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.

Validity of the ESSENCE-Q neurodevelopmental screening tool in Japan.

AIM: To assess the validity of the Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations-Questionnaire (ESSENCE-Q), a simple screening tool for neurodevelopmental problems, in Japan. METHOD: Parents/caregivers completed the 11-item ESSENCE-Q for 77 612 children aged 2 years 6 months included in a national birth cohort study. Information about neurodevelopmental disorders (NDDs: autism spectrum disorder; intellectual disability and/or developmental language disorder; motor delay/motor disorder) was collected at age 3 years. Each ESSENCE-Q item was scored on a binary (0,1) scale, with a total score range of 0 to 11. Total scores and individual items were compared across children with and without NDDs. RESULTS: NDDs were recorded in 854 children (1.1%). With a total ESSENCE-Q score cut-off of ≥3, receiver operating characteristic curve analysis showed an area under the curve of 0.91, with sensitivity 84.9%, specificity 84.8%, positive predictive value 5.9%, and negative predictive value 99.8%. The proportion of parental concerns at 2 years 6 months differed significantly by NDD status for communication (89.5% vs 14.2%) and general development (80.2% vs 7.4%). ESSENCE-Q total scores were moderately negatively correlated (-0.36, p < 0.001) with Japanese Ages and Stages Questionnaire scores. INTERPRETATION: The parent/caregiver-completed ESSENCE-Q is useful as a tool for screening out children with neurotypical development at this early age. Further research into longer-term predictive validity will be possible as more NDD diagnoses are given as the children grow up.

Vitamin D deficiency associated with neurodevelopmental problems in 2-year-old Japanese boys.

AIM: While associations between vitamin D deficiency and neurodevelopmental disorders have been found, large studies on child vitamin D, neurodevelopment, and sex differences among the general population are lacking. This study aimed to investigate the association between child serum 25-hydroxyvitamin D (25(OH)D)) levels and neurodevelopmental problems (NDPs). METHODS: Serum 25(OH)D and NDPs were measured at age two among the subcohort study of the Japan Environment and Children's Study. NDPs were assessed with the Kyoto Scale of Psychological Development 2001 (Kyoto scale). Adjusted odds ratios (aORs) for the Kyoto-scale developmental quotient scores <70 were calculated, for postural-motor, cognitive-adaptive, and language-social domains and overall scores, adjusted for test month, latitude, small for gestational age, maternal age, and daycare attendance. RESULTS: Among 2363 boys and 2290 girls, boys had higher 25(OH)D levels, but scored lower in the Kyoto scale. For boys in the vitamin D deficiency (<20 ng/mL) group, aORs of scoring the Kyoto-scale DQs <70 were 2.33 (p = 0.006) for overall DQs, 1.91 (p = 0.037) for cognitive-adaptive, and 1.69 (p = 0.024) for language-social domains. For girls, results were inconclusive. CONCLUSION: Only boys showed a clear and cross-modal association between vitamin D deficiency and NDPs.

Paediatric testicular torsion in low- and middle-income countries: an OxPLORE scoping study.

BACKGROUND: Literature on paediatric surgical conditions in low- and middle-income countries (LMICs) remains limited. As a common emergency, timely treatment of testicular torsion acts as a benchmark of adequate emergency service delivery in paediatric surgery. This scoping study aims to synthesise all existing literature on paediatric testicular torsion in LMICs. METHODS: A database search was conducted by the OxPLORE global paediatric surgery research group to identify studies containing the terms 'testicular torsion' or 'acute scrotum' originating from LMICs. A thematic analysis was applied to the results of the search and the quality of evidence was appraised for all included articles. RESULTS: This review included 17 studies with 1798 patients. All studies originated from middle-income countries and the majority (76%) had sample sizes smaller than 100 patients. All studies were appraised as providing less than adequate evidence. Included studies identified long delays to treatment and highlighted ongoing debates on the value of scoring systems and Doppler ultrasonography in diagnosing torsion. Major heterogeneity in surgical approaches to treatment of testicular torsion in children was also observed. CONCLUSIONS: Literature on paediatric testicular torsion in LMICs is scarce and heterogeneous. Prospective, multi-centre research on the management of this common paediatric surgical emergency is urgently required.

