Thyroid Function of Twin-Pregnant Women in Early Pregnancy
Thyroid dysfunction is a common condition among pregnant women, with significant implications for both maternal and fetal health. The prevalence of various thyroid disorders, including overt hypothyroidism, subclinical hypothyroidism, isolated hypothyroidism, overt hyperthyroidism, and subclinical hyperthyroidism, has been well-documented. In China, the prevalence of clinical hypothyroidism, subclinical hypothyroidism, and thyroid peroxidase antibody (TPOAb) positivity during the first half of pregnancy is reported to be 0.6%, 5.27%, and 8.6%, respectively. Abnormal thyroid function or thyroid autoimmunity during pregnancy can increase the risk of adverse pregnancy outcomes, such as premature delivery and miscarriage, as well as obstetric complications like gestational diabetes, gestational hypertension, and preeclampsia. Furthermore, it may influence the neurocognitive development of the offspring.
To accurately diagnose thyroid dysfunction during pregnancy, the 2012 Chinese Guidelines for the Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum recommend that different regions establish their own specific reference ranges for thyroid-related indicators according to the National Academy of Clinical Biochemistry (NACB) recommendations. However, most established thyroid-specific reference ranges for pregnancy are based solely on singleton pregnancies. Only a few studies have focused on establishing reference ranges for thyroid indicators in twin pregnancies, and data for the Chinese population are particularly scarce. Given that different ethnicities and iodine statuses can influence the establishment of reference ranges, there is an urgent need for data specific to Chinese twin-pregnant women.
In twin pregnancies, serum human chorionic gonadotrophin (hCG) levels are higher than in singleton pregnancies. Since hCG stimulates the thyroid to produce more free thyroxine (FT4), this may lead to decreased thyroid-stimulating hormone (TSH) levels. Consequently, the reference ranges for thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and compare them with those in singleton pregnancies.
The study extracted data from 820 twin-pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018. After applying strict inclusion and exclusion criteria, 160 twin-pregnant women were included to establish reference ranges for TSH and FT4. Additionally, 480 singleton-pregnant women were screened from the same database as controls. The inclusion criteria for the control group were similar age, same gestational age, and thyroid function detection at the same gestational weeks as the twin-pregnant women. The time interval of thyroid function detection between the paired single- and twin-pregnant women was within two months.
Serum TSH and FT4 were measured using electrochemiluminescence immunoassays, and TPOAb was measured using electrochemiluminescence immunoassays with a Cobas 601 immunoanalyzer. The normal reference ranges of the kit for the non-pregnant population were as follows: TSH 0.55 to 4.78 mIU/L and FT4 11.48 to 22.70 pmol/L; TPOAb over 34 IU/mL was considered positive. The inter-assay coefficients of TSH, FT4, and TPOAb were as follows: 2.05% to 5.31%, 0.8% to 2.7%, and 2.8% to 4.8%.
The reference ranges for TSH and FT4 in twin pregnancies during the first trimester (4–12 gestational weeks) were established as follows: TSH 0.69 (0.01–3.35) mIU/L and FT4 16.38 (12.45–23.34) pmol/L. The median TSH level was significantly lower at 7 to 12 gestational weeks than at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z = -1.964, P = 0.049); however, FT4 levels did not significantly differ between the two groups. Compared to singleton pregnancies, the median TSH level was significantly lower (0.69 vs. 1.27 mIU/L, Z = -6.538, P < 0.001), and the FT4 level was significantly higher (16.38 vs. 14.85 pmol/L, Z = -7.399, P < 0.001) in twin pregnancies during the first trimester.
At 4 to 6 gestational weeks, TSH in twin-pregnant women was significantly lower (0.96 vs. 1.66 mIU/L, Z = -2.691, P = 0.007), and an increasing trend in FT4 levels was observed in twin-pregnant women (16.08 vs. 15.39 pmol/L, Z = -1.823, P = 0.068), though the difference was not statistically significant. At 7 to 12 gestational weeks, TSH was lower (0.62 vs. 1.20 mIU/L, Z = -6.165, P < 0.001), and FT4 was higher (16.46 vs. 14.77 pmol/L, Z = -7.163, P < 0.001) in twin pregnancies than in singleton pregnancies.
The distribution of TSH levels in twin-pregnant women was shifted to the left compared to singleton-pregnant women in the first trimester, indicating that the median TSH level in twin-pregnant women was significantly lower than that in singleton-pregnant women. This phenomenon is likely due to the higher and more prolonged levels of hCG in twin pregnancies, which have a greater impact on TSH suppression. The a-hCG sub-unit is structurally similar to TSH, and hCG exhibits thyrotropic properties, particularly in the first trimester of pregnancy. Studies have shown that the peak of both intact and free b-hCG is strikingly higher and lasts longer in twin pregnancies than in singleton pregnancies, leading to a more pronounced physiological suppression of TSH.
The upper limit of the TSH reference range in twin-pregnant women was slightly higher than that in singleton-pregnant women (3.35 vs. 3.28 mIU/L). However, due to the small sample size of twin-pregnant women, the upper limit of the reference range for TSH would be elevated even if only a few cases showed high TSH levels. Additionally, women with serum TSH levels above 2.5 mIU/L who received levothyroxine (L-T4) treatment were excluded from the study, which may have suppressed the upper limit of the reference range for TSH.
Serum FT4 levels were significantly higher in twin pregnancies than in singleton pregnancies during the first trimester. This finding is consistent with other studies, which have demonstrated that fetal number correlates positively with serum FT4 levels. The higher FT4 levels in twin pregnancies may be attributed to the greater impact of hCG on thyroid function.
The study also highlighted the importance of establishing separate reference ranges for 4 to 6 weeks and 7 to 12 weeks of gestation in twin pregnancies. The median TSH level at 7 to 12 gestational weeks was significantly lower than that at 4 to 6 gestational weeks in twin pregnancies, likely due to the greater impact of hCG on TSH suppression. Establishing reference ranges for thyroid indicators at much earlier gestational periods (4–6 weeks) has clinical significance for the early diagnosis of thyroid dysfunction and intervention.
In conclusion, serum TSH and FT4 levels in early pregnancy differ significantly between singleton and twin pregnancies. Therefore, it is essential to establish specific reference ranges for thyroid-related indicators for twin pregnancies to avoid misdiagnosis of thyroid dysfunction in the first trimester. Additionally, establishing separate reference ranges for 4 to 6 weeks and 7 to 12 weeks of gestation may be important for assessing thyroid function in twin pregnancies. This study provides valuable data for the Chinese population and emphasizes the need for further research to establish reference ranges for the second and third trimesters of twin pregnancies.
doi.org/10.1097/CM9.0000000000000381
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