新生儿期高促甲状腺素血症的短期预后研究及其影响因素

Short-term prognosis and influencing factors of hyperthyrotropinemia in neonates

背景关于新生儿期高促甲状腺激素血症(HT)患儿的临床转归,在我国尚缺乏相关报道。目的了解NICU中HT患儿的临床转归及其影响因素。设计病例对照研究。方法纳入2011年1月1日至2021年12月31日在新疆维吾尔自治区人民医院NICU住院,生后3~21 d首次检测TSH浓度6~20 mU·L^(-1)、FT4在正常范围的HT连续病例。出院后随访TSH<6 mU·L^(-1)为TSH正常;TSH≥10 mU·L^(-1)者酌情予左甲状腺素钠(LT4)治疗。当给药剂量<3μg·kg^(-1)·d^(-1)时尝试停药,1个月后复查TSH正常即停药。主要结局指标①3月龄[(90±15)d]TSH异常的影响因素;②LT4治疗患儿3岁时是否停药。结果836例纳入本研究。①3月龄时390例失访或无法判断,TSH正常304例[TSH为3.6(2.7,4.5)mU·L^(-1),FT4为18.3(15.6,20.4)pmol·L^(-1)],异常142例[TSH为17.7(9.6,22.1)mU·L^(-1),FT4为15.7(13.3,19.4)pmol·L^(-1)]。TSH异常的影响因素:女性(OR=1.68,95%CI:1.07~2.64),剖宫产(OR=0.52,95%CI:0.32~0.83),母亲孕期患甲状腺疾病(OR=0.31,95%CI:0.15~0.67),合并先天性畸形或综合征(OR=7.92,95%CI:2.22~28.25),入院时有感染性疾病(OR=0.56,95%CI:0.33~0.96)。②3月龄时TSH异常的142例患儿在3岁时失访18例(12.6%),在未服用LT4状态下TSH恢复正常48例(33.8%),服用LT476例,45例在3岁时(59.2%,45/77)已停药,31例仍在服药。3岁前不能停LT4的风险:合并先天性畸形或综合征的患儿是未合并的4.89倍(OR=4.89,95%CI:1.06~22.57)。结论对于NICU中的HT患儿,尤其应重视女孩、合并先天性畸形或综合征者的甲状腺功能随访。

BackgroundThere are few reports about the outcomes of neonatal hyperthyrotropin(HT)in China.ObjectiveTo investigate the outcome and influencing factors of HT in neonatal intensive care units(NICU).DesignCase-control study.MethodsConsecutive cases of HT infants were enrolled in the NICU of Xinjiang Uygur Autonomous Region People's Hospital from January 1,2011,to December 31,2021.The inclusion criteria were as follows:the concentration of thyroid-stimulating hormone(TSH)was 6-20 mU·L^(-1)at the first test between 3 and 21 days after birth and the free thyroxine(FT4)was within the normal range.During the follow-up after discharge,TSH<6 mU·L^(-1)was considered as the normal level and TSH≥10 mU·L^(-1)was the indicator for levothyroxine(LT4)as needed.A dosage less than 3μg·kg^(-1)·d^(-1)could be an indicator for considering discontinuation of LT4 treatment.The administration could be stopped if TSH was tested normal in the re-examination 1 month later.Main outcome measuresThe influencing factors of abnormal TSH levels at 3 months of age(90±15 days)and LT4 treatment discontinuation at the age of 3 years.ResultsA total of 836 neonates were included in this study.At 3 months of age,390 cases were lost to follow-up or unable to be assessed.Normal thyroid function was found in 304 cases[TSH:3.6(2.7,4.5)mU·L^(-1),FT4:18.3(15.6,20.4)pmol·L^(-1)],and thyroid dysfunction was found in 142 cases[TSH:17.7(9.6,22.1)mU·L^(-1),FT4 is 15.7(13.3,19.4)pmol·L^(-1)].The influencing factors of thyroid dysfunction were female(OR=1.68,95%CI:1.07-2.64),cesarean section(OR=0.52,95%CI:0.32-0.83),maternal thyroid disease during pregnancy(OR=0.31,95%CI:0.15-0.67),comorbid congenital malformation or syndrome(OR=7.92,95%CI:2.22-28.25),infectious disease at admission(OR=0.56,95%CI:0.33-0.96).At the age of 3 years,among 142 children with thyroid dysfunction,18(12.6%)were lost to follow-up,48(33.8%)turned into normal TSH levels without taking LT4,and 45 out of 76 cases taking LT4 stopped the administration and 31 still continued the treatment.The risk of not being able to discontinue LT4 treatment before the age of 3 years was 4.89 times higher in infants with congenital malformations or syndromes compared to those without the comorbidity(OR=4.89,95%CI:1.06-22.57).ConclusionSpecial attention should be paid to the follow-up of thyroid function in HT infants in the NICU,especially for female infants and those with comorbid congenital malformations or syndromes.