The cost-effectiveness of home phototherapy for hyperbilirubinemia in neonates: results from a randomized controlled trial.

This study aimed to establish the cost-effectiveness of home phototherapy versus hospital phototherapy treating hyperbilirubinemia in neonates more than 36 weeks. Based on clinical results from a randomised controlled trial showing that home phototherapy for hyperbilirubinemia in term neonates is as effective as hospital phototherapy, we performed a cost-minimisation analysis to identify the most cost-effective alternative. We included costs for health care resource use as well as costs for transportation in connection with re-visits. The cost per patient was €337 for home phototherapy compared with €1156 for the hospital alternative indicating average cost savings of €819 (95% confidence interval €613-1025) or 71% per patient. Transportation and outpatient costs were higher in the home treatment group and hospital care costs were higher in the hospital group. Sensitivity analysis shows that results are robust also when allowing for uncertainty. Home phototherapy for neonates more than 36 weeks costs less than in-hospital phototherapy while being equally effective, meaning that home phototherapy is a cost-effective alternative to hospital treatment for infants with neonatal hyperbilirubinemia.Trial registration NCT03536078 . Date of registration: 24/05/2018.

Home phototherapy of term neonates improves parental bonding and stress: Findings from a randomised controlled trial.

AIM: We aimed to evaluate whether in-home phototherapy for hyperbilirubinaemia could reduce the poorer parent-infant bonding and increased parental stress associated with neonatal hospital treatment. METHODS: In this multicentre randomised controlled trial, we allocated families to either home phototherapy or standard hospital care. The primary outcome was parent-infant bonding measured on the Postpartum Bonding Questionnaire directly after therapy and 4 months later. Secondary outcomes were results on four other instruments measuring parental bonding, quality of life and mental health. RESULTS: We randomised 78 of 147 newborn infants to intervention and 69 to the control group. No significant differences were detected in length of stay, mean bilirubin, or weight gain. Parents in the intervention group had better scores on bonding both at discharge (p = 0.034) and at 4 months (p = 0.008; effect size r = 0.2) and lower levels of stress at 4 months (p = 0.024) than controls. No statistically significant outcomes were found for the secondary outcomes. CONCLUSION: In-home phototherapy improved bonding and reduced parental stress in comparison with usual in-hospital treatment. Caregivers should consider offering home phototherapy to families of non-immunised term infants with hyperbilirubinaemia.

Leakage of isopropanol from port protectors used in neonatal care-Results from an in vitro study.

BACKGROUND: To decrease contamination of needleless catheter hubs, caps or port protectors impregnated with isopropanol (IPA) have been developed and shown to be superior to other disinfection methods. The safety of the caps has been questioned, as they can be associated with alcohol leakage across the hub membrane. OBJECTIVES: We evaluated the use of IPA caps and the scrub-the-hub method from the safety standpoint of possible alcohol leakage across the hub membrane. METHODS: Circuits imitating an intravenous line were constructed. Circuits with an IPA cap were flushed with sodium chloride after the hub had been exposed to the cap for 1 hour, 24 hours, and 7 days. At the end of each period the fluid was collected and amounts of IPA in it were measured, using gas chromatography. Scrub circuits without IPA caps were also tested and ethanol from these was measured using the same method. RESULTS: In this in vitro study, IPA was detected in all samples from cap circuits, and ethanol was detected from all scrub circuits. Leakage increased over time in IPA circuits. After 24 hours and 7 days of exposure, the first injection resulted in higher amounts of IPA; thereafter, the levels decreased. The amounts of ethanol measured from the scrub circuits were low. CONCLUSIONS: IPA caps can cause leakage of alcohol across the hub membrane. Leakage increased over time, and a 30 sec drying time was not sufficient to solve the problem. Scrub-the-hub seems safe to use with regard to alcohol leakage.

Seizures in newborn infants without hypoxic ischemic encephalopathy - antenatal and labor-related risk factors: a case-control study.

