Systematic review: Body composition in children with inflammatory bowel disease.

BACKGROUND: Paediatric inflammatory bowel disease (IBD) is associated with weight loss, growth restriction and malnutrition. Bone mass deficits are well described, little is known about other body composition compartments. AIMS: To define the alterations in non-bone tissue compartments in children with IBD, and explore the effects of demographic and disease parameters. METHODS: A systematic search was carried out in the PubMed (www.ncbi.nlm.nih.gov/pubmed) and Web of Science databases in May 2014 (limitations age <17 years, and composition measurements compared with a defined control population). RESULTS: Twenty-one studies were included in this systematic review, reporting on a total of 1479 children with IBD [1123 Crohn's disease, 243 ulcerative colitis], pooled mean age 13.1 ± 3.2 years, and 34.9% female. Data were highly heterogeneous, in terms of methodology and patients. Deficits in protein-related compartments were reported. Lean mass deficits were documented in 93.6% of Crohn's disease and 47.7% of ulcerative colitis patients when compared with healthy control populations. Lower lean mass was common to both sexes in Crohn's disease and ulcerative colitis, deficits in females with persisted for longer. Fat-related compartment findings were inconsistent, some studies report reductions in body fat in new diagnosis/active Crohn's disease. CONCLUSIONS: It is clear that almost all children with Crohn's disease and half with ulcerative colitis have reduced lean mass, however, body fat alterations are not well defined. To understand what impact this may have on health and disease in children with IBD, further studies are needed to identify in which tissues these deficits lie, and to quantify body fat and its distribution.

Sexual dimorphism in relation to adipose tissue and intrahepatocellular lipid deposition in early infancy.

Sexual dimorphism in adiposity is well described in adults, but the age at which differences first manifest is uncertain. Using a prospective cohort, we describe longitudinal changes in directly measured adiposity and intrahepatocellular lipid (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63 days, infants underwent quantification of adipose tissue depots by whole-body magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys and 30 girls). In the neonatal period girls are more adipose in relation to body size than boys. At follow-up (median age 63 days), girls remained significantly more adipose. The greater relative adiposity that characterises girls is explained by more subcutaneous adipose tissue and this becomes increasingly apparent by follow-up. No significant sex differences were seen in IHCL. Sex-specific differences in infant adipose tissue distribution are in keeping with those described in later life, and suggest that sexual dimorphism in adiposity is established in early infancy.

The effects of designation and volume of neonatal care on mortality and morbidity outcomes of very preterm infants in England: retrospective population-based cohort study.

OBJECTIVE: To examine the effects of designation and volume of neonatal care at the hospital of birth on mortality and morbidity outcomes in very preterm infants in a managed clinical network setting. DESIGN: A retrospective, population-based analysis of operational clinical data using adjusted logistic regression and instrumental variables (IV) analyses. SETTING: 165 National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing and Clinical Outcomes Project. PARTICIPANTS: 20 554 infants born at <33 weeks completed gestation (17 995 born at 27-32 weeks; 2559 born at <27 weeks), admitted to neonatal care and either discharged or died, over the period 1 January 2009-31 December 2011. INTERVENTION: Tertiary designation or high-volume neonatal care at the hospital of birth. OUTCOMES: Neonatal mortality, any in-hospital mortality, surgery for necrotising enterocolitis, surgery for retinopathy of prematurity, bronchopulmonary dysplasia and postmenstrual age at discharge. RESULTS: Infants born at <33 weeks gestation and admitted to a high-volume neonatal unit at the hospital of birth were at reduced odds of neonatal mortality (IV regression odds ratio (OR) 0.70, 95% CI 0.53 to 0.92) and any in-hospital mortality (IV regression OR 0.68, 95% CI 0.54 to 0.85). The effect of volume on any in-hospital mortality was most acute among infants born at <27 weeks gestation (IV regression OR 0.51, 95% CI 0.33 to 0.79). A negative association between tertiary-level unit designation and mortality was also observed with adjusted logistic regression for infants born at <27 weeks gestation. CONCLUSIONS: High-volume neonatal care provided at the hospital of birth may protect against in-hospital mortality in very preterm infants. Future developments of neonatal services should promote delivery of very preterm infants at hospitals with high-volume neonatal units.

The impact of a regional care bundle on maternal breast milk use in preterm infants: outcomes of the East of England quality improvement programme.

