Maternal Serum AFP

A screened negative result means the fetus is unlikely to have an open neural tube defect (ONTD). This test is not diagnostic and should not replace second-trimester ultrasound screening for neural tube defects (NTDs). A negative maternal serum AFP screening result does not rule out chromosome abnormalities.

A screen positive result means risk for a fetal neural tube defect is increased, but it could also indicate fetal abdominal wall defects, fetal nephrosis, fetal demise, and placental conditions that increase risk of adverse events later in pregnancy. Inaccurately estimated gestational age (GA) can also lead to false-positive AFP screening tests. Therefore, it is recommended that all patients with screen positive test results, and confirmed GA, follow up with diagnostic ultrasound testing and other diagnostic tests such as amniocentesis and genetic analyses, as needed, to aid in diagnosis and pregnancy management.¹

The GA is derived from the estimated date of delivery (EDD) reported at time of sample collection. For the most accurate estimate of GA, the earliest ultrasound-derived EDD should be used.²

The earliest ultrasound-derived EDD should be used for dating purposes.² An ultrasound-derived EDD is most accurate when determined in the first trimester. If a first-trimester ultrasound EDD is available and is within ±7 days of the GA used for the screening test, the GA should not be changed for screening purposes. If a second-trimester (but not first-trimester) EDD is available and the GA is  ±10 days of the EDD used for screening, the GA should not be changed for screening purposes. If the GA used for screening is outside the ultrasound EDD range, it may be appropriate to change the GA used for screening.²

If you want to change the EDD or GA used for a specific patient’s screening test, please contact your local Quest Diagnostics laboratory or call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463). If the revised GA is between 15.0 to 22.9 weeks gestation, we can calculate and report a new NTD risk. If the revised GA is <15.0 weeks, we cannot calculate a new risk. Consider submitting a second specimen for screening, collected when the patient is between 15.0 to 22.9 weeks gestation (preferably 16 to 18 weeks). 

The NTD detection rate is significantly lower at 14.0 to 14.9 weeks gestation than at 15.0 to 22.9 weeks gestation. Therefore, samples collected during the 14th week of gestation with an alpha-fetoprotein (AFP) value below 2.5 multiples-of-median (MoM) (single gestation, nondiabetic) will be reported as screen negative without a patient-specific risk. For optimal NTD screening, collect samples when the patient is at 16 to 18 weeks gestation.

Alpha-fetoprotein (AFP) concentrations seen in NTD-affected and unaffected singleton pregnancies are well known. Therefore, an adjusted AFP multiples-of-median (MoM) can be used to calculate an NTD risk in singleton pregnancies. However, AFP concentration data are insufficient to allow similar calculations for twin and triplet pregnancies. Nevertheless, twin and triplet pregnancies can still be interpreted as screen positive or screen negative based on the AFP MoM.

Please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to talk with a genomic science specialist. Documentation of the abnormality in the family may enable a more specific risk assessment or indicate whether additional studies should be performed.