Neonatal therapeutic hypothermia in a regional swedish cohort: Adherence to guidelines, transport and outcomes.

AIM: Swedish guidelines for therapeutic hypothermia (TH) after perinatal asphyxia were established in 2007, following several randomised studies that demonstrated improved outcomes. We assessed the implementation of hypothermia treatment in a mid-Swedish region with a sizeable proportion of outborn infants. METHOD: A population-based TH cohort from 2007 to 2015 was scrutinised for adherence to national guidelines, interhospital transport, including the use of a cooling mattress made of phase change material for thermal management, and outcomes. RESULTS: Of 136 admitted infants, 99 (73 %) were born outside the hospital. Ninety-eight percent fulfilled the criteria for postnatal depression/acidosis, and all patients had moderate-to-severe encephalopathy. Treatment was initiated within 6 h in 85 % of patients; amplitude-integrated electroencephalography/electroencephalography was recorded in 98 %, cranial ultrasound in 78 %, brain magnetic resonance imaging in 79 %, hearing tests in all, and follow-up was performed in 93 %. Although target body temperature was attained later (p < 0.01) in outborn than in inborn infants, at a mean (standard deviations) age of 6.2 (3.2) h vs 4.4 (2.6) h, 40 % of those transported using the cooling mattress were already within the therapeutic temperature range on arrival, and few were excessively cooled. The mortality rate was 23 %, and 38 % of the survivors had neurodevelopmental impairment at a median of 2.5 years. CONCLUSION: The regionalisation of TH, including interhospital transport, was feasible and resulted in outcomes comparable to those of randomised controlled studies.

Nordic survey showed wide variation in discharge practices for very preterm infants.

AIM: We aimed to describe clinical practices and criteria for discharge of very preterm infants in Nordic neonatal units. METHODS: Medical directors of all 89 level-2 and level-3 units in Denmark, Finland, Iceland, Norway and Sweden were invited by e-mail to complete a web-based multiple-choice survey with the option to make additional free-text comments. RESULTS: We received responses from 83/89 units (93%). In all responding units, discharge readiness was based mainly on clinical assessment with varying criteria. In addition, 36% used formal tests of cardiorespiratory stability and 59% used criteria related to infant weight or growth. For discharge with feeding tube, parental ability to speak the national language or English was mandatory in 45% of units, with large variation among countries. Post-discharge home visits and video-consultations were provided by 59% and 51%, respectively. In 54% of units, parental preparation for discharge were not initiated until the last two weeks of hospital stay. CONCLUSION: Discharge readiness was based mainly on clinical assessment, with criteria varying among units despite similar population characteristics and care structures. This variation indicates a lack of evidence base and may unnecessarily delay discharge; further studies of this matter are needed. Earlier parental preparation and use of interpreters might facilitate earlier discharge.

A follow up on the feasibility after national implementation of magnesium sulfate for neuroprotection prior to preterm birth.

INTRODUCTION: The risk for brain injury manifested as cerebral palsy is higher in very preterm born children than in term. Prenatal administration of magnesium sulfate (MgSO4 ) has been shown to be neuroprotective and reduces the proportion of very preterm born children later diagnosed with cerebral palsy. A Swedish national clinical practice guideline was implemented in March 2020, stipulating the administration of a single intravenous dose of 6 g MgSO4 1-24 h prior to delivery before gestational age 32+0, aiming for 90% treatment coverage. The aim of this study was to evaluate the feasibility of this new clinical practice guideline in the first year of its implementation. MATERIAL AND METHODS: Data on MgSO4 treatment were collected by reviewing the medical charts of women who gave birth to live born children in gestational age 22+0-31+6 during the period of March 1, 2020 to February 28, 2021, at five Swedish university hospitals. Women with pre-eclampsia, eclampsia, or high elevated liver enzymes low platelets (HELLP) were excluded. RESULTS: A total of 388 women were eligible and 79% received treatment with MgSO4 . Of the 21% not receiving treatment, 9% did not receive treatment due to lack of knowledge about the clinical practice guideline, 9% were not possible to treat and 3% had missing data. The proportion treated increased from 72% to 87% from the first to the last 3 months. Of those treated, 81% received the drug within the stipulated timeframe (mean 8.7 h, median 3.4 h). CONCLUSIONS: There was a positive trend over time in the proportion of women receiving MgSO4 treatment, but the a priori target of 90% was not reached during the first year of implementation. Our findings indicate that this target could be reached with additional information to clinicians.

