Inter-rater reliability of the Silverman and Andersen index-a measure of respiratory distress in preterm infants.

BACKGROUND: There are various methods of respiratory support available to optimize respiratory function in preterm infants. Respiratory scoring tools might provide information on which method to choose and the level and duration of support needed. Before implementing a respiratory scoring tool in our clinical practice, we aimed to test the inter- and intra-rater reliability of the Silverman and Andersen index (SA index) among neonatologists and nurses when applied to preterm infants on respiratory support. We also examined the association between the SA index and the electrical activity of the diaphragm (Edi signals). METHODS: This was a multicenter study including three newborn intensive care units in Norway. Four neonatologists and 10 nurses applied the SA index when assessing 80 videos of 44 preterm infants on High Flow Nasal Cannula, Continuous Positive Airway Pressure and Neurally Adjusted Ventilatory Assist. The inter- and intra-rater reliability for the sum scores were measured by the intra-class correlation coefficient (ICC), and Kendall's W was used to assess the degree of agreement for each item. We quantified the association between the Edi signals and the SA index scores by the Spearman's correlation coefficient. RESULTS: We found poor inter-rater reliability with an ICC for absolute agreement of 0.34 (95% CI: 0.20 to 0.53). There was fair agreement measuring each item separately for upper chest movements (Kendall's W 0.30), and moderate for lower chest movements (0.43) and xiphoid retractions (0.44). Expiratory grunting showed substantial agreement (0.67). The intra-rater reliability was good (ICC for absolute agreement 0.77; 95% CI: 0.68 to 0.84). We found a moderate positive correlation (r = 0.468, p = 0.028) between the maximum inspiratory diaphragm activity (Edi peak) and the mean inspiratory SA index scores. CONCLUSION: Our study showed poor inter-rater and good intra-rater reliability of the SA index when nurses and neonatologists assessed videos of preterm infants on various types of respiratory support. Edi peak and SA index had a moderate positive correlation. Formal training might be essential to improve the inter-rater reliability. TRIAL REGISTRATION: Registered 26th June 2017, ClinicalTrials.gov Identifier: NCT03199898.

Skin-to-skin contact in the delivery room for very preterm infants: a randomised clinical trial.

OBJECTIVE: Evaluating safety, feasibility and effects on physiological parameters of skin-to-skin contact (SSC) from birth between mothers and very preterm infants in a high-income setting. DESIGN: Open-label randomised controlled trial. SETTING: Three Norwegian neonatal units. PATIENTS: Preterm infants at gestational age (GA) 280-316 weeks and birth weight >1000g delivered vaginally or by caesarean section (C-section). INTERVENTION: Two hours of early SSC between the mother and the infant compared to standard care (SC) where the infant is separated from the mother and transferred to the neonatal unit in an incubator. RESULTS: 108 infants (63% male, 57% C-section, mean (SD) GA 30.3 weeks (1.3) and birth weight 1437 g (260)) were included. Median (IQR) age at randomisation was 23 min (17-30). During the first 2 hours after randomisation, 4% (2 of 51) and 7% (4 of 57) were hypothermic (<36.0°C) in the SSC and SC group, respectively (p=0.68, OR 0.5, 95% CI 0.1 to 3.1). Significantly fewer infants in the SSC group had hyperthermia (>37.5°C) (26% (13 of 57) vs 47% (27 of 51), respectively, p=0.02, OR 0.4, 95% CI 0.2 to 0.9). No infant needed mechanical ventilation within the first 2 hours. Median (IQR) duration of SSC was 120 (80-120) min in the intervention group. There was no difference in heart rate, respiratory rate and oxygen saturation between groups during the first 24 hours. CONCLUSION: This study from a high-income setting confirmed that SSC from birth for very preterm infants was safe and feasible. Physiological parameters were not affected by the intervention. The long-term effects on neurodevelopment, maternal-infant bonding and maternal mental health will be collected. TRIAL REGISTRATION NUMBER: NCT02024854.

Iterative Development, Validation, and Certification of a Smartphone System to Assess Neonatal Jaundice: Development and Usability Study.

