Trouva Anastasia, Alvarsson Michael, Calissendorff Jan, Åsvold Bjørn Olav, Ujvari Dorina, Hirschberg Angelica Lindén, Vanky Eszter
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Front Endocrinol (Lausanne). 2024 May 29;15:1388473. doi: 10.3389/fendo.2024.1388473. eCollection 2024.
Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Our aim was to investigate whether maternal thyroid function is associated with newborn anthropometrics in PCOS and explore the potential modifying effect of metformin.
analyses of two RCTs in which pregnant women with PCOS were randomized to metformin or placebo, from first trimester to delivery. Maternal serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at gestational weeks (gw) 5-12, 19, 32 and 36 in 309 singleton pregnancies. The mean z-scores of birthweight, birth length, and head circumference were estimated in the offspring. Associations of maternal thyroid parameters with offspring anthropometrics and the outcomes large for gestational age (LGA) and small for gestational age (SGA) were studied using linear and logistic regression models, with adjustment for body mass index (BMI) when relevant.
Maternal fT4 at baseline was negatively associated with birth length (b= -0.09, p=0.048). Furthermore, ΔfT4 during pregnancy correlated positively to z-score of both birth weight and length (b=0.10, p=0.017 and b=0.10, p=0.047 respectively), independently of treatment group. TSH at baseline and gw19 was inversely associated with LGA (OR 0.47, p=0.012 and OR 0.58, p=0.042), while ΔTSH was positively associated with LGA (OR 1.99, p=0.023). There were inverse associations between TSH at baseline and SGA (OR 0.32, p=0.005) and between ΔfT4 and SGA (OR 0.59, p=0.005) in the metformin group only. There were no associations between maternal thyroid function and head circumference of the newborns.
In women with PCOS, a higher maternal fT4 in early pregnancy and a greater decrease in fT4 during pregnancy was associated with a lower offspring birthweight and shorter birth length. Higher TSH by mid-gestation and smaller increase in TSH during pregnancy was associated with less risk of LGA. Subclinical variations in maternal thyroid function might play a role for birth anthropometrics of PCOS offspring.
多囊卵巢综合征(PCOS)和甲状腺疾病均与不良妊娠及新生儿结局相关。即使甲状腺功能在正常范围内有微小变化也可能影响胎儿生长。我们的目的是研究PCOS患者的母体甲状腺功能是否与新生儿人体测量学指标相关,并探讨二甲双胍的潜在调节作用。
对两项随机对照试验进行分析,其中PCOS孕妇从孕早期至分娩被随机分为二甲双胍组或安慰剂组。在309例单胎妊娠中,于妊娠第5 - 12周、19周、32周和36周测量母体血清促甲状腺激素(TSH)和游离甲状腺素(fT4)水平。估算子代出生体重、出生身长和头围的平均z评分。使用线性和逻辑回归模型研究母体甲状腺参数与子代人体测量学指标以及大于胎龄儿(LGA)和小于胎龄儿(SGA)结局之间的关联,并在相关时对体重指数(BMI)进行校正。
基线时母体fT4与出生身长呈负相关(b = -0.09,p = 0.048)。此外,孕期ΔfT4与出生体重和身长的z评分均呈正相关(分别为b = 0.10,p = 0.017和b = 0.10,p = 0.047),与治疗组无关。基线时及妊娠19周时的TSH与LGA呈负相关(OR = 0.47,p = 0.012和OR = 0.58,p = 0.042),而ΔTSH与LGA呈正相关(OR = 1.99,p = 0.023)。仅在二甲双胍组中,基线时的TSH与SGA呈负相关(OR = 0.32,p = 0.005),ΔfT4与SGA呈负相关(OR = 0.59,p = 0.005)。母体甲状腺功能与新生儿头围之间无关联。
在PCOS女性中,孕早期母体fT4较高且孕期fT4下降幅度较大与子代出生体重较低和出生身长较短相关。妊娠中期TSH较高且孕期TSH升高幅度较小与LGA风险较低相关。母体甲状腺功能的亚临床变化可能对PCOS子代的出生人体测量学指标有影响。