Search Results (28)

Objectives: To investigate the potential mechanisms of maternal pregestational diabetes-induced neural tube defects (NTDs) by integrating proteomic data and histone H4 lysine 5 acetylation (H4K5ac) ChIP-seq data from the mouse model. Methods: The diabetic mouse model was established by intraperitoneal injection of streptozotocin (STZ) into female friend leukemia virus B strain (FVB) mice, with subsequent blood glucose monitoring. Diabetic females were then mated with healthy males, and embryonic tissues were collected on embryonic day 9.5. Among the embryos obtained from diabetic pregnancies, six NTDs embryos and six control embryos were selected for protein expression profiling using tandem mass tag (TMT)-labeled liquid chromatography-tandem mass spectrometry (LC-MS/MS), as well as for assessment of H4K5ac modification by ChIP-seq. Multi-omics integration was performed to identify common differentially expressed genes, followed by functional enrichment analysis. Key genes were validated using RT-qPCR. Results: Proteomic analysis revealed that differentially expressed proteins were significantly enriched in focal adhesion pathway. Protein–protein interaction (PPI) network analysis indicated that these proteins (e.g., Integrin alpha 3 (Itga3), glycogen synthase kinase 3 beta (Gsk3b), mitogen-activated protein kinase 9 (Mapk9)) were associated with focal adhesion and cytoskeletal functions. Integrated multi-omics analysis identified 923 common differentially expressed genes, which were also significantly enriched in focal adhesion pathway. Within this pathway, the protein expression levels of Itga3, Gsk3b, and Mapk9 exhibited a consistent co-variation trend with H4K5ac enrichment. RT-qPCR results confirmed that Itga3 was significantly up-regulated, while Gsk3b was down-regulated in the NTDs group (p < 0.05). Conclusions: Maternal pregestational diabetes may contribute to NTDs by disrupting cytoskeletal reorganization, cell adhesion, and migration processes. This disruption is likely mediated through H4K5ac-regulated expression of key focal adhesion pathway genes such as Itga3 and Gsk3b. Full article

Existing research on quality gain-loss functions predominantly focuses on single variables or separable quality characteristics, overlooking the correlations among multiple quality attributes and the complexity of spatiotemporal factors. To address this issue, this study proposes a multivariate and multidimensional quality gain-loss function model based on a nonseparable Gaussian process (NSGP). A spatiotemporal interaction term is constructed using the Matérn kernel function, while the Kalman filtering and smoothing algorithms are introduced to improve computational efficiency. In addition, the signal-to-noise ratio is employed to determine the joint gain-loss weights, thereby establishing the multivariate and multidimensional quality gain-loss function model. Taking hydraulic concrete construction as the research background, simulation experiments and a practical engineering case are used to examine the performance and applicability of the proposed model. The results indicate that, compared with conventional machine learning methods, the NSGP model achieves superior predictive accuracy and can effectively characterize the spatiotemporal evolution patterns of concrete slump and segregation resistance. However, the interval coverage probability in the dam concrete case study remains lower than the nominal level, indicating that uncertainty quantification requires further improvement. The proposed model does not require prior determination of covariance separability during computation. Under the given dataset and assumptions, it provides an exploratory quantitative tool for point prediction, multivariate quality evaluation, and parameter optimization of selected fresh concrete indicators. Full article

