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Journal articleJackson FL, Georgakopoulou N, Kaluarachchi M, et al., 2016,
Development of a pipeline for exploratory metabolic profiling of infant urine
, Journal of Proteome Research, Vol: 15, Pages: 3432-3440, ISSN: 1535-3907Numerous metabolic profiling pipelines have been developed to characterize the composition ofhuman biofluids and tissues, the vast majority of these being for studies in adults. To accommodatelimited sample volume and to take into account the compositional differences between adult andinfant biofluids, we developed and optimized sample handling and analytical procedures for studyingurine from newborns. A robust pipeline for metabolic profiling using NMR spectroscopy wasestablished, encompassing sample collection, preparation, spectroscopic measurement andcomputational analysis. Longitudinal samples were collected from five infants from birth until 14months of age. Methods of extraction, effects of freezing and sample dilution were assessed andurinary contaminants from breakdown of polymers in a range of diapers and cotton wool balls wereidentified and compared, including propylene glycol, acrylic acid and tert-butanol. Finally,assessment of urinary profiles obtained over the first few weeks of life revealed a dramatic change in composition, with concentrations of phenols, amino acids and betaine altering systematically overthe first few months of life. Therefore, neonatal samples require more stringent standardization ofexperimental design, sample handling and analysis compared to adult samples in order toaccommodate the variability and limited sample volume.
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Journal articleAndreas NJ, Hyde M, Herbert B, et al., 2016,
Impact of maternal BMI and sampling strategy on the concentration of leptin, insulin, ghrelin and resistin in breast milk across a single feed: a longitudinal cohort study
, BMJ Open, Vol: 6, ISSN: 2044-6055Objectives: We tested the hypothesis that there is a positive association between maternal BMI and the concentration of appetite-regulating hormones leptin, insulin, ghrelin and resistin in breast milk. We also aimed to describe the change in breast milk hormone concentration within each feed, and over time.Setting: Mothers were recruited from the post-partum ward at a university hospital in London. Breast milk samples were collected in the participants homes.Participants: We recruited 120 healthy, primiparous, breastfeeding mothers, over 18 years old. Mothers who smoked, had multiple births, or had diabetes were excluded. Fore and hind milk samples were collected from 105 women at one week post-partum and 92 women at three months post-partum. Primary and secondary outcome measures: We recorded maternal and infant anthropometric measurements at each sample collection and measured hormone concentrations using a multiplex assay.Results: The concentration of leptin in fore milk correlated with maternal BMI at time of sample collection, at seven days (r=0.31, p=0.02), and three months post-partum (r=0.30, p=<0.00). Fore milk insulin correlated with maternal BMI at three months post-partum (r=0.22, p=0.04). Breast milk ghrelin and resistin were not correlated with maternal BMI. Ghrelin concentrations at three months post-partum were increased in fore milk compared to hind milk (p=0.01). Concentrations of ghrelin were increased in hind milk collected at one week post-partum compared to samples collected at three months post-partum (p=0.03). A trend toward decreased insulin concentrations in hind milk was noted. Concentrations of leptin and resistin were not seen to alter over a feed.
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Journal articleAndreas NJ, Al-Khalidi A, Jaiteh M, et al., 2016,
Role of human milk oligosaccharides in Group B Streptococcus colonisation
, Clinical and Translational Immunology, Vol: 5, ISSN: 2050-0068Group B Streptococcus (GBS) infection is a major cause of morbidity and mortality in infants. The major risk factor for GBSdisease is maternal and subsequent infant colonisation. It is unknown whether human milk oligosaccharides (HMOs) protectagainst GBS colonisation. HMO production is genetically determined and linked to the Lewis antigen system. We aimed toinvestigate the association between HMOs and infant GBS colonisation between birth and postnatal day 90. Rectovaginal swabswere collected at delivery, as well as colostrum/breast milk, infant nasopharyngeal and rectal swabs at birth, 6 days and days60–89 postpartum from 183 Gambian mother/infant pairs. GBS colonisation and serotypes were determined using culture andPCR. 1H nuclear magnetic resonance spectroscopy was used to characterise the mother’s Lewis status and HMO profile in breastmilk. Mothers who were Lewis-positive were significantly less likely to be colonised by GBS (X2 = 12.50, Po0.001). Infants ofLewis-positive mothers were less likely GBS colonised at birth (X2 = 4.88 P = 0.03) and more likely to clear colonisation betweenbirth and days 60–89 than infants born to Lewis-negative women (P = 0.05). There was no association between Secretor statusand GBS colonisation. In vitro work revealed that lacto-N-difucohexaose I (LNDFHI) correlated with a reduction in the growth ofGBS. Our results suggest that HMO such as LNDFHI may be a useful adjunct in reducing maternal and infant colonisation andhence invasive GBS disease. Secretor status offers utility as a stratification variable in GBS clinical trials.
