The impact of the Covid-19 lockdown on the experiences and feeding practices of new mothers in the UK: Preliminary data from the COVID-19 New Mum Study.

BACKGROUND: The COVID-19 New Mum Study is recording maternal experiences and infant feeding during the UK lockdown. This report from week 1 of the survey describes and compares the delivery and post-natal experiences of women who delivered before (BL) versus during (DL) the lockdown. METHODS: Women living in the UK aged ≥18 years with an infant ≤12 months of age completed an anonymous online survey (https://is.gd/covid19newmumstudy). Information/links are shared via websites, social media and existing contacts. RESULTS: From 27.5.20-3.6.20, 1365 women provided data (94% white, 95% married/with partner, 66% degree/higher qualification, 86% living in house; 1049 (77%) delivered BL and 316 (23%) DL. Delivery mode, skin-to-skin contact and breastfeeding initiation did not differ between groups. DL women had shorter hospital stays (p < 0.001). 39% reported changes to their birth plan. Reflecting younger infant age, 59% of DL infants were exclusively breast-fed/mixed fed versus 39% of BL (p < 0.05). 13% reported a change in feeding; often related to lack of breastfeeding support, especially with practical problems. Important sources of feeding support were the partner (60%), health professional (50%) and online groups (47%). 45% of DL women reported insufficient feeding support. Among BL women, 57% and 69% reported decreased feeding support and childcare, respectively. 40% BL/45% DL women reported insufficient support with their own health, 8%/9% contacted a mental health professional; 11% reported their mental health was affected. 9% highlighted lack of contact/support from family and distress that they had missed seeing the baby. CONCLUSION: Lockdown has impacted maternal experiences, resulting in distress for many women. Our findings suggest the need for better infant feeding support, especially 'face-to-face' support for practical issues; and recognising and supporting mothers who are struggling with mental health challenges or other aspects of their health. The effectiveness of online versus face-to-face contact is currently uncertain, and requires further evaluation.

Bioelectric impedance vector analysis (BIVA) in hospitalised children; predictors and associations with clinical outcomes.

BACKGROUND: Clinical use of bioelectric impedance is limited by variability in hydration. Analysis of raw bioelectric impedance vectors (BIVA), resistance (R), reactance (Xc) and phase angle (PA) may be an alternative for monitoring disease progression/treatment. Clinical experience of BIVA in children is limited. We investigated predictors of BIVA and their ability to predict clinical outcomes in children with complex diagnoses. METHODS: R, Xc and PA were measured (BODYSTAT Quadscan 4000) on admission in 108 patients (4.6-16.8 years, mean 10.0). R and Xc were indexed by height (H) and BIVA-SDS for age and sex calculated using data from healthy children. Potential predictors and clinical outcomes (greater-than-expected length-of-stay (LOS), complications) were recorded. RESULTS: Mean R/H-SDS was significantly higher (0.99 (SD 1.32)) and PA-SDS lower (-1.22 (1.68))) than expected, with a wide range for all parameters. In multivariate models, the Strongkids risk category predicted R/H-SDS (adjusted mean for low, medium and high risk = 0.49, 1.28, 2.17, p = 0.009) and PA-SDS (adjusted mean -0.52, -1.53, -2.36, p = 0.01). BIVA-SDS were not significantly different in patients with or without adverse outcomes. CONCLUSIONS: These complex patients had abnormal mean BIVA-SDS suggestive of reduced hydration and poor cellular health according to conventional interpretation. R/H-SDS was higher and PA-SDS lower in those classified as higher malnutrition risk by the StrongKids tool. Further investigation in specific patient groups, including those with acute fluid shifts and using disease-specific outcomes, may better define the clinical role of BIV.

Body mass index adjustments to increase the validity of body fatness assessment in UK Black African and South Asian children.

