Arild Erland Rønnestad

• Rozé, Jean Christophe; Cambonie, Gilles; Flamant, Cyril; Patkaï, Juliana; Mühlbacher, Tobias & Gascoin, Geraldine [Show all 53 contributors for this article] (2026). Prophylactic Treatment of Patent Ductus Arteriosus With Acetaminophen: A Randomized Clinical Trial. JAMA pediatrics. ISSN 2168-6203. 180(4), p. 374–383. doi: 10.1001/jamapediatrics.2025.6150. Full text in Research Archive
• Hapnes, Nina; Stensvold, Hans Jørgen; Dalen, Ingvild; Guthe, Hans Jørgen Timm; Støen, Ragnhild & Solevåg, Anne Lee [Show all 9 contributors for this article] (2026). Probiotics for extremely preterm infants: a Norwegian population-based study. Archives of Disease in Childhood: Fetal and Neonatal Edition. ISSN 1359-2998. doi: 10.1136/archdischild-2025-330176. Full text in Research Archive Show summary

  Objective: To compare mortality and morbidity in extremely preterm (EPT) and/or extremely low birthweight (ELBW) infants receiving or not receiving probiotic supplementation. Design: Nationwide, population-based registry study. Setting: All neonatal intensive care units (NICUs) in Norway. Participants: All EPT (<28 weeks)/ELBW (<1000 g) infants born between 2014 and 2021, admitted to an NICU. Infants who within the first week of life died, underwent surgery for necrotising enterocolitis (NEC) or did not receive enteral feeds or started with probiotics after the first week of life were excluded from the main analyses. Logistic regression, propensity score matching, inverse probability of treatment weighting (IPTW) and clustering analyses were applied. Main outcome measures: The primary outcome was all-cause mortality after the first week of life. Secondary outcomes were surgical NEC and late-onset sepsis after the first week of life, growth and probiotic sepsis. Results: Among 1596 live-born EPT/ELBW infants, 1268 were included in the main analysis and 676 (53.5%) started probiotics in the first week of life. Probiotics were associated with lower all-cause mortality (IPTW analysis; adjusted OR (aOR) 0.65, 95% CI 0.43 to 0.97), but no reduction in surgical NEC (aOR 0.83, 95% CI 0.49 to 1.43). However, in an emulated intention-to-treat scenario, high (>80%) probiotic use versus low (< 30%) was associated with a reduction in surgical NEC (aOR 0.40, 95% CI 0.19 to 0.86). We found no association between probiotics and sepsis or growth. 5 out of 858 infants (0.58%) exposed to probiotics developed probiotic-associated sepsis, all survived. Conclusion: Probiotic supplementation to EPT/ELBW infants was associated with lower all-cause mortality and possibly reduced NEC.

• Huncikova, Zuzana; Christensen, Martin; Wolden, Runa; Venter, Hermoine Jean; Gammelsrud, Karianne Wiger & Bjørnholt, Jørgen [Show all 15 contributors for this article] (2026). CoNS blood culture isolates from very preterm infants: antibiotic susceptibility, synergy testing and mecA gene expression. JAC-Antimicrobial Resistance (JAC-AMR). 8(2). doi: 10.1093/jacamr/dlag058. Full text in Research Archive Show summary

  Objectives: Previous reports suggest that neonatal sepsis with methicillin-resistant (MR) CoNS can be treated with first-generation cephalosporins. We have evaluated the in vitro effect of cefazolin and other antibiotics, synergy between β-lactams and aminoglycosides, and mecA expression in MR-CoNS isolates. Patients and methods: Antimicrobial susceptibility testing was performed in 167 CoNS isolates from 135 very preterm infants (&lt;32 weeks gestation) with late-onset sepsis. Microbroth dilution chequerboard assay explored antibiotic synergy. PCR detected mecA and three aminoglycoside-modifying enzyme genes. Induction experiments evaluated if exposure to cefazolin induces resistance. RT-PCR determined mecA expression in selected MR-CoNS isolates with different cefazolin/oxacillin MICs. Results: All CoNS isolates were susceptible to amikacin and vancomycin. Most were phenotypically resistant to gentamicin (92%) and cefoxitin (93%), and 89% carried the mecA gene. MIC90 values of cefazolin and oxacillin were 16 mg/L and &gt;256 mg/L, respectively. At the cefazolin breakpoint of 8 mg/L, 83% of isolates were susceptible in vitro. No antibiotic combinations showed synergy using the FIC index, but cefazolin combined with aminoglycosides had favourable susceptibility breakpoint index values. In a simplified synergy screen of ‘highly resistant’ isolates, growth was inhibited with a combination of gentamicin and cefazolin at sub-MIC concentrations in 8/42 (19%) isolates. Exposure to cefazolin sub-MICs caused reduced susceptibility in 1/30 (3%) tested isolates. The highest mecA expression was observed in isolates with high oxacillin/cefazolin MICs. Conclusions: CoNS isolates had lower MICs for cefazolin than oxacillin, and 83% were in vitro susceptible to cefazolin. A clinical trial comparing cefazolin with vancomycin as empirical therapy for suspected neonatal sepsis is warranted.

• Lappegård, Jostein; Lyeng, Ulrik Båtstrand; Støen, Ragnhild; Moster, Dag; Vatne, Anlaug & Nordvik, Tone [Show all 10 contributors for this article] (2026). Neonatal Seizures Were Associated With Higher Mortality, Epilepsy and Cerebral Palsy in Term‐Born Children up to 5 Years of Age. Acta Paediatrica. ISSN 0803-5253. 115(6), p. 1202–1209. doi: 10.1111/apa.70463. Full text in Research Archive Show summary

  Aim: This study described the aetiological factors associated with neonatal seizures and the risks for adverse neurological outcomes. Methods: We identified all infants born at ≥ 36 weeks of gestation between 2009 and 2015 who were diagnosed with or treated for neonatal seizures and registered in the Norwegian Neonatal Network. Data from four nationwide registries provided information on perinatal factors and neurological outcomes until 5 years of age. Results: There were 892 infants with seizures, which was an incidence of 2.2 per 1000 live births. More than half (58.5%) underwent electroencephalography monitoring and examinations. Mortality before discharge was 8.4% and deaths occurred a median of 5 days after birth. The most frequent presumed aetiology for neonatal seizures was moderate to severe hypoxic‐ischaemic encephalopathy (25.1%). Of the 817 survivors, 115 (14.1%) were diagnosed with post‐neonatal epilepsy, 119 (14.6%) with cerebral palsy (CP), and 43 (5.3%) had both diagnoses. The epilepsy risk was greatest after neonatal encephalopathy with normal Apgar scores (40.9%) and the CP risk was greatest after an ischaemic stroke (29.9%). Conclusion: Neonatal seizures were associated with a high risk of mortality and about a quarter were later diagnosed with epilepsy and/or CP. Improved access to electroencephalography and higher usage could improve diagnostics.

• Mjelle, Anders Batman; Solberg, Vilde; Rød, Emma; Stenersen, Eydis Oddsdottir; Garberg, Håvard Tetlie & Tølløfsrud, Per Arne [Show all 8 contributors for this article] (2025). C-Reactive Protein Levels of Healthy Term Infants Born After Prolonged Rupture of Membranes. Pediatric Reports. 17(6). doi: 10.3390/pediatric17060133. Full text in Research Archive Show summary

  Background/Objective: Even in the absence of infection, prolonged rupture of membranes (PROM) has been associated with elevated neonatal C-reactive protein (CRP). As both the sensitivity and specificity of CRP in predicting early-onset neonatal sepsis (EOS) may be low, we aimed to describe CRP levels during the first 36 h of life in term infants born after PROM ≥ 24 h. Methods: CRP was measured at 1, 12, and 36 h. Descriptive statistics and correlation analyses were performed, taking gestational age, birth weight, sex, delivery mode, and antibiotic treatment into account. Reference CRP values in healthy neonates without sepsis born after PROM were established. Results: Median (range) CRP was 0 (0–62) mg/L, 0 (0–82) mg/L, and 4 (0–92) mg/L at 1, 12, and 36 h, respectively. CRP at 12 and 36 (p < 0.001) but not 1 h was positively correlated with gestational age and birth weight. There was no difference in CRP after C-section vs. vaginal delivery. Among infants without sepsis, CRP was higher at all time points in infants who did vs. those who did not receive antibiotics (p < 0.001). Conclusions: CRP was low in term infants without sepsis born after PROM but with outliers above 60, 80, and 90 mg/L after 1, 12, and 36 h, respectively. Research is needed on the long-term outcomes of infants with inflammation, as evidenced by an elevated CRP after PROM.

• Server, Andrés; Latysheva, Anna; Nedregaard, Bård; Rønnestad, Arild Erland & Marthinsen, Pål Bache (2025). Neonatal subpial hemorrhage: clinical presentation, neuroimaging findings and outcome. Neuroradiology. ISSN 0028-3940. 67(4), p. 1071–1080. doi: 10.1007/s00234-025-03589-y. Full text in Research Archive
• Solvang, Thale Amalie Westre; Bråten, Vilde; Størdal, Ketil; Tveiten, Lars; Lang, Astri Maria & Eriksen, Beate Horsberg [Show all 8 contributors for this article] (2025). Admission temperature in very preterm infants 2012–2021: a Nationwide Quality Registry Study, Norway. BMJ Paediatrics Open. 9(1), p. 1–10. doi: 10.1136/bmjpo-2024-003263. Full text in Research Archive Show summary

  Objective To examine the distribution and time trends of admission temperature in very preterm infants, effects of temperature-preserving interventions and associations between hypothermia and outcomes. Methods Population-based cohort study of infants <32 gestational weeks without lethal malformations admitted to a neonatal intensive care unit within 2 hours of birth between 1 January 2012 and 31 December 2021. Hypothermia was defined as mild (36.0°C–36.4°C), moderate (34.5°C–35.9°C) or severe (<34.5°C). Associations between admission temperature and outcomes were investigated using multivariate logistic regression, adjusting for sex, weight Z-score, gestational age, antenatal steroids, surfactant and hospital. Results In total, 2457/4879 (50.4%) had normal admission temperatures between 36.5°C and 37.5℃, 1314 (26.9%) had mild hypothermia and 886 (18.2%) had moderate to severe hypothermia, with a significant interhospital variance of 7%–40%. Moderate to severe hypothermia decreased from 24% in 2012 to 16% in 2021 (ptrend<0.001). Measuring temperature before leaving the delivery unit correlated with lower incidence of moderate to severe hypothermia (42% vs 58%, p<0.001). Admission temperature was inversely associated with mortality (adjusted OR 1.5, 95% CI 1.1 to 2.0 for moderate and 2.4, 95% CI 1.1 to 4.9 for severe hypothermia) and with surgical necrotising enterocolitis or intestinal perforation (adjusted OR 1.7, 95% CI 1.1 to 2.7 for moderate and 3.1, 95% CI 1.3 to 7.7 for severe hypothermia). Conclusions Although the incidence of hypothermia decreased during the study period, it remains a concern due to significant associations with adverse outcomes. Areas for further improvement include addressing interhospital variance and enhancing temperature monitoring in the delivery unit.

• Dimopoulou, Varvara; Klingenberg, Claus Andreas; Navér, Lars; Nordberg, Viveka; Berardi, Alberto & Helou, Salhab el [Show all 46 contributors for this article] (2024). Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: an international study. Pediatric Research. ISSN 0031-3998. doi: 10.1038/s41390-024-03532-6. Full text in Research Archive Show summary

  Background - Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed the contribution of culture-negative cases to the overall antibiotic exposure in the first postnatal week.<p> <p>Methods - We conducted a retrospective analysis across eleven countries in Europe, North America, and Australia. All late-preterm and term infants born between 2014 and 2018 who received intravenous antibiotics during the first postnatal week were classified as culture-negative cases treated for ≥5 days (CN ≥ 5d), culture-negative cases treated for <5 days (CN < 5d), or CP-EOS cases.<p> <p>Results - Out of 757,979 infants, 21,703 (2.9%) received intravenous antibiotics. The number of infants classified as CN ≥ 5d, CN < 5d, and CP-EOS was 7996 (37%), 13,330 (61%), and 375 (1.7%). The incidence of CN ≥ 5d, CN < 5d, and CP-EOS was 10.6 (95% CI 10.3–10.8), 17.6 (95% CI 17.3–17.9), and 0.49 (95% CI 0.44–0.54) cases per 1000 livebirths. The median (IQR) number of antibiotic days administered for CN ≥ 5d, CN < 5d, and CP-EOS was 77 (77–78), 53 (52–53), and 5 (5-5) per 1000 livebirths.<p> <p>Conclusions - CN ≥ 5d substantially contributed to the overall antibiotic exposure, and was 21-fold more frequent than CP-EOS. Antimicrobial stewardship programs should focus on shortening antibiotic treatment for culture-negative cases.