Objective: To identify antepartum and intrapartum risk factors for neonatal seizures in the absence of hypoxic ischemic encephalopathy (HIE).Methods: Population-based case-control study. Of 98 484 births, 40 newborns at 34 gestational weeks or later had seizures within the first 7 days of life. Cases (n = 40) and controls (n = 160) were retrieved from the University hospitals of Örebro for 1994-2013 and Uppsala for 2003-2013. Demographics and characteristics of pregnancy, labor, delivery, and neonatal data were analyzed. Crude odds ratio (OR) and adjusted odds ratios (AOR) with 95% confidence intervals (CIs) for antenatal and intrapartum factors were calculated using logistic regression analysis. Main outcome measure was neonatal seizures within the first 7 days of life.Results: The incidence of neonatal seizures without HIE was 0.41/1000 live births. Antenatal risk factors for neonatal seizures were as follows: short maternal stature (AOR: 5.4; 1.8-16.5); previous caesarean section (AOR: 4.8; 1.5-15.0); and assisted fertilization (AOR: 6.8; 1.3-35.2). Intrapartum risk factors were as follows: induction of labor (AOR: 5.7; 1.8-17.7); preterm birth (AOR: 13.5; 3.7-48.9); and head circumference >37 cm (AOR: 6.9; 1.4-34.8).Conclusions: Preterm birth was the strongest risk factor for neonatal seizures in the absence of HIE. The results also indicate that feto-pelvic disproportion is associated with the occurrence of seizures.Rationale: Antepartum and intrapartum risk factors for newborn seizures in the absence of HIE were investigated in a case-control study. Out of 98 484 births at 34 gestational weeks or more, 40 newborns had seizures without HIE. All had a normal Apgar score although they later presented with seizures. Preterm birth was the strongest risk factor (OR: 13.5; 95% CI: 3.7-48.9). Our results also indicate that feto-pelvic disproportion is of importance. Furthermore, a history of prior caesarean was associated with seizures. This is the first study to assess obstetric risk factors for newborn seizures separate from those with seizures and concomitant HIE. The distinction is of importance due to different etiologies, treatments, and preventive strategies.

Neurophysiological and behavioral measures of pain during neonatal hip examination.

Introduction: The aim of this study was to test the hypothesis that neonatal hip examination causes pain in newborns. Pain assessment using instruments such as the Premature Infant Pain Profile-Revised (PIPP-R) scale is recommended, but recently physiological and neurophysiological measures, for example, near-infrared spectroscopy (NIRS) and galvanic skin response (GSR), have been used as well. Methods: Heart auscultation and hip examination were performed, and the response of the newborn was registered by NIRS optodes, GSR electrodes, and a pulse oximeter probe attached to the infant. The face of the newborn was filmed. Heart auscultation was used as a nonpainful reference. Results: The pain scores for hip examination were higher than for the heart auscultation. Near-infrared spectroscopy showed a significant higher increase from baseline in oxygenated hemoglobin (HbO2) on both sides of the cortex at hip examination compared with at heart auscultation (P = .011 and P = .017). Mean PIPP-R scores for the hip examination compared with heart auscultation increased from 3.0 to 8.1 (P = .000). The GSR analyses of hip examination compared with heart auscultation showed a significant increase in area under small peaks during the hip examination (P = .016), however, not when measured in peaks per second (P = .104). Interrater reliability was calculated for the NIRS interpretations, with an intraclass correlation coefficient (ICC) range of 0.93-1.0 (P = .000). Discussion: Pain in newborns can have negative consequences, and pain prevention and treatment are therefore important. We conclude that neonatal hip examinations are painful and that the pain should be treated, for example, with oral sweet solution. This is a change from present routines during neonatal hip examination and is hoped to lead to a change in national guidelines.

Oral sweet solution to prevent pain during neonatal hip examination: a randomised controlled trial.

AIM: To determine if oral glucose can have a pain-relieving effect during routine hip examinations in newborn infants. METHODS: In this randomised controlled study 100 newborn infants undergoing the routine physical examination including the potentially painful hip examination were included between March 2016 and April 2017. Fifty infants were randomised to water (control) and 50 to oral glucose (intervention) before their examination. Pain was assessed using crying time, Astrid Lindgren and Lund Children's Hospital Pain and Stress Assessment Scale (ALPS-Neo) and Visual analogue scale (VAS). RESULTS: Total crying time (p = 0.006), crying time during the hip examination (p = 0.026), ALPS-Neo (p = 0.004) and VAS (p = 0.006) (when assessed by the physician) were all significantly decreased in the group of infants receiving glucose. VAS assessment made by the parents did not reach statistical significance (p = 0.127). CONCLUSION: Oral glucose given before the examination has a pain-relieving effect during the hip examination in healthy newborn infants.

Neurodevelopmental Outcomes Among Extremely Preterm Infants 6.5 Years After Active Perinatal Care in Sweden.

