Angiogenin: a marker for preterm delivery in midtrimester amniotic fluid

Neovascularization is a response of tissue to ischemic damage. Placental ischemia is thought to underlie a significant portion of preterm deliveries. Our objective was to evaluate whether angiogenin, a potent inducer of neovascularization, is increased in midtrimester amniotic fluid of patients destined to be delivered preterm.

We designed a case-control study of singleton gestations undergoing midtrimester amniocentesis for standard genetic indications. Inclusion criteria were (1) pregnancy outcome information available, (2) gestational age at amniocentesis 15 to 20 weeks, (3) no evidence of fetal structural or chromosomal anomalies, and (4) absence of conditions associated with preterm delivery. Amniotic fluid angiogenin levels were measured by immunoassay and normalized by natural log transformation for statistical analysis.

Eleven patients with preterm deliveries were matched with 33 controls. Amniotic fluid angiogenin levels were significantly higher in patients with preterm deliveries compared with controls (median 30.1 ng/ml [range 13.6 to 71.0 ng/ml] vs 17.8 ng/ml [7.8 to 43.3 ng/ml], p = 0.002). Demographic data were not significantly different. The association between angiogenin levels and preterm delivery persisted after small-for-gestational-age neonates were excluded (p = 0.02). Receiver-operator characteristic curve analysis showed that an angiogenin level of 31.0 ng/ml was the optimal cutoff point for prediction of preterm delivery (sensitivity 45.5%, specificity 91.0%, p = 0.03, odds ratio 6.0).

Midtrimester amniotic fluid angiogenin levels are elevated in patients with preterm delivery. This supports the theory that preexisting intrauterine ischemia and inflammation are important risk factors for preterm delivery and may be already present in the early midtrimester.