Podcast Summary: The OB/GYN Resident Survival Guide

Episode #19: Make SENSE of Prenatal Genetic Screening – cfDNA, First & Second Trimester, Sequential & Integrated Screen

Host: Dr. KC Miller
Date: February 7, 2026

Episode Overview

This episode, hosted by Dr. KC Miller, offers a focused, high-yield breakdown of prenatal genetic screening modalities. Dr. Miller covers the most up-to-date tests—including cell-free DNA (cfDNA), first and second trimester screening, sequential and integrated screens—clarifying indications, test timing, and clinical pearls. The content is tailored for OB/GYN residents and medical students seeking to master core knowledge for clinical practice and exam preparation.

Key Discussion Points & Insights

1. Who Should Be Offered Prenatal Genetic Screening?

• Universal Offering:

  • Every pregnant person should be offered prenatal genetic screening, regardless of age or risk factors.
  • Screening is not mandatory; it’s opt-in with the right to decline.

• Screening vs. Diagnostic Testing:

  • All screenings discussed are screening tests—they cannot confirm or rule out genetic disease.
  • Next Steps after Abnormal Results:
    • Abnormal screens should lead to genetic counseling, detailed anatomic ultrasound, and offer of diagnostic testing (amniocentesis or CVS), per best practice.

  “Any pregnant person, regardless of their age or whether or not they have risk factors for genetic disease, should be offered prenatal genetic screening.” — Dr. KC Miller (01:17)

2. Cell-Free DNA (cfDNA) Screening

Main Takeaways:

• Description: A maternal serum test evaluating fragments of fetal DNA (cfDNA) in maternal plasma—primarily placental in origin.

• Timing: Can be performed as early as 9–10 weeks gestation.

• Accuracy: Currently the most sensitive and specific screening for common trisomies (21, 18, 13) and sex chromosome aneuploidies.

• Additional Capabilities:

  • Can determine fetal sex, RH status, and screen for certain single gene disorders/microdeletions.

• Notable Applications:

  • Most recommended by SMFM and ACOG when available.
  • Not suitable for some scenarios (e.g., vanishing twins, maternal mosaicism, organ transplants).

  “Screening with cell free DNA is considered by the Society of Maternal Fetal Medicine and ACOG to be the most sensitive and specific screening modality.” — Dr. KC Miller (04:26)

3. First and Second Trimester Serum Screening

• First Trimester Screen (FTS):

  • Timing: 10–13 weeks gestation.
  • Components:
    • Maternal serum HCG
    • Pregnancy associated plasma protein A (PAPP-A)
    • Nuchal translucency (NT) by ultrasound
  • Interpretation: Normal NT is <3 mm.
  • Follow-up: Positive screens → offer diagnostic testing (amnio/CVS).

  “The first trimester screen should be completed between 10 and 13 weeks and includes a serum human chorionic gonadotropin or HCG, a serum pregnancy associated plasma protein A or PAPA and a nuchal translucency measurement performed by ultrasound.” — Dr. KC Miller (08:44)

• Second Trimester Screen (Quad Screen):

  • Timing: 15–22 weeks (AFP ideally by 20 weeks)
  • Components:
    • HCG
    • Estriol
    • Inhibin
    • Maternal serum alpha-fetoprotein (AFP)
  • AFP Pearls: Elevated in neural tube/abdominal wall defects

  “The second trimester screen is also called the quad screen because it is a blood draw that assesses four serum analytes...” — Dr. KC Miller (11:10)

• Why Still Relevant? If cfDNA is inaccessible/not desired/contraindicated (insurance, patient preference, special maternal histories), traditional screens remain important.

4. Sequential and Integrated Screening

• Sequential Screen:

  • First perform first trimester screen.
  • If negative, continue to second trimester (quad) screen.
  • Results reported twice—after each segment.

  “The sequential screen is simply a combination of the first and second trimester screens done in sequential order.” — Dr. KC Miller (10:22)

• Integrated Screen:

  • FTS (NT + PAPP-A) plus second trimester quad screen, but results provided only after both are complete—one comprehensive risk assessment in the second trimester.

  “The integrated screen comes packaged as a single test result with the risk assessment in the second trimester.” — Dr. KC Miller (13:36)

5. Recap and Clinical Pearls

Dr. Miller offers a succinct wrap-up, reinforcing main points:

• cfDNA has the highest sensitivity/specificity for aneuploidy (including sex chromosomes) and can identify additional conditions.

• First Trimester Screen: HCG + PAPP-A + nuchal translucency

• Second Trimester Screen: HCG + estriol + inhibin + AFP (key for neural tube defects)

• Sequential Screen: First trimester screen, then second if negative

• Integrated Screen: Combines above, reporting only after both are complete

  “I know that's a lot to digest and sometimes these things are easier to read than to hear, so feel free to check out the transcript in the show notes along with the references for additional reading.” — Dr. KC Miller (15:30)

Notable Quotes & Memorable Moments

• On Screening Necessity:

  “Testing is not mandatory and should be considered opt-in only with the right to decline.” — Dr. KC Miller (01:30)

• On Diagnostic Follow-Up:

  “Positive or abnormal screening results should be followed up with a combination of genetic counseling, a detailed anatomic ultrasound survey, and the patients should be offered diagnostic testing...” — Dr. KC Miller (02:08)

• On Clinical Relevance of Traditional Screening:

  “These screening tests are still relevant and important to know, especially because not all patients will have insurance that covers cell free DNA.” — Dr. KC Miller (07:50)

Timestamps for Key Segments

• 00:00 – Episode Introduction; universal offering of screening
• 04:00 – Cell-Free DNA (cfDNA) overview
• 08:44 – First Trimester Screen: components and timing
• 10:22 – Sequential Screen: definition and workflow
• 11:10 – Second Trimester (Quad) Screen: analytes and timing
• 13:36 – Integrated Screen: definition and workflow
• 15:30 – Recap and additional resources

Episode Tone

Dr. Miller keeps the episode focused, clinically relevant, and encouraging, using direct and inclusive language tailored for busy residents and students.

Further Learning

• Check episode show notes for transcript and reference links, including the recommended “Ethical Considerations for Genetic Testing and Counseling.”
• Visit www.drkcmiller.com or follow @drkcmiller for further resources.

This episode delivers a concise yet thorough review of a topic critical for exam prep and real-world residency efficiency, staying true to Dr. Miller’s mission to distill OBGYN knowledge into high-yield, digestible pearls.