Investigating low birth weight and preterm birth as potential mediators in the relationship between prenatal infections and early child development: a linked administrative health data analysis.

BACKGROUND: Prenatal infections are associated with childhood developmental outcomes such as reduced cognitive abilities, emotional problems and other developmental vulnerabilities. However, there is currently a lack of research examining whether this arises due to potential intermediary variables like low birth weight or preterm birth, or due to some other mechanisms of maternal immune activation arising from prenatal infections. METHODS: Administrative data from the National Health Service health board of Greater Glasgow & Clyde, Scotland, were used, linking birth records to hospital records and universal child health review records for 55 534 children born from 2011 to 2015, and their mothers. Causal mediation analysis was conducted to examine the extent to which low birth weight and preterm birth mediate the relationship between hospital-diagnosed prenatal infections and having developmental concern(s) identified by a health visitor during 6-8 weeks or 27-30 months child health reviews. RESULTS: Model estimates suggest that 5.18% (95% CI 3.77% to 7.65%) of the positive association observed between hospital-diagnosed prenatal infections and developmental concern(s) was mediated by low birth weight, while 7.37% (95% CI 5.36 to 10.88%) was mediated by preterm birth. CONCLUSION: Low birth weight and preterm birth appear to mediate the relationship between prenatal infections and childhood development, but only to a small extent. Maternal immune activation mechanisms unrelated to low birth weight and preterm birth remain the most likely explanation for associations observed between prenatal infections and child developmental outcomes, although other factors (for example, genetic factors) may also be involved.

Prenatal maternal infections and early childhood developmental outcomes: analysis of linked administrative health data for Greater Glasgow & Clyde, Scotland.

BACKGROUND: Previous research has linked prenatal maternal infections to later childhood developmental outcomes and socioemotional difficulties. However, existing studies have relied on retrospectively self-reported survey data, or data on hospital-recorded infections only, resulting in gaps in data collection. METHODS: This study used a large linked administrative health dataset, bringing together data from birth records, hospital records, prescriptions and routine child health reviews for 55,856 children born in Greater Glasgow & Clyde, Scotland, 2011-2015, and their mothers. Logistic regression models examined associations between prenatal infections, measured as both hospital-diagnosed prenatal infections and receipt of infection-related prescription(s) during pregnancy, and childhood developmental concern(s) identified by health visitors during 6-8 week or 27-30 month health reviews. Secondary analyses examined whether results varied by (a) specific developmental outcome types (gross-motor-skills, hearing-communication, vision-social-awareness, personal-social, emotional-behavioural-attention and speech-language-communication) and (b) the trimester(s) in which infections occurred. RESULTS: After confounder/covariate adjustment, hospital-diagnosed infections were associated with increased odds of having at least one developmental concern (OR: 1.30; 95% CI: 1.19-1.42). This was broadly consistent across all developmental outcome types and appeared to be specifically linked to infections occurring in pregnancy trimesters 2 (OR: 1.34; 95% CI: 1.07-1.67) and 3 (OR: 1.33; 95% CI: 1.21-1.47), that is the trimesters in which foetal brain myelination occurs. Infection-related prescriptions were not associated with any clear increase in odds of having at least one developmental concern after confounder/covariate adjustment (OR: 1.03; 95% CI: 0.98-1.08), but were associated with slightly increased odds of concerns specifically related to personal-social (OR: 1.12; 95% CI: 1.03-1.22) and emotional-behavioural-attention (OR: 1.15; 95% CI: 1.08-1.22) development. CONCLUSIONS: Prenatal infections, particularly those which are hospital-diagnosed (and likely more severe), are associated with early childhood developmental outcomes. Prevention of prenatal infections, and monitoring of support needs of affected children, may improve childhood development, but causality remains to be established.

Sociodemographic predictors of parenting stress among mothers in socio-economically deprived settings in rural and urban Kenya and Zambia.

