Fetal and Perinatal Exposure to Drugs and Chemicals: Novel Biomarkers of Risk

Abstract

Pregnant women are almost always excluded from randomized controlled clinical trials, as the risks to the fetus posed by most new chemical entities or approved drugs cannot be sufficiently ruled out. Hence, a major scientific challenge in this field is to discover and validate alternative tools that will fill the knowledge gap created by the lack of participation in gold-standard randomized trials. This review focuses on novel tools that allow estimation of fetal risks after exposure to therapeutic agents, such as placental perfusion studies, biomarkers of fetal exposure, and novel epidemiological and pharmacogenetic tools, all of which have been tested successfully in recent years.

Risks of congenital malformations in offspring exposed to valproic acid in utero: A systematic review and cumulative meta‐analysis

“…Understandably, results from large‐scale studies such as registry‐based research tend to have substantial influences on our views on adverse drug effects, and hence pharmacotherapy decisions both at the patient and population levels. However, our findings from the present cumulative analysis confirm an important role of small‐scale studies collectively analyzed in a systematic manner . We believe that both research approaches, conducting large‐scale registry analyses and synthesizing multiple datasets of existing small‐scale cohort studies, are complementary to each other.…”

“…However, our findings from the present cumulative analysis confirm an important role of small-scale studies collectively analyzed in a systematic manner. 27 We believe that both research approaches, conducting large-scale registry analyses and synthesizing multiple datasets of existing small-scale cohort studies, are complementary to each other.…”

On the Slow Diffusion of Point-of-Care Systems in Therapeutic Drug Monitoring

“…Advancement in PK–PD modeling allow for prediction of the average response profile to a given dosage and evaluation of a therapeutic margin; for identification of susceptibility factors that alter the therapeutic/toxic response, and for quantification of variability response, that can account also for random population variability (Lledó-García et al, 2009; Muller and Milton, 2012; Momper and Wagner, 2013). Establishment of proper PK–PD characterization during drug development generates detailed knowledge of PK–PD parameters that constitute solid reference for translation of dosage adjustment (or for subsequent clinical trials) in the targeted patient’s population and, more importantly, in subpopulations overly under-represented in drug development (Walson, 1998), like pregnancy (Ke et al, 2014), infants (Koren, 1997; Momper and Wagner, 2013), and elderlies (Battino et al, 1995; Perucca, 2005, 2006; Steinman et al, 2011; Etwel et al, 2014). …”

Clinical Data for Informed Medication Use in Pregnancy: Strengths, Limitations, Gaps, and a Need to Continue Moving Forward

“…In an attempt to assess the validity of the conclusions of these analyses by comparing them to more recent large-cohort studies, a recent study identified all relevant meta-analyses of observational studies published in peer-reviewed journals. 35 Meta-analyses with outcome measures of risk of congenital malformation and/or long-term neurodevelopment of children after first trimester in utero exposure to a therapeutic drug were eligible for consideration. Next, large registries published at a later date on the same drug and the same endpoint were identified.…”