Elevated amniotic fluid interleukin-6 levels at genetic amniocentesis predict subsequent pregnancy loss

Our purpose was to determine the proportion of pregnancy loss after genetic amniocentesis that is related to preexisting subclinical intrauterine inflammation.

We accessed our bank of stored second-trimester amniotic fluid and maternal serum samples obtained from women undergoing genetic amniocentesis at our institution from 1988 to 1995 (N = 11,971). Interleukin-6 levels were measured by enzyme-linked immunosorbent assay in samples from every case resulting in spontaneous postprocedure loss (excluding fetal aneuploidy and anomalies) within 30 days after the procedure (n = 66) and from 66 normal control women delivered at term and matched for year of test, gestational age, maternal age, and indication for amniocentesis.

Mean maternal serum interleukin-6 levels were the same in each group (0.02 +/- 0.07 ng/ml for cases and 0.06 +/- 0.25 ng/ml for controls, p = 0.45). Mean amniotic fluid interleukin-6 levels were higher in cases (4.0 +/- 13.1 ng/ml) than in controls (0.5 +/- 0.7 ng/ml, p = 0.04). The higher mean amniotic fluid interleukin-6 levels in the cases resulted from the inclusion of eight very high values (> or = 3 SD or > or = 2.5 ng/ml). When these samples were excluded, the means and range of values were the same in each group (0.4 +/- 0.4 ng/ml for cases and 0.5 +/- 0.7 ng/ml for controls, p = 0.58). Twelve percent (8/66) of the cases and 3% (2/66) of the controls had amniotic fluid interleukin-6 levels > or = 2.5 ng/ml (p = 0.048, odds ratio 4.1, 95% confidence interval 1.0 to 31.2). Although the overall correlation between maternal serum and amniotic fluid interleukin-6 levels was good (r = 0.50, p < 0.002), only one of the eight cases would have been identified by a maternal serum interleukin-6 level > or = 3 SD above the mean (> or = 0.8 ng/ml).

Analysis of our complete unselected group of postamniocentesis pregnancy losses indicates that up to 12% may result from preexisting subclinical intrauterine inflammation. This inflammation is most likely localized and may not be identified by a maternal serum interleukin-6 level before the procedure.