Parental stress occurs when parenting demands exceed the resources available to cope with parenting. Previous research has identified household wealth, educational level, marital status, age, and number of dependent children as predictors of parental stress. However, limited evidence exists from sub-Saharan Africa. This study investigated the sociodemographic predictors of parenting stress among mothers in Kenya and Zambia. This cross-sectional study utilised baseline secondary data from parenting intervention programs implemented in Kisumu County (rural Kenya), Nairobi County (Urban Kenya), and Chisamba District (rural Zambia). Out of 913 caregivers recruited for the parenting program, 844 with complete data were included in the analysis. The mean age was 1.0 (SD = 0.7) years. Parental stress was measured using the Parental Stress Score (PSS) tool and demographic questionnaires were used to collect demographic information. Mean PSS were compared across study sites, and a multiple linear regression model was used to examine associations between sociodemographic predictors (household income, educational level, marital status, maternal age, child age, and number of children aged < 5 years) and PSS, adjusting for clustering and other predictors. From the results, the mean PSS in rural Kenya was 37.6 [SD = 11.8], in urban Kenya was 48.4 [SD = 4.2], and in rural Zambia was 43.0 [SD = 9.1]. In addition, the significant association between PSS and mothers' income and educational level was only observed in Kenyan study sites (income: Kenya rural ß = -0.40, p < 0.001**; Kenya urban, ß = - 0.33, p = .02*; Zambia rural, ß = - 0.01, p = 0.7) education: Kenya rural, ß = - 0.25, p = .005**; Kenya urban, ß = - 0.14, p = 0.07; Zambia rural, ß = 0.04, p = 0.3). However, marital status, mother's age, child's age, and the number of children below five years were not associated with PSS. The results revealed that mothers' income and education level were negatively associated with PSS, indicating that higher socioeconomic status can buffer the effects of parental stress.Trial registration Pan African Clinical Trials Registry ( https://pactr.samrc.ac.za/ ) database (ID Number: PACTR20180774832663 Date: 26/July/2018; (ID number: PACTR201905787868050 Date: 06/May/2019.

Autistic Traits and Psychosocial Predictors of Depressive Symptoms.

Higher rates of depression and of depressed mood are associated with autistic traits, and both are associated with social interaction factors, such as social self-efficacy, social motivation and loneliness. This study examined whether these social factors explain the association between autistic traits and depression. 658 participants (527 women) completed an online survey with measures of autistic traits (AQ), social self-efficacy (Social Self-Efficacy Scale), social motivation (Social Striving Assessment Scale), loneliness (UCLA Loneliness Scale) and depressive symptoms (Beck Depression Inventory-II). A mediation analysis found the relationship between autistic traits and depressive symptoms was fully mediated by the other three factors (ß[indirect] = .005, z = 2.63, p < .01; ß[direct] = .05, z = 1.58, p > .05), forming a pathway from autistic traits, to social self-efficacy, to social motivation, to loneliness and finally to depressive symptoms. These results suggest that targeting social self-efficacy may break this pathway and disrupt this relationship. Interventions targeting supporting positive social interaction should be considered.

Parental stress and child stimulation practices: examining associations with child developmental outcomes over time in Kenya and Zambia.

BACKGROUND: Parental stress often arises when parenting demands exceed the expected and actual resources available for parents to succeed in the parenting role. Parental stress is an important contributor to parent-child relationships. This, in turn, affects opportunities to engage their children in stimulating activities which could improve their development outcomes. However, limited evidence exists from sub-Saharan Africa (SSA) on the association between parental stress, caregiving practices, and child developmental outcomes. METHODS: The findings reported in this paper were derived from data collected through previous longitudinal work on nurturing care evaluation studies in Kisumu and Nairobi Counties in Kenya, and Chisamba District in Zambia. A total of 341 caregivers and their children who participated in the three rounds of data collection were included in this study. The children's mean age was 9.3 (SD = 8.2) months pre-intervention, 25.5 (SD = 8.6) months in mid-intervention, and 36 (SD = 10.0) months post-intervention. The Ages and Stages Questionnaire (ASQ), Parental Stress Scale (PSS), and caregiving tools were used to assess children's developmental outcomes, parental stress, and stimulation practices, respectively. A Random Intercept Cross-Lagged Panel model (RI-CLPM) was used to determine the association between caregivers' parenting stress, child stimulation practices, and child developmental outcomes. RESULTS: The findings showed that caregiver stimulation practices were positively associated with developmental outcomes. Findings on the associations between parental stress and caregivers' stimulation practices and children's developmental outcomes were not universally supported. CONCLUSION: The findings show that improved caregiver stimulation practices are likely to improve children's developmental outcomes. The policy implications of the findings from this study focus on improving parenting practices by addressing the predictors of parental stress. This includes subsidising childcare services to reduce costs. TRIAL REGISTRATION: Pan African Clinical Trials Registry ( https://pactr.samrc.ac.za/ ) database (ID number: PACTR20180774832663 Date: 26/July/2018.

