Is the Sequential Integrated Screening Protocol (SIPS) the same as the quad screen, and does someone who has completed SIPS part 1 and 2 need to undergo the quad screen?

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SIPS vs. Quad Screen: Understanding Prenatal Screening Options

No, the Sequential Integrated Screening Protocol (SIPS) is not the same as the quad screen, and someone who has completed both parts of SIPS does not need to undergo the quad screen as SIPS already includes the components of quad screening in its second part.

Understanding SIPS and Quad Screen

Sequential Integrated Screening Protocol (SIPS)

SIPS is a two-part screening protocol for fetal chromosomal abnormalities:

  • Part 1 (First Trimester): Includes nuchal translucency (NT) ultrasound and serum analytes (PAPP-A, free or total β-hCG)
  • Part 2 (Second Trimester): Includes the quad screen components (AFP, unconjugated estriol, hCG, and inhibin A)

Quad Screen

The quad screen is a second-trimester screening test that measures four maternal serum markers:

  • Alpha-fetoprotein (AFP)
  • Unconjugated estriol (uE3)
  • Human chorionic gonadotropin (hCG)
  • Inhibin A

Comparison of Screening Methods

According to the American College of Medical Genetics and Genomics (ACMG) guidelines, different screening protocols have varying detection rates for trisomy 21 (Down syndrome) 1:

Screening Method Detection Rate (%)
First trimester screening alone 82-87
Second trimester quad screen alone 81
Sequential screening (both trimesters) 95

The stepwise sequential screening approach (which is what SIPS represents) has a detection rate of approximately 95% for Down syndrome, which is significantly higher than the quad screen alone (81%) 1.

Clinical Implications

When a patient completes both parts of SIPS:

  • They have already received the quad screen components as part of SIPS part 2
  • The integrated results provide a more comprehensive risk assessment than the quad screen alone
  • Repeating the quad screen would be redundant and unnecessary

Detection Rates and False Positives

The positive predictive value (PPV) varies significantly between different screening approaches:

  • Sequential screening (both trimesters) has a PPV of approximately 2.2% for Down syndrome
  • This means about 45 diagnostic procedures would be needed to confirm one case of Down syndrome
  • By comparison, newer screening methods like NIPS (Non-Invasive Prenatal Screening) have much higher PPVs (50-95%) 1

Management Recommendations

For patients who have completed both parts of SIPS:

  • No additional quad screening is needed
  • If SIPS results are negative, no further aneuploidy evaluation is typically required
  • If SIPS results are positive or concerning, options include:
    1. Cell-free DNA screening (if not already done)
    2. Diagnostic testing via amniocentesis
    3. Detailed ultrasound evaluation for soft markers

Important Considerations

  • Accurate gestational dating is crucial for proper interpretation of screening results 2
  • If there is a discrepancy in gestational age of 2 or more weeks after ultrasound, test results must be reinterpreted 2
  • The quad screen alone detects approximately 75% of Down syndrome cases in women younger than 35 years and over 80% in women 35 and older 2
  • In most cases of Down syndrome, both AFP and uE3 levels are lower than normal, while hCG and inhibin-A levels are higher 2

Conclusion

SIPS is a more comprehensive screening protocol that includes the quad screen components in its second part. Therefore, someone who has completed both parts of SIPS has already received the equivalent of a quad screen and does not need to undergo a separate quad screen test.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Prenatal Screening for Genetic Abnormalities

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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