We examined a sample of 17281 women, representing more than 92% of the pregnant women in the Lleida health region in the period analysed. The annual prevalence of hypothyroidism was 6.52% (0.07% clinical and 6.45% subclinical), with an oscillation between 5.67 and 7.05% in the different years. The mean age of these patients was 31.7 ± 5.7 years. Of the total of women in the sample, 3.3% received hormone replacement therapy. Among them, the mean adherence score was 79.6 ± 22.2. Those with high adherence had a higher mean age (32.8 years), in comparison to those with low adherence (30.7 years), being this difference statistically significant. Also, treated patients with low adherence had a higher abortion rate, even if with a wide confidence interval. Finally, high adherence to treatment was associated with better TSH control during pregnancy.
The prevalence of hypothyroidism in this study is higher in comparison to some other studies conducted in Spain, such as: the study by López Espinosa et. al. in the Valencia region in 2009, where the prevalence was 3.2% (4); or the one by Diéguez et.al. in Asturias in 2016, where the prevalence was 5.5% (95% CI 4.6–6.3) (3). This variability can be explained by differences in the population studied, as well as in our study, we analysed pregnant women, whereas the others evaluated the general population. In another study in pregnant women by Jaén Díaz, JL. performed in Toledo, the prevalence of hypothyroidism was higher than the one we found (9.5%, 95% CI 6-14.7) (18). Moreover, in Europe, a study carried out in Belgium by Rodrigo Moreno-Reyes et al. showed a prevalence of hypothyroidism of 7.2% (19). Finally, a meta-analysis in the Iranian population observed the highest prevalence of hypothyroidism during pregnancy (13.01%, 95% CI 9.15–18.17) (8), probably because of the lower degree of iodination in the population studied.
Various studies analysing adherence to treatment of multiple pathologies report different results. In a study in Denmark, data from the North Jutland prescription database were compared with the information provided by pregnant women through interviews carried out during the previous 120 days, and an adherence of 43% was described (11). In agreement with it, another study on pregnant women at 36 weeks of gestation, which was carried out in Australia by means of a survey, obtained an adherence of 40.9% (12). However, these data contrast with the ones obtained in studies that specifically analyse adherence to hypothyroid treatment in pregnant women. In this regard, in a cross-sectional multinational study carried out by Juch H. et. in 18 countries in 2016, it was reported that 39% of the treated patients had high adherence (95% CI, 32.7–45.7% ); 44.1% medium (95% CI 12.5–22.5%); and 16.9% low (95% CI, 12.5–22.5%) (20). In our study, we observe slightly higher degree of adherence: 54% high, 32.9% medium, and 13% low. In this case, the different percentages could be due to a methodological difference: we analysed the proportion of days covered (PDC), whereas the study by Juch H. et. al. used interviews (20).
In our study, the mean age of patients with high adherence was 32.8 ± 4.77 years. On the contrary, patients with low adherence were 30.7 ± 6.24 years old. Such difference is statistically significant, in agreement with the study by Juch H. et. al., that significantly associated young age with low adherence in pregnant women (20). Moreover, in the study by Briesacher et. al., the analysis of adherence to treatment for various pathologies revealed that lower adherence was associated with younger age also in the general population (21).
There are few studies where TSH control is related to therapeutic adherence. In the study by Lage MJ et. al., the authors analysed 3448 pregnant women with hypothyroidism between 18 and 49 years. They observed that 52.61% of the women had a TSH value that was in the range established by the American Thyroid Association (ATA) guidelines (22). In this regard, we observed differences according to the trimesters of pregnancy. Indeed, the prevalence of women showing TSH value in the range oscillated between 31.5% and 33.9% in the first trimester; 69% and 76.1% in the second trimester; and 83.7% and 92.6% in the third trimester, depending on the degree of therapeutic adherence. These results indicate that a sufficient control of the disease is obtained at the third trimester by patients showing different levels of adherence to treatment.
Finally, Lee SY et. al. concluded that both clinical and subclinical hypothyroidism are associated with abortions, prematurity, and low scores in the infant cognitive evaluation; and that the risk caused by the treatment necessary to maintain TSH in a specific reference range during pregnancy is minimal (23). Also, Barišić T et. al. suggested that early detection and optimization of hypothyroidism treatment before and during the first trimester reduces the risk of adverse pregnancy outcomes (24). In agreement with these data, in our study, greater adherence has been associated with greater TSH control; therefore, we consider important to involve the different professionals taking care of pregnant women, to improve therapeutic adherence. In poorly controlled patients, adherence should be assessed prior to adjusting the levothyroxine dose using the information provided by the patient (25).
Among the limitations of our study, we have to consider the loss of some cases during data collection. In particular, we missed pregnant women whose follow-up was carried out in centres that do not belong to the Social Security. However, it is estimated that they only represented around 2.2% of the total of pregnant women in the health region of Lleida (26). Therefore, given the universal coverage of the Spanish National Health System, it is unlikely that this loss affected the results of our study.
Another limitation is that we could not to fully address the multifactorial origin of the adherence to treatment. Such multifactorial origin involves patient, family, beliefs, and psychosocial factors. All these variables should be considered in further studies.