BACKGROUND/OBJECTIVES: Body mass index (BMI) (weight per height2) is the most widely used marker of childhood obesity and total body fatness (BF). However, its validity is limited, especially in children of South Asian and Black African origins. We aimed to quantify BMI adjustments needed for UK children of Black African and South Asian origins so that adjusted BMI related to BF in the same way as for White European children. METHODS: We used data from four recent UK studies that made deuterium dilution BF measurements in UK children of White European, South Asian and Black African origins. A height-standardized fat mass index (FMI) was derived to represent BF. Linear regression models were then fitted, separately for boys and girls, to quantify ethnic differences in BMI-FMI relationships and to provide ethnic-specific BMI adjustments. RESULTS: We restricted analyses to 4-12 year olds, to whom a single consistent FMI (fat mass per height5) could be applied. BMI consistently underestimated BF in South Asians, requiring positive BMI adjustments of +1.12 kg m-2 (95% confidence interval (CI): 0.83, 1.41 kg m-2; P<0.0001) for boys and +1.07 kg m-2 (95% CI: 0.74, 1.39 kg m-2; P<0.0001) for girls of all age groups and FMI levels. BMI overestimated BF in Black Africans, requiring negative BMI adjustments for Black African children. However, these were complex because there were statistically significant interactions between Black African ethnicity and FMI (P=0.004 boys; P=0.003 girls) and also between FMI and age group (P<0.0001 for boys and girls). BMI adjustments therefore varied by age group and FMI level (and indirectly BMI); the largest adjustments were in younger children with higher unadjusted BMI and the smallest in older children with lower unadjusted BMI. CONCLUSIONS: BMI underestimated BF in South Asians and overestimated BF in Black Africans. Ethnic-specific adjustments, increasing BMI in South Asians and reducing BMI in Black Africans, can improve the accuracy of BF assessment in these children.

Predictors of expressed breast milk volume in mothers expressing milk for their preterm infant.

BACKGROUND: An understanding of predictors of breast milk production may enable the provision of better advice and support to mothers with preterm infants who may need to express milk for long periods. OBJECTIVE: To investigate factors predicting the amount of milk expressed by mothers for their preterm infant (1) during the first 10 days and (2) during the infant's whole hospital stay. METHODS: 62 mothers with preterm infants <34 weeks who participated in a randomised trial comparing two breast pumps completed 10-day diaries including weight of milk expressed and questionnaires giving their opinion of the breast pump; 47 mothers provided data on milk expression up to the infant's hospital discharge. RESULTS: Significant predictors of 10-day milk weight in multivariate models were the number of episodes of 'breast feeding' (17 g (95% CI 8 to 26, p=0.001) increase per episode), the use of double versus single pumping (109 (31-186, p=0.007) g/day more) and the number of complete daily records (17 (1-33, p=0.04) g increase/day). Significant multivariate predictors of total milk production were double versus single pumping (491 (55) mL/day vs 266 (44) mL/day), expressing 500 mL/day by day 10 (525 (53) mL/day vs 232 (43) mL/day) and a higher score for breast pump 'comfort' (best=489 (39) mL/day, middle=335 (57) mL/day, worst=311 (78) mL/day). CONCLUSIONS: These results suggest that relatively simple, modifiable factors can favourably impact milk production in the neonatal intensive care unit setting and emphasise the importance of double pumping, early establishment of milk production and design features of the breast pump that promote comfort. TRIAL REGISTRATION NUMBER: NCT00887991.

Body composition in young female eating-disorder patients with severe weight loss and controls: evidence from the four-component model and evaluation of DXA.

BACKGROUND/OBJECTIVES: Whether fat-free mass (FFM) and its components are depleted in eating-disorder (ED) patients is uncertain. Dual energy X-ray absorptiometry (DXA) is widely used to assess body composition in pediatric ED patients; however, its accuracy in underweight populations remains unknown. We aimed (1) to assess body composition of young females with ED involving substantial weight loss, relative to healthy controls using the four-component (4C) model, and (2) to explore the validity of DXA body composition assessment in ED patients. SUBJECTS/METHODS: Body composition of 13 females with ED and 117 controls, aged 10-18 years, was investigated using the 4C model. Accuracy of DXA for estimation of FFM and fat mass (FM) was tested using the approach of Bland and Altman. RESULTS: Adjusting for age, height and pubertal stage, ED patients had significantly lower whole-body FM, FFM, protein mass (PM) and mineral mass (MM) compared with controls. Trunk and limb FM and limb lean soft tissue were significantly lower in ED patients. However, no significant difference in the hydration of FFM was detected. Compared with the 4C model, DXA overestimated FM by 5 ± 36% and underestimated FFM by 1 ± 9% in ED patients. CONCLUSION: Our study confirms that ED patients are depleted not only in FM but also in FFM, PM and MM. DXA has limitations for estimating body composition in individual young female ED patients.