Outcomes in children after mild neonatal hypoxic ischaemic encephalopathy: A population-based cohort study.

OBJECTIVE: To investigate whether mild neonatal hypoxic ischaemic encephalopathy (HIE) in term born infants is associated with cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. DESIGN: Population-based cohort study. SETTING: Sweden, 2009-2015. POPULATION: Live term born infants without congenital malformations or chromosomal abnormalities (n = 505 075). METHODS: Birth and health data were retrieved from Swedish national health and quality registers. Mild HIE was identified by diagnosis in either the Swedish Medical Birth Register or the Swedish Neonatal Quality Register. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: A composite of the outcomes cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. RESULTS: Median follow-up time was 3.3 years after birth. Of 414 infants diagnosed with mild HIE, 17 were classified according to the composite outcome and incidence rates were 12.6 and 2.9 per 1000 child-years in infants with and without HIE respectively. Infants with mild HIE was four times as likely to be diagnosed with the composite outcome (HR 4.42, 95% CI 2.75-7.12) compared with infants without HIE. When analysed separately, associations were found with cerebral palsy (HR 21.50, 95% CI 9.59-48.19) and death (HR 19.10, 95% CI 7.90-46.21). HRs remained essentially unchanged after adjustment for covariates. CONCLUSIONS: Mild neonatal HIE was associated with neurological morbidity and mortality in childhood. Challenges include identifying infants who may develop morbidity and how to prevent adverse outcomes.

Early Hyperglycemia in Very Preterm Infants Is Associated with Reduced White Matter Volume and Worse Cognitive and Motor Outcomes at 2.5 Years.

INTRODUCTION: Hyperglycemia in very preterm infants is associated with increased morbidity and mortality. We aimed to investigate potential associations between early hyperglycemia, neonatal cerebral magnetic resonance imaging (MRI), and neurodevelopment at 2.5 years. METHODS: The study population included 69 infants with gestational age (GA) 22.3-31.9 weeks (n = 29 with GA <28 weeks), born 2011-2014. Plasma glucose concentrations during the first week were checked according to clinical routines. Hyperglycemia was defined as glucose concentrations above 8.3 mmol/L (150 mg/dL) and above 10 mmol/L (180 mg/dL), respectively, categorized as the highest glucose days 0-2, number of days above 8.3 and 10 mmol/L, and prolonged (yes/no) 2 days or more above 8.3 and 10 mmol/L. The MRI analysis included morphological assessment, regional brain volumes, and assessment of apparent diffusion coefficient (ADC). Neurodevelopmental impairment (NDI) developed in 13 of 67 infants with available outcomes, of which 57 were assessed with the Bayley-III. Univariate and multiple linear and logistic regressions were performed with adjustments for GA, birth weight z-scores, and illness severity expressed as days on mechanical ventilation. RESULTS: Hyperglycemia above 8.3 mmol/L and 10 mmol/L was present in 47.8% and 31.9% of the infants. Hyperglycemia correlated independently with lower white matter volume, but not with other regional brain volumes, and was also associated with lower ADC values in white matter. Hyperglycemia also correlated with lower Bayley-III cognitive and motor scores in infants with GA <28 weeks, but there was no significant effect on NDI. CONCLUSION: Early hyperglycemia is associated with white matter injury and poorer neurodevelopment in very preterm infants.

Randomized controlled trial of low vs high oxygen during neonatal anesthesia: Oxygenation, feasibility, and oxidative stress.

