Case identification of non-traumatic brain injury in youth using linked population data.

BACKGROUND: Population-level administrative data provides a cost-effective means of monitoring health outcomes and service needs of clinical populations. This study aimed to present a method for case identification of non-traumatic brain injury in population-level data and to examine the association with sociodemographic factors. METHODS: An estimated resident population of youth aged 0-24 years was constructed using population-level datasets within the New Zealand Integrated Data Infrastructure. A clinical consensus committee reviewed the International Classification of Diseases Ninth and Tenth Editions codes and Read codes for inclusion in a case definition. Cases were those with at least one non-traumatic brain injury code present in the five years up until 30 June 2018 in one of four databases in the Integrated Data Infrastructure. Rates of non-traumatic brain injury were examined, both including and excluding birth injury codes and across age, sex, ethnicity, and socioeconomic deprivation groups. RESULTS: Of the 1 579 089 youth aged 0-24 years on 30 June 2018, 8154 (0.52%) were identified as having one of the brain injury codes in the five-years to 30 June 2018. Rates of non-traumatic brain injury were higher in males, children aged 0-4 years, Maori and Pacific young people, and youth living with high levels of social deprivation. CONCLUSION: This study presents a comprehensive method for case identification of non-traumatic brain injury using national population-level administrative data.

Age at first exposure to antibiotics and neurodevelopmental outcomes in childhood.

RATIONALE: Viral illnesses in children are common and are frequently treated with antibiotic medication. Antibiotics reduce the diversity and composition of the gut microbiota, leading to poor developmental outcomes. OBJECTIVES: To investigate the relationship between age at first exposure to antibiotics and cognitive and behavioural development at 4.5 years while controlling for multiple confounders, including otitis media. METHODS: Study participants were 5589 children enrolled in the broadly generalisable Growing Up in New Zealand cohort study, with antibiotic exposure data, maternal antenatal information, and age 4.5-year behaviour and cognitive outcome data. Children were categorised as first exposed to antibiotics according to the following mutually exclusive ages: 0-2 months; 3-5 months; 6-8 months; 9-11 months; 12-54 months or not exposed by 54 months. Developmental outcome measures included the Strengths and Difficulties Questionnaire, Luria hand clap task, and the Peabody Picture Vocabulary Test-III. RESULTS: In univariate analysis, there was an evident dose-response relationship where earlier exposure to antibiotics in the first year of life was associated with behavioural difficulties, lower executive function scores, and lower receptive language ability. After adjusting for confounders, pairwise comparisons showed that first antibiotic exposure between birth and 3 months or between 6 and 9 months was associated with lower receptive vocabulary. Antibiotic exposure at any age prior to 12 months was associated with increases in behavioural difficulties scores at 4.5 years. CONCLUSIONS: Following adjustment for socioeconomic factors and otitis media, there is evidence that antibiotic exposure during potentially sensitive windows of development is associated with receptive language and behaviour later in childhood.

A randomized trial of probiotic supplementation in nurses to reduce stress and viral illness.

Animal studies demonstrate how the gut microbiota influence psychological health and immunity to viral infections through their actions along multiple dynamic pathways in the body. Considerable interest exists in probiotics to reduce stress and illness symptoms through beneficial effects in the gut, but translating pre-clinical evidence from animal models into humans remains challenging. We conducted a large trial in nurses working during the 2020 COVID19 pandemic year to establish whether daily ingestion of the probiotic Lactobacillus rhamnosus HN001 reduced perceived stress and the number of days participants reported symptoms of a viral illness. Our results showed no significant difference in perceived stress or the average number of illness days between probiotic supplemented nurses and the placebo group. Stress and viral illness symptoms reduced during the study for all participants, a trajectory likely influenced by societal-level factors. The powerful effect of a well-managed public health response to the COVID19 pandemic and the elimination of COVID19 from the community in 2020 may have altered the trajectory of stress levels and reduced circulating viral infections making it difficult to detect any effect of probiotic supplementation. Our study highlights the challenge in controlling environmental factors in human trials.

Probiotics for Reduction of Examination Stress in Students (PRESS) study: A randomized, double-blind, placebo-controlled trial of the probiotic Lacticaseibacillus rhamnosus HN001.