Acute effects of violent video-game playing on blood pressure and appetite perception in normal-weight young men: a randomized controlled trial.

Watching television and playing video game being seated represent sedentary behaviours and increase the risk of weight gain and hypertension. We investigated the acute effects of violent and non-violent video-game playing on blood pressure (BP), appetite perception and food preferences. Forty-eight young, normal-weight men (age: 23.1±1.9 years; body mass index: 22.5±1.9 kg/m(2)) participated in a three-arm, randomized trial. Subjects played a violent video game, a competitive, non-violent video game or watched TV for 1 h. Measurements of BP, stress and appetite perception were recorded before a standardized meal (∼300 kcal) and then repeated every 15 min throughout the intervention. Violent video-game playing was associated with a significant increase in diastolic BP (Δ±s.d.=+7.5±5.8 mm Hg; P=0.04) compared with the other two groups. Subjects playing violent video games felt less full (P=0.02) and reported a tendency towards sweet food consumption. Video games involving violence appear to be associated with significant effects on BP and appetite perceptions compared with non-violent gaming or watching TV.

Breast-feeding and formula feeding in healthy term infants and bone health at age 10 years.

Few studies have investigated the effects of infant nutrition on later bone health in term infants, although low sn-2 palmitate in infant formulas has been shown to result in the formation of stool fatty acid soaps, reduced Ca absorption and lower bone mass in the short term. To investigate the effect of (1) breast-feeding (BF) and (2) the type of infant formula (standard fat blend v. high-sn-2 fat blend) on bone mass at age 10 years, anthropometry and bone mass (from dual-energy X-ray absorptiometry (GE Lunar Prodigy); lumbar spine (LS) and total body less head; adjusted for size (bone mineral apparent density standard deviation score (SDS) and regression)) were measured in 10-year-old subjects born at term and either breast-fed (n 34) or randomised to a standard control formula (n 27) or a high-sn-2 palmitate formula (n 30) for the first 12 weeks of life. At follow-up, previously BF children were older but lighter (by 0·5 SDS, P= 0·03) than formula-fed children with a lower LS bone mineral density SDS (by 0·44, P= 0·03), but size-adjusted bone mass did not differ. There were no significant differences in bone mass between the formula-fed groups. These findings suggest that there is no significant effect of BF or high-sn-2 infant formula on size-adjusted bone mass in mid-childhood, and that the effects of infant nutrition on bone mass previously reported may be confined to the short term. A larger study would be required to exclude smaller effects.

Is a single bioelectrical impedance equation valid for children of wide ranges of age, pubertal status and nutritional status? Evidence from the 4-component model.

BACKGROUND/OBJECTIVES: Bioelectrical impedance analysis (BIA) is widely used to predict body composition in paediatric research and clinical practice. Many equations have been published, but provide inconsistent predictions. AIMS: To test whether a single equation for lean mass (LM) estimation from BIA is appropriate across wide ranges of age, pubertal status and nutritional status, by testing whether specific groups differ in the slope or intercept of the equation. SUBJECTS/METHODS: In 547 healthy individuals aged 4-24 years (240 males), we collected data on body mass (BM) and height (HT), and lean mass (LM) using the 4-component model. Impedance (Z) was measured using TANITA BC418MA instrumentation. LM was regressed on HT(2)/Z. Multiple regression analysis was conducted to investigate whether groups based on gender, age, pubertal status or nutritional status differed in the association of LM with HT(2)/Z. RESULTS: BM ranged from 5 to 128 kg. HT(2)/Z was a strong predictor of LM (r (2)=0.953, s.e.e.=2.9 kg). There was little evidence of a sex difference in this relationship, however, children aged 4-7 years and 16-19 years differed significantly from other age groups in regression slopes and intercepts. Similar variability was encountered for pubertal stage, but not for nutritional status. CONCLUSIONS: No single BIA equation applies across the age range 4-24 years. At certain ages or pubertal stages, the slope and intercept of the equation relating LM to HT(2)/Z alters. Failure to address such age effects is likely to result in poor accuracy of BIA (errors of several kg) for longitudinal studies of change in body composition.

