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.

Within-family relations of mental health problems across childhood and adolescence.

BACKGROUND: While transactional models suggest that parent and child mental health reciprocally influence one another over development, research has largely focused on parent-to-child effects. Additionally, it is not known whether observed associations hold when appropriate statistical tools are used to operationalise within-family dynamics. METHODS: We investigated within-family mental health dynamics using autoregressive latent trajectory models with structured residuals, stratified by child gender. Parental psychological distress was assessed using the Kessler (K6) scale, and children's internalising and externalising problems were assessed using the Strengths and Difficulties Questionnaire. Both measures were administered at the age 3, 5, 7, 11, 14 and 17 waves of the Millennium Cohort Study (N = 10,746, ~50% female). RESULTS: Maternal psychological distress was positively associated with subsequent internalising and externalising problems for girls but only with internalising problems for boys. Paternal psychological distress was associated with boys' later internalising and externalising problems during early adolescence. Among boys, internalising problems were associated with later maternal psychological distress, while externalising problems were associated with later paternal psychological distress. Among girls, internalising problems were associated with subsequent paternal psychological distress, while externalising problems were associated with later maternal psychological distress. Finally, maternal and paternal psychological distress showed negative bidirectional associations in early childhood but positive associations in middle childhood and early adolescence. CONCLUSIONS: Findings support a transactional model of family mental health, with both child-to-parent and parent-to-child effects playing a role in the development of mental health difficulties. Mental health intervention efforts should, therefore, target the whole family system.

Polygenic risks for joint developmental trajectories of internalizing and externalizing problems: findings from the ALSPAC cohort.

BACKGROUND: Joint developmental trajectories of internalizing and externalizing problems show considerable heterogeneity; however, this can be parsed into a small number of meaningful subgroups. Doing so offered insights into risk factors that lead to different patterns of internalizing/externalizing trajectories. However, despite both domains of problems showing strong heritability, no study has yet considered genetic risks as predictors of joint internalizing/externalizing problem trajectories. METHODS: Using parallel process latent class growth analysis, we estimated joint developmental trajectories of internalizing and externalizing difficulties assessed across ages 4 to 16 using the Strengths and Difficulties Questionnaire. Multinomial logistic regression was used to evaluate a range of demographic, perinatal, maternal mental health, and child and maternal polygenic predictors of group membership. Participants included 11,049 children taking part in the Avon Longitudinal Study of Parents and Children. Polygenic data were available for 7,127 children and 6,836 mothers. RESULTS: A 5-class model was judged optimal: Unaffected, Moderate Externalizing Symptoms, High Externalizing Symptoms, Moderate Internalizing and Externalizing Symptoms and High Internalizing and Externalizing Symptoms. Male sex, lower maternal age, maternal mental health problems, maternal smoking during pregnancy, higher child polygenic risk scores for ADHD and lower polygenic scores for IQ distinguished affected classes from the unaffected class. CONCLUSIONS: While affected classes could be relatively well separated from the unaffected class, phenotypic and polygenic predictors were limited in their ability to distinguish between different affected classes. Results thus add to existing evidence that internalizing and externalizing problems have mostly shared risk factors.

The role of harsh parenting practices in early- to middle-childhood socioemotional development: An examination in the Millennium Cohort Study.

Patterson's coercion model describes a gradual escalation in maladaptive parent-child transactions whereby externalizing behaviors lead to increases in maladaptive parenting and vice versa. The current study investigates the role of (predominantly mother-reported) harsh parenting practices in the within-person development of conduct problems, hyperactive/inattentive behaviors, and emotional problems. A random-intercept cross-lagged panel model was fit across ages 3, 5, and 7 (N = 14,037, 49% female, 84% White) using the UK population-representative Millennium Cohort Study. Findings support Patterson's coercion model, providing evidence for reciprocal within-family relations between parenting practices and child behaviors. They suggest the importance of addressing parenting difficulties in families where children present with socioemotional difficulties in order to help prevent the accumulation of additional issues.