IMPORTANCE: Active perinatal care increases the rate of survival of extremely preterm infants, but there are concerns that improved survival might increase the rate of disabled survivors. OBJECTIVE: To determine the neurodevelopmental outcomes of a national cohort of children 6.5 years of age who had been born extremely preterm (<27 weeks' gestational age) in Sweden. DESIGN, SETTING, AND PARTICIPANTS: Population-based prospective cohort study of consecutively born extremely preterm infants. All of these infants were born in Sweden during the period from April 1, 2004, to March 31, 2007. Of 707 live-born extremely preterm infants, 486 (68.7%) survived to 6.5 years of age. These children were assessed and compared with matched controls who had been born at term. Comparison estimates were adjusted for demographic differences. Assessments ended in February 2014, and analysis started thereafter. MAIN OUTCOMES AND MEASURES: Cognitive ability was measured with the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV), and the mean (SD) scores of the children who had been born extremely preterm were compared with those of the controls. Clinical examinations and parental questionnaires were used for diagnosis of cerebral palsy, hearing and vision impairments, and cognition for the children who were not assessed with the WISC-IV. RESULTS: Of 486 eligible infants who were born extremely preterm, 441 (90.7%) were assessed at 6.5 years of age (59 by medical record review only) alongside 371 controls. The adjusted mean (SD) full-scale WISC-IV score was 14.2 (95% CI, 12.1-16.3) points lower for children who had been born extremely preterm than for controls. Cognitive disability was moderate for 18.8% of extremely preterm children and 2.2% of controls (P < .001), and it was severe for 11.1% of extremely preterm children and 0.3% of controls (P < .001). Cerebral palsy was observed in 9.5% of extremely preterm children and 0.0% of controls (P < .001), blindness was observed in 2.0% of extremely preterm children and 0.0% of controls (P < .001), and hearing impairment was observed in 2.1% of extremely preterm children and 0.5% of controls (P = .07). Overall, 36.1% (95% CI, 31.7%-40.6%) of extremely preterm children had no disability, 30.4% (95% CI 26.3%-34.8%) had mild disability, 20.2% (95% CI, 16.6%-24.2%) had moderate disability, and 13.4% (95% CI, 10.5%-16.9%) had severe disability. For extremely preterm children, moderate or severe overall disability decreased with gestational age at birth (adjusted odds ratio per week, 0.65 [95% CI, 0.54-0.79]; P < .001) and increased from 26.6% to 33.5% (P = .01) for children assessed both at 2.5 and 6.5 years. CONCLUSIONS AND RELEVANCE: Of the 441 extremely preterm infants who had received active perinatal care, 293 (66.4%) had no or mild disability at 6.5 years; of the 371 controls, 11 (3.0%) had moderate or severe disability. Disability rates at 6.5 years increased relative to the rates at 2.5 years. Results are relevant for health care professionals and planners, and for clinicians counseling families facing extremely preterm births.

Sepsis as a risk factor for neonatal morbidity in extremely preterm infants.

AIM: This study evaluated sepsis as a risk factor for neonatal morbidities and investigated the association between specific pathogens and neonatal morbidities. METHODS: This was a nationwide Swedish prospective cohort study, consisting of the 497 extremely premature children, who were born before 27 weeks of gestation between 2004 and 2007 and survived their first year of life. Neonatal sepsis was evaluated as a risk factor for neonatal morbidity using multiple logistic linear regression analyses. RESULTS: We found that 326 (66%) of the infants had at least one sepsis episode and coagulase-negative staphylococci was the most common pathogen. Definite sepsis, with an odds ratio (OR) of 1.6, was associated with severe bronchopulmonary dysplasia, but not clinical sepsis (OR 1.1). Definite sepsis was also associated with a prolonged hospital stay (OR 1.6). Sepsis was not significantly associated with a higher risk of retinopathy of prematurity or intraventricular haemorrhage. CONCLUSION: Extremely preterm infants face a great risk of acquiring neonatal sepsis, with coagulase-negative staphylococci being the most common pathogen in this population. Definite sepsis seemed to be a risk factor for severe bronchopulmonary dysplasia and prolonged hospital stay, but the associations were weaker than in previous studies.

Scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec reduced neonatal sepsis.

