Neonatal emergency transport teams and general emergency departments: Who will intubate the neonate?

OBJECTIVE: Confidence treating critically ill infants presenting to general ED may be limited by inexperience, with procedures deferred until specialised transport teams arrive. METHODS: This retrospective cohort study analysed critical procedures performed by referring ED physicians, compared with a neonatal emergency transport service, on infants transferred over a 12-month period. RESULTS: All 150 eligible infants were included, with median (interquartile range) age 28 (16-43) days. Forty critical procedures were performed in this cohort. Of 26 intubations, 17 (65%) were performed by local ED physicians. CONCLUSION: Referring ED physicians perform the majority of critical procedures where infants require inter-hospital transfer by neonatal emergency transport service.

Diagnosing uncertainty, producing neonatal abstinence syndrome.

The use of alcohol and other drugs during pregnancy is understood to be an important public health problem. One way in which this problem is expressed and responded to is via the identification and treatment of neonatal abstinence syndrome (NAS). In this article, we demonstrate how the processes of anticipating, identifying and responding to NAS are characterised by significant uncertainty among parents and health and social care practitioners. We draw on interviews with 16 parents who had recently had a baby at risk of NAS, and multidisciplinary focus groups with 27 health and social care professionals, held in Scotland, UK. NAS, and drug use in pregnancy, is a fraught and complex arena. Parents in the UK who use opioids risk losing custody of children, and must navigate a high degree of surveillance, governance and marginalisation. We suggest that considering NAS as a social diagnosis, further informed by Mol's political ontology of 'multiple' bodies/diseases, may help to produce clinical and social responses to uncertainty which avoid, rather than promote, further marginalisation of parents who use drugs. One such response is to develop a culture of relationship-based care which empowers both service providers and service users to challenge existing practice and decision-making.

Problematisation and regulation: Bodies, risk, and recovery within the context of Neonatal Abstinence Syndrome.

BACKGROUND: Neonatal Abstinence Syndrome (NAS) is an anticipated effect of maternal drug use during pregnancy. Yet it remains a contested area of policy and practice. In this paper, we contribute to ongoing debates about the way NAS is understood and responded to, through different treatment regimes, or logics of care. Our analysis examines the role of risk and recovery discourses, and the way in which the bodies of women and babies are conceptualised within these. METHODS: Qualitative interviews with 16 parents (9 mothers, 7 fathers) and four focus groups with 27 health and social care professionals based in Scotland. All the mothers were prescribed opioid replacement therapy and parents were interviewed after their baby was born. Data collection explored understandings about the causes and consequences of NAS and experiences of preparing for, and caring for, a baby with NAS. Data were analysed using a narrative and discursive approach. RESULTS: Parent and professional accounts simultaneously upheld and subverted logics of care which govern maternal drug use and the assessment and care of mother and baby. Despite acknowledging the unpredictability of NAS symptoms and the inability of the women who are opioid-dependent to prevent NAS, logics of care centred on 'proving' risk and recovery. Strategies appealed to the need for caution, intervening and control, and obscured alternative logics of care that focus on improving support for mother-infant dyads and the family as a whole. CONCLUSION: Differing notions of risk and recovery that govern maternal drug use, child welfare and family life both compel and trouble all logics of care. The contentious nature of NAS reflects wider socio-political and moral agendas that ultimately have little to do with meeting the needs of mothers and babies. Fundamental changes in the principles, quality and delivery of care could improve outcomes for families affected by NAS.

Implications of a negative abdominal CT in the management of pediatric blunt abdominal trauma.