• Hapnes, Nina; Stensvold, Hans Jørgen; Bjørnland, Kristin; Sæter, Thorstein; Guthe, Hans Jørgen Timm & Støen, Ragnhild [Show all 9 contributors for this article] (2024). Surgery for intestinal injuries in very preterm infants: a Norwegian population-based study with a new approach to disease classification. BMJ Paediatrics Open. 8(1), p. 1–9. doi: 10.1136/bmjpo-2024-002722. Full text in Research Archive Show summary

  Objective: To evaluate population-based data on very preterm infants (<32 weeks gestation) operated for intestinal injuries, focusing on necrotising enterocolitis (NEC) and focal intestinal perforation (FIP). Design: Nationwide, population-based registry cohort study. Setting: All 21 neonatal units in Norway. Participants: All very preterm infants born from 2014 through 2021 and admitted to a neonatal unit. Main outcome measures: Incidence of surgery for subgroups of intestinal injuries, medical record data on laboratory-radiology results, anatomical location of affected bowel, length of resections, number of reoperations, morbidities of prematurity and/or death before discharge. Results: Abdominal surgery was performed in 124/4009 (3.1%) very preterm infants and in 97/1300 (7.5%) extremely preterm infants <28 weeks. The main intestinal injuries operated were NEC (85/124; 69%), FIP (26/124; 21%) and ‘other abdominal pathologies’ (13/124; 10%). NEC cases were divided in (i) acute NEC, extensive disease (n=18), (ii) non-extensive disease (n=53) and (iii) NEC with surgery >3 days after disease onset (n=14). High lactate values immediately prior to surgery was predominantly seen in acute NEC-extensive disease and associated with high mortality. Other laboratory values could not discriminate between acute NEC and FIP. Timing of surgery for acute NEC and FIP overlapped. Radiological absence of portal venous gas was typical in FIP. Most infants (62.5%) underwent a stoma formation at initial surgery. The overall survival rate was 67% for NEC and 77% for FIP. Conclusion: NEC cases have different presentation and prognosis depending on the extent of bowel affected. Revised classifications for intestinal injuries in preterm infants may improve prognostication and better guide therapy.

• Glaser, Kirsten; Härtel, Christoph; Klingenberg, Claus Andreas; Herting, Egbert; Fortmann, Mats I. & Speer, Christian P. [Show all 13 contributors for this article] (2024). Neonatal Sepsis Episodes and Retinopathy of Prematurity in Very Preterm Infants. JAMA Network Open. 7(7). doi: 10.1001/jamanetworkopen.2024.23933. Full text in Research Archive Show summary

  Importance Retinopathy of prematurity (ROP) is a major morbidity of preterm infants causing visual impairment, including blindness, for which timely treatment is vital and prevention is key. Increasing evidence suggests that exposure to neonatal sepsis contributes to ROP development. Objective To investigate the association between neonatal sepsis and ROP in 2 large-scale cohorts of preterm infants born at less than 29 weeks’ gestation. Design, Setting, and Participants This retrospective cohort study was conducted using data from the German Neonatal Network (GNN) and Norwegian Neonatal Network (NNN). The GNN involves 68 and the NNN includes 21 level III neonatal intensive care units. Participants were infants born at a gestation of 22 weeks and 0 days to 28 weeks and 6 days and enrolled in the GNN between January 1, 2009, and December 31, 2022, and NNN between January 1, 2009, and December 31, 2018. Data were analyzed from February through September 2023. Exposure Single or multiple episodes of culture-proven sepsis. Main Outcomes and Measures Any ROP and treatment-warranted ROP. Results Among 12 794 infants in the GNN (6043 female [47.2%] and 6751 male [52.8%]; mean [SD] gestational age, 26.4 [1.5] weeks) and 1844 infants in the NNN (866 female [47.0%] and 978 male [53.0%]; mean [SD] gestational age, 25.6 [1.5] weeks), the mean (SD) birth weight was 848 (229) g and 807 (215) g, respectively. Any ROP was present in 6370 infants (49.8%) in GNN and 620 infants (33.6%) in NNN, and treatment-warranted ROP was present in 840 infants (6.6%) in GNN and 140 infants (7.6%) in NNN. In both cohorts, there were increasing rates of treatment-warranted ROP with each sepsis episode (no sepsis: 572 of 10 658 infants [5.4%] in GNN and 85 of 1492 infants (5.7%) in NNN; 1 episode: 190 of 1738 infants in GNN [10.9%] and 29 of 293 infants [9.9%] in NNN; 2 episodes: 53 of 314 infants in GNN [16.9%] and 13 of 49 infants [26.5%] in NNN; 3 episodes: 25 of 84 infants [29.8%] in GNN and 3 of 10 infants [30.0%] in NNN). After adjusting for multiple confounders in the GNN dataset, the number of sepsis episodes was associated with ROP and treatment-warranted ROP compared with 0 episodes (1 episode: adjusted odds ratio [aOR], 1.44 [95% CI, 1.27-1.63]; P < .001 and OR, 1.60 [95% CI, 1.31-1.96]; P < .001, respectively; 2 episodes: OR, 1.81 [95% CI, 1.35-2.42]; P < .001 and OR, 2.38 [95% CI, 1.68-3.37]; P < .001, respectively; 3 episodes: OR, 4.39 [95% CI, 2.19-8.78]; P < .001 and OR, 3.88 [95% CI, 2.29-6.55]; P < .001, respectively). These associations were confirmed for any ROP by propensity score matching (for example, the aOR with propensity score matching was 1.76 [95% CI, 1.54-2.02]; P < .001 for 1 episode vs 0 episodes and 1.58 [95% CI, 1.12-2.22]; P = .007 for 3 episodes vs 0 or 1 episode). In the NNN dataset, surgical NEC was associated with treatment-warranted ROP (multivariable analysis: aOR, 3.37 [95% CI, 1.78-6.37]; P < .001). Conclusions and Relevance This study found that in the large-scale GNN cohort, recurrent culture-proven sepsis was associated with ROP and treatment-warranted ROP in infants born at less than 29 weeks.

• Server, Andrés; Latysheva, Anna; Nedregaard, Bård; Rønnestad, Arild Erland; Heiberg, Lise & Marthinsen, Pål Bache (2024). Perinatal Stroke as It is: Updates, Insights and Challenges. Neurographics. p. 1–17. doi: 10.3174/ng.2200042. Full text in Research Archive
• Arribas, Cristina; Cavallaro, Giacomo; Gonzalez, Juan-Luis; Lagares, Carolina; Raffaeli, Genny & Smits, Anne [Show all 84 contributors for this article] (2024). Global cross-sectional survey on neonatal pharmacologic sedation and analgesia practices and pain assessment tools: impact of the sociodemographic index (SDI). Pediatric Research. ISSN 0031-3998. 96, p. 964–975. doi: 10.1038/s41390-024-03032-7. Full text in Research Archive Show summary

  Background There is variability in the use of sedatives and analgesics in neonatal intensive care units (NICUs). We aimed to investigate the use of analgesics and sedatives and the management of neonatal pain and distress. Methods This was a global, prospective, cross-sectional study. A survey was distributed May–November 2022. The primary outcome of this research was to compare results between countries depending on their socio-sanitary level using the sociodemographic index (SDI). We organized results based on geographical location. Results The survey collected 1304 responses, but we analyzed 924 responses after database cleaning. Responses from 98 different countries were analyzed. More than 60% of NICUs reported having an analgosedation guideline, and one-third of respondents used neonatal pain scales in more than 80% of neonates. We found differences in the management of sedation and analgesia between NICUs on different continents, but especially between countries with different SDIs. Countries with a higher SDI had greater availability of and adherence to analgosedation guidelines, as well as higher rates of analgosedation for painful or distressing procedures. Countries with different SDIs reported differences in analgosedation for neonatal intubation, invasive ventilation, and therapeutic hypothermia, among others.

• Berisha, Gazmend; Boldingh, Anne Marthe; Nakstad, Britt; Blakstad, Elin Wahl; Rønnestad, Arild Erland & Solevåg, Anne Lee (2023). Retrospectively Assessed Muscle Tone and Skin Colour following Airway Suctioning in Video-Recorded Infants Receiving Delivery Room Positive Pressure Ventilation. Children. 10(1). doi: 10.3390/children10010166. Full text in Research Archive Show summary

  Background: Recently, the International Liaison Committee on Resuscitation published a systematic review that concluded that routine suctioning of clear amniotic fluid in the delivery room might be associated with lower oxygen saturation (SpO2) and 10 min Apgar score. The aim of this study was to examine the effect of delivery room airway suctioning on the clinical appearance, including muscle tone and skin colour, of video-recorded term and preterm infants born through mainly clear amniotic fluid. Methods: This was a single-centre observational study using transcribed video recordings of neonatal stabilizations. All infants who received delivery room positive pressure ventilation (PPV) from August 2014 to November 2016 were included. The primary outcome was the effect of airway suctioning on muscle tone and skin colour (rated 0–2 according to the Apgar score), while the secondary outcome was the fraction of infants for whom airway suction preceded the initiation of PPV as a surrogate for “routine” airway suctioning. Results: Airway suctioning was performed in 159 out of 302 video recordings and stimulated a vigorous cry in 47 (29.6%) infants, resulting in improvements in muscle tone (p = 0.09) and skin colour (p &lt; 0.001). In 43 (27.0%) infants, airway suctioning preceded the initiation of PPV. Conclusions: In this single-centre observational study, airway suctioning stimulated a vigorous cry with resulting improvements in muscle tone and skin colour. Airway suctioning was often performed prior to the initiation of PPV, indicating a practice of routine suctioning and guideline non-compliance.

• Norman, Mikael; Padkær Petersen, Jesper; Stensvold, Hans Jørgen; Thorkelsson, Thordur; Helenius, Kjell & Brix Andersson, Charlotte [Show all 17 contributors for this article] (2023). Preterm birth in the Nordic countries—Capacity, management and outcome in neonatal care. Acta Paediatrica. ISSN 0803-5253. 112(7), p. 1422–1433. doi: 10.1111/apa.16753. Full text in Research Archive Show summary

  Aim Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this hypothesis. Methods Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case-mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (<32 weeks) and extremely preterm infants (<28 weeks of gestational age) were compared. Results Out of 287 642 infants born alive, 16 567 (5.8%) were preterm, 2389 (0.83%) very preterm and 800 (0.28%) were extremely preterm. In very preterm infants, exposure to antenatal corticosteroids varied from 85% to 98%, live births occurring at regional centres from 48% to 100%, surfactant treatment from 28% to 69% and use of mechanical ventilation varied from 13% to 77% (p < 0.05 for all comparisons). Significant regional variations within and between countries were also seen in capacity in neonatal care, case-mix and number of admissions, whereas there were no statistically significant differences in survival or major neonatal morbidities. Conclusion Management of very preterm infants exhibited significant regional variations in the Nordic countries.

• Wik, Gunnar; Jortveit, Jarle; Sitras, Vasilis; Perminow, Karl Viktor; Pripp, Are Hugo & Døhlen, Gaute [Show all 8 contributors for this article] (2023). Detection of severe congenital heart defects in live-born infants in Norway 2017–2020. Acta Paediatrica. ISSN 0803-5253. 113(1), p. 135–142. doi: 10.1111/apa.16953. Full text in Research Archive
• Stenersen, Eydis Oddsdottir; Olsen, Annette; Melheim, Maria; Solberg, Rønnaug; Dannevig, Ingrid & Schmölzer, Georg [Show all 11 contributors for this article] (2023). A Piglet Perinatal Asphyxia Model to Study Cardiac Injury and Hemodynamics after Cardiac Arrest, Resuscitation, and the Return of Spontaneous Circulation. Journal of Visualized Experiments. 2023(191). doi: 10.3791/64788. Full text in Research Archive Show summary

  Neonatal piglets have been extensively used as translational models for perinatal asphyxia. In 2007, we adapted a well-established piglet asphyxia model by introducing cardiac arrest. This enabled us to study the impact of severe asphyxia on key outcomes, including the time taken for the return of spontaneous circulation (ROSC), as well as the effect of chest compressions according to alternative protocols for cardiopulmonary resuscitation. Due to the anatomical and physiological similarities between piglets and human neonates, piglets serve as good models in studies of cardiopulmonary resuscitation and hemodynamic monitoring. In fact, this cardiac arrest model has provided evidence for guideline development through research on resuscitation protocols, pathophysiology, biomarkers, and novel methods for hemodynamic monitoring. Notably, the incidental finding that a substantial fraction of piglets have pulseless electrical activity (PEA) during cardiac arrest may increase the applicability of the model (i.e., it may be used to study pathophysiology extending beyond the perinatal period). However, the model generation is technically challenging and requires various skill sets, dedicated personnel, and a fine balance of the measures, including the surgical protocols and the use of sedatives/analgesics, to ensure a reasonable rate of survival. In this paper, the protocol is described in detail, as well as experiences with adaptations to the protocol over the years.