Background/Objectives: Maternal valaciclovir therapy is increasingly used to reduce fetal viral replication in cases of primary cytomegalovirus (CMV) infection during pregnancy. However, data on its impact on early neurodevelopmental outcomes remain limited. This study aimed to evaluate the association between prenatal valaciclovir exposure and early neurodevelopment in infants with confirmed congenital CMV infection (cCMV). Methods: In this retrospective monocentric cohort study, 30 infants with PCR-confirmed cCMV infection were assessed at 4–8 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Infants were stratified according to prenatal exposure to maternal valaciclovir. Univariate analyses and multivariable linear regression models were performed to evaluate the association between prenatal antiviral exposure and cognitive outcome, adjusting for brain MRI findings and selected clinical variables. Results: Fifteen infants (50%) were exposed to prenatal valaciclovir. Exposed infants demonstrated higher cognitive composite scores compared with unexposed infants (median 105 [IQR 100–110] vs. 90 [85–110]; p = 0.030). In multivariable analysis, prenatal valaciclovir exposure remained significantly associated with higher cognitive scores (β = 11.89, 95% CI 2.86–20.92; p = 0.012), while neonatal MRI abnormalities were not independently associated with outcome. No significant differences were observed in language or motor domains. The final model explained 30% of the variance in cognitive scores (R² = 0.30). Conclusions: Prenatal valaciclovir exposure was associated with higher cognitive composite scores after adjustment for selected covariates. Although causality cannot be inferred, these findings suggest a potential association with early neurodevelopmental outcomes and support the inclusion of functional neurodevelopmental endpoints in future prospective studies. These results should be considered exploratory and hypothesis-generating Full article

Background: Although there is substantial research into individual nutrients during pregnancy, such as folate, iron, and vitamin D, little is known about the impact of mixtures of essential nutrients. We investigated the associations between mixtures of maternal essential minerals and vitamin concentrations and child cognition and executive functions at age 7. Methods: Data from 348 mother–child pairs in the Growing up in Singapore Towards Healthy Outcomes birth cohort with both plasma nutrient and neurodevelopmental outcome data were used. Gestational fasting plasma samples between 26 and 28 weeks of gestation were analyzed for 10 essential minerals and 12 B and D vitamers. Child cognition and executive functions at 7 years were assessed using the Wechsler Abbreviated Scale of Intelligence 2nd Edition (WASI-II) [n = 331] and the Behavior Rating Inventory of Executive Function 2nd Edition (BRIEF-2) [n = 348], respectively. Generalized weighted quantile sum regression (gWQS) was used to investigate the associations between nutrient mixtures and child cognitive executive function scores. Single-nutrient analysis using covariate-adjusted multivariable regressions was performed as a sensitivity analysis. Results: A one-quartile increase in the positively weighted nutrient mixture index was associated with higher block design T-scores (β = 2.17, 95% CI: 0.03, 4.31). Additionally, the negatively weighted mixture was associated with lower block design (β = −2.25, 95% CI: −4.92, 0.41, p = 0.02) and perceptual reasoning (β = −1.94, 95% CI: −5.17, 1.29, p = 0.04) scores in boys only. We found no association between the nutrient mixture and BRIEF-2 subscale T-scores. Conclusions: In this study, we found that a positively weighted nutrient mixture index of maternal gestational minerals and vitamins was associated with a greater ability in children to analyze and understand abstract visual items. Full article

Civil registration of births and deaths underpins people’s legal identity, access to essential services, and evidence-based policy. Over the last two decades, the expansion of the National Health Mission (NHM) and the dramatic increase in institutional deliveries have created new opportunities to link maternal healthcare with critical event documentation. Primary health centres (PHCs) and community health centres (CHCs), which are frequently the initial point of contact for rural households, are emerging as important places for birthing and registration. Despite their expanding importance, the particular role of these grassroots facilities in birth registration results has not been thoroughly investigated. This study addresses that gap by assessing their role in increasing registration coverage among children under the age of five. We analyzed nationally representative data from the National Family Health Survey rounds 4 (2015–2016) and 5 (2019–2021). This study focused on children under five, examining the association between place of delivery and registration status. Descriptive analysis and multivariable logistic regression estimated the odds of registration across delivery settings. Pooled data from both survey rounds captured temporal shifts, and predicted probabilities were calculated for institutional deliveries, adjusting for socio-demographic covariates. The proportion of institutional births occurring in PHCs and CHCs rose from 30.5% to 34.7% between the two survey rounds. Registration among children delivered in these facilities increased from 80.8% to 90.2%, the highest gain among all delivery settings. Regression analysis showed that births in PHCs/CHCs were associated with 38% higher odds of being registered compared to private facilities. States designating PHCs and CHCs as official registrars, such as Delhi, Rajasthan, and Uttar Pradesh, reported the greatest improvements. Lower-level government health facilities are not only advancing safe delivery but also acting as pivotal nodes for civil registration. Their dual function creates a scalable model for integrating healthcare with legal identity creation, supporting equity and accelerating progress toward Sustainable Development Goal 16.9. Full article

