What are the implications of elevated hCG (Human Chorionic Gonadotropin) and inhibin A levels, along with slightly elevated AFP (Alpha-Fetoprotein), in a quadruple test result?

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From the Guidelines

Elevated hCG, inhibin A, and slightly elevated AFP in a quadruple test result indicate an increased risk of chromosomal abnormalities, particularly Down syndrome (trisomy 21), and warrant further diagnostic testing such as amniocentesis or chorionic villus sampling (CVS) to confirm or rule out chromosomal issues. The pattern of results, with high hCG and inhibin A levels, and low unconjugated estriol (uE3) levels, is consistent with an increased risk of Down syndrome, as noted in the study by 1. The quadruple test, which measures four markers (hCG, inhibin A, AFP, and unconjugated estriol) between 15-22 weeks of pregnancy, calculates risk ratios and can detect approximately 75% of Down syndrome cases in women younger than 35 years, and over 80% of Down syndrome fetuses in women 35 and older, as reported in the study by 1.

Key Points to Consider

  • The elevated hCG and inhibin A levels, combined with slightly elevated AFP, suggest an increased risk of chromosomal abnormalities, particularly Down syndrome (trisomy 21) 1.
  • Further diagnostic testing, such as amniocentesis or chorionic villus sampling (CVS), is necessary to confirm or rule out chromosomal issues.
  • Non-invasive prenatal testing (NIPT), which analyzes cell-free fetal DNA in maternal blood, can be used as an intermediate step with high sensitivity and specificity for common trisomies.
  • A genetic counselor should discuss these results with the patient to explain the implications and available options, as the psychological impact of such results can be significant for expectant parents.
  • Other potential explanations for the elevated markers include multiple pregnancy, incorrect gestational age dating, or placental abnormalities, which should be considered and evaluated by a healthcare provider.

Next Steps

  • Consult with a genetic counselor to discuss the implications of the quadruple test results and available options for further testing and diagnosis.
  • Consider non-invasive prenatal testing (NIPT) as an intermediate step to assess the risk of common trisomies.
  • Prepare for potential further diagnostic testing, such as amniocentesis or chorionic villus sampling (CVS), to confirm or rule out chromosomal issues.

From the Research

Implications of Elevated hCG and Inhibin A Levels

  • Elevated hCG (Human Chorionic Gonadotropin) and inhibin A levels, along with slightly elevated AFP (Alpha-Fetoprotein), in a quadruple test result may indicate an increased risk of Down syndrome 2, 3.
  • The combination of these markers can increase the detection rate for Down syndrome, with studies suggesting a detection rate of approximately 70% for the quadruple marker test 2.
  • Elevated inhibin A levels have been shown to be a strong predictor of Down syndrome, with a median level of 1.62 multiples of the gestation-specific median (MOM) in affected pregnancies compared to unaffected pregnancies 3.

Association with Adverse Pregnancy Outcomes

  • Elevated AFP, hCG, and inhibin A levels have also been associated with an increased risk of adverse pregnancy outcomes, including stillbirth, small for gestational age (SGA), severe preeclampsia, and preterm delivery, in women with antiphospholipid antibody syndrome (APS) 4.
  • The predictive value of these markers for adverse pregnancy outcomes is high, with area under the ROC curve values ranging from 0.692 to 0.932 for inhibin A and AFP 4.

Limitations and Variations

  • The levels of these markers can vary depending on the gestational age and ethnic background of the pregnant woman 5.
  • The use of these markers in twin pregnancies may be limited due to the differential increases in AFP, hCG, and uE3 levels compared to singleton pregnancies 5.
  • The combination of these markers with other serum parameters, such as unconjugated estriol (uE3), can improve the detection rate for Down syndrome, but the optimal combination and cutoff values may vary depending on the population being screened 6.

References

1
Guideline

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Dr.Oracle Medical Advisory Board & Editors, 2025

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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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