Widespread prevalence of a CREBRF variant amongst Maori and Pacific children is associated with weight and height in early childhood.

OBJECTIVE: Investigating a large and ethnically diverse cohort from the Pacific region, we aimed to replicate and extend the recently reported findings that a CREBRF genetic variant is strongly associated with body mass index in Samoans. METHODS: A birth cohort of more than six thousand children was utilised. In this study, genotyping of two markers (rs12513649 and rs373863828) was undertaken in Maori, Pacific, European and Asian individuals in the cohort. RESULTS: We report that these CREBRF genetic variants are not confined to Samoans but are prevalent in all other Pacific populations sampled, including Maori. We found that the rs373863828 variant was significantly associated with growth at 4 years of age. On average, we observed allele-specific increases in weight (P=0·004, +455 g, s.e. 0.158), height (P=0·007, +0·70 cm, s.e. 0.26) and waist circumference (P=0·004, +0·70 cm, s.e. 0.24) at 4 years of age. The rs373863828 variant was not associated with birth weight (P=0·129). CONCLUSIONS: We replicated the finding that a CREBRF variant is associated with increased body mass. We then built on the original findings by demonstrating the prevalence of the rs12513649 and rs373863828 variants in multiple Pacific population groups and by demonstrating that the rs373863828 variant is associated with growth in early childhood. Pacific population groups experience a disproportionately high burden of obesity, starting in early childhood. This new knowledge offers potential for evidence-based interventions aimed at establishing healthy growth trajectories from the earliest possible age.

Improving rates of overweight, obesity and extreme obesity in New Zealand 4-year-old children in 2010-2016.

BACKGROUND: Prevalence of childhood obesity is high in developed countries, and there is a growing concern regarding increasing socio-economic disparities. OBJECTIVES: To assess trends in the prevalence of overweight, obesity and extreme obesity among New Zealand 4-year olds, and whether these differ by socio-economic and ethnic groupings. METHODS: A national screening programme, the B4 School Check, collected height and weight data for 75-92% of New Zealand 4-year-old children (n = 317 298) between July 2010 and June 2016. Children at, or above, the 85th, 95th and 99.7th percentile for age and sex adjusted body mass index (according to World Health Organization standards) were classified as overweight, obese and extremely obese, respectively. Prevalence rates across 6 years (2010/11 to 2015/16) were examined by sex, across quintiles of socio-economic deprivation, and by ethnicity. RESULTS: The prevalence of overweight, obesity and extreme obesity decreased by 2.2 [95% CI, 1.8-2.5], 2.0 [1.8-2.2] and 0.6 [0.4-0.6] percentage points, respectively, between 2010/2011 and 2015/2016. The downward trends in overweight, obesity and extreme obesity in the population persisted after adjustment for sex, ethnicity, deprivation and urban/rural residence. Downward trends were also observed across sex, ethnicity and deprivation groups. CONCLUSIONS: The prevalence of obesity appears to be declining in 4-year-old children in New Zealand across all socio-economic and ethnic groups.

Adolescent understanding of DOHaD concepts: a school-based intervention to support knowledge translation and behaviour change.

A life-course approach to reduction of risk of non-communicable diseases (NCD) suggests that early-life interventions may be more effective than lifestyle modifications in middle age. Knowledge translation to develop understanding of the Developmental Origins of Health and Disease (DOHaD) within the community offers the potential to encourage informed diet and lifestyle choices supporting reduction of NCD risk in current and future generations. Many women do not make sustained dietary change before or during pregnancy, therefore appropriate nutritional behaviours need to be established prior to adulthood. This makes adolescence an appropriate stage for interventions to establish suitable dietary and lifestyle behaviours. Therefore, we engaged adolescents in a school-based educational intervention, and assessed the value of this in development of understanding of DOHaD concepts to support behaviour change that could lead to NCD risk reduction in the next generation. Modules of course work were written for 11-14 year olds and trialled in nine schools. Matched pre- and post-intervention questionnaire responses from 238 students and 99 parents, and post-intervention interviews evaluated the intervention. Understanding of a link between maternal diet during pregnancy and the health of the foetus in adulthood increased from 46% to 76% following intervention. Post-intervention evidence suggests the programme facilitated discussion of diet, lifestyle and DOHaD concepts in most families. The intervention was effective in improving understanding of DOHaD concepts and in some cases led to appropriate behaviour change. However, the sustainability of these changes remains to be determined through on-going evaluation of attitudes and behaviour within this cohort.

