Exposure to psychotropic drugs during fetal life and ADHD in children
The aim is to study if prenatal exposure to a selected group of psychotropic drugs and analgesics (antidepressants, anxiolytics/hypnotics, triptans, opioids and NSAIDs) is associated with increased risk of ADHD in childhood.
Psychiatric symptoms and disorders and different pain conditions are all relative common conditions among pregnant women and drugs to treat these conditions are used during pregnancy. Psychotropic drugs like antidepressants, anxiolytics/hypnotics and different analgesics (both opioids, triptans and NSAIDs) are used by pregnant women. Both the psychotropic drugs and analgesics cross the placenta and thereby impose potential harm to the fetus. Caution is generally recommended with use of all psychotropic drugs in pregnancy, however, it is also well acknowledged that for some women the benefits of pharmacological treatment will outweigh the potential risks to the unborn infant. Studies on the effect of psychotropic drug use and analgesics on neurocognitive development in general and on development of ADHD are scares.
The aim of the present study is therefore to study if prenatal exposure to a selected group of psychotropic drugs and analgesics (antidepressants, anxiolytics/hypnotics, triptans, opioids and NSAIDs) are associated with increased risk of ADHD in childhood? We will also study if any of the associations that might be identified will be due to unmeasured confounding or if they will reflect causal relationships. In a later stage when linkage to the Norwegian Prescription Database (NorPD) has been established we would study agreement between self-reported drug use in MoBa and data in NorPD).
In the first phase of the project we will use the MoBa NPR linked data (Umbrella project 1223). At a later stage we plan to link the MoBa NPR dataset to the Norwegian Prescription Database.
Participants (children and parents) in the MoBa study will constitute the cohort for this project. We expect slightly less than 90 000 pregnancies where the mother has answered all three questionnaires concerning drug use in pregnancy. The MoBa children were born in 1999-2009. Their age range is now 4 to 14 years with a mean age of 7.5 years. There are 17,942 sibships in the cohort, of whom 1,900 are twins.
The exposure variable will be defined as self-reported use of drugs from MoBa in Q1, Q3 and Q4. Through linkage of the Norwegian Patient Registry (NPR) we will identify all participants in MoBa who have received a diagnosis of ADHD (F90, Hyperkinetic disorders corresponds to ADHD in the DSM system). We have recently linked the MoBa and the NPR and identified 1178 children, 628 mothers and 373 fathers with a diagnosis of ADHD in the NPR.
Two types of approaches will be used. The first includes data from the entire MoBa cohort in a cohort design. Different control groups are possible; all non-exposed women or e.g. women with psychiatric disease/symptoms not treated with the drug of interest during pregnancy. The second approach is similar to the first, but is based on a family design; comparing children with an ADHD diagnosis with their siblings and/or cousins/parents. This approach will be used if the numbers of exposed allows it.
When possible we will use a variety of causal analytic methods to determine if associations identified in the primary analyses reflect causal relationships or are the result of unmeasured confounding. These include sibling-comparison, children-of-sisters design, Mendelian randomization, and maternal-paternal comparison. The first approach will be done using stratified Cox regression to calculate the within pair associations in the 17,942 sibling pairs in MoBa. This will be conducted if we have 80% study power to detect a 30% increase in the risk of ADHD. The superiority of this design is based on the fact that siblings share stable aspects of family and genetic predisposition thereby reducing the potential for unmeasured confounding substantially.
Hedvig Marie Egeland Nordeng, Norwegian Institute of Public Health
Svetlana Ondrasova Skurtveit, Mental Disorders, Norwegian Institute of Public Health
Eivind Ystrøm, Mental Disorders, Norwegian Institute of Public Health
Ted Reichborn-Kjennerud, Mental Disorders, Norwegian Institute of Public Health
Sven Ove Samuelsen, Physical Health and Ageing, Norwegian Institute of Public Health
Marte Handal, Mental Disorders, Norwegian Institute of Public Health
Angela Lupatelli, Universitetet i Oslo, University of Oslo
Mollie Wood, Seksjon for galenisk farmasi og samfunns, University of Oslo
Johanne Naper Trønnes, Seksjon for galenisk farmasi og samfunns, University of Oslo
Emil Aas Stoltenberg, Universitetet i Oslo, University of Oslo
Gerd Marie Eskerud Harris, Universitetet i Oslo, University of Oslo
Sarah Hjorth Andersen, Seksjon for galenisk farmasi og samfunns, University of Oslo