UNASSIGNED: Genetically high-risk children carry indicators of brain dysfunctions that adult patients with schizophrenia or bipolar disorder display. The accumulation of risk indicators would have a higher predictive value of a later transition to psychosis or mood disorder than each individual risk indicator. Since more than 50% of adult patients report having been exposed to childhood trauma, we investigated whether exposure to trauma during childhood was associated with the early accumulation of risk indicators in youths at genetic risk.
UNASSIGNED: We first inspected the characteristics of childhood trauma in 200 young offspring (51% male) born to a parent affected by DSM-IV schizophrenia, bipolar disorder, or major depressive disorder. A subsample of 109 offspring (51% male) had measurements on four risk indicators: cognitive impairments, psychotic-like experiences, nonpsychotic nonmood childhood DSM diagnoses, poor global functioning. Trauma was assessed from direct interviews and reviews of lifetime medical and school records of offspring.
UNASSIGNED: Trauma was present in 86 of the 200 offspring (43%). The relative risk of accumulating risk indicators in offspring exposed to trauma was 3.33 (95% CI 1.50, 7.36), but more pronounced in males (RR = 4.64, 95% CI 1.71, 12.6) than females (RR = 2.01, 95% CI 0.54, 7.58).
UNASSIGNED: Childhood trauma would be related to the accumulation of developmental precursors of major psychiatric disorders and more so in young boys at high genetic risk. Our findings may provide leads for interventions targeting the early mechanisms underlying the established relation between childhood trauma and adult psychiatric disorders.

The widespread use of microplastics and their harmful effects on the environment have emerged as serious concerns. However, the effect of microplastics on the immune system of mammals, particularly their offspring, has received little attention. In this study, polystyrene microplastics (PS-MPs) were orally administered to male mice during lactation. Flow cytometry was used to assess the immune cells in the spleens of both adult male mice and their offspring. The results showed that mice exposed to PS-MPs exhibited an increase in spleen weight and an elevated number of B and regulatory T cells (Tregs), irrespective of dosage. Furthermore, the F1 male offspring of the PS-MPs-exposed group had enlarged spleens; an increased number of B cells, T helper cells (Th cells), and Tregs; and an elevated ratio of T helper cells 17 (Th17 cells) to Tregs and T helper cells 1 (Th1 cells) to T helper cells 2 (Th2 cells). These results suggested a pro-inflammatory state in the spleen. In contrast, in the F1 female offspring exposed to PS-MPs, the changes in splenic immune cells were less pronounced. In the F2 generation of mice with exposed to PS-MPs, minimal alterations were observed in spleen immune cells and morphology. In conclusion, our study demonstrated that exposure to real human doses of PS-MPs during lactation in male mice altered the immune status, which can be passed on to F1 offspring but is not inherited across generations.

Maternal high-fat diet intake has profound effects on the long-term health of offspring, predisposing them to a susceptibility to metabolic dysfunction-associated steatotic liver disease. However, the detailed mechanisms remain largely unclear. In this study, female C57BL/6J mice were randomly assigned to either a high-fat diet or a control diet, and lipid metabolism parameters were assessed in male offspring at weaning. Gut microbiota analysis and targeted metabolomics of short-chain fatty acids (SCFAs) in these offspring were further performed. Both in vivo and in vitro studies were conducted to explore the role of butyrate in hepatic cholesterol excretion in the liver and HepG2 cells. Our results showed maternal high-fat feeding led to obesity and dyslipidemia, and exacerbated hepatic lipid accumulation in offspring\'s liver at weaning. We observed decreases in the abundance of the Firmicutes phylum and the Allobaculum genus, known as producers of SCFAs, particularly butyrate, in the offspring of high-fat dams. Additionally, maternal high-fat diet feeding markedly decreased serum butyrate levels and downregulated ATP-binding cassette transporters G5 (ABCG5) in the liver, accompanied by decreased phosphorylated AMP-activated protein kinase (AMPK) and histone deacetylase 5 (HADC5) expressions. Subsequent in vitro studies revealed that butyrate could induce ABCG5 activation and alleviate lipid accumulation via the AMPK-pHDAC5 pathway in HepG2 cells. Moreover, knockdown of HDAC5 upregulated ABCG5 expression and promoted cholesterol excretion in HepG2 cells. In conclusion, our study provides novel insights into how maternal high-fat diet feeding inhibits hepatic cholesterol excretion and downregulates ABCG5 through the butyrate-AMPK-pHDAC5 pathway in offspring at weaning.