The relationship between social cognitive processes and behavior changes in people with amnestic mild cognitive impairment or dementia using the Edinburgh Social Cognition Test (ESCoT).

OBJECTIVE: People with amnestic mild cognitive impairment (aMCI) or dementia often exhibit a decline in their social abilities, but few tests of social cognition exist that are suitable for clinical use. Moreover, the relationship between changes in behavior and impairments in social cognition is poorly understood. We examined the utility of the Edinburgh Social Cognition Test (ESCoT) in people with aMCI/dementia and explored associations between social cognition performance and behavior changes. METHOD: We administered the ESCoT and two established social cognition tests (the Reading the Mind in the Eyes and the Social Norms Questionnaire) to 28 people with aMCI or dementia and 28 age and sex matched cognitively healthy controls. Behavior change was measured using a semistructured interview which assesses behavioral abnormalities found in frontotemporal dementia. RESULTS: People with aMCI/dementia were impaired on the ESCoT affective theory of mind, ESCoT total score and the Reading the Mind in the Eyes. Behavior changes in the domains of apathy, loss of sympathy/empathy, perseveration, and psychotic symptoms were associated with poorer affective theory of mind scores. Disinhibition, loss of sympathy/empathy and hyperorality or altered food preferences were associated with cognitive theory of mind. All behaviors were significantly associated with poorer performance on ESCoT total score, but were not associated with performance on the Reading the Mind in the Eyes or the Social Norms Questionnaire. CONCLUSIONS: The ESCoT was sensitive to social cognition impairments in people with aMCI/dementia and it relates to behavior change in aMCI/dementia unlike established tests. Different subtests of the ESCoT were related to different behavior changes. These findings suggest that the ESCoT may be a clinically valuable tool when examining social cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Associations Between Reward and Future-Related Orientations and General and Specific Mental Health Issues in Adolescence.

Adolescence is characterised by a peak in sensation seeking accompanied by gradually developing self-control skills. Adolescents typically show steeper delay discounting performance than other age groups; a feature that is transdiagnostically related to a variety of mental health disorders. However, delay discounting performance is not a singular mental process but involves both risk/reward and future orientation elements, usually operationalised as probability/risk and time discounting tasks, respectively. To clarify the specific relations between the risk/reward and future orientation elements of delay discounting and different types of mental health problems, two bi-factor models and a series of structural equation models (SEMs) were fitted to multi-informant (parent and adolescent self-reported) mental health data from a large UK study. A transdiagnostic promotive role of future orientation was found using bi-factor modelling to separate general and dimension-specific mental health variation; however, this was limited to parent reports. In addition, future orientation was negatively associated with conduct problems and ADHD symptoms, but positively associated with emotional problems. Risk aversion was negatively associated with conduct problems, but positively associated with emotional and peer problems. The findings highlight that risk/reward and future orientation elements of delay discounting play partly distinct roles in different mental health problems and can serve both promotive and risk roles during adolescence. Findings also illuminate which elements of delay discounting should be intervention targets for different mental health concerns.

Examining Maternal Cardiometabolic Markers in Pregnancy on Child Emotional and Behavior Trajectories: Using Growth Curve Models on a Cohort Study.

