What is a prenatal biochemistry screen and when would it be sent to a children's hospital for further evaluation?

Prenatal Biochemistry Screening: Purpose and Referral to Children's Hospitals

A prenatal biochemistry screen is a blood test performed during pregnancy to assess the risk of fetal chromosomal abnormalities and neural tube defects, and would be sent to a children's hospital when abnormal results require specialized pediatric genetic evaluation or when preparing for management of a high-risk fetal condition that will require immediate neonatal intervention after birth. 1

Components of Prenatal Biochemistry Screening

Prenatal biochemistry screening consists of several testing options:

• First-trimester screening (10-14 weeks):

  • Maternal serum PAPP-A (pregnancy-associated plasma protein A)
  • Free β-hCG or total hCG
  • Combined with nuchal translucency ultrasound measurement 2

• Second-trimester screening (15-20 weeks):

  • Alpha-fetoprotein (AFP)
  • Unconjugated estriol (uE3)
  • Beta-human chorionic gonadotropin (β-hCG)
  • Sometimes inhibin A (quad screen) 3

• Integrated/Sequential screening:

  • Combines first and second-trimester markers
  • Provides higher detection rates (85-92%) with lower false-positive rates 1, 2

• Cell-free DNA (cfDNA) screening:

  • Analyzes placental DNA fragments in maternal blood
  • Higher sensitivity and specificity for trisomies 21,18, and 13
  • Can detect sex chromosome abnormalities 1

When Prenatal Biochemistry Screens Are Sent to Children's Hospitals

1. Abnormal screening results requiring specialized evaluation:

   • When screening indicates high risk for chromosomal abnormalities (trisomy 21,18,13)
   • When sex chromosome abnormalities are detected 1
   • For interpretation of complex or unusual results that require pediatric genetic expertise

2. Preparation for specialized neonatal care:

   • When a fetal diagnosis requires immediate intervention after birth
   • For multidisciplinary planning of postnatal care for conditions identified prenatally
   • To coordinate specialized pediatric services before delivery 4

3. Genetic counseling and family planning:

   • When results indicate need for specialized genetic counseling
   • For families with history of genetic disorders requiring pediatric expertise 2

4. Diagnostic confirmation after screening:

   • Following abnormal cfDNA results that require diagnostic confirmation
   • When amniocentesis or chorionic villus sampling confirms a genetic condition 1

Clinical Implications and Interpretation

• Detection rates vary by screening method:

  • First-trimester combined screening: ~85% detection of Down syndrome (5% false-positive)
  • Integrated/sequential screening: 83-92% detection
  • cfDNA screening: 99% detection for trisomy 21 (1% false-positive) 1, 2

• Risk assessment incorporates:

  • Maternal age
  • Gestational age
  • Serum marker levels (reported as multiples of the median - MoM)
  • Ultrasound measurements
  • Family history 2, 5

Important Considerations

• Prenatal screening provides risk assessment, not definitive diagnosis
• Diagnostic testing (amniocentesis or CVS) is required for confirmation 4
• False-positive and false-negative results occur with all screening methods 1
• Screening performance differs for twin pregnancies and requires specialized interpretation 1
• Children's hospitals provide specialized expertise for interpreting complex results and planning appropriate neonatal care

Common Pitfalls

• Confusing screening tests with diagnostic tests
• Failing to offer diagnostic testing after abnormal screening results
• Not recognizing that cfDNA screening, while highly sensitive, still requires diagnostic confirmation
• Overlooking the need for specialized pediatric planning when abnormalities are detected
• Delaying referral to children's hospital specialists when abnormal results are identified

Prenatal biochemistry screening is an essential component of modern prenatal care, allowing for early risk assessment and appropriate planning for pregnancies affected by genetic conditions that will require specialized pediatric care.