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OBJECTIVE: To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants. DESIGN: Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage ≥II) were validated against hospital records. PATIENTS: All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden. MAIN OUTCOME MEASURES: NEC incidence. RESULTS: The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047). CONCLUSIONS: The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.

Objective: To explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden. Design/Setting: Data on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions. Main outcome: One-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined. Results: 977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4). Conclusion: Increased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.

Background Preterm infants are vulnerable and sensitive to stimuli, during their stay in neonatal intensive care they undergo frequent stressful and painful procedures. One of these painful procedures is the screening for retinopathy of prematurity, ROP. In Sweden all preterm infants born before gestation week 30 undergo ROP-screening. The screening involves regular eye examinations to detect ROP at the early stages and these examinations are both stressful and painful. Several studies have investigated different ways of pain management during eye examinations with inconsequent results. No study has investigated Clonidine as pain management during ROP-screening. Aim The aim of this clinical trial is to investigate the analgesic effect of clonidine during ROP eyeexaminations. Method This study is a multicenter randomized controlled clinical trial with a crossover design. Infants born before gestation week 30 and therefore undergoing ROP-screening, will be eligible for inclusion in the study. Infants will be recruited from two Swedish NICUs (neonatal intensive care units). The NICUs use different examination techniques, where NICU A uses indirect ophthalmoscopy while NICU B uses RetCam. A total of 50 infants will be recruited (25 at each NICU). During the first eye examination the infant will be randomized to either clonidine 4mcg/kg or sterile water in the equivalent dose 60 minutes before the eye examination. The order of the treatment is blinded for everyone except the nurse preparing the study solution. During the second eye examination the infant will receive the study solution, (intervention or placebo) that he/she did not receive the first time. The primary outcome of the study is pain assessment with the Premature Infant Pain Profile – Revised. The infants´ face and monitor showing oxygen saturation and heart rate will be videorecorded to be able to assess the pain afterwards. The secondary outcome is Galvanic Skin Response where three probes are attached

Introduction: The communication skills of healthcare professionals play a crucial role in successful shared decision-making with parents in neonatal intensive care. Improving communication skills can be achieved through practice and reflection on personal experiences after authentic interaction events with parents. The process of reflection typically involves three phases: description, reflection, and critical reflection. In this study, our aim was to explore the acceptability of the Reflective Group Dialogue intervention and its effectiveness in supporting the reflective process. Methods: This qualitative pilot study was conducted in the neonatal intensive care unit at Uppsala University Children's Hospital, Sweden. The sample consisted of nine medical rounds with seven families, five neonatologists, seven registered nurses, and five assistant nurses. Purposive sampling was used to collect the data. The intervention comprised four elements: (1) before the intervention, a recorded presentation on shared decision-making was given to the entire unit staff, (2) an observation of a normal medical round discussion with parents, (3) an interview with parents about their experience after the same round, and (4) a reflective discussion with the participating health care professionals after the round. The parent interviews and reflective discussions were audio-recorded and transcribed verbatim. They were analyzed using thematic analysis as a theoretical strategy. Results: Both parents and staff widely accepted the intervention and found it beneficial. We identified four discussions that remained in the descriptive phase of the reflection process, four that reached the reflective phase, and one that reached the critical reflection phase. The descriptive discussions were characterized by using a single perspective to reflect, often based on personal opinions. The reflective discussions included analyzing interaction sequences from both staff and parent perspectives and were pr

Objective: To explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden. Design/Setting: Data on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions. Main outcome: One-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined. Results: 977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4). Conclusion: Increased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.

OBJECTIVE: To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants. DESIGN: Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage ≥II) were validated against hospital records. PATIENTS: All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden. MAIN OUTCOME MEASURES: NEC incidence. RESULTS: The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047). CONCLUSIONS: The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.

Introduction: Preterm infants are at risk of negative consequences from stress and pain at the same time as they often are in need of intensive care that includes painful interventions. One of the frequent painful procedures preterm infants undergo is eye examination screening to detect early signs of ROP (retinopathy of prematurity). These examinations are both stressful and painful, and despite a multitude of research studies, no conclusive pain-relieving treatment has been demonstrated. The main aim of this trial is to investigate the analgesic effect of clonidine during ROP eye examinations. Methods and analysis: The planned study is a multicentre randomised controlled trial with a crossover design. Infants will be recruited from two different neonatal intensive care units (NICUs) in Sweden. Infants born before gestation week 30 (and therefore eligible for ROP screening) and cared for in either of the NICUs will be eligible for inclusion in the study. The primary outcome will be Premature Infant Pain Profile-Revised score within 30 s after starting the examination. Secondary outcomes will be changes in the galvanic skin response parameters (area small peaks, area huge peaks, peaks per second and average rise time) within 30s after starting the eye examination, together with the number and evaluation of adverse events reported within 72 hours after the examination and the examining physician's assessment of how easy the infant was to examine. Ethics and dissemination: Approval from the Swedish Ethical Review Authority and the Swedish Medical Products Agency has been obtained for the study. Parents of eligible infants will be getting both verbal and written information about the study including that participation is voluntary. Data will be collected and treated in accordance with the European general data protection regulations. The results will be reported on group level and published in a scientific journal.