BACKGROUND: To reduce risk for intermittent hypoxia a high fraction of inspired oxygen is routinely used during anesthesia induction. This differs from the cautious dosing of oxygen during neonatal resuscitation and intensive care and may result in significant hyperoxia. AIM: In a randomized controlled trial, we evaluated oxygenation during general anesthesia with a low (23%) vs a high (80% during induction and recovery, and 40% during maintenance) fraction of inspired oxygen, in newborn infants undergoing surgery. METHOD: Thirty-five newborn infants with postconceptional age of 35-44 weeks were included (17 infants in low and 18 in high oxygen group). Oxygenation was monitored by transcutaneous partial pressure of oxygen, pulse oximetry, and cerebral oxygenation. Predefined SpO2 safety targets dictated when to increase inspired oxygen. RESULTS: At start of anesthesia, oxygenation was similar in both groups. Throughout anesthesia, the high oxygen group displayed significant hyperoxia with higher (difference-20.3 kPa, 95% confidence interval (CI)-28.4 to 12.2, p < .001) transcutaneous partial pressure of oxygen values than the low oxygen group. While SpO2 in the low oxygen group was lower (difference - 5.8%, 95% CI -9.3 to -2.4, p < .001) during anesthesia, none of the infants spent enough time below SpO2 safety targets to mandate supplemental oxygen, and cerebral oxygenation was within the normal range and not statistically different between the groups. Analysis of the oxidative stress biomarker urinary F2 -Isoprostane revealed no differences between the low and high oxygen group. CONCLUSION: We conclude that in healthy newborn infants, use of low oxygen during general anesthesia was feasible, while the prevailing practice of using high levels of inspired oxygen resulted in significant hyperoxia. The trade-off between careful dosing of oxygen and risks of hypo- and hyperoxia in neonatal anesthesia should be further examined.

Nursing care of infants born extremely preterm.

With improving survival at the lowest gestations an increasing number of tiny and vulnerable infants are being cared for, and optimal outcomes require an approach to care that takes their specific characteristics into account. These include immature organ function and a risk for iatrogenic injury, and parental/familial strain due to the high degree of uncertainty, infant-mother separation, and long hospital stay. While the challenges in providing nursing care to these infants are obvious it is also clear that this field has tremendous potential to influence both short and long-term outcomes of this population. This mini-review discusses aspects of the nursing care provided to infants born at the very lowest gestations and their families, with focus on doing less harm by establishing an adequate care environment, actively promoting parental closeness and care-giving, and conservative skin care.

Sodium supply from administered blood products was associated with severe intraventricular haemorrhage in extremely preterm infants.

AIM: The aim of this study was to investigate the associations between sodium supply, fluid volume, sodium imbalances and severe intraventricular haemorrhage (IVH) in extremely preterm (EPT) infants. METHODS: We used data from the EXtremely PREterm infants in Sweden Study (EXPRESS) cohort consisting of all infants born at 22 to 26 gestational weeks from 2004 to 2007 and conducted a nested case-control study. For every infant with severe IVH (grade 3 or peri-ventricular haemorrhagic infarction), one IVH-free control infant with the birthday closest to the case infant and matched for hospital, sex, gestational age and birth weight was selected (n = 70 case-control pairs). RESULTS: Total sodium supply and fluid volume were higher in infants with severe IVH compared with controls [daily total sodium supply until postnatal Day 2: mean ± SD (mmol/kg/day): 5.49 ± 2.53 vs. 3.95 ± 1.91, p = 0.009]. These differences were accounted for by sodium and fluid from transfused blood products. High plasma sodium concentrations or large sodium fluctuations were not associated with severe IVH. CONCLUSION: Our results suggest a relationship between sodium-rich transfusions of blood products and severe IVH in EPT infants. It is unclear whether this is an effect of sodium load, volume load or some other transfusion-related factor.

