Recommended Prenatal Screening Tests and Interventions During Pregnancy
All pregnant women should be offered comprehensive prenatal screening including first trimester combined screening (NT, PAPP-A, and hCG), second trimester MSAFP screening for neural tube defects, and multiple marker screening unless they have elected for diagnostic testing. 1, 2
First Trimester Screening (11-13+6 weeks)
Ultrasound Assessment
- Crown-rump length (CRL) measurement between 45-84mm for accurate dating 1
- Nuchal translucency (NT) measurement for aneuploidy screening 2, 1
- Limited structural survey for major abnormalities of fetal head, abdominal wall, and urinary tract 1
- Determination of chorionicity in multiple gestations 1
Biochemical Markers
- PAPP-A and free beta-hCG or total/intact hCG 2, 1
- Should be measured at the same time as NT ultrasound (11-13+6 weeks) 1
- Detection rate for Down syndrome is approximately 70% with a 5% false-positive rate using NT alone 2
- Combined first trimester screening can detect 75-80% of Trisomy 18 fetuses at a 1% false-positive rate 2
Second Trimester Screening (15-20 weeks)
Multiple Marker Screening (Quad Screen)
- Optimal timing: 16-18 weeks' gestation 2, 1
- Includes:
- Detects approximately 75% of Down syndrome cases in women younger than 35 years with a 5% positive screening rate 2
- Detects at least 70% of trisomy 18 cases 2
- Women should be offered MSAFP screening for neural tube defects at 16-18 weeks, even if they had first trimester screening 2, 1
Factors Affecting Screening Results
- Maternal weight (heavier women have lower serum marker levels)
- Race (Black/African American women have 10-15% higher AFP levels)
- Insulin-dependent diabetes (10-20% lower AFP levels)
- Gestational age accuracy (ultrasound dating preferred over LMP) 1
Integrated Screening Approaches
Full Integrated Test
- Combines first trimester NT measurement and PAPP-A with second trimester quad screen
- Provides highest detection rate (92% at 5% false-positive rate) 1
- Results categorized as high risk, intermediate risk, or low risk 1
Sequential or Contingency Screening
- First trimester results disclosed
- High-risk patients offered immediate diagnostic testing
- Intermediate-risk patients proceed to second trimester testing
- Low-risk patients provided reassurance 1, 2
Diagnostic Testing Options
Chorionic Villus Sampling (CVS)
- Offered between 10-13 weeks
- Diagnoses all major aneuploidies and large chromosomal rearrangements 2
- Should be offered to women 35 years and older 2
Amniocentesis
- Offered after 15 weeks
- Diagnoses all major aneuploidies and large chromosomal rearrangements 2
- Should be offered to women 35 years and older 2
- Recommended for women with positive second trimester screening test 2
Additional Recommended Interventions
Folic Acid Supplementation
- Recommended for all women of childbearing age and during pregnancy
- Usual therapeutic dosage is up to 1 mg daily
- Maintenance dose of 0.8 mg for pregnant and lactating women 3
- Prevents neural tube defects when started before conception and continued through early pregnancy 3
Detailed Anatomy Ultrasound
- Comprehensive fetal anatomy assessment at 18-22 weeks
- Evaluates placental location and appearance
- Assesses amniotic fluid volume
- Measures cervical length 1
Special Considerations
Multiple Gestations
- NT measurement alone is useful in screening multiple gestations for Down syndrome
- Twin-specific screening protocols recommended
- More frequent growth assessments
- Screening for twin-specific complications like twin-to-twin transfusion syndrome in monochorionic twins 1, 2
Increased NT Measurement
- NT measurement of 3.5 mm or greater, even with low risk for aneuploidy or normal karyotype, should prompt:
- Detailed anatomic ultrasound
- Echocardiogram or both 2
- Associated with increased risk of congenital heart defects, diaphragmatic hernias, skeletal dysplasias, and genetic syndromes 2
Potential Pitfalls to Avoid
- Dating errors when relying on LMP rather than ultrasound dating
- Missing the timing window for NT ultrasound (must be done between 11-13+6 weeks)
- Incomplete follow-up with second trimester screening for neural tube defects after first trimester screening
- Failing to adjust serum marker levels for maternal weight, race, and diabetes status 1
- Administering high doses of folic acid (>0.1 mg daily) without ruling out vitamin B12 deficiency 3
Recent evidence suggests that detailed first-trimester ultrasound identifies more fetuses with potential abnormalities than cell-free DNA testing alone, supporting the continued use of combined screening approaches 4.