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BackgroundAn extensive body of animal literature supports the premise that maternal obesity during pregnancy can alter the development of the fetal hypothalamus (HTH, a critical regulator of energy balance) with implications for offspring obesity risk (i.e., long-term energy imbalance). Yet, the relationship in humans between maternal overweight/obesity during pregnancy and fetal hypothalamic development remains largely unknown. Here, using an international (Finland and California, USA) multi-site diffusion tensor imaging (DTI) dataset, we test the hypothesis that maternal pre-pregnancy BMI is associated with newborn offspring HTH mean diffusivity (HTH MD, a replicable neural correlate of BMI in adults).MethodsHTH MD was independently quantified in two separate BMI-matched cohorts (up to class II obesity; BMIRange = 17-35) using a high-resolution atlas-based definition of HTH. A total of n = 231 mother-child dyads were available for this analysis (nSite,1 = 152, age at MRI = 26.7 ± 8.1 days, gestational age at birth = 39.9 ± 1.2 weeks, nM/F = 82/70, BMI = 24.2 ± 3.8; nSite,2 = 79, age at MRI = 25.6 ± 12.5 days, gestational age at birth = 39.3 ± 1.5 weeks, nM/F = 45/34, BMI = 25.1 ± 4.0). The association between maternal pre-pregnancy BMI and newborn offspring HTH MD was examined separately in each cohort using linear regression adjusting for gestational age at birth, postnatal age at scan, sex, whole white matter mean diffusivity, and DTI quality control criteria. In post hoc analyses, additional potentially confounding factors including socioeconomic status, ethnicity, and obstetric risk were adjusted where appropriate.ResultsThe distribution of maternal pre-pregnancy BMI was comparable across sites but differed by ethnicity and socioeconomic status. A positive linear association between maternal pre-pregnancy BMI and newborn offspring HTH MD was observed at both sites ([Formula: see text]Site,1 = 0.17, pSite,1 = 0.01; [Formula: see text]Site,2 = 0.22, pSite,2 = 0.03) and remained significant after adjusting for cohort-relevant covariates.ConclusionsThese findings translate the preclinically established association between maternal obesity during pregnancy and offspring hypothalamic microstructure to the human context. In addition to further replication/generalization, future efforts to identify biological mediators of the association between maternal obesity and fetal HTH development are warranted to develop targeted strategies for the primary prevention of childhood obesity.

The normative, developmental changes in affect-biased attention during the preschool years are largely unknown. To investigate the attention bias for emotional versus neutral faces, an eye-tracking measurement and free viewing of paired pictures of facial expressions (i.e., happy, fearful, sad, or angry faces) and nonface pictures with neutral faces were conducted with 367 children participating in a Finnish cohort study at the age of 2.5 years and with 477 children at the age of 5 years, 216 of which having follow-up measurements. We found an attention-orienting bias for happy and fearful faces versus neutral faces at both age points. An attention-orienting bias for sad faces emerged between 2.5 and 5 years. In addition, there were significant biases in sustained attention toward happy, fearful, sad, and angry faces versus neutral faces, with a bias in sustained attention for fearful faces being the strongest. All biases in sustained attention increased between 2.5 and 5 years of age. Moderate correlations in saccadic latencies were found between 2.5 and 5 years. In conclusion, attention biases for emotional facial expressions seem to be age-specific and specific for the attentional subcomponent. This implies that future studies on affect-biased attention during the preschool years should use small age ranges and cover multiple subcomponents of attention.

The study aimed to investigate the persistence or changes in trait resilience of parents over a 6‐year period and its association with stressful life events (SLEs). Furthermore, we explored the potential protective effect of trait resilience against exposure to stressful life events and their negative mental health consequences. The study population was drawn from the ongoing FinnBrain Birth Cohort Study and included 1388 mothers and 657 fathers who completed the CD‐RISC‐10 questionnaire during pregnancy and again 6 years later. Data collection involved self‐report questionnaires, including CD‐RISC‐10, EPDS, SCL‐90, and a questionnaire on SLEs. Data analysis utilised linear regression and statistical assessments. Parents in the highest or lowest quartile of resilience showed greater stability in resilience scores over time compared to those in the middle quartiles. Trait resilience during pregnancy was significantly associated with resilience 6 years later. SLEs did not moderate this association. Additionally, higher trait resilience consistently associated with lower levels of distress symptoms. The investigation of SLEs may require more nuance due to their event‐specific variability of impact. Furthermore, the study's sample size of individuals who experienced a high frequency of stressful life events was limited. Trait resilience appears to be rather stable, but also susceptible to some change. Because of its persistency and the positive impact on mental health it is worthwhile to be assessed as a part of comprehensive evaluation of parents' mental health. [ABSTRACT FROM AUTHOR]

