Johns Lauren E, Ferguson Kelly K, McElrath Thomas F, Mukherjee Bhramar, Seely Ellen W, Meeker John D
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, United States.
Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
PLoS One. 2017 Jan 6;12(1):e0169542. doi: 10.1371/journal.pone.0169542. eCollection 2017.
Overt thyroid disease in pregnancy is associated with numerous maternal and neonatal complications including preterm birth. Less is known about the contribution of trimester-specific subclinical alterations in individual thyroid hormones, especially in late gestation, on the risk of preterm birth. Herein, we examined the associations between subclinical changes in maternal thyroid hormone concentrations (TSH, total T3, free and total T4), measured at multiple time points in pregnancy, and the odds of preterm birth in pregnant women without clinical thyroid disease.
Data were obtained from pregnant women participating in a nested case-control study of preterm birth within on ongoing birth cohort study at Brigham and Women's Hospital in Boston, MA (N = 439; 116 cases and 323 controls). We measured thyroid hormones in plasma collected at up to four time points in pregnancy (median = 10, 18, 26, and 35 weeks). We used multivariate logistic regression models stratified by study visit of sample collection to examine associations. To reveal potential biological pathways, we also explored these relationships by obstetric presentation of preterm birth (e.g., spontaneous preterm delivery) that have been previously hypothesized to share common underlying mechanisms.
In samples collected at median 10 and 26 weeks of gestation, we found inverse associations between FT4 and the odds of overall preterm birth (odds ratio [OR] = 0.57, 95% confidence interval (CI) = 0.33, 1.00; and OR = 0.53, 95% CI = 0.34, 0.84, respectively). Positive associations were detected for total T3 at these same time points (OR = 2.52, 95% CI = 1.20, 5.31; and OR = 3.40, 95% CI = 1.56, 7.40, respectively). These effect estimates were stronger for spontaneous preterm birth.
Our results suggest that subclinical alterations in individual maternal thyroid hormones may influence the risk of preterm birth, and the strength of these associations vary by gestational age.
妊娠期显性甲状腺疾病与包括早产在内的众多母婴并发症相关。关于孕期特定阶段单个甲状腺激素的亚临床改变，尤其是妊娠晚期，对早产风险的影响知之甚少。在此，我们研究了孕期多个时间点测量的孕妇甲状腺激素浓度（促甲状腺激素、总三碘甲状腺原氨酸、游离和总甲状腺素）的亚临床变化与无临床甲状腺疾病孕妇早产几率之间的关联。
数据来自参与马萨诸塞州波士顿布里格姆妇女医院一项正在进行的出生队列研究中的早产巢式病例对照研究的孕妇（N = 439；116例病例和323例对照）。我们在孕期最多四个时间点（中位数为10、18、26和35周）采集的血浆中测量甲状腺激素。我们使用按样本采集研究访视分层的多变量逻辑回归模型来检查关联。为揭示潜在的生物学途径，我们还按先前假设具有共同潜在机制的早产产科表现（例如，自发性早产）来探索这些关系。
在妊娠中位数为10周和26周采集的样本中，我们发现游离甲状腺素与总体早产几率之间呈负相关（优势比[OR] = 0.57，95%置信区间[CI] = 0.33，1.00；以及OR = 0.53，95% CI = 0.34，0.84）。在这些相同时间点检测到总三碘甲状腺原氨酸呈正相关（分别为OR = 2.52，95% CI = 1.20，5.31；以及OR = 3.40，95% CI = 1.56，7.40）。这些效应估计值在自发性早产中更强。
我们的结果表明，孕妇个体甲状腺激素的亚临床改变可能影响早产风险，且这些关联的强度因孕周而异。
