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Background Experiments have shown improved cardiovascular stability in lambs if umbilical cord clamping is postponed until positive pressure ventilation is started. Studies on intact cord resuscitation on human term infants are sparse. The purpose of this study was to evaluate differences in clinical outcomes in non-breathing infants between groups, one where resuscitation is initiated with an intact umbilical cord (intervention group) and one group where cord clamping occurred prior to resuscitation (control group). Methods Randomized controlled trial, inclusion period April to August 2016 performed at a tertiary hospital in Kathmandu, Nepal. Late preterm and term infants born vaginally, non-breathing and in need of resuscitation according to the ‘Helping Babies Breathe’ algorithm were randomized to intact cord resuscitation or early cord clamping before resuscitation. Main outcome measures were saturation by pulse oximetry (SpO2), heart rate and Apgar at 1, 5 and 10 minutes after birth. Results At 10 minutes after birth, SpO2 (SD) was significantly higher in the intact cord group compared to the early cord clamping group, 90.4 (8.1) vs 85.4 (2.7) %, P

During fetal development, the hippocampal structures fold around the hippocampal sulcus into the temporal lobe. According to the literature, this inversion should be completed at gestation week (GW) 21. Thereafter, the hippocampal shape should resemble the adult shape. However, incomplete hippocampal inversion (IHI) is found in 19% of the common population. The aim of this study was to study fetal hippocampal development by examining neonates born preterm.We analyzed cranial ultrasound examinations, performed as a part of the routine assessment of all preterm infants, over a 3-year period and excluded the infants with brain pathology. The final material consisted of 158 children born35 GW. A rounded form (the ratio between the horizontal and vertical diameters of the hippocampal bodyor=1) in coronal slices was considered the sign of IHI.The age at examination was 23-24 GW in 24 neonates, 25-28 GW in 70 neonates, and 29-36 GW in 64 neonates. IHI was found in 50%, 24%, and 14%, respectively. The difference between the neonates25 GW andor=25 GW was statistically highly significant (p0.001). The frequency of bilateral IHI was highest in the youngest age group. In the other groups, the left-sided IHI was the most common.In about 50% of the neonates, hippocampal inversion is not completed up to GW 24; but from 25 GW onwards, the frequency and laterality of IHI is similar to that in the adult population.

Background and objective: Preterm and term newborn infants show wide interindividual variability (IIV) in pharmacokinetic parameters of gentamicin. More extensive knowledge and use of predictive covariates could lead to faster attainment of therapeutic concentrations and a reduced need for concentration monitoring. This study was performed to characterize the population pharmacokinetics of gentamicin in preterm and term neonates and to identify and quantify relationships between patient characteristics and IIV. A secondary aim was to evaluate cystatin C as a marker for gentamicin clearance in this patient population. Methods: Data were collected in a prospective study performed in the Neonatal Intensive Care Unit at the University Children’s Hospital, Uppsala, Sweden. Population pharmacokinetic modelling was performed using nonlinear mixed-effects modelling (NONMEM) software. Bodyweight was included as the primary covariate according to an allometric power model. Other evaluated covariates were age (postmenstrual age, gestational age [GA], postnatal age [PNA]), markers for renal function (serum creatinine, serum cystatin C) and concomitant medication with cefuroxime, vancomycin or indometacin. Covariate-parameter relationships were explored using a stepwise covariate model building procedure. The predictive performance of the developed model was evaluated using an independent external dataset for a similar patient population. Results: Sixty-one newborn infants (GA range 23.3–42.1 weeks, PNA range 0–45 days) were enrolled in the study. In total, 894 serum gentamicin samples were included in the analysis. The concentration-time profile was described using a three-compartment model. Gentamicin clearance increased with the GA and PNA (included in a nonlinear fashion). The GA was also identified as having a significant influence on the central volume of distribution, with a preterm neonate having a larger central volume of distribution per kilogram of bodyweight than a term neonate. Cystatin C and creatinine were not correlated with gentamicin clearance in this study population. The external dataset was well predicted by the developed model. Conclusion: Bodyweight and age (GA and PNA) were found to be major factors contributing to IIV in gentamicin clearance in neonates. Based on these data, cystatin C and serum creatinine were not correlated with gentamicin clearance and therefore not likely to be predictive markers of renal function in this patient population. Based on predictions from the developed model, preterm neonates do not reach targeted peak and trough gentamicin concentrations after a standard dosage regimen of 4 mg/kg given once daily, suggesting a need for higher loading doses and prolonged dosing intervals in this patient population.