A taxonomy-free diatom eDNA-based technique for assessing lake trophic level using lake sediments.

Anthropogenic eutrophication is one of the most pressing issues facing lakes globally. Our ability to manage lake eutrophication is hampered by the limited spatial and temporal extents of monitoring records, stemming from the time-consuming and expensive nature of physiochemical and biological monitoring. Diatom-based biomonitoring presents an alternative to traditional eutrophication monitoring, yet it is restricted by the high degree of taxonomic expertise required. Environmental DNA metabarcoding, while providing a promising substitute for diatom community enumeration, is plagued by inadequate taxonomic coverage of reference databases and methodological bias, limiting its use for biomonitoring. Here we show that taxonomy-free diatom-biomonitoring, in which environmental DNA metabarcoding data is utilised but not assigned to specific taxonomic classes, presents an accurate, fast, and relatively automated alternative to taxonomically assigned eutrophication biomonitoring. Our taxonomy-free index accounted for 85% of trophic level variability across 89 lakes and had the lowest average prediction error of the three approaches tested. By not relying on taxonomic identification or metabarcoding reference databases, taxonomy-free biomonitoring maintains diatom diversity that is lost in taxonomic assignment using molecular approaches. Furthermore, by utilising lake sediments, the approach outlined here presents a time-integrated estimation of lake trophic level and thus does not require time-consuming seasonal sampling. Taxonomy-free biomonitoring addresses the limitations of traditional physicochemical eutrophication monitoring and taxonomic biomonitoring alternatives and can be used to extend the spatial and temporal extents of eutrophication monitoring.

A protocol for a systematic review of randomised evaluations of strategies to improve recruitment of rural participants to randomised controlled trials.

INTRODUCTION: People living rurally face health inequities fuelled by social exclusion, access to and awareness of health services, and poor transport links. In order to improve the acceptability, accessibility and applicability of health and care interventions, it is important that clinical trial participant populations include people living rurally. Identifying strategies that improve recruitment of rural participants to trials will support trialists, reduce research waste and contribute to alleviating health inequalities experienced by rural patients. The objective of the review is to quantify the effects of randomised evaluations of strategies to recruit rural participants to randomised controlled trials. METHODS: The following databases will be searched for relevant studies: Ovid MEDLINE, Embase, Cochrane Library, Web of Science All, EBSCO CINAHL, Proquest, ERIC, IngentaConnect, Web of Science SSCI and AHCI, and Scopus. Any randomised evaluation of a recruitment intervention aiming to improve recruitment of rural participants to a randomised trial will be included. We will not apply any restriction on publication date, language or journal. The primary, and only, outcome of our review will be the proportion of participants recruited to a randomised controlled trial. Two reviewers will independently screen abstracts and titles for eligible studies, and then full texts of relevant records will be reviewed by the same two reviewers. Where disagreements cannot be resolved through discussion, a third reviewer will adjudicate. RESULTS: We will assess the methodological quality of individual studies using the Cochrane risk of bias tool, and the GRADE approach will be applied to determine the certainty of the evidence within each comparison. CONCLUSION: This systematic review will quantify the effects of randomised evaluations of strategies to recruit rural participants to trials. Our findings will contribute to the evidence base to support trial teams to recruit a participant population that represents society as a whole, informing future research and playing a part to alleviate health inequalities between rural and urban populations.

Recommendations for occupational therapy interventions for adults with ADHD: a consensus statement from the UK adult ADHD network.

BACKGROUND: ADHD is neurodevelopmental disorder which persists into adulthood. Presently, therapeutic approaches are mainly pharmacological and psychological whilst the role, scope and approaches of occupational therapists have not been adequately described. RESULTS: In this consensus statement we propose that by assessing specific aspects of a person's occupation, occupational therapists can deploy their unique skills in providing specialist interventions for adults with ADHD. We also propose a framework with areas where occupational therapists can focus their assessments and give practice examples of specific interventions. CONCLUSIONS: Occupational therapists have much to offer in providing interventions for adults with ADHD. A unified and flexible approach when working with adults with ADHD is most appropriate and further research on occupational therapy interventions is needed.

