Fetal Sex as Moderating Factor for the Relationship Between Maternal Childhood Trauma and Salivary Kynurenic Acid and Tryptophan in Pregnancy: A Pilot Study.

Traumatic experiences and fetal development influence tryptophan (TRP) and its neuroactive byproduct, kynurenic acid (KYNA). Maternal TRP metabolite levels during pregnancy vary by fetal sex, with higher concentrations in mothers carrying male fetuses. This pilot study aimed to explore the relationship between offspring sex, maternal childhood trauma, and maternal salivary KYNA and TRP levels during pregnancy. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine KYNA and TRP levels in maternal saliva samples collected from 35 late-pregnancy participants. Maternal childhood trauma was assessed using the Childhood Trauma Questionnaire, including subscales for emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect. Among mothers pregnant with boys, salivary KYNA significantly correlated with physical and emotional neglect, and salivary TRP with emotional neglect. No significant correlations were found in mothers who delivered female offspring. Significant associations of childhood trauma and offspring sex were found for salivary KYNA but not TRP concentrations. Mothers with higher trauma levels who delivered boys exhibited higher levels of salivary KYNA compared to those with lower trauma levels. Moreover, mothers with higher trauma levels who delivered boys had higher salivary KYNA levels than those with higher trauma levels who delivered girls. This pilot study provides evidence of an association between maternal childhood trauma and TRP metabolism, measured in saliva, especially in mothers pregnant with boys. However, longitudinal studies with larger sample sizes are required to confirm these results.

Stress during pregnancy and fetal serum BDNF in cord blood at birth.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 (ß=0.404, 95% CI [7.057, 306.041], p=0.041) and lower net income per person in the household (ß=-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. CONCLUSION: 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.