Background: Poor maternal cardiometabolic health in pregnancy is associated with negative effects on child health outcomes, but there is limited literature on child and adolescent socioemotional outcomes. The study aimed to investigate associations between maternal cardiometabolic markers during pregnancy with child and adolescent socioemotional trajectories. Methods: Growth curve models were run to examine how maternal cardiometabolic markers in pregnancy affected child socioemotional trajectories from ages 4 to 16. Models were adjusted for all pregnancy trimesters and maternal, child, and socioeconomic covariates. This study used the Avon Longitudinal Study of Parents and Children (United Kingdom) cohort. Participants consisted of mother-child pairs (N = 15,133). Maternal predictors of fasting glucose, triglycerides, high-density lipoprotein, low-density lipoprotein, and body mass index were taken from each pregnancy trimester (T1, T2, T3). Child outcomes included emotional problems, conduct problems, and hyperactivity problems from the Strengths and Difficulties Questionnaire. Results: Fully adjusted models showed significant associations between elevated T1 fasting glucose and increased conduct problems, higher T1 body mass index and increased hyperactivity problems, lowered T1 high-density lipoprotein and decreased hyperactivity problems, and elevated T2 triglycerides and increased hyperactivity problems. Conclusions: Maternal cardiometabolic risk is associated with conduct and hyperactivity outcomes from ages 4 to 16. This study suggests that maternal markers of fasting glucose, low-density lipoprotein, high-density lipoprotein, and triglycerides during pregnancy could be added as supplements for clinical measures of risk when predicting child and adolescent socioemotional trajectories.

The effect of metacognitive executive function training on children's executive function, proactive control, and academic skills.

The current study investigated the effects of metacognitive and executive function (EF) training on childhood EF (inhibition, working memory [WM], cognitive flexibility, and proactive/reactive control) and academic skills (reading, reasoning, and math) among children from disadvantaged backgrounds. Children (N = 134, Mage = 8.70 years) were assigned randomly to the three training groups: (a) metacognitive training of basic EF processes (meta-EF), (b) training of basic EF processes (basic-EF), and (c) active controls (active control). They underwent 16 training sessions over the course of 2 months. No effects of EF and/or metacognitive training were found for academic outcomes. However, both meta-EF and basic-EF groups demonstrated greater gains than the active control group on proactive control engagement and WM, suggesting that EF training promotes a shift to more mature ways of engaging EF. Our findings suggest minimal near- and far-transfer effects of metacognitive training but highlight that proactive engagement of EF can be promoted through EF training in children. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers.

BACKGROUND: There is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children's developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother-child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators. METHODS: Maternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age. RESULTS: In mediation models, significant total effects were found for MetS associations with children's development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child's COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models. CONCLUSIONS: The results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children's LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child's cord blood markers (total indirect effects).

Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study.

OBJECTIVES: To examine neonates in Scotland aged 0-27 days with SARS-CoV-2 infection confirmed by viral testing; the risk of confirmed neonatal infection by maternal and infant characteristics; and hospital admissions associated with confirmed neonatal infections. DESIGN: Population-based cohort study. SETTING AND POPULATION: All live births in Scotland, 1 March 2020-31 January 2022. RESULTS: There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100 000 live births (141/92 009, 0.15%). Among infants born to women with confirmed infection around the time of birth, the confirmed neonatal infection rate was 1812 per 100 000 live births (15/828, 1.8%). Two-thirds (92/141, 65.2%) of neonates with confirmed infection had an associated admission to neonatal or (more commonly) paediatric care. Six of these babies (6/92, 6.5%) were admitted to neonatal and/or paediatric intensive care; however, none of these six had COVID-19 recorded as their main diagnosis. There were no neonatal deaths among babies with confirmed infection. IMPLICATIONS AND RELEVANCE: Confirmed neonatal SARS-CoV-2 infection was uncommon over the first 23 months of the pandemic in Scotland. Secular trends in the neonatal confirmed infection rate broadly followed those seen in the general population, although at a lower level. Maternal confirmed infection at birth was associated with an increased risk of neonatal confirmed infection. Two-thirds of neonates with confirmed infection had an associated admission to hospital, with resulting implications for the baby, family and services, although their outcomes were generally good. Ascertainment of confirmed infection depends on the extent of testing, and this is likely to have varied over time and between groups: the extent of unconfirmed infection is inevitably unknown.

