Adherence to the infant vitamin D supplementation policy in Ireland.

PURPOSE: From September 2010 until November 2019, Ireland's infant vitamin D supplementation policy recommended administration of 5 µg/day of vitamin D3 from birth to 12 months to all infants, regardless of feeding method. This study aims to examine policy adherence. METHODS: In the prospective COMBINE birth cohort study (recruited 2015-2017), detailed longitudinal supplement data were examined in 364 infants across the first year of life, according to product type, dose, frequency, and duration. Vitamin D supplement use at 2, 6, and 12 months in COMBINE was compared with the BASELINE cohort (recruited 2008-2011, n = 1949). RESULTS: In COMBINE, 92% of infants initiated supplementation at birth. The median supplementation duration was 51 (40, 52) weeks, with a range of 3-52 weeks. While supplementing, most parents (92%) used an exclusive vitamin D supplement as recommended and 88% gave 5 µg/day. Half (51%) gave vitamin D daily and a further 33% supplemented at least 3-6 times/week. Overall, 30% adhered fully to the policy, providing 5 µg vitamin D3 daily from birth to 12 months. A further 16% were broadly compliant, giving 5 µg frequently for the full 12 months. Vitamin D supplement use at 2, 6, and 12 months in COMBINE was 93%, 89%, and 72%, considerably higher than our earlier BASELINE cohort at 49%, 64%, and 44% at the same time points (all P < 0.001). CONCLUSIONS: We report a high level of vitamin D supplementation initiation at birth, with full to broad policy adherence among more than half of infants. There is scope to improve overall compliance by focusing on supplementation frequency.

Listeria Meningitis in an Immunocompetent Child: Case Report and Literature Review

We present a case of a 23 month-old boy presenting with fever, irritability and diarrhea who subsequently developed symptoms of photophobia and lethargy. Cerebrospinal fluid culture grew Listeria monocytogenes. Immunology investigations were normal. This patient had a complete and uncomplicated recovery. Listeria meningitis is a rare presentation in immunocompetent children, but should be considered in the setting of diarrhea, failure to respond to cephalosporin therapy, or suspected immunodeficiency.

Organisational factors and mortality after an emergency laparotomy: multilevel analysis of 39 903 National Emergency Laparotomy Audit patients.

BACKGROUND: Studies across healthcare systems have demonstrated between-hospital variation in survival after an emergency laparotomy. We postulate that this variation can be explained by differences in perioperative process delivery, underpinning organisational structures, and associated hospital characteristics. METHODS: We performed this nationwide, registry-based, prospective cohort study using data from the National Emergency Laparotomy Audit organisational and patient audit data sets. Outcome measures were all-cause 30- and 90-day postoperative mortality. We estimated adjusted odds ratios (ORs) for perioperative processes and organisational structures and characteristics by fitting multilevel logistic regression models. RESULTS: The cohort comprised 39 903 patients undergoing surgery at 185 hospitals. Controlling for case mix and clustering, a substantial proportion of between-hospital mortality variation was explained by differences in processes, infrastructure, and hospital characteristics. Perioperative care pathways [OR: 0.86; 95% confidence interval (CI): 0.76-0.96; and OR: 0.89; 95% CI: 0.81-0.99] and emergency surgical units (OR: 0.89; 95% CI: 0.80-0.99; and OR: 0.89; 95% CI: 0.81-0.98) were associated with reduced 30- and 90-day mortality, respectively. In contrast, infrequent consultant-delivered intraoperative care was associated with increased 30- and 90-day mortality (OR: 1.61; 95% CI: 1.01-2.56; and OR: 1.61; 95% CI: 1.08-2.39, respectively). Postoperative geriatric medicine review was associated with substantially lower mortality in older (≥70 yr) patients (OR: 0.35; 95% CI: 0.29-0.42; and OR: 0.64; 95% CI: 0.55-0.73, respectively). CONCLUSIONS: This multicentre study identified low-technology, readily implementable structures and processes that are associated with improved survival after an emergency laparotomy. Key components of pathways, perioperative medicine input, and specialist units require further investigation.