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Journal articleMann JP, Statnikov E, Modi N, et al., 2016,
Management and outcomes of neonates with down syndrome admitted to neonatal units
, Birth Defects Research Part A-Clinical and Molecular Teratology, Vol: 106, Pages: 468-474, ISSN: 1542-9768BackgroundStudies have reported that advanced maternal age is a risk factor for congenital heart disease (CHD), but none of these have been performed in the United Kingdom. Currently, women in the United Kingdom are not referred for specialist fetal echocardiography based on maternal age alone. The aim of this study is to examine the association between maternal age at delivery and CHD prevalence in the North of England.MethodsSingleton cases of CHD notified to the Northern Congenital Abnormality Survey and born between January 1, 1998, to December 31, 2013, were included. Cases with chromosomal anomalies were excluded. The relative risk (RR) of CHD according to maternal age at delivery was estimated using Poisson regression.ResultsThere were 4024 singleton cases of nonchromosomal CHD, giving a prevalence of 8.1 (95% confidence interval [CI], 7.8–8.3) per 1000 live and stillbirths. There was no association between maternal age at delivery and CHD prevalence (p = 0.97), with no evidence of an increased risk of CHD in mothers aged ≥35 compared to aged 25 to 29 (RR = 0.99; 95% CI, 0.89–1.09). There were no significant associations between maternal age at delivery and severity III CHD (p = 0.84), severity II CHD (p = 0.74), or severity I CHD (p = 0.66), although there was a slight increased risk of severity I CHD in mothers aged ≥35 (RR = 1.27; 95% CI, 0.83–1.95).ConclusionWe found little evidence that advanced maternal age is a risk factor for CHD. There is no evidence that women in the United Kingdom should be referred for specialist prenatal cardiac screening based on their age.
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Journal articleLogan K, Gale C, Hyde M, et al., 2016,
Diabetes in pregnancy and infant adiposity: systematic review and meta-analysis
, Archives of Disease in Childhood-Fetal and Neonatal Edition, Vol: 102, Pages: F65-F72, ISSN: 1468-2052Objective: Maternal glycaemia and anthropometry-derived newborn adiposity are stronglycorrelated. The children of mothers with diabetes are at greater risk of adverse metabolichealth, and increased adiposity is a plausible mediator. We undertook a systematic review andmeta-analysis to compare adiposity in infants of mothers with (IDM) and without diabetes(NIDM).Design: We identified observational studies reporting adiposity in IDM and NIDM. We searchedreferences, traced forward citations and contacted authors for additional data. We consideredall body composition techniques and compared fat mass, fat-free mass, body fat % and skinfoldthickness. We used random effects meta-analyses and performed subgroup analyses bymaternal diabetes type (type 1, type 2, gestational) and infant sex. We examined the influenceof pre-pregnancy BMI and conducted sensitivity analyses.Results: We included data from 35 papers and over 24,000 infants. IDM have greater fatmass than NIDM (mean difference [95% CI]); 83g [49, 117]. Fat mass is greater in infants ofmothers with gestational diabetes; 62g [29, 94] and type 1 diabetes; 268g [139, 397].Insufficient studies reported data for type 2 diabetes separately. Compared with NIDM, fatmass was greater in IDM boys; 87g [30, 145], but not significantly different in IDM girls; 42g [-33, 116]. There was no attenuation after adjustment for maternal BMI.Conclusions: IDM have significantly greater adiposity in comparison to NIDM. These findingsare justification for studies to determine whether measures to reduce infant adiposity willimprove later health.
