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

Intestinal Colonization Patterns of Staphylococci in Preterm Infants in Relation to Type of Enteral Feeding and Bacteremia

Abstract Objective: This study investigated the intestinal colonization with staphylococci in very low birth weight infants in relation to the type of enteral feeding and evaluated the intestine as potential source for staphylococcal bacteremia. Patients and Methods: Infants born in the Level III neonatal intensive care unit of a university hospital with a gestational age below 32 weeks and/or birth weight below 1,500 g were included in a prospective, observational study. The infants received either preterm formula or mother's own milk, with random allocation to raw or pasteurized milk. Precise viable staphylococcal counts of serial fecal specimens were examined in the first 8 weeks of life. In the case of bloodstream infection, fecal and blood isolates of staphylococci were compared by antibiotypes or pulsed-field gel electrophoresis. Results: One hundred fifty neonates, with a mean of 29 weeks of gestation and 1,260 g at birth, had 1,045 fecal samples analyzed and were found to be heavy carriers of staphylococci in the intestine with 10(6)-10(7) colony-forming units/g of feces from the first week of life. Colonization rate and patterns were not different in relation to the type of enteral feeding. In nearly 80% of 42 patients exhibiting a staphylococcal bloodstream infection, intestinal colonization retrieved a predominant strain that was different from the one recovered from the blood. Conclusions: In very low birth weight infants, predominance of staphylococci in the gut is not related to the type of enteral feeding. An endogenous origin of staphylococcal bloodstream infection seems to play a minor role.status: publishe

From Birth to Death? A Personalist Approach to End-of-Life Care of Severely Ill Newborns

In this paper, a personalist ethical perspective on end-of-life care of severely ill newborns is presented by posing two questions. (1) Is it ethically justified to decide not to start or to withdraw life-sustaining treatment in severely ill newborns? (2) Is it ethically justified, in exceptional cases, to actively terminate the life of severely ill newborns? Based on five values-respect for life and for the dignity of the human person, quality of life, respect for the process of dying, relational autonomy, and justice-an ethical assessment is conducted that brings us answers to the two ethical questions. (1) Noninitiation or withdrawal of life-sustaining medical treatment in severely ill newborns is ethically acceptable, and might even be a moral duty, when initiation or continuation of medical treatment can be considered futile or even harmful. (2) However, according to the personalist approach, it is not ethically acceptable to actively terminate the life of a severely ill newborn. © The Author 2013. Published by Oxford University Press, on behalf of The Journal of Christian Bioethics, Inc. All rights reserved.status: publishe

The use of human milk in the neonatal intensive care unit: practices in Belgium and Luxembourg

Human milk remains the preferred feeding for all infants, including premature and sick newborns. However, mother's milk is not sterile, and expressed milk can be a source of commensal and pathogenic microorganisms. Microbiological quality standards for the use of expressed human milk in hospitals are not available, unlike for donor or formula milk.status: publishe

Expressed breast milk on a neonatal unit: a hazard analysis and critical control points approach

With the increasing use of human milk and growing evidence of the benefits of mother's milk for preterm and ill newborns, guidelines to ensure its quality and safety are an important part of daily practice in neonatal intensive care units. Operating procedures based on hazard analysis and critical control points can standardize the handling of mother's expressed milk, thereby improving nutrition and minimizing the risk of breast milk-induced infection in susceptible newborns. Because breast milk is not sterile, microorganisms can multiply when the milk is not handled properly. Additional exogenous contamination should be prevented. Strict hygiene and careful temperature and time control are important during the expression, collection, transport, storage, and feeding of maternal milk. In contrast to formula milk, no legal standards exist for the use of expressed maternal milk. The need for additional measures, such as bacteriological screening or heat treatment, remains unresolved.status: publishe

Evolution of circulating thyroid hormone levels in preterm infants during the first week of life: perinatal influences and impact on neurodevelopment