• Huncikova, Zuzana; Vatne, Anlaug; Stensvold, Hans Jørgen; Lang, Astri Maria; Støen, Ragnhild & Brigtsen, Anne Karin [Show all 10 contributors for this article] (2023). Late-onset sepsis in very preterm infants in Norway in 2009-2018: A population-based study. Archives of Disease in Childhood: Fetal and Neonatal Edition. ISSN 1359-2998. 108(5). doi: 10.1136/archdischild-2022-324977. Full text in Research Archive Show summary

  Objective To evaluate epidemiology and outcomes among very preterm infants (<32 weeks’ gestation) with culture-positive and culture-negative late-onset sepsis (LOS). Design Cohort study using a nationwide, population-based registry. Setting 21 neonatal units in Norway. Participants All very preterm infants born 1 January 2009–31 December 2018 and admitted to a neonatal unit. Main outcome measures Incidences, pathogen distribution, LOS-attributable mortality and associated morbidity at discharge. Results Among 5296 very preterm infants, we identified 582 culture-positive LOS episodes in 493 infants (incidence 9.3%) and 282 culture-negative LOS episodes in 282 infants (incidence 5.3%). Extremely preterm infants (<28 weeks’ gestation) had highest incidences of culture-positive (21.6%) and culture-negative (11.1%) LOS. The major causative pathogens were coagulase-negative staphylococci (49%), Staphylococcus aureus (15%), group B streptococci (10%) and Escherichia coli (8%). We observed increased odds of severe bronchopulmonary dysplasia (BPD) associated with both culture-positive (adjusted OR (aOR) 1.7; 95% CI 1.3 to 2.2) and culture-negative (aOR 1.6; 95% CI 1.3 to 2.6) LOS. Only culture-positive LOS was associated with increased odds of cystic periventricular leukomalacia (cPVL) (aOR 2.2; 95% CI 1.4 to 3.4) and severe retinopathy of prematurity (ROP) (aOR 1.8; 95% CI 1.2 to 2.8). Culture-positive LOS-attributable mortality was 6.3%, higher in Gram-negative (15.8%) compared with Gram-positive (4.1%) LOS, p=0.009. Among extremely preterm infants, survival rates increased from 75.2% in 2009–2013 to 81.0% in 2014–2018, p=0.005. In the same period culture-positive LOS rates increased from 17.1% to 25.6%, p<0.001. Conclusions LOS contributes to a significant burden of disease in very preterm infants and is associated with increased odds of severe BPD, cPVL and severe ROP.

• Brekke, Stine Marie; Halvorsen, Silje Torp; Bjørkvoll, Julie; Thorsby, Per Medbøe; Rønnestad, Arild Erland & Zykova, Svetlana [Show all 12 contributors for this article] (2023). The association between infant salivary cortisol and parental presence in the neonatal intensive care unit during and after COVID-19 visitation restrictions: A cross-sectional study. Early Human Development. ISSN 0378-3782. 182. doi: 10.1016/j.earlhumdev.2023.105788. Full text in Research Archive Show summary

  Objectives: Parent-infant interaction in the neonatal intensive care unit (NICU) promotes health and reduces infant stress. During the COVID-19 pandemic, however, NICUs restricted parent-infant interaction to reduce viral transmission. This study examined the potential relationship between pandemic visitation restrictions, parental presence and infant stress as measured by salivary cortisol. Methods: A two-NICU cross-sectional study of infants with gestational age (GA) 23–41 weeks, both during (n = 34) and after (n = 38) visitation restrictions. We analysed parental presence with and without visitation restrictions. The relationship between infant salivary cortisol and self-reported parental NICU presence in hours per day was analysed using Pearson's r. A linear regression analysis included potential confounders, including GA and proxies for infant morbidity. The unstandardised B coefficient described the expected change in logtransformed salivary cortisol per unit change in each predictor variable. Results: Included infants had a mean (standard deviation) GA of 31(5) weeks. Both maternal and paternal NICU presence was lower with versus without visitation restrictions (both p ≤0.05). Log-transformed infant salivary cortisol correlated negatively with hours of parental presence (r = − 0.40, p = .01). In the linear regression, GA (B = -0.03, p = .02) and central venous lines (B = 0.23, p = .04) contributed to the variance in salivary cortisol in addition to parental presence (B = -0.04 p = .04). Conclusion: COVID-19–related visitation restrictions reduced NICU parent-infant interaction and may have increased infant stress. Low GA and central venous lines were associated with higher salivary cortisol. The interaction between immaturity, morbidity and parental presence was not within the scope of this study and merits further investigation.

• Berisha, Gazmend; Kvenshagen, Line Norman; Boldingh, Anne Marthe; Nakstad, Britt; Blakstad, Elin Wahl & Rønnestad, Arild Erland [Show all 7 contributors for this article] (2023). Video-Recorded Airway Suctioning of Clear and Meconium-Stained Amniotic Fluid and Associated Short-Term Outcomes in Moderately and Severely Depressed Preterm and Term Infants. Children. 11(1). doi: 10.3390/children11010016. Full text in Research Archive Show summary

  Background: The aim of this study was to investigate delivery room airway suctioning and associated short-term outcomes in depressed infants. Methods: This is a single-centre prospective observational study of transcribed video recordings of preterm (gestational age, GA < 37 weeks) and term (GA ≥ 37 weeks) infants with a 5 min Apgar score ≤ 7. We analysed the association between airway suctioning, breathing, bradycardia and prolonged resuscitation (≥10 min). For comparison, non-suctioned infants with a 5 min Apgar score ≤ 7 were included. Results: Two hundred suction episodes were performed in 19 premature and 56 term infants. Breathing improved in 1.9% of premature and 72.1% of term infants, and remained unchanged in 84.9% of premature and 27.9% of term infants after suctioning. In our study, 61 (81.3%) preterm and term infants who were admitted to the neonatal intensive care unit experienced bradycardia after airway suctioning. However, the majority of the preterm and more than half of the term infants were bradycardic before the suction procedure was attempted. Among the non-airway suctioned infants (n = 26), 73.1% experienced bradycardia, with 17 non-airway suctioned infants being admitted to the neonatal intensive care unit. There was a need for resuscitation ≥ 10 min in 8 (42.1%) preterm and 32 (57.1%) term infants who underwent airway suctioning, compared to 2 (33.3%) preterm and 19 (95.0%) term infants who did not receive airway suctioning. Conclusions: In the infants that underwent suctioning, breathing improved in most term, but not preterm infants. More non-suctioned term infants needed prolonged resuscitation. Airway suctioning was not directly associated with worsening of breathing, bradycardia, or extended resuscitation needs.

• Huncikova, Zuzana; Stensvold, Hans Jørgen; Øymar, Knut Asbjørn Alexander; Vatne, Anlaug; Lang, Astri Maria & Støen, Ragnhild [Show all 12 contributors for this article] (2023). Variation in antibiotic consumption in very preterm infants-a 10 year population-based study. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 79(1), p. 143–150. doi: 10.1093/jac/dkad358. Full text in Research Archive Show summary

  Objectives Wide variations in antibiotic use in very preterm infants have been reported across centres despite similar rates of infection. We describe 10 year trends in use of antibiotics and regional variations among very preterm infants in Norway. Patients and Methods All live-born very preterm infants (<32 weeks gestation) admitted to any neonatal unit in Norway during 2009–18 were included. Main outcomes were antibiotic consumption expressed as days of antibiotic therapy (DOT) per 1000 patient days (PD), regional variations in use across four health regions, rates of sepsis and sepsis-attributable mortality and trends of antibiotic use during the study period. Results We included 5296 infants: 3646 (69%) were born at 28–31 weeks and 1650 (31%) were born before 28 weeks gestation with similar background characteristics across the four health regions. Overall, 80% of the very preterm infants received antibiotic therapy. The most commonly prescribed antibiotics were the combination of narrow-spectrum β-lactams and aminoglycosides, but between 2009 and 2018 we observed a marked reduction in their use from 100 to 40 DOT per 1000 PD (P < 0.001). In contrast, consumption of broad-spectrum β-lactams remained unchanged (P = 0.308). There were large variations in consumption of vancomycin, broad-spectrum β-lactams and first-generation cephalosporins, but no differences in sepsis-attributable mortality across regions. Conclusions The overall antibiotic consumption was reduced during the study period. Marked regional variations remained in consumption of broad-spectrum β-lactams and vancomycin, without association to sepsis-attributable mortality. Our results highlight the need for antibiotic stewardship strategies to reduce consumption of antibiotics that may enhance antibiotic resistance development.

• Ohnstad, Mari Oma; Stensvold, Hans Jørgen; Pripp, Are Hugo; Tvedt, Christine Raaen; Jelsness-Jørgensen, Lars-Petter & Astrup, Henriette [Show all 15 contributors for this article] (2023). Associations between unit workloads and outcomes of first extubation attempts in extremely premature infants below a gestational age of 26 weeks. Frontiers in Pediatrics. 11, p. 1–9. doi: 10.3389/fped.2023.1090701. Full text in Research Archive Show summary

  Objective: The objective was to explore whether high workloads in neonatal intensive care units were associated with short-term respiratory outcomes of extremely premature (EP) infants born <26 weeks of gestational age. Methods: This was a population-based study using data from the Norwegian Neonatal Network supplemented by data extracted from the medical records of EP infants <26 weeks GA born from 2013 to 2018. To describe the unit workloads, measurements of daily patient volume and unit acuity at each NICU were used. The effect of weekend and summer holiday was also explored. Results: We analyzed 316 first planned extubation attempts. There were no associations between unit workloads and the duration of mechanical ventilation until each infant’s first extubation or the outcomes of these attempts. Additionally, there were no weekend or summer holiday effects on the outcomes explored. Workloads did not affect the causes of reintubation for infants who failed their first extubation attempt. Conclusion: Our finding that there was no association between the organizational factors explored and short-term respiratory outcomes can be interpreted as indicating resilience in Norwegian neonatal intensive care units.

• Vatne, Anlaug; Hapnes, Nina; Stensvold, Hans Jørgen; Dalen, Ingvild; Guthe, Hans Jørgen Timm & Støen, Ragnhild [Show all 9 contributors for this article] (2023). Early empirical antibiotics and adverse clinical outcomes in infants born very preterm: A population-based cohort. Journal of Pediatrics. ISSN 0022-3476. 253, p. 107–114. doi: 10.1016/j.jpeds.2022.09.029. Full text in Research Archive Show summary

  Objective: The objective of this study was to evaluate the association between empirical antibiotic therapy in the first postnatal week in uninfected infants born very preterm and the risk of adverse outcomes until discharge. Study design: Population-based, nationwide registry study in Norway including all live-born infants with a gestational age <32 weeks surviving first postnatal week without sepsis, intestinal perforation, or necrotizing enterocolitis (NEC) between 2009 and 2018. Primary outcomes were severe NEC, death after the first postnatal week, and/or a composite outcome of severe morbidity (severe NEC, severe bronchopulmonary dysplasia [BPD], severe retinopathy of prematurity, late-onset sepsis, or cystic periventricular leukomalacia). The association between empirical antibiotics and adverse outcomes was assessed using multivariable logistic regression models, adjusting for known confounders. Results: Of 5296 live-born infants born very preterm, 4932 (93%) were included. Antibiotics were started in first postnatal week in 3790 of 4932 (77%) infants and were associated with higher aOR of death (aOR 9.33; 95% CI: 1.10-79.5, P = .041), severe morbidity (aOR 1.88; 95% CI: 1.16-3.05, P = .01), and severe BPD (aOR 2.17; 95% CI: 1.18-3.98; P = .012), compared with those not exposed. Antibiotics ³ 5 days were associated with higher odds of severe NEC (aOR 2.27; 95% CI: 1.02-5.06; P = .045). Each additional day of antibiotics was associated with 14% higher aOR of death or severe morbidity and severe BPD. Conclusions: Early and prolonged antibiotic exposure within the first postnatal week was associated with severe NEC, severe BPD, and death after the first postnatal week.

• Strømmen, Kenneth; Lyche, Jan Ludvig; Moltu, Sissel Jennifer; Müller, Mette Helen Bjørge; Blakstad, Elin Wahl & Brække, Kristin [Show all 12 contributors for this article] (2022). Estimated daily intake of phthalates, parabens, and bisphenol A in hospitalised very low birth weight infants. Chemosphere. ISSN 0045-6535. 309(Part 1). doi: 10.1016/j.chemosphere.2022.136687. Full text in Research Archive Show summary

  Very low birth weight infants (VLBW, birth weight (BW) < 1500 g) are exposed to phthalates, parabens and bisphenol A (BPA) early in life. We estimated daily intake (EDI) of these excipients in 40 VLBW infants the first and fifth week of life while hospitalised. Based on urinary samples collected in 2010, EDI was calculated and compared to the tolerable daily intake (TDI) with hazard quotients (HQs) evaluated. A HQ > 1 indicates that EDI exceeded TDI with increased risk of adverse health effects. EDI was higher in VLBW infants compared to term-born infants and older children. VLBW infants born at earlier gestational age (GA), or with lower BW, had higher EDI than infants born at later GA or with higher BW. First week median EDI for BPA was higher than TDI in 100% of infants, in 75% for di(2-ethylhexyl) phthalate (DEHP), 90% for the sum of butyl benzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), DEHP and di-iso-nonyl phthalate (DiNP) = ∑BBzP+DnBP+DEHP+DiNP, and in 50% of infants for propylparaben (PrPa), indicating increased risk of adverse effects. Fifth week EDI remained higher than TDI in all infants for BPA, in 75% for DEHP and ∑BBzP+DnBP+DEHP+DiNP, and 25% of infants for PrPa, indicating prolonged risk. Maximum EDI for di-iso-butyl phthalate was higher than TDI suggesting risk of adverse effects at maximum exposure. VLBW infants born earlier than 28 weeks GA had higher EDI, above TDI, for PrPa compared to infants born later than 28 weeks GA. Infants with late-onset septicaemia (LOS) had higher EDI for DEHP, ∑BBzP+DnBP+DEHP+DiNP and BPA, above TDI, compared to infants without LOS. More 75% of the infants' EDI for DEHP and ∑BBzP+DnBP+DEHP+DiNP, 25% for PrPa, and 100% of infants' EDI for BPA, were above TDI resulting in HQs 1, indicating increased risk of adverse health effects.

