Journal of Thyroid Research / 2011 / Article / Tab 5

Research Article

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.

StudyCountry (subgroups)Sample sizeExclusion criteriaAssay used/test (units)Reference limits
1st trimester2nd 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 ( ):
TSH: 0.7–1.1
Free T4: 12.0–12.8
Asians ( ):
TSH: 0.6–1.3
Free T4: 11.8–13.4
Caucasians ( ):
TSH: 1.2–1.5
Free T4: 11.2–11.8
Asians ( ):
TSH: 1.0–1.8
Free T4: 10.9–12.1

Panesar et al., 2001 [9]China406(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)
aa

Haddow et al., 2004 [13]USA1126(i) Thyroid Ab(+)CL (Immulite, Siemens)
TSH (mIU/L)
( )
TSH: 0.08–2.73
( )
TSH: 0.39–2.70

Kurioka et al., 2005 [14]Japan522(i) Multiple pregnanciesECL (Elecsys, Roche)
TSH mIU/mL
Free T4 (ng/dL)
Free T3 (pg/mL)
( )
TSH: 0.04–3.39
Free T4: 1.16–1.95
Free T3: 2.68–4.59
( )
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 ( ):
TSH: 0.06–8.3
Free T4: 8.9–24.6
Other Arabs ( ):
TSH: 0.04–9.3
Free T4: 10.5–22.3
Asians ( ):
TSH: 0.12–7.4
Free T4: 11.3–2.19
United Arabs ( ):
TSH: 0.17–5.9
Free T4: 8.4–19.3
Other Arabs ( ):
TSH: 0.23–5.7
Free T4: 9.5–18.7
Asians ( ):
TSH: 0.3–5.5
Free T4: 9.7–18.5

Stricker et al., 2007 [12]Switzerland2272(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)
( )
TSH: 0.0888–2.8293
Free T4: 10.53–18.28
Free T3: 3.52–6.22
( )
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)
( )b
TSH: 0.15–3.11
Free T4: 9.3–15.2
Free T3: 3.83–5.96

Cotzias et al., 2008 [15]UK335(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)
aa

Lambert-Messerlian et al., 2008 [16]USA9562(i) Multiple pregnancies
(ii) Thyroid disease
CL (Immulite, Siemens)
TSH (mIU/L)
( )
TSH: 0.13–4.15
( )
TSH: 0.36–3.77

Gong and Hoffman, 2008 [17]Canada340(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)
( )
Free T4: 11–19
( )
Free T4: 9.7–17.5

Pearce et al., 2008 [25]USA668(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)
( )
TSH: 0.04–3.6

Marwaha et al., 2008 [11]India541 (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)
( )
TSH: 0.6–5.0
Free T4: 12–19.45
Free T3: 1.92–5.86
( )
TSH: 0.435–5.78
Free T4: 9.48–19.58
Free T3: 3.2–5.7

Gilbert et al., 2008 [26]Australia2159(i) Thyroid Ab(+)
(ii) Thyroid disease
CL (Architect, Abbott)
TSH (mIU/L)
Free T4 (pmol/L)
Free T3 (pmol/L)
( )
TSH: 0.02–2.15
Free T4: 10.4–17.8
Free T3: 3.3–5.7

Springer et al., 2009 [18]Czech republic5520(i) Thyroid Ab(+)
(ii) Thyroid diseases
(iii) β-HCG > 56 mg/L
CL (Advia Centaur, Siemens)
TSH (mIU/L)
( )
TSH: 0.06–3.67

Bocos-Terraz et al., 2009 [10]Spain1198(i) Thyroid Ab(+)
(ii) Thyroid disease
CL (Architect, Abbott)
TSH ( IU/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]Spain441(i) Thyroid Ab(+)
(ii) Thyroid disease incl. goiter
(iii) Thyroid medication
ECL (Cobas, Roche)
TSH (mUI/L)
Free T4 (ng/dL)
( )
TSH: 0.130–3.710
Free T4: 0.89–1.50

Yu et al., 2010 [30]China538(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)
( )
TSH: 0.02–3.65
Free T4: 11.85– 21.51
( )
TSH: 0.36– 3.46
Free T4: 9.45–16.26

Männistö et al., 2011 [31]Finland5805(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)
aa

Yan et al., 2011 [8]China505(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)
( )
TSH: 0.03–4.51
Free T4: 11.8–21
Free T3: 3.57– 5.61
( )
TSH: 0.05–4.50
Free T4: 10.6–17.6
Free T3: 3.55– 5.25

Santiago et al., 2011 [28]Spain429(i) Thyroid Ab(+)
(ii) TSH > 5  IU/mL
(iii) Major health problems
CL (Beckman access)
TSH ( IU/mL)
Free T4 (ng/dL)
Free T3 (pg/mL)
( )
TSH: 0.23– 4.18
Free T4: 0.60–1.06
Free T3: 2.33–3.84
( )
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
FT3: pmol/L = pg/mL .

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