Development and internal validation of a novel risk adjustment model for adult patients undergoing emergency laparotomy surgery: the National Emergency Laparotomy Audit risk model.

BACKGROUND: Among patients undergoing emergency laparotomy, 30-day postoperative mortality is around 10-15%. The risk of death among these patients, however, varies greatly because of their clinical characteristics. We developed a risk prediction model for 30-day postoperative mortality to enable better comparison of outcomes between hospitals. METHODS: We analysed data from the National Emergency Laparotomy Audit (NELA) on patients having an emergency laparotomy between December 2013 and November 2015. A prediction model was developed using multivariable logistic regression, with potential risk factors identified from existing prediction models, national guidelines, and clinical experts. Continuous risk factors were transformed if necessary to reflect their non-linear relationship with 30-day mortality. The performance of the model was assessed in terms of its calibration and discrimination. Interval validation was conducted using bootstrap resampling. RESULTS: There were 4458 (11.5%) deaths within 30-days among the 38 830 patients undergoing emergency laparotomy. Variables associated with death included (among others): age, blood pressure, heart rate, physiological variables, malignancy, and ASA physical status classification. The predicted risk of death among patients ranged from 1% to 50%. The model demonstrated excellent calibration and discrimination, with a C-statistic of 0.863 (95% confidence interval, 0.858-0.867). The model retained its high discrimination during internal validation, with a bootstrap derived C-statistic of 0.861. CONCLUSIONS: The NELA risk prediction model for emergency laparotomies discriminates well between low- and high-risk patients and is suitable for producing risk-adjusted provider mortality statistics.

Association of nucleated red blood cells and severity of encephalopathy in normothermic and hypothermic infants.

AIM: To determine whether hypothermia alters the discriminative ability of postnatal nucleated red blood cells (NRBCs) to distinguish between mild and moderate/severely encephalopathic infants. METHODS: A prospective cohort study recruited full-term neonates with hypoxic ischaemic encephalopathy (HIE) from 2003 to 2012 (prehypothermic and hypothermic eras). The NRBC count was analysed in the first 24 h in all infants and compared between normothermic and hypothermic cohorts. The severity of encephalopathy was categorized using both clinical Sarnat score and continuous multichannel EEG. RESULTS: Eighty-six infants with HIE were included: in the normothermic group, 19 were clinically mild, 24 moderate/severe; in the hypothermic group, 22 were mild, 21 moderate/severe encephalopathy. NRBC count discriminated between mild and moderate/severe Sarnat scores in the normothermic group (p = 0.03) but not in the hypothermic group (p = 0.9). This change was due to a decrease in NRBCs among moderately encephalopathic infants in the hypothermic cohort. CONCLUSION: Postnatal NRBCs distinguished between mild and moderate/severe encephalopathy in normothermic infants but not in infants undergoing therapeutic hypothermia. We advise caution when using postnatal blood samples to study diagnostic biomarkers for HIE without first analysing the potential impact of hypothermia upon these markers.

Maternal Mid-Gestation Cytokine Dysregulation in Mothers of Children with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a developmental disorder characterised by deficits in social interactions and communication, with stereotypical and repetitive behaviours. Recent evidence suggests that maternal immune dysregulation may predispose offspring to ASD. Independent samples t-tests revealed downregulation of IL-17A concentrations in cases, when compared to controls, at both 15 weeks (p = 0.02), and 20 weeks (p = 0.02), which persisted at 20 weeks following adjustment for confounding variables. This adds to the growing body of evidence that maternal immune regulation may play a role in foetal neurodevelopment.

Neonatal encephalopathy: Etiologies other than hypoxic-ischemic encephalopathy.

Neonatal encephalopathy (NE) describes the clinical syndrome of a newborn with abnormal brain function that may result from a variety of etiologies. HIE should be distinguished from neonatal encephalopathy due to other causes using data gathered from the history, physical and neurological exam, and further investigations. Identifying the underlying cause of encephalopathy has important treatment implications. This review outlines conditions that cause NE and may be mistaken for HIE, along with their distinguishing clinical features, pathophysiology, investigations, and treatments. NE due to brain malformations, vascular causes, neuromuscular causes, genetic conditions, neurogenetic disorders and inborn errors of metabolism, central nervous system (CNS) and systemic infections, and toxic/metabolic disturbances are discussed.

Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome - A systematic review.

AIMS: Hypoxic ischaemic encephalopathy (HIE) remains a significant cause of long term neurodisability despite therapeutic hypothermia (TH). Infants with mild HIE, representing 50% of those with HIE, are perceived as low risk and are currently not eligible for TH [1]. This review examines the available evidence of outcome in term infants with mild HIE. METHODS: Medline, Embase and Cochrane Clinical Trials databases were searched in March 2017. Studies with well-defined HIE grading at birth and standardised neurodevelopmental assessment at ≥18 months were included. Abnormal outcome was defined as death, cerebral palsy or standardised neurodevelopmental test score more than 1 standard deviation below the mean. RESULT: Twenty studies were included. Abnormal outcome was reported in 86/341 (25%) of infants. There was insufficient evidence to examine the effect of TH on outcome. CONCLUSION: A significant proportion of infants with mild HIE have abnormal outcome at follow up.

Downstream mRNA Target Analysis in Neonatal Hypoxic-Ischaemic Encephalopathy Identifies Novel Marker of Severe Injury: a Proof of Concept Paper.

Human microRNA miR-374a is downregulated in the umbilical cord blood (UCB) of infants with hypoxic-ischaemic encephalopathy (HIE). The downstream targets of this microRNA (miRNA) are unclear, but one putative target is the activin-A receptor type IIb (ACVR2B). ACVR2B is required for activin-A function and previous reports have shown alterations of activin-A levels in neonatal HIE. Our aim was to investigate the expression of the potential downstream targets of miR-374a, activin-A and ACVR2B, at birth in a cohort of full-term infants with perinatal asphyxia (PA) only, and those with PA who developed clinical and electrographic HIE. UCB was drawn and processed immediately after delivery. Levels of serum activin-A were measured using ELISA. mRNA levels of ACVR2B in whole blood were quantified using qRT-PCR. Outcome was assessed at 3 years of age using standardised developmental assessment. In total, 171 infants were enrolled: 88 healthy controls, 56 PA and 27 HIE. A statistically significant elevation of median (IQR) ACVR2B was detected in infants with severe HIE compared to moderate/mild HIE, PA and control groups (3.3 (2.94-3.67) vs. 0.91 (0.55-1.21) vs. 0.88 (0.57-1.38) vs. 0.84 (0.74-1.24), p values = 0.04, 0.027 and 0.025, respectively). Although serum activin-A levels were elevated in infants with severe HIE, this elevation did not reach significance. ACVR2B may be a potential novel marker of HIE severity. This is the first study to examine the relationship between activin-A, its receptor AVCR2B and potentially upstream miRNA miR-374a in a cohort of carefully categorised and phenotyped infants. We have shown that miRNA analysis, combined with downstream target exploration, may yield novel biomarkers for the prediction of HIE severity.

Impact of maternal, antenatal and birth-associated factors on iron stores at birth: data from a prospective maternal-infant birth cohort.

BACKGROUND/OBJECTIVES: Low serum ferritin concentrations at birth, which reflect neonatal iron stores, track through to early childhood and have been associated with poorer neurodevelopmental outcomes. We aimed to identify maternal, antenatal and birth-associated factors that influence iron stores at birth in a prospective maternal-infant birth cohort. SUBJECTS/METHODS: In a population-based, longitudinal, birth cohort in Ireland, 413 maternal-infant dyads with prospectively collected lifestyle and clinical data from 15 weeks' gestation had umbilical cord serum ferritin concentrations measured. Regression models were developed to identify independent factors associated with cord ferritin concentrations. RESULTS: Median (IQR) cord ferritin concentrations were 185.7 (131.7, 385.5) µg/l, and 8% (n=33) of infants had low iron stores (ferritin <76 µg/l) at birth. Maternal obesity (BMI ⩾30 kg/m2) at 15 weeks' gestation (adj. estimate (95% confidence interval (CI)): -66.4 (-106.9, -25.9) µg/l, P<0.0001) and delivery by caesarean section (-38.8 (-70.2, -7.4) µg/l, P=0.016) were inversely associated with cord ferritin concentrations. In addition, maternal smoking at 15 weeks' gestation (adj. odds ratio (95% CI): 2.9 (1.2, 7), P=0.020) and being born small-for-gestational age (3.4 (1.3, 8.9), P=0.012) were associated with an increased risk of low iron stores (ferritin <76 µg/l) at birth. CONCLUSIONS: We have identified a number of potentially modifiable lifestyle factors that influence iron stores at birth, with the important role of overall maternal health and lifestyle during pregnancy highlighted. Public health policies targeting women of child-bearing age to improve nutrition and health outcomes should be prioritised for the health of the next generation.