Clinical safety assessment of infant nutrition.

Data on clinical safety and efficacy are ideally collected in a randomized clinical trial or, failing this, an observational study. Suitable outcomes vary depending on the intervention and population group, and certain outcomes such as growth may test both efficacy and safety. The use of growth as an important safety outcome has some limitations since it is currently not clear what represents an 'optimal' growth pattern. Several issues currently make the conduct and interpretation of infant nutrition trials challenging. These include difficulties in recruiting exclusively formula-fed infants, particularly given the emotive nature of infant feeding; the involvement of industry leading to real or perceived conflicts of interest; increased regulation and bureaucracy; and particular issues with long-term follow-up studies, notably cohort attrition. This paper addresses the implications of these issues and some potential solutions.

Dual energy x-ray absorptiometry and quantitative ultrasound are not interchangeable in diagnosing abnormal bones.

OBJECTIVE: To evaluate whether dual energy x-ray absorptiometry (DXA) and quantitative ultrasound (QUS) classify the same children as 'abnormal' (SD (z) score (SDS) ≤-2). METHODS: Speed of sound (SOS) was measured at the radius and tibia using QUS and lumbar spine bone mineral density (BMD) using DXA in 621 subjects aged 5-20 years; healthy 412, cystic fibrosis 117 and obese 92. RESULTS: BMD SDS positively (p<0.001) and tibia SOS SDS negatively correlated with size (p<0.05). Disagreement between DXA and QUS for 'abnormal' scans occurred in 6-31%. Those with abnormal BMD and normal SOS SDS had lower mean BMI SDS than those with normal BMD and abnormal SOS SDS. SOS measurements were unobtainable in some children, especially in the obese group. CONCLUSIONS: DXA and QUS identify different individuals as 'abnormal'. Agreement between BMD and tibia SOS is lower in obese subjects. Without a gold-standard, it is difficult to determine which technique is more 'correct'.

Infant feeding bottle design, growth and behaviour: results from a randomised trial.

BACKGROUND: Whether the design of an anti-vacuum infant feeding bottle influences infant milk intake, growth or behavior is unknown, and was the subject of this randomized trial. SUBJECTS: 63 (36 male) healthy, exclusively formula-fed term infants. INTERVENTION: Randomisation to use Bottle A (n = 31), one-way air valve: Philips Avent) versus Bottle B (n = 32), internal venting system: Dr Browns). 74 breast-fed reference infants were recruited, with randomisation (n = 24) to bottle A (n = 11) or B (n = 13) if bottle-feeding was subsequently introduced. Randomisation: stratified by gender and parity; computer-based telephone randomisation by independent clinical trials unit. SETTING: Infant home. PRIMARY OUTCOME MEASURE: infant weight gain to 4 weeks. SECONDARY OUTCOMES: (i) milk intake (ii) infant behaviour measured at 2 weeks (validated 3-day diary); (iii) risk of infection; (iv) continuation of breastfeeding following introduction of mixed feeding. RESULTS: Number analysed for primary outcome: Bottle A n = 29, Bottle B n = 25. PRIMARY OUTCOME: There was no significant difference in weight gain between randomised groups (0-4 weeks Bottle A 0.74 (SD 1.2) SDS versus bottle B 0.51 (0.39), mean difference 0.23 (95% CI -0.31 to 0.77). SECONDARY OUTCOMES: Infants using bottle A had significantly less reported fussing (mean 46 versus 74 minutes/day, p < 0.05) than those using bottle B. There was no significant difference in any other outcome measure. Breast-fed reference group: There were no significant differences in primary or secondary outcomes between breast-fed and formula fed infants. The likelyhood of breastfeeding at 3 months was not significantly different in infants subsequently randomised to bottle A or B. CONCLUSION: Bottle design may have short-term effects on infant behaviour which merit further investigation. No significant effects were seen on milk intake or growth; confidence in these findings is limited by the small sample size and this needs confirmation in a larger study. TRIAL REGISTRATION: Clinical Trials.gov NCT00325208.

The evidence for public health recommendations on infant feeding.

