By: Dr. Haywood Brown 

As providers who specialize in the care of pregnant patients, our goals are to help foster patient understanding of maternal and fetal health risks. We partner with our patients to identify the best course of care to reduce maternal, fetal, and infant health risks.  At nearly every prenatal care appointment, our patients express concern about the health of their babies.  “Is my baby going to be healthy?” is a common refrain.  Although we can never answer that question with 100% certainty, we as care providers aspire to be as complete as possible in our risk assessments and discussions about risk-reducing interventions. Carrier screening for recessive and X-linked conditions is a key component of our risk assessments and discussions with our patients.

Last July, the American College of Medical Genetics and Genomics (ACMG) issued a new carrier screening practice resource¹, which recommends genetic screening for more than 100 conditions, for all patients who are pregnant or planning to become pregnant, regardless of race or ethnicity. This replaced previous recommendations by medical societies that endorsed more limited screening based primarily on each patient’s reported ethnicity. In addition, ACMG indicated that this routine screening for a larger panel of conditions commonly referred to as “expanded carrier screening” be referred to as simply “carrier screening.”  This is good news for providers and patients alike because the limitations of ethnicity-based screening are well known. For instance, 40% of U.S. adults do not know the ethnicity of their four grandparents², which may have impacted what screening was ordered in the past, potentially missing the identification of couples at risk for pregnancies impacted by severe or profound genetic conditions. Further, we know from the data set collected by Haque et al³, which included more than 15 ethnicities, that at-risk couple detection increases for everyone when larger panels are used routinely for all patients, compared to the ethnicity-based approach.

For our pregnant patients, the identification of heritable conditions via carrier screening is also important because recessive and x-linked conditions impact medical management of the pregnancy and empower patients with valuable knowledge to make informed decisions. We know from clinical utility studies^4,5 that when couples learn that an ongoing pregnancy is at risk for a recessive or X-linked condition identified on carrier screening, 37% pursue prenatal diagnosis.

Further, for couples who are identified as at-risk for an affected child prior to establishing a pregnancy, 77% elect to pursue actions to avert or reduce the risk of an affected pregnancy, including pursuing IVF with pre-implantation genetic testing, pursuing prenatal diagnosis once a pregnancy is established, electing to use a donor egg or sperm, adopt, or avoid pregnancy. Even for couples who decline invasive diagnostic testing, advanced knowledge of risk status can help them to inform and customize medical management plans to optimize outcomes for their newborn.^4,6

Significant and appropriate evidence-based information suggests that providers should counsel couples with regard to genetic risk during the course of a pregnancy. Sometimes patients arrive to their appointments with assumptions about genetics that we should explore further. Many couples have the tendency to overestimate the efficacy of family history in determining individual risk for being a carrier of a heritable genetic condition. It is important to counsel couples on the limitations of family history in assessing risk, the role of diagnostic testing for pregnancies identified at risk, and how genetic risk assessment informs medical care plans. In addition, we can and should collaborate with geneticists and genetic counselors to build referral networks and awareness with patients about the additional services available from these specialists.

Technology and medicine work together over time to continually improve care. As our knowledge about various heritable conditions increases, seeds of innovation emerge that fuel new and increasingly effective treatments. Armed with current knowledge that risk for serious and potentially treatable, heritable disorders can be more appropriately identified with carrier screening both early in pregnancy and prior to conception, it is important that providers and patients adopt advances beyond current screening guidelines and protocol options. The age of precision medicine is on the horizon, but in order to bring it to reality, the first critical step is changing our routine risk assessments. Pan-ethnic carrier screening, with panels like ACMG has recommended, has the immediate impact of helping close the gaps in risk assessments for all populations regardless of their ethnicities, empowering patients with vital information, while planting the seeds for increasingly better outcomes for affected individuals.

Dr. Haywood Brown is the Executive Medical Director of the Access to Expanded Carrier Screening (AECS) Coalition. Dr. Brown is a professor of Obstetrics and Gynecology and Maternal Fetal Medicine and serves as the senior vice president for Academic Affairs, USF Health, and vice dean, Faculty Affairs, at the Morsani College of Medicine.

1. Gregg AR, Aarabi M, Klugman S, Leach NT, Bashford MT, Goldwaser T, Chen E, Sparks TN, Reddi HV, Rajkovic A, Dungan JS; ACMG Professional Practice and Guidelines Committee. Correction to: Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021 Oct;23(10):2015. doi: 10.1038/s41436-021-01300-z. Erratum for: Genet Med. 2021 Oct;23(10):1793-1806. PMID: 34453133; PMCID: PMC8776567.
2. Wapner, R.  A Case for Improved Carrier Screening.  Contemporary OB/GYN Journal, Vol 65 No 09, Volume Vol 65, Issue No 09
3. Haque IS, Lazarin GA, Kang HP, Evans EA, Goldberg JD, Wapner RJ. Modeled fetal risk of genetic diseases identified by expanded carrier screening. JAMA. 2016;316(7):734-42. 
4. Johansen Taber KA, Beauchamp KA, Lazarin GA, Muzzey D, Arjunan A, Goldberg JD. Clinical utility of expanded carrier screening: results‐guided actionability and outcomes. Genet Med. 2019;21(5):1041-1048.
5. Ghiossi, C. E., Goldberg, J. D., Haque, I. S., Lazarin, G. A., & Wong, K. K. (2018). Clinical Utility of Expanded Carrier Screening: Reproductive Behaviors of At-Risk Couples. J Genet Couns. 2018;27(3):616-625.
6. Lazarin GA, Haque IS, Nazareth S, Iori K, Patterson AS, Jacobson JL, Marshall JR, Seltzer WK, Patrizio P, Evans EA, Srinivasan BS. An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. Genet Med. 2013;15(3):178-86.