Patient satisfaction with general practice in urban and rural areas of Scotland.

INTRODUCTION: The aim of the study was to determine if there is a systematic difference between urban and rural patient experience across Scottish general practices associated with urban/rural status measured by the Scottish eightfold urban/rural classification (UR8). METHODS: The study was a secondary analysis of data from the Scottish National Health and Care Experience (HACE) survey of patient satisfaction. Cross-sectional and longitudinal datasets were used to illustrate recent findings and temporal trends. The general practices were matched to HACE survey responses and practice code numbers, which in turn were assigned to a code from the UR8 classification (where UR8 is the most rural and UR1 is the most urban) based on postal code. Due to the low number of practices in some UR8 classifications, categories (UR3-5 and UR6-8) were merged for some analyses. Patient-centred care and continuity of care were assessed based on a selection of questions from the 2017/18 survey where respondents were asked to indicate their level of agreement to numerous statements. The response alternatives to the survey questions were 'very positive', 'positive', 'neutral' and 'negative'. Responses of 'very positive' and 'positive' were aggregated to give 'percentage satisfied'. One-way analysis of variance (ANOVA) was used to assess cross-sectional and longitudinal datasets. RESULTS: A total of 1008 GP practices participated in the 2009/10 HACE survey. Of these, 166 practices were excluded from the study for a range of reasons including closures or mergers. A total of 71 practices had changed UR8 classification between 2010 and 2018 and were also excluded. Five very small practices were excluded as these were considered likely to offer services to atypical populations. Data relating to 766 practices were analysed: average response rates were 18-31%, highest in the most remote areas. In the most recent 2017/18 survey results, there were significant differences in percentage positive responses by merged UR8 category for all questions (all p<0.001): patients in the most rural/remote UR6-8 practices were significantly more satisfied for all questions analysed. For some questions, such as 'I was listened to', UR1 was significantly different from UR2 and UR3-5, but there was no significant difference between UR2 and UR3-5. For all questions, patients in UR3-5 practices reported having the lowest satisfaction. Overall satisfaction was lowest for the questions 'I was given the opportunity to involve the people that matter to me' and 'I knew the healthcare professional well'. Regarding the longitudinal data for patient satisfaction, patients within the UR6-8 classifications tend to be most satisfied, and this trend has stayed consistent over time. In particular, 'I was given enough time' showed a statistically significant difference across all years for UR6-8, compared to the other urban/rural categories, which did not differ significantly. CONCLUSION: Individuals residing in remote and rural areas of Scotland tend to have the highest satisfaction with their general practice in terms of patient-centred care and continuity of care. Residents in suburban populations tend to be least satisfied in the same domains. Additional work is needed in order to understand the underlying mechanisms behind these findings.

Preschool developmental concerns and adjustment in the early school years: Evidence from a Scottish birth cohort.

BACKGROUND: Preschool language and behavioural difficulties impact on multiple domains of the child's early life and can endure into adulthood, predicting poor educational, social, and health outcomes. Highlighting risk factors associated with poor outcomes following language and behavioural difficulties raised in early childhood may facilitate early identification and intervention. METHODS: Data from the Growing Up in Scotland national birth cohort study were used. Language and behavioural difficulties were assessed at age 4 years using parent-reported language concerns and the Strengths and Difficulties Questionnaire. Measures of adjustment were collated into four key outcome domains: attitude to school life, language and general development, behaviour, and general health at age 6 years. Both univariate and multivariate logistic regression models were fitted in order to explore independent associations between language and behavioural difficulties at age 4 years and adjustment to life circumstances at age 6 years, whilst controlling for other risk factors. RESULTS: Language difficulties at age 4 years increased the odds of the child experiencing difficulty with language and general development, poorer health outcomes, and behavioural difficulties at age 6 years. Behavioural difficulties alone at age 4 years were associated with increased odds of the child experiencing all of the aforementioned outcomes and difficulties in early school life. Lone parent family, low income, and male gender were identified as risk factors for poorer outcomes in the domains measured. At age 4 years, there was no additive effect found with the presence of behaviour difficulties on the relationship between language difficulties and language and developmental outcomes at 6 years. CONCLUSIONS: This paper demonstrates language and behavioural difficulties are associated with poor social, educational, health, and behavioural outcomes. Taking seriously parent-reported concerns and identifying risk factors could limit negative outcomes for the child, their family, and society.

