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

Abstract

PurposeA reliable definition of exposure and knowledge about long-term medication patterns is important for drug safety studies during pregnancy. Few studies have investigated these measures for thyroid hormone replacement therapy (THRT). The purpose of this study was to 1) calculate the agreement between self-report and dispensed prescriptions of THRT and 2) classify women with similar adherence patterns to THRT into disjoint longitudinal trajectories.MethodsOur analysis used data from the Norwegian Mother and Child Cohort Study (MoBa), a prospective population-based cohort study. MoBa was linked to prescription records from the Norwegian Prescription Database (NorPD). We estimated Cohen’s kappa coefficients (k) and approximate 95% CIs for agreement between self-report and prescription records for the 6-month period prior to pregnancy and for each pregnancy trimester. Using group-based trajectory models (GBTMs), we estimated adherence trajectories among women who self-reported and had a THRT prescription.ResultsThere were 56,148 women in MoBa, who had both a record in NorPD and available prescription history up to 1 year prior to pregnancy. Of these, 1,171 (2.1%) self-reported and received a prescription for THRT. Agreement was “perfect” in the 6-month period prior to pregnancy (k=0.86; CI 0.85–0.88), in the first (k=0.83; CI 0.82–0.85) and in the second trimesters (k=0.89; CI 0.87–0.90), while this was moderate (k=0.57; CI 0.54–0.59) in the third trimester. Among the subset of the 1,171 women, we identified four disjoint GBTM adherence groups: Constant-High (50.2%), Constant-Medium (32.9%), Increasing-Medium (11.0%), and Decreasing-Low (5.8%).ConclusionAgreement between self-report and prescription records was high for THRT in the early pregnancy period. Based on our GBTM results, about one in two women with hypothyroidism had adequate adherence to prescribed THRT throughout pregnancy. Given the potential consequences, evidence of low adherence in 5.8% of pregnant women with hypothyroidism is of concern.

Safe Expectations: Current State and Future Directions for Medication Safety in Pregnancy Research

“…Some studies have assessed time-varying exposures by estimating trimester-specific effects of triptans on neurodevelopment 47 and acetaminophen on cerebral palsy, 48 using marginal structural models. Additional methods such as group-based trajectory models 49 and k-means longitudinal cluster analysis 50 have been used to identify groups of women with specific exposure patterns. Future research should consider whether these more complex methods are relevant for the questions they are trying to answer.…”

Thyroid hormone replacement therapy patterns in pregnant women and perinatal outcomes in the offspring

“…First, we split the exposure period, starting from 6 months prior to pregnancy and ending with gestational week 32, into months (in total 14 months). To classify women in the medicated hypothyroid group into trajectories, we then applied the GBTM approach to each woman's dispensing of prescription over the 14 months (ie, exposed/unexposed), similar to Frank et al, who used GBTM to define long‐term THRT adherence patterns before, during, and after pregnancy.…”

“…Though MAR is untestable, by including a wide variety of predictors in the imputation model, the assumption is likely to be plausible (see also Supporting Information) . The optimal number of THRT trajectories was selected by the highest (least negative) BIC value and estimated group proportions greater than 5.0% . Boosted logistic regression models were applied to determine the conditional probability of six group comparisons, where the THRT trajectories from the medicated and the THRT after delivery group were compared with the nonhypothyroid group .…”

“…A number of previous studies failed to include first trimester exposure information or lacked information on dosage and severity levels, eg, thyroid hormone blood levels . Exposure groups reflecting variations in THRT use with respect to timing, duration, and dosage during gestation may be biologically more appropriate than simply grouping women into users and nonusers when assessing the impact of THRT on pregnancy outcomes …”

“…The current study builds on our prior work showing that Group‐Based Trajectory Models (GBTMs) could be used to identify women with distinct patterns of THRT use in pregnancy . Our primary aim is to analyze the association between THRT patterns during pregnancy (using GBTM) and immediate pregnancy outcomes, such as infant birth weight, gestational age at birth, and head circumference.…”