• Rød, Irene; Jørstad, Anna-Kristi; Aagaard, Hanne; Rønnestad, Arild Erland & Solevåg, Anne Lee (2022). Advanced Clinical Neonatal Nursing Students’ Transfer of Performance: From Skills Training With Real-Time Feedback on Ventilation to a Simulated Neonatal Resuscitation Scenario. Frontiers in Pediatrics. 10, p. 1–11. doi: 10.3389/fped.2022.866775. Full text in Research Archive Show summary

  Background: Advanced clinical neonatal nurses are expected to have technical skills including bag-mask ventilation. Previous studies on neonatal bag-mask ventilation skills training focus largely on medical students and/or physicians. The aim of this study was to investigate whether advanced clinical neonatal nursing students’ bag-mask ventilation training with real-time feedback resulted in transfer of bag-mask ventilation performance to a simulated setting without feedback on ventilation. Materials and Methods: Students in advanced clinical neonatal nursing practiced bagmask ventilation on a premature manikin (Premature Anne, Laerdal Medical, Stavanger, Norway) during skills training. A flow sensor (Neo Training, Monivent AB, Gothenburg, Sweden) was placed between the facemask and the self-inflating bag (Laerdal Medical), and visual feedback on mask leak (%), expiratory tidal volume (VTe in ml/kg), ventilation rate and inflation pressure was provided. Two months later, the students participated in a simulated neonatal resuscitation scenario. The same variables were recorded, but not fed back to the students. We compared ventilation data from skills- and simulation training. A structured questionnaire was used to investigate the students’ self-perceived neonatal ventilation competence before and after the skills- and simulation training. Results: Mask leakage and ventilation rate was higher, and VTe lower and highly variable in the simulated scenario compared with skills training (all p < 0.001). There was no statistically significant difference in inflation pressure (p = 0.92). The fraction of ventilations with VTe within the target range was lower during simulation (21%) compared to skills training (30%) (p < 0.001). There was no difference in the students’ self-perceived competence in bag-mask ventilation before vs. after skills- and simulation training. Conclusion: Skills training with real-time feedback on mask leak, ventilation rate, tidal volume, and inflation pressure did not result in objective or subjective improvements in bag-mask ventilation in a simulated neonatal resuscitation situation. Incorrect VTe delivery was common even when feedback was provided. It would be of interest to study whether more frequent training, and training both with and without feedback, could improve transfer of performance to a simulated resuscitation setting.

• Ohnstad, Mari Oma; Stensvold, Hans Jørgen; Pripp, Are Hugo; Tvedt, Christine Raaen; Jelsness-Jørgensen, Lars-Petter & Astrup, Henriette [Show all 15 contributors for this article] (2022). Predictors of extubation success: a population-based study of neonates below a gestational age of 26 weeks. BMJ Paediatrics Open. 6(1), p. 1–7. doi: 10.1136/bmjpo-2022-001542. Full text in Research Archive Show summary

  The aim of the study was to investigate first extubation attempts among extremely premature (EP) infants and to explore factors that may increase the quality of clinical judgement of extubation readiness. Design and method A population-based study was conducted to explore first extubation attempts for EP infants born before a gestational age (GA) of 26 weeks in Norway between 1 January 2013 and 31 December 2018. Eligible infants were identified via the Norwegian Neonatal Network database. The primary outcome was successful extubation, defined as no reintubation within 72 hours after extubation. Results Among 482 eligible infants, 316 first extubation attempts were identified. Overall, 173 (55%) infants were successfully extubated, whereas the first attempt failed in 143 (45%) infants. A total of 261 (83%) infants were extubated from conventional ventilation (CV), and 55 (17%) infants were extubated from high-frequency oscillatory ventilation (HFOV). In extubation from CV, pre-extubation fraction of inspired oxygen (FiO2) ≤0.35, higher Apgar score, higher GA, female sex and higher postnatal age were important predictors of successful extubation. In extubation from HFOV, a pre-extubation FiO2 level ≤0.35 was a relevant predictor of successful extubation. Conclusions The correct timing of extubation in EP infants is important. In this national cohort, 55% of the first extubation attempts were successful. Our results suggest that additional emphasis on oxygen requirement, sex and general condition at birth may further increase extubation success when clinicians are about to extubate EP infants for the first time.

• Reigstad, Hallvard; Hufthammer, Karl Ove; Rønnestad, Arild Erland; Klingenberg, Claus Andreas; Stensvold, Hans Jørgen & Markestad, Trond Jacob (2022). Early surfactant and non-invasive ventilation versus intubation and surfactant: a propensity score-matched national study. BMJ Paediatrics Open. 6(1). doi: 10.1136/bmjpo-2022-001527. Full text in Research Archive Show summary

  Objective To compare outcome after less invasive surfactant administration (LISA) and primary endotracheal intubation (non-LISA) in infants born before gestational age (GA) 28 weeks. Setting All neonatal intensive care units (NICUs) in Norway during 2012–2018. Methods Defined population-based data were prospectively entered into a national registry. We compared LISA infants with all non-LISA infants and with non-LISA infants who received surfactant following intubation. We used propensity score (PS) matching to identify non-LISA infants who were similar regarding potential confounders. Main outcome variables Rate and duration of mechanical ventilation (MV), survival, neurological and gastrointestinal morbidity, and need of supplemental oxygen or positive pressure respiratory support at postmenstrual age (PMA) 36 and 40 weeks. Results We restricted analyses to GA 25–27 weeks (n=843, 26% LISA) because LISA was rarely used at lower GAs. There was no significant association between NICUs regarding proportions treated with LISA and proportions receiving MV. In the PS-matched datasets, fewer LISA infants received MV (61% vs 78%, p<0.001), and they had fewer days on MV (mean difference 4.1, 95% CI 0.0 to 8.2 days) and lower mortality at PMA 40 weeks (absolute difference 6%, p=0.06) compared with all the non-LISA infants, but only a lower rate of MV (64% vs 97%, p<0.001) and fewer days on MV (mean difference 5.8, 95% CI 0.6 to 10.9 days) compared with non-LISA infants who received surfactant after intubation. Conclusion LISA reduced the rate and duration of MV but had no other clear benefits. Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. Relevant data are included in text. Data files may be obtained from a third party and are not publicly available. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

• Rød, Emma; Solberg, Vilde; Stenersen, Eydis Oddsdottir; Garberg, Håvard Tetlie; Mjelle, Anders Batman & Tølløfsrud, Per Arne [Show all 8 contributors for this article] (2022). Biochemical surveillance versus clinical observation of term infants born after prolonged rupture of membranes – A quality assurance initiative. Acta Paediatrica. ISSN 0803-5253. 112(3), p. 391–397. doi: 10.1111/apa.16617. Full text in Research Archive Show summary

  Aim To examine whether biochemical surveillance vs clinical observation of term infants with prolonged rupture of membranes as a risk factor for early-onset sepsis is associated with differences in patient trajectories in maternity and neonatal intensive care units. Methods A retrospective study of live-born infants with gestational age ≥ 37 + 0 weeks born after prolonged rupture of membranes (≥24 h) in four Norwegian hospitals 2017–2019. Two hospitals used biochemical surveillance, and two used predominantly clinical observation to identify early-onset sepsis cases. Results The biochemical surveillance hospitals had more C-reactive protein measurements (p < 0.001), neonatal intensive care unit admissions (p < 0.001) and antibiotic treatment (p < 0.001). Hospitals using predominantly clinical observation initiated antibiotic treatment earlier in infants with suspected early-onset sepsis (p = 0.04) but not in infants fulfilling early-onset sepsis diagnostic criteria (p = 0.09). There was no difference in antibiotic treatment duration (p = 0.59), fraction of infants fulfilling early-onset sepsis diagnostic criteria (p = 0.49) or length of hospitalisation (p = 0.30), and no early-onset sepsis-related adverse outcomes. Conclusion The biochemical surveillance hospitals had more C-reactive protein measurements, but there was no difference in antibiotic treatment duration, early-onset sepsis cases, length of hospitalisation or adverse outcomes. Personnel resources needed for clinical surveillance should be weighed against the limitation of potentially painful procedures.

• Ohnstad, Mari Oma; Stensvold, Hans Jørgen; Tvedt, Christine Raaen & Rønnestad, Arild Erlend (2021). Duration of Mechanical Ventilation and Extubation Success among Extremely Premature Infants. Neonatology. ISSN 1661-7800. 118, p. 90–97. doi: 10.1159/000513329. Full text in Research Archive Show summary

  Objective: The objective of this study was to examine the duration of mechanical ventilation (MV) in days until the first successful extubation and the cumulative duration of MV until discharge of infants with gestational age (GA) <26 weeks. We also aimed to explore associations between early clinical variables and the cumulative duration of MV. Design and Setting: This population-based study analysed data reported to the Norwegian Neonatal Network on extremely premature infants admitted between January 1, 2013, and December 31, 2018. Results: A total of 406 infants were included, of which 293 (72%) survived to discharge. The proportion successfully extubated on their first attempt was 34% of the infants born at GA 22–23 weeks, 50% at GA 24 weeks, and 70% at GA 25 weeks. Median postmenstrual age (PMA) at the first successful extubation was 27 weeks. The median duration of MV was 35, 24, and 12 days for infants born at GA 22–23, 24, and 25 weeks, respectively. Male sex and low 5-min Apgar score were independent early predictors for prolonged MV duration adjusted for GA in regression analyses. Conclusions: Most of the infants born at GA 25 weeks were successfully extubated on the first attempt. However, half of the infants born <26 weeks experienced unsuccessful extubations, indicating a lack of useful clinical predictors of successful extubation. The median duration of MV in survivors was 4 weeks longer for infants at GA 22–23 weeks than for infants born at GA 25 weeks, while the difference in median PMA at the first successful extubation was 2 weeks.

• Berisha, Gazmend; Boldingh, Anne Marthe; Blakstad, Elin Wahl; Rønnestad, Arild Erlend & Solevåg, Anne Lee (2021). Management of the Unexpected Difficult Airway in Neonatal Resuscitation. Frontiers in Pediatrics. 9, p. 1–10. doi: 10.3389/fped.2021.699159. Full text in Research Archive
• Størdal, Eline Hasselgård; Solevåg, Anne Lee; Bjørnholt, Jørgen; Rønnestad, Arild Erland & Stensvold, Hans Jørgen (2021). Sepsis treatment options identified by 10-year study of microbial isolates and antibiotic susceptibility in a level-four neonatal intensive care unit. Acta Paediatrica. ISSN 0803-5253. doi: 10.1111/apa.16189. Full text in Research Archive Show summary

  Aim: This observational study investigated the microbiology of blood culture-positive sepsis episodes and susceptibility to empiric antibiotics in early-onset sepsis (EOS) and late-onset sepsis (LOS) in a level-four neonatal intensive care unit (NICU) from 2010 to 2019. Methods: It was based on patient records and data that Oslo University Hospital, Norway, routinely submitted to the Norwegian Neonatal Network database. Clinical data were merged with blood culture results, including antibiotic susceptibility. Results: We studied 5249 infants admitted to the NICU 6321 times and identified 324 positive blood cultures from 287 infants, with 30 EOS and 305 LOS episodes. Frequent causative agents for EOS were group B streptococci (33.3%), Escherichia coli (20.0%) and Staphylococcus aureus (16.7%). All were susceptible to empiric ampicillin and gentamicin. LOS was most frequently caused by coagulase-negative staphylococci (CONS) (73.8%), Staphylococcus aureus (15.7%) and Enterococci (6.9%). CONS, Staphylococcus aureus, Enterococci, Escherichia coli, Klebsiella and Enterobacter represented 91.9% of LOS episodes and were susceptible to vancomycin and cefotaxime (96.1%), vancomycin and gentamicin (97.0%) and cloxacillin and gentamicin (38.1%). Conclusion: Empiric treatment with ampicillin and gentamicin was adequate for EOS. Combining vancomycin and gentamicin may be a safer alternative to cefotaxime for LOS, as this reduces exposure to broad-spectrum antibiotics.

• Strømmen, Kenneth; Lyche, Jan Ludvig; Moltu, Sissel; Müller, Mette Helen Bjørge; Blakstad, Elin Wahl & Almaas, Astrid Nylander [Show all 12 contributors for this article] (2021). High urinary concentrations of parabens and bisphenol A in very low birth weight infants. Chemosphere. ISSN 0045-6535. 271, p. 1–9. doi: 10.1016/j.chemosphere.2021.129570. Full text in Research Archive Show summary

  Very low birth weight infants (VLBW; birth weight < 1500 g) are treated with pharmaceuticals and medical equipment containing parabens and bisphenol A (BPA). Parabens are used in pharmaceuticals, whereas BPA in medical equipment where concentrations are rarely reported in hospitalised VLBW infants. We measured urinary concentrations of parabens and BPA and hypothesised high and increasing concentrations in infants born at lower gestational ages (GAs), and among infants with bronchopulmonary dysplasia (BPD) and late-onset septicaemia (LOS) due to higher exposure from pharmaceuticals and medical equipment. Urinary samples were collected during the first (n = 38) and fifth (n = 36) week of life. Methylparaben, ethylparaben, propylparaben, butylparaben, and BPA concentrations were measured using ultra high-performance liquid chromatography coupled to tandem mass spectrometry. VLBW infants had very high urinary concentrations of parabens and BPA compared to term infants and older children. The Σ paraben concentration was higher than detected in previous studies on premature infants. Lower GA at birth was associated with higher concentrations of parabens and BPA. Infants born before 28 weeks GA had higher first week concentrations of propylparaben (38.6 vs. 9.05 ng/mL, p = 0.007), butylparaben (0.28 vs. 0.09 ng/mL, p = 0.05) and fifth week concentrations of BPA (15.1 vs. 6.02 ng/mL, p = 0.02) than infants born after 28 weeks GA. Infants with LOS and BPD had higher fifth week concentrations of BPA than infants without LOS and BPD (LOS: 14.2 vs. 6.77 ng/mL, p = 0.07; BPD: 18.6 vs. 7.62 ng/mL, p = 0.05).

