First- and Second-Trimester Reference Intervals for Thyroid Hormones during Pregnancy in “Rhea” Mother-Child Cohort, Crete, Greece

Table 5

Worldwide summary of studies reporting 1st and 2nd trimester-specific reference intervals for thyroid hormones during pregnancy.

Study	Country (subgroups)	Sample size	Exclusion criteria	Assay used/test (units)	Reference limits
					1st trimester	2nd trimester
Price et al., 2001 [23]	UK (Caucasians/Asians)	120	(i) Serious gestational events; (ii) Endocrinological medication	CL (ACS 180, Bayer); TSH (mIU/L); Free T4 (pmol/L)	Caucasians (𝑛=50): TSH: 0.7–1.1; Free T4: 12.0–12.8; Asians (𝑛=20): TSH: 0.6–1.3; Free T4: 11.8–13.4	Caucasians (𝑛=50): TSH: 1.2–1.5; Free T4: 11.2–11.8; Asians (𝑛=20): TSH: 1.0–1.8; Free T4: 10.9–12.1
Panesar et al., 2001 [9]	China	406	(i) Thyroid disease; (ii) Serious gestational events (incl. hyperemesis, trophoblastic disease, preeclampsia)	CL (ACS 180, Chiron Diagn.); TSH (mIU/L); Free T4 (pmol/L); Free T3 (pmol/L)	—^a	—^a
Haddow et al., 2004 [13]	USA	1126	(i) Thyroid Ab(+)	CL (Immulite, Siemens); TSH (mIU/L)	(𝑛=1005); TSH: 0.08–2.73	(𝑛=1005); TSH: 0.39–2.70
Kurioka et al., 2005 [14]	Japan	522	(i) Multiple pregnancies	ECL (Elecsys, Roche); TSH mIU/mL; Free T4 (ng/dL); Free T3 (pg/mL)	(𝑛=119); TSH: 0.04–3.39; Free T4: 1.16–1.95; Free T3: 2.68–4.59	(𝑛=132); TSH: 0.17–3.72; Free T4: 0.89–1.39; Free T3: 2.56–4.11
Dhatt et al., 2006 [24]	United Arab Emirates; (United Arabs/Other Arabs/Asians)	1140	(i) Multiple pregnancies; (ii) Thyroid Ab(+); (iii) Thyroid disease; (iv) Thyroid medication; (v) Serious gestational events (incl. hyperemesis)	CL (Architect, Abbott); TSH (mIU/L); Free T4 (pmol/L)	United Arabs (𝑛=97): TSH: 0.06–8.3; Free T4: 8.9–24.6; Other Arabs (𝑛=122): TSH: 0.04–9.3; Free T4: 10.5–22.3; Asians (𝑛=79): TSH: 0.12–7.4; Free T4: 11.3–2.19	United Arabs (𝑛=252): TSH: 0.17–5.9; Free T4: 8.4–19.3; Other Arabs (𝑛=283): TSH: 0.23–5.7; Free T4: 9.5–18.7; Asians (𝑛=174): TSH: 0.3–5.5; Free T4: 9.7–18.5
Stricker et al., 2007 [12]	Switzerland	2272	(i) Thyroid Ab(+); (ii) Thyroid medication; (iii) Miscarriage; (iv) Fetal genetic abnormality	CL (Architect, Abbott); TSH (mIU/L); Free T4 (pmol/L); Free T3 (pmol/L)	(𝑛=783); TSH: 0.0888–2.8293; Free T4: 10.53–18.28; Free T3: 3.52–6.22	(𝑛=528); TSH: 0.1998–2.7915; Free T4: 9.53–15.68; Free T3: 3.41–5.78
La’ulu and Roberts, 2007 [19]	USA (Asians/Blacks/; Hispanics/Whites)	3064	(i) Thyroid Ab(+)	CL (Architect, Abbott); TSH (mIU/L); Free T4 (pmol/L); Free T3 (pmol/L)	—	(𝑛=2683)^b; TSH: 0.15–3.11; Free T4: 9.3–15.2; Free T3: 3.83–5.96
Cotzias et al., 2008 [15]	UK	335	(i) Multiple pregnancies; (ii) Thyroid/endocrine disease; (iii) Serious gestational events (incl. preeclampsia, hyperemesis); (iv) Medication; (v) Age < 15 & >45	CL (Advia Centaur, Siemens); TSH (mIU/L),; Free T4 (pmol/L); Free T3 (pmol/L)	—^a	—^a
Lambert-Messerlian et al., 2008 [16]	USA	9562	(i) Multiple pregnancies; (ii) Thyroid disease	CL (Immulite, Siemens); TSH (mIU/L)	(𝑛=9562); TSH: 0.13–4.15	(𝑛=9562); TSH: 0.36–3.77
Gong and Hoffman, 2008 [17]	Canada	340	(i) Thyroid Ab(+); (ii) TSH < 0.1 mIU/L; (iii) TSH > 2.5 mIU/L (1st trimester); (iv) TSH > 3.0 mIU/L (2nd trimester); (v) TSH > 3.5 mIU/L (3rd trimester)	ECL (Modular E170, Roche); Free T4 (pmol/L)	(𝑛=224); Free T4: 11–19	(𝑛=240); Free T4: 9.7–17.5
Pearce et al., 2008 [25]	USA	668	(i) Multiple pregnancies; (ii) Thyroid Ab(+); (iii) Thyroid disease; (iv) Thyroid medication; (v) TSH >5.5 mIU/L in Ab(−) women; (vi) Miscarriages/fetal death	CL (Advia Centaur, Bayer); TSH (mIU/L)	(𝑛=585); TSH: 0.04–3.6	—
