The Clinical Value and Variation of Antithyroid Antibodies during Pregnancy

Table 1

The diseases and guidelines associated with TRAbs, TPOAbs, and TgAbs.

	Diseases associated with antibodies	Relevant guidelines cited from the 2012 Guidelines of the Chinese Society of Endocrinology and Chinese Society of perinatal medicine for the diagnosis and management of thyroid disease during pregnancy and the postpartum period	Relevant guidelines cited from the 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum period
TRAbs	GD, GO, humoral immunity-induced hypothyroidism, infertility, miscarriage, preterm delivery, postpartum depression, PIH, left ventricular dysfunction, congestive heart failure, still birth, intrauterine growth restriction, GDM, preterm birth, and cesarean delivery; Low birth weight, poor growth, tachycardia, goiter, hyperthyroidism, and neonatal hypothyroidism	TSH implied the possibility of thyrotoxicosis, and the titer of FT4, TT4, TRAbs, and TPOAbs should be measured (recommendation rank A).; SGH needs to be distinguished from GD, which is accompanied by oculopathy and positive TRAbs and TPOAbs.; Thyroidectomy is the best choice in patients planning to conceive in 2 years with high TRAb titer.; The dosage of ATDs can be reduced in the middle or late trimester of pregnancy of GD patients, 20 to 30% who can stop the use of ATDs. However, pregnant patients with a high level of TRAbs should be excluded and they should be treated with ATDs until the end of pregnancy.; TRAb titer should be tested during thyroidectomy in order to assess the potential possibility of the occurrence of hyperthyroidism in the fetus.; Indications for the monitoring of TRAbs in GD patients are active maternal hyperthyroidism, medical history of I131 treatment, medical history of delivery of hyperthyroid infants, medical history of thyroidectomy as the treatment for hyperthyroidism during pregnancy.; Testing the TRAb titer is helpful to assess the pregnancy outcome. If the TRAb level is higher than three times than that of the reference level, the fetus should be monitored closely and with the involvement of a mother-infant therapist is recommended.; The measurement of TRAbs between 20 and 24 weeks of pregnancy in GD patients or patients who had GD before is recommended, because the titer of TRAbs will help doctors assess the outcome of pregnancy (recommendation rank B).; Monitoring fetal heart rate and fetal thyroid volume is recommended beginning in the middle period of pregnancy in pregnant women with high TRAb level (recommendation rank I).	Women with GD effectively treated with I131 ablation or surgical resection require TRAb monitoring beyond measurement of maternal thyroid function (strong recommendation, moderate-quality evidence).; Measurement of TRAbs and maternal TT3 may prove helpful in clarifying the etiology of thyrotoxicosis (strong recommendation, moderate-quality evidence).; In a newly pregnant woman with GD, who is euthyroid on a low dose of MMI (£5–10 mg/d) or PTU (£100– 200 mg/d), the physician should consider discontinuing all antithyroid medication given potential teratogenic effects. The decision to stop medication should take into account the disease history, goiter size, duration of therapy, the results of recent thyroid function tests, TRAb measurement, and other clinical factors (weak recommendation, low-quality evidence).; If maternal TRAb concentration is high (>3 times the upper reference for the assay), the fetus should be carefully monitored for the development of fetal hyperthyroidism throughout pregnancy, even if the mother is euthyroid post thyroidectomy (strong recommendation, high-quality evidence).; (a) If the patient has a past history of GD treated with ablation (radioiodine or surgery), a maternal serum determination of TRAbs is recommended during initial thyroid function testing during early pregnancy (strong recommendation, moderate-quality evidence).; (b) If maternal TRAb concentration is elevated in early pregnancy, repeat testing should occur at weeks 18–22 (strong recommendation, moderate-quality evidence).; (c) If maternal TRAbs are undetectable or low in early pregnancy, no further TRAb testing is needed (weak recommendation, moderate-quality evidence).; (d) If a patient is taking ATDs for treatment of Graves’ hyperthyroidism when pregnancy is confirmed, a maternal serum determination of TRAbs is recommended (weak recommendation, moderate-quality evidence).; (e) If the patient requires treatment with ATDs for GD through midpregnancy, a repeat determination of TRAbs is again recommended at weeks 18–22 (strong recommendation, moderate-quality evidence).; (f) If elevated TRAbs are detected at weeks 18–22 or the mother is taking ATD in the third trimester, a TRAb measurement should again be performed in late pregnancy (weeks 30–34) to evaluate the need for neonatal and postnatal monitoring (strong recommendation, high-quality evidence).; Fetal surveillance should be performed in women who have uncontrolled hyperthyroidism in the second half of pregnancy and in women with a high TRAb level detected at any time during pregnancy (greater than 3 times the upper limit of normal). A consultation with an experienced obstetrician or maternal–fetal medicine specialist is recommended. Monitoring may include ultrasound to assess heart rate, growth, amniotic fluid volume, and the presence of fetal goiter (strong recommendation, moderate-quality evidence).; A history of maternal thyroid illness, use of antithyroid medications (PTU, MMI) during gestation, or measurements of abnormal maternal thyroid function or TRAbs during gestation should be communicated to the newborn’s neonatologist or pediatrician (strong recommendation, moderate-quality evidence).
