Thyroid Laboratory Testing and Management in Women on Thyroid Replacement Before Pregnancy and Associated Pregnancy Outcomes

Abstract

Background: Women with hypothyroidism before pregnancy often require an increase in their levothyroxine dosage to maintain a euthyroid state during pregnancy. The objectives of this study were to investigate: (i) the frequency and distribution of thyrotropin (TSH) testing and levothyroxine dosage adjustment by gestational age, (ii) the magnitude of levothyroxine increase by the underlying etiology of hypothyroidism, and (iii) the relationship of overtreatment or undertreatment during pregnancy with adverse pregnancy outcomes among women using thyroid replacement before pregnancy. Methods: A retrospective cohort study of pregnancies in women on thyroid replacement before pregnancy in Alberta, Canada, was performed. Women using thyroid replacement anytime during the two years before pregnancy who delivered between October 2014 and September 2017 were included. Delivery records, physician billing, and laboratory and pharmacy administrative data were linked. Outcomes included characteristics of TSH testing, levothyroxine dosing, and pregnancy outcomes. The frequency and gestational timing of TSH testing and levothyroxine adjustments were calculated. Multiple logistic regression was used to test whether pregnancies with TSH <0.10 mIU/L (overtreatment) or TSH ≥10.00 mIU/L (undertreatment) compared with control pregnancies (TSH 0.10–4.00 mIU/L) were associated with adverse pregnancy and neonatal outcomes. Results: Of the 10,680 deliveries, 8774 (82.2%) underwent TSH testing at least once during pregnancy, at a median gestational age of six weeks. An adjustment of levothyroxine dosage was made for 4321 (43.7%) during pregnancy. TSH in pregnancy below 0.10 mIU/L increased the odds of preterm delivery when compared with control pregnancies (adjusted odds ratio, 2.14 [95% confidence interval 1.51–2.78]). TSH ≥10.00 mIU/L during pregnancy was not associated with any adverse pregnancy or neonatal outcomes in the multivariable analysis. Conclusions: Although most women on thyroid replacement before conception had TSH measured at some point during pregnancy, it is concerning that 17.8% did not. Levothyroxine overtreatment in pregnancy was associated with preterm delivery. These findings suggest that clinicians should be careful to avoid overtreatment with levothyroxine in pregnancy.

The magnitude of increased Levothyroxine dose during pregnancy in patients on thyroid-stimulating hormone (TSH) suppression treatment after total thyroidectomy for papillary carcinoma

“…Conversely, it has been reported that women on L-T 4 supplementation with TSH below 0.1 μIU/mL have an increased odds of preterm birth [16]. However, the report by Lemieux et al does not discuss the pregnancy course for each cause of hypothyroidism.…”

Description of thyroid disorders the year before conception: a population-based study

“…Data on the follow-up preconception thyroid disorders are limited. A Canadian study analysed TSH levels 4 months prior to gestation in 10,680 women; amongst them, 44.4% had a TSH measurement ( 18 ). This is a lower figure than the one observed in the present study (64.16%), partly due to the shorter period considered (4 months vs. 12 months).…”

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study

“…Previous studies suggested that L-T4 overtreatment and excessive T4 may lead to infants being born preterm [ 43 , 44 ], which could be one potential explanation for the observed increased risk of preterm birth observed in the comparison between gestational users and both euthyroid controls and pre-pregnancy users. Nevertheless, in this study, we observed an increased risk of preterm birth in both high and low cumulative dose groups when compared to the euthyroid group.…”