Philippa Prentice

Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk

Size at birth, postnatal weight gain, and adult risk for type 2 diabetes may reflect environmental exposures during developmental plasticity and may be mediated by epigenetics. Both low birth weight (BW), as a marker of fetal growth restraint, and high birth weight (BW), especially after gestational diabetes mellitus (GDM), have been linked to increased risk of adult type 2 diabetes. We assessed DNA methylation patterns using a bead chip in cord blood samples from infants of mothers with GDM (group 1) and infants with prenatal growth restraint indicated by rapid postnatal catch‐up growth (group 2), compared with infants with normal postnatal growth (group 3). Seventy‐five CpG loci were differentially methylated in groups 1 and 2 compared with the controls (group 3), representing 72 genes, many relevant to growth and diabetes. In replication studies using similar methodology, many of these differentially methylated regions were associated with levels of maternal glucose exposure below that defined by GDM [the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study] or were identified as changes observed after randomized periconceptional nutritional supplementation in a Gambian cohort characterized by maternal deprivation. These studies provide support for the concept that similar epigenetic modifications may underpin different prenatal exposures and potentially increase long‐term risk for diseases such as type 2 diabetes.—Quilter, C. R., Cooper, W. N., Cliffe, K. M., Skinner, B. M., Prentice, P. M., Nelson, L., Bauer, J., Ong, K. K., Constância, M., Lowe, W. L., Affara, N. A., Dunger, D. B., Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk. FASEB J. 28, 4868–4879 (2014). www.fasebj.org

Even transient rapid infancy weight gain is associated with higher BMI in young adults and earlier menarche

Background:Early postnatal rapid ‘catch-up’ weight gain has been consistently associated with subsequent higher obesity risk and earlier pubertal development. In many low- and middle-income countries, infancy catch-up weight gain is transient and often followed by growth faltering. We explored the hypothesis that even transient catch-up weight gain during infancy is associated with later obesity risk and earlier puberty.Methods:A total of 2352 (1151 male, 1201 female) black South African children in the birth to twenty prospective birth cohort study (Johannesburg–Soweto) underwent serial measurements of body size and composition from birth to 18 years of age. At the age of 18 years, whole-body fat mass and fat-free mass were determined using dual-energy X-ray absorptiometry. Pubertal development was assessed by the research team between ages 9 and 10 years, and it was recorded annually from the age of 11 years using a validated self-assessment protocol.Results:Catch-up weight gain from birth to the age of 1 year, despite being followed by growth faltering between ages 1 and 2 years, was associated with greater mid-upper arm circumference (P=0.04) and skinfold thickness (P=0.048) at 8 years of age, and with higher weight (P<0.001) and body mass index (P=0.001) at 18 years of age after adjustment for sex, age, smoking during pregnancy, birth order, gestational age, formula-milk feeding and household socio-economic status. Infancy catch-up weight gain was also associated with younger age at menarche in girls (P<0.001). This association persisted after adjustment for smoking during pregnancy, birth order, gestational age, formula-milk feeding and household socio-economic status (P=0.005).Conclusion:Transient catch-up weight gain from birth to the age of 1 year among children born in a low-income area of South Africa was associated with earlier menarche and greater adiposity in early adulthood. This observation suggests that modifiable determinants of rapid infancy weight gain may be targeted in order to prevent later obesity and consequences of earlier puberty in girls.

Breast milk nutrient content and infancy growth

Benefits of human breast milk (HM) in avoiding rapid infancy weight gain and later obesity could relate to its nutrient content. We tested the hypothesis that differential HM total calorie content (TCC) or macronutrient contents may be associated with infancy growth.

Risk factors for obesity in childhood survivors of suprasellar brain tumours: a retrospective study

Aim:  To characterize postdiagnosis changes in body mass index (BMI) among childhood survivors of suprasellar brain tumours, and to determine the risk factors associated with obesity.

