Reproductive Carrier Screening Results With Maternal Health Implications During Pregnancy

Abstract

OBJECTIVE: To identify conditions on a reproductive carrier screening panel with the potential for carrier manifestations during pregnancy and review the implications for obstetric care. METHODS: This was a retrospective cross-sectional study of consecutive samples from female patients aged 18–55 years submitted to a commercial laboratory for a 274-gene carrier screening panel (January 2020 to September 2022). A literature review was performed to identify genes on the panel with potential for pregnancy complications in carriers. Carrier expression and published recommendations for clinical management were reviewed. RESULTS: We identified 12 genes with potential for carrier manifestations during pregnancy based on reports in the literature: nine with manifestations irrespective of the fetal genetic status (ABCB11, COL4A3, COL4A4, COL4A5, DMD, F9, F11, GLA, and OTC) and three (CPT1A, CYP19A1, and HADHA) with manifestations only if the fetus is affected by the condition. Manifestations included cardiomyopathy, hemorrhage, gestational hypertensive disorders, cholestasis of pregnancy, acute fatty liver, hyperammonemic crisis, and maternal virilization. Published recommendations for carrier management were identified for 11 of the 12 genes. Of 91,637 tests performed during the study period, a pathogenic or likely pathogenic variant was identified in 2,139 (2.3%), giving a carrier frequency for any of the 12 genes of 1 in 43 (95% CI 1/41–45) 1,826 (2.0%) of the study population were identified as carriers for one of the nine genes with the potential for carrier manifestations irrespective of an affected or unaffected fetus. CONCLUSION: Approximately 1 in 40 female patients were identified as carriers for a condition with potential for maternal manifestations in pregnancy, including some serious or even life-threatening complications. Obstetric care professionals should be aware of the possibility of pregnancy complications among carriers and the available recommendations for management. FUNDING SOURCE: This study was funded by Natera, Inc.

Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States

“… 32 We have previously advocated greater use of early, preconception carrier screening with testing of both reproductive partners. 33 , 34 Identification of FH in women who are pregnant or considering pregnancy would allow early treatment for their FH (after discontinuation of breastfeeding), and assessment of the risk for HoFH in the fetus by testing of her reproductive partner. Given the higher incidence and earlier onset of cardiovascular disease in men, the provision of early genetic-based screening for males can be expected to be useful in assessing their personal predisposition to cardiovascular disease as well as assessing risk for their children.…”