Maternal and Fetal Adverse Event Reporting in Interventional Clinical Trials in Pregnancy: Current Use of MFAET Standardised Definitions and Grading

Adverse event (AE) monitoring is central to assess clinical trial safety, especially in pregnancy for maternal or fetal conditions. MFAET, the first comprehensive terminology to define and grade maternal and fetal AEs in pregnancy therapy trials was launched in 2016. It contains definitions for 12 maternal and 19 fetal AEs, which were mapped to MedDRA, the Medical Dictionary of Regulatory Activities. In 2021, severity grades 1-5 were published for each MFAET definition, developed through an international modified Delphi consensus process. Uniquely, the system grades AEs in the mother and fetus independently, allowing holistic measurement of safety for the pregnancy.
We reviewed completed pregnancy trials registered from 22 September 2021 across 17 international clinical trial registries and with publicly accessible results. Registry records, published results and available protocols were assessed for the terminology used to describe maternal and fetal AEs, use of standardised systems including MedDRA, MFAET, CTCAE and GAIA, and approaches to severity grading. The study also examines inconsistencies in the classification and reporting of pregnancy-specific adverse outcomes and identifies terminology gaps relevant to future development of pregnancy-specific AE reporting frameworks.

To evaluate how maternal and fetal adverse events are currently described, classified and graded in registered, completed and reported interventional clinical trials in pregnancy following the introduction of MFAET, with particular focus on the use or absence of standardised AE terminology and severity grading systems.

Adverse event reporting; Adverse events; CTCAE; Clinical Trials; Common Terminology Criteria for Adverse Events; Fetal safety; Interventional studies; MFAET; Maternal and Fetal Adverse Event Terminology; Maternal safety; Maternity research; MedDRA; Medical Dictionary for Regulatory Activities; Pregnancy; Safety reporting; Severity grading

https://www.ucl.ac.uk/population-health-sciences/womens-health/research/maternal-and-fetal-medicine/prenatal-therapy-0/current-projects-professor-anna-david-prenatal-therapy/maternal-and-fetal-adverse-event-terminology-mfaet

Design and conduct of studies; Equality, Diversity and Inclusion​​; Reporting standards

Other Areas: Clinical trials in pregnancy

Database analysis

Other Designs: Review of publicly available data from international clinical trial registries, supplemented by linked trial publications, results and available protocols. Trials were identified using structured, registry-specific searches and analysed descriptively to characterise current AE terminology, classification and severity grading practices.

Quantitative

Clinical trial registries; Not applicable

Complete

Publication (writing, submitting, in review, published); Study is complete and only conducting dissemination activities (e.g., stakeholder engagement, presentations, conferences and seminars, social media campaigns)

Student research project

Other(s): Prenatal Therapy Fund, UCLH Charity

Conferences; Publications (all types)