Publications by authors named "Philippa Prentice"

27 Publications

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Fifteen-minute consultation: Clinical pubertal assessment.

Arch Dis Child Educ Pract Ed 2021 May 14. Epub 2021 May 14.

Department of Paediatric Endocrinology, The Royal London Hospital, London, UK

A pubertal assessment is an important part of the clinical examination of a young person. Clinicians must be empowered to do this confidently and in a sensitive manner. Tanner staging allows an objective measurement of pubertal status, including pubic and axillary hair growth, and breast or genital development. Alongside history, age and growth patterns, pubertal assessment can identify normal, precocious, delayed or arrested puberty and be suggestive of underlying pathology. This article aims to familiarise clinicians with the pubertal assessment, both the examination and interpretation.
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http://dx.doi.org/10.1136/archdischild-2020-320386DOI Listing
May 2021

Updated NICE guidance: diabetic ketoacidosis in children and young people 2020.

Arch Dis Child Educ Pract Ed 2021 Mar 10. Epub 2021 Mar 10.

Paediatric Endocrinology, The Royal London Hospital, London, UK

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http://dx.doi.org/10.1136/archdischild-2021-321669DOI Listing
March 2021

Guideline review: congenital adrenal hyperplasia clinical practice guideline 2018.

Arch Dis Child Educ Pract Ed 2020 Dec 3. Epub 2020 Dec 3.

Paediatric Endocrinology, Great Ormond Street Hospital, London WC1N 3JH, UK

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http://dx.doi.org/10.1136/archdischild-2019-317573DOI Listing
December 2020

Evidence from 3-month-old infants shows that a combination of postnatal feeding and exposures in utero shape lipid metabolism.

Sci Rep 2019 10 4;9(1):14321. Epub 2019 Oct 4.

Core Metabolomics and Lipidomics Laboratory, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Level 4 Pathology, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.

We tested the hypothesis that both postnatal feeding and conditions in utero affect lipid metabolism in infants. Infants who experienced restrictive growth conditions in utero and others exposed to maternal hyperglycaemia were compared to a control group with respect to feeding mode. Dried blood spots were collected from a pilot subset of infant participants of the Cambridge Baby Growth Study at 3mo. Groups: (a) a normal gestation (control, n = 40), (b) small for gestational age (SGA, n = 34) and (c) whose mothers developed hyperglycaemia (n = 59). These groups were further stratified by feeding mode; breastfed, formula-fed or received a mixed intake. Their phospholipid, glyceride and sterol fractions were profiled using direct infusion mass spectrometry. Statistical tests were used to identify molecular species that indicated differences in lipid metabolism. The abundance of several phospholipids identified by multivariate analysis, PC(34:1), PC(34:2) and PC-O(34:1), was 30-100% higher across all experimental groups. SM(39:1) was around half as abundant in in utero groups among breastfed infants only. The evidence from this pilot study shows that phospholipid metabolism is modulated by both conditions in utero and postnatal feeding in a cohort of 133 Caucasian infants, three months post partum.
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http://dx.doi.org/10.1038/s41598-019-50693-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778076PMC
October 2019

Reduced size at birth and persisting reductions in adiposity in recent, compared with earlier, cohorts of infants born to mothers with gestational diabetes mellitus.

Diabetologia 2019 11 9;62(11):1977-1987. Epub 2019 Aug 9.

Department of Paediatrics, University of Cambridge, Box 116, Level 8, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.

Aims/hypothesis: This study aimed to explore the infancy growth trajectories of 'recent' and 'earlier' offspring of mothers with gestational diabetes mellitus (OGDM), each compared with the same control infants, and investigate whether 'recent' OGDM still exhibit a classical phenotype, with macrosomia and increased adiposity.

