CATS II Long-term Anthropometric and Metabolic Effects of Maternal Sub-optimal Thyroid Function in Offspring and Mothers

Context and Objectives: The Controlled Antenatal Thyroid Screening Study I (CATS-I) was a randomized controlled trial investigating the effects of levothyroxine therapy for suboptimal gestational thyroid function (SGTF), comparing outcomes in children of treated (SGTF-T) with untreated (SGTF-U) women during pregnancy. This follow-up study, CATS-II, reports the longterm effects on anthropometric, bone, and cardiometabolic outcomes in mothers and offspring and includes a group with normal gestational thyroid function (NGTF). Design & Participants. 332 mothers (197 NGTF, 56 SGTF-U, 79 SGTF-T) aged 41.2 +/- 5.3 years (mean +/- SD) and 326 paired children assessed 9.3 +/- 1.0 years after birth for (i) body mass index (BMI); (ii) lean, fat, and bone mass by dual-energy X-ray absorptiometry; (iii) blood pressure, augmentation index, and aortic pulse-wave-velocity; and (iv) thyroid function, lipids, insulin, and adiponectin. The difference between group means was compared using linear regression. Results. Offspring's measurements were similar between groups. Although maternal BMI was similar between groups at CATS-I, after 9 years (at CATS-II) SGTF-U mothers showed higher BMI (median [interquartile ratio] 28.3 [24.6-32.6] kg/m(2)) compared with NGTF (25.8 [22.9-30.0] kg/m(2) ; P= 0.029), driven by fat mass increase. At CATS-II SGTF-U mothers also had higher thyroid-stimulating hormone (TSH) values (2.45 [1.43-3.50] mU/L) than NGTF (1.54 [1.12-2.07] mU/L; P = 0.015), since 64% had never received levothyroxine. At CATS-II, SGTF-T mothers had BMI (25.8 [23.1-29.8] kg/m(2), P = 0.672) and TSH (1.68 [0.89-2.96] mU/L; P= 0.474) values similar to NGTF mothers. Conclusions. Levothyroxine supplementation of women with SGTF did not affect long-term offspring anthropometric, bone, and cardiometabolic measurements. However, absence of treatment was associated with sustained long-term increase in BMI and fat mass in women with SGTF.