Public health recommendations should be based on the best available scientific evidence, and this necessitates careful appraisal of the available data and management of scientific uncertainty. This paper discusses the difficulties in collecting and interpreting scientific data on infant feeding, in particular the fact that since it is not feasible to randomise healthy infants to be breast or formula-fed, the majority of available data come from observational studies with associated methodological limitations. The scientific evidence available to underpin recommendations for breastfeeding and for 6months exclusive breastfeeding are presented in the context of these limitations, noting disagreement between expert groups considering the same scientific data. Finally, the use of science to formulate infant feeding recommendations, and communication of information, including scientific uncertainty, to parents are discussed.

Association between infant correlates of impulsivity--surgency (extraversion)--and early infant growth.

Increasing evidence suggests that rapid postnatal weight gain is associated with increased risks of being overweight or obese later in life and of co-morbidities, such as diabetes, the metabolic syndrome and cardiovascular disease. In children as young as two years of age, as well as in adults, an appetitive system-linked impulsivity trait has been demonstrated to be linked with increased overweight, and postulated to act via increased food intake, through greater responsiveness to food and lower self-inhibitory control skills. In this study, we hypothesized that growth in infancy, a critical window for metabolic programming, would be predicted by measures of infant surgency/extraversion, assessed using the Rothbart Infant Behaviour Questionnaire (revised version). Anthropometry was measured at birth and at 3, 6 and 12 months, and weight gains expressed as increases in standardized scores, allowing for adjustment for gender and age, including gestational age. We used conditional weight (CW), a residual of current weight regressed on prior weights, to represent deviations from expected weight gains, from 0 to 3, 3 to 6 and 6 to 12 months. Controlling for significant sociodemographic correlations, multiple regression analyses showed significant prediction of CWs at 3 months but not of CWs at 6 or 12 months by surgency/extraversion. These pilot findings of association between infant growth, during a critical period, and surgency/extraversion, early correlates of impulsivity, warrant further investigation, to ascertain implications for childhood and later weight and body composition.

Evaluation of lean tissue density for use in air displacement plethysmography in obese children and adolescents.

BACKGROUND/OBJECTIVES: Body composition techniques are required for monitoring response to treatment in individual obese children, and assessing the efficacy of weight loss programmes. Densitometry is readily undertaken, using air displacement plethysmography (ADP), but requires appropriate information on the density of lean tissue (D(LT)). The aims of this study were to develop predictive equations for D(LT) in obese children and adolescents, and to test the accuracy of ADP when using such predicted D(LT) values in an independent longitudinal sample using the four-component model as the reference method. SUBJECTS/METHODS: Equations for the prediction of D(LT) from age, gender and body mass index standard deviation score were developed in 105 children (39 boys). Accuracy of ADP, when incorporating predicted D(LT) values, was tested for baseline body composition and its change over time in a separate sample of 51 children (20 boys). RESULTS: The predictive equation explained 33% of the variance in D(LT). Fat mass obtained from ADP using such predicted values had a mean (s.d.) bias of 0.32 (1.39) kg, nonsignificant, whereas change in fat mass had an error of -0.25 (1.38) kg, nonsignificant. Hydration was strongly correlated with D(LT). CONCLUSIONS: Use of ADP with predicted D(LT) values was associated with nonsignificant bias when estimating fat mass and its change over time. This study aids the application of ADP in childhood obesity research and clinical practise. The limits of agreement (±2.8 kg) relative to four-component values are moderately better than those for X-ray absorptiometry (±3.2 kg). Further improvement to accuracy would require assessment of lean tissue hydration by bioelectrical impedance.

Prenatal and postnatal programming of body composition in obese children and adolescents: evidence from anthropometry, DXA and the 4-component model.

