Pharmacovigilance of pregnancy exposures to medicinal products focusing on the risk of orofacial clefts

Background: It is important to obtain robust scientific information on possible safety concerns related to the use of drugs during pregnancy in post-approval settings. Since pregnant women are actively excluded from trials in the clinical development of most products, at the time of the drug entry in the market meaningful human data on the effects of that drug during pregnancy are rarely available. There are approximately 5 million pregnancies in the EU each year, and about 1 in every 10 women of childbearing age is pregnant each year. Insufficient information for management of maternal disease during pregnancy can have teratogenic impact on fetus.
Aim and objectives: This reach comprises three studies, in the first study; the goal was to evaluate the maternal use of medicines and the associated risks of cleft lip and/or palate in fetus and to link this to the accuracy and currency of safety information available in prescribing information. The second area of research was aimed at identifying and exploring social and digital media to understand patients’ experiences regarding medicine use during pregnancy. Last, but not least, I contributed to the development of an enhanced pharmacovigilance programme for analysing drug exposure during pregnancy and outcomes in neonate.
Method: Firstly, I identified medication-induced risk factors for oral clefts with safety signal detection and safety signal evaluation techniques. Then I assessed the completeness of the safety information for pregnancy exposures in the Summary of Product Characteristics and the Patient Information in the UK and the US.
In second study, the content of posts concerning pregnancy and use of medicines in online pregnancy forums was analysed using artificial intelligence in the form of natural language processing and machine learning algorithms.
Third, the PRIM (PRegnancy outcomes Intensive Monitoring) system was developed as an enhanced pharmacovigilance data collection method. This was used to improve the quality and content of prospective case reports using sets of targeted checklists, structured follow-up, a rigorous process of data entry and data quality control, and programmed aggregate analysis.
Results: For 12 antiepileptic drugs studied there was a statistical disproportionality in individual case safety reports indicative of an increased risk of cleft lip and/or palate.
There are inconsistencies between the UK and US safety labels, despite the same evidence being available for assessment.
The second study showed that in social media forums many pregnant women with MS shared profound uncertainties and specific concerns about taking medicines during the reproductive period. There was evidence of concealment of information with health care professionals; however, the same evidence was shared with a peer group.
The PRIM method of enhanced pharmacovigilance has yielded substantially more information on the safety of fingolimod exposure during pregnancy than has been achieved via the regulatory authority-mandated pregnancy registry.
Conclusion: Use of medicines during pregnancy is an important topic for public health. There is a significant need to provide inclusive, unbiased, up to- date information to prescribers and women of childbearing age concerning the use of medicines in pregnancy and postpartum during breastfeeding. Information must be provided in a timely manner by a trusted source and patients should have access to health care professionals with the relevant expertise and knowledge. It is important that the full anonymised data set, along with evidence-based conclusions are made publicly available to inform decision-making.