Non-invasive biomarker to identify subject at risk of preterm delivery
Methods for diagnosis to allow prediction of the likelihood of preterm birth based upon the concentration of lipocalin-type prostaglandin D2 synthase (L-PGDS) in cervical vaginal secretions. In addition, specific prostaglandin D2 receptor antagonists may represent novel tocolytic therapeutics.
1. A method for predicting preterm delivery of a fetus, comprising:
collecting a cervical vaginal secretion sample from a pregnant woman having an intact amniotic membrane;
measuring with an immunoassay lipocalin-type prostaglandin D2 synthase (L-PGDS) concentration in the collected cervical vaginal secretion sample; and
determining a likelihood of preterm delivery based on a comparison of the measured lipocalin-type prostaglandin D2 synthase concentration to corresponding values from a gestational age-matched population.
2. The method of claim 1 , wherein the L-PGDS concentration in the cervical vaginal secretion rises prior to rupture in membranes.
3. The method of claim 1 , wherein measuring lipocalin-type prostaglandin D2 synthase concentration comprises measuring ratios of isoforms of L-PGDS in the collected cervical vaginal secretion sample.
4. The method of claim 1 , wherein the cervical vaginal secretion is collected with a sponge.
5. The method of claim 4 , wherein the sponge is treated with at least a protease inhibitor and a bacteriocide.
6. The method of claim 1 , wherein L-PGDS levels of above 1.8 μg/ml indicate the increased likelihood of preterm delivery.
7. The method of claim 1 , wherein the likelihood of preterm delivery is the likelihood of preterm delivery within a period greater than 2 weeks.
8. The method of claim 1 , wherein the pregnant woman is at week 28 of gestation or later.
9. The method of claim 1 , further comprising repeating cervical vaginal secretion collection from the pregnant woman and L-PGDS measurement every two weeks.
10. The method of claim 1 , further comprising delaying the preterm delivery by administering to the pregnant woman a composition comprising a tocolytic agent.
11. The method of claim 10 , wherein the tocolytic agent is a β2 agonist, an NSAID cyclooxygenase inhibitor, a calcium channel blocker, a prostaglandin DP1 or DP2 receptor antagonist, or an oxytocin inhibitor.
12. The method of claim 1 , wherein the L-PGDS concentration is measured using a radioimmunoassay, enzyme-linked immunoassay, or fluorescent immunoassay.
13. The method of claim 1 , wherein measuring L-PGDS comprises contacting the cervical vaginal secretion sample with at least one antibody against L-PGDS.
14. The method of claim 2 , wherein measuring L-PGDS concentration comprises contacting the cervical vaginal secretion sample with multiple antibodies against isoforms of L-PGDS.
15. The method of claim 1 , wherein the cervical vaginal secretion sample is collected at or after 25 weeks gestation.