BACKGROUND: Medical device development is an area facing multiple challenges, resulting in a high number of products not reaching the clinical setting. Neonatal hyperbilirubinemia, manifesting as neonatal jaundice (NNJ), is an important cause of newborn morbidity and mortality. It is important to identify infants with neonatal hyperbilirubinemia at an early stage, but currently there is a lack of tools that are both accurate and affordable. OBJECTIVE: This study aimed to develop a novel system to assess the presence of NNJ. The device should provide accurate results, be approved as a medical device, be easy to use, and be produced at a price that is affordable even in low-resource settings. METHODS: We used an iterative approach to develop a smartphone-based system to detect the presence of NNJ. We performed technical development, followed by clinical and usability testing in parallel, after which we initiated the regulatory processes for certification. We updated the system in each iteration, and the final version underwent a clinical validation study on healthy term newborns aged 1 to 15 days before all documentation was submitted for conformity assessment to obtain Conformité Européenne (CE) certification. We developed a system that incorporates a smartphone app, a color calibration card, and a server. RESULTS: Three iterations of the smartphone-based system were developed; the final version was approved as a medical device after complying with Medical Device Regulation guidelines. A total of 201 infants were included in the validation study. Bilirubin values using the system highly correlated with total serum or plasma bilirubin levels (r=0.84). The system had a high sensitivity (94%) to detect severe jaundice, defined as total serum or plasma bilirubin >250 µmol/L, and maintained a high specificity (71%). CONCLUSIONS: Our smartphone-based system has a high potential as a tool for identifying NNJ. An iterative approach to product development, conducted by working on different tasks in parallel, resulted in a functional and successful product. By adhering to the requirements for regulatory approval from the beginning of the project, we were able to develop a market-ready mobile health solution.

Bilirubin estimates from smartphone images of newborn infants' skin correlated highly to serum bilirubin levels.

AIM: Neonatal jaundice is an important cause of morbidity and mortality, and identifying the condition remains a challenge. This study evaluated a novel method of estimating bilirubin levels from colour-calibrated smartphone images. METHODS: A cross-sectional prospective study was undertaken at two hospitals in Norway from February 2017 to March 2019, with standardised illumination at one hospital and non-standardised illumination at the other hospital. Healthy term-born infants with a normal birthweight were recruited up to 15 days of age. The main outcome measures were bilirubin estimates from digital images, plus total bilirubin in serum (TSB) and transcutaneous bilirubin (TcB). RESULTS: Bilirubin estimates were performed for 302 newborn infants, and 76 had severe jaundice. The correlation between the smartphone estimates and TSB was measured by Pearson's r and was .84 for the whole sample. The correlation between the image estimates and TcB was 0.81. There were no significant differences between the hospitals. Sensitivity was 100%, and specificity was 69% for identifying severe jaundice of more than 250 µmol/L. CONCLUSION: A smartphone-based tool that estimated bilirubin levels from digital images identified severe jaundice with high sensitivity and could provide a screening tool for neonatal jaundice.

A nine-day-old girl with fever. / En ni dager gammel jente med feber.

Nowadays severe illness in neonates is fortunately rare in Norway. However, newborns present with non-specific symptoms, making diagnostics in this age group challenging, and neonatologists need to think broadly in order not to overlook serious illness. We present the case of a nine-day-old who was severely ill when she arrived at hospital. She was born in gestational week 37 after a normal pregnancy. The birth was complicated by shoulder dystocia, rupture of the umbilical cord and fracture of the clavicle. Thereafter she had a normal stay in the maternity ward for three days. At home she appeared healthy and gained weight until she returned to hospital after thirteen hours of poor feeding, irritability and fever. The symptoms turned out to be caused by bacterial meningitis. During the first week of hospitalisation she developed ventriculitis, brain abscesses and sinus vein thrombosis. It was later discovered that she had severely impaired hearing, and thereafter she developed hydrocephalus requiring surgical drainage. The mortality from neonatal bacterial meningitis has dropped from almost 50 % in the 1970s to less than 10 % today, but the morbidity has remained unchanged. It is crucial that clinicians are alert to this diagnosis, as delayed treatment can worsen the prognosis.

Skin-to-skin contact during eye examination did not reduce pain compared to standard care with parental support in preterm infants.

