Placental efflux transporters and antiseizure or antidepressant medication use impact birth weight in MoBa cohort
Marta H. Hernandez,
Jacqueline M. Cohen,
Karoline H. Skåra,
Thea K. Grindstad,
Yunsung Lee,
Per Magnus,
Pål R. Njølstad,
Ole A. Andreassen,
Elizabeth C. Corfield,
Alexandra Havdahl,
Espen Molden,
Kari Furu,
Maria C. Magnus,
Alvaro Hernaez
Affiliations
Marta H. Hernandez
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Blanquerna School of Health Sciences, University Ramon Llull, Barcelona, Spain; Corresponding author
Jacqueline M. Cohen
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway
Karoline H. Skåra
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Department of Community Medicine and Global Health, Institute of Health and Society, University of Oslo, Oslo, Norway
Thea K. Grindstad
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
Yunsung Lee
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
Per Magnus
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
Pål R. Njølstad
Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Children and Youth Clinic, Haukeland University Hospital, Bergen, Norway
Ole A. Andreassen
Norwegian Centre for Mental Disorders Research, NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Elizabeth C. Corfield
Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Nic Waals Institute, Lovisenberg Diakonale Hospital, Oslo, Norway
Alexandra Havdahl
Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Nic Waals Institute, Lovisenberg Diakonale Hospital, Oslo, Norway; PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
Espen Molden
Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway; Section for Pharmacology and Pharmaceutical Department of Pharmacy, University of Oslo, Oslo, Norway
Kari Furu
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway
Maria C. Magnus
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
Alvaro Hernaez
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Blanquerna School of Health Sciences, University Ramon Llull, Barcelona, Spain
Summary: Low birth weight raises neonatal risks and lifelong health issues and is linked to maternal medication use during pregnancy. We examined data from the Norwegian Mother, Father, and Child Cohort Study and the Medical Birth Registry of Norway, including 69,828 offspring with genotype data and 81,189 with maternal genotype data. We identified genetic risk variants in placental efflux transporters, calculated genetic scores based on alleles related to transporter activity, and assessed their interaction with prenatal use of antiseizure or antidepressant medication on offspring birth weight. Our study uncovered possible genetic variants in both offspring (rs3740066) and mothers (rs10248420; rs2235015) in placental efflux transporters (MRP2-ABCC2 and MDR1-ABCB1) that modulated the association between prenatal exposure to antiseizure medication and low birth weight in the offspring. Antidepressant exposure was associated with low birth weight, but there were no gene-drug interactions. The interplay between MRP2-ABCC2 and MDR1-ABCB1 variants and antiseizure medication may impact neonatal birth weight.
