-
摘要:
目的 研究孕期妇女甲状腺激素敏感性与出生结局的关系。 方法 依托武汉市大型出生队列，以符合入选标准的5 411对孕妇-新生儿为研究对象。利用孕期体检的血清三碘甲状腺素(free triiodothyronine, FT3)、游离甲状腺素(free thyroxine, FT4)和甲状腺刺激激素(thyroid stimulating hormone, TSH)，计算甲状腺激素中枢敏感性的指标：促甲状腺激素指数(thyroid stimulating hormone index, TSHI)、促甲状腺激素细胞-T4抵抗指数(thyrotroph thyroxine resistance index, TT4RI)和甲状腺反馈分位数指数(thyroid feedback quantile-based index, TFQI)。结局指标包括出生体重、出生孕周、出生体重Z评分，以及低出生体重、早产和小于胎龄儿(small for gestational age, SGA)。分别利用多元线性回归、logistic回归分析模型对甲状腺指标和出生结局中的连续型变量、分类变量进行回归分析，并控制可能混杂因素。 结果 FT4、TSHI、TFQI与出生体重和出生体重Z评分呈负相关(均P≤0.01)；甲状腺激素敏感性指标TSHI、TT4RI、TFQI与SGA存在统计学意义的正相关(TSHI: OR=1.52, 95% CI: 1.12~2.06, P＜0.01; TT4RI: OR=1.15, 95% CI: 1.03~1.29, P=0.02; TFQI: OR=1.41, 95% CI: 1.10~1.81, P＜0.01)；甲状腺功能和甲状腺激素敏感性与低出生体重、早产的差异均无统计学意义。将妊娠合并甲状腺功能减退(甲减)人群排除后进行敏感性分析，研究结果一致。 结论 孕期妇女甲状腺激素敏感性受损是不良出生结局SGA的独立风险因素。 Abstract:Objective The objective of this study was to explore the association between sensitivity to thyroid hormones during pregnancy and birth outcomes. Methods A total of 5 411 pairs of mother-newborn from large birth cohorts in Wuhan were included based on the inclusion criteria. The thyroid hormones sensitivity indicators, including thyroid stimulating hormone index (TSHI), thyrotroph thyroxine resistance index (TT4RI), and thyroid feedback quantile-based index (TFQI) were calculated based on values of thyroid function indicators free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH) which were detected during routinely prenatal care. The outcomes included birth weight, gestational duration, birth weight Z-score, low birth weight, preterm birth, and small for gestational age (SGA). Multiple linear regression and logistic regression were used to assess associations of exposures with continuous and categorical outcomes, respectively, adjusting for potential confounders. Results FT4, TSHI, TFQI were significantly negatively associated with birth weight and birth weight Z-score (all P≤0.01). Higher TSHI, TT4RI, TFQI were associated with higher risk of SGA (TTSHI: OR=1.52, 95% CI: 1.12-2.06, P<0.01; TT4RI: OR=1.15, 95% CI: 1.03-1.29, P=0.02; TFQI: OR=1.41, 95% CI: 1.10-1.81, P<0.01). No thyroid indicators were significantly related to low birth weight or preterm birth. The associations were almost unchanged when pregnant women with hypothyroidism were excluded. Conclusions Impaired sensitivity to thyroid hormones during pregnancy is an independent risk factor of SGA. -
表 1 研究人群的基本特征
Table 1. Demographic characteristics of the study population
基本特征Basic characteristic 研究人群①
Study population ①排除人群①
Excluded population ①孕母基本特征Maternal characteristics 年龄组/岁Age group/years, (x±s) 28.6±3.5 28.3±3.8 孕前BMI/(kg·m-2) Pre-pregnancy BMI/(kg·m-2) 偏瘦Thin (≤18.5) 1 134(21.0) 2 636(22.1) 正常Normal (18.5~＜24.0) 3 608(66.7) 7 924(66.4) 超重或肥胖Overweight or obese (≥24.0) 666(12.3) 1 325(11.1) 缺失值Missing 3(0.1) 47(0.4) 家庭年均收入/元Average annual household income/yuan <100 000 3 158(58.4) 9 090(76.2) ≥100 000 2 208(40.8) 2 648(22.2) 缺失值Missing 45(0.8) 194(1.6) 产次Parity 初产Primiparous 4 466(82.5) 9 987(83.7) 经产Multiparous 942(17.4) 1 944(16.3) 缺失值Missing 3(0.1) 1(<0.1) 受教育水平Educational level 高中及以下High school or below 1 266(23.4) 3 813(32.0) 大专及以上Associate degree or above 4 145(76.6) 8 113(68.0) 缺失值Missing 0(0) 6(<0.1) 孕期补钙Calcium supplementation during pregnancy 4 941(91.3) 10 089(84.6) 孕期补铁Iron supplementation during pregnancy 2 522(46.6) 4 941(41.4) 孕期补充复合维生素Multivitamin supplementation during pregnancy 4 772(88.2) 8 804(73.8) 孕前和孕期补充叶酸Folic acid supplementation before and during pregnancy 4 698(86.8) 10 157(85.1) 孕期被动吸烟Passive smoking during pregnancy 1 342(24.8) 2 643(22.2) 胎儿基本特征和体格测量指标Infant characteristics 新生儿性别Infant sex 男Boy 2 854(52.7) 6 279(52.6) 女Girl 2 557(47.3) 5 653(47.4) 出生孕周/周Gestational week/week, (x±s) 39.3±1.2 39.1±1.4 出生体重/g Birth weight/g, (x±s) 3 329.2±429.3 3 294.5±456.2 低出生体重Low birth weight 136(2.5) 485(4.0) 早产Preterm 172(3.2) 709(6.0) 小于胎龄儿Small for gestational age 532(9.8) 1 205(10.1) 注：①以[人数(占比/%)]表示。
Note：①[Number of people (proportion/%)].
