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.

Effect of low‐molecular‐weight heparin on placenta‐mediated fetal growth restriction in a tertiary referral hospital: A 7‐year retrospective cohort study

“…So far, there is no effective treatment available for placenta‐mediated FGR, which is an active field for clinical research. As reported recently, LMWH becomes a medium‐potential candidate for treating FGR 5 . One study reported that LMWH does not cross the placenta, indicating that LMWH is a safe therapeutic option for FGR 24 .…”

Tadalafil for Treatment of Fetal Growth Restriction: A Review of Experimental and Clinical Studies

“…The Dutch STRIDER group reported an increased risk of neonatal persistent pulmonary hypertension (PPHN) due to maternal sildenafil administration, which generated global media interest [37]. Based on the above, the benefits of sildenafil for the treatment of FGR are considered negative, and even harmful [11,41]. Subsequent data from neonates born to the Dutch STRIDER participants have been evaluated for causes of PPHN [40].…”

“…The review determined that tadalafil was safe for pregnant women, fetuses, and neonates. Lim et al described an analysis of new candidates for the prevention and treatment of FGR [11]. Tadalafil was ranked as a "medium-potential" drug for the treatment of FGR.…”

“…Recently, phosphodiesterase 5 (PDE5) inhibitors have been investigated as promising medications for the treatment of FGR associated with placental insufficiency [11]. We studied tadalafil, a PDE5 inhibitor with a long half-life and high selectivity for PDE5, as a treatment option for FGR.…”

Gut Microbiota, Inflammation, and Probiotic Supplementation in Fetal Growth Restriction—A Comprehensive Review of Human and Animal Studies

“…The early detection of pregnant women at high risk of developing FGR would allow the application of promising treatment strategies to improve fetal growth. Several randomized controlled trials (RCTs) have shown that FGR-specific treatments, such as maternal micronutrient and amino acid supplementation (iron, zinc, calcium, magnesium, N-acetyl cysteine/L-Arginine), maternal nitric oxide supplementation, maternal growth hormone supplementation, aspirin, antiplatelet/anticoagulant agents, calcium channel blockers, proton pump inhibitors, and melatonin/heparin, can improve birth weight in FGR pregnancies [15][16][17][18][19][20][21][22][23][24]. These treatments appear to largely reflect the current understanding of the etiology of this condition.…”