Enzyme/prodrug gene therapy: comparison of cytosine deaminase/5-fluorocytosine versus thymidine kinase/ganciclovir enzyme/prodrug systems in a human colorectal carcinoma cell line.

We have been developing an enzyme/prodrug gene therapy approach for the treatment of primary and metastatic tumors in the liver. This system uses the cytosine deaminase/5-fluorocytosine (CD/5-FCyt) enzyme/prodrug combination. Another system that has received considerable attention is the herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) enzyme/prodrug combination. The purpose of the present study was to compare these two enzyme/prodrug systems. The human colorectal tumor cell line, WiDr, was genetically modified to express either the CD gene (WiDr/CD) or the HSV-TK gene (WiDr/TK). The IC50 (concentration of drug producing 50% inhibition of cell growth) for GCV was approximately 3.4 microM in WiDr/TK cells, while the IC50 for 5-FCyt was approximately 27 microM in WiDr/CD cells. In vivo antitumor studies were conducted using high but nontoxic levels of GCV (50 mg/kg/day) or 5-FCyt (500 mg/kg/day). When tumor xenografts were composed of 100% of cells expressing either HSV-TK or CD, 100% tumor-free animals were observed after GCV or 5-FCyt treatment, respectively. However, when only 10% of the tumor cells expressed HSV-TK, no antitumor effect by GCV treatment could be observed. In contrast, when tumors were composed of 4% of the cells expressing CD, 60% of the animals were tumor-free after 5-FCyt treatment. Transmission electron microscopy of the WiDr solid tumors revealed the presence of desmosomes but no gap junctions.

The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors: potential therapy for cancer.

The type I receptor tyrosine kinases constitute a family of transmembrane proteins involved in various aspects of cell growth and survival and have been implicated in the initiation and progression of several types of human malignancies. The best characterized of these proteins are the epidermal growth factor receptor (EGFR) and ErbB-2 (HER-2/neu). We have developed potent quinazoline and pyrido-[3,4-d]-pyrimidine small molecules that are dual inhibitors of ErbB-2 and EGFR. The compounds demonstrate potent in vitro inhibition of the ErbB-2 and EGFR kinase domains with IC(50)s <80 nM. Growth of ErbB-2- and EGFR-expressing tumor cell lines is inhibited at concentrations <0.5 microM. Selectivity for tumor cell growth inhibition versus normal human fibroblast growth inhibition ranges from 10- to >75-fold. Tumor growth in mouse s.c. xenograft models of the BT474 and HN5 cell lines is inhibited in a dose-responsive manner using oral doses of 10 and 30 mg/kg twice per day. In addition, the tested compounds caused a reduction of ErbB-2 and EGFR autophosphorylation in tumor fragments from these xenograft models. These data indicate that these compounds have potential use as therapy in the broad population of cancer patients overexpressing ErbB-2 and/or EGFR.

Early Cord Metabolite Index and Outcome in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy.

