Clinical proteomics in obstetrics and neonatology

Abstract

Clinical proteomics has been applied to the identification of biomarkers of obstetric and neonatal disease. We will discuss a number of encouraging studies that have led to potentially valid biomarkers in the context of Down's syndrome, preterm birth, amniotic infections, preeclampsia, intrauterine growth restriction and obstructive uropathies. Obtaining noninvasive biomarkers (e.g., from the maternal circulation, urine or cervicovaginal fluid) may be more feasible for obstetric diseases than for diseases of the fetus, for which invasive methods are required (e.g., amniotic fluid, fetal urine). However, studies providing validated proteomics-identified biomarkers are limited. Efforts should be made to save well-characterized samples of these invasive body fluids so that many valid biomarkers of pregnancy-related diseases will be identified in the coming years using proteomics based analysis upon adoption of ‘clinical proteomics guidelines’.

Keywords::

• amniotic fluid
• biomarkers
• blood
• mass spectrometry
• neonatal diseases
• obstetrical care
• proteomics
• urine

Financial & competing interests disclosure

J Klein is an employee, and H Mischak is the founder and co-owner of Mosaiques Diagnostics, who developed the CE-MS technology for clinical application. A Vlahou, J Klein, H Mischak and JP Schanstra acknowledge support from the FP7-PEOPLE-2009-IAPP program Protoclin (GA 251368). H Mischak, JL Bascands and JP Schanstra acknowledge the support of EURenOmics (GA2012-305608). J Klein acknowledges the support from the FP7-PEOPLE-2011-IEF program Proteasix. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Discovery of biomarkers for obstetric and neonatal disorders will become of outmost importance in the near future with increased late pregnancies and their associated risks.

• The aim of these biomarkers will be to detect specific pregnancy-related disorders, improve prenatal counseling, help in decision making for the surveillance process after birth for neonates at risk for complications during childhood and help to understand the mechanisms of the disease.

• Technical and conceptual issues for clinical proteomics have progressed significantly over the last years.

• The number of clinical proteomics studies that successfully identified biomarkers of obstetrics and neonatology is still limited thus far, mostly due to inappropriate study setup in the early studies.

• Maternal plasma seems a good noninvasive source for protein disease markers pregnancy disorders mostly associated with the mother (e.g., preeclampsia) but is less appropriate for diseases of the fetus (e.g., Down syndrome).

• More invasive but more closely related to the fetus body fluids, such as amniotic fluid or fetal urine seems to provide good biomarkers of obstetric diseases.

• In neonatal medicine, urine is a good noninvasive source of protein biomarkers of disease.

• Well-designed studies (high patient numbers, appropriate statistics and independent validation) should lead in the near future to new markers for pregnancy-associated disease.

Notes