OBJECTIVE: To evaluate a quality improvement (QI) programme to increase the use of maternal breast milk (MBM) in preterm infants. DESIGN: Interrupted time series analysis. SETTING: 17 neonatal units in the East of England (EoE) Perinatal Network; 144 in the rest of the UK Neonatal Collaborative (UKNC). PATIENTS: Infants born ≤32(+6) weeks gestation admitted to neonatal care between 2009 and 2012. INTERVENTION: A 'care bundle' to promote MBM in the EoE. OUTCOMES: Percentage of infants receiving exclusive or any MBM at discharge and care days where any MBM was received. METHODS: Data were extracted from the National Neonatal Research Database; outcomes were compared preintervention and postintervention, and in relation to the rest of the UKNC. RESULTS: Exclusive and any MBM use at discharge increased from 26% to 33% and 50% to 57% respectively in the EoE, though there was no evidence of a step or trend change following the introduction of the care bundle. Exclusive MBM use at discharge improved significantly faster in EoE than the rest of the UKNC; 0.22% (95% CI 0.11 to 0.34) increase per month versus 0.05% (95% CI 0.01 to 0.09, p=0.007 for difference). The percentage of infants receiving MBM at discharge and care days where any MBM was received was not significantly different between EoE and the rest of the UKNC. CONCLUSIONS: This QI programme was associated with some improvement in MBM use in preterm infants that would not have been evident without the use of routinely recorded national comparator data.

Adjustment of directly measured adipose tissue volume in infants.

BACKGROUND: Direct measurement of adipose tissue (AT) using magnetic resonance imaging is increasingly used to characterise infant body composition. Optimal techniques for adjusting direct measures of infant AT remain to be determined. OBJECTIVES: To explore the relationships between body size and direct measures of total and regional AT, the relationship between AT depots representing the metabolic load of adiposity and to determine optimal methods of adjusting adiposity in early life. DESIGN: Analysis of regional AT volume (ATV) measured using magnetic resonance imaging in longitudinal and cross-sectional studies. SUBJECTS: Healthy term infants; 244 in the first month (1-31 days), 72 in early infancy (42-91 days). METHODS: The statistical validity of commonly used indices adjusting adiposity for body size was examined. Valid indices, defined as mathematical independence of the index from its denominator, to adjust ATV for body size and metabolic load of adiposity were determined using log-log regression analysis. RESULTS: Indices commonly used to adjust ATV are significantly correlated with body size. Most regional AT depots are optimally adjusted using the index ATV/(height)(3) in the first month and ATV/(height)(2) in early infancy. Using these indices, height accounts for<2% of the variation in the index for almost all AT depots. Internal abdominal (IA) ATV was optimally adjusted for subcutaneous abdominal (SCA) ATV by calculating IA/SCA(0.6). CONCLUSIONS: Statistically optimal indices for adjusting directly measured ATV for body size are ATV/height(3) in the neonatal period and ATV/height(2) in early infancy. The ratio IA/SCA ATV remains significantly correlated with SCA in both the neonatal period and early infancy; the index IA/SCA(0.6) is statistically optimal at both of these ages.

The diabetic pregnancy and offspring blood pressure in childhood: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Offspring of diabetic mothers have increased risk of the metabolic syndrome in adulthood. Studies examining BP in offspring of diabetic mothers have conflicting conclusions. We performed a systematic review and meta-analysis of studies reporting offspring BP in children born to diabetic mothers. METHODS: Citations were identified in PubMed. Authors were contacted for additional data. Systolic and diastolic BP in offspring of diabetic mothers and controls were compared. Subgroup analysis of type of maternal diabetes and offspring sex were performed. Fixed-effects models were used, and random-effects models where significant heterogeneity was present. Meta-regression was used to test the relationship between offspring systolic BP and prepregnancy BMI. RESULTS: Fifteen studies were included in the review and 13 in the meta-analysis. Systolic BP was higher in offspring of diabetic mothers (mean difference 1.88 mmHg [95% CI 0.47, 3.28]; p = 0.009). Offspring of mothers with gestational diabetes had similar diastolic BP to controls, but higher systolic BP (1.39 mmHg [95% CI 0.00, 2.77]; p = 0.05); results for type 1 diabetes were inconclusive and there were no separate data available on offspring of type 2 diabetic mothers. Male offspring of diabetic mothers had higher systolic BP (2.01 mmHg [95% CI 0.93, 3.10]; p = 0.0003) and diastolic BP (1.12 mmHg [95% CI 0.36, 1.88]; p = 0.004) than controls; in female offspring there was no difference (systolic: 0.54 mmHg [95% CI -1.83, 2.90], p = 0.66; diastolic: 0.51 mmHg [95% CI -1.07, 2.09], p = 0.52). The correlation between offspring systolic BP and maternal prepregnancy BMI was not significant (p = 0.37). CONCLUSIONS/INTERPRETATION: Offspring of diabetic mothers have higher systolic BP than controls. Differences related to sex and type of maternal diabetes require further investigation.

