Table 3.

Thyroid function test results in multiple pregnancies.

Authors and year of publication	Adopted criteria/reference ranges	TSH	FT4 and FT3	Thyroid diseases
Grün, Meuris et al. 1997	TSH: 0.2-4.0 mU/l FT4: 10-26 pmol/l	• TSH decreased progressively until 10-11 GWs in SP and TP • TSH reduction appeared deeper and more prolonged in TP, however, no statistical difference was confirmed at each time point • 6/10 TP and 3/14 SP reached TSH ≦̸0.2 mU/l	• An elevation in FT4 appeared ↑ in TP, however, no statistical difference was confirmed at each time point • There was a rise in FT4 between 10-18 GWs in TP, while in SP, FT4 slightly decreased during pregnancy, however, no statistical difference was found at each time point • Pooled FT4 was ↑ between 8-15 GWs in TP than in SP • Although FT4 remained normal in SP, it was transiently supranormal in 4/13 TP	Not studied
Sakaguchi, Yoshimura et al. 1998	TSH: 0.4-4.7 mU/l FT4: 1.0-1.8 ng/dl FT3: 2.5-4.3 pg/ml	• In both SP and MP serum TSH levels were lowest in the 1st trimester • No difference was found in TSH levels between SP and MP in each trimester	• The mean FT3 and FT4 concentrations in MP did not differ from SP in each trimester	Not studied
Ogueh, Hawkins et al. 2000	No data	• There was no difference in TSH between SP and TP (at 10–12, 14–16 and 18–20 GWs), • Before fetal reduction, in MP TSH was ↓ compared to SP, but not to TP • After reduction to TP, TSH in MP was no different to TP values by 8 weeks	• There was no difference in FT4 between SP and TP (at 10–12, 14–16 and 18–20 GWs) • Before fetal reduction, FT4 was ↑ in MP than in SP or TP • After reduction to TP, FT4 decreased progressively in MP, but remained ↑ than in TP at 4 weeks after reduction	Not studied
Dashe, Casey et al. 2005	TSH: ± 2SD for the mean for GW on nomogram For details see Figure 1 in the original manuscript	• The decrease in TSH during the 1st trimester was ↑ in TP than in SP • In the 1st half of pregnancy, the threshold for identifying TSH elevation was approximately 0.4 mU/L ↓ in TP than in SP • For 1st trimester SP, the approximate upper limit of normal TSH was 4.0 MoM, and for TPs – 3.5 MoM; thereafter, the approximate upper limit was 2.5 MoM for SP and TP	Not studied	Not studied
Ashoor, Muto et al. 2013	Population-based: TSH and FT4 (2.5-97.5th pc of the healthy population: no thyroid disease, no DM, fetal abnormalities, PE, SGA, LBW), and depending on ethnicity, BMI and age For details see Table 2 and Table 3 in the original manuscript	• TSH MoM was ↓ in the ATA-negative TP with normal outcomes than in SP • TSH was no different between MC and DC • In the TTTS ATA-negative group, TSH was no different compared to normal TP For details see Table 2 and Table 3 in the original manuscript	• FT4 MoM was not different in the normal TP ATA-negative group than in SP • FT4 was not different between MC and DC • FT4 was not different in the TTTS ATA-negative group compared to normal TP	Not studied
Hanaoka, Arata et al. 2015	Hyperthyroidism: increased FT3 or FT4 levels with decreased or suppressed TSH	• TSH remained suppressed during 4 weeks after laser therapy	• When laser therapy was effective, FT3 and FT4 decreased progressively with HCG	Not studied
Rosner, Fox et al. 2017	Overt hypothyroidism – TSH >2.5 IU/mL and decreased FT4 based on the reference value provided via laboratory testing	The average level of TSH was 1.22 mIU/L	The average level of FT4 was 1.21 ng/dL	• 14% of TP had overt hypothyroidism at entry to healthcare • TP with overt hypothyroidism were more likely to have had IVF and pregestational diabetes • There was no difference in overt hypothyroidism rates between MC and DC
