Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Abstract

Open neural tube defects (ONTDs) include open spina bifida (OSB) andanencephaly. These defects are caused by incomplete closure of the neural tube atabout 4 weeks of pregnancy. Levels of early second-trimester maternal serum (ms)alpha-fetoprotein (AFP) are sufficiently elevated in affected pregnancies to be usedas a population-based screening test. The basic screening methodology was describedin the late 1970s and screening programs were active a few years later. Byidentifying pregnancies with the highest msAFP levels, about 80% of OSB and 95% ofanencephaly can be identified as early as 16 weeks gestation. The interpretation ofmsAFP levels is complicated by the need to consider multiple factors such asgestational age, maternal weight, maternal race, multiple gestations, and more.Testing for AFP and acetylcholinesterase in amniotic fluid and/or identification ofthe lesion by targeted ultrasound is considered diagnostic of ONTD. When a diagnosisis made, options include termination, surgery after delivery, or in utero surgery,depending on factors such as location and size of the defect, and the presence ofany additional anomalies. Screening for ONTD should be performed as part of acomprehensive program linking primary obstetrical care providers, laboratorians, andhigh-risk clinicians.