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

Anna S Frank,Hedvig Nordeng,Helle Margrete Meltzer,Angela Lupattelli,David S Matteson

doi:10.1002/pds.4927

Abstract

AbstractPurposeIt remains unknown to what degree thyroid hormone replacement therapy (THRT) during and initiation after pregnancy determines pregnancy outcomes. The present study primarily aimed to quantify the impact of THRT patterns (including trajectories) on gestational age, birth weight, and head circumference of infants. The secondary aim was to compare results of trajectory with traditional analysis.MethodsWe combined data from the Norwegian Mother, Father and Child Cohort Study (MoBa) to other Norwegian registry data and the Norwegian Environmental Biobank. The study population included 54 020 women enrolled in MoBa in 2005 to 2008. On the basis of prescription records, we classified women into nonhypothyroid (n = 51 390; reference group), THRT after delivery (n = 1397), or medicated (n = 1233) groups. Applying Group‐Based‐Trajectory Models (GBTMs), we determined THRT trajectories among women in the medicated group. Propensity score weighting linked multiple treatment groups to pregnancy outcomes.ResultsPatterns were identified among women using medication during (Decreasing‐Low, Increasing‐Medium, Constant‐Medium, and Constant‐High) and after pregnancy. Women in the Increasing‐Medium (adjusted Odds Ratio [aOR] = 1.69; 95% Confidence Interval [CI], 1.06‐2.73) and the THRT after delivery (aOR = 1.19; 95% CI, 1.01‐1.42) groups had increased risk of giving birth to an LGA infant. In the traditional analysis, only women in the THRT after delivery group showed increased risk for an LGA infant (aOR = 1.19; 95% CI, 1.00‐1.42). We found no other differential effect among the five THRT patterns on the other outcomes.ConclusionsWomen with THRT after delivery or late onset THRT treatment showed increased risk of LGA infants.

Highlights

3% of women of reproductive age experience overt or subclinical hypothyroidism.[1]
We considered the sufficient set of confounders to be maternal age, body mass index (BMI), parity, marital status, comorbidities, fiber intake, educational level, income, supplement use, smoking and alcohol habits, gender of child, FT3, FT4, TSH severity, and the thyroid peroxidase antibodies (TPOAb) category
We found an increased risk of large‐for‐gestational age (LGA) infants among women initiating thyroid hormone replacement therapy (THRT) late in pregnancy or after delivery

Summary

Introduction

3% of women of reproductive age experience overt or subclinical hypothyroidism.[1] In addition, during pregnancy, women are more vulnerable to developing hypothyroidism because of the increased demand for thyroid hormone production.[2] Inadequate treatment of hypothyroidism during gestation has been associated with adverse pregnancy outcomes, like preterm delivery.[3] thyroid hormone replacement therapy (THRT) is recommended.[4] The literature has reported conflicting results on the beneficial effect of THRT on pregnancy outcomes.[5,6] there is evidence that the effectiveness of THRT depends on timing (first trimester) and dosage to match severity of the condition.[3] 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.[6,7] Exposure groups reflecting variations in THRT use with respect to timing, duration, and dosage during gestation may be biologically more appropriate than grouping women into users and nonusers when assessing the impact of THRT on pregnancy outcomes.[8]

Results

Discussion

Conclusion