BACKGROUND: Studies suggest that bioactive compounds such as probiotics may positively influence psychological health. This study aimed to determine whether supplementation with the probiotic Lacticaseibacillus rhamnosus HN001 reduced stress and improve psychological wellbeing in university students sitting examinations. METHODS: In this randomized, double-blind, placebo-controlled study, 483 undergraduate students received either the probiotic L. rhamnosus HN001, or placebo, daily during a university semester. Students completed measures of stress, anxiety, and psychological wellbeing at baseline and post-intervention before examinations. Mann Whitney U tests compared the change in psychological outcomes between groups. RESULTS: Of the 483 students, 391 (81.0%) completed the post-intervention questions. There was no significant difference between the probiotic and placebo supplemented groups in psychological health outcomes. The COVID19 pandemic restrictions may have influenced the typical trajectory of stress leading up to examinations. CONCLUSION: We found no evidence of significant benefit of probiotics on the psychological health of university students. These findings highlight the challenges of conducting probiotic trials in human populations where the potential for contextual factors such as COVID19 response, and participant adherence to the intervention may influence results.

Improvement in the psychological health of nurses working during the COVID-19 pandemic.

BACKGROUND: Nurses are a critical component of any healthcare system. The novel coronavirus pandemic has resulted in an increased workload for nurses and heightened stress. AIMS: To assess the psychological health over time of nurses working during the COVID-19 pandemic and to examine the factors associated with stress, anxiety, and psychological wellbeing. METHODS: Nurses enrolled in the study between 2 July and 26 August 2020 andcompleted questionnaires about stress, anxiety, and psychological wellbeing at baseline and at a second time point T2 12 weeks later. A paired sample t-test was used to examine whether changes in stress, anxiety, and psychological wellbeing were significantly different between baseline and T2. Linear regression models examined factors associated with psychological health outcomes. RESULTS: Of the 600 nurses initially enrolled, 484 (80.7%) completed psychological health measures at T2. Stress, anxiety, and poor psychological wellbeing scores were high at baseline. Unexpectedly, stress and psychological wellbeing significantly improved between baseline and T2, while anxiety levels increased. Younger nurses had higher baseline stress and anxiety scores. CONCLUSIONS: This study demonstrates the potential beneficial effect of effective public health management of the COVID-19 pandemic on nurses' stress and psychological wellbeing and highlights the importance of longitudinal research to understand psychological health in nurses.

Neuropsychological assessment of paediatric brain tumour survivors: Factors associated with assessment.

AIM: Paediatric brain tumour survivors are at increased risk of neurocognitive deficits that affect their education. The aim of this study was to assess the proportion of brain tumour survivors who historically received a neuropsychological assessment and examine the demographic and treatment-related variables associated with neuropsychological assessment. A further aim was to determine the number and treatment profile of brain tumour survivors who would benefit from neuropsychological assessment. METHODS: Data from the New Zealand Children's Cancer Registry including treatments received, was used to identify children treated for a brain tumour at Starship Children's Hospital between January 2009 and December 2015. Clinical records were examined for evidence of a neuropsychological assessment in the form of a written report. Logistic regression models were used to determine factors associated with receipt of an assessment. RESULTS: Of the 132 brain tumour survivors, 37 (28.0%) had evidence of a neuropsychological assessment in their clinical records. In adjusted analysis, children who were treated with all three of surgery, chemotherapy and radiotherapy (n = 38) were more likely to have had an assessment (odds ratio: 12.90; 95% confidence interval: 4.76-34.93) than children who had either no treatment, chemotherapy alone, surgery alone or chemotherapy and surgery (n = 73). Treatment with radiotherapy alone or with either chemotherapy or surgery (n = 21) was not significantly associated with receipt of assessment (odds ratio = 2.40; 95% confidence interval: 0.69-8.37). CONCLUSIONS: It is important to identify the number of children who might benefit from neuropsychological assessment to inform prioritisation within existing resource and plan for additional resource if required. With a focus on reducing late effects, it is imperative that neuropsychological assessment is an integral component of a paediatric brain tumour programme.

Factor structure of the SDQ and longitudinal associations from pre-school to pre-teen in New Zealand.