IGF-I is important for somatic growth and development of the human fetus and neonate. IGF-I also plays an important role in normal vascularization of human retina, as it has been suggested that insufficient IGF-I may be a factor in the development of retinopathy of prematurity. The principal regulator of the bioavailability of IGF-I in the circulation is IGF binding protein 3 (IGFBP-3). The aim of this study was to study factors associated with postnatal serum concentrations of IGF-I and of IGFBP-3 in preterm infants from birth to an age corresponding to 40 wk postmenstruation. We conducted a prospective, longitudinal study in which we measured serum IGF-I and IGFBP-3 concentrations in 76 preterm infants from birth (postmenstrual ages 23-32 wk) until discharge from hospital around 40 wk. Information regarding nutrition, weight gain, maternal factors, and treatment with corticosteroids were collected weekly. Variables found to be associated with postnatal change over time of serum IGF-I and IGFBP-3 were postmenstrual age (p

Background Facilitation of local women’s groups may reportedly reduce neonatal mortality. It is not known whether facilitation of groups composed by local healthcare staff and politicians can improve perinatal outcomes. We hypothesized that facilitation of local stakeholder groups would reduce neonatal mortality (primary outcome) and improve maternal, delivery and newborn care indicators (secondary outcomes) in Quang Ninh province, Vietnam. Trial registration: Current Controlled Trials ISRCTN44599712.

The high affinity Fcgamma-receptor I (FcgammaRI, CD64) is normally expressed only to a very low extent by neutrophils. During bacterial infections, however, neutrophils from adult patients significantly increase their expression of FcgammaRI. Stimulation through FcgammaRI is a highly effective way to improve various aspects of neutrophil function, including phagocytosis. In our study the expression of FcgammaRI on neutrophils from preterm (n = 9) and term (n = 3) newborn infants, children (n = 14), and adults (n = 6) during the early phase of an acute bacterial infection was investigated. Our results showed that neutrophils from newborn infants with bacterial infection expressed FcgammaRI to a significantly higher extent than both noninfected preterm (p < 0.001) and term (p < 0.001) newborn infants and that neutrophils from preterm neonates expressed FcgammaRI to the same extent as neutrophils from term neonates and older infants, children, and adults. No difference in the neutrophil cell surface expression of FcgammaRI during bacterial infections was found among newborn infants, children, and adults. Expression of FcgammaRI probably represents an important mechanism to improve neutrophil phagocytosis as well as other aspects of neutrophil function during bacterial infections, especially in preterm infants. Our study indicates that measurement of cell surface expression of FcgammaRI on neutrophils could be a useful indicator of severe bacterial infections in preterm and term neonates, as well as in older children and adults.

Extremely preterm infants have been shown capable of producing glucose at a rate comparable to that of term infants, but virtually no data are available on their capacity for lipolysis and gluconeogenesis. To address this issue, we studied the flux of glycerol and its gluconeogenic contribution to hepatic glucose output by determining the endogenous plasma appearance rate of glycerol (glycerol Ra) and its conversion to glucose in 10 newborn infants, 24-27 wk of gestational age. The study was performed during the 1st d of life by tracer dilution technique using [6,6-2H2]glucose and [2-13C]glycerol given as constant rate i.v. infusions. Plasma isotopic enrichments of the tracers were obtained by gas chromatography/mass spectrometry. Endogenous glycerol Ra ranged from 2.4 to 21.6 (median 5.0) mumol.kg-1.min-1, of which 31.5% (25.6-64.4%) was converted to glucose. The glucose production rate averaged 17.5 +/- 5.4 mumol.kg-1.min-1 (3.2 +/- 1.0 mg.kg-1.min-1), of which 5.0% (1.6-37.6%) was derived from glycerol. The results show that extremely preterm infants, despite limited fat stores, are capable of generating glycerol at a rate within the range reported for term and near term newborns. The infants were also capable of converting part of this glycerol to glucose, providing a contribution to hepatic glucose production comparable to that found in more mature newborns.