TPOAbs	Overt hypothyroidism, subclinical hypothyroidism, latent hypothyroidism GD, HT, GDM, anemia, miscarriage, premature delivery, perinatal death, low delivery rate, polyhydramnios, placental abruption, PPTD, PPT, postpartum depression, and infertility; Respiratory distress, neurodevelopmental deficits, low IQ, learning difficulties, and hearing deficits	The guideline does not support or oppose LT4 treatment in subclinical hypothyroid pregnant women with negative TPOAbs (recommendation rank I).; Hypothyroid patients accompanied with positive TPOAbs during pregnancy should be treated with LT4 (recommendation rank B).; The diagnostic criterion of positive thyroid autoantibodies is a TPOAb titer that surpasses the upper limit of the provided kit (recommendation rank A).; The TSH titer of euthyroid pregnant women with positive TPOAbs should be checked every 4 to 6 weeks in the first half of pregnancy. During 26 to 32 weeks of pregnancy, the TSH titer should be detected at least once. Once TSH surpasses the normal range, LT4 treatment should be implemented (recommendation rank B).; Treatment with LT4 cannot prevent the occurrence of PPT in TPOAb-positive pregnant women.; The screening of TSH, FT4, and TPOAbs before the eighth week of pregnancy is recommended (recommendation rank B).	When possible, population-based trimester-specific reference ranges for serum TSH should be defined through assessment of local population data representative of a health care provider’s practice. Reference range determinations should only include pregnant women with no known thyroid disease, optimal iodine intake, and negative TPOAb status (strong recommendation, moderate-quality evidence).; Euthyroid pregnant women who are TPOAb-positive or TgAb-positive should have the measurement of serum TSH concentration performed at time of pregnancy confirmation and every 4 weeks through midpregnancy (strong recommendation high-quality evidence).; Selenium supplementation is not recommended for the treatment of TPOAb-positive women during pregnancy (weak recommendation, moderate-quality evidence).; Insufficient evidence exists to conclusively determine whether LT4 therapy decreases pregnancy loss risk in TPOAb-positive euthyroid women who are newly pregnant. However, administration of LT4 to TPOAb-positive euthyroid pregnant women with a prior history of loss may be considered given its potential benefits in comparison with its minimal risk. In such cases, 25–50 lg of LT4 is a typical starting dose (weak recommendation, low-quality evidence).; Insufficient evidence exists to determine whether LT4 therapy improves the success of pregnancy following ART in TPOAb-positive euthyroid women. However, administration of LT4 to TPOAb-positive euthyroid women undergoing ART may be considered given its potential benefits in comparison to its minimal risk. In such cases, 25–50 lg of LT4 is a typical starting dose (weak recommendation, low-quality evidence).; When available, population- and trimester-specific reference ranges for serum TSH during pregnancy should be defined by a provider’s institute or laboratory and should represent the typical population for whom care is provided. Reference ranges should be defined in healthy TPOAb-negative pregnant women with optimal iodine intake and without thyroid illness (strong recommendation, high-quality evidence).; Pregnant women with TSH should be evaluated for TPOAb status.; Subclinical hypothyroidism in pregnancy should be approached as follows: (a) LT4 therapy is recommended for; (i) TPOAb-positive women with a TSH greater than the pregnancy-specific reference range (see recommendation 1) (strong recommendation, moderate-quality evidence).; (ii) TPOAb-negative women with a TSH greater than 10.0 mU/L (strong recommendation, low-quality evidence).; (b) LT4 therapy may be considered for; (i) TPOAb-positive women with TSH and below the upper limit of the pregnancy-specific reference range (weak recommendation, moderate-quality evidence).; (ii) TPOAb-negative women and TPOAb-negative women with TSH concentrations greater than the pregnancy-specific reference range and below 10.0 mU/L (weak recommendation, low-quality evidence).; (c) LT4 therapy is not recommended for - TPOAb-negative women with a normal TSH (TSH within the pregnancy-specific reference range or <4.0 mU/L if unavailable) (strong recommendation, high-quality evidence).; Women with overt and subclinical hypothyroidism (treated or untreated) or those at risk for hypothyroidism (e.g., patients who are euthyroid but TPOAb-positive or TgAb-positive, posthemithyroidectomy, or treated with radioactive iodine) should be monitored with a serum TSH measurement approximately every 4 weeks until midgestation and at least once near 30 weeks gestation (strong recommendation, high-quality evidence).; There is insufficient evidence to recommend for or against universal screening for abnormal TSH concentrations preconception, with the exception of women planning assisted reproduction or those known to have TPOAb positivity (no recommendation, insufficient evidence).
TgAbs	AITDs, gestational hypertension, and neonatal hypothyroidism