• Wik, Gunnar; Jortveit, Jarle; Sitras, Vasilis; Døhlen, Gaute; Rønnestad, Arild Erlend & Holmstrøm, Henrik (2021). Unexpected death in children with severe congenital heart defects in Norway 2004-2016. Archives of Disease in Childhood. ISSN 0003-9888. 106, p. 961–966. doi: 10.1136/archdischild-2020-319936. Full text in Research Archive
• Mundal, Håkon S.; Rønnestad, Arild Erland; Klingenberg, Claus Andreas; Stensvold, Hans Jørgen & Størdal, Ketil (2021). Antibiotic Use in Term and Near-Term Newborns. Pediatrics. ISSN 0031-4005. 148(6). doi: 10.1542/peds.2021-051339. Full text in Research Archive Show summary

  OBJECTIVES - We aimed to study whether national and local antibiotic stewardship projects have reduced the antibiotic use in newborns and to monitor potential changes in adverse outcomes.<p> <p>METHODS - In a nationwide, population-based study from Norway, we included all hospital live births from 34 weeks' gestation (n = 282 046) during 2015 to 2019. The primary outcome was the proportion of newborns treated with antibiotics from 0 to 28 days after birth. The secondary outcomes were the overall duration of antibiotic treatment and by categories: culture-positive sepsis, clinical sepsis, and no sepsis.<p> <p>RESULTS - A total of 7365 (2.6%) newborns received intravenous antibiotics during the period, with a reduction from 3.1% in 2015 to 2.2% in 2019 (30% decrease; P < .001). Hospitals with antibiotic stewardship projects experienced the largest reduction (48% vs 23%; P < .001). We found a small decrease in the median duration of antibiotic treatment in newborns without sepsis from 2.93 to 2.66 days (P = .011), and geographical variation was reduced during the study period. The overall number of days with antibiotic treatments was reduced by 37% from 2015 to 2019 (119.1 of 1000 vs 75.6 of 1000; P < .001). Sepsis was confirmed by blood culture in 206 newborns (incidence rate: 0.73 cases per 1000 live births). We found no increase in sepsis with treatment onset >72 hours of life, and sepsis-attributable deaths remained at a low level.<p> <p>CONCLUSIONS - During the study period, a substantial decrease in the proportion of newborns treated with antibiotics was observed together with a decline in treatment duration for newborns without culture-positive sepsis.

• Strand, Janne Maren; Gul, Kiran Aftab; Erichsen, Hans Christian; Lundman, Emma; Berge, Mona C. & Trømborg, Anette Kjoshagen [Show all 28 contributors for this article] (2020). Second-Tier Next Generation Sequencing Integrated in Nationwide Newborn Screening Provides Rapid Molecular Diagnostics of Severe Combined Immunodeficiency. Frontiers in Immunology. 11. doi: 10.3389/fimmu.2020.01417. Full text in Research Archive Show summary

  Severe combined immunodeficiency (SCID) and other T cell lymphopenias can be detected during newborn screening (NBS) by measuring T cell receptor excision circles (TRECs) in dried blood spot (DBS) DNA. Second tier next generation sequencing (NGS) with an amplicon based targeted gene panel using the same DBS DNA was introduced as part of our prospective pilot research project in 2015. With written parental consent, 21 000 newborns were TREC-tested in the pilot. Three newborns were identified with SCID, and disease-causing variants in IL2RG, RAG2, and RMRP were confirmed by NGS on the initial DBS DNA. The molecular findings directed follow-up and therapy: the IL2RG-SCID underwent early hematopoietic stem cell transplantation (HSCT) without any complications; the leaky RAG2-SCID received prophylactic antibiotics, antifungals, and immunoglobulin infusions, and underwent HSCT at 1 year of age. The child with RMRP-SCID had complete Hirschsprung disease and died at 1 month of age. Since January 2018, all newborns in Norway have been offered NBS for SCID using 1st tier TRECs and 2nd tier gene panel NGS on DBS DNA. During the first 20 months of nationwide SCID screening an additional 88 000 newborns were TREC tested, and four new SCID cases were identified. Disease-causing variants in DCLRE1C, JAK3, NBN, and IL2RG were molecularly confirmed on day 8, 15, 8 and 6, respectively after birth, using the initial NBS blood spot. Targeted gene panel NGS integrated into the NBS algorithm rapidly delineated the specific molecular diagnoses and provided information useful for management, targeted therapy and follow-up i.e., X rays and CT scans were avoided in the radiosensitive SCID. Second tier targeted NGS on the same DBS DNA as the TREC test provided instant confirmation or exclusion of SCID, and made it possible to use a less stringent TREC cut-off value. This allowed for the detection of leaky SCIDs, and simultaneously reduced the number of control samples, recalls and false positives. Mothers were instructed to stop breastfeeding until maternal cytomegalovirus (CMV) status was determined. Our limited data suggest that shorter time-interval from birth to intervention, may prevent breast milk transmitted CMV infection in classical SCID.

• Vatne, Anlaug; Klingenberg, Claus; Øymar, Knut; Rønnestad, Arild Erlend; Manzoni, Paolo & Rettedal, Siren (2020). Reduced antibiotic exposure by serial physical examinations in term neonates at risk of early-onset sepsis. The Pediatric Infectious Disease Journal. ISSN 0891-3668. 39(5), p. 438–443. doi: 10.1097/INF.0000000000002590. Full text in Research Archive
• Wik, Gunnar; Jortveit, Jarle; Sitras, Vasilis; Døhlen, Gaute; Rønnestad, Arild Erlend & Holmstrøm, Henrik (2020). Severe congenital heart defects: Incidence, causes and time trends of preoperative mortality in Norway. Archives of Disease in Childhood. ISSN 0003-9888. 105(8), p. 738–743. doi: 10.1136/archdischild-2019-317581. Full text in Research Archive
• Blakstad, Elin Wahl; Korpela, Katri; Lee-Ødegård, Sindre; Nakstad, Britt; Moltu, Sissel & Strømmen, Kenneth [Show all 11 contributors for this article] (2019). Enhanced nutrient supply and intestinal microbiota development in very low birth weight infants. Pediatric Research. ISSN 0031-3998. doi: 10.1038/s41390-019-0412-x. Full text in Research Archive
• Korpela, Katri; Blakstad, Elin Wahl; Moltu, Sissel; Strømmen, Kenneth; Nakstad, Britt & Rønnestad, Arild Erlend [Show all 10 contributors for this article] (2018). Intestinal microbiota development and gestational age in preterm neonates. Scientific Reports. 8:2453, p. 1–9. doi: 10.1038/s41598-018-20827-x. Full text in Research Archive Show summary

  The intestinal microbiota is an important contributor to the health of preterm infants, and may be destabilized by a number of environmental factors and treatment modalities. How to promote the development of a healthy microbiota in preterm infants is largely unknown. We collected fecal samples from 45 breastfed preterm very low birth weight (birth weight<1500g) infants from birth until 60 days postnatal age to characterize the intestinal microbiota development during the frst weeks of life in preterm infants. Fecal microbiota composition was determined by 16S rRNA amplicon sequencing. The main driver of microbiota development was gestational age; antibiotic use had strong but temporary efects and birth mode had little infuence. Microbiota development proceeded in four phases indicated by the dominance of Staphylococcus, Enterococcus, Enterobacter, and fnally Bifdobacterium. The Enterococcus phase was only observed among the extremely premature infants and appeared to delay the microbiota succession. The results indicate that hospitalized preterm infants receiving breast milk may develop a normal microbiota resembling that of term infants.

• Rosa-Carrillo, Daniel de la; Vindenes, Harald Bjarte; Kinsler, Veronica A; Rønnestad, Arild Erlend; Ringstad, Geir & Müller, Lil-Sofie Ording [Show all 10 contributors for this article] (2018). Aggressive melanoma in an infant with congenital melanocytic nevus syndrome and multiple, NRAS and BRAF mutation-negative nodules. Pediatric dermatology. ISSN 0736-8046. 35(5), p. e281–e285. doi: 10.1111/pde.13595. Full text in Research Archive Show summary

  We report the case of a newborn boy with multinodular NRAS- and BRAF-mutation negative congenital melanocytic nevi and cerebral lesions compatible with congenital intraparenchymal melanosis. Histopathology from skin lesions showed atypical nodular melanocytic proliferation with marked melanocytic atypia and a high number of mitoses and apoptosis, indicating aggressive proliferation. The child developed several new subcutaneous tumors and multiple internal lesions, which were confirmed to be metastases, and died five months old. This case may represent an infantile melanoma developing from a giant congenital melanocytic nevus, or a congenital melanoma.

• Stensvold, Hans Jørgen; Klingenberg, Claus; Støen, Ragnhild; Moster, Dag; Brække, Kristin & Guthe, Hans Jørgen Timm [Show all 10 contributors for this article] (2017). Neonatal morbidity and 1-year survival of extremely preterm infants. Pediatrics. ISSN 0031-4005. 139(3). doi: 10.1542/peds.2016-1821. Full text in Research Archive
• Strømmen, Kenneth; Haag, Alexander; Moltu, Sissel; Veierød, Marit Bragelien; Blakstad, Elin Wahl & Nakstad, Britt [Show all 12 contributors for this article] (2017). Enhanced nutrient supply to very low birth weight infants is associated with higher blood amino acid concentrations and improved growth. Clinical Nutrition ESPEN. ISSN 2405-4577. 18, p. 16–22. doi: 10.1016/j.clnesp.2017.01.003. Full text in Research Archive
• Stensvold, Hans Jørgen; Lang, Astri Maria; Strømmen, Kenneth; Abrahamsen, Tore G; Øglænd, Bjørn Edvin & Pripp, Are Hugo [Show all 7 contributors for this article] (2017). Strictly controlled glucose infusion rates are associated with a reduced risk of hyperglycaemia in extremely low birth weight preterm infants. Acta Paediatrica. ISSN 0803-5253. 107(3), p. 442–449. doi: 10.1111/apa.14164. Full text in Research Archive
• Klitkou, Søren Toksvig; Iversen, Tor; Stensvold, Hans Jørgen & Rønnestad, Arild Erlend (2017). Use of hospital-based health care services among children aged 1 through 9 years who were born very preterm - a population-based study. BMC Health Services Research. 17:571(571), p. 1–13. doi: 10.1186/s12913-017-2498-3. Full text in Research Archive Show summary

  Background Very preterm (VPT) children, with a birth weight below 1500 g or delivered before 32 weeks of gestational age, are at increased risk of poorer long-term health outcomes and higher rates of hospitalization in childhood. However, considerable variation exists in the need for in-hospital care within this population. We assessed the utilization and distribution of hospital-based care from ages 1 through 9 years for a nationwide population. Methods This was a population-based cohort of VPT children born in the period 2001–2009. We evaluated their utilization of hospital care in 2008–2010, when aged 1–9 years old. Outcomes were the incidence of hospital admissions and outpatient visits. We used Poisson regression models with multiple imputation of missing data. Results Children born VPT had more hospital admissions compared with the general population of children aged 1–9 years. The rates of hospital admissions and outpatient visits were strongly related to clinical characteristics of the child at birth and age at admission/outpatient visit but to only a variable and minor degree to characteristics pertaining to maternal health, the sociodemographic factors, and geographical proximity to hospital services. Conclusions Prior to this study, hospital utilization during the period 5–9 years old has been poorly documented. We found that excess utilization of hospital resources on average declines with increasing age. We also noted substantial differences in the use of hospital care across age groups and clinical factors for VPT children. The added information from the health status of mothers, social background, and geographic measures of access was limited.