The optimal fluid requirements for extremely preterm infants are not fully known. We examined retrospectively the fluid intakes during the first week of life in two cohorts of extremely preterm infants born at 22-26 weeks of gestation before (n = 63) and after a change from a restrictive to a more liberal (n = 112) fluid volume allowance to improve nutrient provision. The cohorts were similar in gestational age and birth weight, but antenatal steroid exposure was more frequent in the second era. Although fluid management resulted in a cumulative difference in the total fluid intake over the first week of 87 mL/kg (p < 0.001), this was not reflected in a mean weight loss (14 +/- 5% at a postnatal age of 4 days in both groups) or mean peak plasma sodium (142 +/- 5 and 143 +/- 5 mmol/L in the restrictive and liberal groups, respectively). The incidences of hypernatremia (>145 and >150 mmol/L), PDA ligation, bronchopulmonary dysplasia, and IVH were also similar. We conclude that in this cohort of extremely preterm infants a more liberal vs. a restricted fluid allowance during the first week had no clinically important influence on early changes in body weight, sodium homeostasis, or hospital morbidities.

Introduction Preterm infants are at risk of negative consequences from stress and pain at the same time as they often are in need of intensive care that includes painful interventions. One of the frequent painful procedures preterm infants undergo is eye examination screening to detect early signs of ROP (retinopathy of prematurity). These examinations are both stressful and painful, and despite a multitude of research studies, no conclusive pain-relieving treatment has been demonstrated. The main aim of this trial is to investigate the analgesic effect of clonidine during ROP eye examinations. Methods and analysis The planned study is a multicentre randomised controlled trial with a crossover design. Infants will be recruited from two different neonatal intensive care units (NICUs) in Sweden. Infants born before gestation week 30 (and therefore eligible for ROP screening) and cared for in either of the NICUs will be eligible for inclusion in the study. The primary outcome will be Premature Infant Pain Profile–Revised score within 30 s after starting the examination. Secondary outcomes will be changes in the galvanic skin response parameters (area small peaks, area huge peaks, peaks per second and average rise time) within 30 s after starting the eye examination, together with the number and evaluation of adverse events reported within 72 hours after the examination and the examining physician’s assessment of how easy the infant was to examine. Ethics and dissemination Approval from the Swedish Ethical Review Authority and the Swedish Medical Products Agency has been obtained for the study. Parents of eligible infants will be getting both verbal and written information about the study including that participation is voluntary. Data will be collected and treated in accordance with the European general data protection regulations. The results will be reported on group level and published in a scientific journal., Funding agency:Lilla Barnets Fond YE1353, cloROP - Clonidine as analgesia during retinopathy of prematurity screening in preterm infants

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

Objective To determine survival and outcomes in infants born at 22-24 weeks of gestation in a centre with a uniformly active approach to management of extremely preterm infants. Study design Single-centre retrospective cohort study including infants born 2006-2015. Short-term morbidities assessed included retinopathy of prematurity, necrotising enterocolitis, patent ductus arteriosus, intraventricular haemorrhage, periventricular malacia and bronchopulmonary dysplasia. Neurodevelopmental outcomes assessed included cerebral palsy, visual impairment, hearing impairment and developmental delay. Results Total survival was 64% (143/222), ranging from 52% at 22 weeks to 70% at 24 weeks. Of 133 (93%) children available for follow-up at 2.5 years corrected age, 34% had neurodevelopmental impairment with 11% classified as moderately to severely impaired. Treatment-requiring retinopathy of prematurity, severe bronchopulmonary dysplasia, visual impairment and developmental delay correlated with lower gestational age. Conclusions A uniformly active approach to all extremely preterm infants results in survival rates that are not distinctly different across the gestational ages of 22-24 weeks and more than 50% survival even in infants at 22 weeks. The majority were unimpaired at 2.5 years, suggesting that such an approach does not result in higher rates of long-term adverse neurological outcome.

