Analysis of a maternal health medicines pipeline database 2000-2021: New candidates for the prevention and treatment of fetal growth restriction

Abstract

Objective: The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy-related conditions, including fetal growth restriction. The objective was to assess medicines for fetal growth restriction and their potential for clinical use globally.

Design: Landscape analysis.

Setting: Global (focus on low- and middle-income countries, LMICs).

Sample: Drugs, dietary supplements and biologics under investigation for prevention or treatment of fetal growth restriction.

Methods: A research pipeline database of medicines was created through searching AdisInsight, PubMed and various grant and clinical trial databases. Analysis of clinical and preclinical candidates were descriptive.

Main outcomes measures: Fetal growth restriction candidates in clinical development were identified and ranked as high, medium or low potential based on prespecified criteria, including efficacy, safety and accessibility.

Results: Of the 444 unique candidates in the database across all five pregnancy-related conditions, 63 were for fetal growth restriction. Of these, 31 were in clinical development (phases I, II or III) and 32 were in preclinical development. Three candidates, aspirin, l-arginine and vitamin D, were ranked as having high potential as preventive agents. There were no high-potential candidates for treating fetal growth restriction, although five candidates were ranked as having medium potential: allylestrenol, dalteparin, omega-3 fatty acids, tadalafil, and United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP).

Conclusions: l-Arginine, aspirin and vitamin D are promising, high-potential preventative agents for fetal growth restriction. Based on the medicines pipeline, new pharmacological agents for fetal growth restriction are unlikely to emerge in the near future.

Keywords: aspirin; drug development; fetal medicine; intrauterine growth restriction; l-arginine; maternal medicine; obstetrics; pre-eclampsia; pregnancy; vitamin D.