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Occult inflammation and/or ischemia may be responsible for the false positivity of biochemical Down syndrome screening test

Abstract Objective: To determine the possible underlying cause of a false-positive first or second trimester biochemical Down syndrome screening test result by means of second trimester amniotic fluid cytokine level analysis. Methods: A total of 74 consecutive patients undergoing amniocentesis for karyotype analysis at 16–20 weeks' gestation were included in this prospective age-matched case-control study. The study group (n=38) had abnormal first or second trimester screening test results and normal karyotype results, while controls (n=36) included those admitted for genetic amniocentesis for other reasons who had normal first or second trimester screening test and normal karyotype results. Four markers [interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and ischemia-modified albumin (IMA)] were studied in amniotic fluid. Results: The mean age of the women in the study and control groups was 34.0±5.6 and 33.6±7.2 years, respectively. The women in the study and control groups had similar clinical and laboratory characteristics. The mean amniotic fluid IL-6 (414.84±83.96 vs. 343.02±110.59, p=0.002) and IL-8 (377.61±243.31 vs. 261.90±201.29, p=0.029), TNF-α (24.91±5.78 vs. 21.60±5.55, p=0.014), and IMA (1.19± 0.10 vs. 1.05±0.12, p<0.001) values were significantly increased in the study group when compared to controls. Conclusion: The higher amniotic fluid cytokine and ischemia-modified albumin levels in patients with false-positive first or second trimester biochemical Down syndrome screening test may result from subclinical fetal membrane inflammation and/or ischemia.