Levothyroxine Treatment in Pregnancy: Indications, Efficacy, and Therapeutic Regimen

Table 1

Intervention studies describing the efficacy of LT4 treatment during pregnancy.

Study	Design	Material	Intervention	Target TSH	Pregnancy complications	Offspring complications
Abalovich et al. [38]	Retrospective study of pregnant women with OH; TSH > 5 mIU/L,; T4 < 4.5 ug/dL; and SH TSH > 5 mIU/L,; T4 normal	114 women; OH 𝑛=52; SH 𝑛=62; 99 pregnancies conceived under euthyroidism, 51 under OH or SH	Treatment with LT4 before or during pregnancy as soon as OH or SH was diagnosed	Optimal treatment TSH < 4 mIU/mL Inadequate treatment; TSH > 4 mIU/L	Among pregnancies conceived under OH or SH; miscarriage rate inadequate versus adequate treated 60% versus 0% in OH and 71.4% versus 0% in SH	Among pregnancies conceived under OH or SH; preterm deliveries rate inadequate versus adequate treated 20% versus 0% in OH and 7.2% versus 9.5% in SH
Hallengren et al. [71]	Prospective observational	63 pregnant women with OH treated with LT4	Adjustment of the LT4 dose	<2 mIU/L	Fetal loss 6% (2/32) of optimally treated patients versus 29% (9/31) of women treated inadequately	Not examined
Negro et al. [72]	Prospective randomized trial	984 euthyroid women with TSH levels <4.2 mIU/L	group A, 𝑛=57 TPO Ab (+) women treated with LT4 initiated at median 10 weeks of gestation versus group B, 𝑛=58; no treatment for TPO Ab (+) women versus groups C 𝑛=869 control TPO Ab (−)	Dose of LT4 stable during pregnancy 0.5 ug/kg/d for TSH < 1.0 mIU/L 0.75 ug/kg/d TSH 1.0-2.0 mIU/L, 1 ug/kg/d; TSH > 2.0 mIU/L or anti-TPO > 1500 kIU/L	The rate of miscarriage lower in intervention group A compared to group B (3.5% versus 13.8%, 𝑃<0.05) and similar to controls (3.5% versus 2.4%, 𝑃=𝑛𝑠)	Not examined
CATS study Lazarus [73]	Prospective randomized trial	22,000 women within the 16th week of gestation	In the intervention group LT4 was initiated during pregnancy in women with FT4 values lower than the 2.5th percentile and/or TSH values above the 97.5th percentile. The control group received no intervention.	<2.5 mIU/L I trimester <3 mIU/L II and III trimester	No data	The primary outcome was the mean WPPS-III score and the percentage of offspring with IQ < 85 points. The primary intention to treat analysis revealed no significant differences. A secondary analysis excluded women noncompliant with LT4 and also revealed no difference in relative risk of full scale IQ being below 85 in the screen group compared to the control group.