AIM: The aim of this study was to investigate whether scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec could reduce the incidence of neonatal sepsis in a level-three neonatal intensive care unit. METHODS: We studied the incidence of neonatal sepsis caused by coagulase-negative staphylococci (CoNS) for 16.5 months before the initiative was launched on May 15, 2012 and then for a further 8.5 months after it was introduced. The hub routine was applied to all intravenous catheters. RESULTS: During the control period before the initiative was launched, there were nine cases of CoNS sepsis compared with no cases after it was introduced, resulting in a decrease in sepsis incidence from 1.5% to 0% with a risk reduction of 1.5% (0.53-2.58%) (p = 0.06). In the preterm infant population, the incidence of sepsis decreased from 3.6% to 0% (1.1-6.0%) (p = 0.11). CONCLUSION: Scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec seemed to be an efficient way of preventing sepsis caused by CoNS in newborn infants. However, the evidence for the benefits will remain weak until a large randomised trial has been completed.

Neonatal encephalopathy and the association to asphyxia in labor.

OBJECTIVE: In cases with moderate and severe neonatal encephalopathy, we aimed to determine the proportion that was attributable to asphyxia during labor and to investigate the association between cardiotocographic (CTG) patterns and neonatal outcome. STUDY DESIGN: In a study population of 71,189 births from 2 Swedish university hospitals, 80 cases of neonatal encephalopathy were identified. Cases were categorized by admission CTG patterns (normal or abnormal) and by the presence of asphyxia (cord pH, <7.00; base deficit, ≥12 mmol/L). Cases with normal admission CTG patterns and asphyxia at birth were considered to experience asphyxia related to labor. CTG patterns were assessed for the 2 hours preceding delivery. RESULTS: Admission CTG patterns were normal in 51 cases (64%) and abnormal in 29 cases (36%). The rate of cases attributable to asphyxia (ie, hypoxic ischemic encephalopathy) was 48 of 80 cases (60%), most of which evolved during labor (43/80 cases; 54%). Both severe neonatal encephalopathy and neonatal death were more frequent with an abnormal, rather than with a normal, admission CTG pattern (13 [45%] vs 11 [22%]; P = .03), and 6 [21%] vs 3 [6%]; P = .04), respectively. Comparison of cases with an abnormal and a normal admission CTG pattern also revealed more frequently observed decreased variability (12 [60%] and 8 [22%], respectively) and more late decelerations (8 [40%] and 1 [3%], respectively). CONCLUSION: Moderate and severe encephalopathy is attributable to asphyxia in 60% of cases, most of which evolve during labor. An abnormal admission CTG pattern indicates a poorer neonatal outcome and more often is associated with pathologic CTG patterns preceding delivery.

Suboptimal care and metabolic acidemia is associated with neonatal encephalopathy but not with neonatal seizures alone: a population-based clinical audit.

OBJECTIVE: To determine the incidence of moderate to severe neonatal encephalopathy (NE) and neonatal seizures without encephalopathy, and the association with metabolic acidemia. Secondly, to investigate the occurrence of suboptimal intrapartum care and its impact on neonatal outcome. DESIGN: Clinical audit. SETTING: Two university hospitals in Sweden. POPULATION: Neonates ≥34 weeks with moderate or severe NE and neonatal seizures alone, i.e. without encephalopathy, from a population of 71 189 births, where umbilical blood gases were routinely analyzed. METHODS: Neonates were categorized depending on the presence of metabolic acidemia at birth by umbilical artery pH < 7.00, base deficit ≥12 mmol/L. Records were audited for suboptimal care and a decision was made on whether management was assessed to have impacted neonatal outcome. MAIN OUTCOME MEASURES: Encephalopathy and seizures alone. RESULTS: We identified 80 neonates with NE and 30 with seizures alone, of which 48 (60%) and none, respectively, had metabolic acidemia. Suboptimal care could be assessed in 77 and occurred in 28 (36%) NE cases and in one neonate with seizures alone (p < 0.001). In 47 NE cases with metabolic acidemia, suboptimal care occurred in 22 (47%) vs. 6/30 (20%) without metabolic acidemia (p = 0.02). Suboptimal care had an impact on outcome in 18/77 (23%) NE cases but in no cases with seizures alone. CONCLUSION: Suboptimal care was commonly seen with NE, particularly in neonates with metabolic acidemia, and also affected neonatal outcome. No such associations were found in neonates with seizures alone.

Diagnosis of neonatal sepsis by broad-range 16S real-time polymerase chain reaction.