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.

Developmental trajectories of ADHD symptoms in a large population-representative longitudinal study.

BACKGROUND: Previous research has suggested that there is substantial heterogeneity in the developmental trajectories of attention-deficit/hyperactivity disorder (ADHD) symptoms. Sometimes, qualitative distinctions between trajectories with different ages of onset and/or patterns of remission are made; however, little is known about the predictors and broader clinical meaningfulness of these candidate 'developmental subtypes' of ADHD symptoms. METHODS: We applied latent class growth analysis to data from the UK Millennium Cohort Study (MCS; N = 11 316; ages 3, 5, 7, 11 and 14) to evaluate whether developmental trajectories of ADHD symptoms differing in early life predictors could be identified. Our optimal model included six trajectory groups, labelled unaffected (34.9% of the sample), mildly affected (24.1%), subclinical remitting (12.8%), pre-school onset partially remitting (14.1%), developmentally increasing (7.6%) and pre-school onset persistent (6.4%). RESULTS: Factors such as gender, conduct problems, cognitive ability, maternal education, premature birth, peer problems and school readiness scores differentiated between specific ADHD symptom trajectories. CONCLUSIONS: Taken together, our findings provide preliminary evidence that distinguishing different trajectories of ADHD symptoms could be clinically informative.

Teacher Versus Parent Informant Measurement Invariance of the Strengths and Difficulties Questionnaire.

BACKGROUND AND OBJECTIVES: Obtaining a multi-informant perspective is important when assessing mental health issues in childhood and adolescence. Obtaining ratings from both parents and teachers also facilitates the evaluation of similarities and contrasts in the nature and severity of symptoms across home and school contexts. However, these informants may differ in their interpretations of observed behaviors, raising questions about the validity of comparing parents' and teachers' ratings. METHODS: We evaluated the cross-informant measurement invariance of one of the most widely used measures of child and adolescent mental health: The Strengths and Difficulties Questionnaire (SDQ). Using data from the UK-population representative Millennium Cohort Study, we evaluated configural, metric, and scalar measurement invariance across parents and teachers when children were aged 7 (N = 10,221) and 11 (N = 10,543). RESULTS: Scalar measurement invariance held at both ages. Parents reported higher levels of symptoms in all domains measured at both ages as well as higher prosociality. CONCLUSIONS: For a UK sample, valid comparisons of parent and teacher SDQ ratings at ages 7 and 11 appear to be possible, facilitating the evaluation of contextual differences in child mental health problems. Further, parents report more problem and prosocial behavior in their children than teachers attribute to them.

Links between perinatal risk factors and maternal psychological distress: A network analysis.

INTRODUCTION: This paper explores a range of perinatal risk factors that may increase maternal vulnerability to postnatal psychological distress in a sample of 17 531 women participating in the Millennium Cohort Study, a diverse British, longitudinal birth cohort study. MATERIAL AND METHODS: Using a graphical network modeling framework, this study models the links between postnatal psychological distress and perinatal risk factors, while controlling for sociodemographic factors and history of depression and anxiety. Postnatal psychological distress was assessed at 9 months postpartum using the Rutter Malaise Inventory. RESULTS: Results of the graphical network models indicate that lower levels of happiness about the pregnancy (Edge weight [w] = 0.084, 95% CI = 0.069-0.100, b = 0.095), smoking during pregnancy (w = 0.026, 95% CI = -0.009-0.060, b = 0.029), infection during pregnancy (w = 0.071, 95% CI = 0.024-0.118, b = 0.090), hyperemesis gravidarum (w = 0.068, 95% CI = 0.013-0.123, b = 0.083), baby in special care (w = 0.048, 95% CI = -0.004-0.099, b = 0.062), not being white (w = 0.101, 95% CI = 0.062-0.140, b = 0.118), being from a more deprived area (w = -0.028, 95% CI = -0.051 to -0.005, b = -0.039), lower income (w = -0.025, 95% CI = -0.055-0.005, b = -0.036), and history of depression or anxiety (w = 0.574, 95% CI = 0.545-0.603, b = 0.764) were associated with increased psychological distress. CONCLUSIONS: Some perinatal risk factors may be directly associated with postnatal psychological distress, but many risk factors appear to be primarily associated with demographic factors. This emphasizes the importance of taking a holistic approach when evaluating an individual's risk of developing postnatal psychological distress.

