Levothyroxine overtreatment during pregnancy increases odds for preterm delivery
A cohort of pregnant women in Canada who were overtreated for hypothyroidism with levothyroxine were more likely to have a preterm delivery than women with normal thyroid-stimulating hormone, according to a study published in Thyroid.
“Overtreatment with levothyroxine in pregnancy was associated with preterm delivery among pregnant women using thyroid replacement therapy prior to conception,” Patricia Lemieux, MD, department of medicine at the University of Calgary Cumming School of Medicine in Alberta, Canada, told Healio. “All pregnant women on thyroid replacement prior to pregnancy should have their TSH checked in pregnancy. This is not happening, but it should be.”
Lemieux and colleagues conducted a retrospective cohort study of women aged 15 to 49 years who delivered a baby in Alberta, Canada, from October 2014 to September 2017. Women who had a prescription filled for any thyroid replacement medication in the 2 years before conception were included.
Researchers collected delivery data from the Alberta Perinatal Health Program database. Data were linked to the Discharge Abstract Database for hospitalization data and province-wide databases and the Pharmaceutical Information Network database for information on prescription medications and outpatient physician visits. Frequency of TSH testing was broken down by trimester.
A normal TSH level was defined as 0.1 mIU/L to 4 mIU/L based on American Thyroid Association guidelines. Women were defined as overtreated with levothyroxine if they had one TSH measurement of less than 0.1 mIU/L during pregnancy, and the undertreated group included women with at least one TSH measurement of 10 mIU/L or higher.
There were 10,680 deliveries with women on thyroid hormone prior to conception during the study period. Of the cohort, 82.2% had at least one TSH measurement during pregnancy, and 62.8% had two or more tests performed.
Of 9,869 women included in analysis of levothyroxine dosage, 43.7% had at least one adjustment during pregnancy, with the most common timing for first adjustment during weeks 5 and 6 of gestation. Levothyroxine dosage increased as pregnancy progressed. Compared with preconception levothyroxine dosage, the median increases were 17.9% at first trimester, 35.7% at second trimester and 43.6% at third trimester.
Of the 8,774 women who had TSH testing during pregnancy, 4% were in the levothyroxine overtreatment group and 9.1% were in the undertreatment group. After adjusting for confounders, the overtreatment group was more likely to have preterm delivery compared with those with a normal TSH level (adjusted OR = 2.14; 95% CI, 1.51-2.78). There were no associations between neonatal ICU admission and overtreatment or undertreatment with levothyroxine in adjusted analysis. However, when researchers restricted analysis to women with two or more prescriptions filled before pregnancy, there was an association between neonatal ICU admission and overtreatment (aOR = 1.49; 95% CI, 1.03-2.16).
Women were more likely to fall in the overtreatment group if their prepregnancy TSH was less than 1.5 mIU/L or the levothyroxine dosage was at least 100 µg per day in the year before pregnancy (P < .001). Women diagnosed with thyroid cancer or treated for Graves’ disease were more likely to have TSH suppression, whereas those diagnosed with primary hypothyroidism were less likely to fall in the overtreatment cohort.
“Clinicians should consider exercising caution to avoid overtreatment with levothyroxine in pregnancy in women on thyroid replacement prior to conception,” Lemieux said. “The usual management of preexisting hypothyroidism is to increase levothyroxine dosage by 25% to 30% in all pregnant women, as recommended by the American Thyroid Association. However, a subgroup of pregnant women with preconception TSH less than 1.5 mIU/L or levothyroxine dose greater than 100 µg per day may benefit from a more conservative approach to levothyroxine increments during pregnancy.”
For more information:
Patricia Lemieux, MD, can be reached at Patricia.Lemieux@albertahealthservices.ca.