C Gale

The Influence of Maternal Body Mass Index on Infant Adiposity and Hepatic Lipid Content

Maternal overweight and obesity are associated with adverse offspring outcome in later life. The causal biological effectors are uncertain. Postulating that initiating events may be alterations to infant body composition established in utero, we tested the hypothesis that neonatal adipose tissue (AT) content and distribution and liver lipid are influenced by maternal BMI. We studied 105 healthy mother-neonate pairs. We assessed infant AT compartments by whole body MR imaging and intrahepatocellular lipid content by 1H MR spectroscopy. Maternal BMI ranged from 16.7 to 36.0. With each unit increase in maternal BMI, having adjusted for infant sex and weight, there was an increase in infant total (8 mL; 95% CI, 0.09–14.0; p = 0.03), abdominal (2 mL; 95% CI, 0.7–4.0; p = 0.005), and nonabdominal (5 mL; 95% CI, 0.09–11.0; p = 0.054) AT, and having adjusted for infant sex and postnatal age, an increase of 8.6% (95% CI, 1.1–16.8; p = 0.03) in intrahepatocellular lipid. Infant abdominal AT and liver lipid increase with increasing maternal BMI across the normal range. These effects may be the initiating determinants of a life-long trajectory leading to adverse metabolic health.

The UK National Neonatal Research Database: using neonatal data for research, quality improvement and more

Electronic data are increasingly recorded in clinical practice. Just as advances in genetics have gradually led to clinical benefit1 so too are ‘big data’ bringing tangible advances to patient care.2 The UK has a long history of using electronic neonatal data for research and is now in the enviable position of having electronic patient data on all admissions to National Health Service (NHS) neonatal units in England, Wales and Scotland. This national resource, the National Neonatal Research Database (NNRD), is available for research, audit, benchmarking and quality improvement. Here, we provide an overview of how data entered into an electronic system (Badger.net; Clevermed Ltd) as a component of day-to-day care, are used to form the NNRD and how this can be used by health professionals. For over 25 years, neonatal data have been collected in regional databases such as The Neonatal Survey. The availability of national neonatal data is, however, a relatively recent phenomenon in the UK and internationally. In the UK the use of electronic patient records shared across neonatal units began in 2004 as a regional initiative. This platform, Badger.net, subsequently expanded nationwide; it is now used by many neonatal units to plan services and record activity for payment by NHS England. In 2007, the Neonatal Data Analysis Unit (NDAU) was established at the Chelsea and Westminster Hospital campus of Imperial College London to improve the quality of electronic clinical data …

Research ethics committee decision-making in relation to an efficient neonatal trial

Objective Randomised controlled trials, a gold-standard approach to reduce uncertainties in clinical practice, are growing in cost and are often slow to recruit. We determined whether methodological approaches to facilitate large, efficient clinical trials were acceptable to UK research ethics committees (RECs). Design We developed a protocol in collaboration with parents, for a comparative-effectiveness, randomised controlled trial comparing two widely used blood transfusion practices in preterm infants. We incorporated four approaches to improve recruitment and efficiency: (i) point-of-care design using electronic patient records for patient identification, randomisation and data acquisition, (ii) short two-page information sheet; (iii) explicit mention of possible inclusion benefit; (iv) opt-out consent with enrolment as the default. With the support of the UK Health Research Authority, we submitted an identical protocol to 12 UK REC. Setting RECs in the UK. Main outcome Number of REC granting favourable opinions. Results The use of electronic patient records was acceptable to all RECs; one REC raised concerns about the short parent information sheet, 10 about inclusion benefit and 9 about opt-out consent. Following responses to queries, nine RECs granted a favourable final opinion and three rejected the application because they considered the opt-out consent process invalid. Conclusions A majority of RECs in this study consider the use of electronic patient record data, short information sheets, opt-out consent and mention of possible inclusion benefit to be acceptable in neonatal comparative-effectiveness research. We identified a need for guidance for RECs in relation to opt-out consent processes. These methods provide opportunity to facilitate large randomised controlled trials.

PPO.23 Top 15 research priorities for preterm birth with clinicians and service users’ involvement – outcomes from a James Lind Alliance priority setting partnership

Background Preterm birth is the single most important determinant of adverse infant outcomes in terms of survival, quality of life, psychosocial and emotional impact on the family, and health care costs. Research agenda in this area has been determined primarily by researchers, and the processes for priority setting in research have often lacked transparency. Objectives To identify 15 most important priorities for future research for practitioners and service users in the area of preterm birth. Methods A priority setting partnership was established by involving clinicians, adults who were born preterm, and parents and families with experience of preterm birth. Research uncertainties were gathered from surveys of service users and clinicians, and analyses of systematic reviews and clinical guidance, and then prioritised in a transparent process, using a methodology advocated by the James Lind Alliance. Results 593 uncertainties were submitted by 386 respondents and 52 were identified from literature reviews. After merging similar questions, a long list of 104 questions were distributed for voting. The 30 most popular items were then prioritised at a workshop. The top 15 research priorities included prevention of preterm birth, management of neonatal infection, necrotising enterocolitis, pain and lung damage, care package at discharge, feeding strategies, pre-eclampsia, emotional and practical support, attachment and bonding, premature rupture of membranes and best time for cord clamping. Conclusions These top research priorities in preterm birth provide guidance for researchers and funding bodies to ensure that future research addresses questions that are important to both clinicians and service users.

360 Sex Differences in Adipose Tissue Quantity and Distribution in Newborn Infants

Background and Aims Adipose tissue (AT) quantity and distribution influence metabolic health. In adult life women have greater total and subcutaneous AT, but men have greater internal abdominal AT (Gender Medicine, 2009; 6: 60–75). We aimed to explore AT volume and distribution in newborn male and female infants using magnetic resonance imaging (MRI). Methods A retrospective observational study was performed, using an existing database of neonatal body composition data, to compare male and female healthy term infants. Results Abstract 360 Table 1 Anthropometry at scan in male and female infants Measurement; mean (SD) Male (n=95) Female (n=90) p value Weight (g) 3590 (456) 3475 (496) 0.104 Length (cm) 53.0 (2.2) 52.7 (2.8) 0.435 Head circumference (cm) 36.4 (1.3) 35.8 (1.3) 0.002 Abstract 360 Table 2 AT volume in male and female infants AT volume (ml); mean [95% CI], after adjustment for scan weight Male (n=95) Female (n=90) p value Total AT 746 [718, 774] 841 [812, 869] <0.001 Abdominal superficial subcutaneous AT (SSAT) 102 [97, 107] 122 [117, 128] <0.001 Non-abdominal SSAT 540 [519, 560] 606 [586, 627] <0.001 Abdominal deep subcutaneous AT (DSAT) 14 [13, 15] 18 [17, 20] <0.001 Non-abdominal DSAT 12 [11, 13] 13 [12, 14] 0.008 Abdominal internal AT (IAT) 22 [20, 24] 21 [20, 23] 0.672 Non-abdominal IAT 56 [53, 60] 59 [55, 63] 0.310 Conclusions Female newborn infants have higher total and subcutaneous AT, but similar internal abdominal AT compared to males. Longitudinal study is required to assess gender specific alterations in AT distribution during infancy and childhood, and may identify possible influences of internal abdominal AT development in males.

Changes in postnatal transfers and place of delivery following introduction of managed neonatal networks in england

Background Following a Department of Health review in 2003, specialist neonatal services in England were re-organised into managed clinical networks with the aim of delivering high quality co-ordinated care.1 Maternity services were not included in this re-organisation. Effective network performance should result in reduced acute, and increased in-utero and back transfers among extremely preterm babies. Aims To test the hypothesis that since establishment of managed networks there has been an increase in the proportion of preterm babies (1) Delivered at units with the greatest intensive care experience, (2) Transferred between age 24 h and 28 days and (3) A reduction in the proportion transferred at age <24 h. Design Caldicott Guardian approval has been obtained to receive routinely collected data from neonatal units for service evaluation. We compared postnatal transfers in infants born at 270–286 weeksdays gestational age before (epoch one 1 September 1998–31 August 2000) and after re-organisation (epoch two 1 January 2009–31 December 2009). Information from epoch one was obtained from the Confidential Enquiry into Stillbirths and Deaths in Infancy report on preterm infants2 and for epoch two from the 121 neonatal units contributing routinely collected data for that period, and differences tested for significance (χ2 test and logistic regression). Results There were no significant between epoch differences in gender, delivery mode or multiple births. In epoch two, a higher proportion of babies were born in units with greater neonatal intensive care experience (p<0.001); the proportion having an acute transfer ≤24 h increased from 6.8 to 12.7% (p<0.001) and survival improved (p<0.001) (table 1). Abstract G65 Table 1 Unit of birth, transfer status and survival by epoch. Epoch 1: 1998–2000 Epoch 2: 2009 p value for difference between epoch 1 and 2 Days n % n % Neonatal unit of birth (categorised by annual intensive care days) 1–499 843 25.1 141 11.4 <0.001 500–999 673 20.1 231 18.7 1000–1499 653 19.5 135 10.9 1500–1999 556 16.6 110 8.9 >2000 631 18.8 619 50.1 Total 3356 1236 Transfer status n % n % Transfers Not transferred 2668 75.8 858 64.0 <0.001 ≤24 h 238 6.8 170 12.7 24 h–28 days 616 17.5 312 23.3 Total 3522 1340 Transfer status % % Survival at 28 days by transfer group Not transferred 86.2% 92.9% <0.001 ≤24 h 87.8% 93.3% 24 h–28 days 95.9% 98.1% Total 88.0% 94.0% Conclusions Since reorganisation, a greater proportion of extremely preterm babies are born in the most experienced neonatal units, and a greater proportion undergo both acute and later postnatal transfer. The increase in delivery at experienced units would be expected to improve outcomes. The increase in acute postnatal transfers may suggest that neonatal and maternity services are not functioning effectively in facilitating in-utero transfers. We suggest that focus should be placed on organisation of perinatal networks, and the commissioning disparity between neonatal and maternity services should be rectified. Preterm babies are highly likely to undergo postnatal transfer; this should be explained to parents.

PS-052 Setting Preterm Birth Research Priorities With Multiple Professions And Service Users In The Uk

Background Preterm birth is the most important determinant of adverse infant outcomes. Research agendas in this area have been determined primarily by researchers. Objectives To identify and prioritise future research areas in preterm birth that are most important to service users and practitioners. Methods A priority setting partnership was established with families with experience of preterm birth and organisations representing them, obstetricians, neonatologists, midwives and neonatal nurses. Research uncertainties were gathered from surveys and analysis of systematic reviews and clinical guidance. Prioritisation was through voting; final ranking occurred at a facilitated workshop, as advocated by the James Lind Alliance. Results 593 uncertainties were submitted by 386 respondents (58% service users, 30% healthcare professionals and 12% from those in both roles); 52 were identified from literature reviews. After merging similar questions, 104 were distributed for voting. From the 30 most popular uncertainties, the top 15 questions were prioritised in a facilitated workshop These include prevention and prediction of preterm birth, neonatal infection, lung damage, necrotising enterocolitis, pre-eclampsia, preterm premature rupture of the membranes, optimal neonatal feeding strategy, pain perception and management, a care package at neonatal discharge, emotional and practical support, attachment and bonding, and the best time for cord clamping. Conclusions These priorities provide guidance to ensure that future research addresses questions that are important to service users and clinicians. Challenges for the priority setting partnership included maximising participation amongst people most affected by preterm birth, the breadth of the topic and securing input from an appropriate range of clinicians.

PC.14 Adjustment of directly measured adipose tissue volume in infants

Background Direct measurement of adipose tissue using magnetic resonance imaging (MRI) is increasingly used to characterise body composition. Optimal techniques for adjusting direct measures of infant adipose tissue remain to be determined. Objectives To explore the relationships between body size and directly measured total and regional adipose tissue volume (ATV), and the relationship between ATV depots representing the metabolic load of adiposity, to determine optimal methods of adjusting adiposity in infancy. Design Analysis of regional ATV measured using MRI 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 (Figure 1) and ATV/(height)2 in early infancy. Internal abdominal (IA) ATV was optimally adjusted for subcutaneous abdominal (SCA) ATV by calculating IA/SCA0.6 (Figure 2). Abstract PC.14 Figure 1 r = 0.15, p = 0.19 Abstract PC.14 Figure 2 r = 0.02, p = 0.97 Conclusions Commonly used methods of adjusting adipose tissue in early infancy, such as percentage adipose tissue, have statistical limitations. We describe statistically optimal indices for adjusting directly measured adipose tissue volume for body size and to represent the metabolic load of adiposity in early infancy.

P04 Adiposity of Healthy, Full-Term Breast-Fed and Formula-Fed Infants: A Prospective Cohort Study

Aims Although an association exists between method of feeding in infancy and increased risk of later overweight and obesity, it is unclear whether this represents a causal relationship. One plausible mechanism of action is through alteration in adiposity in infancy. We aimed to compare longitudinal changes in adiposity in healthy, full-term, breast-fed (BF) and formula-fed infants (FF). Methods Research Ethics Committee and NHS approvals were obtained. With informed maternal consent, healthy, term infants underwent whole body magnetic resonance imaging and hepatic spectroscopy to assess body composition and intrahepatocellular lipid (IHCL) content. Investigations were performed in natural sleep on two occasions, shortly after birth (T1), and between two and three months (T2) in accordance with our previously published protocols. Anthropometric measurements were obtained at both visits. Feeding was categorised according to World Health Organisation definitions. Comparison was made between exclusively or predominantly BF, and exclusively or predominantly FF infants. We used independent sample t-tests to compare body weights and multivariable regression to examine total and regional adipose tissue volumes at T2, with adjustment for baseline adiposity and body weight. Adipose tissue volumes (litres) and IHCL (ratio of lipid to water peak) are presented as mean (95% confidence interval). Results Eighty-six infants were studied at T1, median [interquartile range] 13 [8–19] days, and 73 at T2, 63 [57–70] days. Of these, 38 infants were wholly or predominantly BF and 26 wholly or predominantly FF at both time points. At T2, while FF infants were heavier (mean, standard deviation: 5.399kg, 0.661kg; FF 5.435kg, 0.68kg); p = 0.045), total adiposity was not significantly different (BF 1.516 (1.433, 1.600); FF 1.633 (1.531, 1.735); p = 0.08). There were no statistically significant differences in regional adipose tissue volumes or IHCL (BF 2.398 (1.838, 2.958); FF 2.406 (1.708, 3.103); p = 0.9). Conclusions While adiposity does not differ substantially between BF and FF infants by 9 weeks of age, further longitudinal evaluation is required to determine if the trend to greater total adiposity in FF infants is subsequently amplified.

46 Change in Regional Adipose Tissue and Intrahepatocellular Lipid in Healthy Fully Breast-Fed Babies, Between Birth and Three Months

Background and aims Total adiposity doubles in early infancy1, however there exists little data describing the change in adipose tissue (AT) distribution and intrahepatocellular lipid (IHCL) over this period. In adults AT distribution and IHCL have important health implications2. We aimed to measure the change in AT distribution and IHCL in healthy breastfed babies. Design Healthy, term, appropriate weight for gestational age infants were recruited from the postnatal ward at Chelsea and Westminster Hospital. Magnetic resonance images and proton spectra were acquired after birth and at 2–3 months as previously described3, 4. IHCL results are presented as the ratio CH2/water. Results We studied 32 infants. Change in AT and IHCL are presented in table 1. While total AT volume doubled, there was variation in the magnitude of change in the different regional AT compartments. Abstract 46 Table 1 First scan Second scan % Change (range) Significance (*paired samples t-test, † related samples Wilcoxon Signed Rank test) Total adipose tissue, litres - mean (SD) 0.776 (0.187) 1.524 (0.388) 101 (18 to 222) <0.001* Abdominal superficial subcutaneous adipose tissue, litres - mean (SD) 0.107 (0.031) 0.253 (0.083) 144 (44 to 323) <0.001* Abdominal deep subcutaneous adipose tissue, litres - mean (SD) 0.017 (0.007) 0.039 (0.015) 151 (–46 to 380) <0.001* Abdominal internal adipose tissue, litres - mean (SD) 0.019 (0.008) 0.030 (0.014) 75 (–25 to 533) <0.001* Ratio of internal abdominal adipose tissue to abdominal subcutaneous adipose tissue - mean (SD) 0.157 (0.056) 0.104 (0.037) <0.001* IHCL - median (IQR) 0.65 (0.37–1.90) 1.84 (1.41–2.43) 0.001† Longitudinal changes in AT compartments and IHCL Conclusions Growth of different regional AT depots occurs at different rates, and IHCL increases in early infancy. The physiological significance of these novel findings is uncertain. References 1. Gale C AJCN 2012; 2. Fabbrini PNAS 2009; 3. Modi N Pediatr Res 2006; 4. Thomas EL ADCFN 2008.