Natural changes of maternal thyroid function among women with subclinical thyroid dysfunction and euthyroid women during pregnancy

Objective To analyze the natural changes of maternal thyroid function among women with subclinical thyroid dysfunction and euthyroid women during pregnancy.Methods A total of 4 042 singleton pregnant women received routine antenatal care in the Obstetrics and Gynecology Hospital of Fudan University between April and November 2012 were enrolled.Thyroid-stimulatinghormones (TSH),freetriiodothyronine (FT3) and free thyroxine (FT4) of 7 136 samples from 4 042 singleton pregnant women were tested at 8-12+6,13-19+6,20-27+6,and 28-40 weeks of gestation and were used to establish the normal gestationalspecific reference values of thyroid function.Among 3 895 women having thyroid function tested at 8-19+6 weeks of gestation with negative thyroid antibodies,there were 93 cases of subclinical hyperthyroidism,91 cases of subclinical hypothyroidism (SCH),three cases of hyperthyroidism and 3 708 cases euthyroid.There were 1 118 women [1 607 euthyroid cases,17 cases of subclinical hypothyroidism (SCH) and 34 cases of subclinical hyperthyroidism] had thyroid function retested at 20-27+6 and 28-40 weeks of gestation,and without medicinal intervention.Analysis of variance and LSD test were used to analyze the changes of maternal thyroid function.Results (1) The reference ranges of TSH at 8-12+6,13-19+6,20 27+6 and 28-40 weeks of gestation [median (Pz5-P97.5)] were 1.32 (0.03-4.17),1.83 (0.19-4.94),2.27 (0.70-5.42) and 2.34 (0.63-5.52) mU/L respectively.(2) Without medicinal intervention,thyroid function became normal in 80％ (45/56) SCH women at 20-27+6 weeks,but 20％ (9/45) of them developed SCH again at 28-40 weeks.The thyroid function became normal in 75％ (70/93) women with subclinical hyperthyroidism at 20-27+6 weeks,but in 15％ (14/93) of them,thyroid function remained abnormal at 28-40 weeks.9.40％ (30/319) and 6.25％ (21/336) euthyroid women with TSH ≥ 3 mU/L at 8-19+6 weeks of gestation developed SCH at 20-27+6 weeks and 28-40 weeks,while 0.42％ (5/1 202) and 0.86％ (10/1 163) euthyroid women with TSH ＜3 mU/L had SCH.1.66％ (20/1 202) and 1.98％ (23/1 163) euthyroid women with TSH＜3 mU/L at 8-19+6 weeks of gestation developed subclinical hyperthyroidism at 20-27+6 weeks and 28-40 weeks of gestation.(3) In comparison between 8-19+6 weeks and 20-27+6 weeks of gestation,TSH levels increased by (0.47±0.03) mU/L in euthyroid women,and more significantly in subclinical hyperthyroidism women [(0.82±0.06) mU/L],but decreased by (1.67±0.25) mU/L in SCH women (LSD test,all P＜0.05).The FT3 levels decreased by (0.47±0.02) pmol/L in euthyroid women,and more significantly in subclinical hyperthyroidism and SCH groups [(1.02± 0.18) and (0.72±0.08) pmol/L,LSD test,all P＜0.05].FT4 decreased by (2.31 ±0.04) pmol/L in euthyroid women,and more significanly in subclinical hyperthyroidism women [(4.63± 0.62) pmol/L] (LSD test,P＜0.05),but the decrement in SCH group [(1.78±0.28) pmol/L] was similar to euthyroid women (LSD test,P＞0.05).There were no significant differences in changes of TSH,FT3 and FT4 at 20-27+6 weeks and 28-40 weeks among euthyroid women,SCH and subclinical hyperthyroidism groups (F=1.01,1.14 and 2.04,all P＞0.05).Conclusions Women with subclinical thyroid dysfunction with negative thyroid antibodies experience significantly different natural changes when compared with euthyroid women,especially before 28 weeks of gestation. Key words: Pregnancy complications;  Hypothyroidism;  Hyperthyroidism;  Thyrotropin;  Triiodothyronine;  Thyroxine;  Reference values