestations as it is in singleton pregnancies. Incorporate this information into pretest counseling of patients with multiple gestations. B Show 2 more Patients with multifetal gestation: https://web.pathway.md/diseases/recegSiinBdaNyiEA 3/4 6/29/23, 11:26 PM Prenatal screening for chromosomal abnormalities Pathway As per ACMG 2022 guidelines, obtain noninvasive prenatal screening for fetal trisomies 21, 18, and 13 in twin pregnancies. A As per CTFPHC 2017 guidelines, obtain fetal nuchal translucency combined with maternal age as first-trimester screening for aneuploidies in twin pregnancies. B Consider obtaining first-trimester serum screening combined with nuchal translucency, B or integrated screening with nuchal translucency and first- and second-trimester serum screening as another options in twin pregnancies. B Show 8 more References 1. American College of Obstetricians and Gynecologists Committee on Practice Bulletins Obstetrics, Committee on Genetics, Society for Maternal-Fetal Medicine. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol. 2020 Oct;136 4):e48-e69. Open 2. Wilson KL, Czerwinski JL, Hoskovec JM et al. NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy. J Genet Couns. 2013 Feb;22 1 4 15. Open 3. Jeffrey S Dungan, Susan Klugman, Sandra Darilek et al. Noninvasive prenatal screening NIPS for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics ACMG . Genet Med. 2022 Dec 13;S1098 3600 22 01004 8. Open 4. Rhonda Zwingerman, Sylvie Langlois. Committee Opinion No. 406 Prenatal Testing After IVF With Preimplantation Genetic Testing for Aneuploidy. J Obstet Gynaecol Can. 2020 Nov;42 11 1437 1443.e1. Open 5. ACOG Practice Bulletin, Number. Multifetal Gestations: Twin, Triplet, and Higher-Order Multifetal Pregnancies. ACOG. 2021 Jun;. Open 6. Fran ois Audibert, Alain Gagnon. No. 262 Prenatal Screening for and Diagnosis of Aneuploidy in Twin Pregnancies. J Obstet Gynaecol Can. 2017 Sep;39 9):e347-e361. Open https://web.pathway.md/diseases/recegSiinBdaNyiEA 4/4