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

Open neural tube defects (ONTDs) include open spina bifida (OSB) and anencephaly. These defects are caused by incomplete closure of the neural tube at about 4 weeks of pregnancy. Levels of early second-trimester maternal serum (ms) alpha-fetoprotein (AFP) are sufficiently elevated in affected pregnancies to be used as a population-based screening test. The basic screening methodology was described in the late 1970s and screening programs were active a few years later. By identifying pregnancies with the highest msAFP levels, about 80% of OSB and 95% of anencephaly can be identified as early as 16 weeks gestation. The interpretation of msAFP levels is complicated by the need to consider multiple factors such as gestational age, maternal weight, maternal race, multiple gestations, and more. Testing for AFP and acetylcholinesterase in amniotic fluid and/or identification of the lesion by targeted ultrasound is considered diagnostic of ONTD. When a diagnosis is 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 of any additional anomalies. Screening for ONTD should be performed as part of a comprehensive program linking primary obstetrical care providers, laboratorians, and high-risk clinicians.