Age at Weaning and Infant Growth: Primary Analysis and Systematic Review

Objective To test whether earlier age at weaning (age 3-6 months) may promote faster growth during infancy. Study design Weaning at age 3.0-7.0 months was reported by 571 mothers of term singletons in a prospective birth cohort study conducted in Cambridge, UK. Infant weight and length were measured at birth and at age 3 months and 12 months. Anthropometric values were transformed into age- and sex-adjusted z-scores. Three linear regression models were performed, including adjustment for confounders in a stepwise manner. Measurements at age 3 months, before weaning, were used to consider reverse causality. Results Almost three-quarters (72.9%) of infants were weaned before age 6 months. Age at weaning of 3.0-7.0 months was inversely associated with weight and length (but not with body mass index) at 12 months (both P ≤ .01, adjusted for maternal and demographic factors). These associations were attenuated after adjustment for type of milk feeding and weight or length at age 3 months (before weaning). Rapid weight gain between 0 and 3 months predicted subsequent earlier age at weaning (P = .01). Our systematic review identified 2 trials, both reporting null effects of age at weaning on growth, and 15 observational studies, with 10 reporting an inverse association between age at weaning and infant growth and 4 reporting evidence of reverse causality. Conclusion In high-income countries, weaning between 3 and 6 months appears to have a neutral effect on infant growth. Inverse associations are likely related to reverse causality.

Stability of metabolites in dried blood spots stored at different temperatures over a 2-year period

BACKGROUND Quantitative LC-ESI-MS/MS, developed from newborn screening, is increasingly used for targeted metabolite profiling. Dried blood spots (DBS) provide easily obtainable biological samples but long-term stability data are sparse. DBS were stored at ambient temperature (room temperature [RT]; 21°C), -20 and -80°C. Metabolites were analyzed at 12 time points (0-104 weeks) by LC-ESI-MS/MS, using fully quantitative stable isotope dilution. RESULTS Principal component analysis showed alterations in metabolite stability at different temperatures, with major changes only at RT. Univariate analysis for individual analytes demonstrated increases or reductions in concentration. CONCLUSION Significant changes are observed in certain DBS metabolites at RT, which are attenuated or not present when frozen. These data will help to inform the design, analysis and interpretation of future DBS studies.

NICE clinical guideline: antibiotics for the prevention and treatment of early-onset neonatal infection

Early-onset neonatal infection, defined as infection within 72 h of birth, is a significant cause of mortality and morbidity,1 where Group B streptococcus (GBS) is most frequently responsible.1 ,2 The National Institute for Health and Clinical Excellence (NICE) guideline: ‘Antibiotics for early-onset neonatal infection: antibiotics for the prevention and treatment of early-onset neonatal infection’1 was published in August 2012. It aims to help identify those neonates at risk of infection, to promote prompt treatment for neonates with suspected infection and to minimise antibiotic exposure to those babies who do not have early-onset neonatal infection. The guideline was developed by the National Collaborating Centre for Womens and Childrens Health. There are no previous detailed national guidelines on the management of early-onset neonatal sepsis. The Royal College of Obstetricians and Gynaecologists published a guideline in 2003 (updated 2012) focusing on prevention of GBS, which included some aspects of the management of early-onset neonatal sepsis.2 Box 2 ### Resources http://guidance.nice.org.uk/CG149 Link to NICE guideline and full guideline http://guidance.nice.org.uk/CG149/PublicInfo/pdf/English English link to public information on antibiotics for early-onset neonatal infection http://www.nice.org.uk/newsroom/podcasts/index.jsp?pid=44 Antibiotics for early-onset neonatal infection podcast with Dr Mark Turner ### For mothers

Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations

Aim We hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy. Methods In the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios). Results Four fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10–4) and INS rs2585 (P-value = 7 × 10–4), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10–3) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10–3), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10–6, n = 981, r2 = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10–3, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10–8, rs2585, P-value = 3.6 × 10–5) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10–8), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2). Conclusion This study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.

Cohort Profile: the Cambridge Baby Growth Study (CBGS)

The Cambridge Baby Growth Study has been supported by the European Union Framework V, the World Cancer Research Foundation International, the Medical Research Council, the NIHR Cambridge Comprehensive Biomedical Research Centre, the Newlife Foundation for disabled children, the Mothercare Group Foundation, Mead Johnson Nutrition, the Evelyn Trust, the Wellbeing of Women, Diabetes UK and a collaborative research grant from the European Society for Paediatric Endocrinology.

American Academy of Otolaryngology: head and neck surgery foundation clinical practice guideline on acute otitis externa 2014

This American guideline updates previous 2006 recommendations providing guidance for primary care and specialist clinicians for treating children of 2 years and older with acute otitis externa (AOE): a diffuse inflammation of the external ear canal±pinna and tympanic membrane .1 ,2