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Journal articleShah PS, Lui K, Sjors G, et al., 2016,
Neonatal Outcomes of Very Low Birth Weight and Very Preterm Neonates: An International Comparison
, Journal of Pediatrics, Vol: 177, Pages: 144-152.e6, ISSN: 0022-3476ObjectiveTo compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes.Study designWe included 58 004 infants born weighing <1500 g at 240–316 weeks' gestation from databases in Australia/New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the United Kingdom. We compared a composite outcome (mortality or any of grade ≥3 peri-intraventricular hemorrhage, periventricular echodensity/echolucency, bronchopulmonary dysplasia, or treated retinopathy of prematurity) between each country and all others by using standardized ratios and pairwise using logistic regression analyses.ResultsDespite differences in population coverage, included neonates were similar at baseline. Composite outcome rates varied from 26% to 42%. The overall mortality rate before discharge was 10% (range: 5% [Japan]-17% [Spain]). The standardized ratio (99% CIs) estimates for the composite outcome were significantly greater for Spain 1.09 (1.04-1.14) and the United Kingdom 1.16 (1.11-1.21), lower for Australia/New Zealand 0.93 (0.89-0.97), Japan 0.89 (0.86-0.93), Sweden 0.81 (0.73-0.90), and Switzerland 0.77 (0.69-0.87), and nonsignificant for Canada 1.04 (0.99-1.09) and Israel 1.00 (0.93-1.07). The adjusted odds of the composite outcome varied significantly in pairwise comparisons.ConclusionsWe identified marked variations in neonatal outcomes between countries. Further collaboration and exploration is needed to reduce variations in population coverage, data collection, and case definitions. The goal would be to identify care practices and health care organizational factors, which has the potential to improve neonatal outcomes.
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Journal articleMartin LJ, Sjörs G, Reichman B, et al., 2016,
Country-Specific vs. Common Birthweight-for-Gestational Age References to Identify Small for Gestational Age Infants Born at 24–28 weeks: An International Study
, Paediatric and Perinatal Epidemiology, Vol: 30, Pages: 450-461, ISSN: 0269-5022BACKGROUND: Controversy exists as to whether birthweight-for-gestational age references used to classify infants as small for gestational age (SGA) should be country specific or based on an international (common) standard. We examined whether different birthweight-for-gestational age references affected the association of SGA with adverse outcomes among very preterm neonates. METHODS: Singleton infants (n = 23 788) of 24(0) -28(6) weeks' gestational age in nine high-resource countries were classified as SGA (<10th centile) using common and country-specific references based on birthweight and estimated fetal weight (EFW). For each reference, the adjusted relative risk (aRR) for the association of SGA with composite outcome of mortality or major morbidity was estimated. RESULTS: The percentage of infants classified as SGA differed slightly for common compared with country specific for birthweight references [9.9% (95% CI 9.5, 10.2) vs. 11.1% (95% CI 10.7, 11.5)] and for EFW references [28.6% (95% CI 28.0, 29.2) vs. 24.6% (95% CI 24.1, 25.2)]. The association of SGA with the composite outcome was similar when using common or country-specific references for the total sample for birthweight [aRRs 1.47 (95% CI 1.43, 1.51) and 1.48 (95% CI 1.44, 1.53) respectively] and for EFW references [aRRs 1.35 (95% CI 1.31, 1.38) and 1.39 (95% CI 1.35, 1.43) respectively]. CONCLUSION: Small for gestational age is associated with higher mortality and morbidity in infants born <29 weeks' gestational age. Although common and country-specific birthweight/EFW references identified slightly different proportions of SGA infants, the risk of the composite outcome was comparable.