A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection.

Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.

The Impact of COVID-19 Restrictions on Psychological Distress in Family Caregivers of Children with Neurodevelopmental Disability in the UK.

Caregivers of a child with a neurodevelopmental disability are more vulnerable to mental health difficulties. These difficulties are influenced by the child's challenging behaviours, and the caregiver's coping strategies; factors impacted by the COVID-19 pandemic. An online mixed methods survey was conducted on caregivers of children with neurodevelopmental disabilities (n = 43) and children who are typically developing (n = 67). The results showed that presence of challenging behaviours related to neurodevelopmental disability, and caregiver coping strategies predicted caregiver psychological distress during lockdown. Themes that emerged included 'confusing messages and guidance', 'loss of freedom' and 'unsupported and forgotten'. The results demonstrate the pressing need for the implementation of appropriate support to protect the mental health of caregivers across the UK.

Longitudinal Invariance of the Strengths and Difficulties Questionnaire Across Ages 4 to 16 in the ALSPAC Sample.

The Strengths and Difficulties Questionnaire (SDQ) has been widely used to study children's psychosocial development longitudinally; however, such analyses assume longitudinal measurement invariance, that is, they presuppose that symptom manifestations are measured comparably across different ages. Violations of this assumption could bias longitudinal analyses and should therefore be empirically tested. This study tested longitudinal measurement invariance within a confirmatory factor analysis framework in the U.K.-based Avon Longitudinal Study of Parents and Children (N = 13,988). Results indicated that SDQ scores showed configural, metric, scalar, and residual invariance across ages 7, 8, 9, 11, 13, and 16, supporting its use for comparing variances, covariances, and means over time within a latent variable model as well as using observed scores. At age 4, configural invariance was not supported, indicating that mental health symptoms as measured by the SDQ manifest differently at this age, thus necessitating caution when comparing symptoms as measured by SDQ scores at this age to later ages.

Maternal infections during pregnancy and child cognitive outcomes.

BACKGROUND: Maternal prenatal infections have been linked to children's neurodevelopment and cognitive outcomes. It remains unclear, however, whether infections occurring during specific vulnerable gestational periods can affect children's cognitive outcomes. The study aimed to examine maternal infections in each trimester of pregnancy and associations with children's developmental and intelligence quotients. The ALSPAC birth cohort was used to investigate associations between maternal infections in pregnancy and child cognitive outcomes. METHODS: Infection data from mothers and cognition data from children were included with the final study sample size comprising 7,410 mother-child participants. Regression analysis was used to examine links between maternal infections occurring at each trimester of pregnancy and children's cognition at 18 months, 4 years, and 8 years. RESULTS: Infections in the third trimester were significantly associated with decreased verbal IQ at age 4 (p < .05, adjusted R2 = 0.004); decreased verbal IQ (p < .01, adjusted R2 = 0.001), performance IQ (p < .01, adjusted R2 = 0.0008), and total IQ at age 8 (p < .01, adjusted R2 = 0.001). CONCLUSION: Results suggest that maternal infections in the third trimester could have a latent effect on cognitive development, only emerging when cognitive load increases over time, though magnitude of effect appears to be small. Performance IQ may be more vulnerable to trimester-specific exposure to maternal infection as compared to verbal IQ. Future research could include examining potential mediating mechanisms on childhood cognition, such as possible moderating effects of early childhood environmental factors, and if effects persist in future cognitive outcomes.

A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection.