Methods: Within a prospective observational birth cohort, 98 'earlier' OGDM born between 2001 and 2009 were identified using 75 g oral glucose tolerance testing at 28 weeks gestation, 122 recent OGDM born between 2011 and 2013 were recruited postnatally through antenatal diabetes clinics, and 876 normal birthweight infants of mothers with no history of diabetes were recruited across the full study period as the control group. All infants followed the same study protocol (measurements at birth, 3, 12 and 24 months, including weight, length and skinfold thickness indicating adiposity, and detailed demographic data). In all cases, GDM was defined using the International Association of Diabetes and Pregnancy Study Group criteria.

Results: Earlier OGDM had higher birthweight SD scores (SDS) than control infants. Conversely, recent OGDM had similar birthweight- and length SDS to control infants (mean ± SD, 0.1 ± 1.0 and- 0.1 ± 0.9, respectively), but lower mean skinfold thickness SDS (-0.4 ± 0.6 vs 0.0 ± 0.9; p < 0.001). After birth, earlier OGDM showed reduced gains in weight and length between 3 and 12 months. In contrast, recent OGDM had increased weight and skinfold thickness gains until 3 months, followed by reduced gains in those variables from 3 to 12 months, compared with control infants. At 24 months, recent OGDM had lower adiposity than control infants (mean skinfold thickness SDS -0.3 ± 0.7 vs 0.0 ± 0.8; p < 0.001). At all time points recent OGDM had lower growth measurements than earlier OGDM.

Conclusions/interpretation: Recent OGDM showed different growth trajectories to the earlier group, namely normalisation of birthweight and reduced adiposity at birth, followed by initial rapid weight gain but subsequent reduced adiposity postnatally. While avoidance of macrosomia at birth may be advantageous, the longer-term health implications of these changing growth trajectories are uncertain.
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http://dx.doi.org/10.1007/s00125-019-4970-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805804PMC
November 2019

Human Milk Short-Chain Fatty Acid Composition is Associated with Adiposity Outcomes in Infants.

J Nutr 2019 05;149(5):716-722

Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom.

Background: Presumed benefits of human milk (HM) in avoiding rapid infancy weight gain and later obesity could relate to its nutrient composition. However, data on breast milk composition and its relation with growth are sparse.

Objective: We investigated whether short-chain fatty acids (SCFAs), known to be present in HM and linked to energy metabolism, are associated with infancy anthropometrics.

Methods: In a prospective birth cohort, HM hindmilk samples were collected from 619 lactating mothers at 4-8 wk postnatally [median (IQR) age: 33.9 (31.3-36.5) y, body mass index (BMI) (kg/m2): 22.8 (20.9-25.2)]. Their offspring, born at 40.1 (39.1-41.0) wk gestation with weight 3.56 (3.22-3.87) kg and 51% male, were assessed with measurement of weight, length, and skinfold thickness at ages 3, 12, and 24 mo, and transformed to age- and sex-adjusted z scores. HM SCFAs were measured by 1H-nuclear magnetic resonance spectroscopy (NMR) and GC-MS. Multivariable linear regression models were conducted to analyze the relations between NMR HM SCFAs and infancy growth parameters with adjustment for potential confounders.

Results: NMR peaks for HM butyrate, acetate, and formic acid, but not propionate, were detected. Butyrate peaks were 17.8% higher in HM from exclusively breastfeeding mothers than mixed-feeding mothers (P = 0.003). HM butyrate peak values were negatively associated with changes in infant weight (standardized B  = -0.10, P = 0.019) and BMI (B = -0.10, P = 0.018) between 3 and 12 mo, and negatively associated with BMI (B = -0.10, P = 0.018) and mean skinfold thickness (B = -0.10, P = 0.049) at age 12 mo. HM formic acid peak values showed a consistent negative association with infant BMI at all time points (B < = -0.10, P < = 0.014), whereas HM acetate was negatively associated with skinfold thickness at 3 mo (B = -0.10, P = 0.028) and 24 mo (B = -0.10, P = 0.036).

