National Health Commission (NHC) Key Lab. of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School of Public Health, Fudan University, Shanghai, China.
NHC Key Lab. of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China.
Front Endocrinol (Lausanne). 2021 Sep 8;12:736505. doi: 10.3389/fendo.2021.736505. eCollection 2021.
Evidence from animal studies has indicated that neonatal thyroid function is vital for the reproductive development. Anogenital distance (AGD), a sensitive biomarker of the fetal hormonal milieu, can be used to predict adult reproductive disorders. However, few human studies have examined the association between neonatal thyroid function and AGD. We aimed to explore their associations in a birth cohort study.
Concentrations of thyroid stimulating hormone (TSH) and thyroid hormones (THs), including total triiodothyronine (TT), total thyroxine (TT), free triiodothyronine (FT), and free thyroxine (FT) were measured in cord plasma in the Shanghai-Minhang Birth Cohort. The offspring AGD (AGD [anus-penis] and AGD [anus-scrotum] for boys and AGD [anus-clitoris] and AGD [anus-fourchette] for girls), body weight and anogenital index (AGI = AGD/weight [mm/kg]) were obtained at each follow-up visit. In total, 344 children (194 boys and 150 girls) with cord plasma concentrations of THs and TSH and at least one AGD measurement at birth and at 6, 12, and 48 months of age were included. Multiple linear regression and generalized estimating equation (GEE) models were used to examine the associations of cord plasma concentrations of THs and TSH with AGI.
Multiple linear regression models showed inverse associations of TT, FT, and FT with female AGI, although statistical significance was only reached at birth, 6 and 48 months of age. These associations were also found in GEE models: higher TT and FT concentrations were associated with lower AGI (TT: β = -0.27, 95% CI: -0.50, -0.03 for middle . lowest tertile; FT: β = -0.38, 95% CI: -0.61, -0.16 for middle and β = -0.30, 95% CI: -0.55, -0.04 for highest . lowest tertile). Besides, girls with the highest tertile of FT concentrations had lower AGI than those with the lowest tertile (the highest . lowest tertile: β = -0.22, 95% CI: -0.36, -0.08). Positive associations between TSH and AGI at birth and at 12 months of age were observed in boys.
This study provides further evidence on the effects of neonatal thyroid function on reproductive development at an early life stage.
动物研究的证据表明，新生儿的甲状腺功能对生殖发育至关重要。肛生殖器距离（AGD）是胎儿激素环境的敏感生物标志物，可用于预测成年生殖障碍。然而，很少有人类研究探讨新生儿甲状腺功能与 AGD 之间的关联。我们旨在探索它们在出生队列研究中的关联。
在上海闵行出生队列中，测量脐带血浆中的促甲状腺激素（TSH）和甲状腺激素（THs）的浓度，包括总三碘甲状腺原氨酸（TT）、总甲状腺素（TT）、游离三碘甲状腺原氨酸（FT）和游离甲状腺素（FT）。在每次随访时，获得新生儿的 AGD（男孩的 AGD[肛门-阴茎]和 AGD[肛门-阴囊]，女孩的 AGD[肛门-阴蒂]和 AGD[肛门-阴唇]）、体重和肛生殖器指数（AGI=AGD/体重[mm/kg]）。共有 344 名儿童（194 名男孩和 150 名女孩）在出生时、6 个月、12 个月和 48 个月时进行了 THs 和 TSH 的脐带血浆浓度检测和至少一次 AGD 测量。使用多元线性回归和广义估计方程（GEE）模型来检验脐带血浆 THs 和 TSH 浓度与 AGI 的关联。
多元线性回归模型显示 TT、FT 和 FT 与女性 AGI 呈负相关，尽管仅在出生、6 个月和 48 个月时达到统计学意义。GEE 模型也发现了这些关联：TT 和 FT 浓度越高，AGI 越低（TT：β=-0.27，95%CI：-0.50，-0.03 为中值. 最低三分位数；FT：β=-0.38，95%CI：-0.61，-0.16 为中值和 β=-0.30，95%CI：-0.55，-0.04 为最高. 最低三分位数）。此外，FT 浓度最高三分位数的女孩与最低三分位数的女孩相比，AGI 较低（最高. 最低三分位数：β=-0.22，95%CI：-0.36，-0.08）。男孩在出生时和 12 个月时观察到 TSH 与 AGI 之间存在正相关。
本研究进一步提供了新生儿甲状腺功能对生命早期生殖发育影响的证据。