Development problems were common five years after positive screening for language disorders and, or, autism at 2.5 years of age.

AIM: This study identified whether children who had screened positive for either developmental language disorder (DLD) or autism spectrum disorder (ASD) at the age of 2.5 years had neurodevelopmental assessments five years later. METHODS: Our study cohort were 288 children born from 1 July 2008 to 20 June 2009 who screened positive for DLD and, or, ASD at 2.5 years. Of these, 237 children were referred to, and assessed, at the Paediatric Speech and Language Pathology clinic (n = 176) or the Child Neuropsychiatry Clinic (n = 61) at the Queen Silvia Children's Hospital, Gothenburg, Sweden. Clinical registers covering all relevant outpatient clinics were reviewed five years later with regard to established diagnoses. RESULTS: When the 237 were followed up five years later, 96 (40%) had established neurodevelopmental disorders or problems, often beyond DLD and ASD. Co-existing problems were common in this cohort and multidisciplinary assessments were indicated. The other 60% did not appear in subsequent clinic records. It is likely that this 40% was a minimum rate and that more children will be referred for developmental problems later. CONCLUSION: Five years after they had been screened positive for DLD and, or autism at 2.5 years, 40% of our cohort had remaining or other developmental problems.

No evidence of whole population mental health impact of the Triple P parenting programme: findings from a routine dataset.

BACKGROUND: The Triple P parenting programme has been reported to improve child mental health at population level, but it consumes substantial resources. Previous published work has suggested improvements in whole population scores in the Strengths and Difficulties Questionnaire (SDQ) Total Difficulties Scale among samples of children following introduction of the programme. This paper aims to explore whether Triple P had an impact on child mental health problems using routinely collected data over 6 years before and during the implementation of the multilevel Triple P programme in Glasgow City. METHODS: Annual monitoring of teacher-rated SDQ Total Difficulties Scale scores among children in their pre-school year in Glasgow City. RESULTS: No significant or consistent changes in SDQ Total Difficulties Scale scores were seen during or after the implementation of Triple P programme on a whole population level. CONCLUSION: Triple P in Glasgow City appears to have had no impact on early child mental health problems over a 6 year period. The Triple P programme, implemented on a whole population level, is unlikely to produce measurable benefits in terms of child mental health.

Access to chlamydia testing in remote and rural Scotland.

INTRODUCTION: The aim of this study was to assess access to sexual health care in remote and rural settings using Chlamydia testing as a focus by measuring the extent of Chlamydia testing and positivity across the Scottish Highlands in relation to the Scottish Index of Multiple Deprivation Quintile (SIMD) and Urban Rural 8-fold index (UR8). METHODS: Tests processed through Raigmore Hospital in Inverness, the main testing laboratory for microbiology tests in North and West and South and Mid Highlands, were studied. Where people are tested in relation to where they live was assessed, as well as the type of test they opt for. Also assessed was the rate of positivity in male and female patients in rural compared with urban settings using the Scottish Government UR8 and in relation to the SIMD. RESULTS: 9644 results were analysed. 77.2% of the results were for females and 22.4% for males. 8.1% of the results were positive and 84.4% were negative. There were proportionately more positive tests from the sexual health sources than from general practice. The proportion of men who had positive tests was almost double that for women (12.7% vs 6.6%) although men made up only 27.9% of the total number of tests. There was no significant difference in positivity when compared with UR8 index or SIMD. 37.7% of people living in the most rural areas (UR8 7-8) had their test performed in a more urban setting (UR8 1-6), and 20.4% people had their test performed in a very urban setting (UR8 1-2). Of these tests, there was a tendency for UR8 7-8 patients to be more likely to have a positive test if tested in an urban setting. CONCLUSIONS: These results are similar to previous results in other countries that suggest that Chlamydia positivity is similar in rural and urban settings. A large proportion of people living in more rurally classified areas, and perhaps those with a higher risk, have their test in a central setting, suggesting that they may be bypassing local resources to get a test. The reason for this is not clear. The results also show that men are more likely to have their test in a genitourinary setting as well as have proportionately more positive results. These results support the case for customising sexual health services to the most rural areas and suggest that providing an anonymous testing service in these areas might be beneficial, especially for men.

