Prenatal Genetic Testing Guidelines

Indications for Prenatal Genetic Testing

Advanced maternal age (≥35 years at delivery for singleton pregnancies and ≥33 years for twin pregnancies) is an indication for prenatal genetic testing, as it increases the risk of chromosomal abnormalities, spontaneous miscarriage, preterm labor, gestational diabetes mellitus, pre-eclampsia, stillbirth, and cesarean delivery 1
Consanguinity, abnormal screening tests, teratogen exposure, fetal anomalies, positive carrier screening, and adverse pregnancy history are indications for prenatal genetic testing 1
Known genetic disorders in family members with identified mutations, cancer predisposition, and ethnic background (e.g., Ashkenazi Jewish ancestry) are indications for prenatal genetic testing 2, 3

Pre-test counseling should include collection of personal and family medical history, education about the disorder, exploration of psychosocial dimensions, informed consent, and disclosure of test results and follow-up planning 2
Pre-test evaluation should include constructing a pedigree tree, analyzing disease severity and genotype-phenotype correlation, assessing reproductive goals and options, evaluating medical history, and reviewing medication use for potential teratogens 4, 5

Universal screening is recommended for conditions like cystic fibrosis, while ethnic-based screening is recommended for Ashkenazi Jewish population (e.g., Tay-Sachs, Gaucher disease) 3
Family history-based screening is recommended when specific mutations are known in the family 3

Prenatal genetic testing is indicated when both parents have identifiable mutations for the same disorder, and DNA samples should be obtained from both parents as controls 3
Preimplantation genetic testing (PGT) is appropriate for couples with high risk of gene transmission and requires a multidisciplinary approach with genetic counseling experts 4
PGT involves IVF/ICSI technology, embryo biopsy, and genetic analysis 4

Positive results should be promptly communicated, and negative results should include clear interpretation and explanation of limitations and residual risk 6
Bayesian calculations should determine remaining carrier risk, and genetic counseling, targeted ultrasound, and amniocentesis are recommended for positive results 6
For uncertain results, additional testing options should be discussed 4

Preconceptional supplementation with folic acid reduces the incidence of neural tube defects (NTDs) by up to 80%, and most North American locations can expect a 20-30% reduction from fortification 6
When a child has a de novo pathogenic variant, consider PGT-M or prenatal diagnosis due to possible gonadal mosaicism, and PGT is appropriate if two or more instances of adverse gene variants exist in pregnancy history 4

Inadequate pretest information, misinterpretation of results, and insufficient counseling can lead to inaccurate results and inadequate patient support 2, 3
Patients should be referred to Maternal-Fetal Medicine (MFM) specialists at age 35 years or older at the time of delivery for singleton pregnancies, and at age 33 years or older for twin pregnancies, as recommended by the American College of Medical Genetics and Genomics and the American College of Obstetricians and Gynecologists 1, 7
Delayed referral to MFM can miss opportunities for early intervention and planning, highlighting the importance of timely referral for advanced maternal age patients 1