(145) Carrier Screening as a Pathway to In-Utero Therapy

Prenatal interventions for genetic conditions are rapidly expanding (such as in-utero transfusions for anemias or in-utero enzyme replacement therapy for lysosomal storage disorders). This study aims to evaluate how reproductive carrier screening can identify pregnancies at risk for genetic conditions in which in-utero (IU) therapy may be an option.

Study Design:
We conducted a retrospective study of carrier screening results from women aged 18–55 years at a US-based commercial lab (Jan 2021-Aug 2024). Thirteen genes were selected based on their association with conditions for which IU therapies are in clinical use or actively enrolling trials (n=10), or those described in published case reports or investigational therapies (n=3). We calculated screening rates and carrier frequencies for women tested for all 13 conditions of interest. Frequencies were also stratified by self-reported race and ethnicity.

Results:
Of the screened population (N = 1,077,487), 97% were screened for at least one gene of interest, most frequently SMN1, CFTR, and HBA1/2. Among those tested for all 13 conditions (N = 117,870, 10.9% of screened population), the aggregate carrier frequency for conditions with established IU therapy or trials was 1 in 24 (4.3%); for investigational therapies, 1 in 16 (6.5%). While individual gene frequencies vary by race, the aggregate probability of carrying any of the conditions with the potential for IU therapy is consistently high across racial and ethnic groups.

Conclusion:
Carrier screening can identify pregnancies at risk for conditions with available or emerging IU therapies. Many of the conditions are rare individually but relatively common in aggregate. Incorporating clinical actionability into screening frameworks, beyond population prevalence alone, may expand equitable access to IU therapy and optimize fetal outcomes. Patient education regarding options for IU therapy may also be valuable in decision-making to pursue carrier screening.