Conclusions: These results suggest that HM SCFAs play a beneficial role in weight gain and adiposity during infancy. Further knowledge of HM SCFA function may inform future strategies to support healthy growth.
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http://dx.doi.org/10.1093/jn/nxy320DOI Listing
May 2019

Predicting puberty in partial androgen insensitivity syndrome: Use of clinical and functional androgen receptor indices.

EBioMedicine 2018 Oct 11;36:401-409. Epub 2018 Oct 11.

University of Cambridge, Department of Paediatrics, Cambridge, United Kingdom. Electronic address:

Background: PAIS exhibits a complex spectrum of phenotypes and pubertal outcomes. The paucity of reliable prognostic indicators can confound management decisions including sex-of-rearing. We assessed whether external masculinisation score (EMS) at birth or functional assays correlates with pubertal outcome in PAIS patients and whether the EMS is helpful in sex assignment.

Methods: We collected pubertal outcome data for 27 male-assigned PAIS patients, all with confirmed androgen receptor (AR) mutations, including two previously uncharacterized variants (I899F; Y916C). Patients were grouped as follows; EMS at birth <5 and ≥ 5 (EMS in normal males is 12; median EMS in PAIS is 4·7) and pubertal outcomes compared.

Findings: Only 6/9 patients (67%) with EMS <5 underwent spontaneous onset of puberty, versus all 18 patients with EMS ≥5 (p = .03). Only 1/6 patients (17%) with EMS <5 developed adult genitalia reaching Tanner stage 4 or 5, versus 11/13 (85%) with EMS ≥5 (p = 0·01). There was no significant difference between the two groups of patients in being prescribed androgen replacement, who reached adult testicular volume ≥ 15 ml, pubic hair Tanner stage 4 or 5, above average adult height, had gynaecomastia, and mastectomy. No correlation was observed between EMS and in vitro AR function.

Interpretation: In PAIS with AR mutation, birth EMS is a simple predictor of spontaneous pubertal onset and satisfactory adult genitalia. This provides useful information when discussing the likely options for management at puberty. FUND: European Commission Framework 7 Programme, NIHR Cambridge Biomedical Research Centre, BBSRC DTP.
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http://dx.doi.org/10.1016/j.ebiom.2018.09.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197786PMC
October 2018

Associations between the maternal circulating lipid profile in pregnancy and fetal imprinted gene alleles: a cohort study.

Reprod Biol Endocrinol 2018 Aug 29;16(1):82. Epub 2018 Aug 29.

Department of Paediatrics, University of Cambridge, Box 116, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK.

Background: Imprinted genes, which are expressed in a parent of origin-specific manner, are thought to mediate the genetic priorities of each parent in pregnancy. Recently we reported that some fetal imprinted gene variants are associated with maternal glucose concentrations and blood pressures in pregnancy. We suggest that the conflict between the effects of paternal and maternal transmitted genes starts at conception and may already be evident in measures of maternal metabolism in early pregnancy, before gestational diabetes is manifest.

Methods: Lipid fractions in maternal non-fasting serum collected around week 15 of pregnancy were profiled using direct infusion mass spectrometry in a subset Discovery Cohort (n = 200) of women from the Cambridge Baby Growth Study using direct infusion mass spectrometry. Associations between 151 haplotype-tag fetal polymorphisms in 16 imprinted genes and lipids were determined using partial least squares discriminant analysis. Variable importance in projection scores were used to identify those lipid species that contribute most to the underlying variation in the lipid profile and the concentrations of these species tested for associations with fetal imprinted gene alleles using linear regression. In an internal Validation Cohort (n = 567 women from the same cohort) the lipid fraction was profiled using liquid chromatography-mass spectrometry and tested for associations with the same fetal imprinted gene variants as above, followed by meta-analysis of associations from the Discovery and Validation Cohorts.