Background/Objective: Anxiety symptoms in preschool children represent early indicators of potential mental health vulnerabilities. Maternal psychological, sociodemographic, lifestyle and dietary factors may be associated with child emotional development; however, evidence regarding their independent contributions to distinct dimensions of child anxiety (trait vs. state) remains limited. This study aimed to examine maternal factors associated with preschool children’s trait and state anxiety. Methods: In this cross-sectional study conducted in Greece, 200 preschool-aged children and their mothers were assessed. Maternal demographic, socioeconomic, anthropometric, lifestyle, dietary, and psychosocial characteristics were evaluated using validated instruments, including the Mediterranean Diet Score (MedDietScore), Beck Depression Inventory–II (BDI-II), and the State–Trait Anxiety Inventory short form (STAI-6). Children’s trait and state anxiety were assessed using the State–Trait Anxiety Inventory for Children (STAI-CH). Bivariate analyses were conducted, followed by separate multivariable linear regression models for trait and state anxiety, with covariate selection guided by a directed acyclic graph (DAG). Results: Maternal anxiety was positively associated with children’s state anxiety (B = 1.508, SE = 0.566, β = 0.196, t = 2.666, p = 0.008; 95% CI [0.43, 2.66]). Higher maternal educational attainment demonstrated a weak positive association with child state anxiety (B = 1.061, SE = 0.509, β = 0.145, t = 2.086, p = 0.038; 95% CI [0.08, 2.09]), which may reflect greater awareness or reporting of child symptoms by more-educated mothers or other unmeasured factors. For trait anxiety, maternal depressive symptomatology exhibited the strongest association (B = 3.578, SE = 0.918, β = 0.276, t = 3.897, p < 0.001; 95% CI [1.77, 5.39]), while maternal anxiety was also independently associated with higher trait anxiety (B = 2.088, SE = 0.744, β = 0.194, t = 2.807, p = 0.006; 95% CI [0.62, 3.56]). The models explained a modest proportion of variance (R² < 0.15), indicating that most variation in child anxiety does not seem to be fully explained by the specific measured maternal factors. Conclusions: Maternal psychological distress was modestly associated with preschool children’s state and trait anxiety, exhibiting differential patterns across anxiety dimensions. These findings should be interpreted as correlational, with unmeasured contributors such as paternal mental health, family functioning, genetics, and school/peer influences likely playing important roles. Early screening and interventions addressing maternal mental health may support children’s emotional well-being, but further multi-informant and longitudinal research is needed to clarify temporal and causal pathways. Full article

Background: Postpartum depression and anxiety are common in the perinatal period and can adversely affect maternal functioning and infant outcomes. Self-esteem is a relevant psychosocial factor, yet evidence from Eastern Europe remains limited. Objectives: To describe self-esteem levels among postpartum Romanian women, examine correlational associations between self-esteem and postpartum depression/anxiety symptoms, and assess whether these associations persist after adjustment for sociodemographic and clinical covariates, across two maternity centers in a cross-sectional design. Methods: This cross-sectional study included 201 postpartum women recruited consecutively during their initial postpartum hospitalization from two public maternity hospitals in Western Romania (Bihor, n = 100; Timiș, n = 101) during 2024–2025. Participants completed the Rosenberg Self-Esteem Scale (RSES), Edinburgh Postnatal Depression Scale (EPDS), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7). Associations were assessed with χ² tests (categorical comparisons), Pearson correlations, and multivariable linear regression models including center and selected sociodemographic/obstetric covariates. Results: Self-esteem showed a strong inverse correlation with postpartum depressive symptoms (RSES–EPDS: r = −0.542 overall; r = −0.537 in Bihor; r = −0.552 in Timiș; all p < 0.001). Negative correlations were also observed with anxiety (RSES–GAD-7: r = −0.400; p < 0.001) and PHQ-9 depressive severity (r = −0.370; p < 0.001). Stratified analyses indicated graded symptom burden across self-esteem categories, with higher EPDS risk proportions among women with moderate/low self-esteem within each center (χ²p ≤ 0.039). In adjusted models, EPDS (B = −0.37; p < 0.001) and GAD-7 (B = −0.15; p = 0.021) remained independently associated with lower RSES, alongside study center (Timiș vs. Bihor: B = −1.08; p = 0.043) and educational attainment. Conclusions: Lower self-esteem co-occurs with postpartum depressive symptoms and, secondarily, anxiety in Romanian women. While the cross-sectional design precludes causal inference, these robust correlational associations support the potential value of self-esteem assessment for early psychosocial risk identification. Longitudinal research is needed to establish temporal relationships and evaluate whether self-esteem can prospectively predict postpartum mental health outcomes. Full article