Exploring the social, emotional and behavioural development of preschool children: is Glasgow different?

BACKGROUND: Glasgow City has poorer adolescent and adult health outcomes in comparison to demographically similar cities in England and the rest of Scotland. Until now, little exploration of differences in child development between Glasgow and other areas has been made. The authors hypothesized that the poorer health outcomes and lifestyle behaviours of adults, coupled with relative economic deprivation, may impact on child social, emotional and behavioural development, compared with children from other parts of Scotland. METHODS: Data from the Growing Up in Scotland national birth cohort study were used. Differences between Strengths and Difficulties Questionnaire (SDQ) scores and child and family characteristics of children living in the Greater Glasgow and Clyde (GGC) Health board vs. other health boards were examined. Logistic regression and linear regression models were fitted in order to explore independent associations between health board and SDQ raw and banded scores, respectively, whilst controlling for other contributing factors. RESULTS: Children in GGC were demographically different from those in other areas of Scotland, being significantly more likely to live in the most deprived areas, yet no difference was found in relation to the mental health of preschool-aged children in GGC. Children in GGC had slightly better SDQ Conduct Problems scores once demographic factors were controlled for. CONCLUSIONS: At 46 months, there does not appear to be any difference in Glasgow with regards to social, emotional and behavioural development. Glaswegian children appear to have slightly fewer conduct problems at this age, once demographics are taken into account. A range of theories are put forward as to why no differences were found, including the inclusion of areas adjacent to Glasgow City in the analysis, sleeper effects, and rater bias.

Mellow Parenting: systematic review and meta-analysis of an intervention to promote sensitive parenting.

AIM: To review and meta-analyse Mellow Parenting interventions for parent-child dyads at high risk of adverse developmental outcomes. METHOD: Using Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guidelines, we extracted all published evaluations of Mellow Parenting and Mellow Babies programmes. We identified published studies with randomized controlled trials, quasi-experimental or within-subject pre-post designs. We incorporated 'grey literature' for unpublished publicly available evaluations. Effect sizes were calculated for impact of Mellow Parenting on parental mental health and child behaviour. Data were extracted on demographics, age of participants, country, and potential sources of bias. RESULTS: We identified eight papers, representing nine data sets, from five of which we calculated effect sizes. There was evidence of a medium treatment effect of Mellow Parenting compared with comparison groups on maternal well-being and child problems. Drop-out from treatment was variable. However, data were heterogeneous and there was evidence of methodological bias. INTERPRETATION: Our data give some support to claims for effectiveness of Mellow Parenting as a group intervention for families with multiple indices of developmental adversity. Given the methodological weaknesses of literature in the area, novel approaches are needed in future trials of low-budget complex interventions in non-commercial settings.

Extreme ("pathological") demand avoidance in autism: a general population study in the Faroe Islands.