OBJECTIVE: The objective of this study was to assess the validity of the Strengths and Difficulties Questionnaire in a cohort of New Zealand children followed from birth to the age of eleven. The study also aimed to assess the stability of the child data in relation to behavioural outcomes during this period. METHODS: Children in the Auckland Birthweight Collaborative Study were assessed at approximately 3½, 7 and 11 years of age. At all time-points parents completed the parent version of the Strengths and Difficulties Questionnaire, and the children themselves completed the self-report version at 11 years of age. The validity and internal consistency were assessed using exploratory factor analysis, Cronbach's alpha, and McDonald's Omega. Cross tabulations and Chi-square statistics were used to determine whether Total Difficulty scores, as per accepted cut-offs, remained stable over time (between normal and abnormal/borderline categories). RESULTS: The factor structure remained relatively consistent across all three time-points, though several questions did not load as per the originally published factor analysis at the earliest age. The internal consistency of the Strengths and Difficulties Questionnaire was good at all time-points and for parent- and child-completed versions. There was low agreement in the total scores between time points. CONCLUSIONS: The factor analysis shows that the Strengths and Difficulties Questionnaire has a similar factor structure, particularly in older ages, to that previously published and shows good internal consistency. At the pre-school follow up, a larger than expected proportion of children were identified with high scores, particularly in the conduct sub-scale. Children's behaviour changes over time, with only poor to moderate agreement between those identified as abnormal or borderline over the longitudinal follow up.

Quality of Life Using General Population Validated Questionnaires in Children With Cleft Lip and/or Palate in New Zealand.

OBJECTIVE: To determine the level of quality of life (QoL) in children with cleft lip and/or palate (CL/P) and whether this differs by cleft phenotype. DESIGN: A cohort of children with CL/P born in New Zealand. SETTING: A nationwide study of children born with CL/P and having primary surgery in New Zealand. PARTICIPANTS: Children with CL/P and their families (n = 397) who attended a cleft clinic between October 1, 2014, and September 30, 2017, and agreed to complete questionnaires on QoL. MAIN OUTCOMES: Primary outcomes were QoL from the PedsQL 4.0 core generic questionnaires and the PedsQL 2.0 Family impact scale. RESULTS: Children with CL/P in New Zealand generally have a high QoL as assessed by the PedsQL. The impact of cleft phenotype had limited effects on the child, however there were significant impacts on parents and families. We found that the family impact scale differed by cleft phenotype with those with CL having the highest QoL and those with cleft palate the lowest, and this was consistent across QoL subscales. Quality of life improved as a whole by age, particularly in physical and cognitive functioning, as well as in the ability to undertake family activities. CONCLUSIONS: Children with CL/P have generally good levels of QoL in New Zealand, however cleft phenotype impacts on the level, with the lowest levels in those with cleft palate. Psychological support of children with cleft and their families should be an integral part of cleft care.

Birth by caesarean section and educational achievement in adolescents.

BACKGROUND: Birth by caesarean section has been shown to alter the composition of the early infant gut microbiota and postulated to influence cognitive outcomes via the gut-brain axis. AIMS: To determine whether birth by caesarean section is associated with secondary school educational achievement. METHODS: Whole-population administrative data were used from anonymised individual level linkage of birth records to educational and health information from the New Zealand Integrated Data Infrastructure (IDI). Participants were 111 843 children born between 1 January 1996 and 31 December 1998 for whom mode of delivery information was available from International Classification of Diseases 9th edition codes in maternal records. The National Certificate of Educational Achievement (NCEA) is the main secondary school qualification undertaken by New Zealand students. Multivariable linear regression models were used to examine the association between mode of delivery and educational achievement. A family fixed effect analysis compared educational achievement outcomes in sibling pairs where one sibling was delivered by caesarean section and one delivered vaginally. RESULTS: After adjustment for potential confounders, there was no significant association between mode of delivery and achievement of university entrance (odds ratio = 0.98, 95% CI: 0.94-1.02). NCEA percentile scores were lower in caesarean born infants (Estimate = -0.37, 95% CI: -0.69 to -0.06)). However, in the fixed effect sibling analysis caesarean section was no longer significantly associated with NCEA percentile scores. CONCLUSIONS: We find that caesarean section is not related to educational outcomes, suggesting that even if the infant gut microbiota is altered in caesarean section, it does not appear to have a measurable impact on adolescent academic achievement.

Behavioral Outcomes in Children With an Orofacial Cleft in a National Study in New Zealand.

