232. From womb to vulnerability: how maternal stress shapes fetal growth factors
Abstract 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.