Results: The most significant associations were between a monounsaturated triglyceride (44:1) and both paternally-transmitted fetal H19 rs7950932 (R = 0.14, p = 2.9 × 10, n = 386) and maternally-transmitted fetal FAM99A rs7131362 (R = 0.18, p = 6.2 × 10, n = 351; association with maternal-untransmitted allele R = 0.08, p = 0.07, n = 328). This same triglyceride isoform was also associated with subsequent week 28 fasting glucose concentrations (R = 0.09, p = 9.9 × 10, n = 673) and homeostasis model assessment of insulin resistance (R = 0.09, p = 0.01, n = 664).

Conclusions: Fetal imprinted genes may influence maternal circulating clinically relevant triglyceride concentrations early in pregnancy.
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http://dx.doi.org/10.1186/s12958-018-0399-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116391PMC
August 2018

Fifteen-minute consultation: Insulin pumps for type 1 diabetes in children and young people.

Arch Dis Child Educ Pract Ed 2018 06 3;103(3):131-136. Epub 2018 Jan 3.

Department of Paediatric Endocrinology, Royal Hospital for Sick Children, Edinburgh, UK.

There is increasing worldwide use of continuous subcutaneous insulin infusions in paediatric type 1 diabetes (T1D), reflecting recent research outcomes and guidance, as well as families' wishes. Children/young people may present acutely with medical or surgical problems, in addition to issues related to T1D. This review provides general paediatricians with an introduction to pump therapy, highlighting common problems, management issues and when to seek specialist advice.
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http://dx.doi.org/10.1136/archdischild-2016-310884DOI Listing
June 2018

The translation of lipid profiles to nutritional biomarkers in the study of infant metabolism.

Metabolomics 2017 28;13(3):25. Epub 2017 Jan 28.

MRC Elsie Widdowson Laboratory, Cambridge, UK.

Introduction: Links between early life exposures and later health outcomes may, in part, be due to in infancy. This hypothesis is supported by observed long-term benefits associated with breastfeeding, such as better cognitive development in childhood, and lower risks of obesity and high blood pressure in later life. However, the possible underlying mechanisms are expected to be complex and may be difficult to disentangle due to the lack of understanding of the metabolic processes that differentiate breastfed infants compared to those receiving just formula feed.

Objective: Our aim was to investigate the relationships between infant feeding and the lipid profiles and to validate specific lipids in separate datasets so that a small set of lipids can be used as nutritional biomarkers.

Method: We utilized a direct infusion high-resolution mass spectrometry method to analyse the lipid profiles of 3.2 mm dried blood spot samples collected at age 3 months from the Cambridge Baby Growth Study (CBGS-1), which formed the discovery cohort. For validation two sample sets were profiled: Cambridge Baby Growth Study (CBGS-2) and Pregnancy Outcome Prediction Study (POPS). Lipidomic profiles were compared between infant groups who were either exclusively breastfed, exclusively formula-fed or mixed-fed at various levels. Data analysis included supervised Random Forest method with combined classification and regression mode. Selection of lipids was based on an iterative backward elimination procedure without compromising the class error in the classification mode.

Conclusion: From this study, we were able to identify and validate three lipids: PC(35:2), SM(36:2) and SM(39:1) that can be used collectively as biomarkers for infant nutrition during early development. These biomarkers can be used to determine whether young infants (3-6 months) are breast-fed or receive formula milk.
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http://dx.doi.org/10.1007/s11306-017-1166-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5272886PMC
January 2017

Breast milk nutrient content and infancy growth.

Acta Paediatr 2016 Jun 6;105(6):641-7. Epub 2016 Apr 6.

Department of Paediatrics, MRL Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Comprehensive Biomedical Research Centre, University of Cambridge, Cambridge, UK.

Aim: 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.

Methods: HM hindmilk samples were collected at ages 4-8 weeks from 614 mothers participating in a representative birth cohort, with repeated infancy anthropometry. HM triglyceride (fat), lipid analytes and lactose (carbohydrate) were measured by (1) H-NMR, and protein content by the Dumas method. TCC and %macronutrients were determined.

