Epidemiological characteristics of congenital hypothyroidism and risk factors for permanent congenital hypothyroidism in Gansu, China

BACKGROUND: Congenital hypothyroidism (CH) is a major endocrine disorder affecting newborn development, and early differentiation between transient CH (T-CH) and permanent CH (P-CH) is essential for individualized management. This study aimed to describe epidemiological patterns of CH in Gansu Province, China from 2019 to 2021, compare clinical characteristics between T-CH and P-CH, and identify risk factors associated with P-CH to support improved early diagnosis and long-term management in primary care. METHODS: This retrospective cohort study was conducted using data from the Newborn Screening Center of Gansu Provincial Maternity and Child-care Hospital, a provincial referral center in Northwest China. A total of 757,157 newborns screened between January 2019 and December 2021 were included. Newborn heel-prick thyroid-stimulating hormone (TSH) was measured using time-resolved immunofluorescence assay, with TSH ≥ 9 mIU/L as the recall threshold. Recalled infants underwent confirmatory serum testing for TSH, free thyroxine (FT4), and total thyroxine (T4) using chemiluminescent immunoassays. Thyroid autoantibodies (TPOAb, TgAb) were assessed via electrochemiluminescence. Based on treatment response and thyroid function recovery after levothyroxine (L-T4) withdrawal, 275, a total of 332 infants were confirmed to have CH. Among them, 26 cases were excluded due to incomplete clinical data, infants diagnosed with CH were classified into T-CH (n = 87) and P-CH (n = 188) groups. RESULTS: The incidence of CH in Gansu was 0.044% (332/757,157, 1:2281), with a gradual increase from 2019 to 2021. Compared with T-CH infants, those with P-CH had significantly higher initial screening TSH (42.70 vs 22.45 mIU/L; P < 0.001), lower pretreatment FT4 and T4 levels (both with P < 0.001), markedly lower thyroid autoantibody positivity (1.1% vs 6.9%; P = 0.007), and higher birth weight (3520 vs 2850 g; P < 0.001). P-CH infants also required consistently higher age-specific maintenance doses of L-T4 throughout follow-up (all with P < 0.001). Multivariable logistic regression identified high birth weight (> 2500 g) as an independent risk factor for P-CH (OR = 7.788; 95% CI: 1.917-31.636), while thyroid autoantibody positivity was strongly associated with T-CH (OR = 0.084; 95% CI: 0.016-0.454). CONCLUSION: The incidence of CH in Gansu was slightly lower than the national average but demonstrated an upward trend. In our cohort of infants with positive newborn screening results, birth weight > 2500 g was associated with an increased likelihood of permanent CH and may serve as an early clinical indicator for distinguishing P-CH from T-CH. Thyroid autoantibody positivity was more commonly observed in transient CH and may suggest a more favorable prognosis. These findings highlight the importance of long-term follow-up and individualized L-T4 dose adjustment in screening-positive infants.