Gestational TSH And FT4 Reference Intervals In Chinese Women:A Systematic Review And Meta-analysis

Background: Serum thyroid-stimulating hormone(TSH)and free thyroxine(FT4)change dynamically during pregnancy.Differences in geographic regions,populations,and manufacturer's methodologies can affect the reference intervals for thyroid function tests.The 2017 guidelines of the American Thyroid Association(ATA)recommended 4.0mU/L as the cut-off point for the upper limit of serum TSH in early pregnancy.A systematic review is called for to establish practical,gestational-specific TSH and FT4 reference intervals for pregnant Chinese women and to explore whether the criteria are suitable for China.Methods: English and Chinese articles published from inception to Aug 2017 were searched in the PubMed,EMBASE,and SCIE English-language databases and Chinese databases.The relative descent or ascent rates of serum TSH and FT4 were calculated,after which Comprehensive Meta-Analysis V2.0 software was used to analyze the data.Results: Eleven studies(6 in English and 5 in Chinese),five kits and 11,629 Chinese women from nine cities were considered in this meta-analysis.Compared with the reference ranges provided by manufacturers,serum TSH decreased in the first trimester,with the upper limit declining by 21.7%(5.0%-36.6%),to a value close to 4.0 mU/L,and the lower limit declining by 85.7%(73.5%-97.1%).It continued decreasing in the second trimester,with the upper limit declining by 24.0%(6.4%-40.9%)and the lower limit declining by 40.7%(9.0%-85.7%).For FT4,the upper limit fluctuated slightly,and the lower limit increased by 6.8%(1.0%-14.6%)in the first trimester.Serum FT4 dropped gradually,with the upper limit declining by 21.8%(2.5%-31.8%)and the lower limit declining by 12.7%(2.6%-19.6%)in the second trimester.During the third trimester,the upper limit decreased by 25.1%(12.7%-35.0%),while the lower limit decreased by 20.9%(14.8%-27.3%).Conclusions: Various regions,kits and test methods affect the gestational TSH and FT4 levels.The non-pregnant serum TSH upper limit minus 22% is very close to 4.0 mU/L,which can be used as a sub-optimal approach to represent the cut-off value for pregnant Chinese women in the first trimester.