Background/Objectives: The establishment of strong prenatal bonding is a key determinant of perinatal well-being, influencing maternal psychological adaptation and infant development. Numerous studies have examined risk factors and psychopathology during pregnancy, but limited research has explored the role of positive psychological constructs, such as positive mental health (PMH). This study aimed to assess whether anxiety mediates the relationship between PMH and the quality of prenatal bonding. Methods: A total of 90 pregnant women participated. PMH was assessed using the Abbreviated Positive Mental Health Questionnaire; anxiety using the Hospital Anxiety and Depression Scale; and prenatal bonding using the Prenatal Assessment Scale for Pregnant Women (EVAP). A simple mediation model was tested, with anxiety as a mediator between PMH (predictor) and prenatal bonding (outcome), controlling the analysis for previous miscarriages, relationship stability, high-risk pregnancy, and employment. Results: The model revealed partial mediation (F = 16.617, p < 0.001). Higher PMH was associated with lower anxiety (B = −0.297, SE = 0.062, p < 0.001) and stronger prenatal bonding (B = 0.777, SE = 0.091, p < 0.001). Interestingly, anxiety emerged as an adaptive response, which could improve maternal sensitivity and communication with the unborn child (B = 0.316, SE = 0.145, p = 0.032). The model explained 56% of the variance in prenatal bonding, even after accounting for relevant covariates. Conclusions: These findings underscore the importance of considering contextual and psychosocial factors when assessing the role of emotions such as anxiety during pregnancy. Rather than being inherently maladaptive, anxiety may play a functional role in facilitating maternal engagement with the baby, especially when grounded in PMH. Given the limited research, our findings support the integration of positive psychology frameworks into perinatal health interventions. Full article

Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 gravida predominantly in <12-week gestation, we correlated the relative quantification of plasma proteins assessed via a multiplexed aptamer assay (SOMAScan^®) with AGP and CRP, quantified by immunoassay. We defined a plasma inflammasome as protein correlates meeting a false discovery rate <0.05. We examined potential pathways using principal component analysis. A total of 147 and 879 of 6431 detected plasma proteins correlated with AGP and CRP, respectively, of which 61 overlapped with both biomarkers. Positive correlates included serum amyloid, complement, interferon-induced, and immunoregulatory proteins. Negative correlates were micronutrient and lipid transporters and pregnancy-related anabolic proteins. The principal components (PCs) of AGP were dominated by negatively correlated anabolic proteins associated with gestational homeostasis, angiogenesis, and neurogenesis. The PCs of CRP were more diverse in function, reflecting cell surface and adhesion, embryogenic, and intracellular and extra-hepatic tissue leakage proteins. The plasma proteome of AGP or CRP reveals wide proteomic variation associated with early gestational inflammation, suggesting mechanisms and pathways that merit future research. Full article

