In these two cohorts of women followed for thyroid dysfunction during pregnancy, we observed that the association between maternal thyroid status and GWG according to IOM are present both for pregnancy as a whole and the three individual trimesters. Remarkably more than half of them go in the opposite direction of what would be usually expected.
For women treated with levothyroxine, significant associations were essentially observed in models addressing maternal thyroid status in individual trimesters (two in the first trimester and one in the second). Hyperthyroidism in the 2nd trimester (model 2) and overt hyperthyroidism at some point during pregnancy (model 3) were associated with a higher risk of iGWG. However, three associations went in an opposite direction of what would be usually expected. Thus, maternal hypothyroidism in the first trimester was associated with a higher risk of iGWG both in model 2 (subclinical and overt hypothyroidism combined) and in model 4 at the expense of overt hypothyroidism. Additionally, maternal hyperthyroidism in the 2nd trimester (model 2) was associated with a higher risk of eGWG, displaying a U-shaped association with both iGWG and eGWG. It is important to highlight that all associations described have large ORs, including those going in apparent paradoxical directions.
For women followed because of hyperthyroidism, significant associations were observed with maternal thyroid status in the last two trimesters or at some point during pregnancy. Similarly with the observations in women treated with levothyroxine, while three associations went in the expected direction, four went in the opposite one. All coefficients were strong and similar or higher for associations going in an unexpected direction.
The observed associations cannot be compared with published data since as mentioned before, GWG according to IOM and its relationship with maternal thyroid status has been rarely addressed. Instead, we can turn to the relationship between thyroid status and weight gain outside pregnancy. In a prospective study in non-pregnant women with hypothyroidism [18], weight gain only ranked eight among presenting symptoms and its sensitivity and specificity for diagnosis were only moderate. In another prospective study, baseline TSH was inversely associated with the odds of weight loss and no association was observed for weight gain [19]. In the Framingham Offspring study [20], baseline TSH was not associated with change in weight but an increase in TSH at follow-up was positively associated with weight gain.
Additional reports illustrate that the association between weight change and thyroid status is not a simple one. Khan et al [21] observed that in patients with subclinical hypothyroidism, 39.2% presented with weight increase and 23.5% presented with weight decrease. Potential mechanisms were not discussed. In turn, hyperthyroidism usually presents with weight loss [20], but there are also reports where weight gain was observed [22]. In turn, hyperthyroidism treatment clearly can lead to weight gain with reported figures ranging from 2.4 kg at 9 months to 12 kg at 24 months[23]. Finally, Tiller et al, combined 5 population-based studies (one cross-sectional, four longitudinal), including more than 16,000 subjects. While in the cross-sectional study, high TSH was positively associated with waist circumference and waist-to-height ratio, TSH at baseline was inversely associated with 5-year change of all examined anthropometric measures [24].The authors consider that results could be explained through treatment of those subjects with higher TSH values. However, this could not be the explanation in the trial of Mooijaart et.al [25] where in elderly subjects with subclinical hypothyroidism, 1-year treatment with levothyroxine induced higher weight, BMI and waist circumference at the expense of decreased values at follow-up in the control group.
The strength of this retrospective cohort study is that to the best of our knowledge it is the first analysis evaluating maternal thyroid status and GWG according to IOM in pregnant women followed by hypo and hyperthyroidism. The main limitation is that the study covered a long period where different analytical methods were used. This may have introduced some misclassification in the categorization of maternal thyroid status, which would likely have decreased the statistical power of the analysis. A second limitation is that we do not have information on diet intake or physical activity during pregnancy that could also contribute to weight gain; unfortunately, the collection of this information is not feasible in usual clinical practice. Additionally, this is a single center study which limits its external validity.