Improving safety assessment of fetal therapy trials: new lactation taxonomy and revised Maternal Fetal Adverse Event Terminology (MFAET) for pharmcovigilence

Anna David, K Maksym, K Kalita-Kurzyńska , R Spencer, Melinda Boss, D Spatz, A Wesolowska

Research output: Contribution to conferencePoster


Assessing safety through adverse event (AEs) data is critical for clinical trials of novel therapeutic interventions. AEs assist both the assessment of safety for first-in-human studies of fetal therapy and Dose Limiting Toxicity Events to guide dose escalation. Formal MFAET taxonomy supports consistency in reporting and grading maternal and fetal AEs in observational and clinical trials of fetal interventions. Maternal and fetal interventions can impact lactation but current lactation AE terminology is limited. The aim of this study was to explore taxonomy to improve lactation safety monitoring and to assess use of MFAET taxonomy in fetal therapy trials.

An international, interdisciplinary group of experts reviewed current lactation AE definitions and grading. Open discussion combined with Delphi methodology for consensus was used to propose new terms and definitions. These were discussed with the Maintenance and Support Services Organization (MSSO) of MedDRA, the Medical Dictionary of Regulatory Activities, a medical terminology developed by ICH. Usage of MFAET in recent fetal therapy studies was reviewed and recommendations to update existing taxonomy were collated.

Existing terminology in MedDRA was inadequate to describe AEs impacting lactation. Three new terms related to problems of initiation and maintenance of lactation: Delayed secretory activation (Lowest Level Terms, LLT: Delayed onset of lactation), Primary lactation insufficiency (LLT: Primary lactation insufficiency) and Secondary lactation insufficiency (LLT: Secondary lactation insufficiency) were added to MedDRA version 26.0 (March 2023).
Recent observational and clinical trials of fetal interventions identified the need for new MFAET taxonomy to describe maternal complications (uterine dehiscence/rupture, amnio-peritoneal fistula) and fetal complications (fetal bradycardia or tachycardia in labour, fetal hypoxia using computerised cardiotocography). Refinement of maternal and fetal terms describing changes to liquor volume such as oligo- and anhydramnios are also needed to improve the range of the taxonomy.

The expanded taxonomy for lactation and maternal / fetal complications following fetal interventions improves safety monitoring of fetal therapy trials.


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