BACKGROUND: No consensus exists on management of children with a negative trauma CT following blunt abdominal trauma (BAT). Asymptomatic children are frequently "admitted for observation" following negative CT owing to concerns about missing an intraabdominal injury (IAI) without evidence for this practice. We aimed to investigate the feasibility of discharge following a negative CT scan in children sustaining blunt abdominal trauma. METHODS: Retrospective audit at a UK paediatric major trauma center and review of the literature. RESULTS: 108 patients were included (median age 11y; 60% male). Commonest mechanisms of injury: road traffic collisions (61 patients; 56%) and falls from a height (37; 34%). 40 (37%) had a normal CT scan, of whom 6 (15%) were discharged from ED. The remaining 34 patients were admitted, of whom 14 (41%) were discharged within 24h. The other 20 children were admitted for other specialty input. None of the 108 children had a missed IAI or reattended with suspicion of IAI. The NPV for CT to detect IAI was 100% (95% CI: 96%-100%). The literature search identified 3 observational cohort studies and 2 patient groups contained in a systematic review (total of 9149 patients with normal CT abdomen after BAT). Only 9 (<0.1%) patients required operative intervention for missed IAI. The NPV for CT to detect IAI was 99.6%-99.8% (95% CI 99%-100%). CONCLUSION: Our study and literature review demonstrate that asymptomatic children with a normal abdominal CT scan in the ED are very unlikely to have IAI and that the NPV of CT is very high (96%-100%). Direct discharge from the ED is possible for asymptomatic children with a negative CT following blunt abdominal trauma, as long as no other reasons for admission exist and should be accompanied by safety-net advice. LEVEL OF EVIDENCE STATEMENT: This is a level II evidence study. In itself it is a retrospective study, with the literature review including one large, high-quality prospective cohort study, and further prospective cohort studies of ordinary quality.

Relationship between insulin-like growth factor I levels, early insulin treatment, and clinical outcomes of very low birth weight infants.

OBJECTIVES: Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. STUDY DESIGN: Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). RESULTS: Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 µg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). CONCLUSIONS: Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.

Levels of neonatal thyroid hormone in preterm infants and neurodevelopmental outcome at 5 1/2 years: millennium cohort study.

CONTEXT: Transient hypothyroxinemia is the commonest thyroid dysfunction of premature infants, and recent studies have found adverse associations with neurodevelopment. The validity of these associations is unclear because the studies adjusted for a differing range of factors likely to influence neurodevelopment. OBJECTIVE: The aim was to describe the association of transient hypothyroxinemia with neurodevelopment at 5.5 yr corrected age. DESIGN: We conducted a follow-up study of a cohort of infants born in Scotland from 1999 to 2001 ≤34 wk gestation. MAIN OUTCOME MEASURES: We measured scores on the McCarthy scale adjusted for 26 influences of neurodevelopment including parental intellect, home environment, breast or formula fed, growth retardation, and use of postnatal drugs. RESULTS: A total of 442 infants ≤34 wk gestation who had serum T(4) measurements on postnatal d 7, 14, or 28 and 100 term infants who had serum T(4) measured in cord blood were followed up at 5.5 yr. Infants with hypothyroxinemia (T(4) level ≤ 10th percentile on d 7, 14, or 28 corrected for gestational age) scored significantly lower than euthyroid infants (T(4) level greater than the 10th percentile and less than the 90th percentile on all days) on all McCarthy scales, except the quantitative. After adjustment for confounders of neurodevelopment, hypothyroxinemic infants scored significantly lower than euthyroid infants on the general cognitive and verbal scales. CONCLUSIONS: Our findings do not support the view that the hypothyroxinemic state, in the context of this analysis, is harmless in preterm infants. Many factors contribute both to the etiology of hypothyroxinemia and neurodevelopment; strategies for correction of hypothyroxinemia should acknowledge its complex etiology and not rely solely on one approach.

Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analyses of the NIRTURE study.

OBJECTIVES: To investigate the prevalence and determinants of hyperglycemia in the preterm population, as part of the Neonatal Insulin Therapy in Europe (NIRTURE) Trial. STUDY DESIGN: We conducted prospective cohort analyses of continuous glucose monitoring data from control infants participating in an international randomized controlled trial. Data were collected from 188 very low birth weight infants (<1500 g). RESULTS: In the first week of life, 80% of infants had evidence of glucose levels >8 mmol/L, and 32% had glucose levels >10 mmol/L >10% of the time. Independent risk factors for hyperglycemia included increasing prematurity, small size at birth, use of inotropes, lipid infusions, and sepsis. There was a lack of association between rate of dextrose infused and risk of hyperglycemia. CONCLUSION: The prevalence of hyperglycemia in the very low birth weight infant is high, with marked variability in prevalence between infants, not simply related to rates of glucose infused, but to other potentially modifiable risk factors.

A re-investigation of saliva collection procedures that highlights the risk of potential positive interference in cortisol immunoassay.

