Recent Advances and Challenges in the Early Diagnosis and Treatment of Preterm Labor

Abstract

Preterm birth (PTB) is the primary cause of neonatal mortality and long-term disabilities. The unknown mechanism behind PTB makes diagnosis difficult, yet early detection is necessary for controlling and averting related consequences. The primary focus of this work is to provide an overview of the known risk factors associated with preterm labor and the conventional and advanced procedures for early detection of PTB, including multi-omics and artificial intelligence/machine learning (AI/ML)- based approaches. It also discusses the principles of detecting various proteomic biomarkers based on lateral flow immunoassay and microfluidic chips, along with the commercially available point-of-care testing (POCT) devices and associated challenges. After briefing the therapeutic and preventive measures of PTB, this review summarizes with an outlook.

Keywords: biomarkers; lateral flow immunoassay (LFIA) device; microfluidics; multi-omics; prelabor rupture of membrane (PROM); preterm birth (PTB).

Figure 2

Multi-omics and AI/ML-based approaches for the early detection of PTB. (a) The diagram shows that single or multi-omic studies can identify PTB biomarkers containing genes, proteins, and metabolites. (b) The workflow shows different stages of AI/ML-based prediction of PTB, data input from electronic health records (EHRs), pre-processing, and classification by a machine learning (ML) algorithm. (c) PTB classification using a transvaginal ultrasound image with the mask as an input for the neural network resulting in preterm or the control as an output (inspired from [117]).

Figure 3

Principles of biomarker detection: (a) lateral flow immunoassay (LFIA), (i) test strip design, (ii) representative images of various steps in a sandwich assay, (iii) interpretation of test results; (b) 3D printed monolith devices for PTB biomarker extraction (i), 3D printed device (A), monolith within the channel (B), SEM images of the monolith (C, D), and schematics of the device (E), (ii) elution of the labeled biomarkers from the monolith containing antibodies (Ab) against CRF, TNF, and TAT (Ab column) or the monolith lacking Ab (control) producing red and blue fluorescence, respectively [124]. Copyright© 2022 Royal Society of Chemistry.

Figure 4

Marketed point-of-care testing (POCT) devices: (a) PartoSure^® [135] for the detection of PAMG-1, whereas the (b) Hologics^® QuikCheck fFN test [136], (c) HealthcheX^® fFN test [128], and (d) Antagen^® fFN Xpresscard [129] are used for the of detection of fetal fibronectin (fFN).

Figure 1

In 2020, there were 13.4 million cases of preterm births (PTBs) around the globe: (a) moderate to late, very, and extreme preterm babies requiring essential newborn care (level 1), special newborn care (level 2), and intensive care (level 3), respectively. (b) India alone accounted for 3.02 million, the most significant number worldwide (data adopted from [6]).