Department of Psychiatry and Psychotherapy, Research-group Stress-related disorders, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Center for Child and Adolescent Health, Pediatrics, University Hospital of Freiburg, Freiburg 79106, Germany.
Psychoneuroendocrinology. 2024 Jul;165:107035. doi: 10.1016/j.psyneuen.2024.107035. Epub 2024 Mar 27.
Adverse environments during pregnancy impact neurodevelopment including cognitive abilities of the developing children. The mediating biological alterations are not fully understood. Maternal stress may impact the neurotrophic regulation of the offspring as early as in utero and at birth. Brain-derived neurotrophic factor (BDNF) is essential for neurodevelopment. Short-term higher levels of BDNF in mice upon stressors associate with lower BDNF later in life, which itself associates with depression in animals and humans. Stress including glucocorticoids may impact BDNF, but there is a lack of data at birth. This study investigated if stress near term associates with fetal BDNF at birth in humans.
Pregnant women near term who underwent primary cesarean sections (at 38.80±0.64 weeks), were included in this study (n=41). Stress at the end of pregnancy was assessed before the cesarean section by determining maternal depressive symptoms (EDPS), maternal state and trait anxiety (STAI-S and STAI-T), maternal prenatal distress (PDQ), stress over the past month (PSS), prenatal attachment to the offspring (PAI), maternal social support (F-Sozu), maternal early life stress (CTQ), socioeconomic status, and the glucocorticoids cortisol and cortisone (n=40) in amniotic fluid at birth. The association with fetal BDNF was analyzed. Cord blood serum of n=34 newborns at birth was analyzed for BDNF and newborn anthropometrics (weight, length and head circumference per gestational age at birth) were assessed. The association of fetal BDNF with anthropometrics at birth was analyzed.
After a BDNF-outlier (>3 SD) was removed, higher fetal BDNF associated significantly with maternal depressive symptoms (r=0.398, p=0.022), with lower socioeconomic status as assessed by the average number of people per room in the household (r=0.526, p=0.002) and with borderline significance with net income per person in the household (r=-0.313, p=0.087) in the bivariate analyses. In multivariable analysis, BDNF stayed positively associated with maternal depressive symptoms (β=0.404, 95% CI [7.057, 306.041], p=0.041) and lower net income per person in the household (β=-0.562, 95% CI [-914.511, -60.523], p=0.027) when controlling for maternal age, maternal pre-pregnancy BMI, fetal sex and gestational age. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed in bivariate analyses or in multivariable analyses when controlling for maternal BMI and fetal sex.
Maternal depressive symptoms and lower socioeconomic status associated with higher fetal BDNF when controlling for confounders. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed. Further studies should investigate how early altered BDNF associate with the development and possibly psychopathology of the offspring.
怀孕期间的不利环境会影响神经发育，包括发育中儿童的认知能力。介导的生物学改变尚不完全清楚。母体应激可能早在宫内和出生时就影响神经发生的神经营养调节。脑源性神经营养因子（BDNF）对神经发育至关重要。在应激源下，小鼠的 BDNF 水平短期升高与生命后期的 BDNF 水平降低有关，而 BDNF 水平降低本身与动物和人类的抑郁有关。应激包括糖皮质激素可能会影响 BDNF，但目前在出生时的数据有限。本研究调查了人类在接近分娩时的应激是否与胎儿出生时的 BDNF 有关。
接受初次剖宫产的孕妇（在 38.80±0.64 周）被纳入本研究（n=41）。在剖宫产前，通过评估产妇的抑郁症状（EDPS）、产妇状态和特质焦虑（STAI-S 和 STAI-T）、产妇产前困扰（PDQ）、过去一个月的压力（PSS）、产前对胎儿的依恋（PAI）、产妇社会支持（F-Sozu）、产妇早期生活压力（CTQ）、社会经济地位以及出生时羊水中的皮质醇和皮质酮（n=40）来评估妊娠末期的应激。分析了与胎儿 BDNF 的关联。在 n=34 名新生儿出生时，分析了脐带血清中的 BDNF 水平，并评估了新生儿的人体测量学指标（出生时按胎龄计算的体重、长度和头围）。分析了胎儿 BDNF 与出生时人体测量学指标的关系。
在去除 BDNF 异常值（>3 SD）后，较高的胎儿 BDNF 与产妇抑郁症状显著相关（r=0.398，p=0.022），与通过家庭人均居住面积评估的较低社会经济地位显著相关（r=0.526，p=0.002），与家庭人均收入有边缘显著相关（r=-0.313，p=0.087）。在多变量分析中，当控制产妇年龄、产妇孕前 BMI、胎儿性别和胎龄时，BDNF 与产妇抑郁症状（β=0.404，95%CI[7.057，306.041]，p=0.041）和家庭人均收入较低呈正相关（β=-0.562，95%CI[-914.511，-60.523]，p=0.027）。在控制产妇 BMI 和胎儿性别后，去除异常值的 BDNF 与新生儿人体测量学指标在双变量分析或多变量分析中均无相关性。
当控制混杂因素时，产妇抑郁症状和较低的社会经济地位与较高的胎儿 BDNF 相关。去除异常值后，胎儿 BDNF 与新生儿人体测量学指标无相关性。进一步的研究应探讨早期改变的 BDNF 如何与后代的发育和可能的精神病理学相关联。