Research into Pathological Demand Avoidance (PDA), which has been suggested to be a subgroup within the Autism Spectrum Disorder (ASD), is almost nonexistent in spite of the frequent reference to the condition in clinical practice. The total population of 15 to 24-year-olds in the Faroe Islands was screened for ASD, and 67 individuals were identified who met diagnostic criteria for ASD (corresponding to a general population prevalence of ASD of almost 1 %). Of these 67, 50 had parents who were interviewed using the Diagnostic Interview for Social and Communication Disorders (DISCO-11) which contains 15 "PDA-specific" items. Nine individuals met criteria for "possible clinical diagnosis of PDA", meaning that almost one in five of all with ASD also had indications of having had PDA in childhood, and that 0.18 % of the total population had had the combination of ASD and PDA. However, at the time of assessment, only one of the 9 individuals with possible PDA still met "full criteria". PDA possibly constitutes a considerable minority of all cases with ASD diagnosed in childhood, but criteria for the condition are unlikely to be still met in later adolescence and early adult life.

Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model.

Despite treatment with therapeutic hypothermia, almost 50% of infants with neonatal encephalopathy still have adverse outcomes. Additional treatments are required to maximize neuroprotection. Melatonin is a naturally occurring hormone involved in physiological processes that also has neuroprotective actions against hypoxic-ischaemic brain injury in animal models. The objective of this study was to assess neuroprotective effects of combining melatonin with therapeutic hypothermia after transient hypoxia-ischaemia in a piglet model of perinatal asphyxia using clinically relevant magnetic resonance spectroscopy biomarkers supported by immunohistochemistry. After a quantified global hypoxic-ischaemic insult, 17 newborn piglets were randomized to the following: (i) therapeutic hypothermia (33.5°C from 2 to 26 h after resuscitation, n = 8) and (ii) therapeutic hypothermia plus intravenous melatonin (5 mg/kg/h over 6 h started at 10 min after resuscitation and repeated at 24 h, n = 9). Cortical white matter and deep grey matter voxel proton and whole brain (31)P magnetic resonance spectroscopy were acquired before and during hypoxia-ischaemia, at 24 and 48 h after resuscitation. There was no difference in baseline variables, insult severity or any physiological or biochemical measure, including mean arterial blood pressure and inotrope use during the 48 h after hypoxia-ischaemia. Plasma levels of melatonin were 10 000 times higher in the hypothermia plus melatonin than hypothermia alone group. Melatonin-augmented hypothermia significantly reduced the hypoxic-ischaemic-induced increase in the area under the curve for proton magnetic resonance spectroscopy lactate/N-acetyl aspartate and lactate/total creatine ratios in the deep grey matter. Melatonin-augmented hypothermia increased levels of whole brain (31)P magnetic resonance spectroscopy nucleotide triphosphate/exchangeable phosphate pool. Correlating with improved cerebral energy metabolism, TUNEL-positive nuclei were reduced in the hypothermia plus melatonin group compared with hypothermia alone in the thalamus, internal capsule, putamen and caudate, and there was reduced cleaved caspase 3 in the thalamus. Although total numbers of microglia were not decreased in grey or white matter, expression of the prototypical cytotoxic microglial activation marker CD86 was decreased in the cortex at 48 h after hypoxia-ischaemia. The safety and improved neuroprotection with a combination of melatonin with cooling support phase II clinical trials in infants with moderate and severe neonatal encephalopathy.

Mellow Babies: A Randomised Feasibility Trial of an Intervention to Improve the Quality of Parent-Infant Interactions and Parental Mental Wellbeing.

Mellow Babies aims to improve mothers' mental wellbeing and the quality of their interactions with their baby. The feasibility of a definitive trial of Mellow Babies was assessed using a waiting-list randomised pilot trial (Clinicaltrials.gov: NCT02277301). Mothers with substantial health/social care needs and a child aged <13 months were randomly allocated either to a 14-week Mellow Babies programme or to receive usual care whilst on a waiting list for the intervention. Rates of recruitment and retention as well as participants' views of their experience in this study were recorded. Outcomes were parenting behaviour, assessed by the blind-rated Mellow Parenting Observation System (primary) and self-report maternal wellbeing pre- and post-intervention/waiting period. We recruited 38 eligible participants: 36 (95%; 18 intervention, 18 control) completed baseline measures, and 28 (74%; 15 intervention, 13 control) provided post-intervention data. Two practitioners took part in feedback interviews. Intervention participants had significantly more positive interactions with their babies at post-intervention compared to those in the control group (p = 0.019), adjusted for pre-intervention scores. There was no significant improvement in mothers' mental wellbeing on any measure. A definitive trial of Mellow Babies is feasible and should include longer follow up of mothers and the opportunity for fathers to take part.

