DETERMINING FETAL LUNG MATURITY USING A MATERNAL SAMPLE

Abstract

A method of determining fetal lung development, by taking a sample from a pregnant subject, applying the sample to a panel including at least one biomarker for fetal lung maturity, measuring a response of the sample to the biomarker, and determining fetal lung maturity. A panel including an assay with at least one biomarker for fetal lung maturity on a solid support.

Claims

1. A method of determining fetal lung development, including the steps of: taking a sample from a pregnant subject; applying the sample to a panel including at least one biomarker for fetal lung maturity; measuring a response of the sample to the biomarker; and determining fetal lung maturity.

2. The method of claim 1, wherein the sample is chosen from the group consisting of blood, plasma, serum, urine, saliva, and nasal fluid.

3. The method of claim 1, wherein the panel is further defined as an immunoassay on a solid support chosen from the group consisting of ELISA, radioimmunoassay, real-time immunoquantitative PCR, protein microarrays, and electrochemiluminescent assays.

4. The method of claim 1, wherein said measuring step further includes the step of reading the panel with colorimetry.

5. The method of claim 1, wherein the biomarker is chosen from the group consisting of anti-LPCAT1 antibodies, anti-LPCAT2 antibodies, anti-LPCAT3 antibodies, anti-LPCAT4 antibodies, and combinations thereof.

6. The method of claim 1, wherein the panel includes a well having a threshold number of biomarkers affixed therein indicating minimal need or no need for newborn respiratory support and said measuring step further includes comparing a colorimetric value of the sample to the threshold well to determine fetal lung maturity.

7. The method of claim 1, further including the step of a doctor performing a medical decision about the pregnant subject based on the results of said determining step.

8. The method of claim 7, wherein the fetal lungs are determined to be mature and the medical decision is chosen from the group consisting of keeping the pregnant subject at a medical site, not treating the pregnant subject with medication, and delivering a baby early.

9. A panel comprising an assay with at least one biomarker for fetal lung maturity on a solid support.

10. The panel of claim 9, wherein said assay is chosen from the group consisting of ELISA, radioimmunoassay, real-time immunoquantitative PCR, protein microarrays, and electrochemiluminescent assays.

11. The panel of claim 9, wherein said at least one biomarker is chosen from the group consisting of anti-LPCAT1 antibodies, anti-LPCAT2 antibodies, anti-LPCAT3 antibodies, anti-LPCAT4 antibodies, and combinations thereof.

12. The panel of claim 9, wherein said panel includes a well having a threshold number of biomarkers affixed therein indicating minimal need or no need for newborn respiratory support and comparable to a sample with colorimetry.

13. The panel of claim 9, wherein said panel is configured to receive a sample chosen from the group consisting of blood, plasma, serum, urine, saliva, and nasal fluid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0011] Generally, the present invention provides for methods and assays for determining fetal lung maturity and development without the need for invasive amniocentesis in the pregnant subject. More specifically, the present invention provides for a method of determining fetal lung development, by taking a sample from a pregnant subject, applying the sample to a panel including at least one biomarker for fetal lung maturity, measuring a response of the sample to the biomarker, and determining fetal lung maturity. The present invention also provides for a panel including an assay with at least one biomarker for fetal lung maturity on a solid support.

[0012] “Pregnant subject” as used herein, refers to any pregnant human or animal.

[0013] “Sample” as used herein, refers to any type of sample taken from the pregnant subject, including, but not limited to, blood, plasma, serum, urine, saliva, nasal fluid, or any other fluid. The sample can be processed as necessary to apply to the panel, such as by centrifugation.

[0014] “Panel” as used herein, refers to an immunoassay assay on a solid support, such as, but not limited to an ELISA (such as sandwich ELISA), radioimmunoassay, real-time immunoquantitative PCR, protein microarrays, or electrochemiluminescent assays. The ELISA panel can use a single threshold well. Results on the panel can be read with colorimetry or by visual analysis, i.e. a result of fetal lung maturity can be one color, and immaturity can be a different color.

[0015] The biomarker for fetal lung maturity is preferably anti-LPCAT1 antibodies. The biomarker can also be anti-LPCAT2 antibodies, anti-LPCAT3 antibodies, or anti-LPCAT4 antibodies. Any other biomarker that provides a measure of fetal lung maturity can also be used. The panel can include combinations of the biomarkers. The biomarkers can be obtained from humans, non-human species, or bacteria.

[0016] Through the use of RT-PCR, it has previously been established that LPCAT1 mRNA in amniotic fluid and maternal plasma correlates with the lamellar body count (LBC) in the amniotic fluid. (Welch, et al. 2016, Welch, et al. 2018) The LBC is a well-established clinical marker of fetal lung maturity. Using some of Welch's samples, the maternal plasma LPCAT1 protein has also recently been measured using ELISA (Aras, et al.). Maternal plasma can be acquired by venipuncture which generally consists of drawing blood from the pregnant subject's arm often along with other routine clinical laboratory studies. Other than occasionally causing a bruise at the venipuncture site, this approach is far better tolerated. Maternal plasma is then prepared from the sample using simple centrifugation.

[0017] Using maternal plasma, ELISA can be used to quantify LPCAT1 protein related to newborn clinical outcomes and need for respiratory support. A threshold number of anti-LPCAT1 antibodies is associated with minimal need or no need for newborn respiratory support. Further, this threshold number of anti-LPCAT1 antibodies can be affixed into an ELISA well. By taking maternal blood, centrifuging the blood to produce plasma, then putting the plasma into a well in a panel while performing an ELISA assay, it can be determined whether the sample meets a colorimetric (or visual) level corresponding to whether the fetal lungs are mature, or not. This procedure does not require invasive testing (i.e., amniocentesis). It also avoids the multiple dilution approach used by traditional ELISA in that the technique uses a “threshold well” containing a preset number of anti-LPCAT1 antibodies corresponding to the number needed to predict fetal lung maturity.

[0018] Depending on the results of the assay, it can be determined if the fetal lungs are mature and medical decisions can be further made for the pregnant subject and baby by a doctor or medical professional. For example, if the fetal lungs are mature, it can be decided to keep the pregnant subject at a medical site and not transfer to a larger hospital that may be further away, putting the pregnant subject at risk. If the fetal lungs are mature, it can be decided to not treat the pregnant subject with certain medication (such as corticosteroids). If the fetal lungs are mature, it can be decided that it is safe to deliver the baby early.

[0019] Throughout this application, various publications, including United States patents, are referenced by author and year and patents by number. Full citations for the publications are listed below. The disclosures of these publications and patents in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.

[0020] The invention has been described in an illustrative manner, and it is to be understood that the terminology, which has been used is intended to be in the nature of words of description rather than of limitation.

[0021] Obviously, many modifications and variations of the present invention are possible in light of the above teachings. It is, therefore, to be understood that within the scope of the appended claims, the invention can be practiced otherwise than as specifically described.

REFERENCES

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