¹Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Mannheim, Germany, ²Praxis Hendlmeier und von Cossel, General Medicine, Feldafing, Germany, ³Westpfalz-Klinikum, Department of Gynecology and Obstetrics, Kaiserslautern, Germany, ⁴Center for Child and Adolescent Health, Pediatrics, Freiburg, Germany, ⁵Charité Universitaetsmedizin Berlin, Department of Psychiatry and Psychotherapy, Berlin, Germany, ⁶Center of Child and Adolescent Medicine, Laboratory for Translational Hormone Analytics, Division of Pediatric Endocrinology and Diabetology, Giessen, Germany

Background: Maternal perinatal stress links to developmental delay and later vulnerability to psychiatric disease in the offspring. Low social support in pregnancy relates to anxiety and attention deficit hyperactivity disorder in 8 year old offspring. The biological mechanisms remain unclear and may involve early alterations of fetal growth factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF)-1.

Aims & Objectives: We aimed to analyze the link between maternal stress and fetal growth factors (IGF-1, BDNF) in amniotic fluid in mid-pregnancy and at birth. The association of fetal growth factors with anthropometrics at birth was assessed.

Method: In two prospective cohorts of women undergoing amniocentesis at 15.9 ± 0.9 weeks (n=79), and women undergoing elective cesarean section at 39.5 ± 1.5 weeks (n=41), maternal stress (childhood trauma, psychiatric symptoms including depressive symptoms, anxiety, social support, socioeconomic status and glucocorticoids in amniotic fluid) was assessed and related to fetal IGF-1 in amniotic fluid in mid-pregnancy and at birth and to BDNF in cord blood and in amniotic fluid at birth.

Results: Presence of maternal childhood trauma was linked to lower fetal IGF-1 in mid-pregnancy in amniotic fluid (M=3.48 vs. 2.98, p=0.012), with the sexual abuse subscale linked to lower IGF-1 in mid-pregnancy (p=0.006) and at birth (p=0.049). Fetal IGF-1 in mid-pregnancy showed a trend-level association with newborn weight at birth (p=0.096). Higher maternal depressive symptoms and lower socioeconomic status at birth were associated with higher fetal BDNF in cord blood at birth (p=0.002; p=0.002). Increased glucocorticoids in amniotic fluid at birth were linked to higher fetal BDNF in amniotic fluid at birth (p<0.001), and fetal BDNF in amniotic fluid at birth was further related to newborn weight adjusted for gestational age (p<0.001).

Discussion & Conclusions: Higher maternal stress was associated with altered levels of fetal growth factors, underlying that specific aspects of maternal stress can influence fetal neurodevelopmental markers. Additionally, IGF-1 and BDNF levels were linked to newborn weight. Birth weight is a known predictor for later somatic and psychiatric disorders. These results may reflect a potential early biological pathway to long-term vulnerability. These findings show that maternal stress can impact fetal endocrine regulation as early as in mid-pregnancy and at birth.