Background Reducing neonatal death has been an emerging challenge in low and middle income countries in the past decade. The development of the low cost interventions and their effective delivery are needed to reduce deaths from birth asphyxia. This study will assess the impact of a simplified neonatal resuscitation protocol provided by Helping Babies Breathe (HBB) at a tertiary hospital in Nepal. Perinatal outcomes and performance of skilled birth attendants on management of intrapartum-related neonatal hypoxia will be the main measurements. Methods/Design The study will be carried out at a tertiary level maternity hospital in Nepal. A prospective cohort-study will include a six-month baseline a six month intervention period and a three-month post intervention period. A quality improvement process cycle will introduce the neonatal resuscitation protocol. A surveillance system, including CCD cameras and pulse oximeters, will be set up to evaluate the intervention. Discussion Along with a technique to improve health workers performance on the protocol, the study will generate evidence on the research gap on the effectiveness of the simplified neonatal resuscitation protocol on intrapartum outcome and early neonatal survival. This will generate a global interest and inform policymaking in relation to delivery care in all income settings. Trial registration ISRCTN97846009

Neonatal hypoglycemia is a frequent complication in immature infants. This may be due to small substrate stores, a high brain:body weight ratio, and immature enzyme systems. The purpose of the present study was to investigate the rate of glucose production in newborn infants with gestational ages of less than 28 wk. The subjects were 10 newborn infants delivered after 25 to 26 gestational wk. Their mean birth weight was 772 g (range 588–1000 g), and their mean postnatal age at the time of the study was 15 h (range 4–24 h). An isotopic compound (d-6,6-2H2-glucose) was given as a constant-rate i.v. infusion. In addition to dideuteroglucose, eight of the infants also received an i.v. infusion of unlabeled glucose at a rate of 1.4–2.6 mg·kg−1·min−1. Blood samples for determination of the concentration and isotopic enrichment of plasma glucose were obtained every 15 min in a 2-h period. Isotopic enrichment, measured by gas chromatography/mass spectrometry, was used for calculating the glucose production rate. The mean glucose production rate related to body weight (± SD) was 6.1 ± 1.5 mg·kg−1·min−1. The results show that infants born at

Background: Infants born very preterm (VPT) i.e.< 32w gestational age (GA) have increased risk of developing impaired visual perception. Previously we have found that visual motion perception in VPT infants, evaluated by smooth pursuit eye movements (SP) was significantly reduced at both 2 and 4 months corrected age (CA) compared to term infants. SP are essential for perception of the moving environment in daily life.

Neurodevelopmental Outcome of Extremely Preterm Infants at 2.5 Years of Age; Extremely Preterm Infants Study in Sweden (Express)

Top of pageAbstract Background: Growth is one of the most important indicators of health in infants and older children. The IGF system is one of the principal regulators of fetal growth. The third trimester is the time of life during which growth velocity is the most rapid. Little is known about how preterm birth may affect longitudinal growth, and about the relationship of the IGF system to post-natal growth. Aim: To prospectively characterise longitudinal growth and the influence on growth of IGF-I, IGF-II and IGFBP-3 in preterm infants with GA

Background: After birth the newborn infant must produce its own glucose until breastfeeding is established. Infants born small for gestational age (SGA) are at risk for neonatal hypoglycemia and development of metabolic syndrome in adulthood. The aim of this study was to investigate glucose production and lipolysis in newborn infants born SGA.