BACKGROUND: Low-birth weight has been proposed to programme central adiposity in childhood. However, there is little information on associations between fetal weight gain and fat distribution within obese individuals. OBJECTIVES: To investigate associations between birth weight and postnatal weight gain with body composition in a sample of obese children and adolescents. SUBJECTS AND METHODS: Body composition was measured using anthropometry, dual-emission X-ray absorptiometry and the 4-component model in 45 male and 76 female obese individuals aged 5-22 years. General linear models were used to investigate associations between birth weight standard deviation score (SDS), or change in weight SDS between birth and follow-up, and body composition, adjusting for age, pubertal status, height and gender. RESULTS: Birth weight SDS ranged from -1.86 to 3.46, and was inversely associated with current weight SDS after adjustment for height SDS. Birth weight SDS was weakly associated with waist and hip girths, but not waist-hip ratio or trunk fat, after adjusting for age, height, pubertal status and gender. Change in weight SDS was strongly associated with total and central adiposity. CONCLUSIONS: Despite incorporating substantial variability, birth weight SDS was only a weak predictor of tissue masses and their distribution in obese children. Variability in central adiposity was more strongly associated with the magnitude of postnatal growth, which in turn was weakly inversely associated with birth weight SDS. In a population uniformly characterised by excess body weight, postnatal weight gain exerted the dominant impact on adiposity and fat distribution.

Evaluation of DXA against the four-component model of body composition in obese children and adolescents aged 5-21 years.

BACKGROUND: Body composition is increasingly measured in pediatric obese patients. Although dual-energy X-ray absorptiometry (DXA) is widely available, and is precise, its accuracy for body composition assessment in obese children remains untested. OBJECTIVE: We aimed to evaluate DXA against the four-component (4C) model in obese children and adolescents in both cross-sectional and longitudinal contexts. DESIGN: Body composition was measured by DXA (Lunar Prodigy) and the 4C model in 174 obese individuals aged 5-21 years, of whom 66 had a second measurement within 1.4 years. The Bland-Altman method was used to assess agreement between techniques for baseline body composition and change therein. RESULTS: A significant minority of individuals (n=21) could not be scanned successfully due to their large size. At baseline, in 153 individuals with complete data, DXA significantly overestimated fat mass (FM; Delta=0.9, s.d. 2.1 kg, P<0.0001) and underestimated lean mass (LM; Delta=-1.0, s.d. 2.1 kg, P<0.0001). Multiple regression analysis showed that gender, puberty status, LM and FM were associated with the magnitude of the bias. In the longitudinal study of 51 individuals, the mean bias in change in fat or LM did not differ significantly from zero (FM: Delta=-0.02, P=0.9; LM: Delta=0.04, P=0.8), however limits of agreement were wide (FM: +/-3.2 kg; LM: +/-3.0 kg). The proportion of variance in the reference values explained by DXA was 76% for change in FM and 43% for change in LM. CONCLUSIONS: There are limitations to the accuracy of DXA using Lunar Prodigy for assessing body composition or changes therein in obese children. The causes of differential bias include variability in the magnitude of tissue masses, and stage of pubertal development. Further work is required to evaluate this scenario for other DXA models and manufacturers.

Quantitative ultrasound (QUS): a useful tool for monitoring bone health in preterm infants?

UNLABELLED: Preterm infants are at risk of osteopenia and metabolic bone disease (MBD) of prematurity. There is a need for simple, reliable methods to detect and monitor this condition. AIMS: The aims were first to describe longitudinal changes in speed of sound (SOS) measured using quantitative ultrasound (QUS; Sunlight Omnisense, Israel) in preterm neonates: and second to determine whether SOS predicts the development of MBD. METHODS: SOS was measured in the tibia in 99 preterm infants (mean (SD)) gestation 29.7 (3.6) weeks; birthweight 1340 (550) g, with longitudinal measurements in 75. SOS z-scores were generated for gestation and sex. Clinical data were recorded. RESULTS: Baseline SOS (but not SOS z-score) was positively associated with gestational age. SOS and SOS z-score fell with age. In multivariate models, peak ALP, minimum phosphate concentrations and markers of illness severity were not predictors of the fall in SOS z-score, and baseline SOS measurements did not predict the development of high peak ALP or low phosphate. INTERPRETATION: Speed of sound measurements fell with age in all infants, but we found no evidence that this measurement could predict biochemical indicators of MBD. We cannot exclude the possibility that this technique could be useful in monitoring the response to interventions designed to improve bone health in this population.

Reduction in bone mineral density in glycogenosis type III may be due to a mixed muscle and bone deficit.