Results: In 614 HM samples, fat content was as follows: [median(IQR)]: 2.6 (1.7-3.6) g/100 mL, carbohydrate: 8.6 (8.2-8.8) g/100 mL, protein: 1.2 (1.1-1.2) g/100 mL; TCC: 61.8 (53.7-71.3) kcal/100 mL. HM of mothers exclusively breast feeding vs. mixed feeding was more calorific with higher %fat, lower %carbohydrate and lower %protein. Higher HM TCC was associated with lower 12-months body mass index (BMI)/adiposity, and lower 3-12 months gains in weight/BMI. HM %fat was inversely related to 3-12 months gains in weight, BMI and adiposity, whereas %carbohydrate was positively related to these measures. HM %protein was positively related to 12-months BMI.

Conclusion: HM analysis showed wide variation in %macronutrients. Although data on milk intakes were unavailable, our findings suggest functional relevance of HM milk composition to infant growth.
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http://dx.doi.org/10.1111/apa.13362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949511PMC
June 2016

Cohort Profile: the Cambridge Baby Growth Study (CBGS).

Int J Epidemiol 2016 Feb 31;45(1):35.a-g. Epub 2015 Dec 31.

Department of Paediatrics, University of Cambridge, Cambridge, UK and.

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http://dx.doi.org/10.1093/ije/dyv318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795564PMC
February 2016

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

J Pediatr 2015 Aug 12;167(2):317-24.e1. Epub 2015 Jun 12.

Department of Pediatrics, University of Cambridge, Cambridge, United Kingdom; Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jpeds.2015.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520860PMC
August 2015

Key messages from a guideline: Identification of cleft palate in the newborn.

Arch Dis Child Educ Pract Ed 2015 16;100(4):222. Epub 2015 Apr 16.

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http://dx.doi.org/10.1136/archdischild-2015-308466DOI Listing
April 2015

Lipidomic analyses, breast- and formula-feeding, and growth in infants.

J Pediatr 2015 Feb 18;166(2):276-81.e6. Epub 2014 Nov 18.

Department of Pediatrics, University of Cambridge Metabolic Research Laboratories Wellcome Trust-Medical Research Council Institute of Metabolic Science, National Institute of Human Research Cambridge Comprehensive Biomedical Research Center, Cambridge, United Kingdom. Electronic address:

Objective: To evaluate lipidomic differences between breast- and formula-fed infants.

Study Design: We utilized high-resolution mass-spectrometry methods to analyze 3.2 mm dried blood spot samples collected at ages 3 months (n = 241) and 12 months (n = 144) from a representative birth cohort study. Lipidomic profiles were compared between infants exclusively breast-fed, formula-fed, or mixed-fed, and related to 12-month infancy weight. Data analysis included supervised multivariate statistics (partial least squares discriminant analysis), and univariate analysis with correction for multiple testing.

Results: Distinct differences in 3-month lipidomic profiles were observed between exclusively breast-fed and formula-fed infants; mixed-fed infants showed intermediate profiles. Principle lipidomic characteristics of breast-fed infants were lower total phosphatidylcholines (PCs), with specifically lower short chain unsaturated PC but higher long chain polyunsaturated PC; higher cholesterol esters; and variable differences in sphingomyelins. At 12 months, lipidomic profiles were markedly different to those at 3 months, and differences between the earlier breast/formula/mixed-feeding groups were no longer evident. However, several specific lipid species, associated with breast-feeding at 3 months, also correlated with differences in 3- to 12-month weight.

Conclusions: State-of-the-art dried blood spot sample lipidomic profiling demonstrated striking differences between breast-fed and formula-fed infants. Although these changes diminished with age, breast-fed lipidomic profiles at 3 months were associated with infancy weight and could potentially represent biomarkers of infant nutrition.
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http://dx.doi.org/10.1016/j.jpeds.2014.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302220PMC
February 2015

The development and validation of a fast and robust dried blood spot based lipid profiling method to study infant metabolism.

