Endocrine Unit, 2nd Department of Obstetrics and Gynecology, Aretaieion University Hospital, Athens Medical School, Athens, Greece; 3rd Department of Obstetrics and Gynecology, Attikon University Hospital, Athens Medical School, Athens, Greece; Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospital Coventry and Warwick Medical School, Coventry, UK.
Endocrine Unit, 2nd Department of Obstetrics and Gynecology, Aretaieion University Hospital, Athens Medical School, Athens, Greece.
Psychoneuroendocrinology. 2020 Apr;114:104591. doi: 10.1016/j.psyneuen.2020.104591. Epub 2020 Jan 25.
During pregnancy, maternal stressors cause changes in both maternal and fetal HPA axes. We therefore investigated the impact of maternal non chronic and chronic stress on fetal glucose metabolism and growth, and serum levels of cortisol in the fetus.
Normal weight pregnant women (n = 192; mean ± SD 27.9 ± 4.2 years old, and; 26.9 ± 2.4 kg/m²) were assessed during the 2nd and 3rd trimester with anthropometry, fetal ultrasound, blood samples for serum CRH, cortisol and IL6, and STAI trait and state stress questionnaires. We measured serum cortisol, insulin and c-peptide, and plasma glucose from cord blood. Neonates underwent anthropometry at the 3rd post-delivery day.
In both 2nd and 3rd trimesters, women with STAI trait scores ≥40 had significantly greater levels of fasting serum CRH and cortisol than those with STAI trait scores<40. 2nd trimester: STAI trait scores correlated positively with cord blood glucose and c-peptide. Maternal serum CRH correlated negatively with U/S fetal biparietal head diameter, while serum cortisol correlated positively with abdominal circumference. Maternal serum IL6, CRH and cortisol all correlated positively with birth waist circumference. 3rd trimester: Women with STAI state scores ≥40 had fetuses with larger U/S abdominal and smaller head circumferences compared to those of women with STAI scores <40. Women with STAI trait scores ≥40 had greater levels of cord blood cortisol, glucose, and c-peptide compared to women with STAI scores <40. STAI state scores ≥40 correlated positively with maternal CRH and U/S fetal abdominal circumference, and negatively with fetal head circumference and biparietal diameter. STAI trait scores correlated positively with cord blood c-peptide, glucose, insulin and cortisol. Maternal serum levels of CRH correlated positively with U/S fetal abdominal circumference and cord blood cortisol, and negatively with fetal head circumference and biparietal head diameter. Maternal serum levels of both CRH and cortisol correlated positively with cord blood c-peptide, glucose, and insulin. STAI trait was the best positive predictor of cord blood cortisol, glucose and c-peptide, whilst STAI state was the best positive and negative predictor, respectively of fetal abdominal circumference and fetal head circumference or biparietal diameter.
Increased maternal chronic stress (reflected by the STAI trait score) associates with increased fetal cortisol, glucose, c-peptide secretion and thus, insulin resistance. Maternal non chronic stress (STAI state) in the 3rd trimester associates with changes in fetal growth pattern, including increased and decreased measurements of fetal abdominal and head growth respectively.
在怀孕期间,母体应激源会导致母体和胎儿 HPA 轴发生变化。因此,我们研究了母体非慢性和慢性应激对胎儿葡萄糖代谢和生长以及胎儿血清皮质醇水平的影响。
正常体重孕妇(n=192;平均年龄±SD 27.9±4.2 岁,体重指数 26.9±2.4kg/m²)在妊娠第 2 至 3 个月期间接受人体测量、胎儿超声、血清 CRH、皮质醇和 IL6 以及 STAI 特质和状态应激问卷评估。我们从脐血中测量血清皮质醇、胰岛素和 C 肽以及血浆葡萄糖。新生儿在产后第 3 天进行人体测量。
在第 2 和第 3 个三个月中,STAI 特质评分≥40 的女性空腹血清 CRH 和皮质醇水平显著高于 STAI 特质评分<40 的女性。第 2 个三个月:STAI 特质评分与脐血血糖和 C 肽呈正相关。母体血清 CRH 与 U/S 胎儿双顶径呈负相关,而皮质醇与腹围呈正相关。母体血清 IL6、CRH 和皮质醇均与出生腰围呈正相关。第 3 个三个月:STAI 状态评分≥40 的女性胎儿的 U/S 腹部较大,头围较小,而 STAI 评分<40 的女性则相反。STAI 特质评分≥40 的女性的脐血皮质醇、血糖和 C 肽水平均高于 STAI 评分<40 的女性。STAI 状态评分≥40 与母体 CRH 和 U/S 胎儿腹围呈正相关,与胎儿头围和双顶径呈负相关。STAI 特质评分与脐血 C 肽、血糖、胰岛素和皮质醇呈正相关。母体血清 CRH 与 U/S 胎儿腹围和脐血皮质醇呈正相关,与胎儿头围和双顶径呈负相关。母体血清 CRH 和皮质醇均与脐血 C 肽、血糖和胰岛素呈正相关。STAI 特质是脐血皮质醇、血糖和 C 肽的最佳正预测因子,而 STAI 状态是胎儿腹围和头围或双顶径的最佳正预测因子和负预测因子。
母体慢性应激(由 STAI 特质评分反映)增加与胎儿皮质醇、葡萄糖、C 肽分泌增加以及胰岛素抵抗有关。妊娠晚期母体非慢性应激(STAI 状态)与胎儿生长模式的变化有关,包括胎儿腹围和头围的增加和减少。