Prenatal maternal infections and children's socioemotional development: findings from the UK Millennium Cohort Study.

Previous research suggests that prenatal maternal infections may be associated with increased odds of children having a neurodevelopmental disorder. However, little evidence exists on associations with broader child outcomes, especially subclinical symptoms. Participants were the N = 14,021 members of the population-representative UK Millennium Cohort Study. We examined associations between prenatal maternal infections, both maternal-reported and hospital-recorded, and children's socioemotional development, using the Strengths and Difficulties Questionnaire (SDQ) at age three. Maternal-reported prenatal infections were associated with increased emotional symptoms, after adjusting for several potential confounds and covariates. Hospital-recorded prenatal infections were not associated with children's socioemotional outcomes, after adjusting for potential confounding and covarying factors. Findings suggest that prenatal maternal infections, particularly those which the mothers remember months later, may be associated with increased emotional problems in early childhood. This emphasises the need for screening for and preventing infections during pregnancy. Further, the occurrence of prenatal infection indicates the potential need for early intervention for children's emotional difficulties.

An epidemiological study of ADHD and conduct disorder: does family conflict moderate the association?

PURPOSE: To examine the role of family conflict in the relationship between attention deficit hyperactivity disorder (ADHD) and conduct disorder (CD). METHODS: A cross-sectional national population survey was carried out among 10,838 14-16 year old students in all secondary schools in Iceland. Three latent measures, financial status, ADHD and CD, and one observed measure, family structure, were included in the study. A structural equation model was used to evaluate direct effects between ADHD and CD for four different groups; females and males, experiencing family conflict and those not experiencing family conflict. RESULTS: ADHD was significantly and positively associated with CD for all groups. When controlling for financial status and family structure it was found that ADHD was positively and significantly associated with CD for adolescent females and males not experiencing family conflict as well as for those experiencing family conflict. The link between ADHD and CD was significantly stronger for those adolescents who had experienced family conflict compared to those who had not experienced family conflict. These results suggest that family conflict moderates the association between ADHD and CD for both girls and boys. CONCLUSIONS: The results of this study indicate that family environment and ADHD symptoms are important when predicting CD among adolescent youth. Most notably, family conflict exacerbates the effects of ADHD symptoms on CD among both females and males.

Prenatal Maternal Infections and Children's Neurodevelopment in the UK Millennium Cohort Study: A Focus on ASD and ADHD.

OBJECTIVE: No clear answer has yet been attained as to the influence of prenatal exposure to infection on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), either alone or as co-occurring issues. The current study examined links between hospital-recorded and maternal-reported prenatal infections and ASD, ADHD, and co-occurring ASD and ADHD. METHODS: Participants were n = 15,462 children and mother pairs from the Millennium Cohort Study (MCS), a population-representative UK sample. RESULTS: Findings show associations between maternal-reported infections and ASD, and some evidence of links with ADHD and co-occurring ASD and ADHD. Hospital-recorded infections were not found to be associated with ASD, ADHD, or their co-occurrence. Agreement between hospital-recorded and maternal-reported infections was low, which may explain the discrepant findings. CONCLUSION: Prenatal maternal infections may be associated with increased odds of ASD and ADHD. Findings point to the importance of drawing on multiple sources of information when ascertaining prenatal infection status.

Analyzing dynamic change in children's socioemotional development using the strengths and difficulties questionnaire in a large United Kingdom longitudinal study.