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that an MBW of <2500 g (low MBW) was associated with an increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075–1.792]), angioma (1.491 [1.079–2.059]), and inguinal hernia (1.746, [1.189–2.565]), while those with an MBW of ≥4000 g (high MBW) were associated with congenital anomalies of the urinary tract (2.194, [1.261–3.819]) and arrhythmia (1.775, [1.157–2.725]) compared with those with an MBW of 3000–3499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052–2.064]), congenital heart disease (1.615, [1.119–2.332]), genital organs (1.648, [1.130–2.405]), hypospadias (1.804, [1.130–2.881]), and inguinal hernia (1.484, [1.189–1.851]) in male infants and CAKUT (1.619, [1.154–2.273]) in female infants, whereas high MBW was associated with congenital heart disease (1.745, [1.058–2.877]) and CAKUT (2.470, [1.350–4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk. Full article

This study examined the associations between maternal pre-pregnancy BMI and gestational weight gain (GWG) and children’s neuropsychological outcomes at 3 to 5 years of age. A total of 379 women and their children from the Alberta Pregnancy Outcomes and Nutrition (APrON) study participated. Covariate-adjusted robust regressions examined associations between maternal pre-pregnancy BMI, GWG class, interaction terms, and child outcomes. Each unit increase in maternal BMI was linked to a 0.48-point decrement (95% CI: −0.75 to −0.21) in children’s Full Scale IQ. Higher pre-pregnancy BMI was related to poorer performance on the other intelligence indexes (B = −0.35 to −0.47, 95% CIs: −0.75, −0.02) and lower performance on measures of language (B = −0.08 to −0.09, 95% CIs: −0.16, −0.02), motor skills (B = −0.08 to −0.11, 95% CIs: −0.18, −0.01), and executive function (B = −0.09 to −0.16, 95% CIs: −0.26, −0.01). GWG below the recommended range was associated with a 4.04-point decrement (95% CI: 7.89, −0.11) in Full Scale IQ, but better performance on a spatial working memory test (B = 0.27, 95% CI: 0.02, 0.52). GWG above the recommended range was associated with lower language (B = −0.79, 95% CI: −1.52, −0.06) and memory scores (B = −0.93, 95% CI: −1.64, −0.22). Interactions were found between pre-pregnancy BMI and GWG on measures of intelligence and executive function. Maternal pre-pregnancy BMI and GWG are related to children’s performance in various neuropsychological domains and may interact to predict outcomes. Optimizing maternal health and weight prior to conception and during pregnancy may enhance children’s neuropsychological outcomes. Full article

Environmental pollutions, particularly toxic elements such as lead, are among the most significant factors affecting the growth and functional development of children. The aim of this study was to evaluate the effect of blood lead levels on handgrip strength (HGS) in urban children resident in the Copper Basin of Lower Silesia, Poland, controlling for the effects of chronological age, body size and socioeconomic status. The study included 165 boys (9–11 years of age) and 79 girls (9–10 years of age) from Polkowice town. Anthropometric measurements involved height, body mass and grip strength of the left and right hands. Maternal education was a proxy for socioeconomic status. Based on the median value of blood lead level (3.10 µg/dL), the two groups-below and above/equal median value-were defined. Analysis of covariance revealed that age (all p < 0.001), sex (at least p < 0.01), BMI (all p < 0.001), and blood lead level (at least p < 0.05) had a significant effect on the three indicators of HGS (right hand, left hand, average), while the level of maternal education did not significantly affect HGS (p > 0.05). The results of this study indicate a potentially negative effect of elevated blood lead level on grip strength in preadolescent children, irrespective of sex. Full article

(1) Background: Lutein and zeaxanthin (L&Z) are essential dietary nutrients that are a crucial component of the human macula, contributing to visual functioning. They easily cross the placental barrier, so that retinal deposition commences during foetal development. This study aims to assess associations between maternal L&Z intake during pregnancy and offspring visual function at 11–12 years. (2) Methods: Using the Spanish INfancia y Medio Ambiente project (INMA) Sabadell birth cohort, 431 mother–child pairs were analysed. L&Z data were obtained from food frequency questionnaires (FFQ) at week 12 and 32 of pregnancy, alongside other nutritional and sociodemographic covariates. Contrast vision (CS) and visual acuity (VA) were assessed using the automated Freiburg Acuity and Contrast Testing (FRACT) battery. Low CS and VA were defined as being below the 20th cohort centile. Associations were explored using multiple logistic regression. (3) Results: After controlling for potential confounders, L&Z intake during the 1st and 3rd trimester did not reveal any statistically significant association with either CS or VA in offspring at age 11/12 years. (4) Conclusions: No evidence of a long-term association between L&Z intake during pregnancy and visual function in offspring was found. Further larger long-term studies including blood L&Z levels are required to confirm this result. Full article