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.

Sudden peak in tetrodotoxin in French oysters during the summer of 2021: Source investigation using microscopy, metabarcoding and droplet digital PCR.

Tetrodotoxin (TTX) is a potent neurotoxin causing human intoxications from contaminated seafood worldwide and is of emerging concern in Europe. Shellfish have been shown to contain varying TTX concentrations globally, with concentrations typically higher in Pacific oysters Crassostrea gigas in Europe. Despite many decades of research, the source of TTX remains unknown, with bacterial or algal origins having been suggested. The aim of this study was to identify potential source organisms causing TTX contamination in Pacific oysters in French coastal waters, using three different techniques. Oysters were deployed in cages from April to September 2021 in an estuary where TTX was previously detected. Microscopic analyses of water samples were used to investigate potential microalgal blooms present prior or during the peak in TTX. Differences in the bacterial communities from oyster digestive glands (DG) and remaining flesh were explored using metabarcoding, and lastly, droplet digital PCR assays were developed to investigate the presence of Cephalothrix sp., one European TTX-bearing species in the DG of toxic C. gigas. Oysters analysed by liquid chromatography-tandem mass spectrometry contained quantifiable levels of TTX over a three-week period (24 June-15 July 2021), with concentrations decreasing in the DG from 424 µg/kg for the first detection to 101 µg/kg (equivalent to 74 to 17 µg/kg of total flesh), and trace levels being detected until August 13, 2021. These concentrations are the first report of the European TTX guidance levels being exceeded in French shellfish. Microscopy revealed that some microalgae bloomed during the TTX peak, (e.g., Chaetoceros spp., reaching 40,000 cells/L). Prokaryotic metabarcoding showed increases in abundance of Rubritaleaceae (genus Persicirhabdus) and Neolyngbya, before and during the TTX peak. Both phyla have previously been described as possible TTX-producers and should be investigated further. Droplet digital PCR analyses were negative for the targeted TTX-bearing genus Cephalothrix.

A paleoecological investigation of recent cyanobacterial blooms and their drivers in two contrasting lakes.

Cyanobacterial blooms are one of the most significant threats to global water security and freshwater biodiversity. Interactions among multiple stressors, including habitat degradation, species invasions, increased nutrient runoff, and climate change, are key drivers. However, assessing the role of anthropogenic activity on the onset of cyanobacterial blooms and exploring response variation amongst lakes of varying size and depth is usually limited by lack of historical records. In the present study we applied molecular, paleolimnological (trace metal, Itrax-µ-XRF and hyperspectral scanning, chronology), paleobotanical (pollen) and historical data to reconstruct cyanobacterial abundance and community composition and anthropogenic impacts in two dune lakes over a period of up to 1200 years. Metabarcoding and droplet digital PCR results showed very low levels of picocyanobacteria present in the lakes prior to about CE 1854 (1839-1870 CE) in the smaller shallow Lake Alice and CE 1970 (1963-1875 CE) in the larger deeper Lake Wiritoa. Hereafter bloom-forming cyanobacteria were detected and increased notably in abundance post CE 1984 (1982-1985 CE) in Lake Alice and CE 1997 (1990-2007 CE) in Lake Wiritoa. Currently, the magnitude of blooms is more pronounced in Lake Wiritoa, potentially attributable to hypoxia-induced release of phosphorus from sediment, introducing an additional source of nutrients. Generalized linear modelling was used to investigate the contribution of nutrients (proxy = bacterial functions), temperature, redox conditions (Mn:Fe), and erosion (Ti:Inc) in driving the abundance of cyanobacteria (ddPCR). In Lake Alice nutrients and erosion had a statistically significant effect, while in Lake Wiritoa nutrients and redox conditions were significant.