Objective: To evaluate an implementation of lower oxygen saturation targets with retinopathy of prematurity (ROP) as primary outcome, in infants at the lowest extreme of prematurity. Study design: Retrospective cohort including infants born at 22-25 weeks of gestation in 2005-2015 (n = 325), comparing high (87-93%) and low (85-90%) targets; infants transferred early were excluded from the main analysis to avoid bias. Results: Overall survival was 76% in high saturation era, and 69% in low saturation era (p = .17). Treatment-requiring ROP was less common in low saturation group (14% vs 28%, p < .05) with the most prominent difference in the most immature infants. Including deceased infants in the analysis, necrotizing enterocolitis was more frequent in low saturation era (21% vs 10%, p < .05). Conclusions: Implementing lower saturation targets resulted in a halved incidence of treatment-requiring ROP; the most immature infants seem to benefit the most. An association between lower oxygenation and necrotizing enterocolitis cannot be excluded.

Objective: To examine outcomes at two institutions with different approaches to care among infants born at 22 weeks of gestation. Study design: Retrospective, cohort study (2006–2015). Enrollment was limited to mother–infant dyads at 22 weeks of gestation. Proactive care was defined as provision of antenatal corticosteroids and neonatal resuscitation and intensive care. One center (Uppsala, Sweden; UUCH) provided proactive care to all mother–infant dyads (comprehensive center); the other center (Nationwide Children’s Hospital, USA; NCH) initiated or withheld treatment based on physician and family preferences (selective center). Differences in outcomes between the two centers were evaluated. Result: Among 112 live-born infants at 22 weeks of gestation, those treated at UUCH had in-hospital survival rates higher than those at NCH (21/40, 53% vs. 6/72, 8%; P < 0.01). Among the subgroup of infants receiving proactive care (UUCH: 40/40, 100%; NCH: 16/72, 22%) survival was higher at UUCH than at NCH (21/40, 53% vs. 3/16, 19%; P < 0.05). Conclusion: Even when mother–infant dyads were provided proactive care at NCH (selective center), survival was lower than infants provided proactive care at UUCH (comprehensive center). Differences between the approaches to care at the two centers at 22 weeks of gestation merits further investigation.

Aim: This study evaluated the medical quality of acute airborne transports carried out by a neonatal emergency transport service in a Swedish healthcare region from 2012 to 2015. Methods: The transport charts and patient records of all infants transported to the regional centre were reviewed for transport indications and vital parameters and outcomes. Results: We identified 187 acute airborne transports and the main indications for referral were therapeutic hypothermia after perinatal asphyxia, extremely preterm birth and respiratory failure. There were 37 deaths, but none of these occurred during transport and none of the deaths that occurred within 24 hours after transport were found to be related to the transport per se. No differences were found in vital parameters or ventilator settings before and after transport, except for an improvement in blood pH (7.22 +/- 0.13 versus 7.27 +/- 0.13, mean +/- SD, p < 0.01), due to a decrease in base deficit (-8.0 +/- 6.8 versus -5.4 +/- 6.3 mmol, p < 0.001), while the partial pressure of carbon dioxide remained unchanged. Conclusion: During air transport, critically ill neonates displayed stable vital parameters and reduced metabolic acidosis. No transport-related mortality was found, but the high number of extremely preterm infants transported indicates the potential for improving in-utero transport.

Aim: The aim of this study was to describe how parents experienced the support at, and preparation for discharge from, the NICU and how they experienced the first time at home. Design: A qualitative design with quantitative elements was applied. Methods: A questionnaire study. Data were analysed using qualitative content analysis with quantitative elements. Results: The majority of included parents felt adequately prepared for going home and sufficiently supported during the first period home. Negative experiences were related to lack of time for preparation, lack of support and information, especially about the infant's food intake, breastfeeding, and tube feeding, and lack of follow-up counselling post discharge. This study supports that parents who are closely involved in their infant's care at the NICU, and who stay with the infant at the NICU around the clock, are well prepared for the transition to home.

Aim: Little is known about the amount of physical parent-infant closeness in neonatal intensive care units (NICUs), and this study explored that issue in six European countries. Methods: The parents of 328 preterm infants were recruited in 11 NICUs in Finland, Estonia, Sweden, Norway, Italy and Spain. They filled in daily diaries about how much time they spent in the NICU, in skin-to-skin contact (SSC) and holding their babies in the first two weeks of their hospitalisation. Results: The parents' NICU presence varied from a median of 3.3 (minimum 0.7-maximum 6.7) to 22.3 (18.7-24.0) hours per day (p < 0.001), SSC varied from 0.3 (0-1.4) to 6.6 (2.2-19.5) hours per day (p < 0.001) and holding varied from 0 (0-1.5) to 3.2 (0-7.4) hours per day (p < 0.001). Longer SSC was associated with singleton babies and more highly educated mothers. Holding the baby for longer was associated with gestational age. The most important factor supporting parent-infant closeness was the opportunity to stay overnight in the NICU. Having other children and the distance from home to the hospital had no impact on parent-infant closeness. Conclusion: Parents spent more time in NICUs if they could stay overnight, underlining the importance that these facilities play in establishing parent-infant closeness.