• Blakstad, Elin Wahl; Moltu, Sissel; Nakstad, Britt; Veierød, Marit Bragelien; Strømmen, Kenneth & Juliusson, Petur Benedikt [Show all 11 contributors for this article] (2016). Enhanced nutrition improves growth and increases blood adiponectin concentrations in very low birth weight infants :. Food & Nutrition Research (FNR). ISSN 1654-6628. 60:33171, p. 1–11. doi: 10.3402/fnr.v60.33171. Full text in Research Archive
• Burns, Margrete Larsen; Stensvold, Hans Jørgen; Risnes, Kari Ravndal; Guthe, Hans Jørgen Timm; Astrup, Henriette & Nordhov, Solveig Marianne [Show all 9 contributors for this article] (2016). Inotropic Therapy in Newborns, A Population-Based National Registry Study. Pediatric Critical Care Medicine. ISSN 1529-7535. 17(10), p. 948–956. doi: 10.1097/PCC.0000000000000898. Full text in Research Archive
• Strømmen, Kenneth; Lyche, Jan Ludvig; Blakstad, Elin Wahl; Moltu, Sissel; Veierød, Marit Bragelien & Almaas, Astrid [Show all 13 contributors for this article] (2016). Increased levels of phthalates in very low birth weight infants with septicemia and bronchopulmonary dysplasia. Environment International. ISSN 0160-4120. 89-90, p. 228–234. doi: 10.1016/j.envint.2016.01.024. Full text in Research Archive
• Fjalstad, Jon Widding; Stensvold, Hans Jørgen; Bergseng, Håkon; Simonsen, Gunnar Skov; Salvesen, Bodil & Rønnestad, Arild Erlend [Show all 7 contributors for this article] (2016). Early-Onset Sepsis and Antibiotic Exposure in Term Infants: A Nationwide Population-Based Study in Norway. The Pediatric Infectious Disease Journal. ISSN 0891-3668. 35(1), p. 1–6. doi: 10.1097/INF.0000000000000906. Full text in Research Archive Show summary

  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. Worldwide, invasive neonatal infections caused approximately 22% of the estimated 2.9 million neonatal deaths in 2012.1 Rates of infection and mortality vary by geographical region. In industrialized countries, the incidence of early-onset sepsis (EOS) in term infants currently ranges between 0.5 and 1.2 per 1000 live births, with a declining rate over the last 20 years.2–4 However, EOS is still a leading cause of mortality and morbidity in this population.3,5 Presenting clinical symptoms are nonspecific, and specific biomarkers are lacking.6,7 Clinical suspicion of EOS, therefore, frequently leads to admission to a neonatal unit and to empirical antibiotic therapy in many infants who do not have infections.8 Antibiotics may be lifesaving for the few infants who are truly infected, but overuse of broad-spectrum antibiotics increases the risk of colonization with resistant bacteria.9 Current evidence also suggests that antibiotic exposure in the neonatal period, and subsequent alteration of the gut flora, may predispose individuals to atopic diseases, asthma, obesity and other adverse outcomes.10–15 There are few registry-based studies reporting detailed epidemiological data on infection rates and antibiotic treatment in term infants.3,4,16,17 Some reports contain information from tertiary care units, making it difficult to examine population-based trends.3,16,17 Several multicentre studies examine predominantly preterm infants who constitute a high-risk group for nosocomial late-onset sepsis.18–20 The primary aim of this study was to investigate the epidemiology of EOS and exposure to systemic antibiotics during the first week of life in an unselected national cohort of live-born (LB) term infants and second to assess regional variations in infection rates, antibiotic use and outcome.

• Stensvold, Hans Jørgen; Strømmen, Kenneth; Lang, Astri Maria; Abrahamsen, Tore G; Steen, Eline Kjørsvik & Pripp, Are Hugo [Show all 7 contributors for this article] (2015). Early enhanced parenteral nutrition, hyperglycemia, and death among extremely low-birth-weight infants. JAMA pediatrics. ISSN 2168-6203. 169(11), p. 1003–1010. doi: 10.1001/jamapediatrics.2015.1667. Full text in Research Archive Show summary

  Importance Efforts to optimize early parenteral nutrition (PN) in extremely low-birth-weight (ELBW) infants to promote growth and development may increase hyperglycemia risk. Recent studies have identified an association between early hyperglycemia and adverse outcomes in ELBW infants. Objectives To examine the prevalence of early hyperglycemia and clinical outcomes among ELBW infants before (2002-2005) and after (2006-2011) the implementation of an early enhanced PN protocol and to assess the independent effects of early enhanced PN and early hyperglycemia on mortality. Design, Setting, and Participants Observational cohort study in a level III neonatal intensive care unit. Prospectively collected clinical data in the neonatal intensive care unit’s medical database, nutritional information, and blood glucose levels were merged for analysis. All ELBW infants born between January 1, 2002, and December 31, 2011, without lethal malformations and still alive at 12 hours of life were eligible for inclusion in the study. Main Outcomes and Measures Mortality was the main outcome measure. Severe hyperglycemia was defined as 2 consecutive blood glucose levels exceeding 216 mg/dL at least 3 hours apart. A multivariable logistic regression model was applied to determine the independent effects of early enhanced PN and hyperglycemia on mortality. Results In total, 343 infants were included in the study, 129 in a historical comparison group before the enhanced PN protocol and 214 in the early enhanced PN group. Baseline characteristics were similar between the study groups. After the introduction of early enhanced PN, the prevalence of severe hyperglycemia during the first week of life was higher in the early enhanced PN group (11.6% [15 of 129] vs 41.6% [89 of 214], P < .001), as was the mortality (10.9% [14 of 129] vs 24.3% [52 of 214], P = .003). When adjusting for background characteristics, treatment, and nutritional data, early severe hyperglycemia remained a strong independent risk factor for death (odds ratio, 4.68; 95% CI, 1.82-12.03), together with gestational age (odds ratio, 0.62; 95% CI, 0.49-0.79). Conclusions and Relevance The implementation of an enhanced PN protocol was correlated with an increased prevalence of severe hyperglycemia and higher mortality. In the multivariable analysis, an enhanced PN regimen per se was not predictive of mortality, whereas early severe hyperglycemia remained strongly predictive of death. To avoid detrimental effects on outcomes in ELBW infants, the optimal composition of early PN to avoid postnatal growth failure must be carefully balanced against hyperglycemia risk.

• Blakstad, Elin Wahl; Strømmen, Kenneth; Moltu, Sissel; Wattam-Bell, John; Nordheim, Trond & Almaas, Astrid [Show all 15 contributors for this article] (2015). Improved visual perception in very low birth weight infants on enhanced nutrient supply. Neonatology. ISSN 1661-7800. 108(1), p. 30–37. doi: 10.1159/000381660. Full text in Research Archive
• Stray-Pedersen, Asbjørg; Backe, Paul Hoff; Sorte, Hanne Sørmo; Mørkrid, Lars; Chokshi, N.Y. & Erichsen, Hans Christian [Show all 39 contributors for this article] (2014). PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia. American Journal of Human Genetics. ISSN 0002-9297. 95(1), p. 96–107. doi: 10.1016/j.ajhg.2014.05.007. Full text in Research Archive
• Moltu, Sissel; Blakstad, Elin Wahl; Strømmen, Kenneth; Almaas, Astrid; Nakstad, Britt & Rønnestad, Arild Erlend [Show all 11 contributors for this article] (2014). Enhanced feeding and diminished postnatal growth failure in very-low-birth-weight infants - a randomized, controlled trial. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 58(3), p. 344–351. doi: 10.1097/MPG.0000000000000220. Full text in Research Archive
• Moltu, Sissel; Sachse, Daniel; Blakstad, Elin Wahl; Strømmen, Kenneth; Nakstad, Britt & Almaas, Astrid [Show all 14 contributors for this article] (2014). Urinary metabolite profiles in premature infants show early postnatal metabolic adaption and maturation. Nutrients. 6(5), p. 1913–1930. doi: 10.3390/nu6051913. Full text in Research Archive
• Strømmen, Kenneth; Blakstad, Elin Wahl; Moltu, Sissel; Almaas, Astrid; Westerberg, Ane Cecilie & Amlien, Inge [Show all 16 contributors for this article] (2014). Enhanced Nutrient Supply to Very Low Birth Weight Infants is Associated with Improved White Matter Maturation and Head Growth. Neonatology. ISSN 1661-7800. 107(1), p. 68–75. doi: 10.1159/000368181. Full text in Research Archive
• Tandberg, Bente Silnes; Sandtrø, Hege Pettersen; Vårdal, Mari H & Rønnestad, Arild Erlend (2013). Parents of preterm evaluation of stress and nursing support. Journal of Neonatal Nursing. ISSN 1355-1841. 19(6), p. 317–326. doi: 10.1016/j.jnn.2013.01.008. Full text in Research Archive
• Mitra, Souvik; Rønnestad, Arild Erlend & Holmstrøm, Henrik (2013). Management of patent ductus arteriosus in preterm infants - where do we stand? Congenital Heart Disease. ISSN 1747-079X. 8(6), p. 500–512. doi: 10.1111/chd.12143. Full text in Research Archive
• Moltu, Sissel; Strømmen, Kenneth; Blakstad, Elin Wahl; Almaas, Astrid; Westerberg, Ane Cecilie & Brække, Kristin [Show all 13 contributors for this article] (2013). Enhanced feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia - A randomized, controlled trial. Clinical Nutrition. ISSN 0261-5614. 32(2), p. 207–212. doi: 10.1016/j.clnu.2012.09.004. Full text in Research Archive
• Leversen, Katrine Tyborg; Sommerfelt, Kristian; Rønnestad, Arild Erlend; Kaaresen, Per Ivar; Farstad, Teresa & Skranes, Janne Helen [Show all 12 contributors for this article] (2011). Prediction of Neurodevelopmental and Sensory Outcome at 5 Years in Norwegian Children Born Extremely Preterm. Pediatrics. ISSN 0031-4005. 127(3), p. E630–E638. doi: 10.1542/peds.2010-1001. Full text in Research Archive
• Westerberg, Ane C.; Henriksen, Christine; Ellingvåg, Asta; Veierød, Marit Bragelien; Juliusson, Petur & Nakstad, Britt [Show all 11 contributors for this article] (2010). First year growth among very low birth weight infants. Acta Paediatrica. ISSN 0803-5253. 99(4), p. 556–562. doi: 10.1111/j.1651-2227.2009.01667.x. Full text in Research Archive
• Granslo, Hildegunn Norbakken; Klingenberg, Claus; Aarag, Elizabeth; Rønnestad, Arild Erlend; Mollnes, Tom Eirik & Flægstad, Trond (2010). Arginine Catabolic Mobile Element Is Associated With Low Antibiotic Resistance and Low Pathogenicity in Staphylococcus epidermidis From Neonates. Pediatric Research. ISSN 0031-3998. 68(3), p. 237–241. doi: 10.1203/PDR.0b013e3181eb01e0. Full text in Research Archive
• Leversen, Katrine Tyborg; Sommerfelt, Kristian; Rønnestad, Arild Erlend; Kaaresen, Per Ivar; Farstad, Teresa & Skranes, Janne Helen [Show all 12 contributors for this article] (2010). Predicting neurosensory disabilities at two years of age in a national cohort of extremely premature infants. Early Human Development. ISSN 0378-3782. 86(9), p. 581–586. doi: 10.1016/j.earlhumdev.2010.07.009. Full text in Research Archive
• Wold, Siw-Helen Westby; Sommerfelt, Kristian; Reigstad, Hallvard; Rønnestad, Arild; Medbø, Sverre & Farstad, Teresa [Show all 11 contributors for this article] (2009). Neonatal mortality and morbidity in extremely preterm small for gestational age infants: a population based study. Archives of Disease in Childhood: Fetal and Neonatal Edition. ISSN 1359-2998. 94(5), p. F363–F367. doi: 10.1136/adc.2009.157800. Full text in Research Archive
• Henriksen, Christine; Westerberg, Ane Cecilie; Rønnestad, Arild Erlend; Nakstad, Britt; Veierød, Marit Bragelien & Drevon, Christian A [Show all 7 contributors for this article] (2009). Growth and nutrient intake among very-low-birth-weight infants fed fortified human milk during hospitalisation. British Journal of Nutrition. ISSN 0007-1145. 102(8), p. 1179–1186. doi: 10.1017/S0007114509371755. Full text in Research Archive
• Henriksen, Christine; Haugholt, Kristin; Lindgren, Magnus; Aurvåg, Anne Karin; Rønnestad, Arild & Ronnestad, A [Show all 15 contributors for this article] (2008). Improved cognitive development among preterm infants attributable to early supplementation of human milk with docosahexaenoic acid and arachidonic acid. Pediatrics. ISSN 0031-4005. 121(6), p. 1137–1145. doi: 10.1542/peds.2007-1511. Full text in Research Archive Show summary

  OBJECTIVE: The objective of our study was to evaluate the effect of supplementation with docosahexaenoic acid and arachidonic acid for human milk-fed preterm infants. The primary end point was cognitive development at 6 months of age. METHODS: The study was a randomized, double-blind, placebo-controlled study among 141 infants with birth weights of <1500 g. The intervention with 32 mg of docosahexaenoic acid and 31 mg of arachidonic acid per 100 mL of human milk started 1 week after birth and lasted until discharge from the hospital (on average, 9 weeks). Cognitive development was evaluated at 6 months of age by using the Ages and Stages Questionnaire and event-related potentials, a measure of brain correlates related to recognition memory. RESULTS: There was no difference in adverse events or growth between the 2 groups. At the 6-month follow-up evaluation, the intervention group performed better on the problem-solving subscore, compared with the control group (53.4 vs 49.5 points). There was also a nonsignificant higher total score (221 vs 215 points). The event-related potential data revealed that infants in the intervention group had significantly lower responses after the standard image, compared with the control group(8.6 vs 13.2). There was no difference in responses to novel images. CONCLUSIONS: Supplementation with docosahexaenoic acid and arachidonic acid for very preterm infants fed human milk in the early neonatal period was associated with better recognition memory and higher problem-solving scores at 6 months.