OBJECTIVE: To determine whether children with an orofacial cleft have higher levels of behavioral problems than the general population and whether this differs by cleft phenotype. DESIGN: A cohort of children with cleft lip and/or palate (CL/P) born in New Zealand from January 1, 2000. SETTING: Cleft clinics in New Zealand participating in a larger outcomes study between 2014 and 2017. PARTICIPANTS: Children (N = 378) aged 5 to 12 years of age and their parents. MAIN OUTCOMES: The Strengths and Difficulties Questionnaire (SDQ) and Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales 4.0 and Family Impact Module 2.0. RESULTS: Compared to standardized norms, children with a cleft had higher than expected (defined as 20%) levels of abnormal/borderline SDQ scores for conduct problems (27.4%, P = .0003) and peer relationship problems (31.6%, P < .0001) but lower than expected levels of problems with pro-social skills (6.3%, P < .0001). There were no significant differences by age-group and or cleft phenotype other than an increased risk of hyperactivity in children with CP compared to children with CL. Total difficulties SDQ scores had moderate correlations with the PedsQL. CONCLUSIONS: While over 90% of children with CL/P had normal prosocial skills, they may not be easily accepted by their peers which may result in behavioral problems. These concerns were moderately related to lower quality of life. Support for establishment and maintenance of peer relationships is important to address externalizing and peer difficulties in children with CL/P. Community knowledge and understanding of CL/P needs to continue to be promoted.

Physical Activity, Sleep, Body Mass Index, and Associated Risk of Behavioral and Emotional Problems in Childhood.

OBJECTIVE: Cross-sectional data indicate that physical activity, longer sleep duration, and normal body weight are associated with better mental health in childhood. It is less clear whether these factors protect against future emotional and behavioral problems. We investigated whether physical activity, sleep duration, and body mass index (BMI) at the age of 7 years are associated with emotional and behavioral problems at the age of 11 years. METHODS: Children born to European mothers enrolled in the prospective longitudinal Auckland Birthweight Collaborative Study (N = 871) were assessed at birth and ages 7 and 11 years. Physical activity and sleep duration were measured using accelerometer. BMI was calculated from height and weight measurement. Outcome variables assessed at the age of 11 years were parent and child self-report Strengths and Difficulties Questionnaire and parent and teacher Conners' Rating Scale scores. RESULTS: Physical activity, sleep duration, and BMI at the age of 7 years were not significantly associated with emotional and behavioral problems at the age of 11 years. In cross-sectional analysis at the age of 11 years, there was no significant association between physical activity or sleep duration and emotional and behavioral problems. Children with a BMI in the overweight or obese range were significantly more likely to have teacher-rated behavior problems and parent-rated emotional or behavioral problems after adjustment for potential confounders. CONCLUSION: Although physical activity and sleep have physical health benefits, they may not be protective against future emotional and behavioral problems in childhood in the general population. BMI in the obese or overweight range was significantly associated with current emotional and behavioral problems at the age of 11 years.

Early adolescent physical activity, sleep and symptoms of depression at 16 years of age.

AIM: To examine early adolescent physical activity and risk of later depressive symptoms at age 16 years in a prospective cohort study. METHODS: Participants were children and parents enrolled at birth of the child. Approximately half the children enrolled in the Auckland Birthweight Collaborative Study were small for gestational age at birth (SGA ≤10th percentile for sex and gestation) and half were appropriate for gestational age (AGA >10th percentile). Maternal demographic data were collected at birth, and children were followed through to age 16 years. Depression at 16 was assessed using the Center for Epidemiological Studies Depression Scale for Children. Accelerometer measures of physical activity and sleep were measured at 11 years of age. RESULTS: Moderate to severe depression was present in 15.6% of the 467 16-year-olds. Objectively measured physical activity and sleep at 11 years were not significantly associated with depressive symptoms at 16 years of age. CONCLUSION: Prospectively collected objective measures of physical activity levels and sleep were not predictive of depressive symptoms later in adolescence in a healthy community cohort. While interventions to promote increased physical activity and sleep in adolescents who are depressed may be effective, physical activity and sleep in the general population of adolescents does not protect against future depression.

Maternal stress during pregnancy and small for gestational age birthweight are not associated with telomere length at 11 years of age.

BACKGROUND: Previous studies indicate that low birth weight and exposure to maternal stress during pregnancy may result in shortened telomeres in infants. Shorter telomere length has in turn been linked with accelerated ageing and with age-related diseases. This study aimed to investigate the association between pregnancy and birth factors and relative telomere length in offspring at 11 years of age. METHODS: Participants were aged 11 years enrolled in the Auckland Birthweight Collaborative Study at birth (n = 380). Half of the children were born small for gestational age (SGA = birthweight ≤ 10th percentile) and half were appropriate for gestational age (AGA = birthweight > 10th percentile). Maternal stress during pregnancy was assessed using the Perceived Stress Scale. Relative leukocyte telomere length (RTL) in leukocytes was measured at 11 years of age using quantitative real-time PCR. RESULTS: RTL was normally distributed (mean = 3.78, SD = 1.05). There were no significant associations between RTL at age 11 years and birthweight, sex, maternal smoking, maternal stress during pregnancy or maternal pre-pregnancy body mass index. CONCLUSION: At age 11 years, RTL did not differ between children by birthweight or pregnancy-related stressors. Further telomere-related studies in newborns, children and adolescents are merited to increase knowledge of potential telomere modulating factors.