下载: 导出CSV
表 2 甲状腺指标与出生体重、出生孕周、出生体重Z评分的关联
Table 2. Association of thyroid markers with birth weight, gestational age at birth, and birth weight Z-score
甲状腺指标①
Thyroid indicators ①出生体重
Birth weight出生孕周
Gestational week出生体重Z评分
Birth weight Z-scoreβ (95% CI) ② P值
valueβ (95% CI) ② P值
valueβ (95% CI) ② P值
valueTSH -4.70 (-16.04~6.65) 0.42 0.01(-0.03~0.05) 0.59 -0.01(-0.04~0.01) 0.33 FT3 56.85 (-21.04~134.74) 0.15 0.02(-0.23~0.27) 0.87 0.13(-0.06~0.31) 0.17 FT4 -54.33 (-93.86~-14.79) <0.01 -0.09(-0.21~0.04) 0.18 -0.12(-0.22~-0.03) 0.01 TSHI -55.60 (-88.55~-22.66) <0.01 -0.06(-0.17~0.04) 0.24 -0.14(-0.21~-0.06) <0.01 TT4RI -9.47 (-21.00~2.06) 0.11 0.00(-0.03~0.04) 0.88 -0.02(-0.05~0.00) 0.08 TFQI -47.38 (-73.62~-21.15) <0.01 -0.06(-0.15~0.02) 0.15 -0.11(-0.18~-0.05) <0.01 注：TSH, 甲状腺刺激激素; FT3, 血清三碘甲状腺素; FT4, 游离甲状腺素; TSHI, 促甲状腺激素指数; TT4RI, 促甲状腺激素细胞-T4抵抗指数; TFQI, 甲状腺反馈分位数指数。
①TSH、FT3、FT4、TSHI、TT4RI为偏态分布，建模前经自然对数转换；②模型校正母亲年龄、孕前BMI、产次、母亲受教育水平、孕期钙剂补充、孕期铁剂补充、孕期复合维生素补充、叶酸补充、被动吸烟、胎儿性别、甲状腺激素检测孕周。在出生体重为因变量的模型中还校正了出生孕周。
Notes: TSH, thyroid stimulating hormone; FT3, free triiodothyronine; FT4, free thyroxine; TSHI, thyroid stimulating hormone index; TT4RI, thyrotroph thyroxine resistance index; TFQI, thyroid feedback quantile-based index.
① TSH, FT3, FT4, TSHI and TT4RI were skewed distributions, transformed by natural logarithm before modeling; ② Models were adjusted for maternal age, pre-pregnancy BMI, number of births, maternal education level, calcium supplementation during pregnancy, iron supplementation during pregnancy, multivitamin supplementation during pregnancy, folic acid supplementation, passive smoking, infant sex, and gestational week of thyroid hormone testing. Gestation period at birth were also adjusted in model which birth weight was the dependent variable.