Data on the safety of COVID-19 vaccines in early pregnancy are limited. We conducted a national, population-based, matched cohort study assessing associations between COVID-19 vaccination and miscarriage prior to 20 weeks gestation and, separately, ectopic pregnancy. We identified women in Scotland vaccinated between 6 weeks preconception and 19 weeks 6 days gestation (for miscarriage; n = 18,780) or 2 weeks 6 days gestation (for ectopic; n = 10,570). Matched, unvaccinated women from the pre-pandemic and, separately, pandemic periods were used as controls. Here we show no association between vaccination and miscarriage (adjusted Odds Ratio [aOR], pre-pandemic controls = 1.02, 95% Confidence Interval [CI] = 0.96-1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92-1.38). We undertook additional analyses examining confirmed SARS-CoV-2 infection as the exposure and similarly found no association with miscarriage or ectopic pregnancy. Our findings support current recommendations that vaccination remains the safest way for pregnant women to protect themselves and their babies from COVID-19.

Pregnancy outcomes after SARS-CoV-2 infection in periods dominated by delta and omicron variants in Scotland: a population-based cohort study.

BACKGROUND: Evidence suggests that the SARS-CoV-2 omicron (B.1·1.529) is associated with lower risks of adverse outcomes than the delta (B.1.617.2) variant among the general population. However, little is known about outcomes after omicron infection in pregnancy. We aimed to assess and compare short-term pregnancy outcomes after SARS-CoV-2 delta and omicron infection in pregnancy. METHODS: We did a national population-based cohort study of women who had SARS-CoV-2 infection in pregnancy between May 17, 2021, and Jan 31, 2022. The primary maternal outcome was admission to critical care within 21 days of infection or death within 28 days of date of infection. Pregnancy outcomes were preterm birth and stillbirth within 28 days of infection. Neonatal outcomes were death within 28 days of birth, and low Apgar score (<7 of 10, for babies born at term) or neonatal SARS-CoV-2 infection in births occurring within 28 days of maternal infection. We used periods when variants were dominant in the general Scottish population, based on 50% or more of cases being S-gene positive (delta variant, from May 17 to Dec 14, 2021) or S-gene negative (omicron variant, from Dec 15, 2021, to Jan 31, 2022) as surrogates for variant infections. Analyses used logistic regression, adjusting for maternal age, deprivation quintile, ethnicity, weeks of gestation, and vaccination status. Sensitivity analyses included restricting the analysis to those with first confirmed SARS-CoV-2 infection and using periods when delta or omicron had 90% or more predominance. FINDINGS: Between May 17, 2021, and Jan 31, 2022, there were 9923 SARS-CoV-2 infections in 9823 pregnancies, in 9817 women in Scotland. Compared with infections in the delta-dominant period, SARS-CoV-2 infections in pregnancy in the omicron-dominant period were associated with lower maternal critical care admission risk (0·3% [13 of 4968] vs 1·8% [89 of 4955]; adjusted odds ratio 0·25, 95% CI 0·14-0·44) and lower preterm birth within 28 days of infection (1·8% [37 of 2048] vs 4·2% [98 of 2338]; 0·57, 95% CI 0·38-0·87). There were no maternal deaths within 28 days of infection. Estimates of low Apgar scores were imprecise due to low numbers (5 [1·2%] of 423 with omicron vs 11 [2·1%] of 528 with delta, adjusted odds ratio 0·72, 0·23-2·32). There were fewer stillbirths in the omicron-dominant period than in the delta-dominant period (4·3 [2 of 462] per 1000 births vs 20·3 [13 of 639] per 1000) and no neonatal deaths during the omicron-dominant period (0 [0 of 460] per 1000 births vs 6·3 [4 of 626] per 1000 births), thus numbers were too small to support adjusted analyses. Rates of neonatal infection were low in births within 28 days of maternal SARS-CoV-2 infection, with 11 cases of neonatal SARS-CoV-2 in the delta-dominant period, and 1 case in the omicron-dominant period. Of the 15 stillbirths, 12 occurred in women who had not received two or more doses of COVID-19 vaccination at the time of SARS-CoV-2 infection in pregnancy. All 12 cases of neonatal SARS-CoV-2 infection occurred in women who had not received two or more doses of vaccine at the time of maternal infection. Findings in sensitivity analyses were similar to those in the main analyses. INTERPRETATION: Pregnant women infected with SARS-CoV-2 were substantially less likely to have a preterm birth or maternal critical care admission during the omicron-dominant period than during the delta-dominant period. FUNDING: Wellcome Trust, Tommy's charity, Medical Research Council, UK Research and Innovation, Health Data Research UK, National Core Studies-Data and Connectivity, Public Health Scotland, Scottish Government Health and Social Care, Scottish Government Chief Scientist Office, National Research Scotland.

Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers.

A significant proportion of the personal and economic burden of schizophrenia can be attributed to the late diagnosis or misdiagnosis of the disorder. A novel, objective diagnostic approaches could facilitate the early detection and treatment of schizophrenia and improve patient outcomes. In the present study, we aimed to identify robust schizophrenia-specific blood biomarkers, with the goal of developing an accurate diagnostic model. The levels of selected serum and peripheral blood mononuclear cell (PBMC) markers relevant to metabolic and immune function were measured in healthy controls (n = 26) and recent-onset schizophrenia patients (n = 36) using multiplexed immunoassays and flow cytometry. Analysis of covariance revealed significant upregulation of insulin receptor (IR) and fatty acid translocase (CD36) levels in T helper cells (F = 10.75, P = 0.002, Q = 0.024 and F = 21.58, P = 2.8 × 10-5, Q = 0.0004, respectively), as well as downregulation of glucose transporter 1 (GLUT1) expression in monocytes (F = 21.46, P = 2.9 × 10-5, Q = 0.0004). The most robust predictors, monocyte GLUT1 and T helper cell CD36, were used to develop a diagnostic model, which showed a leave-one-out cross-validated area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI: 0.66-0.92). The diagnostic model was validated in two independent datasets. The model was able to distinguish first-onset, drug-naïve schizophrenia patients (n = 34) from healthy controls (n = 39) with an AUC of 0.75 (95% CI: 0.64-0.86), and also differentiated schizophrenia patients (n = 22) from patients with other neuropsychiatric conditions, including bipolar disorder, major depressive disorder and autism spectrum disorder (n = 68), with an AUC of 0.83 (95% CI: 0.75-0.92). These findings indicate that PBMC-derived biomarkers have the potential to support an accurate and objective differential diagnosis of schizophrenia.

Using network analysis to illuminate the intergenerational transmission of adversity.

Objective: The effects of maternal exposure to adverse childhood experiences (ACEs) may be transmitted to subsequent generations through various biopsychosocial mechanisms. However, studies tend to focus on exploring one or two focal pathways with less attention paid to links between different pathways. Using a network approach, this paper explores a range of core prenatal risk factors that may link maternal ACEs to infant preterm birth (PTB) and low birthweight (LBW). Methods: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 8379) to estimate two mixed graphical network models: Model 1 was constructed using adverse infant outcomes, biopsychosocial and environmental risk factors, forms of ACEs, and sociodemographic factors. In Model 2, ACEs were combined to represent a threshold ACEs score (≥4). Network indices (i.e., shortest path and bridge expected influence [1-step & 2-step]) were estimated to determine the shortest pathway from ACEs to infant outcomes, and to identify the risk factors that are vital in activating other risk factors and adverse outcomes. Results: Network analyses estimated a mutually reinforcing web of childhood and prenatal risk factors, with each risk connected to at least two other risks. Bridge influence indices suggested that childhood physical and sexual abuse and multiple ACEs were highly interconnected to others risks. Overall, risky health behaviours during pregnancy (i.e., smoking & illicit drug use) were identified as 'active' risk factors capable of affecting (directly and indirectly) other risk factors and contributing to the persistent activation of the global risk network. These risks may be considered priority candidate targets for interventions to disrupt intergenerational risk transmission. Our study demonstrates the promise of network analysis as an approach for illuminating the intergenerational transmission of adversity in its full complexity. HIGHLIGHTS: We took a network approach to assessing links between ACEs and birth outcomes.ACEs, other prenatal risk factors, and birth outcomes had complex inter-connectionsHealth behaviours in pregnancy were indicated as optimal intervention targets.