Background: During late gestation the fetus accumulates fat and glycogen for the immediate postnatal period. Newborn infants of diabetic mothers as well as other infants with hyperinsulinemia have particularly large energy depots and are at risk for hypoglycemia. Large for gestational age (LGA) infants, without known predisposing factors, also have increased energy stores. The relative proportion of this group of infants is increasing. Only limited data is available on the metabolic adaptation of these infants. Aim: To study lipolysis and glucose production in infants born LGA of non diabetic mothers. Methods: Eight term LGA infants, were studied at a postnatal age of 19±8-h. Gestational age was 40±1.5 w and birthweight 4.87±0.44 kg. Rates of lipolysis and glucose production (GPR) were analysed by gas chromatography-mass spectrometry following constant rate infusion of [2–13C]-glycerol and [6,6–2H2]-glucose. Results: Plasma glucose and glycerol averaged 3.8 ± 0.6 mmol. L-1 and 418 ± 190 ±mol. L-1, respectively. Glycerol production, reflecting lipolysis, was 13.2±2.9 imol. kg-1. min-1 and GPR averaged 5.5±0.9 mg. kg-1. min-1 (30.6±5.imol. kg-1. min-1). The fraction of glycerol converted into to glucose was 54±22 % contributing to 11±6 % of the total glucose production. Lipolysis and GPR correlated to birth weight. Plasma concentrations of insulin and glucagon averaged 11±3 mU. L-1 and 39±4 pmol. L-1, respectively. Conclusion: The results show that term LGA infants have a markedly increased lipolysis during the first day of life as compared to term infants born appropriate for gestational age (AGA). The correlation to birth weight indicates that the degree of lipolysis is dependent on the amount of stored fat in the LGA infants. GPR was similar to that observed in AGA infants. There was no pronounced hyperinsulinemia, which contradicts the occurrence of insulin resistance in this particular group of infants.

Of 7 tertiary care centers in Sweden, the University Hospitals in Uppsala and Umea have consistently had an aggressive approach to the treatment of newborns with gestational age (GA) of < 25 weeks.

The Preterm Infant Breastfeeding Behavior Scale (PIBBS), A New Tool For Describing Maturational Steps in Infant Behavior 108

Background: The high affinity Fc-receptor CD64 (FcγRI) is normally expressed by monocytes but only to a very small extent by neutrophils. Cytokines like IFNγ and G-CSF are known to induce the expression of CD64 on neutrophils. The aim of this study was to investigate the expression of CD64 by neutrophils during bacterial infections in preterm and term infants, children and adults as well as during viral infections and non-infectious inflammatory conditions.

Immature infants have small, rapidly depleted glycogen stores. Therefore, other energy substrates are necessary to meet the metabolic demands. The aim of the present study was to determine production rates of glucose and glycerol, and the degree of conversion of glycerol to glucose in infants born after < 28 w. Subjects and methods: Five infants with birth weights of 665-1173 g and gestational ages of 25-27 w were studied at postnatal ages of 13-24 h. Tracer dilution technique with 6,6-2H2-glucose and 2-13C-glycerol was used. Production rates of glucose and glycerol were calculated from isotopic enrichments, determined by use of gas chromatography/mass spectrometry. Conversion of glycerol to glucose was calculated from the 13C-enrichment of glucose. Insulin and glucagon were measured by RIA. Results: The production rate of glucose was 16.4±7.2 and that of glycerol 11.3 ±6.9 μmol·kg−1·min−1. The fraction of glycerol converted to glucose was 42.1−116.3 %, corresponding to 16.5±13.8 % of the glucose production rate. The plasma concentration of glucose was 2.5±1.0 mM, that of glycerol 346±454 μM and those of insulin and glucagon 6.6±2.2 μUmL−1 and 294±57pgmL−1, respectively. (X±SD) Conclusion: Very immature infants are capable to produce glucose and glycerol during their first postnatal day. The results also show, that in these immature infants glycerol contributes to glucose production.

Newborn infants have an increased susceptibility to serious infections. Neutrophil granulocytes play an important role in the defence against infections. We have studied the expression of the receptors for phagocytosis and adhesion (CD11 b, CD16, CD18, CD32, CD35 and Leu8) on neutrophil granulocytes from newborn infants and compared with results found in adults. Subjects and methods: Blood samples were taken from 18 term newborn infants (cord; blood) and 30 healthy adults. The granulocytes were fixed with formaldehyde and incubated with monoclonal antibodies against each receptor. The cells were then analyzed by flow cytometry (Epics Profil II). Results: For CD11b, CD16, CD18, CD32, and Leu8, there was no significant difference in receptor expression between granulocytes from newborns and those from adults. There was a trend towards increased expression of the CD35 receptor (p=O,068), and the expression of CD16 was significantly decreased (p=0,046) on granulocytes from newborns. Conclusion: With exception for a tendency of an increased expression of the complement receptor CD35 and a decreased expression of the Fc-receptor CD16, no significant differences were found between newborn infants and adults.