下载: 导出CSV
表 3 甲状腺指标与低出生体重、早产、小于胎龄儿的关联
Table 3. Association of thyroid markers with low birth weight, preterm birth, and small for gestational age infants
甲状腺指标①
Thyroid indicators ①低出生体重
Low birth weight早产
Preterm小于胎龄儿
Small for gestational age infantsOR值value
(95% CI) ②P值
valueOR值value
(95% CI) ②P值
valueOR值value
(95% CI) ②P值
valueTSH 1.16 (0.91~1.47) 0.23 0.97 (0.82~1.15) 0.71 1.11 (1.00~1.25) 0.06 FT3 0.68 (0.15~3.10) 0.62 0.57 (0.17~1.95) 0.37 0.60 (0.28~1.27) 0.18 FT4 0.51 (0.23~1.15) 0.11 1.14 (0.61~2.14) 0.68 1.37 (0.94~2.00) 0.10 TSHI 1.45 (0.73~2.91) 0.29 1.19 (0.73~1.96) 0.49 1.52 (1.12~2.06) <0.01 TT4RI 1.10 (0.87~1.40) 0.43 0.98 (0.82~1.16) 0.80 1.15 (1.03~1.29) 0.02 TFQI 1.15 (0.66~1.98) 0.63 1.12 (0.74~1.69) 0.59 1.41 (1.10~1.81) <0.01 注：TSH, 甲状腺刺激激素; FT3, 血清三碘甲状腺素; FT4, 游离甲状腺素; TSHI, 促甲状腺激素指数; TT4RI, 促甲状腺激素细胞-T4抵抗指数; TFQI, 甲状腺反馈分位数指数。
①TSH、FT3、FT4、TSHI、TT4RI为偏态分布，建模前经自然对数转换；②模型校正母亲年龄、孕前BMI、产次、母亲受教育水平、孕期钙剂补充、孕期铁剂补充、孕期复合维生素补充、叶酸补充、被动吸烟、胎儿性别、甲状腺激素检测孕周。在出生体重为因变量的模型中还校正了出生孕周。
Note: TSH, thyroid stimulating hormone; FT3, free triiodothyronine; FT4, free thyroxine; TSHI, thyroid stimulating hormone index; TT4RI, thyrotroph thyroxine resistance index; TFQI, thyroid feedback quantile-based index.
① TSH, FT3, FT4, TSHI, and TT4RI were skewed distributions, transformed by natural logarithm before modeling; ② Models were adjusted for maternal age, pre-pregnancy BMI, number of births, maternal education level, calcium supplementation during pregnancy, iron supplementation during pregnancy, multivitamin supplementation during pregnancy, folic acid supplementation, passive smoking, infant sex, and gestational week of thyroid hormone testing. Gestation period at birth were also adjusted in model which birth weight was the dependent variable.
下载: 导出CSV
-
[1] Korevaar TIM, Derakhshan A, Taylor PN, et al. Association of thyroid function test abnormalities and thyroid autoimmunity with preterm birth[J]. JAMA, 2019, 322(7): 632-641. DOI: 10.1001/jama.2019.10931. [2] Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child[J]. N Engl J Med, 1999, 341(8): 549-555. DOI: 10.1056/NEJM199908193410801. [3] Thangaratinam S, Tan A, Knox E, et al. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence[J]. BMJ, 2011, 342: d2616. DOI: 10.1136/bmj.d2616. [4] Derakhshan A, Peeters RP, Taylor PN, et al. Association of maternal thyroid function with birthweight: a systematic review and individual-participant data meta-analysis[J]. Lancet Diabetes Endo, 2020, 8(6): 501-510. DOI: 10.1016/S2213-8587(20)30061-9. [5] 吴金华, 姜雯, 徐海耿, 等. 孕期甲状腺激素水平与新生儿出生体重的关系[J]. 预防医学, 2017, 29(6): 633-635. DOI: 10.19485/j.cnki.issn1007-0931.2017.06.026.Wu JH, Jiang W, Xu HG, et al. Association between prenatal thyroid hormone levels and neonatal birth weight[J]. Preventive Medicine, 2017, 29(6): 633-635. DOI: 10.19485/j.cnki.issn1007-0931.2017.06.026. [6] 刘田田, 孙敏, 周晶敏, 等. 妊娠合并甲状腺功能减退症对后代出生结局及早期神经行为发育的影响[J]. 同济大学学报(医学版), 2021, 42(6): 814-818. DOI: 10.12289/j.issn.1008-0932.21272.Liu TT, Sun M, Zhou JM, et al. lmpact of hypothyroidism in pregnancy on infant birth outcomes and early neurobehavioral development[J]. Journal of Tongji University(Medical Science), 2021, 42(6): 814-818. DOI: 10.12289/j.issn.1008-0932.21272. [7] 谢俊豪, 李文文, 金百翰, 等. 甲状腺素水平对妊娠糖尿病及妊娠结局的影响[J]. 