UNLABELLED: Glycogen storage disease type III (GSD III; OMIM 232400) is an autosomal recessive deficiency of the glycogen debrancher enzyme, amylo-1,6-glucosidase (EC 3.2.1.33). Patients with other hepatic glycogenoses are known to have reduced bone mineral content (BMC) and to be at consequent risk of fractures. They have key metabolic differences from GSD III patients, however. This study examines bone density and metabolism in 15 GSD III patients (6 female) from childhood to adulthood (aged 10-34 years). The results demonstrate that patients with GSD III have low bone mass at all skeletal sites compared with healthy individuals of the same age and sex, with a significant proportion (40-64%) having BMD > 2 standard deviations below the mean for whole body and lumbar spine. The deficiency seems to be attributable to a mixed muscle andbone deficit. Lower bone mass was found at all sites for GSD IIIa patients (combined liver and muscle defect) compared with GSD IIIb patients (liver only defect). CONCLUSION: Patients with GSD III have significantly abnormal bone mass, placing them at increased risk of potential fracture. The underlying mechanism is probably multifactorial with contributions from abnormal muscle physiology, abnormal metabolic milieu and altered nutrition affecting micronutrient intake. Therapies need to address all these factors to be successful.

Undercarboxylated osteocalcin and bone mass in 8-12 year old children with cystic fibrosis.

UNLABELLED: Young adults with cystic fibrosis (CF) frequently develop bone disease. One suggested aetiological factor is suboptimal vitamin K status with impaired carboxylation of osteocalcin and abnormal bone formation. METHODS: We measured bone mineralization and turnover in thirty-two 8-12 year old CF patients (14 boys) using Dual Energy X-ray absorptiometry (whole body (WB) and lumbar spine (LS)), 25-OH Vitamin D, PTH and markers of bone formation (plasma osteocalcin, N-terminal pro-peptide of type 1 collagen (P1NP)), plus an indirect measure of vitamin K status, undercarboxylated osteocalcin (uc-OC). RESULTS: LS bone mineral density (BMD) standard deviation (SD) scores were < -1.0 in 20% of subjects. Size-adjusted LS and WB bone mass was normal. Compared to reference data, % uc-OC was high and P1NP low. LS bone mass was predicted by % uc-OC but not other markers (0.4% decrease in size-adjusted LSBMC (p=0.05); 0.04 SD decrease in LSBMAD (p=0.04) per 1% increase in uc-OC). CONCLUSION: Markers suggestive of sub-optimal vitamin K status and low bone formation were present despite normal size-adjusted bone mass. The association between LSBMC and % uc-OC is consistent with the hypothesis that sub-optimal vitamin K status is a risk factor for CF bone disease. This should ideally be investigated in an intervention trial.

Session 6: Infant nutrition: future research developments in Europe EARNEST, the early nutrition programming project: EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research.

Increasing evidence from lifetime experimental studies in animals and observational and experimental studies in human subjects suggests that pre- and postnatal nutrition programme long-term health. However, key unanswered questions remain on the extent of early-life programming in contemporary European populations, relevant nutritional exposures, critical time periods, mechanisms and the effectiveness of interventions to prevent or reverse programming effects. The EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST) consortium brings together a multi-disciplinary team of scientists from European research institutions in an integrated programme of work that includes experimental studies in human subjects, modern prospective observational studies and mechanistic animal work including physiological studies, cell-culture models and molecular techniques. Theme 1 tests early nutritional programming of disease in human subjects, measuring disease markers in childhood and early adulthood in nineteen randomised controlled trials of nutritional interventions in pregnancy and infancy. Theme 2 examines associations between early nutrition and later outcomes in large modern European population-based prospective studies, with detailed measures of diet in pregnancy and early life. Theme 3 uses animal, cellular and molecular techniques to study lifetime effects of early nutrition. Biomedical studies are complemented by studies of the social and economic importance of programming (themes 4 and 5), and themes encouraging integration, communication, training and wealth creation. The project aims to: help formulate policies on the composition and testing of infant foods; improve the nutritional value of infant formulas; identify interventions to prevent and reverse adverse early nutritional programming. In addition, it has the potential to develop new products through industrial partnerships, generate information on the social and economic cost of programming in Europe and help maintain Europe's lead in this critical area of research.