Reproductive genetic carrier screening: A tool for reproductive decision-making

Reproductive genetic carrier screening: A tool for reproductive decision-making | Image Credit: © Chinnapong - © Chinnapong - stock.adobe.com.

Couple-based reproductive genetic carrier screening is an accessible and effective method of reproductive decision making, according to a recent study published in the New England Journal of Medicine.¹

Childhood-onset autosomal recessive and X-linked conditions have been linked to over 2500 genes, with most parents carrying these genes only learning about their carrier status after childbirth. Reproductive decision making may be improved through the use of reproductive genetic carrier screening.

The availability of reproductive genetic carrier screening has been improved by commercial providers, but health care professionals must remain aware about how to best offer screening and how their patients may view this option.

This critical information has been detailed by the Australian Reproductive Genetic Carrier Screening Project.² The project included over 10,000 reproductive couples and provided reproductive genetic carrier screening for at least 1281 genes.

Investigators conducted a study to evaluate screening uptake, the rate of couples with an increased risk of having an affected child, reproductive decisions, psychosocial outcomes, and screening acceptability.¹ Participating health care centers offered free reproductive genetic carrier screening to their patients.

Reproductive couple included 2 individuals of the opposite sex who were the genetic parents in pregnancy. Those in the analysis were aged 18 years or older and planning to conceive or at under 10 weeks’ gestation. Demographic data was obtained from participants at enrollment.

The panel covered 1300 genes linked to 750 childhood-onset autosomal recessive or X-linked conditions. Most of these conditions had available treatment, but this treatment was often limited in availability or burdensome. After revision, 1281 genes were included in the final panel.

Autosomal genes were assessed in male and female partners while X-linked genes were only assessed in female partners. Exome sequencing and a targeted gene panel were used during testing.

Increased risks were determined based on the presence of a pathogenic or likely pathogenic variant in the same autosomal gene across both partners and a pathogenic or likely pathogenic variant in an X-linked gene for the female partner. When these criteria were not met, the odds were considered “low chance.”

Participants with an increased risk of having an offspring with a genetic condition received genetic counseling, with referral to a subspecialist given when necessary. During genetic counseling, participants were told about reproductive options available through the study.

Reproductive genetic carrier screening was given to 9107 couples. Couples who were invited to participate but did not undergo screening were more often residing in the most socioeconomic disadvantaged area, had a lower education level, and had 2 or more children.

Low odds of having a child with a genetic condition were reported in 96.1% of couples who received reproductive genetic carrier screening, while new identification of an increased chance was reported in 1.9% and knowledge prior to screening in 2%. Of the 180 couples with knowledge prior to the screening, 4 learned about an increased risk of a different condition.

Having previously been assumed to have the same level of risk as the general population before screening was reported in 78.3% of couples with a newly identified risk. The remaining 21.7% had family history or consanguinity leading them to be considered at an increased risk.

Of newly identified couples with current pregnancy when receiving the result, 64% had the fetus genetically tested, with 24 of these 29 couples receiving normal test results. In impacted pregnancy was found in 5, with 4 deciding to terminate the pregnancy.

Sixteen of the newly identified couples did not elect to receive testing. Of these, 1 had a miscarriage, 2 had babies with a condition identified in genetic screening after birth, 4 had unaffected babies, 4 had ongoing pregnancy during the assessment, and 5 had unknown outcomes.

These results highlighted the efficacy and availability of providing reproductive genetic carrier screening to a diverse population. Investigators noted reproductive genetic carrier screening is acceptable for patients and providers when delivered using this method.

References

1. Kirk EP, Delatycki MB, Archibald AD, et al. Nationwide, couple-based genetic carrier screening. N Engl J Med. 2024;391:1877-1889. doi:10.1056/NEJMoa2314768
2. Archibald AD, McClaren BJ, Caruana J, et al. The Australian Reproductive Genetic Carrier Screening Project (Mackenzie’s Mission): design and implementation. J Pers Med. 2022;12:1781-1781. doi:10.3390/jpm12111781