Metabolomics 2014 11;10(5):1018-1025. Epub 2014 Feb 11.

Department of Paediatrics, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 0QQ UK.

Early life exposures and metabolic programming are associated with later disease risk. In particular lipid metabolism is thought to play a key role in the development of the metabolic syndrome and insulin resistance in later life. Investigative studies of metabolic programming are limited by the ethics and practicalities of sample collection in small infants. Dried blood spots on filter paper, derived from heel pricks are considered as the most suitable option for this age group. We validated a novel lipid profiling method, based on high resolution mass spectrometry to successfully determine the lipid composition of infants using dried blood spots. The spotting and air drying of blood on paper has noticeable effects on many of the lipids, leading to lipid oxidation and hydrolysis, which demand careful interpretation of the obtained data. We compared the lipid profiles from plasma or whole blood samples and the results from dried blood spots to determine if these revealed the same inter-subject differences. The results from dried blood spots were no less reproducible than other lipid profiling methods which required comparatively larger sample volumes. Therefore, lipid profiles obtained from dried blood spots can be successfully used to monitor infancy lipid metabolism and we show significant differences in the lipid metabolism of infants at age 3 versus 12 months.
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http://dx.doi.org/10.1007/s11306-014-0628-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145199PMC
February 2014

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 2014 Nov 21;28(11):4868-79. Epub 2014 Aug 21.

National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Department of Paediatrics, University of Cambridge, Cambridge, UK; and.

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.
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http://dx.doi.org/10.1096/fj.14-255240DOI Listing
November 2014

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

Arch Dis Child Educ Pract Ed 2014 Jun 13;99(3):98-100. Epub 2013 Dec 13.

Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

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http://dx.doi.org/10.1136/archdischild-2013-304629DOI Listing
June 2014

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

Bioanalysis 2013 Jun;5(12):1507-14

WellChild Laboratory, King's College London, Evelina Children's Hospital, London, UK.

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.
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http://dx.doi.org/10.4155/bio.13.121DOI Listing
June 2013

Psychosis and schizophrenia.

Arch Dis Child Educ Pract Ed 2013 Aug 14;98(4):128-30. Epub 2013 Jun 14.

Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Box 116, Level 8, Cambridge CB2 0QQ, UK.

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http://dx.doi.org/10.1136/archdischild-2013-304355DOI Listing
August 2013

Prediction of mortality in community-acquired pneumonia in hospitalized patients.

Am J Med Sci 2011 Dec;342(6):489-93

Norwich Medical School, Faculty of Medicine and Health Sciences, United Kingdom.

Introduction: Community-acquired pneumonia (CAP) is common and associated with a significant mortality. Currently recommended criteria to assess severity of CAP could be improved.

Methods: We derived 2 new criteria CARSI [confusion, age (<65, ≥65 to <85 or≥ 85), respiratory rate and shock index] and CARASI, where shock index is replaced by temperature-adjusted shock index based on previous observations. By using data of a prospective study performed in Norfolk and Suffolk, United Kingdom, we compare these new indices with the CURB-65 criteria.

Results: A total of 190 patients were included (men, 53%). The age range was 18 to 101 years (median, 76 years). There were a total of 54 deaths during a 6-week follow-up, all within 30 days of admission. Sixty-five (34%) had severe pneumonia by CURB-65. Using CARSI and CARASI, 39 (21%) and 36 (19%) had severe pneumonia, respectively. Sensitivity was slightly less, but specificity was higher with CARSI and CARASI indices than that of CURB-65. Positive and negative predictive values in predicting death during 6-week follow-up were comparable among 3 indices examined. The receiver operating characteristic curve values (95% confidence interval) for the criteria were 0.67 (0.60-0.75) for CURB-65, 0.64 (0.60-0.71) for CARSI and 0.64 (0.57-0.71) for CARASI. Comparing receiver operating characteristic curves for CURB-65 versus CARSI, or CURB-65 versus CARASI, there was no evidence of a difference between the tools, P = 0.35 and 0.33, respectively. There was good agreement, which was strongly statistically significant (kappa = 0.56, P < 0.0001 and kappa = 0.54, P < 0.0001, respectively).

