Treatment of spontaneous preterm birth
The present disclosure relates to biomarkers of preterm birth, biomarkers of term birth, and methods of use thereof. In particular, the present disclosure provides methods of determining whether a pregnant woman is at an increased risk for premature delivery. The present disclosure further provides methods for decreasing a pregnant woman's risk for premature delivery.
1. A method of treating a pregnant subject at risk of spontaneous preterm birth, the method comprising:
(a) detecting the protein levels of at least Inter-alpha trypsin inhibitor H4 (ITIH4), Transferrin (TF), and Plasma protease C1 inhibitor (SERPING1) in microparticles isolated from the blood of a pregnant subject, wherein the pregnant subject (i) is asymptomatic, (ii) is either multigravida who did not previously have a spontaneous preterm birth or is primigravida, and (iii) is at 8 to 20 weeks of gestation;
(b) selecting for treatment the pregnant subject at risk of spontaneous preterm birth, when the levels of at least ITIH4, TF, and SERPING1 are above a threshold level in the microparticles isolated from the blood of the pregnant subject; and
(c) administering cervical cerclage or a progesterone treatment to the pregnant subject at risk of spontaneous preterm birth in an amount effective to decrease the risk of spontaneous preterm birth.
2. The method of claim 1 , wherein the detecting step comprises detecting the level of at least 4 proteins in the fraction.
3. The method of claim 1 , wherein the protein levels are detected in the microparticles isolated from the blood of a pregnant subject who is in the second trimester.
4. The method of claim 1 , wherein the protein levels are detected in the microparticles isolated from the blood of a pregnant subject who is at 10, 11, or 12 weeks of gestation.
5. The method of claim 1 , wherein the microparticles are isolated using size-exclusion chromatography with an agarose solid phase and non-buffered aqueous liquid phase.
6. The method of claim 5 , wherein the non-buffered aqueous liquid phase is water.
7. The method of claim 1 , wherein the detecting step comprises measuring binding of an antibody specific to each of the proteins.
8. The method of claim 1 , wherein the detecting step comprises liquid chromatography/mass spectrometry (LC/MS).
9. The method of claim 1 , wherein the pregnant subject is primigravida.
10. The method of claim 1 , wherein the pregnant subject is multigravida.
11. The method of claim 1 , wherein the protein levels are detected in the microparticles isolated from the blood of the pregnant subject who is in the first trimester.
12. The method of claim 1 , wherein the microparticles are isolated from plasma.
13. A method of treating a pregnant subject at risk of spontaneous preterm birth, the method comprising:
(a) detecting the protein levels of at least Inter-alpha trypsin inhibitor H4 (ITIH4), Transferrin (TF), and Plasma protease C1 inhibitor (SERPING1) in microparticles isolated from the blood of a pregnant subject, wherein the pregnant subject (i) is asymptomatic, (ii) is either multigravida who did not previously have a spontaneous preterm birth or is primigravida, and (iii) is at 8 to 20 weeks of gestation;
(b) calculating a risk score of spontaneous preterm birth based on the levels of the proteins determined in step (a);
(c) identifying a pregnant subject at risk of spontaneous preterm birth based on the risk score; and
(d) treating the pregnant subject at risk of spontaneous preterm birth comprising administering cervical cerclage or a progesterone treatment to the pregnant subject in an amount effective to decrease the risk of spontaneous preterm birth.
14. The method of claim 13 , wherein the protein levels are detected in the microparticles isolated from the blood of a pregnant subject who is at 10, 11, or 12 weeks of gestation.
15. The method of claim 13 , wherein the microparticles are isolated using size-exclusion chromatography with an agarose solid phase and a non-buffered aqueous liquid phase.
16. The method of claim 13 , wherein the detecting step comprises liquid chromatography/mass spectrometry (LC/MS).
17. The method of claim 13 , wherein the pregnant subject is primigravida.
18. The method of claim 13 , wherein the pregnant subject is multigravida.
19. The method of claim 13 , wherein the protein levels are detected in the microparticles isolated from the blood of a pregnant subject who is in the first trimester.
20. The method of claim 13 , wherein the protein levels are detected in the microparticles isolated from the blood of a pregnant subject who is in the second trimester.
21. The method of claim 13 , wherein the microparticles are isolated from plasma.
22. A treatment method comprising administering an effective amount of cervical cerclage or a progesterone treatment to a pregnant subject characterized as having a set of differentially expressed proteins in microparticles isolated from the blood of the pregnant subject, indicative of an increased risk of spontaneous preterm birth, wherein the set of proteins comprises at least Inter-alpha trypsin inhibitor H4 (ITIH4), Transferrin (TF), and Plasma protease C1 inhibitor (SERPING1), wherein the set of proteins is expressed at above a threshold level, wherein the expression of the set of proteins is assessed in microparticles isolated from the blood of a pregnant subject, and wherein the pregnant subject (i) is asymptomatic, (ii) is either a multigravida who did not previously have a spontaneous preterm birth or is a primigravida, and (iii) is at 8 to 20 weeks of gestation.
23. The method of claim 22 , wherein the protein levels are detected in the microparticles isolated from the blood of a pregnant subject who is at 10, 11, or 12 weeks of gestation.
24. The method of claim 22 , wherein the pregnant subject is primigravida.
25. The method of claim 22 , wherein the pregnant subject is multigravida.
26. The method of claim 22 , wherein the protein levels are detected in the microparticles isolated from the blood of a pregnant subject who is in the first trimester.
27. The method of claim 22 , wherein the protein levels are detected in the microparticles isolated from the blood of a pregnant subject who is in the second trimester.
28. The method of claim 22 , wherein the characterization of differentially expressed proteins comprises liquid chromatography/mass spectrometry (LC/MS).
29. The method of claim 22 , wherein the microparticles are isolated from plasma.