OBJECTIVE: Bipolar disorder (BD) is a highly heritable disorder characterized by emotion dysregulation and recurrent oscillations between mood states. Despite the proven efficacy of early interventions, vulnerability markers in high-risk individuals are still lacking. BD patients present structural alterations of the hippocampus, a pivotal hub of emotion regulation networks composed of multiple subregions with different projections. However, the hippocampal dynamic functional connectivity (dFC) in BD remains unclear. We aim to investigate whether the dFC of hippocampal subdivisions differentiates BD patients, offspring of BD patients (BDoff), and healthy controls (HC); and whether it correlates with symptoms differently between these groups.
METHODS: We studied for the first time the dFC of the hippocampus through a cutting-edge micro-co-activation patterns (μCAPs) analysis of resting-state functional MRI data of 97 subjects (26 BD, 18 BDoff, 53 HC). μCAPs allow a data-driven differentiation within the seed region.
RESULTS: dFC between the hippocampal body and a somatomotor-μCAP was lower both in BD patients (p-valueFDR:0.00015) and in BDoff (p-valueFDR:0.020) than in HC. Inversely, dFC between the hippocampal head and a limbic-μCAP was higher in BD patients than in HC (p-valueFDR: 0.005). Furthermore, the correlations between a frontoparietal-μCAP and both depression and emotion dysregulation symptoms were significantly higher in BD than HC (p-valueFDR <0.02).
CONCLUSIONS: Overall, we observed alterations of large-scale functional brain networks associated with decreased cognitive control flexibility and disrupted somatomotor, saliency, and emotion processing in BD. Interestingly, BDoff presented an intermediate phenotype between BD and HC, suggesting that dFC of hippocampal subregions might represent a marker of vulnerability to BD.

BACKGROUND: As the global consumption of sugary and non-sugar sweetened beverages continues to rise, there is growing concern about their health impacts, particularly among pregnant women and their offspring.
OBJECTIVE: This study aimed to investigate the consumption patterns of various beverages among pregnant women in Shanghai and their potential health impacts on both mothers and offspring.
METHODS: We applied a multi-stage random sampling method to select participants from 16 districts in Shanghai. Each district was categorised into five zones. Two towns were randomly selected from each zone, and from each town, 30 pregnant women were randomly selected. Data were collected through face-to-face questionnaires. Follow-up data on births within a year after the survey were also obtained.
RESULTS: The consumption rates of total beverages (TB), sugar-sweetened beverages (SSB), and non-sugar sweetened beverages (NSS) were 73.2%, 72.8%, and 13.5%, respectively. Logistic regression analysis showed that compared to non-consumers, pregnant women consuming TB three times or less per week had a 38.4% increased risk of gestational diabetes mellitus (GDM) (OR = 1.384; 95% CI: 1.129-1.696) and a 64.2% increased risk of gestational hypertension (GH) (OR = 1.642; 95% CI: 1.129-2.389). Those consuming TB four or more times per week faced a 154.3% higher risk of GDM (OR = 2.543; 95% CI: 2.064-3.314) and a 169.3% increased risk of GH (OR = 2.693; 95% CI: 1.773-4.091). Similar results were observed in the analysis of SSB. Regarding offspring health, compared to non-consumers, TB consumption four or more times per week was associated with a substantial increase in the risk of macrosomia (OR = 2.143; 95% CI: 1.304-3.522) and large for gestational age (LGA) (OR = 1.695; 95% CI: 1.219-2.356). In the analysis of NSS, with a significantly increased risk of macrosomia (OR = 6.581; 95% CI:2.796-13.824) and LGA (OR = 7.554; 95% CI: 3.372-16.921).
CONCLUSIONS: The high level of beverage consumption among pregnant women in Shanghai needs attention. Excessive consumption of beverages increases the risk of GDM and GH, while excessive consumption of NSS possibly has a greater impact on offspring macrosomia and LGA.

Micro-nanoplastic particulates (MNPs) have been identified in both indoor and outdoor environments. From these real-world exposures, MNPs have been identified in human fluids and organ tissues, including the placenta and breastmilk. Laboratory studies have identified MNPs are capable of crossing the placental barrier and depositing in fetal tissues; however, it remained unclear if MNPs persist in offspring tissues after birth. Six pregnant Sprague-Dawley rats were divided equally into two groups: control and exposed to polyamide-12 (PA-12) MNP aerosols (11.46 ± 3.78 mg/m3) over an average of 4.35 h ± 0.39 for 10 non-consecutive days between gestational day (GD) 6 - GD 19, in our custom rodent exposure chamber, allowing for whole-body inhalation. Two-weeks after delivery in-house, offspring tissues (i.e. lung, liver, kidney, heart, brain) from 1 male and 1 female pup per litter were fixed in 4 % paraformaldehyde, sectioned, stained with hematoxylin and eosin, and assessed using hyperspectral dark-field microscopy. PA-12 MNPs were identified in all offspring tissues of the exposed dams. No MNPs were visualized in control tissues. These findings have important implications for human MNPs translocation, deposition, maternal/fetal health, and the developmental origins of health and disease. Further research is warranted to quantify MNPs mass deposition, biological accumulation, and systemic toxicity.

