International Pregnancy Drug Safety Studies (InPreSS). Short- and longer-term safety of drug use in pregnancy

InPreSS-studien er et internasjonalt prosjektsamarbeid og kombinerer landsdekkende helseregistre fra fem nordiske land og helsedata fra USA. Studien har vært en av de største forskningsprosjekter på gravide kvinner med kobling av data om legemiddeleksponering i svangerskapet og utfall hos fosteret. Formålet med prosjektet har vært å studere konsekvenser av legemiddelbruk hos gravide for fosterutvikling, misdannelser og langsiktige utfall (nevroutviklingsforstyrrelser og skoleprestasjoner) hos barnet, samt sosiale og helsemessige konsekvenser for kvinnen hvis hun avslutter nødvendig legemiddelbehandling mens hun er gravid. Vi har fokusert primært på legemidler som brukes ved kroniske lidelser som epilepsi, diabetes, ADHD og andre psykiatriske lidelser. Vi har samarbeidet tett med andre forskere ved FHI, klinikere og fremragende forskningsmiljøer i de andre nordiske landene, USA og etterhvert også Australia. Resultater er presentert på nasjonale og internasjonale konferanser. Pr desember 2023 er 22 artikler publisert i vitenskapelige tidsskrifter som JAMA, JAMA Neurology, JAMA Psychiatry, Diabetes Care, Neurology, Acta Obstetricia et Gynecologica Scandinavia, Epidemiology, Schizophrenia Research and Pharmacoepidemiology and Drug Safety. Vi har arrangert 2-dagers konferanse med fokus på behandling av epilepsi hos gravide: Antiepileptic drugs in pregnancy and risk for the mother and child - an international conference. Forskere i InPreSS og andre verdensledende forskere fra både Europa og USA presenterte resultater fra InPreSS og annen internasjonal forskning og konsekvensene av disse ble diskutert. Konferansen har bidratt til å øke kunnskapen og bevisstheten om konsekvensene og utfordringene ved bruk av legemidler generelt og antiepileptika spesielt før og under graviditet. Deltakerne (200 fra 17 land/5 kontinent) kom fra viktige målgrupper: ulike kliniske miljøer, forskning/universitet, pasientorganisasjoner og bivirkningsmiljøer (internasjonalt og norske: SLV, RELIS, Trygg Mammamedisin). Kunnskapen som frembringes i dette prosjektet er av stor betydning og resultatene er viktige for et bredt spekter av ulike grupper: kvinner i fertil alder og deres partnere og helsepersonell ansatt i ulike deler av helsevesenet.

We have had several meetings with the Norwegian Medicine Agency (Legemiddelverket) where we have communicated findings from the studies even before they were published. Impact on regulatory decisions and guidelines: e.g. Our publication in JAMA Neurology 2022 leading to further restrictions by the European Medicine Agency (EMA) on topiramate (a drug used to treat epilepsy) use in pregnant women in the fall 2023 and a pregnancy prevention programme put in place. In letter to health personnel in Europe, three of our InPreSS publications on antiseizure drug exposure in pregnant women were cited. (https://www.ema.europa.eu/en/medicines/human/referrals/topiramate). In total, our results make an important contribution to the issue of safety in the use of medicines in pregnant women. Epidemiological studies of such a size are crucial and the only way that can give us more reliable knowledge about the consequences of drug use and higher precision in the risk estimates. The new knowledge will be important to different groups: healthy women of childbearing age (who are either pregnant or planning to be) and their partners, health personnel employed in various parts of the health system, who are responsible for the care and guidance of fertile women, regulatory authorities, and bodies responsible for giving advice on the use of medicines. We have increased our international research collaboration which in turn has led to new studies using the established data set and the common data model in InPreSS. Showcasing a positive impact on junior researcher careers: The two positions (postdoc and researcher) fully financed by InPreSS, secured permanent positions at NIPH.The researcher also managed to receive a Young Research Talent funding from RCN.

InPreSS is an international collaboration to study safety of drug use in pregnancy. About 60% of Nordic pregnant women are prescribed drugs during pregnancy, some of them due to chronic diseases that necessitate long-term drug therapy also during the pregnancy. At the time of marketing of new drugs, limited knowledge on outcomes in children exposed to drugs in-utero exists, because pregnant women are not included in randomized trials of drugs. Further, knowledge concerning the health consequences for women with chronic illness, abstaining from their drugs during pregnancy is sparse. It is urgent to investigate these issues. The overarching objective is to better understand the consequences of in-utero drug exposure for fetal development, birth defects and longer-term outcomes (neurodevelopment outcomes and academic performance) in the child, comparative drug safety, as well as maternal social and health consequences of discontinued drug treatment. We focus on treatments mainly used for chronic conditions, including but not limited to treatment of epilepsy, ADHD and other psychiatric conditions and severe acne. By combining multiple nationwide datasets from all five Nordic countries and large-scale, representative data from the US we aim to study in-utero drug exposures and rare outcomes not otherwise possible to examine in smaller datasets or in pre-marketing settings. The study population (about 5 million pregnant women) will be the largest pregnant population linked to data on drug exposure to date and has sufficient power to answer the research questions. The benefits for the users (fertile women, Norwegian Medicine Agency, Advisory Unit on Women's Health, and regional pharmacovigilance centers) will be new information on potential adverse effects of certain types of medication used during pregnancy, and a heightened awareness if adverse effects are found.