Vitamin D-related 'molecular switches' predict childhood bone mass

Main Category: Bones / Orthopedics
Also Included In: Nutrition / Diet;  Pregnancy / Obstetrics
Article Date: 19 Aug 2013 - 1:00 PDT Current ratings for:
Vitamin D-related 'molecular switches' predict childhood bone mass

Researchers at the MRC Lifecourse Epidemiology Unit, University of Southampton, have demonstrated that the degree to which a gene related to vitamin D action is switched on or off, when measured at birth, predicts bone density of the child at four years of age.

In the study, 230 boys and girls were assessed at 4 years as part of the Southampton Women's Survey (SWS), a large ongoing mother-offspring cohort. The children visited the Osteoporosis Centre at Southampton General Hospital for measurement of their bone size and density using a DXA scanner. The researchers were able to measure the extent to which a particular gene, RXRA, is switched on or off by measuring epigenetic marks on the DNA sequence of the gene in cells taken from umbilical cord tissue which had been collected at birth. They found that the less marking (which usually means greater gene activity), at birth, the greater the bone density of the child at four years old. Furthermore, one of the epigenetic marks was related to the mother's blood vitamin D concentrations in late pregnancy.

Dr Nicholas Harvey, Senior Lecturer at the MRC Lifecourse Epidemiology Unit, University of Southampton, who led this project said, "RXRA is essential for the action of vitamin D and several other hormones; taken together with the relationship we found between mothers' vitamin D levels and RXRA marking, this study provides further support for the potential importance of vitamin D in pregnancy. We are now testing whether mothers should be supplemented with vitamin D in pregnancy in a randomised controlled trial, the MAVIDOS Maternal Vitamin D Osteoporosis Study, which will report early next year."

Professor Cooper, Professor of Rheumatology and Director of the MRC Lifecourse Epidemiology Unit, University of Southampton and who oversaw this work, added "This study forms part of a larger programme of research at the MRC Lifecourse Epidemiology Unit and University of Southampton in which we are seeking to understand how factors such as diet and lifestyle in the mother during pregnancy, and of the child in early life, influence a child's body composition and bone development. This work should help us to design interventions aimed at optimising body composition in childhood and later adulthood and thus improve the health of future generations".

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth.

Harvey NC, Sheppard A, Godfrey KM, McLean C, Garratt E, Ntani G, Davies L, Murray R, Inskip HM, Gluckman PD, Hanson MA, Lillycrop KA, Cooper C. J Bone Miner Res. 2013 Aug 1. DOI: 10.1002/jbmr.2056. [Epub ahead of print]

International Osteoporosis Foundation

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Association between childhood physical abuse and obesity in women

Main Category: Obesity / Weight Loss / Fitness
Also Included In: Women's Health / Gynecology
Article Date: 15 Aug 2013 - 1:00 PDT Current ratings for:
Association between childhood physical abuse and obesity in women

Women with a history of childhood physical abuse are more likely to become obese adults, according to a new study by University of Toronto researchers.

Results indicate that women who were physically abused in childhood were more likely to be obese than women from non-abusive homes.

"After adjusting for age and race, childhood physical abuse was associated with 47% higher odds of obesity for women" says lead author Esme Fuller-Thomson, Professor and Sandra Rotman Endowed Chair in the University of Toronto's Factor-Inwentash Faculty of Social Work. "Among men, obesity wasn't associated with childhood physical abuse."

"We had anticipated that the association between childhood physical abuse and obesity among women would be explained by factors including depression and anxiety, adult socio-economic position, alcohol abuse, and other childhood adversities, such as having a parent addicted to drugs or alcohol," says study co-author and doctoral student Deborah Sinclair. "However, even after taking into account all these factors, women from physically abusive families still had 35% higher odds of obesity."

The study could not determine the reason for the relationship between childhood physical abuse and women's obesity. "It is unclear why childhood physical abuse is associated with adult obesity among women but not men; it may reflect gender differences in coping mechanisms," says study co-author and doctoral candidate Sarah Brennenstuhl.

This research appears online this month in the journal Obesity Facts. Researchers examined the association between childhood physical abuse and adult obesity in a representative sample of 12,590 adults, drawn from the 2005 Canadian Community Health Survey. Of these, 976 reported being physically abused by someone close to them before they turned 18 and 2,786 were classified as "obese" based on a body mass index of 30 or greater which was calculated from self-report of respondents' height and weight.

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Leap in survival rates for childhood leukaemia patients with rare genetic abnormality

Main Category: Lymphoma / Leukemia / Myeloma
Article Date: 15 Aug 2013 - 2:00 PDT Current ratings for:
Leap in survival rates for childhood leukaemia patients with rare genetic abnormality

A pioneering genetic study means that children with a rare subtype of leukaemia have 75% less chance of their leukaemia recurring.

A study by Newcastle University scientists, published online on August 12th in the Journal of Clinical Oncology, has shown that lives have already been saved as a result of identifying children carrying a chromosomal abnormality known as iAMP21 and giving these patients a very intensive treatment regimen.

Overall survival for acute lymphoblastic leukaemia (ALL) patients, a cancer of the white blood cells, is now very high, with up to 90% of children being cured. A minority of patients, however, still do not respond to standard treatment.