Impact of managed clinical networks on NHS specialist neonatal services in England: population based study.

OBJECTIVE: To assess the impact of reorganisation of neonatal specialist care services in England after a UK Department of Health report in 2003. DESIGN: A population-wide observational comparison of outcomes over two epochs, before and after the establishment of managed clinical neonatal networks. SETTING: Epoch one: 294 maternity and neonatal units in England, Wales, and Northern Ireland, 1 September 1998 to 31 August 2000, as reported by the Confidential Enquiry into Stillbirths and Sudden Deaths in Infancy Project 27/28. Epoch two: 146 neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit, 1 January 2009 to 31 December 2010. PARTICIPANTS: Babies born at a gestational age of 27(+0)-28(+6) (weeks+days): 3522 live births in epoch one; 2919 babies admitted to a neonatal unit within 28 days of birth in epoch two. INTERVENTION: The national reorganisation of neonatal services into managed clinical networks. MAIN OUTCOME MEASURES: The proportion of babies born at hospitals providing the highest volume of neonatal specialist care (≥ 2000 neonatal intensive care days annually), having an acute transfer (within the first 24 hours after birth) and/or a late transfer (between 24 hours and 28 days after birth) to another hospital, assessed by change in distribution of transfer category ("none," "acute," "late"), and babies from multiple births separated by transfer. For acute transfers in epoch two, the level of specialist neonatal care provided at the destination hospital (British Association of Perinatal Medicine criteria). RESULTS: After reorganisation, there were increases in the proportions of babies born at 27-28 weeks' gestation in hospitals providing the highest volume of neonatal specialist care (18% (631/3495) v 49% (1325/2724); odds ratio 4.30, 95% confidence interval 3.83 to 4.82; P<0.001) and in acute and late postnatal transfers (7% (235) v 12% (360) and 18% (579) v 22% (640), respectively; P<0.001). There was no significant change in the proportion of babies from multiple births separated by transfer (33% (39) v 29% (38); 0.86, 0.50 to 1.46; P=0.57). In epoch two, 32% of acute transfers were to a neonatal unit providing either an equivalent (n=87) or lower (n=26) level of specialist care. CONCLUSIONS: There is evidence of some improvement in the delivery of neonatal specialist care after reorganisation. The increase in acute transfers in epoch two, in conjunction with the high proportion transferred to a neonatal unit providing an equivalent or lower level of specialist care, and the continued separation of babies from multiple births, are indicative of poor coordination between maternity and neonatal services to facilitate in utero transfer before delivery, and continuing inadequacies in capacity of intensive care cots. Historical data representing epoch one are available only in aggregate form, preventing examination of temporal trends or confounding factors. This limits the extent to which differences between epochs can be attributed to reorganisation and highlights the importance of routine, prospective data collection for evaluation of future health service reorganisations.

Sonographic predictors of surgery in fetal coarctation of the aorta.

OBJECTIVES: Isolated fetal coarctation of the aorta (CoA) has high false-positive diagnostic rates by cardiologists in tertiary centers. Isthmal diameter Z-scores (I), ratio of isthmus to duct diameters (I:D), and visualization of CoA shelf (Shelf) and isthmal flow disturbance (Flow) distinguish hypoplastic from normal aortic arches in retrospective studies, but their ability to predict a need for perinatal surgery is unknown. The aim of this study was to determine whether these four sonographic features could differentiate prenatally cases which would require neonatal surgery in a prospective cohort diagnosed with CoA by a cardiologist. METHODS: From 83 referrals with cardiac disproportion (January 2006 to August 2010), we identified 37 consecutive fetuses diagnosed with CoA. Measurements of I and I:D were made and the presence of Shelf or Flow recorded. Sensitivity, specificity and areas under receiver-operating characteristics curves, using previously reported limits of I < - 2 and I:D < 0.74, as well as Shelf and Flow were compared at first and final scan. Associations between surgery and predictors were compared using multivariable logistic regression and changes in measurements using ANCOVA. RESULTS: Among the 37 fetuses, 30 (81.1%) required surgery and two with an initial diagnosis of CoA were revised to normal following isthmal growth, giving an 86% diagnostic accuracy at term. The median age at first scan was 22.4 (range. 16.6-7.0) weeks and the median number of scans per fetus was three (range, one to five). I < - 2 at final scan was the most powerful predictor (odds ratio, 3.6 (95% CI, 0.47-27.3)). Shelf was identified in 66% and Flow in 50% of fetuses with CoA. CONCLUSION: Incorporation of these four sonographic parameters in the assessment of fetuses with suspected CoA at a tertiary center resulted in better diagnostic precision regarding which cases would require neonatal surgery than has been reported previously.

In-utero transfer is too difficult: results from a prospective study.

BACKGROUND: Perinatal transfer is an unavoidable part of neonatal care. In-utero as opposed to postnatal transfer is recommended whenever possible. AIMS: To quantify prevalence of in-utero transfers, determine the duration of time spent arranging in-utero transfers and whether failures in the organisation of potential in-utero transfers were occurring. STUDY DESIGN: Prospective study of in-utero transfers referred and completed, and questionnaire study of failed potential in-utero transfers. SUBJECTS: Women referred to the Emergency Bed Service (EBS), women undergoing in-utero transfer by London Ambulance Service (LAS), and preterm infants undergoing postnatal transfer where in-utero transfer had been potentially achievable, in the London area, over a six month period in 2009. OUTCOME MEASURES: Number of in-utero transfers being undertaken, duration of time spent arranging in-utero transfer, and number of failed in-utero transfers. RESULTS: Over the study period LAS undertook 438 in-utero transfers and there were 338 referrals for in-utero transfer to EBS, of which 180 (53%) were successful. Of 69 emergency postnatal transfers of preterm infants (<29 weeks gestational age), 11 were classified as failed in-utero transfers. Median (IQR) duration of EBS involvement in in-utero referrals was 340 (200-696)min. A median (IQR) of 240 (150-308)min was spent contacting a median (IQR) of 7 (6-8)units when attempting to arrange in-utero transfer in the failed in-utero transfer group. CONCLUSIONS: Arranging in-utero transfer consumes considerable clinical time; an important number of in-utero transfer attempts fail for non-clinical reasons; establishment of a centralised in-utero transfer planning service will save clinical time and may improve outcomes.

The diabetic pregnancy and offspring BMI in childhood: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Offspring of mothers with diabetes are at increased risk of metabolic disorders in later life. Increased offspring BMI is a plausible mediator. We performed a systematic review and meta-analysis of studies examining offspring BMI z score in childhood in relation to maternal diabetes. METHODS: Papers reporting BMI z scores for offspring of diabetic (all types, and pre- and during-pregnancy onset) and non-diabetic mothers were included. Citations were identified in PubMed; bibliographies of relevant articles were hand-searched and authors contacted for additional data where necessary. We compared offspring BMI z score with and without adjustment for maternal pre-pregnancy BMI. We performed fixed effect meta-analysis except where significant heterogeneity called for use of a random effects analysis. RESULTS: Data were available from nine studies. In the diabetic group unadjusted mean offspring BMI z score was 0.28 higher (all diabetic mothers vs controls (95% CI 0.09, 0.47; p = 0.004; nine studies; offspring of diabetic mothers n = 927, controls n = 26,384) and with adjustment for maternal pre-pregnancy BMI, 0.07 higher (95% CI -0.15, 0.28; p = 0.54; three studies; offspring of diabetic mothers n = 244, controls n = 11,206). There was no evidence of a difference in offspring BMI z score in relation to type of diabetes (gestational vs type 1, p = 0.95). CONCLUSIONS/INTERPRETATION: Maternal diabetes is associated with increased offspring BMI z score, although this is no longer apparent after adjustment for maternal pre-pregnancy BMI in the limited number of studies in which this is reported. Causal mediators of the effect of maternal diabetes on offspring outcomes remain to be established; we recommend that future research includes adjustment for maternal pre-pregnancy BMI.