BACKGROUND: The standard diagnostic test (blood culture) for suspected neonatal sepsis has limitations in sensitivity and specificity, and 16S polymerase chain reaction (PCR) has been suggested as a new diagnostic tool for neonatal sepsis. OBJECTIVES: To develop and evaluate a new real-time PCR method for detection of bacterial DNA in blood samples collected from infants with suspected neonatal sepsis. METHODS: Immediately after blood culture, a study sample of 0.5-1.0 ml whole blood was collected and used for a novel 16S real-time PCR assay. All positive samples were sequenced. Detailed case studies were performed in all cases with conflicting results, to verify if PCR could detect pathogens in culture negative sepsis. RESULTS: 368 samples from 317 infants were included. When compared with blood culture, the assay yielded a sensitivity of 79%, a specificity of 90%, a positive predictive value of 59%, and a negative predictive value of 96%. Seven of the 31 samples with a positive PCR result and a negative blood culture had definite or suspected bacterial sepsis. In five samples, PCR (but not blood culture) could detect a pathogen that was present in a blood culture collected more than 24 h prior to the PCR sample. CONCLUSIONS: This study presents an evaluation of a new real-time PCR technique that can detect culture-positive sepsis, and suggests that PCR has the potential to detect bacteria in culture-negative samples even after the initiation of intravenous antibiotics.

Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis.

AIM: To identify which clinical signs at presentation are most predictive of sepsis subsequently confirmed by blood culture and to investigate whether the predictive power of the clinical signs varies by gestational age. METHODS: Among 401 newborn infants < 28 days of age with suspected sepsis, nine signs of sepsis and C-reactive protein (CRP) values were prospectively recorded. Logistic regression assessed the association of these signs and laboratory values with a subsequently confirmed diagnosis of sepsis by positive blood culture. The analysis was stratified by gestational age with mutual simultaneous adjustment for the signs and sex. RESULTS: Five of the nine clinical signs (feeding intolerance, distended abdomen, blood pressure, bradycardia and apnoea), along with CRP were statistically significantly associated with a positive blood culture. After simultaneous adjustment for all of the signs, apnoea, hypotension and CRP were independently predictive of positive blood culture. When the material was stratified by gestational age, differences in the association with positive blood culture were found for bradycardia, tachypnea and irritability/seizures. CONCLUSION: In this selected population of infants with suspected sepsis, apnoea and hypotension are independently predictive of a confirmed diagnosis, while bradycardia is more predictive among preterm infants and tachypnea among term infants.

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. PATIENTS AND METHODS: Two hundred ninety-five plasma samples from 288 newborns with suspected neonatal sepsis were collected prospectively for the purpose of polymerase chain reaction (PCR)-based bacterial detection. A real-time PCR targeting the bacterial gene for 16S-rRNA gene combined with four specific probes designed to detect Gram-negative bacteria, Staphylococcus aureus and coagulase-negative staphylococci (CoNS) was developed. All samples positive in the universal PCR were further sequenced for bacterial identification. RESULTS: When applied to a material from 50 patients with positive blood culture and 245 patients with negative blood culture, the universal PCR showed a sensitivity of 42% (28-57), a specificity of 95% (92-97), a positive predictive value of 64% (45-80), and a negative predictive value of 89% (84-92) (95% confidence intervals in brackets). CONCLUSION: A new real-time PCR technique was for the first time applied to a well-defined prospectively and consecutively enrolled material of newborns with suspected sepsis, combining the benefits of real-time PCR with specific probes and sequencing. The method managed to detect bacteraemia with high specificity even though the sensitivity was low. Factors causing the low sensitivity are identified and further strategies to develop the method are described.

Multiple group-specific sequencing primers for reliable and rapid DNA sequencing.

Pyrosequencing technology is a bioluminometric DNA sequencing method that employs a cascade of four enzymes to deliver sequence signals. To date this technology has been limited to the sequencing of short stretches of DNA. As an improvement to this technique, we have introduced a bacterial group-specific, multiple sequencing primer approach that circumvents sequencing of less informative semi-conservative regions of the 16S rRNA gene. This new approach is suitable for challenging templates, improving sequence data quality, avoiding sequencing of non-specific amplification products, lessening sequencing time, and moreover, this strategy should open the way for many new applications in the future. The group-specific, multiple sequencing primers can be applied in the Sanger dideoxy sequencing method as well. In addition, we have improved the chemistry of the Pyrosequencing system enabling sequencing of longer stretches of DNA, which allows numerous new applications.