Conclusions: Both CARSI and CARASI are useful in predicting deaths associated with CAP, including older patients, and may be particularly useful in the emergency and community settings.
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http://dx.doi.org/10.1097/MAJ.0b013e31822cb95fDOI Listing
December 2011

Are shock index and adjusted shock index useful in predicting mortality and length of stay in community-acquired pneumonia?

Eur J Intern Med 2011 Jun 17;22(3):282-5. Epub 2011 Jan 17.

Department of Respiratory Medicine, Norfolk and Norwich University Hospital, UK.

Background: Community Acquired Pneumonia (CAP) is a common infection which is associated with a significant mortality. Shock index, heart rate divided by blood pressure, has been shown to predict mortality in several conditions including sepsis, acute myocardial infarction and traumatic injuries. Very little is known about the prognostic value of shock index in community acquired pneumonia (CAP).

Objective: To examine the usefulness of shock index (SI) and adjusted shock index (corrected to temperature) (ASI) in predicting mortality and hospital length of stay in patients admitted to hospital with CAP.

Methods: A prospective study was conducted in three hospitals in Norfolk & Suffolk, UK. We compared risk of mortality and longer length of stay for low (=<1.0, i.e. heart rate =< systolic BP) and high (>1.0, i.e. heart rate > systolic BP) SI and ASI adjusting for age, sex and other parameters which have been shown to be associated with mortality in CAP.

Results: A total of 190 patients were included (males=53%). The age range was 18-101 years (median=76 years). Patients with SI & ASI >1.0 had higher likelihood of dying within 6 weeks from admission. The adjusted odds ratio for 30 days mortality were 2.48 (1.04-5.92; p=0.04) for SI and 3.16 (1.12-8.95; p=0.03) for ASI. There was no evidence to suggest that they predict longer length of stay.

Conclusion: Both SI and ASI of >1.0 predict 6 weeks mortality but not longer length of stay in CAP.
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http://dx.doi.org/10.1016/j.ejim.2010.12.009DOI Listing
June 2011

Menarche: onset and management in London schools.

Arch Dis Child 2011 Jan 29;96(1):111-2. Epub 2010 Sep 29.

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http://dx.doi.org/10.1136/adc.2010.195404DOI Listing
January 2011

Confusion, Urea, Respiratory Rate and Shock Index or Adjusted Shock Index (CURSI or CURASI) criteria predict mortality in community-acquired pneumonia.

Eur J Intern Med 2010 Oct 1;21(5):429-33. Epub 2010 Aug 1.

School of Medicine, Health Policy and Practice, Health and Social Sciences Research Institute, Faculty of Health, University of East Anglia, Norwich, Norfolk, UK.

Background: Community-acquired pneumonia (CAP) is common and associated with a significant mortality. Shock index, heart rate divided by systolic blood pressure, has been shown to be associated with outcome in sepsis.

Objective: To examine the usefulness of two new criteria CURSI (confusion, urea, respiratory rate and shock index), and CURASI where shock index is replaced by temperature adjusted shock index in mortality assessment of CAP.

Methods: A prospective study was conducted in Norfolk and Suffolk, UK. We explored the usefulness of CURSI and CURASI which we derived and performed mapping exercise using a different cohort. In this study we compared these new indices with the CURB-65 criteria in correctly predicting mortality in CAP.

