Maternal Serum AFP

A negative screen means it is unlikely the fetus has an open neural tube defect. But a negative screen does not guarantee the birth of a healthy baby. The single AFP marker is not recommended as a screening tool for Down syndrome and other chromosomal abnormalities. If the patient has undergone a chorionic villus sampling (CVS) and had a normal chromosome analysis test result, no additional follow up testing for Down syndrome is needed. Similarly, if the patient has had a negative result on a first-trimester maternal serum screen or a noninvasive prenatal screen (NIPS) during this pregnancy, no follow-up testing is needed for Down syndrome. If not, it is standard practice to offer a second trimester maternal serum screen that includes markers for Down syndrome and trisomy 18.¹ Second trimester screening options include the Quad Screen (test code 30294) or Penta Screen (test code 15934), and/or noninvasive prenatal screening (NIPS; test code 92777 or 91933[NY]). Please contact Quest Genomics Client Services at 866-GENE-INFO to discuss the case with a genetic counselor.

A positive ONTD screen result means there is an increased risk for the fetus to be affected with a neural tube defect or other congenital abnormality. If the patient’s AFP is less than 3.5 multiple of median (MoM), if ultrasound dating confirms the gestational age and a singleton pregnancy, and if the gestational age is less than 18 weeks, testing a newly collected sample can be considered. If this second sample confirms an elevated AFP MoM or if a second AFP test is not performed, genetic counseling, ultrasound examination, and possible amniocentesis would be appropriate.

Note that underestimation of gestational age is one of the most frequent causes of an elevated AFP MoM.

The gestational age is derived from the estimated date of delivery (EDD) and the collection date provided; it is an exact calculation by calendar days. Gestational wheels may be inaccurate by several days or more.

Note that the gestational age is reported in decimal weeks. For example, 15 weeks 4 days is reported as 15.6 weeks.

It’s appropriate to change the gestational age or EDD when the data used for screening are substantially above or below that determined by ultrasound.

The earliest EDD calculated by ultrasound should be used for dating purposes.² An ultrasound derived EDD is most accurate when determined in the first trimester. Accuracy decreases with advancing gestational age. For example, accuracy of an ultrasound EDD is ±7 days in the first trimester and ±10 days in the second trimester.

If a first trimester ultrasound EDD is available and the gestational age used for screening is within the EDD ±7 days, the gestational age should not be changed for screening purposes. Similarly, if second trimester (but not first trimester) EDD is available and the gestational age used for screening is within the EDD ±10 day range, the gestational age should not be changed for screening purposes. If the gestational age used for screening is outside the ultrasound EDD range, it may be appropriate to change the gestational age used for screening.

If you want to change the EDD/gestational age used for a specific patient’s screening test, please contact your local Quest Diagnostics laboratory or call Quest Genomics Client Services at 866-GENE-INFO. If the revised gestational age is between 15.0 to 22.9 weeks gestation, we can calculate and report a new NTD risk. If the revised gestational age 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). If the revised gestational age is >22.9 weeks gestation, we cannot calculate a new NTD risk, and a more accurate risk assessment cannot be provided.

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 AFP value below 2.5 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.

AFP concentrations seen in NTD-affected and unaffected singleton pregnancies are well known. Therefore, an adjusted AFP MoM can be used to calculate an NTD risk in singleton pregnancies. AFP concentration data are insufficient, however, 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 866-GENE-INFO to discuss this case with a genetic counselor. Documentation of the abnormality in the family may enable a more specific risk assessment or indicate whether additional studies should be performed.

Elevated AFP screen results have been associated with pregnancy complications including fetal ventral wall defects (VWD) and other fetal anomalies, low birth weight, intrauterine growth retardation, preterm labor, preeclampsia, and fetal demise. If diagnostic testing is negative for ONTD, consider high risk prenatal care.