BACKGROUND: A 1H-NMR-derived metabolomic index based on early umbilical cord blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE) severity. OBJECTIVE: To evaluate whether this metabolite score can predict 3-year neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared with current standard biochemical and clinical markers. METHODS: From September 2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a single maternity hospital. Cord blood was drawn and biobanked at delivery. Neonates were monitored for development of encephalopathy both clinically and electrographically. Neurodevelopmental outcome was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death and cerebral palsy were also considered as abnormal end points. RESULTS: Thirty-one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42 months. No child had a severely abnormal BSID-III result. The metabolite index significantly correlated with outcome (ρ2 = 0.30, p < 0.01), which is robust to predict both severe outcome (area under the receiver operating characteristic curve: 0.92, p < 0.01) and intact survival (0.80, p = 0.01). There was no correlation between the index score and performance in the individual BSID-III subscales (cognitive, language, motor). CONCLUSIONS: The metabolite index outperformed other standard biochemical markers at birth for prediction of outcome at 3 years, but was not superior to EEG or the Sarnat score.

Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning.

Plasma and urinary levels of malondialdehyde-like products (MDA) and isoprostanes were identified as markers of in vivo lipid peroxidation in an animal model of CCl4 poisoning. We sought to determine the extent to which the formation of these oxidation products is influenced by inhibition of the cyclooxygenase enzymes which catalytically generate proinflammatory lipid peroxidation products known as prostaglandins and thromboxane. In the present studies, after induction of oxidant stress in rats with CCl4, lipid peroxidation products measured in plasma and urine demonstrate that isoprostanes and MDA can be partially inhibited by cyclooxygenase inhibitors, albeit to different extents. The lowering of isoprostane and MDA formation, however, may not to due primarily to the diminution of catalytic generation of isoprostanes or MDA by the cyclooxygenases but, rather, may be the result of the suppression of nonenzymatic lipid peroxidation. This is suggested since 8,12-iso-iPF2alpha-VI is also reduced by indomethacin, yet, unlike other isoprostanes and MDA, it is not generated catalytically by the cyclooxygenase. Thus, although the two cyclooxygenase inhibitors we tested have statistically significant effects on the measurements of both isoprostanes and MDA in this study, the results provide evidence that these lipid-degradation products primarily constitute markers of oxidative stress.

Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?

Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects.

Usefulness of biochemical screening of diabetic patients for hemochromatosis.

We assessed the prevalence of previously unrecognized hemochromatosis among patients in whom diabetes mellitus was diagnosed after the age of 30 yr, and we evaluated the positive predictive value of biochemical screening tests for hemochromatosis in diabetic subjects. Thirty-eight of 572 patients screened (6.6%) had a serum ferritin level greater than 324 micrograms/L; 16 patients had normal levels on repeat testing. Four patients' serum ferritin levels fell to less than 400 micrograms/L. Seven of 18 patients with a persistently elevated serum ferritin level did not undergo a liver biopsy because of a recognized cause of hyperferritenemia (carcinoma, alcoholism, or systemic lupus erythematosus). The diagnosis of hemochromatosis seemed certain in 1 of 3 patients who were not biopsied for technical reasons. Of 8 patients biopsied, 2 had hemochromatosis, 4 had fatty liver, 1 had hemosiderosis, and 1 had a chronic inflammatory cell infiltrate with no iron deposition. Of 4 patients with a raised transferrin saturation level, 2 had raised serum ferritin levels and hemochromatosis, 1 had raised serum ferritin and hemosiderosis on liver biopsy, and 1 had a normal transferrin saturation level on repeat testing. Two of 3 cases of hemochromatosis had other clinical markers of the condition. Therefore, routine screening of diabetic patients for hemochromatosis is not necessary, because patients with hemochromatosis will often have other clinical features of the disease. When screening diabetic patients for hemochromatosis, it should be remembered that a persistently raised serum ferritin level has a low positive predictive value (16.6%) and that a normal transferrin saturation level does not exclude the diagnosis.

The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo.