Marwaha et al., 2008 [11]	India	541	(i) Thyroid Ab(+); (ii) Thyroid disease; (iii) Thyroid medication; (iv) Family history of thyroid disease; (v) Thyroid hypoechogenicity/nodularity (US); (vi) History of abortions and hyperemesis	ECL (Elecsys, Roche); TSH (mIU/mL); Free (T4 pmol/L); Free (T3 pmol/L)	(𝑛=107); TSH: 0.6–5.0; Free T4: 12–19.45; Free T3: 1.92–5.86	(𝑛=137); TSH: 0.435–5.78; Free T4: 9.48–19.58; Free T3: 3.2–5.7
Gilbert et al., 2008 [26]	Australia	2159	(i) Thyroid Ab(+); (ii) Thyroid disease	CL (Architect, Abbott); TSH (mIU/L); Free T4 (pmol/L); Free T3 (pmol/L)	(𝑛=1817); TSH: 0.02–2.15; Free T4: 10.4–17.8; Free T3: 3.3–5.7	—
Springer et al., 2009 [18]	Czech republic	5520	(i) Thyroid Ab(+); (ii) Thyroid diseases; (iii) β-HCG > 56 mg/L	CL (Advia Centaur, Siemens); TSH (mIU/L)	(𝑛=4337); TSH: 0.06–3.67	—
Bocos-Terraz et al., 2009 [10]	Spain	1198	(i) Thyroid Ab(+); (ii) Thyroid disease	CL (Architect, Abbott); TSH (𝜇IU/mL); Free T4 (ng/dL); Free T3 (pg/mL)	—^a	—
Ashoor et al., 2010 [27]	UK (Blacks/Whites)	4318	(i) Multiple pregnancies; (ii) Thyroid Ab(+); (iii) Thyroid disease; (iv) Serious gestational events (incl. preeclampsia, miscarriage/fetal death, delivery <34 weeks); (v) Major fetal abnormalities; (vi) Birth weight < 5th percentile	CL (Advia Centaur, Siemens); TSH (mIU/L); Free T4 (pmol/L); Free T3 (pmol/L)	—^a	—
Garía de Guadiana Romualdo et al., 2010 [29]	Spain	441	(i) Thyroid Ab(+); (ii) Thyroid disease incl. goiter; (iii) Thyroid medication	ECL (Cobas, Roche); TSH (mUI/L); Free T4 (ng/dL)	(𝑛=400); TSH: 0.130–3.710; Free T4: 0.89–1.50	—
Yu et al., 2010 [30]	China	538	(i) Multiple pregnancies; (ii) Thyroid disease incl. goiter; (iii) Thyroid Ab(+); (iv) History of autoimmune diseases; (v) Serious gestational events (incl. hyperemesis, hypertension, gestational diabetes, premature delivery); (vi) Medical history affecting thyroid function; (vii) Abnormal urinary iodine	ECL (Cobas, Roche); TSH (mUI/L); Free T4 (pmol/L)	(𝑛=301); TSH: 0.02–3.65; Free T4: 11.85– 21.51	(𝑛=301); TSH: 0.36– 3.46; Free T4: 9.45–16.26
Männistö et al., 2011 [31]	Finland	5805	(i) Multiple pregnancies; (ii) Thyroid Ab(+); (iii) Thyroid disease; (iv) Thyroid medication	CL (Architect, Abbott); TSH (mIU/L); Free T4 (pmol/L); Free T3 (pmol/L)	— ^a	—^a
Yan et al., 2011 [8]	China	505	(i) Multiple pregnancies; (ii) Thyroid Ab(+); (iii) Thyroid disease incl. goitre; (iv) Family history of thyroid disease; (v) TSH > 5.0 mIU/l; (vi) Serious gestational events; (vii) Endocrinological medication	CL (Advia Centaur, Bayer); TSH (mIU/L); Free T4 (pmol/L); Free T3 (pmol/L)	(𝑛=168); TSH: 0.03–4.51; Free T4: 11.8–21; Free T3: 3.57– 5.61	(𝑛=168); TSH: 0.05–4.50; Free T4: 10.6–17.6; Free T3: 3.55– 5.25
Santiago et al., 2011 [28]	Spain	429	(i) Thyroid Ab(+); (ii) TSH > 5 𝜇IU/mL; (iii) Major health problems	CL (Beckman access); TSH (𝜇IU/mL); Free T4 (ng/dL); Free T3 (pg/mL)	(𝑛=279); TSH: 0.23– 4.18; Free T4: 0.60–1.06; Free T3: 2.33–3.84	(𝑛=210); TSH: 0.36–3.89; Free T4: 0.43–0.85; Free T3: 2.04–3.51

^areference intervals other than trimester-specific (data not shown);
^bcombined reference interval for all ethnicities; reference intervals also provided for ethnicity subgroups (data not shown).
CL: Chemiluminescence assay; ECL: Electrochemiluminescence assay; TSH; thyroid-stimulating hormone; Free T4; serum-free thyroxine; Free T3; serum-free triiodothyronine;
to convert to SI units, for
FT4: pmol/L = ng/dL 𝑥12.87
FT3: pmol/L = pg/mL 𝑥1.536.