Antibiotics in the first year of life and subsequent neurocognitive outcomes.

AIM: There may be a link between disruption to the gut microbiota in early life and later neurocognitive outcomes. We hypothesised that antibiotic use in early life is associated with a detrimental effect on later neurocognitive outcomes. METHODS: Eight hundred and seventy-one European mothers and their children enrolled in the Auckland Birthweight Collaborative Study at birth. Information on antibiotic use during the first year of life and between 12 months and three-and-a-half years of age was gathered via maternal interview. Intelligence test scores and measures of behavioural difficulties were obtained when children were three-and-a-half years, seven years and 11 years of age. RESULTS: Antibiotic use in the first year of life was reported in 70% of the 526 children with antibiotic data assessed at age three-and-a-half years. Those who had received antibiotics had more behavioural difficulties and more symptoms of depression at follow-up. Results were consistent across all standardised psychologist administered tests, as well as parent rated, teacher rated and self-report measures. CONCLUSION: This study demonstrates an association between antibiotic use in the first year of life and subsequent neurocognitive outcomes in childhood. If confirmed by further research, these findings could have implications for the use of antibiotics for minor illnesses in infancy.

The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.

BACKGROUND: Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum. METHODS/DESIGN: The PiP Study is a two-centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14-16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 × 10(9) colony-forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding. Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35-37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action. DISCUSSION: The study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registration: ACTRN12612000196842. Date Registered: 15/02/12.

Maternal stress during pregnancy is associated with moderate to severe depression in 11-year-old children.

AIM: Maternal stress during pregnancy has been associated with negative outcomes in children. We examined the risk factors for symptoms of depression in 11-year-old children, including the interaction between birthweight and other variables. METHODS: We collected maternal, obstetric and demographic information from birth through to the age of 11. Approximately, half of the 609 children were born small-for-gestational-age (SGA). Information collected at 3.5 and 7 years of age included intelligence testing and parent-reported behavioural and emotional development. At 11 years of age, the children completed the Center for Epidemiological Studies Depression Scale for Children. Multivariable logistic regression analysis examined the relationship between self-reported symptoms of moderate to severe depression at the age of 11 and explanatory variables. RESULTS: Symptoms of moderate to severe depression were related to increasing maternal stress during pregnancy, young maternal age, lower intelligence test scores at 7-years-old and being bullied at school in the previous 6 months. There was also a significant interaction between maternal stress in pregnancy and symptoms of depression in 11-year-old children born SGA. CONCLUSION: Increasing maternal stress during pregnancy was associated with increased risk of symptoms of moderate to severe depression in 11-year-old children, especially those who were born SGA.

Determinants of developmental delay in infants aged 12 months.

The aim of this study was to determine which demographic, maternal, obstetric and postnatal variables were associated with achievement of developmental milestones at the age of 12 months in term infants. Mothers and babies were enrolled in the Auckland Birthweight Collaborative Study shortly after birth. All infants were full term (gestation >or= 37 weeks). Approximately half of the sample were small for gestational age (SGA = birthweight 10th percentile). A maternal interview was conducted soon after birth. Phase 2 of the study occurred 12 months later when mothers were sent a postal questionnaire requesting information about the child's health and development during the first year of life using the Denver Prescreening Developmental Questionnaire. Seven hundred and forty-four (85.4%) European mothers returned the postal questionnaire. SGA children were not at increased risk of developmental delay at 12 months of age. In a sample representative of New Zealand European children, after adjustment for the effects of potential confounders, maternal smoking during pregnancy (OR = 2.1 [95% CI 1.1, 4.0]), maternal smoking during the first year of life (OR = 1.9 [95% CI 1.0, 3.8]) and low levels of satisfaction with parenting (OR = 2.4 [95% CI 1.1, 5.2]) were associated with significantly increased risk of developmental delay. In the subgroup of SGA children, maternal smoking during pregnancy (OR = 2.9 [95% CI 1.4, 6.2]), high levels of stress associated with parenting (OR = 2.2 [95% CI 1.2, 4.0]), and low levels of satisfaction with parenting (OR = 4.3 [95% CI 1.3, 13.5]) were significantly associated with developmental delay after adjustment for the effects of potential confounders. In conclusion, maternal and postnatal factors were better predictors of developmental delay than demographic variables.