Šálek, Dhaifalah et al. 2018	Population-based: for TSH and FT4 (2.5-97.5th pc of the healthy part of the Caucasian population: no thyroid disease or TPOAb positivity) TSH [mU/L] SP 11-13+6 GWs: 0.16-3.43 TP 11-13+6 GWs: 0.02-2.95 FT4 [pmol/L] SP 11-13+6 GWs: 11.8-18.4 TP 11-13+6 GWs: 12.2-23.2	• In TP TSH during 1st trimester screening was ↓ than that in SP For details see Figure 2 in original manuscript	No details provided	Not studied
Šálek, Dhaifalah et al. 2019		No details provided	• FT4 was similar in TP and SP	• TP was associated with similar hypothyroidism prevalence as SP (6.4% vs 5.3%). However, all cases with TP were subclinical, while 92.4% of SP cases were subclinical and 7.6% were overt
Jiang, Sun et al. 2019	TP Population-based: for TSH and FT4 (2.5-97.5th pc of the healthy population: no thyroid disease, thyroid-interfering drugs or TPOAb positivity) 4-12 GWs TSH: 0.01–3.35 mIU/L FT4: 12.45–23.34 pmol/L 4-6 GWs TSH: 0.06–3.25 mIU/L FT4: 13.28–19.86 pmol/L 7-12 GWs TSH: 0.01–3.28 mIU/L FT4: 12.31–23.61 pmol/L	• In TP, TSH during 7-12 GWs was ↓ than that during 4-6 GWs • Between 4-12 GWs, TSH was ↓ in TP than in SP • Between 4-6 GWs, TSH was ↓ in TP than in SP • Between 7-12 GWs, TSH was ↓ in TP than in SP	• In TP, no difference was observed in FT4 levels between 7-12 GWs vs 4-6 GWs • In TP, an increasing trend was found in FT4 between 4-6 GWs; however, it was not statistically different from SP • Between 7-12 GWs, FT4 was ↑ in TP than in SP	Not studied
Chen, Yang et al. 2021	SP Population-based: for TSH and FT4 (2.5-97.5th pc of the healthy population: no TPs, IVF, thyroid disease, thyroid-interfering drugs or TPOAb positivity) TSH early: 0.03-3.60 mU/L late: 0.39-3.69 mU/L FT4 early: 11.7-19.8 pmol/L late: 9.1-14.4 pmol/L	• During early pregnancy TP was associated with ↓ TSH than SP • During late pregnancy TP was associated with ↑ TSH than SP	• During early pregnancy TP was associated with ↑ FT4 than in SP • During late pregnancy TP was associated with comparable FT4	At GWs 8-14 TP was associated with: • ↑ risk of overt hyperthyroidism, subclinical hyperthyroidism and isolated hypothyroxinemia, • ↓ risk of subclinical hypothyroidism, • The rate of subclinical hypothyroidism was 0.7%, overt hypothyroidism 1.8%, isolated hypothyroxinemia 4.7%, subclinical hyperthyroidism 7.2%, overt hyperthyroidism 8.5%, At GWs 28-35 TP was associated with: • ↑ risk of subclinical hypothyroidism, isolated hypothyroxinemia and subclinical hyperthyroidism • The rate of subclinical hypothyroidism was 8.2%, overt hypothyroidism 1.3%, isolated hypothyroxinemia 3.3%, subclinical hyperthyroidism 3.9%, overt hyperthyroidism 0.5%,
Liu, Su et al. 2022	TSH 2.5-97.5th pc for SP FT4 2.5-97.5th pc for SP	The median level of TSH was 0.85 mU/L	The median level of FT4 was 16.79 pmol/L	Not studied

ATA, anti-thyroid antibodies; DC, dichorionic; GA, gestational age; GW, gestational week; HCG, human chorionic gonadotropin; FT3, free triiodothyronine; FT4, free thyroxine; MC, monochorionic; MoM, multiples of median; MP, multiple pregnancies; pc, percentiles; SP, single pregnancies; TrP, triple pregnancies; TSH, thyroid stimulating hormone; TTTS, twin-to-twin transfusion syndrome; ↑, higher; ↓, lower.

Bolded values refer to studied population (multiple pregnancy and/or twin pregnancy).