Early-onset pre-eclampsia is believed to arise from defective placentation in the first trimester, leading to placental ischaemia/reperfusion (I/R) and oxidative stress. However, our current understanding of the effects of I/R and oxidative stress on trophoblast function is ambiguous in part due to studies exposing trophoblasts to hypoxia instead of I/R, and which report conflicting results. Here, we present a model of simulated ischaemia/reperfusion (SI/R) to recapitulate the pathophysiological events of early-onset pre-eclampsia (PE), by exposing first trimester cytotrophoblast HTR-8/SVneo cells to a simulated ischaemia buffer followed by reperfusion. We examined different ischaemia and reperfusion times and observed that 1 h ischaemia and 24 h reperfusion induced an increase in reactive oxygen species (ROS) production (P<0.0001) and oxygen consumption rate (P<0.01). SI/R-exposed trophoblast cells exhibited deficits in migration, proliferation, and invasion (P<0.01). While the deficits in migration and proliferation were rescued by antioxidants, suggesting an ROS-dependent mechanism, the loss of invasion was not affected by antioxidants, which suggests a divergent ROS-independent pathway. In line with this, we observed a decrease in MMP-9, the key regulatory enzyme necessary for trophoblast invasion (P<0.01), which was similarly unaffected by antioxidants, and pharmacological inhibition of MMP-9 replicated the phenotype of deficient invasion (P<0.01). Collectively, these data demonstrate that I/R impairs trophoblast migration and proliferation via a ROS-dependent mechanism, and invasion via an ROS-independent loss of MMP-9, disambiguating the role of oxidative stress and providing insights into the response of trophoblasts to I/R in the context of early-onset PE. [ABSTRACT FROM AUTHOR]

Research on the longitudinal courses of child social–emotional symptoms and sleep during the COVID-19 pandemic within societies would be of key value for promoting child well-being in global crises. We characterized the course of children's social–emotional and sleep symptoms before and throughout the pandemic in a Finnish longitudinal cohort of 1825 5- to 9-year-old children (46% girls) with four follow-up points during the pandemic from up to 695 participants (spring 2020–summer 2021). Second, we examined the role of parental distress and COVID-related stressful events in child symptoms. Child total and behavioral symptoms increased in spring 2020 but decreased thereafter and remained stable throughout the rest of the follow-up. Sleep symptoms decreased in spring 2020 and remained stable thereafter. Parental distress was linked with higher child social–emotional and sleep symptoms. The cross-sectional associations between COVID-related stressors and child symptoms were partially mediated by parental distress. The findings propose that children can be protected from the long-term adverse influences of the pandemic, and parental well-being likely plays a mediating role between pandemic-related stressors and child well-being. Further research focusing on the societal and resilience factors underlying family and child responses to the pandemic is warranted. [ABSTRACT FROM AUTHOR]

Pre-eclampsia (PE) is a hypertensive disorder of pregnancy which is associated with increased risk of neurodevelopmental disorders in exposed offspring. The pathophysiological mechanisms mediating this relationship are currently unknown, and one potential candidate is the anti-angiogenic factor soluble Fms-like tyrosine kinase 1 (sFlt-1), which is highly elevated in PE. While sFlt-1 can impair angiogenesis via inhibition of VEGFA signalling, it is unclear whether it can directly affect neuronal development independently of its effects on the vasculature. To test this hypothesis, the current study differentiated the human neural progenitor cell (NPC) line ReNcell® VM into a mixed culture of mature neurons and glia, and exposed them to sFlt-1 during development. Outcomes measured were neurite growth, cytotoxicity, mRNA expression of nestin, MBP, GFAP, and ßIII-tubulin, and neurosphere differentiation. sFlt-1 induced a significant reduction in neurite growth and this effect was timingand dose-dependent up to 100 ng/ml, with no effect on cytotoxicity. sFlt-1 (100 ng/ml) also reduced ßIII-tubulin mRNA and neuronal differentiation of neurospheres. Undifferentiated NPCs and mature neurons/glia expressed VEGFA and VEGFR-2, required for endogenous autocrine and paracrine VEGFA signalling, while sFlt-1 treatment prevented the neurogenic effects of exogenous VEGFA. Overall, these data provide the first experimental evidence for a direct effect of sFlt-1 on neurite growth and neuronal differentiation in human neurons through inhibition of VEGFA signalling, clarifying our understanding of the potential role of sFlt-1 as a mechanism by which PE can affect neuronal development. [ABSTRACT FROM AUTHOR]

Maternal prenatal distress (PD), frequently defined as in utero prenatal stress exposure (PSE) to the developing fetus, influences the developing brain and numerous associations between PSE and brain structure have been described both in neonates and in older children. Previous studies addressing PSE-linked alterations in neonates' brain activity have focused on connectivity analyses from predefined seed regions, but the effects of PSE at the level of distributed functional networks remains unclear. In this study, we investigated the impact of prenatal distress on the spatial and temporal properties of functional networks detected in functional MRI data from 20 naturally sleeping, term-born (age 25.85 ± 7.72 days, 11 males), healthy neonates. First, we performed group level independent component analysis (GICA) to evaluate an association between PD and the identified functional networks. Second, we searched for an association with PD at the level of the stability of functional networks over time using leading eigenvector dynamics analysis (LEiDA). No statistically significant associations were detected at the spatial level for the GICA-derived networks. However, at the dynamic level, LEiDA revealed that maternal PD negatively associated with the stability of a frontoparietal network. These results imply that maternal PD may influence the stability of frontoparietal connections in neonatal brain network dynamics and adds to the cumulating evidence that frontal areas are especially sensitive to PSE. We advocate for early preventive intervention strategies regarding pregnant mothers. Nevertheless, future research venues are required to assess optimal intervention timing and methods for maximum benefit. [ABSTRACT FROM AUTHOR]