Experimental drugs for the inhibition of preterm labor

ABSTRACT

Introduction

Preterm birth is the leading cause of neonatal morbidity and mortality globally and poses a substantial economic burden. Consequently, there is a need for the identification of therapeutic targets and novel experimental drugs for the inhibition of preterm labor to improve neonatal outcomes.

Areas covered

The authors review the pathophysiology of labor and the inflammatory pathways underpinning it. The interruption of these pathways forms the basis of therapeutic targets to inhibit preterm labor. Current drugs available for the treatment of preterm labor are reviewed, followed by experimental drugs including toll-like receptor 4 (TLR-4) antagonists, cytokine suppressive anti-inflammatory drugs (CSAIDs), N-acetyl cysteine (NAC), Sulfasalazine (SSZ), tumor necrosis factor-alpha (TNF-α) antagonists, interleukin-1 receptor (IL-1) inhibitors, omega-3 polyunsaturated fatty acids and lipid metabolites, and the polyphenols.

Expert opinion

A number of new therapeutic strategies for the prevention of preterm labor are being investigated. These have the potential to improve neurodevelopmental outcomes and survival in babies born preterm, reducing the economic and healthcare costs of caring for the complex needs of these children in the immediate and long term. It is likely that over the next decade there will be a new treatment option that targets the pathological inflammatory processes involved in preterm labor.

KEYWORDS:

• Preterm labor
• inhibition of preterm labor
• cytokine suppressive anti-inflammatory drugs
• NF-κB inhibitors
• TLR-4
• TNF-α inhibitors
• statins
• IL-1 inhibition
• polyphenols
• omega-3 polyunsaturated fatty acids and lipid metabolites

Acknowledgment

We would like to acknowledge Dr Hassendrini Peiris for her assistance with producing the illustration in Figure 1.

Article highlights

• Preterm birth is the world’s leading cause of neonatal morbidity and mortality and imposes a substantial economic burden worldwide.

• Current treatments primarily target myometrial contractions, which is a downstream consequence of the inflammatory cascade responsible for the onset of preterm labor.

• Multiple therapeutic options which target aspects of the inflammatory cascade are currently in the pipeline and include (+) naloxone, a class of drugs known as cytokine suppressive anti-inflammatory drugs, and Rytvela: a direct cytokine inhibitor targeting IL-1.

• Statins may also have a new role as their anti-inflammatory properties appear promising in the context of preterm birth prevention.

• These drugs will all require robust and established maternal and fetal safety profiles prior to clinical use, and long-term follow-up data will be essential to ensure no adverse long-term consequences.

• Safe treatment durations will also need to be addressed if treatments are to be commenced prophylactically.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.