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

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Eva Kathrin Lamadé , Bruno Pedraz-Petrozzi , Ole Lindner , Pascal Meininger , Antonia Pisters , Maria Gilles , Stephanie H. Witt , Marcella Rietschel , Helene Dukal , Fabian Schunk , Michaela Coenen , Stefan A. Wudy , Rainer Hellweg , Michael Deuschle
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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 (R2 = 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.

孕期压力--对胎儿出生时羊水中 BDNF 的影响
在妊娠期的母胎界面上,妊娠期的压力会导致胎儿日后更容易出现精神病态。这种关联的潜在介导因素目前还鲜有研究,其中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其值得关注,因为在羊水中进行评估可以测量一个时间整体。本研究假设,母亲的心理测量、社会经济地位和糖皮质激素与出生时羊水中的 BDNF 水平有关。研究还检验了胎儿 BDNF 与新生儿人体测量的关系。研究对象为接受选择性剖宫产的临产妇女及其新生儿(37 人)。分析了产妇的心理测量、社会经济状况和出生时羊水中的糖皮质激素(皮质醇和可的松的总和)与胎儿出生时羊水中 BDNF 的关系。新生儿的人体测量指标包括身长、体重、头围和出生时的胎龄。在双变量分析中,母亲的心理测量和社会经济地位与胎儿出生时羊水中的BDNF无关。皮质醇和可的松的总和与胎儿出生时羊水中 BDNF 的增加有关(r = 0.745,p < 0.001)。羊水中的BDNF与胎儿每胎龄出生体重(r = -0.519,p < 0.001)、每胎龄身长(r = -0.374,p = 0.023)、每胎龄头围(r = -0.508,p = 0.001)呈负相关,但与出生时胎龄无关。在多元回归分析中,当控制了胎儿性别和母体年龄后,皮质醇和可的松的总和(p < 0.001)以及每个胎龄的出生体重(p = 0.012)与胎儿出生时羊水中较高的 BDNF 水平有关(R = 0.740,p < 0.001)。在控制了混杂因素后,每胎龄头围对胎儿BDNF的预测具有边缘显著性(p = 0.058)。羊水中的糖皮质激素与胎儿出生时的高BDNF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的BDNF没有联系。出生体重和每胎龄头围与胎儿出生时的BDNF成反比,这可能是低人体测量值胎儿BDNF的补偿性上调。需要进行纵向研究,以评估孕期压力对后代发育的影响。有必要进一步分析胎盘等生物材料在母体压力下产生的其他胎儿生长因子和炎症,以了解母体压力如何与胎儿发育和心理病理学易感性增加之间的机理变化。
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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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