Objetivo: Los efectos de la exposición materna a experiencias adversas en la infancia (ACEs, en sus siglas en inglés) pueden ser transmitidos a las generaciones posteriores a través de varios mecanismos biopsicosociales. Sin embargo, los estudios tienden a centrarse en la exploración de una o dos vías focales, prestando menos atención a los vínculos entre diferentes vías. Utilizando un abordaje de red, este trabajo explora una serie de factores de riesgo prenatales centrales que pueden vincular las ACEs maternas con el nacimiento prematuro (PTB, en sus siglas en inglés) y el bajo peso al nacer (LBW, en sus siglas en inglés) de los bebés.Métodos: Se utilizaron datos del Estudio Longitudinal de Padres e Hijos de Avon (ALSPAC) (n = 8.379) para estimar dos modelos de red gráfica mixta: El modelo 1 se construyó utilizando los resultados adversos del lactante, los factores de riesgo biopsicosociales y ambientales, las formas de las ACE y los factores sociodemográficos. En el modelo 2, las ACEs se combinaron para representar una puntuación de ACEs umbral (≥ 4). Se estimaron los índices de red (es decir, el camino más corto y la influencia esperada del puente [1 y 2 pasos]) para determinar el camino más corto desde las ACEs hasta los resultados infantiles, y para identificar los factores de riesgo que son vitales para activar otros factores de riesgo y resultados adversos.Resultados: Los análisis de redes estimaron una red de factores de riesgo prenatales y de la infancia que se refuerzan mutuamente, y cada riesgo está conectado con al menos otros dos riesgos. Los índices de influencia de los puentes sugirieron que el abuso físico y sexual en la infancia y los múltiples ACEs estaban altamente interconectados con otros riesgos. En general, las conductas de riesgo para la salud durante el embarazo (es decir, el tabaquismo y el consumo de drogas ilícitas) se identificaron como factores de riesgo "activos" capaces de afectar (directa e indirectamente) a otros factores de riesgo y de contribuir a la activación persistente de la red de riesgo global. Estos riesgos pueden considerarse objetivos candidatos prioritarios para las intervenciones destinadas a interrumpir la transmisión intergeneracional del riesgo. Nuestro estudio demuestra la promesa del análisis de redes como abordaje para iluminar la transmisión intergeneracional de la adversidad en toda su complejidad.

Within-person Relations between Domains of Socio-emotional Development during Childhood and Adolescence.

Adolescence is a critical period in the development of mental health with nearly 1 in 5 adolescents suffering from mental health problems and more than 40 percent of these experiencing at least one co-occurring mental health disorder. This study investigates whether there are differences in the relations between key dimensions of child and adolescent mental health in adolescence compared to childhood. Mental health and related socio-emotional traits were measured longitudinally at ages 4, 7, 8, 9, 11, 13, and 16 in the Avon Longitudinal Study of Parents and Children (N = 11279) using the Strengths and Difficulties Questionnaires. Graphical Vector Autoregression models were used to analyse the temporal within-person relations between conduct problems, emotional problems, hyperactivity/inattention, peer problems and prosociality across childhood (ages 4 to 9) and adolescence (11 to 16). Results suggest that adolescence is characterised by an increase in the number and strength of temporal relations between socio-emotional difficulties. In particular, in adolescence there were bidirectional connections between peer problems and emotional problems, between conduct problems and hyperactivity/inattention and between prosociality and conduct problems as well as hyperactivity/inattention. In childhood, conduct problems and prosociality were reciprocally related. Results also suggested peer problems as a potential mediating factor between conduct and emotional problems in childhood. Overall, this study suggests that different domains of socio-emotional development influence each other over development. Adolescence is characterised by an increase in temporal connections, which may be one factor underlying the increased vulnerability to the onset of mental health problems during that period.