A decade ago, the same scientists, funded by the blood cancer charity Leukaemia & Lymphoma Research, discovered the genetic error known as iAMP21. This abnormality occurs when parts of chromosome 21 - one of 23 pairs of chromosomes that contain our genetic instructions - are copied and shuffled around, resulting in extra copies of some genes. The researchers found that this abnormality was present in around 2% of children diagnosed with ALL and that it gave them a much greater chance of suffering a relapse.

The team, led by Professor Christine Harrison and Professor Anthony Moorman from the Leukaemia Research Cytogenetics Group, tracked the progress of patients with iAMP21 using samples from clinical trials between 1997 and 2002. They found that more than 80% of patients with iAMP21 had relapsed, compared to less than for 25% for children overall. The long-term survival for the iAMP21 group was also much lower.

Since 2003, bone marrow samples from every child diagnosed with ALL have been tested for the presence of iAMP21 using a genetic test known as 'fluorescence in situ hybridisation' (FISH), which binds glowing tags to DNA and "lights-up" the abnormal sequences. Children with iAMP21 registered on the UKALL2003 trial, which was funded by Leukaemia & Lymphoma Research and the Medical Research Council, were immediately recommended for treatment using a very intensive protocol.

The results of the UKALL2003 trial show that if children with iAMP21 are treated with intensive chemotherapy they have a dramatically reduced risk of relapse. In addition the proportion surviving for five years or more increased to nearly 90%.

Anthony Moorman, Professor of Genetic Epidemiology at Newcastle University, said: "Although using the presence of genetic abnormalities to guide treatment is not new within childhood leukaemia, such a clear demonstration of its beneficial impact on survival is extremely rare. In time we may be able to design drugs to actually target the iAMP21 abnormality, sparing these children from toxic treatment."

Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said: "By establishing how different genetic abnormalities found in leukaemia cells dictate how well the child will respond to treatment, we can identify high-risk patients early on. These new results demonstrate the huge potential of personalised medicine."

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The report is published online in the Journal of Clinical Oncology under the title, ‘Risk directed treatment intensification significantly reduces the risk of relapse among children and adolescents with acute lymphoblastic leukaemia and intrachromosomal amplification of chromosome 21: A comparison of MRC ALL97/99 and UKALL2003 trials’. Principal authors: Prof Anthony V Moorman, Professor Ajay Vora and Prof Christine J Harrison, Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, UK, doi: 10.1200/JCO.2013.48.9377

Newcastle University

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Link between DHA-enriched formula in infancy and positive cognitive outcomes in childhood

Main Category: Pediatrics / Children's Health
Also Included In: Nutrition / Diet;  Psychology / Psychiatry
Article Date: 14 Aug 2013 - 1:00 PDT Current ratings for:
Link between DHA-enriched formula in infancy and positive cognitive outcomes in childhood

University of Kansas scientists have found that infants who were fed formula enriched with long-chain polyunsaturated fatty acids (LCPUFA) from birth to 12 months scored significantly better than a control group on several measures of intelligence conducted between the ages of three to six years.

Specifically, the children showed accelerated development on detailed tasks involving pattern discrimination, rule-learning and inhibition between the ages of three to five years of age as well as better performance on two widely-used standardized tests of intelligence: the Peabody Picture Vocabulary Test at age five and the Weschler Primary Preschool Scales of Intelligence at age six.

"These results support the contention that studies of nutrition and cognition should include more comprehensive and sensitive assessments that are administered multiple times through early childhood," said John Colombo, study director and KU professor of psychology.

The results of LCPUFA supplementation studies have been mixed according to Colombo, a neuroscientist who specializes in the measurement of early neurocognitive development, but many of those studies have relied mainly on children's performance on the Bayley Scales of Infant Development at 18 months.

In the randomized, double-blind study, 81 infants were fed one of four formulas from birth to 12 months; three with varying levels of two LCPUFAs (DHA and ARA) and one formula with no LCPUFA. Beginning at 18 months, the children were tested every six months until six years of age on age-appropriate standardized and specific cognitive tests.

At 18 months the children did not perform any better on standardized tests of performance and intelligence, but by age three study directors Colombo and Susan E. Carlson, A. J. Rice Professor of Dietetics and Nutrition at KUMC, began to see significant differences in the performance of children who were fed the enriched formulas on finer-grained, laboratory-based measures of several aspects of cognitive function.

DHA or docosahexaenoic acid is an essential long-chain fatty acid that affects brain and eye development, and babies derive it from their mothers before birth and up to age two. But the American diet is often deficient in DHA sources such as fish.

ARA or arachidonic acid is another LCPUFA that is present in breast milk and commercial formula.

The study was designed to examine the effects of postnatal DHA at levels that have been found to vary across the world, said study co-director Carlson.

The results on the children's development from the first 12 months of this study were published in Pediatric Research in 2011, and showed improved attention and lower heart rate in infants supplemented with any level of LCPUFA. Colombo and Carlson's earlier work and collaborations influenced infant formula manufacturers to begin adding DHA in 2001.

The study was published ahead of print in the June 2013 issue of the American Journal of Clinical Nutrition.

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Long-term effects of LCPUFA supplementation on childhood cognitive outcomes

John Colombo, Susan E Carlson, Carol L Cheatham, D Jill Shaddy, Elizabeth H Kerling, Jocelynn M Thodosoff, Kathleen M Gustafson, and Caitlin Brez; Am J Clin Nutr August 2013 98: 403-412; First published online June 26, 2013. doi:10.3945/ajcn.112.040766

University of Kansas

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