Neonatal hypoglycemia is frequently observed following pregnancies complicated by diabetes. This might be a result of decreased glycogenolysis/gluconeogenesis caused by neonatal hyperinsulinemia. The aim of the study was to investigate the capacity for production of glucose and glycerol, a glucose precursor, in infants of diabetic and healthy mothers. Subjects and methods: Eight normoglycaemic, fasting, term infants from diabetes pregnancies (IDDM/GDM) and two control infants were studied at a postnatal age of 4-10 h. The glucose (GPR) and glycerol production rates (GlycPR) were studied by use of 6,62H2-glucose and 2-13C-glycerol. The isotopic enrichments and concentrations of glucose (P-gluc) and glycerol (P-glyc) in plasma were analyzed Isotopic enrichments were measured by gas chromatography/mass spectrometry during periods of steady slate and were used for calculation of production rates. Conclusion: Normoglycaemic infants of diabetic mothers have capacity for glucose and glycerol production, at rates similar to those in control infants.

Before feeding regulatory mechanisms maintain blood glucose concentrations of the newborn to meet the demands of the central nervous system. The role of glucagon in this process has been investigated. Healthy, term babies without clinical signs of hypoglycemia were studied. A capillary blood sample was obtained at 3-15 hours (median 6 hours) of age, a second sample 24 hours later and serum concentrations of glucose, insulin and glucagon were measured. Glucose concentrations at the first sampling averaged 2.1 ± 0.5 mM (mean ± SD; n = 51) and were positively correlated with postnatal age. At the second sampling glucose concentrations had increased to 3.0 ± 0.5 mM. Glucagon concentrations were 541 ± 219 pg/ml at the first sampling and inversely correlated with glucose concentrations. At the second sampling glucagon concentrations had decreased to 406 ± 163 pg/ml. Insulin concentrations were 12.1 ± 2.4 and 10.6 ± 2.1 μU/ml, respectively, and did not correlate with glucose concentrations. In a multiple regression analysis glucose concentrations were inversely correlated with glucagon concentrations and positively correlated with birth weights but not correlated with insulin concentrations or other neonatal and maternal characteristics. The results suggest that glucagon is part of normal counterregulation against hypoglycemia and that neonatal energy stores, as indicated by birth weight, influence the ability to maintain normoglycemia.

Serum lipoprotein lipid and apolipoprotein concentrations were determined in 27 diabetic children (5-18 years old) and 13 matched healthy controls. The serum cholesterol concentrations in the diabetics were slightly higher than in the controls (P less than 0.05) due to a significantly higher level of the high density lipoprotein cholesterol (P less than 0.01). Also the serum concentration of apolipoprotein A-I, the major protein constituent of the high density lipoprotein fraction, was higher in the diabetic children (P = 0.05). There were no significant differences between the groups with regard to the serum triglyceride concentrations or the apolipoprotein C-II and C-III concentrations. Neither the lipoprotein lipid nor the apolipoprotein levels were significantly correlated with variables related to the degree of regulation of the diabetic disease. No obvious explanation, based on the present data, can be given for the increased high density lipoprotein cholesterol concentrations in insulin-treated diabetics in comparison with the healthy children. It is possible, however, that the increased high density lipoprotein cholesterol concentration may be caused by an increased level of insulin in the circulation of insulin-treated diabetic children.

A diminished vascular response to hypoxia has been demonstrated in type 1 diabetes (IDDM). This functional abnormality might be a phenomenon preceding the late structural vascular disease. In order to evaluate the prognostic value of this vascular dysfunction a prospective study has been started. Vascular reactivity of skin vessels was evaluated as changes in transcutaneous PO2 at 37° C during postocclusive hyperemia (Clin Physiol 1984;4:413). All children in our county, acquiring IDDM 1983-4 (n=38) comprised the study group. Vascular reactivity was evaluated at admission before insulin therapy and then at 1, 6, 12 and 24 months after diagnosis. Vascular reactivity at admission (3.0±0.2 kPa, M±SEM) was impaired (p