解放军医学杂志, 2020, 45(4): 423-429. DOI: 10.11855/j.issn.0577-7402.2020.04.13.Xie JH, Li WW, Jin BH, et al. Effect of thyroxine level on gestational diabetes mellitus and pregnancy outcome[J]. Med J Chin PLA, 2020, 45(4): 423-429. DOI: 10.11855/j.issn.0577-7402.2020.04.13. [8] Zhang C, Yang X, Zhang Y, et al. Association between maternal thyroid hormones and birth weight at early and late pregnancy[J]. J Clin Endocrinol Metab, 2019, 104(12): 5853-5863. DOI: 10.1210/jc.2019-00390. [9] 孙笑, 张蕾, 杨慧霞, 等. 548例妊娠期甲状腺功能筛查指征及亚临床甲减对妊娠结局影响的分析[J]. 中国妇产科临床杂志, 2014, 15(1): 45-48. DOI: 10.13390/j.issn.1672-1861.2014.01.013.Sun X, Zhang L, Yang HX, et al. The screening indication of thyroid function of 548 cases and the effects of subclinical hypothyroidism on pregnancy outcomes[J]. Chin J Clin Obstetrics Gynecol, 2014, 15(1): 45-48. DOI: 10.13390/j.issn.1672-1861.2014.01.013. [10] Ortiga-Carvalho TM, Sidhaye AR, Wondisford FE. Thyroid hormone receptors and resistance to thyroid hormone disorders[J]. Nat Rev Endocrinol, 2014, 10(10): 582-591. DOI: 10.1038/nrendo.2014.143. [11] Laclaustra M, Moreno-Franco B, Lou-Bonafonte JM, et al. Impaired sensitivity to thyroid hormones is associated with diabetes and metabolic syndrome[J]. Diabetes Care, 2019, 42(2): 303-310. DOI: 10.2337/dc18-1410. [12] Mikolajczyk RT, Zhang J, Betran AP, et al. A global reference for fetal-weight and birthweight percentiles[J]. Lancet, 2011, 377(9780): 1855-1861. DOI: 10.1016/S0140-6736(11)60364-4. [13] Liu L, Nevo D, Nishihara R, et al. Utility of inverse probability weighting in molecular pathological epidemiology[J]. Eur J Epidemiol, 2018, 33(4): 381-392. DOI: 10.1007/s10654-017-0346-8. [14] Alexander EK, Pearce EN, Brent GA, et al. 2017 guidelines of the american thyroid association for the diagnosis and management of thyroid disease during pregnancy and the postpartum[J]. Thyroid, 2017, 27(3): 315-389. DOI: 10.1089/thy.2016.0457. [15] Medici M, Timmermans S, Visser W, et al. Maternal thyroid hormone parameters during early pregnancy and birth weight: the generation R study[J]. J Clin Endocrinol Metab, 2013, 98(1): 59-66. DOI: 10.1210/jc.2012-2420. [16] Zhou Z, Zheng D, Wu H, et al. Epidemiology of infertility in China: a population-based study[J]. BJOG, 2018, 125(4): 432-441. DOI: 10.1111/1471-0528.14966. [17] Chawanpaiboon S, Vogel JP, Moller AB, et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis[J]. Lancet Glob Health, 2019, 7(1): e37-e46. DOI: 10.1016/S2214-109X(18)30451-0. [18] Chen Y, Li G, Ruan Y, et al. An epidemiological survey on low birth weight infants in China and analysis of outcomes of full-term low birth weight infants[J]. BMC Pregnancy Childb, 2013, 13(1): 2-12. DOI: 10.1186/1471-2393-13-242. [19] Medici M, Korevaar T, Visser W, et al. Thyroid function in pregnancy: what is normal?[J]. Clinical Chemistry, 2015, 61(5): 704-713. DOI: 10.1373/clinchem.2014.236646. [20] Dhillon-Smith RK, Coomarasamy A. TPO antibody positivity and adverse pregnancy outcomes[J]. Best Pract Res Clin Endocrinol Metab, 2020, 34(4): 101433. DOI: 10.1016/j.beem.2020.101433. [21] 刘丽娜, 李忠原, 李春香, 等. 3 513例妊娠早期妇女TPOAb阳性与不良妊娠结局的关系[J]. 中国继续医学教育, 2019, 11(22): 99-103. DOI: 10.3969/j.issn.1674-9308.2019.22.042.Liu LN, Li ZY, Li CX, et al. Relationship between TPOAb positive and adverse pregnancy outcome in 3 513 cases of early pregnancy women[J]. Chin Cont Med Edu, 2019, 11(22): 99-103. DOI: 10.3969/j.issn.1674-9308.2019.22.042. -
- 中国精品科技期刊
- 《中文核心期刊要目总览》收录期刊
- RCCSE 中国核心期刊(5/114,A+)
- Scopus收录期刊
- 美国《化学文摘》(CA)收录期刊
- WHO 西太平洋地区医学索引(WPRIM)收录期刊
- 《中国科学引文数据库(CSCD)》核心库期刊 (C)
- 中国科技核心期刊
- 中国科技论文统计源期刊
- 《日本科学技术振兴机构数据库(中国)》(JSTChina)收录期刊
- 美国《乌利希期刊指南》(UIrichsweb)收录期刊
- 中华预防医学会系列杂志优秀期刊(2019年)
留言板
尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!
| 姓名 | |
|---|---|
| 邮箱 | |
| 手机号码 | |
| 标题 | |
| |