• Klingenberg, Claus; Rønnestad, A; Anderson, A S; Abrahamsen, TG; Zorman, J & Villaruz, A [Show all 10 contributors for this article] (2007). Persistent strains of coagulase-negative staphylococci in a neonatal intensive care unit: virulence factors and invasiveness. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 13, p. 1100–1111. doi: 10.1111/j.1469-0691.2007.01818.x. Full text in Research Archive
• Saugstad, Ola Didrik; Hansen, Thor Willy; Rønnestad, Arild Erlend; Nakstad, Britt; Tølløfsrud, Per Arne & Reinholt, Finn P. [Show all 12 contributors for this article] (2007). Novel mutations in the gene encoding ATP binding cassette protein member A3 (ABCA3) resulting in fatal neonatal lung disease. Acta Paediatrica. ISSN 0803-5253. 96, p. 185–190. doi: 10.1111/j.1651-2227.2007.00016.x. Full text in Research Archive Show summary

  Aim: To investigate whether intractable respiratory distress syndrome in three Norwegian term infants was due to mutations in the ABCA3 gene. Methods: The genes encoding SP-B (SFTPB), SP-C (SFTPC), and ABCA3 (ABCA3) were sequenced from the parents of one infant and two unrelated infants with fatal neonatal lung disease. Lung tissue was examined by histology, immunohistochemistry and electron microscopy. Results: Novel ABCA3 mutations were identified in each family. One patient had a phenotype differing from previous descriptions of this disease with an initial uneventful period. The diagnosis was established 19 years after death by analysing DNA material from the parents, with an ABCA3 mutation identified on one allele in each parent. The other two infants had more typical clinical courses with the onset of respiratory symptoms immediately after birth. ABCA3 mutations were identified on both alleles from these two infants, and electron microscopy of alveolar type 2 cells demonstrated abnormal lamellar body formation characteristic of this disorder. Conclusion: ABCA3 mutations were the basis for lung disease in all three patients. Children with lung disease due to ABCA3 deficiency may not have symptoms at birth. The finding of five novel mutations indicates allelic heterogeneity for ABCA3 mutations within the Norwegian population

• Markestad, Trond; Kaaresen, Per Ivar; Rønnestad, Arild Erlend; Reigstad, Hallvard; Lossius, Kristin & Medbø, Sverre [Show all 10 contributors for this article] (2005). Early Death, Morbidity, and Need of Treatment Among Extremely Premature Infants. Pediatrics. ISSN 0031-4005. 115(5), p. 1289–1298. doi: 10.1542/peds.2004-1482. Full text in Research Archive Show summary

  Objective. To determine outcomes, in terms of perinatal and early death, need for treatment, and morbidity at the time of discharge home, among extremely preterm infants. Design. A prospective observational study of all infants with a gestational age (GA) of 22 to 27 completed weeks or a birth weight of 500 to 999 g who were born in Norway in 1999 and 2000. Results. Of 636 births, 174 infants (27%) were stillborn or died in the delivery room, 86 (14%) died in the NICU, and 376 (59%) were discharged from the hospital. The risk of being registered as stillborn or not being resuscitated increased with decreasing GA below 25 weeks. The survival rates for all births and for infants admitted to a NICU were, respectively, 0% for <23 weeks, 16% and 39% for 23 weeks, 44% and 60% for 24 weeks, 66% and 80% for 25 weeks, 72% and 84% for 26 weeks, 82% and 93% for 27 weeks, and 69% and 90% for >27 weeks. For the survivors, days of mechanical ventilation decreased from a median of 37 days to 3 days and the proportion in need of oxygen at 36 weeks� postconceptional age decreased from 67% to 26% at 23 and 27 weeks� GA, respectively. At 40 weeks� postconceptional age, the respective figures were 11% and 6%. The proportion with retinopathy of prematurity (ROP) requiring treatment decreased from 33% for GA of 23 weeks to 0% for >25 weeks. Periventricular hemorrhage of more than grade 2 occurred for 6% of the survivors and significant periventricular leukomalacia occurred for 5%, with no significant association with GA. The proportion of survivors without severe neurosensory or pulmonary morbidity increased from 44% for 23 weeks� to 86% for 27 weeks� GA. Apart from ROP, the morbidity rate was not associated with GA. Conclusions. The survival rate was high and the morbidity rate at discharge home was low in the present study, compared with previous population-based studies. With the exception of ROP, the morbidity rates among the survivors were not higher at the lowest GAs, possibly because withholding treatment was considered more acceptable for the most immature infants. The need for intensive care increased markedly for survivors with the lowest GAs.

• Klingenberg, Claus; Aarag, Elizabeth; Rønnestad, A; Sollid, johanna u ericson; Abrahamsen, TG & Kjeldsen, Gry [Show all 7 contributors for this article] (2005). Coagulase-negative Staphylococcal Sepsis among Neonates: Association between Antibiotic Resistance, Biofilm Formation and the Host Inflammatory Response. The Pediatric Infectious Disease Journal. ISSN 0891-3668. 24, p. 817–822. Full text in Research Archive
• Rønnestad, Arild Erlend; Abrahamsen, Tore G; Medbø, Sverre; Reigstad, Hallvard; Lossius, Kristin & Kaaresen, Per Ivar [Show all 9 contributors for this article] (2005). Septicemia in the First Week of Life in a Norwegian National Cohort of Extremely Premature Infants. Pediatrics. ISSN 0031-4005. 115(3), p. 262–268. Full text in Research Archive Show summary

  OBJECTIVES.: To investigate the incidence, causes, predictors, and outcomes of septicemia in the first week of life in a national cohort of extremely premature infants. METHODS.: A prospective study of survival of all infants with gestational age of <28 weeks or birth weight of <1000 g who were born in Norway in 1999�2000 was performed. Data on the maternal prenatal history, delivery, and neonatal course, including detailed information on episodes of microbiologically verified septicemia, were collected on predefined forms. Septicemia was reported in 2 groups, ie, episodes diagnosed on the day of delivery (ie, very early-onset septicemia [VEOS]) and episodes diagnosed from day 2 to day 7 of life (ie, early-onset septicemia [EOS]). Logistic regression models were used for the selection of variables for predictor analysis in each group. RESULTS.: Of 462 included infants, VEOS occurred for 15 (32.5 per 1000 population) and EOS for 15 (35.5 per 1000 population). The most prevalent bacteria were Escherichia coli in VEOS (n = 9) and staphylococci (coagulase-negative staphylococci and Staphylococcus aureus) (n = 15) in EOS. Case fatality rates were 40% and 13%, respectively. Independent predictive factors for VEOS were clinical chorioamnionitis (odds ratio [OR]: 10.5; 95% confidence interval [CI]: 3.3-33.4) and high maternal age (OR: 1.2; 95% CI: 1.0-1.3), whereas not receiving systemic antibiotic therapy within 2 days of age (OR: 13.6; 95% CI: 3.7-50.2) and receiving nasal continuous positive airway pressure (n-CPAP) support at 24 hours of age (OR: 9.8; 95% CI: 2.5-38.4) independently predicted septicemia after the first day of life. CONCLUSIONS.: Whereas vertically transmitted septicemia was dominated by Gram-negative bacteria, with predictors being exclusively of maternal origin, EOS was dominated by typically nosocomial flora, with n-CPAP treatment at 24 hours of age being a powerful predictor. Early n-CPAP treatment, as opposed to mechanical ventilation, as a powerful predictor of septicemia in the early neonatal period, even with adjustment for early systemic antibiotic treatment, is a new observation among extremely premature infants that warrants additional study. Key Words: early-onset septicemia � neonatal septicemia � population-based study � prospective study � very low birth weight � extreme prematurity � predictor analysis � logistic regression Abbreviations: GA, gestational age � BW, birth weight � n-CPAP, nasal continuous positive airway pressure � VEOS, very early-onset septicemia � EOS, early-onset septicemia � CRIB, Clinical Risk Index for Babies � FSC, forward stepwise conditional � OR, odds ratio � CI, confidence interval � VLBW, very low birth weight � CONS, coagulase-negative staphylococci � IQR, interquartile range

• Rønnestad, Arild Erlend; Abrahamsen, Tore G; Medbø, Sverre; Reigstad, Hallvard; Lossius, Kristin & Kaaresen, Per Ivar [Show all 10 contributors for this article] (2005). Late-Onset Septicemia in a Norwegian National Cohort of Extremely Premature Infants Receiving Very Early Full Human Milk Feeding. Pediatrics. ISSN 0031-4005. 115(3), p. 269–275. Full text in Research Archive Show summary

  OBJECTIVES.: To investigate the occurrence of and risk factors for late-onset septicemia (LOS) in a national cohort of extremely premature infants who received very early full human milk feeding. METHODS.: A prospective study of all infants born in Norway in 1999 and 2000 with gestational age of <28 weeks or birth weight of <1000 g was performed. Extensive clinical information, including data on feeding practices and episodes of septicemia, was collected on predefined forms. LOS was defined as growth of bacteria or fungi in blood cultures in conjunction with clinical symptoms consistent with systemic infection occurring after day 6 of life. Cox regression models, including models allowing for time-dependent covariates, were applied in the analysis of LOS. RESULTS.: Of 464 eligible infants, 462 (99.6%) were enrolled and 405 (87.7%) survived until day 7. LOS was diagnosed for 80 (19.7%). The predominant pathogens were coagulase-negative staphylococci, followed by Candida spp. Case fatality rates associated with septicemia were 10% in general and 43% for Candida spp septicemia. Necrotizing enterocolitis or bowel perforation was diagnosed for 19 infants (4%). Enteral feeding with human milk was initiated within the third day for 98% of patients, and 92% were receiving full enteral feeding (FEF) with human milk within the third week. Both high Clinical Risk Index for Babies scores and an umbilical venous catheter in situ at 7 days of age significantly predicted LOS. However, the overall most influential risk factor for LOS was the number of days without establishment of FEF with human milk, with an adjusted relative risk of 3.7 (2.0�6.9) for LOS if FEF was not established within the second week of life. CONCLUSIONS.: The incidence and case fatality rate of septicemia for this cohort of extremely preterm infants were lower than values in comparable studies. The main difference, compared with other studies, was the feeding practice, and the data suggest that very early FEF with human milk significantly reduces the risk of LOS among extremely premature infants

• Markestad, Trond; Kaaresen, Per Ivar; Rønnestad, Arild; Reigstad, Hallvard; Lossius, Kristin & Medbø, Sverre [Show all 10 contributors for this article] (2005). Early death, morbidity, and need of treatment among extremely premature infants. Pediatrics. ISSN 0031-4005. 115(5), p. 1289–1298. Full text in Research Archive
• Rønnestad, Arild; Abrahamsen, Tore G.; Medbø, Sverre; Reigstad, Harald; Lossius, Kristin & Kaaresen, Per Ivar [Show all 10 contributors for this article] (2005). Late-Onset Septicemia in a Norwegian National Cohort of Extremely Premature Infants Receiving Very Early Full Human Milk Feeding. Pediatrics. ISSN 0031-4005. 115, p. e269–e276. doi: 10.1542/peds.2004-1833. Full text in Research Archive Show summary

  doi:10.1542/peds.2004-1833

• Klingenberg, C.; Sundsfjord, A; Rønnestad, Arild Erlend; Mikalsen, J; Gaustad, Peter & Flægstad, Trond (2004). Phenotypic and genotypic aminoglycoside resistance in blood culture isolates of coagulase-negative staphylococci from a single neonatal intensive care unit, 1989�2000. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 54(5), p. 889–896. doi: 10.1093/jac/dkh453. Full text in Research Archive Show summary

  Objectives: To investigate the prevalence of aminoglycoside resistance and genes encoding aminoglycoside-modifying enzymes (AME) in blood culture isolates of coagulase-negative staphylococci (CoNS) from neonates. Materials and methods: A total of 180 isolates from 148 patients collected in a single neonatal unit over a 12 year period were examined for susceptibility to gentamicin, tobramycin, netilmicin, amikacin and arbekacin by Etest and/or disc diffusion. AME genes were detected by PCR. Results: The overall non-susceptibility rates to gentamicin, tobramycin, netilmicin, amikacin and arbekacin were 66%, 68%, 52%, 38% and 1%, respectively. Gentamicin non-susceptibility rates were 4% and 91% in methicillin-susceptible and -resistant isolates, respectively. aac(6')-Ie-aph(2'')-Ia, aph(3')-IIIa and/or ant(4')-Ia were encountered in 125 (69%), 1 (0.5%) and 30 (16.6%) isolates, respectively. Forty-six (26%) isolates negative for AME genes were susceptible to all aminoglycosides. In contrast, 115 (92%), 91 (73%) and 66 (53%) of aac(6')-Ie-aph(2'')-Ia positive isolates were non-susceptible to gentamicin, netilmicin and amikacin, respectively. Only one isolate showed arbekacin resistance. However, aac(6')-Ie-aph(2'')-Ia positive isolates and isolates with gentamicin MIC 128 mg/L displayed a significant reduction in arbekacin inhibition zones. Conclusions: A high prevalence of aminoglycoside resistance was detected and associated with methicillin resistance. Discrepancies between phenotypic and genetic detection of aminoglycoside resistance were discerned. Gentamicin was the preferred substrate for phenotypic detection of aac(6')-Ie-aph(2'')-Ia. Arbekacin showed favourable antibacterial activity even in aac(6')-Ie-aph(2'')-Ia-positive isolates. We suggest including arbekacin in future clinical trials of empirical treatment of late onset neonatal sepsis.

