Elevated amniotic fluid ferritin levels are associated with inflammation-related pregnancy loss following mid-trimester amniocentesis

Objective: Occult infection accounts for up to 12% of pregnancy losses following genetic amniocentesis. Elevated serum and cervical fluid levels of ferritin, an acute-phase reactant, have been associated with spontaneous preterm delivery. We determined the association between amniotic fluid (AF) ferritin levels and post-amniocentesis pregnancy loss. Methods: We performed a case-control study involving 66 women with a non-anomalous fetus who had a spontaneous pregnancy loss within 30 days following genetic amniocentesis and 66 term controls matched for maternal age, gestational age, time of test and indication for amniocentesis. Amniotic fluid ferritin and interleukin-6 (IL-6) levels were measured using commercially available kits. Results: Mean (± SD) AF ferritin levels were similar between the cases (19.3 ± 21.4 ng/ml) and the controls (19.8 ± 22.7 ng/ml) (p = 0.9). Mean (±SD) AF IL-6 levels were significantly higher in the women with post-amniocentesis pregnancy loss (4.0 ± 13.1 ng/ml) than in controls (0.5 ± 0.7 ng/ml) (p = 0.04). A significant proportion (12.1%, 8/66) of the women with post-amniocentesis pregnancy loss had elevated amniotic fluid IL-6 levels (> 3 SD, 2.5 ng/ml) indicating inflammation, as compared to none in the control group (p = 0.01). In this subgroup of women with pregnancy loss and elevated IL-6 levels, AF ferritin levels were significantly elevated (52.0 ± 45.5 ng/ml) compared to the level in women who had a term delivery (19.8 ± 22.7 ng/ml) (p = 0.002), and were strongly correlated with IL-6 levels among the cases (r = 0.67, p < 0.001). Conclusion: The strong correlation of AF ferritin with IL-6 levels, along with the high ferritin values in cases with high AF IL-6, indicates that ferritin is a marker of inflammation in asymptomatic women destined to have an early pregnancy loss.