BACKGROUND: The use of saliva for measurement of cortisol permits non-invasive study of adrenal function, but collection can be technically difficult, particularly in small infants. Saliva collection can be assisted by citric acid to increase saliva flow, or by the use of cotton or polyester swabs in the mouth. AIM: To determine whether different methods of saliva collection affect cortisol radioimmunoassay (RIA) performance. EXPERIMENTAL: Cortisol was measured in saliva collected from 16 adults using intra-oral cotton swabs or polyester swabs, compared with saliva dribbled directly into a pot either alone (plain saliva) or after citric acid had been placed on the tongue. An in-house RIA, without prior extraction, was used to measure cortisol with an encapsulated sheep antibody. RESULTS: Mean (median) salivary cortisol was 10.9 (10.5) nmol L(-1) in plain saliva, 10.4 (8.4) nmol L(-1) in citric acid stimulated saliva; 25.3 (25.1) nmol L(-1) in saliva collected on cotton swabs, and 27.9 (27.3) nmol L(-1) collected on polyester swabs. Cortisol in saliva collected using citric acid was not significantly different from plain saliva (p=0.997), but cortisol in saliva collected using cotton and polyester swabs was significantly higher than that of plain saliva (p<0.01). CONCLUSION: The use of cotton or polyester swabs for collection of saliva can result in spuriously high levels of cortisol when measured by RIA.

Early insulin therapy in very-low-birth-weight infants.

BACKGROUND: Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates. METHODS: In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm. RESULTS: As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04). CONCLUSIONS: Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)

A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe).

BACKGROUND: Studies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and beta cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer beta cells are linked to risk of type 2 diabetes later in life. METHODS: A multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia (4-8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth.

Lack of adult-type salivary cortisol circadian rhythm in hospitalized preterm infants.

BACKGROUND/AIMS: Knowledge of the presence or absence of cortisol (F) circadian rhythm in preterm infants is important for the interpretation of F measurements made in samples taken for both clinical and research purposes. Little is known about its emergence in very preterm infants. This study examines circadian rhythm in F secretion in hospitalized infants born before 30 weeks' gestation. DESIGN: Prospective longitudinal observational study. SUBJECTS: 11 infants admitted consecutively and born before 30 completed weeks of gestation. MEASUREMENTS: F was measured by highly specific radioimmunoassay on morning and evening saliva samples gathered at weekly intervals until discharged home. Circadian rhythm was defined as > or =40% reduction from morning to evening level. RESULTS: For all data, the median salivary F was 10.3 nmol/l (range <0.5-372.8). F levels were highest in the first 3 weeks of life. No infants displayed classical circadian rhythm for 4 weeks or more prior to being discharged from hospital. The other infants showed randomly distributed morning and evening F values with a trend in 4 infants towards periods of consistently higher evening than morning values. CONCLUSION: Adult-type F circadian rhythm is rarely evident in hospitalized preterm infants born before 30 weeks' gestation.

Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations.

Glucokinase (GCK) is a key regulatory enzyme in the pancreatic beta-cell and catalyzes the rate-limiting step for beta-cell glucose metabolism. We report two novel GCK mutations (T65I and W99R) that have arisen de novo in two families with familial hypoglycemia. Insulin levels, although inappropriately high for the degree of hypoglycemia, remain regulated by fluctuations in glycemia, and pancreatic histology was normal. These mutations are within the recently identified heterotropic allosteric activator site in the theoretical model of human beta-cell glucokinase. Functional analysis of the purified recombinant glutathionyl S-transferase fusion proteins of T65I and W99R GCK revealed that the kinetic changes result in a relative increased activity index (a measure of the enzyme's phosphorylating potential) of 9.81 and 6.36, respectively, compared with wild-type. The predicted thresholds for glucose-stimulated insulin release using mathematical modeling were 3.1 (T65I) and 2.8 (W99R) mmol/l, which were in line with the patients' fasting glucose. In conclusion, we have identified two novel spontaneous GCK-activating mutations whose clinical phenotype clearly differs from mutations in ATP-sensitive K(+) channel genes. In vitro studies confirm the validity of structural and functional models of GCK and the putative allosteric activator site, which is a potential drug target for the treatment of type 2 diabetes.