Many children who suffer from one mental health issue also suffer from at least one co-occurring disorder and a range of developmental psychopathology theories, including developmental cascade and network models, have been proposed to explain this widespread co-occurrence. Autoregressive latent trajectory models with structured residuals (ALT-SR) and multilevel graphical vector autoregression (GVAR) are recently proposed complementary approaches that can help operationalize and test these theories and provide new insights into the reciprocal relations between multiple mental health domains to advance the understanding of the development of co-occurring mental health problems. This study uses ALT-SR and multilevel GVAR models to analyze the temporal, contemporaneous, and between-person relations between key dimensions of child mental health: emotional problems, peer problems, conduct problems, hyperactivity/inattention, and prosociality as measured by the parent-reported Strengths and Difficulties Questionnaire (SDQ) in 17,478 children from the U.K. Millennium Cohort study at ages 3, 5, 7, 11, 14, and 17 years. Children's strengths and difficulties in different domains of psychosocial functioning were dynamically associated with each other over- and within-time. The ALT-SR highlighted that hyperactivity/inattention plays a central role in affecting other domains over developmental time, while the GVAR model highlighted comparably strong bidirectional relations between conduct problems and prosociality as well as between emotional problems and peer problems. This study confirms that mental health difficulties influence one another dynamically over time. The complementary techniques of ALT-SR and GVAR models offer different insights into co-occurring mental health problems and hold promise for supporting the building of more comprehensive developmental psychopathological theories that acknowledge the interconnectedness of different domains of mental health. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Analgesic drug use in pregnancy and neurodevelopment outcomes: an umbrella review.

Emerging evidence from reviews suggests that analgesic drug exposure during pregnancy may contribute to child neurodevelopment outcomes. A comprehensive overview of existing evidence is needed for firm conclusions to inform clinical guidelines. This umbrella review aims to synthesise high-quality evidence on prenatal analgesic drug exposure and risk of ASD and ADHD in children. Seven databases were searched from inception to May 2021 to identify relevant reviews of any design. The AMSTAR 2 and the GRADE quality assessments were used to evaluate risk of bias and heterogeneity. A narrative synthesis approach was used to summarise findings. Five systematic reviews and meta-analyses met the inclusion criteria. All reviews reported significant associations between maternal prenatal acetaminophen use and ADHD outcomes (risk ratio range: 1.08-1.34; no pooled incidence rate), with a potential dose-dependent relationship. Potential sources of heterogeneity included usage timing and dosage. Findings suggest minimisation of prenatal acetaminophen exposure due to risk for ADHD outcomes. Future studies should include assessing potentially interacting mechanisms associating acetaminophen use with future neurodevelopmental outcomes.

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.

A Longitudinal and Gender Invariance Analysis of the Strengths and Difficulties Questionnaire Across Ages 3, 5, 7, 11, 14, and 17 in a Large U.K.-Representative Sample.

Developmental invariance is important for making valid inferences about child development from longitudinal data; however, it is rarely tested. We evaluated developmental and gender invariance for one of the most widely used measures of child mental health: the parent-reported Strengths and Difficulties Questionnaire (SDQ). Using data from the large U.K. population-representative Millennium Cohort Study (N = 10,207; with data at ages 3, 5, 7, 11, 14, and 17 years), we tested configural, metric, scalar, and residual invariance in emotional problems, conduct problems, hyperactivity/inattention, prosociality, and peer problems. We found that the SDQ showed poor fit at age 3 in both males and females and at age 17 in males; however, it fit reasonably well and its scores were measurement invariant up to the residual level across gender at ages 5, 7, 11, and 14 years. Scores were also longitudinally measurement invariant across this age range up to the partial residual level. Results suggest that the parent-reported SDQ can be used to estimate developmental trajectories of emotional problems, conduct problems, hyperactivity/inattention, prosociality, and peer problems and their gender differences across the age range 5 to 14 years using a latent model. Developmental differences outside of this range may; however, partly reflect measurement differences.