AIM: We compared the pain relieving effect of skin-to-skin contact versus standard care in the incubator during screening for retinopathy of prematurity. METHODS: This randomised crossover study included 35 preterm infants of less than 32 weeks of gestational age admitted to St Olavs University Hospital, Trondheim, Norway, between January 2014 and June 2016. Randomisation was for skin-to-skin with one of the parents or standard care with supportive positioning by parents for the first of two consecutive eye examinations. The pain score was measured twice using the Premature Infant Pain Profile (PIPP) during and after the eye examination. The infants' movement activity was video recorded after the examination. RESULTS: There was no difference in mean pain scores with skin-to-skin contact versus standard care during (10.2 vs. 10.3, p = 0.91) or after (7.0 vs. 6.8, p = 0.76) the procedure. Independent of the randomisation group, PIPP scores were lower than previous comparable studies have found. Bouts of movement activity were also the same whether the examination was conducted in skin-to-skin position or in the incubator (p = 0.91). CONCLUSION: Skin-to-skin contact during the eye examination did not provide additional pain relief compared to standard care where the parents were already a part of the multidimensional approach.

Randomised controlled trial showed that neonates received better pain relief from a higher dose of sucrose during venepuncture.

AIM: We compared the effect of two different doses of sucrose on neonatal pain scores during venepuncture. METHODS: This randomised crossover study focused on neonates born weighing more than 1000 g from December 2014 to June 2016, who received neonatal intensive care at two hospitals: one in Empangeni, South Africa, and one in Trondheim, Norway. During two consecutive venepuncture procedures, 27 neonates from South Africa and 26 neonates from Norway were randomised to receive 0.2 mL or 0.5 mL sucrose. Half was administered two minutes before venepuncture and the rest immediately before the procedure. South Africa used 25% sucrose and Norway 24%. Pain scores were measured twice using the Premature Infant Pain Profile-Revised: during skin puncture and after the needle was removed. RESULTS: The mean pain scores during skin puncture were significantly lower with 0.5 mL sucrose than with 0.2 mL (5.3 versus 6.8, p=0.008), but the mean pain scores after the needle was removed were similar with both doses (4.7 versus 5.4, p=0.29). We found no significant association between weight and pain scores. CONCLUSION: We showed that neonates received better pain relief from 0.5 mL than 0.2 mL sucrose during venepuncture but not after the needle was removed.

A randomised cross-over study showed no difference in diaphragm activity during weaning from respiratory support.

AIM: We measured electrical activity of the diaphragm (Edi) to compare the breathing effort in preterm infants during weaning from respiratory support with high-flow nasal cannulae (HFNC) or nasal continuous positive airway pressure (nCPAP). METHODS: This randomised cross-over study was carried out at St Olav's University Hospital, Trondheim, Norway, from December 2013 to June 2015. We gave 21 preterm infants weighing at least 1000 g HFNC 6 L/minute for four hours and nCPAP 3 cmH2 O for four hours with a one-hour wash-out period. Measurements included diaphragmatic load, Edi, vital signs and a modified Silverman-Andersen Retraction Score. RESULTS: We found no differences in HFNC and nCPAP in the median Edi peak (8.0 µV versus 7.8 µV, p = 0.095), median Edi min (1.1 µV versus 1.2 µV in, p = 0.958) or mean heart rate (157 versus 159, p = 0.300) in the 21 infants who took part. The mean respiratory rate was significantly lower during HFNC than nCPAP (47 versus 52, p = 0.012). The modified Silverman-Andersen Retraction Score showed no significant differences. CONCLUSION: This study of preterm infants found no difference in the breathing effort measured by Edi between HFNC 6 L/minute and nCPAP 3 cmH2 O. HFNC could replace nCPAP when preterm infants are ready for weaning.

Early skin-to-skin contact or incubator for very preterm infants: study protocol for a randomized controlled trial.

