Barjaktarovic M, Korevaar T I M, Chaker L, Jaddoe V W V, de Rijke Y B, Visser T J, Steegers E A P, Peeters R P
The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus Medical Center, Dr Molewaterplein 50, Room Ee 502a, 3015 GE, Rotterdam, The Netherlands.
Hum Reprod. 2017 Mar 1;32(3):653-661. doi: 10.1093/humrep/dew357.
What is the clinical association of maternal thyroid function with placental hemodynamic function?
A higher free thyroxine (FT4) concentration in early pregnancy is associated with higher placental vascular resistance.
Suboptimal placental function is associated with preeclampsia (which, in turn, further deteriorates placental hemodynamics and impairs the fetal blood supply), fetal growth restriction and premature delivery. Studies have suggested that thyroid hormone (TH) has a role in placental development through effects on trophoblast proliferation and invasion.
STUDY DESIGN, SIZE, DURATION: This study was embedded in The Generation R cohort, a population-based prospective study from early fetal life onwards in Rotterdam, the Netherlands. In total, 7069 mothers with expected delivery date between April 2002 and January 2006 were enrolled during early pregnancy.
PARTICIPANTS/MATERIALS, SETTING, METHOD: Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentrations were measured during early pregnancy (median 13.4 weeks, 95% range 9.7-17.6 weeks). Placental function was assessed by Doppler ultrasound via measurement of arterial vascular resistance, i.e. umbilical artery pulsatility index (PI) and uterine artery resistance index (RI) (both measured twice, between 18-25th and after 25th gestational weeks) and the presence of uterine artery notching (once after the 25th gestational week) in 5184 pregnant women.
FT4 was positively linearly associated with umbilical artery PI in the second and third trimesters as well as with uterine artery RI in the second trimester and the risk of uterine artery notching in the third trimester (P < 0.05 for all). The association of thyroid function with preeclampsia and birth weight was partially mediated through changes in placental function, with the percentages of mediated effects being 10.4% and 12.5%, respectively.
LIMITATIONS, REASONS FOR CAUTION: A potential limitation is the availability of only a single time point for TH measurements and different numbers of missing placental ultrasound measurements for the adverse outcomes.
A higher FT4 concentration in early pregnancy is associated with higher vascular resistance in the second and third trimesters in both the maternal and fetal placental compartment. These effects on placental function might explain the association of FT4 with adverse pregnancy outcomes, including preeclampsia and fetal growth restriction.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a fellowship from ERAWEB, a project funded by the European Commission (to M.B.) and by clinical fellowship from The Netherlands Organization for Health Research and Development (ZonMw), Project 90700412 (to R.P.P.). The authors have no conflict of interest.
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孕妇甲状腺功能与胎盘血流动力学功能之间的临床关联是什么？
孕早期较高的游离甲状腺素（FT4）浓度与较高的胎盘血管阻力相关。
胎盘功能欠佳与子痫前期（进而会进一步使胎盘血流动力学恶化并损害胎儿供血）、胎儿生长受限和早产有关。研究表明，甲状腺激素（TH）通过对滋养层细胞增殖和侵袭的影响在胎盘发育中发挥作用。
研究设计、规模、持续时间：本研究纳入了“Generation R队列研究”，这是一项在荷兰鹿特丹开展的基于人群的前瞻性研究，从胎儿早期开始。共有7069名预计在2002年4月至2006年1月分娩的母亲在孕早期入组。
参与者/材料、研究环境、方法：在孕早期（中位时间为13.4周，95%范围为9.7 - 17.6周）测量促甲状腺激素（TSH）和游离甲状腺素（FT4）浓度。通过多普勒超声测量动脉血管阻力来评估胎盘功能，即测量5184名孕妇的脐动脉搏动指数（PI）和子宫动脉阻力指数（RI）（均在孕18 - 25周和孕25周之后各测量两次）以及子宫动脉切迹的情况（在孕25周之后测量一次）。
FT4与孕中期和孕晚期的脐动脉PI呈正线性相关，与孕中期的子宫动脉RI以及孕晚期子宫动脉切迹的风险也呈正线性相关（所有P值均<0.05）。甲状腺功能与子痫前期和出生体重之间的关联部分是通过胎盘功能的变化介导的，介导效应的百分比分别为10.4%和12.5%。
局限性、需谨慎的原因：一个潜在的局限性是甲状腺激素测量仅提供了一个时间点的数据，并且不同不良结局的胎盘超声测量缺失数据数量不同。
孕早期较高的FT4浓度与孕中期和孕晚期母体和胎儿胎盘区室的较高血管阻力相关。这些对胎盘功能的影响可能解释了FT4与不良妊娠结局（包括子痫前期和胎儿生长受限）之间的关联。
研究资金/利益冲突：这项工作得到了ERAWEB的一项奖学金支持，ERAWEB是由欧盟委员会资助的一个项目（授予M.B.），以及荷兰卫生研究与发展组织（ZonMw）的临床奖学金，项目90700412（授予R.P.P.）。作者没有利益冲突。
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