Exposure to repeat doses of antenatal glucocorticoids is associated with altered cardiovascular status after birth.

OBJECTIVE: To determine if exposure to more than one course of antenatal glucocorticoids is associated with changes in infant blood pressure and myocardial wall thickness in the first month after birth. DESIGN: Prospective cohort study. SETTING: Tertiary neonatal intensive care unit. PARTICIPANTS: Mothers who were eligible for but declined to enter a randomised trial of repeated doses of antenatal glucocorticoids (ACTORDS)-that is, who had a singleton, twin, or triplet pregnancy at <32 weeks gestation, had received an initial course of glucocorticoids seven or more days previously, and were considered to be at continued risk of preterm birth. MAIN OUTCOME MEASURES: Blood pressure daily for the first week then weekly until 4 weeks of age. End diastolic interventricular septal and left ventricular posterior wall (EDIVS and EDLVPW) thickness at 48-72 hours after birth. RESULTS: Thirty seven women were enrolled and delivered 50 infants. Thirty mothers (39 infants) were exposed to one course of glucocorticoids, and seven mothers (11 infants) to more than one course. Blood pressures were higher in the first week after birth in infants exposed to multiple courses of glucocorticoids, and in infants with a latency between last exposure and delivery of less than seven days. Systolic blood pressure on day 1 was >2SD above published normal ranges in 67% of babies exposed to multiple courses and 24% of babies exposed to a single course of glucocorticoids (p = 0.04). There was no difference between groups in thickness of the EDIVS or EDLVPW. However, 44/50 (88%) babies had EDIVS and 49/50 (98%) babies had EDLVPW thickness >2 SD above the expected mean for birth weight and gestation. EDIVS but not EDLVPW thickness increased with increasing latency (mean 0.02 mm/day, p = 0.03). CONCLUSION: Future randomised trials should assess the long term effects of exposure to antenatal glucocorticoids, particularly multiple courses, on the cardiovascular status of the infant.

Inter- and intra-limb generalization of adaptation during catching.

We have previously shown that healthy adults require a few trials to adapt to a changed ball weight during catching. It is not known whether this adaptation generalizes to the opposite arm or to different configurations of the same arm. We tested healthy adult subjects catching balls of different weight while maintaining the hand within a vertical spatial "window." In experiment 1, subjects caught a series of light and heavy balls, first with one hand and then with the other. In experiment 2, subjects caught a series of light and heavy balls, first with the catching arm in either a "bent" or a "straight" configuration and then with the same arm in the other configuration. A percentage transfer value was calculated to determine the degree to which previous experience with a given ball weight in one context affected performance of the same task in a new context (i.e., different arm or different arm configuration). Results showed that generalization occurred both between arms and within an arm. However, the subjects who switched arms showed less generalization than those who switched arm positions. Specifically, the percentage transfer value for subjects who switched arms was 58%, while the percentage transfer for those who switched arm positions was 100%. These results support the idea that the motor system is able to generalize adaptive control of ball catching to the contralateral arm and to different arm configurations. Our findings are also in agreement with the recent notion that multiple internal representations of a task may exist in the CNS. Because there was partial generalization between the two arms, we conclude that there must be a representation stored and used for catching that is not effector specific, but rather can be utilized by brain regions controlling either arm. However, because generalization was only complete within an arm, we conclude that another sensorimotor representation exists, which might only be stored in brain regions specific to a single arm.

Subregional localization of 21 chromosome 7-specific expressed sequence tags (ESTs) by FISH using newly identified YACs and P1s.

Twenty-one putative chromosome 7-derived expressed sequence tags (ESTs) identified 33 yeast artificial chromosomes (YACs) or P1 clones, which were then used as reagents for physical mapping. FISH mapping established that the ESTs contained within these clones were distributed throughout chromosome 7, with all major cytogenetic bands represented, except 7p13-p15, 7p11, 7q31.2, and 7q35. Each EST sequence identified at least one other sequence in publicly available databases (using search tools such as BLASTN, basic local alignment search tool), and many of the ESTs identified cDNAs and several genomic DNA sequences. However, 7 ESTs did not identify highly significant matches (P < 1 x 10(-5)). Only one (EST01924-D7S2281E) failed to identify any other EST from the dbEST homology searches. BLAST analysis identified at least five genes from EST sequence comparisons: protein tyrosine phosphatase zeta (PTPRZ, also known as RPTPZ) (EST02092), which we had mapped to 7q31.3, in agreement with previous studies; cAMP-dependent protein kinase regulatory subunit bI (EST01644); rat integral membrane glycoprotein (EST00085); human IFNAR gene for interferon alpha/beta receptor (EST00817); and rat 14-3.3 protein gamma subtype (putative protein kinase C regulatory protein) (EST00762). These ESTs will help to develop the map of chromosome 7, which integrates physical, transcriptional, and cytogenetic data, as well as to provide candidate disease genes for chromosome 7-specific disorders.