Smoking during pregnancy is associated with increased perinatal morbidity and mortality. Disturbed prostaglandin metabolism might be an important causal factor since the regulation of umbilical-placental blood flow and vasomotor function in the newborn infant is partly prostaglandin-dependent. The aim was to evaluate the impact of maternal smoking on reduced prostacyclin formation in umbilical arteries. Segments from human umbilical arteries were collected at 87 unselected term deliveries. The capacity for prostacyclin formation was estimated, blindly as to smoking habits, using a bioassay technique. In umbilical arteries from infants of non-smoking mothers the prostacyclin-like activity amounted to 81 ± 37 ng/g of umbilical arterial tissue, and in those from all smokers to 66 ± 34 (p

The initiation and development of vascular disease might start already in childhood. Functional vascular disturbances should be possible to find in many progressive disorders as e.g. diabetes mellitus before structural lesions develop. Such findings could suggest clues for understanding and be suitable for studies of pathogenetic mechanisms. Postocclusive reactive hyperaemia is a coomonly used physiological test of vascular function. We have earlier shown that this response is readily detected by a transcutaneous oxygen electrode used at 37°C (SJCLI 1981; 41: 641, Lancet 1981; i: 1287). The method has the advantage of being non-invasive and measures changes occuring in defined skin vessel regions.

Disturbances in carbohydrate metabolism, lipid pattern and platelet function are potential risk factors in the development of vascular complications in juvenile diabetics. In a prospective study including 29 diabetic children the relationship between these factors has been studied. Carbohydrate control was measured by HbA1, by Clinitest analysis of three urine portions a day, three days a week for two months, and by clinical judgement. Platelet function was studied by Born aggregometry. Results: The relative number of positive Clinitest results was highly correlated to HbAl (r=0.83). There was a complete accordance between clinical judgement and HbA1. A positive correlation was also found between HbAl and serum triglycerides (r=0.61). The platelets from poorly controlled children often lacked shape change and showed slower aggregation velocity and less pronounced maximal aggregation. Summary: HbA1 is a very good indicator of carbohydrate control. Serum triglycerides and platelet aggregation are affected by the degree of diabetic control.

Transcutaneous PO2 (tcPO2) at 37°C reflects tissue PO2 at the border between living and dead epidermis (50 um depth). In contrast to its conventional use at 45°C tcPO2 at 37°C is hardly affected by changes in arterial PO2 but very dependent on changes in skin blood flow. Laser Doppler velocimetry (LDV) measures the speed of moving erythrocytes in the skin to a depth of 1000 um. The aim of this work was to compare these methods for noninvasive recording of reactive hyperemia in the skin. A combined tcPO2 electrode incorporating the LDV measuring probe (PerifluxR) was constructed in Huch's laboratory, Zurich, allowing recordings from the same skin site simultaneously under identical experimental conditions. The combined sensor was placed on the volar aspect of the forearm. Exercise induced and postocclusive reactive hyperemia were recorded in healthy children and adults. Both signals detected small rhytmical variations in steady state and recorded biphasically the changes in skin blood flow during and after reactive hyperemia. The time course differed between the tcPO2 and the LDV signal, the former being delayed about 30 s for the postocclusive response. A significant correlation between the postocclusive maximal peaks measured by the two methods was found (r=0.7; p

Postnatal circulatory adaptation is characterized by increased peripheral vascular tone and redistribution of blood flow. This view is supported by the results of this study with a new non-invasive technique. A transcutaneous PO2 electrode (TransoxodeR, Drager, FRG) used at a temperature of 37°C has been shown to detect changes in PO2 at the skin surface reflecting changes in blood flow in a defined area of skin vasculature. Postischaemic hyperaemia was measured after 4 min of cuff occlusion of the forearm circulation. Twelwe vaginally delivered, non-asphyxiated, healthy, term and appropriate for gestational age neonates of healthy drug-free mothers were studied 4-7h and 24-32h post partum. The newborn infants demonstrated a higher basal blood flow 4-7h after birth (median 1.7 kPa, range 0.1-3.1) than at the later registration (median 0.2, range 0.0-0.5)(p