Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology.

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care.

Controversies in implementing non-invasive prenatal testing in a public antenatal care program.

Women's autonomy and an inclusive society for all individuals are highly valued in Norway. The Norwegian Biotechnology Act changed in 2020 allowing first-trimester screening and cell-free DNA for common trisomies to all pregnant women. However, implementing non-invasive prenatal testing (NIPT) in a public antenatal care program is difficult, because many patients, politicians, and medical professionals do not consider trisomy 21 a severe medical disease. Screening for trisomies at an early gestation might inevitably lead to an increase in pregnancy terminations and making cost-benefit calculations is ethically challenging. Moreover, offering NIPT to all pregnant women is debatable because of the lower prevalence of fetal trisomies in younger women. Therefore, appropriate genetic pre-test counseling is essential. Furthermore, organizing the service between private institutions and public hospitals poses another debate and challenges both quality and equal access to health services for women across the country.