Mapping human telomere regions with YAC and P1 clones: chromosome-specific markers for 27 telomeres including 149 STSs and 24 polymorphisms for 14 proterminal regions.

A YAC library enriched for telomere clones was constructed and screened for the human telomere-specific repeat sequence (TTAGGG). Altogether 196 TYAC library clones were studied: 189 new TYAC clones were isolated, 149 STSs were developed for 132 different TY-ACs, and 39 P1 clones were identified using 19 STSs from 16 of the TYACs. A combination of mapping methods including fluorescence in situ hybridization, somatic cell hybrid panels, clamped homogeneous electric fields, meiotic linkage, and BLASTN sequence analysis was utilized to characterize the resource. Forty-five of the TYACs map to 31 specific telomere regions. Twenty-four linkage markers were developed and mapped within 14 proterminal regions (12 telomeres and 2 terminal bands). The polymorphic markers include 12 microsatellites for 10 telomeres (1q, 2p, 6q, 7q, 10p, 10q, 13q, 14q, 18p, 22q) and the terminal bands of 11q and 12p. Twelve RFLP markers were identified and meiotically mapped to the telomeres of 2q, 7q, 8p, and 14q. Chromosome-specific STSs for 27 telomeres were identified from the 196 TYACs. More than 30,000 nucleotides derived from the TYAC vector-insert junction regions or from regions flanking TYAC microsatellites were compared to reported sequences using BLASTN. In addition to identifying homology with previously reported telomere sequences and human repeat elements, gene sequences and a number of ESTs were found to be highly homologous to the TYAC sequences. These genes include human coagulation factor V (F5), Weel protein tyrosine kinase (WEE1), neurotropic protein tyrosine kinase type 2 (NTRE2), glutathione S-transferase (GST1), and beta tubulin (TUBB). The TYAC/P1 resource, derivative STSs, and polymorphisms constitute an enabling resource to further studies of telomere structure and function and a means for physical and genetic map integration and closure.

Outcome of neonates transported between Level III centres depends upon centre of care.

This study aimed to clarify whether the adverse outcomes seen in babies transported between New Zealand Level III intensive care nurseries were due to the transport itself or to possible differences in care in different centres. The outcomes of 34 infants inborn at National Women's Hospital, Auckland but transported to other centres were compared with those of 68 matched controls inborn at the receiving centres and with 68 controls inborn and cared for at National Women's Hospital. Transport was associated with a transient (non-significant) deterioration in respiratory status but no increase in chronic lung disease. However, infants cared for elsewhere, whether transported or control, had more periventricular hemorrhage than Auckland babies (23% and 29% vs 15%, P = 0.03) and worse neurodevelopmental outcome (70% and 66% vs 88% of those whose outcomes were known were normal at follow up, P = 0.002). We conclude that differences in care between centres may be more important than the transport itself in determining the long-term outcome of transported neonates.

Adverse effects of neonatal transport between level III centres.

The effect of neonatal transport between level III intensive care nurseries was studied by comparing the outcome of 40 infants inborn at a regional level III centre but transported to other level III nurseries for intensive care, with 80 matched inborn controls. Transport appeared to affect respiratory status adversely but transiently. However, transported infants grew less well than control infants (32% were below 3rd centile for weight at 36 weeks vs 15% of controls), were more likely to suffer periventricular haemorrhage (40 vs 21% of controls) and had a worse neurodevelopmental outcome (70% normal at follow up vs 83% of controls). It can be concluded that for infants inborn at the National Women's Hospital, Auckland, transport to another level III centre for intensive care is associated with an increased risk of adverse outcome.

The Newcastle Adolescent Behaviour Screening Questionnaire.

As part of a larger study, a brief rating-scale was developed which focuses on the mid-adolescent phase of development. Completed by teachers, the questionnaire has an inter-rater reliability of 0.78, with a test-retest correlation of 0.82. When the performances of various screening instruments were compared it became clear that no single questionnaire was obviously more efficient than the others at detecting potential disturbance in an urban adolescent population. Indeed, different questionnaires seemed to highlight particular facets of functioning. The Newcastle Adolescent Questionnaire proved to be a reliable and valid screening measure.