Integrating preconception carrier screening into public health: lessons learned from a pilot implementation study

Carrier screening identifies individuals at risk of transmitting autosomal recessive or X-linked recessive conditions, supporting informed reproductive decisions. Despite international recommendations for universal carrier screening, integration into public healthcare systems remains limited. This study evaluated the feasibility of implementing a carrier screening program in Spain's public health system.

Non-pregnant women aged 18 to 38 with reproductive intent were recruited through text messages sent from a primary care center, along with their partners. A sequential screening approach was used: women underwent a 351-gene massively parallel sequencing panel and complementary tests, while male partners were tested only if their partner carried autosomal recessive variants. Specific genetic counselling was provided, and emotional responses were assessed through pre- and post-test questionnaires.

Of 518 candidates contacted, 400 (77%) responded positively and 152 couples (50.8% of those eligible) enrolled. Among 218 individuals screened, 62% (135) carried at least one pathogenic variant. Six carrier couples (4%) were identified as being at reproductive risk of non-syndromic hearing loss (GJB2, 2 couples), cystic fibrosis (CFTR), Stargardt disease and retinitis pigmentosa (ABCA4), Smith-Lemli-Opitz syndrome (DHCR7), and Fabry disease (GLA). Of four couples followed post-disclosure, 75% opted for in vitro fertilization with preimplantation genetic testing or prenatal diagnosis. Prevention of severe genetic conditions was the most frequently reported motivation for participation.

This study proves the feasibility and clinical utility of carrier screening within a public healthcare system. Our findings demonstrate high participation rates, clinical relevance through the identification of 4% of carrier couples, and strong motivation among participants to prevent the transmission of severe genetic conditions.