• Klingenberg, Claus; Sundsfjord, Arnfinn; Rønnestad, A; Mikalsen, J; Gaustad, P & Flægstad, Trond (2004). Correlation between aminoglycoside resistance phenotype and genotype in blood culture isolates of coagulase negative staphylococci from a single neonatal intensive care unit, 1989-2000. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 54(5), p. 889–896. Full text in Research Archive

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• Barlinn, Regine; Helbig, Anne; Rønnestad, Arild Erland; Hilde, Katarina; Klingenberg, Claus Andreas & Lang, Astri Maria (2025). Medfødt cytomegalovirusinfeksjon kan forebygges. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(5). doi: 10.4045/tidsskr.25.0092. Full text in Research Archive
• Berisha, Gazmend; Boldingh, Anne Marthe; Blakstad, Elin Wahl; Rønnestad, Arild Erland & Solevåg, Anne Lee (2023). Corrigendum: Management of the unexpected difficult airway in neonatal resuscitation(Front Pediatr., (2021), 9, (699159), 10.3389/fped.2021.699159). Frontiers in Pediatrics. 10. doi: 10.3389/fped.2022.1124050. Full text in Research Archive
• Ohnstad, Mari Oma; Stensvold, Hans Jørgen; Pripp, Are Hugo; Tvedt, Christine Raaen; Jelsness-Jørgensen, Lars-Petter & Astrup, Henriette [Show all 15 contributors for this article] (2022). Extubating extremely premature newborns: predictors of success and reasons for failure. Full text in Research Archive
• Strømmen, Kenneth; Lyche, Jan Ludvig; Moltu, Sissel; Müller, Mette Helen Bjørge; Blakstad, Elin Wahl & Almaas, Astrid Nylander [Show all 12 contributors for this article] (2021). Corrigendum to “High urinary concentrations of parabens and bisphenol A in very low birth weight infants”. Chemosphere. ISSN 0045-6535. 275. doi: 10.1016/j.chemosphere.2021.130613. Full text in Research Archive
• Rønnestad, Arild Erlend & Hansen, Thor Willy Ruud (2014). Nevrologiske tilstander hos nyfødte, Nevrologi og nevrokirurgi fra barn til voksen, 6.utgave. Forlaget Vett & Viten AS. ISSN 9788241207099. p. 155–172. Full text in Research Archive
• Blakstad, Elin Wahl; Strømmen, Kenneth; Moltu, Sissel; Wattam-Bell, J; Nordheim, Trond & Almaas, Astrid [Show all 14 contributors for this article] (2013). Enhanced feeding improved global motion visual event-related potentials in very low birth weight infants. Full text in Research Archive
• Strømmen, Kenneth; Blakstad, Elin Wahl; Moltu, Sissel; Almaas, Astrid; Amlien, Inge & Rønnestad, Arild Erlend [Show all 13 contributors for this article] (2013). Enhanced Nutrition to very low birth weight infants improves nutrition of cerebral connective tracts. Full text in Research Archive
• Moltu, Sissel; Blakstad, Elin Wahl; Strømmen, Kenneth; Almaas, Astrid; Nakstad, Britt & Rønnestad, Arild Erlend [Show all 11 contributors for this article] (2013). Enhanced nutritional support enables postnatal growth similar to normal in utero growth in very low birth weight infants. Full text in Research Archive
• Strømmen, Kenneth; Blakstad, Elin Wahl; Moltu, Sissel; Almaas, Astrid; Westerberg, Ane Cecilie & Amlien, Inge [Show all 16 contributors for this article] (2012). Enhanced Nutrition to Very Low Birth Weight Infants Improves Maturation of Cerebral Connective Tracts. Full text in Research Archive
• Moltu, Sissel; Blakstad, Elin Wahl; Strømmen, Kenneth; Almaas, Astrid; Nakstad, Britt & Rønnestad, Arild Erlend [Show all 11 contributors for this article] (2012). Økt tilførsel av næring-stoffer gir bedret vekst hos svært premature barn. Full text in Research Archive
• Lindenskov, Paal Helge H.; Rønnestad, Arild Erlend & Skari, Hans (2012). Et spedbarns mistrivsel endte med døden. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 18(132), p. 1964–1967. doi: 10.4045/tidsskr.11.1026. Full text in Research Archive
• Tandberg, Bente Silnes; Sandtrø, Hege Pettersen & Rønnestad, Arild Erlend (2012). DO MOTHERS AND FATHER TO PRETERM EVALUATE THEIR EXPERIENCE OF STRESS AND NURSE’S SUPPORT DIFFERENTLY WHEN HOSPITALIZED IN A NICU? Full text in Research Archive
• Rønnestad, Arild Erlend; Rootwelt, Terje & Hansen, Thor Willy (2010). Nevrologiske tilstander hos nyfødte. In Gjerstad, Leif; Helseth, Eirik & Rootwelt, Terje (Ed.), Nevrologi og nevrokirurgi. Fra barn til voksen. 5.utgave. Forlaget Vett & Viten AS. ISSN 9788241206863. p. 159–176. Full text in Research Archive
• Haugen, Guttorm; Rønnestad, Arild Erlend & Kroken, Mette (2009). Variations in fetal phenotype in Prader-Willi syndrome. Prenatal Diagnosis. ISSN 0197-3851. 29(3), p. 294–294. doi: 10.1002/pd.2207. Full text in Research Archive
• Klingenberg, Claus; Rønnestad, Arild Erlend; Anderson, Annaliesa; Abrahamsen, Tore G; Flægstad, Trond & Sollid, J.E. (2006). Persistent strains of coagulase negative staphylococci in a neonatal intensive care unit are characterized by high levels of biofilm production and antibiotic resistance. European Society for Pediatric Infectious Diseases, Meeting Abstract Book. Full text in Research Archive Show summary

  Background and aims Coagulase-negative staphylococci (CoNS) are the major cause of nosocomial sepsis in the neonatal intensive care unit (NICU). We wanted to investigate whether persistent CoNS strains possess specific bacterial characteristics compared with sporadic strains. Methods During a 12-year period we obtained 180 CoNS blood culture isolates from 150 neonates at one single NICU. All isolates were typed with pulsed field gel electrophoresis (PFGE). We also performed multi locus sequence typing (MLST) on 90 S. epidermidis isolates. Phenotypic antibiotic susceptibility to a broad range of antibiotics was analyzed with Etest. Virulence genes encoding methicillin and aminoglycoside resistance were detected with PCR. In addition, we analyzed phenotypic biofilm production and genetic determinants for biofilm formation. Results There was a high degree of concurrence between PFGE- and MLST- typing. Four S. epidermidis clusters contained 66 (6 - 9 - 15 - 36) isolates, one S. haemolyticus cluster 14 isolates, and one S. hominis cluster 7 isolates. The other 93 isolates were divided among 62 PFGE-types. S. epidermidis cluster strains were isolated from children with lower birth weight compared with non-clusters strains (1420 g versus 2034 g, p = 0.001). Cluster strains were evenly distributed among isolates causing sepsis and isolates considered as contaminants. Antibiotic resistance rates (methicillin, gentamicin, erythromycin, clindamycin and fusidic acid) and biofilm production were significantly higher among cluster strains compared with non-cluster strains. Conclusions CoNS cluster isolates were characterized by high levels of biofilm production and antibiotic resistance, enabling them to survive and persist in the NICU environment. Persistent strains colonized and invaded the smallest infants who were exposed to more invasive procedures and had longer hospital stay.

• Klingenberg, Claus; Aarag, E.; Rønnestad, Arild Erlend; Sollid, J.E.; Abrahamsen, Tore G & Flægstad, Trond (2005). Biofilm forming coagulase-negative Staphylococci are associated with decreased neonatal inflammatory response in late onset sepsis. Full text in Research Archive Show summary

  Background: Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens causing late onset sepsis in neonates. They are often multi-resistant to antibiotics and the ability to form biofilm is considered their main virulence determinant. The relationship between antibiotic resistance, biofilm formation and clinical outcome of CoNS infections is largely unknown. Methods: During a 12-year period we identified 150 neonates having 164 suspected septic episodes with growth of CoNS in blood culture. We examined the relationship between antibiotic resistance, phenotypic biofilm production and genetic determinants for biofilm formation in different CoNS species, and their correlation with neonatal inflammatory response. Results: Eighty-five episodes were defined as true sepsis, and 79 episodes of CoNS growth in blood culture were considered contaminations. Significantly higher prevalences of both phenotypic and genotypic β-lactam and aminoglycoside resistance were seen in invasive isolates compared with contaminants. Sixty-one percent of S. epidermidis isolates produced biofilm compared with 26 % of CoNS non-epidermidis (P < 0.001). As expected there was a strong correlation between the presence of icaD and biofilm production. We observed no difference in phenotypic biofilm production or genetic determinants for biofilm formation between invasive isolates and contaminants. C-reactive protein (CRP) levels as a marker of inflammatory response were higher in CoNS sepsis caused by methicillin and aminoglycoside resistant versus susceptible isolates (P = 0.031). In contrast, there was a significant association between a lower CRP response and biofilm positive isolates (P = 0.018). Antibiotic resistance was significantly correlated with biofilm production in S. epidermidis, but not in other CoNS species. Conclusions: Evasion of the host immune system by biofilm formation seems to be a clinically relevant mechanism in CoNS causing neonatal sepsis. The close contact of bacteria within a biofilm may facilitate horizontal exchange of genetic information. This might explain the high level of multidrug-resistance in biofilm positive S. epidermidis. The impact of antibiotic resistance and virulence determinants on clinical outcome of neonatal CoNS sepsis warrants additional clinical studies.

• Matthews, Iren; Brun, Henrik; Rønnestad, Arild Erlend & Saugstad, Ola Didrik (2005). Mekonium aspirasjon øker NO i ekspirasjonsluft. Paidos: Tidsskrift for Norsk barnelegeforening. ISSN 1503-5360. p. 10–10. Full text in Research Archive
• Rønnestad, Arild Erlend (2005). Infeksjoner hos barnet i forbindelse med fødsel og nyfødtperioden. Full text in Research Archive
• Rønnestad, Arild Erlend (2005). Oppdatering om Norsk Nyfødtmedisinsk Nettverk. Full text in Research Archive Show summary

  Subgruppemøte Neonatologi Pediaterdagene UUS, H2005, Torsdag 13.10 kl 17-19

• Rønnestad, Arild Erlend (2005). Nasjonale diagnosekriterier og Nasjonalt Nyfødtregister vil gi mer lik (likere) koding i nyfødtmedisin. Full text in Research Archive
• Rønnestad, Arild Erlend (2005). Reddes av morsmelk. [Journal]. Verdens Gang. Full text in Research Archive Show summary

  En ny studie viser at morsmelk reduserer dødelighet og forekomst av alvorlig infeksjon hos ekstremt tidlig fødte barn. I samarbeid med Medisinsk Fødselsregister har et team av forskere fulgt ekstremt premature barn over en periode på to år. - Det som viste seg å ha aller størst betydning for risikoen for alvorlig infeksjon, var hvor raskt de for tidlig fødte barna var fullt ernært på morsmelk, sier Arild Rønnestad, overlege ved Rikshospitalet. - I en del land er det vanlig praksis å bruke intravenøs ernæring over en lang periode hos premature barn. Dette er den første undersøkelsen vi kjenner til som dokumenterer at man med suksess kan gi ekstremt premature barn morsmelk veldig tidlig, forteller Rønnestad.

• Rønnestad, Arild Erlend (2005). Hvordan går det med de minste premature. Resultater fra den norske Ekstrem Prematuritet studien. Full text in Research Archive
• Klingenberg, C.; Sundsfjord, A; Rønnestad, Arild Erlend; Mikalsen, J; Gaustad, Peter & Flægstad, Trond (2004). Phenotypic and genotypic aminoglycoside resistance in blood culture isolates of coagulase-negative staphylococci from a single neonatal intensive care unit, 1989�2000. Pediatric Research. ISSN 0031-3998. 56(3), p. 464–464. Full text in Research Archive Show summary

  ESPR EUROPEAN SOCIETY FOR PEDIATRIC RESEARCH: Stockholm, Sweden September 19-22, 2004

• Klingenberg, Claus; Sundsfjord, Arnfinn; Rønnestad, A; Mikalsen, J; Gausiad, P & Flægstad, Trond (2004). Phenotypic and genotypic aminoglycoside resistance in blood culture isolates of coagulase negative staphylococci from a single neonatal intensive care unit, 1989-2000. Pediatric Research. ISSN 0031-3998. 56, p. 486–486. Full text in Research Archive
• Rønnestad, Arild Erlend (2004). Sepsis in a Norwegian national cohort of extremely premature infants during 1999 and 2000. A population based prospective study. Full text in Research Archive
• Brun, Henrik; Matthews, Iren; Rønnestad, Arild Erlend & Saugstad, Ola Didrik (2004). Hypoksi og Mekonium-aspirasjon øker NO i ekspirasjonsluft. Full text in Research Archive
• Rønnestad, Arild Erlend & Abrahamsen, Tore G (2006). Neonatal septicaemia: Epidemiology, diagnostic and therapeutic aspects. Universitetet i Oslo. ISSN 9788280728333. Full text in Research Archive

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