Maternal Thyroid-Stimulating Hormone, Free Thyroxine Associated With BMI

Maternal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels during early pregnancy are directly linked to maternal body mass index (BMI) and total weight gain during pregnancy, according to research published in Clinical Endocrinology.¹ 

Romy Gaillard, MD, PhD, from the Department of Pediatrics and the Department of Epidemiology at Erasmus University Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands, and colleagues conducted a population-based, prospective cohort study assessing the relationships among BMI, prepregnancy obesity, gestational weight gain, and maternal thyroid function in expectant woman between 2002 and 2006.

Data were collected from the population-based prospective Generation R Study²; Dr Gaillard and colleagues examined 5726 mothers (mean age, 29.7±5.0 years; prepregnancy BMI, 24.5±4.4 kg/m²). At baseline, median TSH and FT4 levels were 1.4 mIU/L (95% range, 0.03-4.5 mIU/L) and 14.8 pmol/L (95% range, 9.4-22.2 pmol/L), respectively. Total weight gain during pregnancy was 15.2±5.6 kg.

 

Researchers collected maternal serum samples at a median 13.5 weeks of pregnancy (95% range, 9.7-17.6 weeks). Reference ranges for TSH and FT4 were 0.03 to 4.04 mU/L and 10.4 to 22 pmol/L, respectively. On the basis of baseline measurements, women were categorized into 1 of 3 groups: overt hypothyroidism, subclinical hypothyroidism, or overt hyperthyroidism, with overt and subclinical hypothyroidism combined into a single category for ease of study of low thyroid activity.

Higher maternal TSH levels in early pregnancy were associated with a low risk for women being underweight prepregnancy (P <.05); higher maternal TSH was lined to a higher risk for “excessive gestational weight gain” (odds ratio [OR], 1.28; 95% CI, 1.13-1.45) per SD increase in TSH. Conversely, mothers with elevated FT4 were more likely to have been underweight prepregnancy and have a lower risk for excessive gestational weight gain while pregnant (OR, 1.30 [95% CI, 1.15-1.46] and OR, 0.83 [95% CI, 0.75-0.92], respectively).

For BMI, higher TSH indicated higher maternal prepregnancy BMI; this remained consistent in models adjusted for both sociodemographic and lifestyle-related characteristics (difference, 0.18 kg/m²; 95% CI, 0.01-0.36). Women with elevated TSH also experienced “slightly higher” weight gain in early pregnancy and in total (differences, 0.03 and 0.02 kg/week [95% CI, 0.01-0.04 and 0.01-0.03, respectively]).

Conversely, patients with elevated FT4 had lower prepregnancy BMI (difference, −0.54 kg/m²; 95% CI, −0.72 to −0.35); adjustments for socioeconomic and lifestyle characteristics “did not explain these associations,” the authors noted. FT4 elevations were also associated with lower early pregnancy and total weight gain (differences, −0.04 and −0.02 kg/week [95% CI, −0.05 to −0.03 and −0.02 and −0.01], respectively).

Overall, when compared with women with normal thyroid function, women with maternal hypothyroidism experienced higher prepregnancy BMI (difference, 0.66 kg/m²; 95% CI, 0.03-1.29), whereas those with maternal hyperthyroidism experienced a lower prepregnancy BMI (difference, −1.79 kg/m²; 95% CI, −3.11 to −0.47).

“Studies among non-pregnant populations have reported that higher TSH and lower FT4 levels are associated with higher weight and higher BMI,” the researchers wrote.^3-8 “In line with…previous studies, our observed associations of maternal FT4 levels in early pregnancy with prepregnancy BMI were stronger and more consistent as compared to the associations for maternal TSH levels.”

However, the investigators noted that direction and mechanisms underlying the link between maternal thyroid function and weight gain in pregnancy remain unclear.

Looking ahead to future studies, Dr Gaillard and colleagues concluded, “[M]aternal weight during pregnancy should be considered as an important covariate in studies focused on the influence of maternal thyroid function during pregnancy on pregnancy and offspring outcomes.

Study Limitations

• Participants were highly educated, healthier, and primarily Dutch; as such, results may not be generalizable to other populations.
• Nonresponse rates may have led to the selection of an overall healthier population, also affecting generalizability of results.
• Maternal thyroid parameters were assessed only once during pregnancy.
• BMI was assessed via questionnaire at study enrollment; self-reported weight “tends to be underestimated,” which may have resulted in some misclassification.
• Because of the cross-sectional design of the study, researchers were not able to draw conclusions about directions and causality of associations.
• Residual confounding resulting from sociodemographic or lifestyle-related factors may be an issue.

References

1. Collares FM, Korevaar TIM, Hoffman A, et al. Maternal thyroid function, prepregnancy obesity, and gestational weight gain – the Generation R Study: a prospective cohort study [published online June 30, 2017]. Clin Endocrinol. doi:10.1111/cen.13412
2. Koojiman MN, Kruithof CJ, van Duijn CM, et al. The Generation R Study: design and cohort update 2017. Eur J Epidemiol. 2016;31(12):1243-1264. doi:10.1007/s10654-016-0224-9
3. Knudsen N, Laurberg P, Rasmussen LB, et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab. 2005;90(7):4019-4024. doi:10.1210/jc.2004-2225
4. Svare A, Nilsen TI, Bjøro T, Asvold BO, Langhammer A. Serum TSH related to measures of body mass: longitudinal data from the HUNT study, Norway. Clin Endocrinol. 2011;74(6):769-775. doi:10.1111/j.1365-2265.2011.04009.x
5. Biondi B. Thyroid and obesity: an intriguing relationship. J Clin Endocrinol Metab. 2010;95(8):3614-3617. doi:10.1210/jc.2010.1245
6. De Pergola G, Ciampolillo A, Paolotti S, Trerotoli P, Giorgino R. Free triiodothyronine and thyroid stimulating hormone are directly associated with waist circumference, independently of insulin resistance, metabolic parameters and blood pressure in overweight and obese women. Clin Endocrinol. 2007;67(2):265-269. doi:10.1111/j.1365-2265.2007.02874.x
7. Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F. Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol. 2005;62(4):487-491. doi: 10.1111/j.1365-2265.2005.02247.x
8. Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol. 2010;316(2):165-171. doi:10.1016/j.mce.2009.06.005