() Diagnostic IV 351 Aim: To establish trimester-specific thyroid function reference intervals throughout pregnancy, and to examine the prevalence of thyroid autoimmunity in otherwise euthyroid women. Setting: Cork University Hospital, Ireland Population: Pregnant women (median age 30) attending a large, tertiary referral maternity hospital. Patients with known thyroid disorders, autoimmune disease, recurrent miscarriage, hyperemesis gravidarum and pre-eclampsia were excluded. Measurements: TFTs were analysed in the CUH biochemistry laboratory Roche Modular E170 electrochemiluminescent immunoassay. Trimester-specific reference ranges (2.5th, 50th and 97.5th centiles) were calculated. TSH concentrations showed slightly increasing median centile throughout gestation (. Free thyroxine (T4) and T3 decreased throughout gestation. Derived reference ranges (2.5th to 97.5th percentiles) for TSH exclusive of TPO positive women were: Week 12: 0.2–3.0 Week 14–16: 0.2–3.1 Week 18–22: 0.3–3.1 Week 24: 0.4–3.1 Week 26–28: 0.4–3.2 Week 30–32: 0.5–3.2 Week 34: 0.5–3.3 Week 36–38: 0.6–3.3 Week 40: 0.7–3.3 trial trial
() Cohort III-2 1,600 Aim: To compare universal testing with targeted high-risk case findings for early diagnosis of thyroid disorders in Iranian pregnant women. Setting: Iran Population: Pregnant women in their first trimester, of whom 656 (44.3%) had at least one risk factor for thyroid diseases and were eligible for the targeted high-risk case finding (high-risk group) approach, while 55.7% had no risk factors (low-risk group; n=944). Observations: A checklist, including all related risk factors recommended by the American Thyroid Association, was completed for all participants. Serum concentrations of thyroxine (T4), T-uptake, TSH and thyroid peroxidase antibody (TPOAb) were measured and thyroid status was documented, based on hormonal measurements and clinical examinations. Using the universal testing approach, there were 974 women (65.8%) with normal thyroid status and 506 participants (34.2%) with thyroid disturbances, including overt hyperthyroidism (0.7%), overt hypothyroidism (1.1%), subclinical hypothyroidism (30.1%; positive TPOAb (5.5%) and negative TPOAb (24.6%); and euthyroid and positive TPOAb (2.3%). Of women with thyroid dysfunction, 64.4% were in the high-risk group and 35.6% were in the low-risk group (P<0.0001). The targeted high-risk case finding approach overlooks one-third of pregnant women with thyroid dysfunction. If ongoing prospective trials provide evidence on the efficacy of treating subclinical hypothyroidism in pregnancy, in populations with a low prevalence of presumed risk factors, the targeted high-risk case finding approach will be proven inefficient.
() Cohort III-2 1,889 Aim: To explore the influence of different testing strategies on the prevalence of thyroid dysfunction and the missed diagnosis during pregnancy. Setting: International Maternity and Child Health Hospital, Shanghai Population: Pregnant (13-27 weeks) divided into high-risk and low-risk groups according to backgrounds collected by questionnaire. High-risk women accounted for 10.69%. Observations: We detected the prevalence of thyroid dysfunction in high-risk groups and low-risk pregnant women by normal reference range during the second trimester. Using targeted high-risk case testing strategy, misdiagnosis rate of pregnancy with hyperthyroidism, subclinical hyperthyroidism, pregnancy with hypothyroidism, subclinical hypothyroidism, low T4 syndrome and positive TPOAb were 87.5% (14 cases), 87.08% (155 cases), 87.08% (155 cases), 83.93% (47 cases), 89.47% (17 cases) and 88.35% (91 cases), respectively. There was no statistically significant difference between the high-risk and low-risk groups in the prevalence of thyroid dysfunction. Therefore, we believe that universal testing of pregnant women can effectively reduce misdiagnosis rate of thyroid dysfunction. Further, we recommend universal testing for thyroid function in second trimester of pregnancy. Another study conducted at the same hospital () notes that the study area is an and adequate area
3.2 Universal testing versus no testing Thyroid dysfunction Study ref Design LoE N Aim, setting, population, measurements/observations Results Limitations/ Comments () SLR I 26,408 (2 RCTs) In the other (n=21,846), before 15 + 6 weeks' gestation, women in the universal testing group had their sera tested; women who tested 'positive' (TSH > 97.5th percentile, fT4 < 2.5th percentile, or both) received levothyroxine. Compared with the no testing group, more women in the universal testing group tested 'positive' for hypothyroidism (RR 998.18, 95% CI 62.36 to 15,978.48; 21,839 women; GRADE: high). More women in the universal testing group received pharmacological treatment for thyroid dysfunction (RR 1102.90, 95% CI 69.07 to 17,610.46; n=1,050); 10% had their dose lowered because of low TSH, high fT4 or minor side effects. Cochrane review () RCT II 1,671 Aim: To evaluate the effect of subclinical hypothyroidism (SCH) testing and intervention on pregnancy outcomes. Setting: Peking Union Medical College Hospital (testing group; n=675) and Haidian Maternal & Child Health Hospital (control group whose serum was stored and measured shortly after delivery; n=996). Population: Exclusion criteria included age <18 years, ectopic pregnancy, twin pregnancy and known thyroid disease. Observations: Thyrotropin levels 2.5–10 mIU/L and free T4 levels in normal were considered SCH. Some of the testing group were treated with levothyroxine. The others had regular follow-up visits. 2.5<TSH≤10 was found in 252/996 from the control group and 167/675 from the testing group. In the testing group, 105 SCH and 4 hypothyroid women received thyroid hormone replacement therapy. High risk of bias; see Section 3.3
() Diagnostic yield IV 2,411 Aim: To determine if thyroid function tests performed with first trimester screening predicts adverse pregnancy outcomes. Setting: Western Australia Population: Women in with singleton pregnancies attending first trimester screening between 9 and 14 weeks gestation. Measurements: We evaluated the association between TSH, free T4, free T3, thyroid antibodies, free beta human chorionic gonadotrophin (beta-hCG) and pregnancy associated plasma protein A (PAPP-A) with a composite of adverse pregnancy events as the primary outcome. Secondary outcomes included placenta praevia, placental abruption, pre-eclampsia, pregnancy loss after 20 weeks gestation, threatened preterm labour, preterm birth, small size for gestational age, neonatal death, and birth defects. TSH exceeded the 97.5th percentile for the first trimester (2.15 mU/L) in 133 (5.5%) women, including 22 (1%) with TSH above the nonpregnant reference range (4 mU/L) and 5 (0.2%) above 10 mU/L. Adverse outcomes occurred in 327 women (15%). TSH and free T4 did not differ significantly between women with or without adverse pregnancy events. On the multivariate analysis, neither maternal TSH >2.15 mU/L nor TSH as a continuous variable predicted primary or secondary outcomes. Adding TSH to first trimester screening tests identifies mainly minor elevations in TSH, which do not predict adverse pregnancy outcomes. A small number of women with more significant hypothyroidism are also detected who should be routinely treated with thyroid replacement therapy. However, it remains uncertain whether testing is justified in order to detect these cases.