Results: A total of 190 patients were included (males=53%). The age range was 18-101 years (median=76 years). There were a total of 54 deaths during a six-week follow-up. All died within 30-days. Sixty-five (34%) had severe pneumonia by CURB-65. Using CURSI and CURASI, 71(37%) and 69(36%) had severe pneumonia, respectively. The sensitivity, specificity, positive and negative predictive values in predicting death during six-week follow-up were comparable among three indices examined. The Receiver Operating Characteristic curve values (95%CI) for the criteria were 0.67(0.60-0.75) for CURB-65, 0.67(0.59-0.74) for CURSI and 0.66(0.58-0.74) for CURASI (p>0.05). There were strong agreements between these three indices (Kappa values > or =0.75 for all). Repeating analyses in those who were aged 65years and over (n=135) did not alter the results.

Conclusions: Both CURSI and CURASI are similarly useful to CURB-65 in predicting deaths associated with CAP including older patients.
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http://dx.doi.org/10.1016/j.ejim.2010.07.005DOI Listing
October 2010

A within-subjects trial to test the equivalence of online and paper outcome measures: the Roland Morris disability questionnaire.

BMC Musculoskelet Disord 2010 Jun 8;11:113. Epub 2010 Jun 8.

Complementary Medicine Research Unit, School of Medicine, University of Southampton, Southampton, UK.

Background: Augmenting validated paper versions of existing outcome measures with an equivalent online version may offer substantial research advantages (cost, rapidity and reliability). However, equivalence of online and paper questionnaires cannot be assumed, nor can acceptability to respondents. The aim was to test whether online and written versions of the Roland Morris Disability Questionnaire (RMDQ), a standard measure of functional disability in back pain, are equivalent at both group and individual levels to establish whether they can be used interchangeably.

Methods: This is a within-participants equivalence study. 167 participants with back pain fully completed both the paper and online versions of the RMDQ in random order. Participants were recruited from a chiropractic clinic and patient support groups in Southern England. Limits of equivalence were pre-defined as 0.5 RMDQ points, the Bland-Altman range was calculated, and participants' comments were examined using content analysis.

Results: The mean score difference was 0.03 (SD = 1.43), with the 95% Confidence Interval falling entirely within our limits of equivalence (-0.19 to 0.25). The Bland-Altman range was -2.77 to 2.83 RMDQ points. Participants identified unique advantages and disadvantages associated with each version of the RMDQ.

Conclusions: The group and individual level data suggest that online and paper versions of the RMDQ are equivalent and can be used interchangeably. The Bland-Altman range appears to reflect the known measurement properties of the RMDQ. Furthermore, participants' comments confirmed the potential value to be had from offering them the choice of completing the RMDQ online or on paper.
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http://dx.doi.org/10.1186/1471-2474-11-113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896920PMC
June 2010

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

Acta Paediatr 2010 Oct 7;99(10):1522-6. Epub 2010 Jun 7.

Department of Paediatrics, University of Cambridge, UK.

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.

Methods: We conducted a retrospective analysis of 46 children (16 boys and 30 girls) with median (IQR) age of 7.49 (3.47-11.59) years at tumour diagnosis, and followed up for 3.93 (1.68-7.27) years. Survival analyses were used to identify risks of developing obesity.

Results: There were no sex differences in age at tumour diagnosis, duration of follow-up, tumour types, endocrinopathies, treatment modalities or baseline BMI SDS. In the first year after tumour diagnosis, ΔBMI SDS (median; IQR) was greater in girls (1.32; 0.07-2.08) than in boys (0.48; -0.40 to 0.89) (p = 0.01). At diagnosis, 3/46 children (6%) were obese; this increased to 20/46 (43%) by last follow-up (p < 0.001) and was more common in girls (17/30; 57%) than in boys (3/16; 19%). Female gender (hazard ratio 5.0, 95% CI 1.2-21.7; p = 0.04) and greater than average baseline BMI (hazard ratio 4.7, 95% CI 1.1-20.8; p = 0.02) were risk factors for subsequent obesity.

Conclusion: Accurate prediction of obesity risk is important and would allow early targeted intervention in high-risk patients.
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http://dx.doi.org/10.1111/j.1651-2227.2010.01867.xDOI Listing
October 2010