Background: There are few studies that look at the intake of all types of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during the different stages of pregnancy along with a long-term neuropsychological follow-up of the child. This study aims to explore the association between maternal n-3 PUFA intake during two periods of pregnancy and the child’s neuropsychological scores at different ages. Methods: Prospective data were obtained for 2644 pregnant women recruited between 2004 and 2008 in population-based birth cohorts in Spain. Maternal n-3 PUFA intake during the first and third trimester of pregnancy was estimated using validated food frequency questionnaires. Child neuropsychological functions were assessed using Bayley Scales of Infant Development version one (BSID) at 1 year old, the McCarthy Scale of Children’s Abilities (MSCA) at 4 years old, and the Attention Network Test (ANT) at 7 years old. Data were analysed using multivariate linear regression models and adjusted for potential covariates, such as maternal social class, education, cohort location, alcohol consumption, smoking, breastfeeding duration, and energy intake. Results: Compared to participants in the lowest quartile (<1.262 g/day) of n-3 PUFA consumption during the first trimester, those in the highest quartile (>1.657 g/day) had a 2.26 points (95% confidence interval (CI): 0.41, 4.11) higher MSCA general cognitive score, a 2.48 points (95% CI: 0.53, 4.43) higher MSCA verbal score, and a 2.06 points (95% CI: 0.166, 3.95) higher MSCA executive function score, and a 11.52 milliseconds (95% CI: −22.95, −0.09) lower ANT hit reaction time standard error. In the third pregnancy trimester, the associations were weaker. Conclusions: Positive associations between n-3 PUFA intake during early pregnancy and child neuropsychological functions at 4 and 7 years of age were found, and further clinical research is needed to confirm these findings. Full article

Congenital heart defects (CHDs) are the most prevalent and serious of all birth defects in the United States. However, little is known about the impact of CHD-affected pregnancies on subsequent maternal health. Thus, there is a need to characterize the metabolic alterations associated with CHD-affected pregnancies. Fifty-six plasma samples were identified from post-partum women who participated in the National Birth Defects Prevention Study between 1997 and 2011 and had (1) unaffected control offspring (n = 18), (2) offspring with tetralogy of Fallot (ToF, n = 22), or (3) hypoplastic left heart syndrome (HLHS, n = 16) in this pilot study. Absolute concentrations of 408 metabolites using the AbsoluteIDQ^® p400 HR Kit (Biocrates) were evaluated among case and control mothers. Twenty-six samples were randomly selected from above as technical repeats. Analysis of covariance (ANCOVA) and logistic regression models were used to identify significant metabolites after controlling for the maternal age at delivery and body mass index. The receiver operating characteristic (ROC) curve and area-under-the-curve (AUC) are reported to evaluate the performance of significant metabolites. Overall, there were nine significant metabolites (p < 0.05) identified in HLHS case mothers and 30 significant metabolites in ToF case mothers. Statistically significant metabolites were further evaluated using ROC curve analyses with PC (34:1), two sphingolipids SM (31:1), SM (42:2), and PC-O (40:4) elevated in HLHS cases; while LPC (18:2), two triglycerides: TG (44:1), TG (46:2), and LPC (20:3) decreased in ToF; and cholesterol esters CE (22:6) were elevated among ToF case mothers. The metabolites identified in the study may have profound structural and functional implications involved in cellular signaling and suggest the need for postpartum dietary supplementation among women who gave birth to CHD offspring. Full article