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Introduction Maternal stress during pregnancy influences fetal neurodevelopment, especially by the dysregulation of the HPA axis. However, less is known about whether maltreatment or stressful life experiences previous to pregnancy influence on developmental outcomes in the offspring. Objectives To analyze newborns’ neurobehavioral profiles in a cohort of healthy pregnant women, according to 1) childhood and recent maternal adverse experiences and 2) mother-infant attachment. Methods 150 women were followed during the three trimesters of pregnancy. CTQ and AAT tests were employed to evaluate childhood and recent experiences of maltreatment, while infant and recent adverse experiences were evaluated using ETI-SR and SRSS, respectively. Newborns neurobehavioral profiles were defined at 8 weeks using the Neonatal Behavioral Assessment Scale (NBAS) and their temperament was assessed with IBQ. PBQ and PAI scales were employed to assess mother-infant attachment. A linear regression model was performed, adjusting for possible confounders. Results Maternal childhood sexual abuse seems to be associated with greater difficulties in the newborns control of reactivity to external stimuli (β=0,517; p-value=0.001), while recent maternal stressful experiences are related to difficulties for states regulation (β=0,29; p-value=0,038). Regarding attachment, maltreated mothers tend to show ambivalent and avoidant styles. Interestingly, postnatal mother-infant attachment seems to modulate autonomous, motor and social-interactive abilities in the offspring (β=-0,227; p-value=0,033 // β=-0,329; p-value=0,006). Conclusions Newborns from mothers exposed to maltreatment and negative life events previous to pregnancy show difficulties to organize and regulate the reactions to psychosocial stimuli. Future studies must disentangle whether maternal attachment style is a modulator of this association. Disclosure No significant relationships.

Introduction The consequences for the COVID-19 pandemic in the newborns of affected mothers remains unknown. Previous clinical experiences with other infections during pregnancy lead to considered pregnant women and their offspring especially vulnerable for SARS-COV-2. That is, the underlying physiopathological changes caused by the infection (e.g. storm of cytokines, micro-coagulation in placenta or vertical transmission) could clearly compromise fetal neurodevelopment. Objectives To analyze the impact of maternal SARS-COV-2 infection during pregnancy in early neurodevelopment of infants gestated during the COVID-19 pandemic period compared to those gestated immediately prior (2017-2021). Methods 212 pregnant women (14% infected) were followed throughout their pregnancy and postpartum, including newborn development. SARS-COV-2 infection was serologically confirmed during pregnancy. The Brazelton Neonatal Assessment Scale (NBAS) was administered at 6 weeks old by a trained neonatologist to evaluate neurological, social and behavioral aspects of newborn’s functioning. Differences in NBAS scores between cases and controls were tested by ANOVAs. All the analysis were adjusted for maternal age, sociodemographic status, anxious-depressive symptomatology, infant’s sex and gestational age at birth and NBAS, and for the period of gestation (previous or during COVID-19 pandemic). Results NBAS social interactive dimension was significantly decreased in those infants exposed to prenatal SARS-COV-2 (F=4.248, p=.043), particularly when the infection occurred before the week 20 of gestation. Gestation during COVID-19 pandemic did not alter NBAS subscales. Conclusions SARS-COV-2 infection during pregnancy seems to be associated with lower NBAS scores on social dimension in 6 weeks old exposed newborns. Disclosure No significant relationships.

Introduction Childhood maltreatment (CM) is one of the best described environmental risk factors for developing any psychiatric disorder, while it also confers increased odds for obesity, cardiometabolic disorders and all-cause mortality. Inflammation has been suggested to mediate the widespread clinical effects of CM. Previously, Ligthart et al. (2016) identified a polyepigenetic signature of circulating CRP levels, a measure of chronic low-grade inflammation, that has been reliably associated with a wide array of complex disorders. The study of this biomarker could dilucidate the mechanistic relationship between CM and psychiatric outcomes. Objectives Thus, CRP-associated epigenetic modifications were explored regarding proximal exposure to CM. Methods Genomic DNA was extracted from peripheral blood mononuclear cells of 157 children and adolescents (7 to 17 years old). Exposure to CM was assessed following the TASSCV criteria. Genome-wide DNA methylation was assessed by means of the EPIC array. Fifty-two out of the 58 original CRP-associated CpG sites surpassed quality control and were included in the analysis. Age, sex, psychopathological status and cell type proportions were included as covariates. Results DNA methylation at 12 out of 52 CpG sites (23%) was significantly associated with exposure to CM (p < .05); 8 of these associations survived correction for multiple testing (q < .05). Conclusions This is the first study to date to explore the relationship between childhood maltreatment and an epigenetic signature of chronic low-grade inflammation. Our findings underscore the presence of immune dysregulation early after exposure to CM; further studies are needed to assess the long-term clinical implications of this signature in psychiatric patients. Disclosure No significant relationships.