BACKGROUND: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) outbreak in 2019 has necessitated investigating its potential adverse effects on pregnancy outcomes and fetal development.
OBJECTIVE: This study aimed to review the evidence on the impact of SARS-CoV-2 infection during pregnancy on fetal outcomes.
METHODS: Literatures since the outbreak of COVID-19 from PubMed and Web of Science were summarized in this narrative review, to show the effects of maternal SARS-CoV-2 infection during pregnancy on fetal development.
RESULTS: SARS-CoV-2 infection during pregnancy can be transmitted vertically through the placenta, both in utero and perinatally, affecting the maternal-fetal immune interface and placental function. Viral infections during pregnancy have been linked to central nervous system development impairments and disorders such as autism. Changes in the structure and function of the respiratory, immune, and visceral systems have also been reported. SARS-CoV-2 infection during pregnancy has been linked with increased risks of stillbirth and preterm birth. However, the mechanisms involved remain unclear and may include cytokine storms, macrophage mediation, genetic mutations, methylation, and other epigenetic changes. Exploring the protective effects of antiviral treatment and other interventions in animal and clinical studies may help improve outcomes.
CONCLUSIONS: SARS-CoV-2 infection during pregnancy activates the maternal-fetal immune interface through vertical transmission, and has short- and long-term effects on fetal development, including the central nervous system. Future long-term studies may help provide evidence that can inform interventions to reduce the risk of adverse outcomes.

UNASSIGNED: This longitudinal study evaluated the association between childhood family structure and health-related quality of life (HRQoL) at middle age.
UNASSIGNED: The data on childhood family structure at the age of 14 years (\'two-parent family\', \'one parent not living at home/no information on father\' and \'father or mother deceased\') and HRQoL (measured by 15D (15-dimensional)) at the age of 46 were collected from the Northern Finland Birth Cohort 1966 using postal questionnaires. We used the binary logistic regression model to estimate the associations between childhood family structures and the lowest 15D quartile (reference: all other quartiles). The associations were adjusted for offspring mothers\' factors during pregnancy (mothers\' educational and occupational status).
UNASSIGNED: Of the 6375 participants, the offspring belonging to the \'one parent not living at home/no information on father\' family structure subgroup had higher odds ratio of belonging to the lowest 15D quartile than the offspring of \'two-parent families\' (adjusted odds ratio (OR) 1.76, 95% confidence interval (CI) 1.31-2.36, p<0.001 for females; adjusted OR 1.86, 95% CI 1.28-2.70, p=0.001 for males). There were no statistically significant associations between the \'father or mother deceased\' subgroup and the lowest 15D quartile among the offspring.
UNASSIGNED: A single-parent family origin (due to reasons other than parental death) in childhood was significantly associated with impaired HRQoL at middle age. These results provide new perspectives for understanding the long-standing associations on living in a single-parent family.

Lung cancer is intricately associated with genetic susceptibility, leading to familial clustering among affected individuals. This cross-sectional study aimed to assess the knowledge, attitude, and practice (KAP) toward lung cancer risk among the offspring of lung cancer patients. This study was conducted at Guangdong Provincial People\'s Hospital between April 2023 and August 2023. Participants\' demographic characteristics and KAP toward lung cancer risk were collected through questionnaires. A total of 481 valid questionnaires were enrolled, with 243 (50.52%) males, and 242 (50.31%) aged > 40 years old. The mean scores for knowledge, attitude, and practice were 8.54 ± 2.60 (range: 0-13), 25.93 ± 3.16 (range: 7-35), and 17.47 ± 4.30 (range: 5-25), respectively. Structural equation modeling indicated that knowledge exerted a negative direct effect on attitude (β = - 0.417, P = 0.006) but a positive direct effect on practice (β = 0.733, P = 0.025). Additionally, attitudes displayed a negative direct effect on practice (β = - 1.707, P = 0.002). In conclusion, offspring of lung cancer patients exhibited insufficient knowledge, positive attitude, and suboptimal practice toward lung cancer risk.

BACKGROUND: As the fetus relies on maternal thyroid hormones in early pregnancy, maternal hypothyroidism plays an important role in fetal development. However, the association between maternal hypothyroidism and metabolic disease in offspring is unclear.
OBJECTIVE: To examine the association between maternal hypothyroidism in pregnancy and metabolic outcomes (obesity, hypertension, type 2 diabetes mellitus, and dyslipidemia) in children < 18 years.
METHODS: We systematically searched 5 databases from inception to May 2023. Eligible studies included cohort, case-control, and randomized controlled trials involving children born to mothers with or without hypothyroidism in pregnancy. Data were pooled across studies using random-effects models for outcomes reported in at least three studies. Quality assessment was performed using the ROBINS-E tool for observational studies and the Cochrane Risk of Bias tool for trials.
RESULTS: The search identified 3221 articles, of which 7 studies were included (1 trial, 6 observational). All studies were conducted outside of North America and ranged in size from 250 to > 1 million children. The follow-up time ranged from 6 to 20 years. Included studies support an increased risk of hypertension and glucose dysregulation in offspring exposed to maternal hypothyroidism (hypertension: OR 1.08, 95% CI 0.75, 1.57 and HR 1.81, 95% CI 1.21, 2.69; diabetes: RR 2.7, 95% CI 0.7, 10). In the pooled analysis, maternal hypothyroidism was not associated with obesity in offspring (OR 1.04, 95% CI 0.64, 1.70).
CONCLUSIONS: This study found inconsistent evidence on the association between maternal hypothyroidism in pregnancy and metabolic outcomes in offspring, though associations with hypertension and glucose dysregulation are possible.