The epidermal growth factor receptor (EGFR) and ErbB-2 transmembrane tyrosine kinases are currently being targeted by various mechanisms in the treatment of cancer. GW2016 is a potent inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively. This report describes the efficacy in cell growth assays of GW2016 on human tumor cell lines overexpressing either EGFR or ErbB-2: HN5 (head and neck), A-431 (vulva), BT474 (breast), CaLu-3 (lung), and N87 (gastric). Normal human foreskin fibroblasts, nontumorigenic epithelial cells (HB4a), and nonoverexpressing tumor cells (MCF-7 and T47D) were tested as negative controls. After 3 days of compound exposure, average IC50 values for growth inhibition in the EGFR- and ErbB-2-overexpressing tumor cell lines were < 0.16 microM. The average selectivity for the tumor cells versus the human foreskin fibroblast cell line was 100-fold. Inhibition of EGFR and ErbB-2 receptor autophosphorylation and phosphorylation of the downstream modulator, AKT, was verified by Western blot analysis in the BT474 and HN5 cell lines. As a measure of cytotoxicity versus growth arrest, the HN5 and BT474 cells were assessed in an outgrowth assay after a transient exposure to GW2016. The cells were treated for 3 days in five concentrations of GW2016, and cell growth was monitored for an additional 12 days after removal of the compound. In each of these tumor cell lines, concentrations of GW2016 were reached where outgrowth did not occur. Furthermore, growth arrest and cell death were observed in parallel experiments, as determined by bromodeoxyuridine incorporation and propidium iodide staining. GW2016 treatment inhibited tumor xenograft growth of the HN5 and BT474 cells in a dose-responsive manner at 30 and 100 mg/kg orally, twice daily, with complete inhibition of tumor growth at the higher dose. Together, these results indicate that GW2016 achieves excellent potency on tumor cells with selectivity for tumor versus normal cells and suggest that GW2016 has value as a therapy for patients with tumors overexpressing either EGFR or ErbB-2.

Eating behaviour and weight status at 2 years of age: data from the Cork BASELINE Birth Cohort Study.

BACKGROUND/OBJECTIVES: To conduct an analysis of associations between eating behaviours and weight status in 2-year-old children. SUBJECTS/METHODS: Data were collected prospectively in the maternal-infant dyad Cork BASELINE Birth Cohort Study. The weight status of children aged 2 years (n=1189) was assigned using the International Obesity Task Force BMI cutoffs using measured heights and weights. Eating behaviours were assessed using the Children's Eating Behaviour Questionnaire (CEBQ). RESULTS: Eighty percent of children were of normal weight, 14% were overweight or obese and 6% were underweight. From the CEBQ, food approach behaviours including Enjoyment of Food (odds ratio (OR)=1.90, 95% confidence interval (CI)=1.46-2.48) and Food Responsiveness (OR=1.73, 95% CI=1.47-2.03) were associated with overweight/obesity (all P<0.001). The food avoidant behaviours of Satiety Responsiveness (OR=2.03, 95% CI=1.38-2.98) and Slowness in Eating (OR=1.44, 95% CI=1.01-2.04) were associated with underweight at 2 years (all P<0.05). CONCLUSIONS: Eating behaviours are associated with weight status as early as 2 years of age.

The effect of haemolysis on the metabolomic profile of umbilical cord blood.

OBJECTIVES: Metabolomics is defined as the comprehensive study of all low molecular weight biochemicals, (metabolites) present in an organism. Using a systems biology approach, metabolomics in umbilical cord blood (UCB) may offer insight into many perinatal disease processes by uniquely detecting rapid biochemical pathway alterations. In vitro haemolysis is a common technical problem affecting UCB sampling in the delivery room, and can hamper metabolomic analysis. The extent of metabolomic alteration which occurs in haemolysed samples is unknown. DESIGN AND METHODS: Visual haemolysis was designated by the laboratory technician using a standardised haemolysis index colour chart. The metabolomic profile of haemolysed and non-haemolysed UCB serum samples from 69 healthy term infants was compared using both (1)H-NMR and targeted DI and LC-MS/MS approach. RESULTS: We identified 43 metabolites that are significantly altered in visually haemolysed UCB samples, acylcarnitines (n=2), glycerophospholipids (n=23), sphingolipids (n=7), sugars (n=3), amino acids (n=4) and Krebs cycle intermediates (n=4). CONCLUSION: This information will be useful for researchers in the field of neonatal metabolomics to avoid false findings in the presence of haemolysis, to ensure reproducible and credible results.