Longitudinal effects of breast feeding on parent-reported child behaviour.

OBJECTIVE: Shorter breastfeeding duration has been linked to a range of difficulties in children. However, evidence linking shorter breastfeeding duration to child behavioural problems has been inconclusive. Owing to an almost exclusive focus on early childhood in previous research, little is known about breastfeeding effects on behaviour throughout childhood and adolescence. This study examines the longitudinal effect of breast feeding on parent-reported behaviour in children aged 3-14. DESIGN: Data come from the Millennium Cohort Study, a large, prospective, UK birth cohort study. PARTICIPANTS: 11 148 children, their parents and teachers. METHODS: This study maps the effect of breastfeeding duration on parent-reported child behaviour longitudinally, using latent growth curve modelling and on teacher-reported child behaviour using multiple regression analyses. Breastfeeding duration was assessed through parent interviews when the child was 9 months old. Children's behavioural development was measured using parent-reported Strengths and Difficulties Questionnaires (SDQ) at 3, 5, 7, 11 and 14 years and teacher-reported SDQs at 7 and 11 years. RESULTS: Breast feeding was associated with fewer parent-reported behavioural difficulties at all ages even after adjusting for potential confounders (<2 months: B=-0.22, 95% CI -0.39 to -0.04; 2-4 months: B=-0.53, 95% CI -0.75 to -0.32; 4-6 months: B=-1.07, 95% CI -1.33 to -0.81; >6 months: B=-1.24, 95% CI -1.44 to -1.04; B=adjusted mean difference of raw SDQ scores at age 3, reference: never breast fed). CONCLUSION: This study provides further evidence supporting links between breastfeeding duration and children's socioemotional behavioural development. Potential implications include intervention strategies encouraging breast feeding.

The association between analgesic drug use in pregnancy and neurodevelopmental disorders: protocol for an umbrella review.

BACKGROUND: Maternal prenatal health has been shown to be an important influence on children's developmental outcomes, which has led to an increased emphasis on providing more information to support clinical decisions in pregnancy. Several systematic reviews suggest that analgesic drug use during pregnancy may have neurodisruptive properties. However, no firm conclusions have yet been drawn on the associations between prenatal analgesic drug use and children's long-term development of neurodevelopmental disorders such as autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD). Therefore, an umbrella review is proposed for the purpose of examining the associations between maternal analgesic drug use during pregnancy and diagnoses of neurodevelopmental disorders. METHODS: Included systematic reviews will consist of studies examining the effect of maternal prenatal analgesic drug use, specifically ibuprofen, acetaminophen, aspirin, naproxen, diclofenac, and ketoprofen, on children's neurodevelopmental disorder status. Examined drugs were restricted to those readily accessible and frequently used by pregnant women, and with characteristics that allow them to cross the placenta and directly affect fetal development. Outcomes will be restricted to formal clinical diagnoses of ASD and/or ADHD. Two reviewers will independently identify eligible reviews from six databases (e.g., PubMed, EMBASE, PsychINFO) from inception dates of databases to the date of data extraction, and conduct manual searches of reference lists, consultation with field experts, and scan of pre-print archives. Extracted data will also include short qualitative summaries by both reviewers. As part of quality assessment, a standardized measurement tool to assess systematic reviews (AMSTAR 2) will be used. A narrative synthesis is proposed to integrate findings from different, potentially methodologically heterogeneous, studies. DISCUSSION: This umbrella review of associations between maternal prenatal use of analgesic drugs and children's neurodevelopmental disorders could allow for firmer conclusions to be drawn through the synthesis of all relevant published research. The synthesis of findings using high-quality evidence could provide more accurate healthcare information on the long-term effects of analgesic drugs on neurodevelopment, to better guide future clinical decisions during pregnancy. This review will also allow gaps and methodological differences in the literature to be identified, informing recommendations for future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020179216 .