Introduction Cortisol, the hormonal endpoint of Hypothalamic Pituitary Adrenal (HPA) axis, coordinates the body response in front of daily stressful situations. Disturbances in cortisol circadian rhythm have been implicated in the pathophysiology of depression and neurodevelopment lasting consequences. Although pregnancy entails a progressively increase in cortisol levels, the consequences of subclinical depression traits during pregnancy in cortisol circadian rhythm remains unclear. Objectives To analyze the impact of prenatal subclinical depressive symptomatology in cortisol circadian rhythm through pregnancy and its relevance for postpartum depression risk. Methods A cohort of 112 healthy pregnant women (Mean age±SD=32.32±4.37) of the general population was followed throughout their first pregnancy and first two months of postpartum period. Diurnal salivary cortisol curve (four measures) was obtained for every trimester; the Area Under the Curve with respect to the ground (AUCg) and with respect to the increase (AUCi) were used as measures of basal HPA axis functioning. Depressive symptomatology was assessed every pregnancy trimester and postpartum period following EPDS criteria. All the analyses were adjusted for maternal age, weight, ethnicity and socioeconomic status and sample collection’s time. Results Prenatal subclinical depressive symptomatology (EPDS>10) was associated with a blunted cortisol rhythm during first trimester (F= 3.913,p=.011) but not during second (F=2.629, p=056) or third trimesters (F=.411,p=.724). Furthermore, a logistic regression model showed a positive association between Prenatal subclinical depressive symptomatology and the risk of postpartum depression (χ2=13.8, p

Context: Maternal obesity, hypertensive pregnancy disorders, and gestational diabetes (GDM) are linked to an increased risk of negative offspring health outcomes. This association may be mediated by maternal hypothalamic-pituitary-adrenal axis (HPA axis) activity, resulting in elevated maternal cortisol levels and fetal exposure, but evidence remains scarce., Objective: We (1) examined maternal diurnal cortisol profiles longitudinally across gestation, and (2) explored associations with maternal cardiometabolic complications., Methods: Women in the InTraUterine sampling in early pregnancy (ITU) study (n = 667) provided 7 salivary cortisol samples from awakening to bedtime up to 3 times during pregnancy (median gestational week 19.3, 25.7, and 38.1; n = 9356 samples). Changes in cortisol awakening response (CAR) and diurnal slope (indicative of HPA axis activity) and their associations with maternal body mass index (BMI), hypertensive pregnancy disorders and GDM were examined using linear mixed models., Results: The CAR declined in 60% to 67% of women, and the diurnal slope attenuated from early to late pregnancy (b = 0.006; P = .001). Higher BMI was associated with less decline in CAR (b = 0.031; P = .0004) and less attenuation in diurnal slope from early to late pregnancy (b = -0.001; P = .006). Hypertensive pregnancy disorders and GDM were not significantly associated with diurnal cortisol profiles., Conclusion: The attenuation in CAR and diurnal slope support HPA axis hyporesponsivity during pregnancy. Less attenuation of both markers in women with a higher BMI may indicate reduced adaption of the HPA axis to pregnancy, presenting a mechanistic link to offspring health outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

The COVID-19 pandemic can seize the opportunity to explore the hypothesis of prenatal exposure to viral infections increases the risk for neurodevelopmental disorders. Advancing our knowledge in this regard would improve primary prevention of mental disorders in children. For this pilot study, six-week-old infants born to mothers exposed (n = 21) or unexposed (n = 21) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were assessed in Santander-Cantabria (Spain) using the Neonatal Behavioral Assessment Scale (NBAS). Groups comparisons were performed to explore the effects that infection and timing of exposure (in terms of the three trimesters of pregnancy). The infants' competencies and performances on the NBAS were generally similar in the exposed and unexposed to SARS-CoV-2 groups. The most significant difference found was a less optimally response to cuddliness (item on the state regulation domain) particularly in infants born to mothers exposed in the third trimester of pregnancy, and in pull-to-sit (item on the motor system domain). Although our interpretations must be careful, these preliminary results highlight the possible association between prenatal SARS-CoV-2 exposure and poorer development in motor skills and infant interactive behavior. Further longitudinal studies are needed to explore these relationships and disentangle the biological mechanisms implicated., (© 2023. The Author(s).)

Background: This study investigates the impact of childhood maltreatment (CM) on hypothalamic-pituitary-adrenal (HPA)-axis functioning and on anxiety perception. Moreover, the influence of CM severity and frequency was also explored., Methods: In total, 187 participants aged 7-17 were assessed for CM history using validated questionnaires and ad hoc interviews to be classified according to the criteria of the Tool for Assessing the Severity of Situations in which Children are Vulnerable (TASSCV). Psychopathology was ascertained using the K-SADS-PL5. To assess HPA-axis functioning, salivary cortisol samples were collected throughout a normal day and during an acute psychosocial stressor, the Trier Social Stress Test for children (TSST-C). Subjective anxiety was evaluated using STAI/-C., Results: Youth with a CM history had higher overall diurnal cortisol levels ( p = 0.001), blunted cortisol response to acute psychosocial stress ( p = 0.002) and greater perceived anxiety ( p = 0.003), than those without CM. Specifically, participants exposed to moderate/severe or often/frequent CM showed the greater diurnal cortisol output ( p severity = 0.002; p frequency = 0.003), and blunted cortisol response during the TSST-C ( p severity = 0.006; p frequency = 0.008). Meanwhile, youth with low CM severity/frequency exhibited a similar cortisol response to those without CM. However, perceived anxiety was higher in those exposed to CM ( p < 0.001), regardless of its severity/frequency., Conclusions: Disturbances in HPA-axis functioning are already evident early after CM exposure, while psychological and physiological responses to an acute stressor are dissociated in youth exposed to CM. The dose-response relationship described in this paper highlights the need to comprehensively evaluate CM so that vulnerable children can be identified and assigned to proper interventions.