Thyroid hormone replacement therapy during pregnancy – Quantifying medication patterns and associated outcomes in the offspring
AbstractHypothyroidism is a thyroid dysfunction defined by inadequate production of thyroid hormones. This dysfunction is common (3%) in pregnant women and women of reproductive age. When the condition occurs during pregnancy, the use of thyroid hormone replacement therapy (THRT) is recommended. Inadequate treatment of the condition has been associated with adverse short- and long-term pregnancy outcomes. Currently, there are inconsistencies and knowledge gaps about the impact of THRT on maternal-fetal health. Also lacking is knowledge about THRT usage patterns. To date, apart from one Danish study, the discontinuation rate of THRT during pregnancy has not been quantified. Although longitudinal patterns of THRT may mirror real life medication use, no prior research exists on the relationship between such patterns and immediate pregnancy outcomes in the offspring. Furthermore, few studies have analyzed the effect of THRT on longterm outcomes, such as language and communication skills in the offspring. The aims of this doctoral thesis were to I) identify factors associated with discontinuation of THRT in early gestation; II) calculate agreement between maternal self-reported medication use and dispensed prescription records, and to explore longitudinal patterns of THRT use before, during, and after pregnancy; III) study the association between THRT patterns and immediate pregnancy outcomes; IV) determine the association between gestational exposure to THRT and language and communication skills in the offspring. The findings in Paper I and II indicate that majority of women during gestation use THRT consistently. The combination of results in Paper III and IV suggests that, when taken prior to, and during pregnancy, THRT can prevent adverse pregnancy outcomes. The thesis makes recommendations that can potentially lead to reduction in incidences of inadequate treatment of hypothyroidism. An increase in public awareness of the condition and its treatment benefits is recommended. A special focus on risk groups identified in the thesis (i.e., those with low education, and/or mental health issues) is advised. A second recommendation calls for evaluation of the adequacy of screening in practice. This is to ensure early identification of women who are likely to develop hypothyroidism, and to help tailor therapy for those already identified.
List of papers
|Paper I: Frank, A. S., Lupattelli A., and Nordeng H. ‘Risk factors for discontinuation of thyroid hormone replacement therapy in early pregnancy: a study from the Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway’. In: Acta Obstet Gynecol Scand 97:7 (2018), pp. 852–860. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1111/aogs.13339|
|Paper II: Frank, A. S., Lupattelli A., Matteson D. S. and Nordeng H. ‘Maternal use of thyroid hormone replacement therapy before, during and after pregnancy: agreement between self-report and prescription records and group-based trajectory modeling of prescription patterns’. In: Clin Epidemiol 10 (2018), pp. 1801—1816. This article is included in the thesis. Also available at: https://doi.org/10.2147/CLEP.S175616|
|Paper III: Frank, A. S., Lupattelli A., Matteson D. S., Meltzer H.M. and Nordeng H. ‘Thyroid hormone replacement therapy patterns in pregnant women and perinatal outcomes in the offspring’. The published version is available at: https://doi.org/10.1002/pds.4927|
|Paper IV: Frank, A. S., Lupattelli A., Brandlistuen R. E. and Nordeng H. ‘Maternal Thyroid Hormone Replacement Therapy Exposure and Language and Communication Skills of Offspring at 8 Years of Age’. The published version is available at: https://doi.org/10.1001/jamanetworkopen.2019.12424|