BACKGROUND: Skin-to-skin care immediately following delivery is a common practice for term infants and has been shown to improve cardiorespiratory stability, facilitate early bonding, and promote breastfeeding. Since 2007, the use of skin-to-skin care has been practiced for preterm infants from 32 weeks of gestation in the delivery room at St. Olav's University Hospital. In the present study we aim to investigate whether skin-to-skin care following delivery is safe, and how it affects early and late outcomes compared to standard care for very preterm infants. METHODS/DESIGN: A randomized controlled trial (RCT) of skin-to-skin care in the delivery room for very preterm infants born at gestational age 280-316 weeks with birth weight >1000 grams. Infants with severe congenital malformations or need of intubation in the delivery room are excluded. A detailed checklist and a flowchart were prepared for the study, and all involved professionals (neonatologists, neonatal nurses, obstetricians, anesthesiologists, midwives) participated in medical simulation training prior to study start on February 1, 2014. A consultant in neonatology and a neonatal nurse are present at all deliveries. Infants with birth weight <1500 grams receive an intravenous line with glucose, amino acids, and caffeine citrate in the delivery room. Infants with gestational age <30 weeks are routinely put on continuous positive airway pressure (CPAP). After initial stabilization, infants are randomized to skin-to-skin care or are transferred to the nursery in an incubator. Primary outcome is cognitive development at 2 years measured with the Bayley Scales of Infant Development, Third Edition. Secondary outcomes are safety defined as hypothermia, respiratory failure, and/or cardiopulmonary resuscitation, physiological stability after birth and motor, language and cognitive development at 1 year for the child, and mental health measured with the State-Trait Anxiety Inventory (STAI) at discharge, and at 3 months and 2 years after expected date of delivery for the mothers. DISCUSSION: The study may have important implications for the initial care for very preterm infants after delivery and increase our understanding of how early skin-to-skin care affects preterm infants and their mothers. TRIAL REGISTRATION: ClinicalTrials, NCT02024854 . Registered on 19 December 2013.

Skin-to-Skin Care After Birth for Moderately Preterm Infants.

OBJECTIVE: To investigate the feasibility and safety of skin-to-skin care after birth for moderately preterm infants. DESIGN: Prospective cohort study. SETTING: The study was conducted at the maternity wards and NICUs of three study sites in Norway. PARTICIPANTS: Ninety preterm infants born vaginally with gestational ages of 32 weeks/0 days to 34 weeks/6 days. METHODS: Comparison of groups of preterm infants who received skin-to-skin care or conventional treatment in incubators after birth. RESULTS: Median gestational age and birth weight were similar in the two groups: 33 weeks/5 days versus 34 weeks/3 days (p = .464) and 2,100 versus 2,010 g (p = .519). There were no differences in the first body temperature (p = .841) and blood glucose level (p = .539) between the groups. CONCLUSION: Early skin-to-skin contact in the delivery room for moderately preterm infants may be feasible and safe.

Early-onset Sepsis and Antibiotic Exposure in Term Infants: A Nationwide Population-based Study in Norway.

BACKGROUND: Sepsis is a leading cause of neonatal morbidity and mortality. Clinical suspicion may lead to overuse of antibiotics. The objective of this study was to assess the epidemiology of early-onset sepsis (EOS) and antibiotic exposure during the first week of life in Norwegian term infants. METHODS: This is a nationwide population-based study from the Norwegian Neonatal Network. During the 3-year study period (2009-2011), 20 of Norway's 21 neonatal units prospectively collected data. Among 168,877 live-born (LB) term infants born during the study period, 10,175 (6.0%) infants were hospitalized in the first week of life and included in the study. RESULTS: There were 91 cases of culture-confirmed EOS (0.54 per 1000 LB) and 1447 cases classified as culture-negative EOS (8.57 per 1000 LB). The majority of culture-confirmed EOS cases were caused by Gram-positives (83/91; 91%), most commonly group B streptococci (0.31 per 1000 LB). Intravenous antibiotics were administered to 3964 infants; 39% of all admissions and 2.3% of all LB term infants. Empiric therapy consisted of an aminoglycoside and either benzylpenicillin or ampicillin in 95% of the cases. The median (interquartile range) treatment duration was 8 (7-10) days for culture-confirmed EOS and 6 (5-7) days for culture-negative EOS. There was 1 EOS-attributable death (group B streptococcal EOS) during the study period. CONCLUSIONS: In this registry-based study, the incidence of culture-confirmed EOS was in line with previous international reports and the mortality was very low. A large proportion of infants without infection were treated with antibiotics. Measures should be taken to spare neonates unnecessary antibiotic treatment.

Group B Streptococcus colonization during pregnancy and maternal-fetal transmission in Zimbabwe.

