Normal Beta-HCG and AFP Levels in Pregnancy: Next Steps
When both beta-HCG and AFP levels are normal during second-trimester screening (typically 15-20 weeks gestation), continue routine prenatal care with standard ultrasound surveillance, as normal values indicate low risk for open neural tube defects and trisomies 21 and 18. 1
Understanding Normal Screening Results
Normal maternal serum screening results provide significant reassurance about fetal well-being:
- Normal AFP levels (typically 0.5-2.5 multiples of the median) indicate low risk for open neural tube defects, with 75-90% of ONTDs and 95% of anencephaly cases showing elevated AFP 1
- Normal beta-HCG levels (typically 0.25-2.5 MoM) combined with normal AFP and unconjugated estriol detect approximately 65-75% of Down syndrome cases when abnormal 1
- The triple or quad screen (AFP, hCG, uE3, and inhibin-A) achieves approximately 75% detection rate for Down syndrome in women under 35 years with a 5% false-positive rate 1
Recommended Management Algorithm
Immediate Actions
- Document the normal results with specific MoM values and gestational age at testing 1
- Confirm accurate gestational dating via ultrasound, as a 2-week discrepancy requires reinterpretation of results 1
- Verify that maternal factors (weight, race, insulin-dependent diabetes status) were properly accounted for in the laboratory interpretation 1
Ongoing Prenatal Care
Continue standard prenatal surveillance including:
- Routine anatomic ultrasound at 18-20 weeks gestation to evaluate fetal anatomy 1
- Standard prenatal visits and monitoring per routine obstetric protocols 1
- No additional invasive testing (amniocentesis or CVS) is indicated based solely on normal screening results 1
Important Clinical Caveats
Screening Limitations to Discuss
Patients must understand that normal screening does not guarantee a normal fetus:
- The triple/quad screen only detects 65-75% of Down syndrome cases, meaning 25-35% of affected pregnancies will have normal results 1
- The screen does not detect other chromosomal abnormalities such as trisomy 13 or Klinefelter syndrome (47,XXY) 1
- Normal AFP does not exclude all structural abnormalities, only reduces risk for neural tube defects and ventral wall defects 1
Special Populations Requiring Adjusted Interpretation
- Insulin-dependent diabetic patients have lower AFP levels on average, requiring separate reference ranges 1
- Race-specific differences exist in median values, with Black/African American women typically having higher AFP levels than Caucasian women 1, 2
- Maternal weight significantly affects MoM calculations and must be accurately recorded 1
When to Reconsider or Repeat Testing
Repeat or additional testing may be warranted if:
- Gestational age was uncertain at initial testing and subsequent ultrasound reveals >2 week discrepancy 1
- Initial sample was drawn before 15 weeks gestation (too early for accurate interpretation) 1
- Patient has additional risk factors (advanced maternal age ≥35 years, family history of genetic conditions) that warrant consideration of diagnostic testing regardless of screening results 1
Advanced Maternal Age Considerations
For women ≥35 years old, normal screening reduces but does not eliminate the age-related risk for chromosomal abnormalities. The baseline risk of Down syndrome at age 35 is approximately 1 in 270 in the second trimester 1. These patients should be counseled that:
- Diagnostic testing (amniocentesis or CVS) remains an option regardless of screening results 1
- The quad screen detects over 80% of Down syndrome in women ≥35 years, but 20% will still have normal screening 1
Documentation Requirements
Ensure the medical record includes: