Sabita Uthaya

Whole Body Magnetic Resonance Imaging of Healthy Newborn Infants Demonstrates Increased Central Adiposity in Asian Indians

Abdominal adiposity and metabolic ill health in Asian Indians are a growing public health concern. Causal pathways are unknown. Preventive measures in adults have had limited success. The aim of this observational case-control study was to compare adipose tissue partitioning in 69 healthy full term Asian Indian and white European newborns born in Pune, India and London, UK, respectively. The main outcome measures were total and regional adipose tissue content measured by whole body magnetic resonance imaging. Although smaller in weight (95% CI for difference −0.757 to −0.385 kg, p < 0.001), head circumference (−2.15 to −0.9 cm, p < 0.001), and length (−2.9 to −1.1 cm p < 0.001), the Asian Indian neonates had significantly greater absolute adiposity in all three abdominal compartments, internal (visceral) (0.012–0.023 L, p < 0.001), deep s.c. (0.003–0.017 L, p = 0.006) and superficial s.c. (0.006–0.043 L, p = 0.011) and a significant reduction in nonabdominal superficial s.c. adipose tissue (−0.184 to −0.029 L, p = 0.008) in comparison to the white European babies despite similar whole body adipose tissue content (−0.175 to 0.034 L, p = 0.2). We conclude that differences in adipose tissue partitioning exist at birth. Investigative, screening, and preventive measures must involve maternal health, intrauterine life, and infancy.

Determinants of Adiposity during Preweaning Postnatal Growth in Appropriately Grown and Growth-Restricted Term Infants

The distribution and quantity of adipose tissue are markers of morbidity risk in children and adults. Poor intrauterine growth and accelerated postnatal growth are believed to add to these risks. The aim of this study was to assess adipose tissue content and distribution at birth and 6 wk in relation to intrauterine growth restriction, postnatal growth, and infant diet. We measured weight, length, and head circumference and adipose content and distribution using magnetic resonance imaging at 6 wk of age in appropriately grown for gestational age (AGA) and growth-restricted (GR) infants and compared this with birth data. By 6 wk, GR infants showed complete catch-up in comparison to AGA infants in relation to head growth and adiposity. Catch-up in length and weight was not complete. Accelerated linear growth, but not accelerated weight gain, was associated with a highly significant increase in adiposity (r = 0.57, p = 0.001) regardless of AGA/GR status. The highest adiposity at 6 wk, allowing for baseline variables and linear growth, was seen in exclusively breast-fed GR infants (mean, 95% confidence interval: 33.5%, 29.51–37.5). Adipose tissue distribution remained constant and was unrelated to growth and diet. Reduced birth adiposity (B = –0.185, p = 0.003), but not low birth head size (B = 0.32, p = 0.093), was a significant predictor of accelerated postnatal head growth (R2 = 0.29, adjusted R2 = 0.23, p = 0.012). Increasing adiposity appears to be an inevitable accompaniment of accelerated linear growth. Low total adipose tissue quantity at birth appears to direct nutrition toward head growth. Adipose tissue may be involved in the signaling of catch-up growth.

A Randomized, Double-Blind, Controlled Trial of the Effect of Prebiotic Oligosaccharides on Enteral Tolerance in Preterm Infants (ISRCTN77444690)

Breast milk prebiotic oligosaccharides are believed to promote enteral tolerance. Many mothers delivering preterm are unable to provide sufficient milk. We conducted a multicenter, randomized, controlled trial comparing preterm formula containing 0.8 g/100 mL short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides in a 9:1 ratio and an otherwise identical formula, using formula only to augment insufficient maternal milk volume. Infants were randomized within 24 h of birth. The primary outcome (PO) was time to establish a total milk intake of 150 mL/kg/d PO and the principal secondary outcome (PSO) was proportion of time between birth and 28 d/discharge that a total milk intake of ≥150 mL/kg/d was tolerated. Other secondary outcomes included growth, fecal characteristics, gastrointestinal signs, necrotizing enterocolitis, and bloodstream infection. Outcomes were compared adjusted for prespecified covariates. We recruited 160 infants appropriately grown for GA <33 wk. There were no significant differences in PO or PSOs. After covariate adjustment, we showed significant benefit from trial formula in PSO with increasing infant immaturity (2.9% improved tolerance for a baby born at 28-wk gestation and 9.9% at 26-wk gestation; p < 0.001) but decreased or no benefit in babies >31-wk gestation. Prebiotic supplementation appears safe and may benefit enteral tolerance in the most immature infants.

Accelerated postnatal head growth follows preterm birth

Background: Poor growth after preterm birth, particularly poor head growth, is associated with impaired neurodevelopmental outcome. Objective: To evaluate weight gain and head growth between birth and term in a contemporary cohort of preterm infants, taking into account breast milk intake and illness severity. Methods: Subjects were inborn infants ⩽32 weeks gestation who remained in the neonatal unit up to ⩾37 weeks postmenstrual age. Weight and head circumference (HC) were expressed as standard deviation score (SDS), growth between birth and discharge as SDS gain (SDSG), and illness severity and breast milk exposure as the number of days of level 1 (full) intensive care (%L1IC) and the number of days on which breast milk was received (%BM) as a percentage of days from birth to discharge. Results: Infants showed poor postnatal weight gain but accelerated head growth. There was a highly significant fall in mean (SD) weight SDS between birth and discharge (−0.31 (0.96) and −1.32 (1.02) respectively, p<0.001) and a highly significant increase in HC SDS (−0.52 (0.95) and −0.03 (1.25) respectively, p  =  0.003). %L1IC had a highly significant negative impact on weight SDSG (p  =  0.006), and %BM had a significant positive impact on HC SDSG (p  =  0.043). Conclusions: Accelerated postnatal head growth suggests catch up after antenatal restraint. This raises the possibility that poor neurocognitive outcomes after extremely preterm birth may in part be consequent on poor intrauterine brain growth. As postnatal head growth may be facilitated by breast milk, there is an urgent need to evaluate the optimal use of breast milk in preterm neonates. Illness severity is a significant determinant of poor postnatal weight gain.

Nutritional Evaluation and Optimisation in Neonates: a randomized, double-blind controlled trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition

Background: Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil–containing lipid emulsions. Objective: The aim of this trial was to compare 1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of amino acids (Inc-AAs)] parenteral amino acid delivery within 24 h of birth on body composition and 2) the effect of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF) with that of soybean oil (SO)-based lipid emulsion on intrahepatocellular lipid (IHCL) content. Design: We conducted a 2-by-2 factorial, double-blind, multicenter randomized controlled trial. Results: We randomly assigned 168 infants born at <31 wk of gestation. We evaluated outcomes at term in 133 infants. There were no significant differences between Imm-RDI and Inc-AA groups for nonadipose mass [adjusted mean difference: 1.0 g (95% CI: −108, 111 g; P = 0.98)] or between SMOF and SO groups for IHCL [adjusted mean SMOF:SO ratio: 1.1 (95% CI: 0.8, 1.6; P = 0.58]. SMOF does not affect IHCL content. There was a significant interaction (P = 0.05) between the 2 interventions for nonadipose mass. There were no significant interactions between group differences for either primary outcome measure after adjusting for additional confounders. Imm-RDI infants were more likely than Inc-AA infants to have blood urea nitrogen concentrations >7 mmol/L or >10 mmol/L, respectively (75% compared with 49%, P < 0.01; 49% compared with 18%, P < 0.01). Head circumference at term was smaller in the Imm-RDI group [mean difference: −0.8 cm (95% CI: −1.5, −0.1 cm; P = 0.02)]. There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, incidence of conjugated hyperbilirubinemia, weight, length, mortality, and brain volumes. Conclusion: Imm-RDI of parenteral amino acids does not benefit body composition or growth to term and may be harmful. This trial was registered at www.isrctn.com as ISRCTN29665319 and at eudract.ema.europa.eu as EudraCT 2009-016731-34.

Neonatal intrahepatocellular lipid

There is increasing evidence that preterm birth is a risk factor for the development of adiposity associated disease, although the pathophysiological basis is unclear. We have previously shown that preterm infants have increased internal abdominal (visceral) adiposity by term. In adults increased internal adiposity is associated with elevated intrahepatocellular lipid (IHCL). We measured IHCL using 1H NMR spectroscopy in 26 infants (eight healthy preterm-at-term and 18 term-born) and compared values with a reference group of 32 adults. There was no significant difference between adult and term-born IHCL content. In preterm-at-term infants IHCL was significantly elevated when compared with term-born infants and with adults (IHCL CH2/water median (interquartile range): preterm 1.69 (1.04–3.53), term 0.21 (0–0.54) and adult 0.55 (0.08–1.57).

Adipose Tissue Magnetic Resonance Imaging in the Newborn

Infancy is a period of rapid adipose tissue accumulation, and influences during early development are plausible determinants of altered adiposity. The distribution, as well as the quantity of adipose tissue, is a marker of health and disease. Previous methods for the assessment of body composition in infants have been indirect and thus unable to determine adipose quantity reliably, nor assess adipose tissue distribution. Adipose tissue magnetic resonance imaging is direct, non-invasive, radiation free and suitable for serial examinations in infancy. Adipose tissue depots are quantified individually and summated to provide an accurate measure of depot-specific and total adiposity. We have adapted this technique for application to newborns and, to date, have imaged over 100 term and preterm infants.

Avoiding sedation in research MRI and spectroscopy in infants: our approach, success rate and prevalence of incidental findings

Performing magnetic resonance investigations in a paediatric population can be difficult; image acquisition is commonly complicated by movement artefact and non-compliance. Sedation is widely used for clinically indicated investigations, but there is controversy when used for research imaging. Over a 10-year period we have performed whole body MRI on over 450 infants and hepatic magnetic resonance spectroscopy on over 270 infants. These investigations have been accomplished without the use of sedation in infants up to 3 months of age. Our overall success rate in achieving good quality images free of movement artefact is 94%. The prevalence of incidental findings on whole body (excluding brain) MRI in our cohort was 0.8%. We conclude that the use of sedation for research MRI in this group is not necessary. Our approach to MRI in infancy is also described.

Ultrasound Estimates of Visceral and Subcutaneous-Abdominal Adipose Tissues in Infancy

Other imaging techniques to quantify internal-abdominal adiposity (IA-AT) and subcutaneous-abdominal adiposity (SCA-AT) are frequently impractical in infants. The aim of this study was twofold: (a) to validate ultrasound (US) visceral and subcutaneous-abdominal depths in assessing IA-AT and SCA-AT from MRI as the reference method in infants and (b) to analyze the association between US abdominal adiposity and anthropometric measures at ages 3 months and 12 months. Twenty-two infants underwent MRI and US measures of abdominal adiposity. Abdominal US parameters and anthropometric variables were assessed in the Cambridge Baby Growth Study (CBGS), n = 487 infants (23 girls) at age 3 months and n = 495 infants (237 girls) at 12 months. US visceral and subcutaneous-abdominal depths correlated with MRI quantified IA-AT (r = 0.48, P < 0.05) and SCA-AT (r = 0.71, P < 0.001) volumes, respectively. In CBGS, mean US-visceral depths increased by ~20 % between ages 3 and 12 months (P < 0.0001) and at both ages were lower in infants breast-fed at 3 months than in other infants. US-visceral depths at both 3 and 12 months were inversely related to skinfold thickness at birth (P = 0.03 and P = 0.009 at 3 and 12 months, resp.; adjusted for current skinfold thickness). In contrast, US-subcutaneous-abdominal depth at 3 months was positively related to skinfold thickness at birth (P = 0.004). US measures can rank infants with higher or lower IA-AT and SCA-AT. Contrasting patterns of association with visceral and subcutaneous-abdominal adiposities indicate that they may be differentially regulated in infancy.

Managing palliation in the neonatal unit

Professionals working in neonatology have a duty to act in the best interests of the infant. Normally, the goal of care is to sustain life and restore health. However, there are circumstances in which treatments that sustain life are not considered to be in the infants best interests. The Royal College of Paediatrics and Child Health (RCPCH) guidance, Withholding or Withdrawing Life Sustaining Treatment in Children: A Framework for Practice ,1 focuses on the decision making process. The British Association of Perinatal Medicine guidance, Palliative Care (Supportive and End of Life Care) A Framework for Clinical Practice in Perinatal Medicine ,2 sets out the principles of palliative care for infants. Following a systematic review of the literature we have developed evidence-based guidance for the practical aspects of caring for an infant receiving palliative and end of life care.3 We define palliative care as the ‘the active, total care of infants whose disease is not responsive to curative treatment; the goal of palliative care is achievement of the best possible quality of life for infants and their families’. Here we summarise the Guidance, a publication from Chelsea and Westminster NHS Foundation Trust developed in collaboration with the RCPCH. We established a Guidance Development Group (GDG). The Guidance was developed in accordance with AGREE II criteria. A systematic search and literature review were carried out focusing on five areas of management: 1. Care of the infant and family 2. Recognising and addressing conflict surrounding end of life decisions 3. Supporting parents and families 4. The postmortem examination and organ donation 5. Supporting staff members. The evidence gathered was synthesised and a series of recommendations were made, graded according to the level of evidence. Where the strength of the evidence was poor or absent, recommendations were based on informal consensus within the GDG. It is …