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孕期应激——对出生时羊水胎儿脑源性神经营养因子的影响。

Stress in pregnancy - Implications for fetal BDNF in amniotic fluid at birth.

作者信息

Lamadé Eva Kathrin, Pedraz-Petrozzi Bruno, Lindner Ole, Meininger Pascal, Pisters Antonia, Gilles Maria, Witt Stephanie H, Rietschel Marcella, Dukal Helene, Schunk Fabian, Coenen Michaela, Wudy Stefan A, Hellweg Rainer, Deuschle Michael

机构信息

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

German Center for Mental Health (DZPG), partner site Mannheim-Heidelberg-Ulm, Germany.

出版信息

Neurobiol Stress. 2024 Jun 22;31:100658. doi: 10.1016/j.ynstr.2024.100658. eCollection 2024 Jul.

Abstract

INTRODUCTION

At the maternal-fetal interface in pregnancy, stress during pregnancy can lead to an increased vulnerability to later psychopathology of the fetus. Potential mediators of this association have scarcely been studied and may include early alterations of fetal brain-derived neurotrophic factor (BDNF). Amniotic fluid is of particular interest for effects on fetal endocrine alterations, as the assessment in amniotic fluid allows for measurements over a time integral. This study hypothesized that maternal psychometrics, socioeconomic status and glucocorticoids are related to BDNF levels in amniotic fluid at birth. The association of fetal BDNF with newborn anthropometrics was tested.

METHODS

Women near term who underwent elective cesarean section and their newborns were investigated (n = 37). Maternal psychometrics, socioeconomic status and glucocorticoids (the sum of cortisol and cortisone) in amniotic fluid at birth were analyzed for an association with fetal BDNF in amniotic fluid at birth. Newborn anthropometrics were assessed by length, weight, head circumference and gestational age at birth.

RESULTS

In bivariate analysis, maternal psychometrics and socioeconomic status were not related to fetal BDNF in amniotic fluid at birth. The sum of cortisol and cortisone related to increased fetal BDNF in amniotic fluid at birth (r = 0.745, p < 0.001). BDNF in amniotic fluid was associated negatively with fetal birth weight per gestational age (r = -0.519, p < 0.001), length per gestational age (r = -0.374, p = 0.023), head circumference per gestational age (r = -0.508, p = 0.001), but not with gestational age at birth. In multiple regression analysis, the sum of cortisol and cortisone (p < 0.001) and birth weight per gestational age (p = 0.012) related to higher fetal BDNF levels in amniotic fluid at birth (R = 0.740, p < 0.001) when controlling for fetal sex and maternal age. Head circumference per gestational age predicted fetal BDNF with borderline significance (p = 0.058) when controlling for confounders.

CONCLUSION

Glucocorticoids in amniotic fluid were positively associated with high fetal BDNF at birth, which may be an adaptive fetal response. Maternal psychological variables and socioeconomic status did not link to fetal BDNF. Birth weight and head circumference per gestational age were inversely associated with fetal BDNF at birth, which may represent a compensatory upregulation of BDNF in fetuses with low anthropometrics. Longitudinal studies are needed to assess the role of stress during pregnancy on later offspring development. The analysis of additional fetal growth factors and inflammation upon maternal stress in further biomaterials such as the placenta is warranted, to understand mechanistic alterations of how maternal stress links to fetal development and an increased vulnerability for psychopathology.

摘要

引言

在孕期的母胎界面,孕期应激会导致胎儿日后患精神病理学疾病的易感性增加。这种关联的潜在中介因素鲜有研究,可能包括胎儿脑源性神经营养因子(BDNF)的早期改变。羊水对胎儿内分泌改变的影响尤为值得关注,因为羊水评估可进行一段时间内的综合测量。本研究假设,母亲的心理测量指标、社会经济地位和糖皮质激素与出生时羊水中的BDNF水平相关。同时对胎儿BDNF与新生儿人体测量学指标的关联进行了测试。

方法

对接受择期剖宫产的足月孕妇及其新生儿进行了研究(n = 37)。分析了母亲的心理测量指标、社会经济地位以及出生时羊水中的糖皮质激素(皮质醇和可的松之和)与出生时羊水中胎儿BDNF的关联。通过出生时的身长、体重、头围和孕周评估新生儿人体测量学指标。

结果

在双变量分析中,母亲的心理测量指标和社会经济地位与出生时羊水中的胎儿BDNF无关。皮质醇和可的松之和与出生时羊水中胎儿BDNF升高相关(r = 0.745,p < 0.001)。羊水中的BDNF与每孕周胎儿出生体重呈负相关(r = -0.519,p < 0.001),与每孕周身长呈负相关(r = -0.374,p = 0.023),与每孕周头围呈负相关(r = -0.508,p = 0.001),但与出生时的孕周无关。在多元回归分析中,控制胎儿性别和母亲年龄后,皮质醇和可的松之和(p < 0.001)以及每孕周出生体重(p = 0.012)与出生时羊水中胎儿BDNF水平升高相关(R = 0.740,p < 0.001)。控制混杂因素后,每孕周头围对胎儿BDNF的预测具有临界显著性(p = 0.058)。

结论

羊水中的糖皮质激素与出生时胎儿BDNF水平升高呈正相关,这可能是胎儿的一种适应性反应。母亲的心理变量和社会经济地位与胎儿BDNF无关。每孕周出生体重和头围与出生时胎儿BDNF呈负相关,这可能代表低人体测量学指标胎儿中BDNF的代偿性上调。需要进行纵向研究来评估孕期应激对后代后期发育的作用。有必要在胎盘等其他生物材料中进一步分析母体应激时额外的胎儿生长因子和炎症,以了解母体应激与胎儿发育以及精神病理学易感性增加之间的机制性改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48da/11294724/bc6e29ecc6cf/gr1.jpg

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