Jens Schollin

Analgesia in newborns given oral glucose

There is evidence that newborn babies feel pain even at the lowest gestational ages when they can survive. Because sweet solutions such as sucrose, given orally, may relieve pain in neonates, we decided to compare the effects of two concentrations of glucose (normally used for intravenous infusions) and of breast milk in a randomized controlled trial in 120 babies requiring heel‐prick tests. Glucose solutions and breast milk are readily available in the neonatal department. No other treatment was given. Our results strongly suggest that 1 ml of a 30% glucose solution given orally alleviates mild pain significantly and can be used for this purpose in newborns. Breast milk and 10% glucose did not have a similar effect.

Impaired phagocytosis and opsonisation towards group B streptococci in preterm neonates

AIMS To study the chemiluminescence response in polymorphonuclear leucocytes (PMNL) at different stages of maturity and the opsonic capacity of sera with defined titres of anti-capsular type III antibodies, after exposure to serotype III group B streptococci (GBS). The influence of GBS type III capsule expression on PMNL chemiluminescence response was also investigated. METHODS Two clinical isolates of serotype III GBS and two serotype III reference strains which form isogenic variants with high and low amounts of capsule substance, respectively, were used. PMNL and sera were obtained from adult healthy blood donors, full term neonates, and preterm neonates. RESULTS PMNL from premature infants showed a significantly lower chemiluminescence response (p<0.0001) than the PMNL from adults and neonates, while the chemiluminescence response with adult, neonatal, and preterm sera gradually diminished. In the presence of a serum pool with a standardised complement value, raised (>10 mg/l), rather than low (<1.0 mg/l) anti-III antibody titres induced a higher chemiluminescence response to the capsule expressing variant. When GBS were cultured at pH 5.0, the bacteria had a higher buoyant density, reflecting decreased expression of capsule substance compared with bacteria grown at pH 7.4. Concomitantly, there was a substantial increase in chemiluminescence response for all isolates cultured at the lower pH, except for the capsule deficient mutant. CONCLUSIONS PMNL function and opsonic capacity are significantly impaired in neonates and correlate with maturation of the newborn child. The combined defect in cellular and humoral defences in preterm neonates may contribute to their increased susceptibility to GBS infection. Growth conditions for GBS, simulating different in vivo environments, greatly affect capsule expression and resistance to phagocytosis.

The Role of Endogenous Opioids in Mediating Pain Reduction by Orally Administered Glucose Among Newborns

Objective. It has been demonstrated clearly that sweet-tasting solutions given before a painful intervention can reduce pain among newborns. There is no fully accepted explanation for this effect, but activation of endogenous opioids has been suggested as a possible mechanism. The aim of this study was to obtain deeper knowledge of the underlying mechanism by investigating whether administration of an opioid antagonist would reduce the effect of orally administered glucose at heel stick among term newborns. Design. A randomized, placebo-controlled, double-blind trial with a validated, neonatal, pain-rating scale. Participants. The trial included 30 term newborns undergoing heel stick, who were assigned randomly to 1 of 2 groups, ie, group I, with naloxone hydrochloride (opioid antagonist) 0.01 mg/kg administered intravenously before oral administration of 1 mL of 30% glucose, or group II, with a corresponding amount of placebo (saline solution) administered intravenously before oral administration of glucose. Outcome Measures. Pain-related behavior during blood sampling was measured with the Premature Infants Pain Profile. Crying time and heart rate were also recorded. Results. The 2 groups did not differ significantly in Premature Infant Pain Profile scores during heel stick. The median crying time during the first 3 minutes was 14 seconds (range: 0–174 seconds) for the naloxone group and 105 seconds (range: 0–175 seconds) for the placebo group. There was no significant difference in heart rate between the 2 groups. Conclusion. Administration of an opioid antagonist did not decrease the analgesic effect of orally administered glucose given before blood sampling.

Skin conductance compared to a combined behavioural and physiological pain measure in newborn infants

Aim: To assess the ability of galvanic skin response (GSR) to differentiate between tactile and painful stimulation in newborn infants, and to compare this with the ability of the premature infant pain profile (PIPP).

Oral glucose and venepuncture reduce blood sampling pain in newborns

The objectives of this study were to measure pain symptoms in healthy fullterm newborns undergoing routine blood sampling with different methods. The 120 study subjects were randomly allocated to one of four groups with 30 babies in each, namely venepuncture or heel stick, with or without oral glucose administration. Pain was assessed from the duration of crying within the first 3 min, the Premature Infant Pain Profile (PIPP) and changes in heart rate. When the babies received 1 ml 30% glucose prior to skin puncture there was no significant difference between the heel stick and venepuncture group either in mean crying time (12.9 and 11.6 s, respectively) or in PIPP score (3.9 and 3.3). When no glucose was given crying time was 57.3 s in the heel stick group and 26.8 s in the venepuncture group (P = 0.0041) and the mean PIPP scores were 8.4 and 6.0, respectively (P = 0.0458). This study suggests that if oral glucose is given prior to skin puncture the choice of blood sampling method has no impact on the pain symptoms.

Coagulase-negative staphylococcal sepsis as a predictor of bronchopulmonary dysplasia.