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Journal articleLogan K, Emsley RJ, Jeffries S, et al., 2016,
Development of Early Adiposity in Infants of Mothers With Gestational Diabetes Mellitus
, Diabetes Care, Vol: 39, Pages: 1045-1051, ISSN: 0149-5992OBJECTIVEInfants born to mothers with gestational diabetes mellitus (GDM) are at greaterrisk of later adverse metabolic health. We examined plausible candidate mediators;adipose tissue (AT) quantity and distribution, and intrahepatocellular lipid(IHCL) content, comparing infants of mothers with GDM and without GDM (controlgroup) over the first 3 postnatal months.RESEARCH DESIGN AND METHODSWe conducted a prospective longitudinal study using MRI and spectroscopy toquantify whole-body and regional AT volumes, and IHCL content, within 2 weeksand 8–12 weeks after birth. We adjusted for infant size and sex, and maternalprepregnancy BMI. Values are reported as the mean difference (95% CI).RESULTSWe recruited 86 infants (GDM group 42 infants; control group 44 infants). Motherswith GDM had good pregnancy glycemic control. Infants were predominantlybreast fed up to the time of the second assessment (GDM group 71%; controlgroup 74%). Total AT volumes were similar in the GDM group compared with thecontrol group at a median age of 11 days (228 cm3 [95% CI 2121, 65], P = 0.55), butwere greater in the GDM group at a median age of 10 weeks (247 cm3 [56, 439], P =0.01). After adjustment for size, the GDM group had significantly greater total ATvolume at 10 weeks than control group infants (16.0% [6.0, 27.1], P = 0.002). ATdistribution and IHCL content were not significantly different at either time point.CONCLUSIONSAdiposity in GDM infants is amplified in early infancy, despite good maternalglycemic control and predominant breast-feeding, suggesting a potential causalpathway to later adverse metabolic health. Reduction in postnatal adiposity maybe a therapeutic target to reduce later health risks.
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Journal articleDuffy JMN, van t'Hooft J, Gale CRK, et al., 2016,
A protocol for developing, disseminating, and implementing a core outcome set for pre-eclampsia
, Pregnancy Hypertension, Vol: 6, Pages: 274-278, ISSN: 2210-7797BackgroundPre-eclampsia is a serious complication of pregnancy and contributes to maternaland offspring mortality and morbidity. Randomised controlled trials evaluatingtherapeutic interventions for pre-eclampsia have reported many different outcomesand outcome measures. Such variation contributes to an inability to compare,contrast, and combine individual studies, limiting the usefulness of research to informclinical practice. The development and use of a core outcome set would help toaddress these issues ensuring outcomes important to all stakeholders, includingpatients, will be collected and reported in a standardised fashion.MethodsAn international steering group including healthcare professionals, researchers, andpatients, has been formed to guide the development of this core outcome set.Potential outcomes will be identified through a comprehensive literature review andsemi-structured interviews with patients. Potential core outcomes will be entered intoan international, multi-perspective online Delphi survey. All key stakeholders,including healthcare professionals, researchers, and patients will be invited toparticipate. The modified Delphi method encourages whole and stakeholder groupconvergence towards consensus ‘core’ outcomes. Once core outcomes have beenagreed upon it is important to determine how they should be measured. The truth,discrimination, and feasibility assessment framework will assess the quality ofpotential outcome measures. High quality outcome measures will be associated withcore outcomes. Mechanisms exist to disseminate and implement the resulting coreoutcome set within an international context. DiscussionEmbedding the core outcome set within future clinical trials, systematic reviews, andclinical practice guidelines could make a profound contribution to advancing theusefulness of research to inform clinical practice, enhance patient care, and improvematernal and offspring outcomes. The infrastructure created by developing a core
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Journal articleModi N, Simon C, 2016,
Child health care: adequate training for all UK GPs is long overdue
, British Journal of General Practice, Vol: 66, Pages: 228-229, ISSN: 1478-5242
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