Thread by @PrenatalTherapy

Can you monitor maternal & fetal safety in clinical trials in pregnancy? Now you can, with #MFAET version 1.0 published this week @ISPDHQ
The 12 maternal & 19 fetal Adverse Event definitions are adopted by @MedDRAMSSO
obgyn.onlinelibrary.wiley.com/doi/10.1002/pd…
ucl.ac.uk/womens-health/…

1/ Researchers @ucl @UCL_IfWH @UCLHresearch have developed a standard terminology for safety monitoring for pregnant women and their fetuses during development of drugs for pregnancy. #Pregnancy #AdverseEvents #MaternalSafety #fetus #MedDRA #MFAET
ucl.ac.uk/news/2021/oct/…

2/ Adverse Event (AE) monitoring is central to assess therapeutic safety. The lack of an AE framework in pregnancy trials severely limits understanding risks in pregnant women. #MFAET was developed by international consensus of healthcare professionals & patient public groups.

3/ We identified existing severity grading for pregnant AEs & definitions of severe conditions relevant to maternal & fetal clinical trials eg guidelines @RCObsGyn @acog @NICEComms @ranzcog @DGGEF7 @WHO @SOGCorg @aepediatria @BAPM_Official @ISUOG @CanPaedSociety @MySMFM @FIGOHQ

4/ Existing terminology was limited for maternal AEs and only had two fetal AEs: poor fetal growth & fetal death:
CTCAE: ctep.cancer.gov/protocoldevelo…
Division of AIDS: rsc.niaid.nih.gov/clinical-resea…
There was a major gap in the tools for maternal and fetal translational medicine research!

5/ We set out to develop a standard terminology for maternal and fetal Adverse Events:
The Steering Group (experts in fetal medicine, fetal surgery, obstetrics, pregnancy clinical trials, neonatology and pharma) met in May 2015.

6/ Maternal AE definitions & severity grading were developed using @theNCI CTCAE generic grading 1-5 for haemorrhage, #PPROM #chorioamnionitis, anaemia #gestationalhypertension #preeclampsia #eclampsia #pretermlabour #puerperalinfection retained placenta & amniotic fluid embolus

7/ For fetal AEs we developed a generic severity grading system 1-5. We considered the potential impacts of maternal or fetal therapies on fetal organ systems. Effects of maternal AEs on the fetus were also included. We adapted AE definitions from existing clinical definitions.

8/ Fetal AEs must be diagnosable in utero eg with USS/MR imaging, CTG/fetal heart rate monitoring & they must have potential to cause a detrimental effect to the fetus. AEs that only manifest after birth were considered to be neonatal AEs, even if they had originated in utero.

9/ Some fetal AEs relate to specific organs/systems eg abnormalities of the gastrointestinal, renal, brain or musculoskeletal systems detected by imaging. Other fetal AEs are disorders of fetal movement, cardiac dysfunction, poor fetal growth & fetal fluid collection.

10/ We graded fetal heart rate abnormalities eg bradycardia & tachyarrhythmia, fetal neoplasm & general fetal structural abnormalities. Definitions were developed specifically for AEs related to fetal interventions eg fetal intraoperative injury, fetal procedural haemorrhage.

11/ Patients & public groups co-developed #MFAET with recommendations in pregnancy clinical trials to assess psychological impact of fetal interventions on the mother & capture data on subsequent fertility @SHINEUKCharity @CDHUK_CHARITY @TwinsTrust @ARCantenatal @SandsUK

12/ We integrated the fetal AE terms with existing MedDRA terms @MedDRAMSSO
Maternal and fetal AEs underwent a 2-stage international Delphi consensus across Europe, US & Canada, South America, Middle East, Asia, Australasia & Africa of clinicians, & patient groups.

13/ Final #MFAET definitions and grading version 1.0 are here:
ucl.ac.uk/womens-health/…
Thanks to our international consortium including @eurofoetus @frafig @GratacosEduard @bekahspencer & @FP7EVERREST team

14/ Funded by @wellcometrust @EPSRC via @GIFT_Surg @EU_Commission via @FP7EVERREST @NIHRresearch via @UCLHresearch German Research Foundation @GOSHCharity & EGA Hospital Charity
uclh.nhs.uk/about-us/what-…