Hernandez Marta H, Cohen Jacqueline M, Skåra Karoline H, Grindstad Thea K, Lee Yunsung, Magnus Per, Njølstad Pål R, Andreassen Ole A, Corfield Elizabeth C, Havdahl Alexandra, Molden Espen, Furu Kari, Magnus Maria C, Hernaez Alvaro
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Blanquerna School of Health Sciences, University Ramon Llull, Barcelona, Spain.
iScience. 2024 Feb 20;27(3):109285. doi: 10.1016/j.isci.2024.109285. eCollection 2024 Mar 15.
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- and MDR1-) 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- and MDR1- variants and antiseizure medication may impact neonatal birth weight.
低出生体重会增加新生儿风险和引发终身健康问题，并且与孕期母亲用药有关。我们研究了来自挪威母婴队列研究和挪威医学出生登记处的数据，包括69828名有基因型数据的后代以及81189名有母亲基因型数据的后代。我们在胎盘外排转运蛋白中鉴定出遗传风险变异，根据与转运蛋白活性相关的等位基因计算遗传分数，并评估它们与产前使用抗癫痫或抗抑郁药物对后代出生体重的相互作用。我们的研究发现，胎盘外排转运蛋白（MRP2和MDR1）中的后代（rs3740066）和母亲（rs10248420；rs2235015）中都存在可能的遗传变异，这些变异调节了产前接触抗癫痫药物与后代低出生体重之间的关联。接触抗抑郁药物与低出生体重有关，但不存在基因-药物相互作用。MRP2和MDR1变异与抗癫痫药物之间的相互作用可能会影响新生儿出生体重。