OBJECTIVE: To explore risk factors for group B Streptococcus (GBS) colonization during pregnancy and at delivery, estimate the predictive value of early GBS colonization for colonization at delivery and in the newborn, and explore the relationship to adverse perinatal factors. DESIGN AND SETTING: Cohort study of pregnant women from three communities in Zimbabwe. METHODS: Information collected by questionnaire at inclusion and from delivery records. Vaginal and rectal swabs collected for GBS culture at 20 and 26 weeks gestation, at delivery and from the newborn infant. MAIN OUTCOME MEASURES: GBS colonization in pregnancy, colonization of mother and newborn, and perinatal factors. RESULTS: GBS culture results were obtained at one or more occasion for 780 (75.2%) of 1,037 women recruited. Altogether, 470/780 women (60.3%) tested positive for GBS, with colonization rates at 20, 26 weeks and delivery of 47%, 24.2% and 21%, respectively. Positive GBS culture at 20 and 26 weeks gestation had a low positive predictive value on colonization at delivery and in the newborn. Women living in rural areas were significantly more often colonized than those who lived in urban areas (p < 0.001). Other socio-economic, demographic and obstetric factors were not statistically associated with GBS colonization. GBS transmission was not statistically significantly associated with adverse perinatal outcomes. CONCLUSIONS: GBS colonization was common among pregnant women in Zimbabwe. Dwelling in a rural area was significantly associated with GBS colonization while other risk factors were not. Early GBS colonization had a low predictive value for colonization at delivery and colonization was not associated with adverse perinatal outcome.

Antimicrobial susceptibility of invasive group B streptococcal isolates from south-west Sweden 1988-2001.

The antibiotic susceptibility of 297 invasive isolates of group B streptococci (GBS) to a panel of 12 antibiotics was analysed using the E-test. The isolates (from 123 neonates and 174 adults) were collected from south-west Sweden during the 2 periods 1988-1997 and 1998-2001. The breakpoints of the Clinical and Laboratory Standards Institute were used. All isolates were sensitive to cefotaxime, meropenem, linezolid, vancomycin, moxifloxacin and quinupristin-dalfopristin. Two strains displayed a slightly decreased susceptibility to penicillin G (MIC 0.25 microg/ml) also when tested by the broth dilution method. Two per cent were resistant to erythromycin and 1% to clindamycin. Strains with intermediate sensitivity to erythromycin and clindamycin increased over the 2 study periods. 68% were resistant to doxycycline, and the resistance rate for doxycycline increased over the 2 study periods. No strain was resistant to trimethoprim-sulfamethoxazole. Serotype V dominated among strains with intermediate susceptibility to erythromycin and clindamycin. There were no other relationships between serotypes and decreased sensitivity to any agent. There were no significant differences in susceptibility to any agent tested between strains isolated from neonates and adults. In conclusion, penicillins remain the drug of choice in the region but with the increasing rates of intermediate susceptibility to both erythromycin and clindamycin, antibiotic sensitivity analysis should be performed on the GBS isolates from penicillin-allergic patients.

Real-time PCR targeting the sip gene for detection of group B Streptococcus colonization in pregnant women at delivery.

Group B streptococcus (GBS) is an important aetiological agent of serious neonatal infections. A rapid and sensitive method for the detection of GBS colonization in pregnant women at delivery could make intrapartum screening for GBS possible. A real-time PCR method targeting the sip gene of GBS in pregnant women at delivery has been evaluated. The performance of the real-time PCR was compared with optimized GBS culture. Separate vaginal and rectal swabs were collected from women hospitalized at the delivery department at St Olavs Hospital, Trondheim, Norway, from January 15 through May 2005. The specimens were cultured on selective blood agar plates and in selective broth and examined by real-time PCR. Of samples from 251 women, 87 (34.7%) were GBS positive by culture and 86 (34.3%) were positive by PCR. Using GBS culture as the 'gold standard', the sensitivity of real-time PCR was 0.97 (95% confidence interval 0.90-0.99) and specificity was 0.99 (95% confidence interval 0.97-1.00). In two women the PCR was positive and the culture negative. Additional analysis using cylE PCR substantiates that these two women were true GBS carriers with negative GBS culture. The rate of GBS colonization was lower in vaginal specimens than in rectal specimens both by culture and PCR. The real-time PCR assay is fast, highly sensitive and specific for detecting GBS colonization in pregnant women at delivery, and has the potential for intrapartum detection of GBS colonization. Both vaginal and rectal samples are required to achieve highest possible detection rate.