Aim: To determine whether sepsis caused by coagulase‐negative staphylococci (CoNS) is a risk factor for developing bronchopulmonary dysplasia (BPD) in premature newborns. Methods: All newborns born at ±30 wk of gestation at Örebro University Hospital during 1994–2001 with clinical sepsis caused by CoNS (group A, n= 22) or by other bacteria (group B, n= 17) were included and compared with premature newborns without sepsis (group C, n= 53). Clinical sepsis was defined as a positive blood culture (monoculture) plus clinical symptoms and laboratory findings. BPD was defined as treatment with oxygen >21% for at least 28 d. Results: The incidence of BPD differed between the three groups, as follows: CoNS sepsis (A) 64%, other sepsis (B) 41% and control (C) 24%. The difference between the control group and the sepsis groups was highly significant (p= 0.006). In a univariate model the crude estimates of relative risk (RR) for occurrence of BPD increased with presence of sepsis and particularly with presence of sepsis with CoNS (A: RR 2.6, 95% CI 1.5–4.6, p= 0.001; B: RR 1.7, CI 0.8–3.5, p= 0.17). When regression was performed with two additional predictive variables in multivariate models including sepsis, gestational age and mechanical ventilation (group A: RR 1.5, CI 1.1–2.0, p= 0.004; group B: RR 0.9, CI 0.6–1.4, p= 0.67), the estimates were lower.

Contribution of interleukin-6 in distinguishing between mild respiratory disease and neonatal sepsis in the newborn infant

The purpose of this study was to investigate if early samples of interleukin‐6 (IL‐6) could distinguish early bacterial sepsis from respiratory diseases in the newborn. IL‐6 and C‐reactive protein (CRP) were measured at onset of symptoms in newborns evaluated for sepsis during the first week of life. Five groups of children were investigated: proven sepsis, clinical sepsis, respiratory distress syndrome (RDS), transient tachypnoea of the newborn (TTN) and controls. IL‐6 was also analysed at the time when CRP was at its maximum level. The results showed that initial IL‐6 distinguished proven and clinical sepsis from TTN, but not from RDS. Initial CRP was of no value for diagnosis. Our conclusion is that early IL‐6 makes it possible to avoid antibiotics in children with TTN and contributes to the diagnosis of sepsis faster than CRP. □C‐reactive protein, interleukin‐6, neonatal septicaemia, respiratory diseases

Phenotypic and genotypic characterisation of blood isolates of coagulase‐negative staphylococci in the newborn

Coagulase‐negative staphylococci (CNS) are the leading cause of late‐onset sepsis in newborns (>72 h of age). Our aim was to determine whether phenotypic and/or genotypic differences existed between blood isolates of CNS regarded as inducers of sepsis or as contaminants. Ninety‐seven bloodisolates of CNS recovered from newborns at the neonatal intensive care unit, Örebro, Sweden in 1983–1997 were analysed. Twenty‐nine of them (30%) were classified as sepsis isolates and 68 (70%) as contaminants. The most prevalent species was Staphylococcus epidermidis (n=59). Staphylococcus haemolyticus (n=16) was most often isolated from newborns with the lowest gestational age and birth weight. Biochemical typing using the Phene Plate system (PhP) and genotyping using pulsed‐field gel electrophoresis (PFGE) showed that the S. epidermidis isolates regarded as inducers of sepsis (n=16) were more homogeneous than isolates considered contaminants (n=37). One main genotypic group, representing seven (44%) isolates, was identified among the sepsis isolates. Phenotypically the S. epidermidis sepsis isolates comprised three major clusters. In contrast, among the S. epidermidis contaminants, eight genotypic groups and two phenotypic clusters were identified. The dominating genotypic group among the sepsis isolates of S. epidermidis may represent strains with higher invasive capacity.

Defective Neutrophil Oxidative Burst in Preterm Newborns on Exposure to Coagulase-Negative Staphylococci

The neutrophil oxidative burst is a product of the regulated assembly of the multicomponent oxidase enzyme. Our aim was to compare the oxidative burst in term (n = 10) and preterm newborns <31 wk gestational age (n = 10) after stimulation with coagulase-negative staphylococci in vitro. Strains of Streptococcus epidermidis with different invasive and slime-producing properties, one strain of S. haemolyticus, and one strain of group B-streptococcus were investigated. A whole-blood flow cytometric assay using the oxidation of hydroethidine to ethidium bromide was used. The oxidative activity in unstimulated neutrophil granulocytes [polymorphonuclear leukocytes (PMNLs)] was similar in term and preterm newborns, but the preterm newborns showed a significantly lower capacity to up-regulate the oxidative burst intensity after bacterial stimulation (p = 0.004). In the term but not in the preterm group, the oxidative burst intensity after bacterial stimulation correlated with the baseline oxidative burst intensity. After bacterial stimulation, there was a trend toward a greater percentage of activated neutrophils in the term group than in the preterm group, but the difference was less pronounced than that in oxidative burst intensity. Significant differences in oxidative burst response to different bacterial strains were observed (p < 0.001), but the differences could not be correlated exclusively to invasive capacity or slime-producing properties. It is concluded that the baseline oxidative activity is similar in term and preterm PMNLs but that preterm PMNLs have a decreased capacity to increase the oxidative burst in response to bacterial stimulation.

Real‐time PCR of the 16S‐rRNA gene in the diagnosis of neonatal bacteraemia

Objective: To evaluate a real‐time PCR assay for the diagnosis of neonatal bacteraemia.