Background For several decades, transient hypothyroxinemia of prematurity (THOP) has been a topic of debate. The pathophysiology is incompletely understood and consensus on the therapeutic approach is lacking. This study aimed at gaining a better insight into the pathogenesis by studying the trends in thyroid hormone (TH) levels during the first week of life. Methods This single-center prospective observational study analyzed the plasma levels of total thyroxine (T4) and free thyroxine (fT4), total triiodothyronine (T3), thyroid-stimulating hormone (TSH) and T4-binding globulin (TBG) in cord blood and at the end of the first week of life in 120 preterm infants (gestational age [GA] <37 weeks). The change over time was calculated (delta, ∆). The impact of perinatal and subsequently postnatal variables on ∆ was studied by hierarchical multiple regression. The impact of ∆ on the neurodevelopmental outcome at the corrected ages of 9 and 24 months, measured by the Bayley Scales of Infant Development (BSID)-II, was assessed by logistic regression. Results ∆fT4 levels were negatively affected by GA and use of dopamine, whereas only GA was associated with low ∆T3 levels. Negative ∆fT4 levels were present in 75% of the extremely low-for-gestational-age infants, whereas 23.5% had a negative ∆T3 level. There was an increased risk for an abnormal mental developmental score (<85) with decreasing ∆T3 at 9 months, corrected age, but not at 24 months. Conclusions A negative evolution in circulating TH levels is principally an immaturity phenomenon, whereas dopamine can further suppress the hypothalamic-pituitary-thyroid axis. There is at least a temporary negative effect of this evolution on the infants' neurodevelopment.status: publishe

Pasteurization of mother's own milk for preterm infants does not reduce the incidence of late-onset sepsis

Feeding preterm infants human milk has a beneficial effect on the risk of late-onset sepsis (LOS). Due to lack of microbiological standards, practices such as pasteurization of mother's own milk differ widely among neonatal intensive care units worldwide.status: publishe

Both postnatal and postmenstrual age contribute to the interindividual variability in tramadol glucuronidation in neonates

INTRODUCTION: Although of pharmacokinetic and -dynamic relevance, data on ontogeny of UDP-glucuronosyltransferase (UGT) activity in neonates are scant. We therefore wanted to assess the impact of both postnatal and postmenstrual age (PNA/PMA) on the interindividual variability of glucuronidation to overall tramadol urinary elimination in neonates. METHODS: O-demethyl tramadol (M1) and M1-glucuronide (M1G) were determined in 24 hour urine collections during continuous intravenous tramadol administration in neonates. Glucuronidation fraction (%) was calculated by the ratio of M1G to the sum of M1G and M1 free (M1total). Fractions (%) in early (<day 8) or late neonatal life (day 8-28) were compared (Mann-Whitney U) and forward multiple regression was applied to assess the impact of various covariates. RESULTS: Urine collections were available in 59 neonates with a PNA of 6 (1-28) days and a PMA of 38 (SD 4) weeks. Mean M1G/M1total was 27 (SD 15) % and was significantly lower in early compared to late neonatal life (22 versus 32%, p=0.0001). In a forward multiple regression model, both PMA and early versus late neonatal life remained independent variables to explain the interindividual variability in M1G/M1total. CONCLUSIONS: Besides PMA, there is an additional, independent impact of PNA since phenotypic glucuronidation activity is significantly lower in the first week of postnatal life. These findings should be taken into account in the assessment of compounds for whom glucuronidation is of pharmacokinetic, pharmacodynamic or toxicological relevance.status: publishe

Risk factors for large-for-gestational age infants in pregnant women with type 1 diabetes

The rate of neonatal overweight remains generally high in type 1 diabetes (T1DM). Since glycemic control has improved over time other contributors need to be identified. Our aim is to evaluate the risk factors for large-for-gestational age infants (LGA) in women with T1DM and to evaluate whether the rate of LGA decreased over time.status: publishe