The Impact of Restricted versus Liberal Early Fluid Volumes on Plasma Sodium, Weight Change, and Short-Term Outcomes in Extremely Preterm Infants.

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.

Risk factors for seizures in the vigorous term neonate: A population-based register study of singleton births in Sweden.

BACKGROUND: Neonatal seizures have been associated with increased mortality and impaired neurodevelopment and, knowledge about risk factors may be useful for prevention. Clear associations have been established between labor-related risk factors and seizures in asphyxiated neonates. However, there is limited information about why some vigorous term-born infants experience seizures. OBJECTIVES: Our aim was to assess antepartum and intrapartum risk factors for seizures in vigorous term-born neonates. METHODS: This was a national cohort study of singleton infants born at term in Sweden from 2009-2015. Vigorous was defined as an Apgar score of at least 7 at 5 and 10 minutes. Data on the mothers and infants were obtained from the Swedish Medical Birth Register and the Swedish Neonatal Quality Register. A diagnosis of neonatal seizures was the main outcome measure and the exposures were pregnancy and labor variables. Logistic regression analysis was used and the results are expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: The incidence of neonatal seizures was 0.81/1,000 for 656 088 births. Seizures were strongly associated with obstetric emergencies (aOR 4.0, 95% CI 2.2-7.4), intrapartum fever and/or chorioamnionitis (aOR 3.4, 95% CI 2.1-5.3), and intrapartum fetal distress (aOR 3.0, 95% CI 2.4-3.7). Other associated intrapartum factors were: labor dystocia, occiput posterior position, operative vaginal delivery, and Cesarean delivery. Some maternal factors more than doubled the risk: a body mass of more than 40 (aOR 2.6, 95% CI 1.4-4.8), hypertensive disorders (aOR 2.3, 95% CI 1.7-3.1) and diabetes mellitus (aOR 2.6, 95% CI 1.7-4.1). CONCLUSION: A number of intrapartum factors were associated with an increased risk of seizures in vigorous term-born neonates. Obstetric emergencies, intrapartum fever and/or chorioamnionitis and fetal distress were the strongest associated risks. The presence of such factors, despite a reassuring Apgar score could prompt close surveillance.

Fluid management considerations in extremely preterm infants born at 22-24 weeks of gestation.

Emerging data regarding the encouraging outcomes of extremely preterm infants from centers taking active approaches to the care of these infants have prompted dialogue regarding optimal medical management. Among the multitude of decisions providers make in caring for extremely premature infants is the prescribing of parenteral fluids. Surprisingly, there are limited data to guide evidenced-based approaches to fluid and electrolyte management in this population. Immaturity of renal function and skin barriers contribute to the impaired capacity of the preterm infant to maintain salt and water homeostasis. This perspective paper highlights developmental physiological properties of the kidney and skin, which the provider needs to understand to provide parenteral fluid therapy. Additionally, we provide recommendations for initial fluid and electrolyte management of the preterm infant based on novel data as well as the published literature.

The proactive approach to mother-infant dyads at 22-24 weeks of gestation: Perspectives from a Swedish center.

The care of infants born at the lowest extreme of gestation requires dedication, skill, and experience. Most centers apply a selective approach where intensive care at these gestational ages is being offered to a varying proportion of infants depending on the views and experiences of the medical community, the individual physician, and the parents. Consequently, the outcomes differ dramatically with survival rates at 22-23 weeks ranging from 0 to greater than 50%. This paper presents the approach in a center with a long tradition of providing a comprehensive and uniformly active care to all mother-infant dyads from 22+0 weeks of gestation. Important features outlined include prenatal maternal referral and transfer, delivery room management, and initial intensive care.

The Swedish approach to nurturing extremely preterm infants and their families: A nursing perspective.

Nurturing extremely premature infants is a complicated task that not only necessitates a systematic approach to the immature physiology and its medical management, but also to the needs of the family. Infants born at 22-24 weeks require many weeks of intensive care including a long duration of mechanical ventilation, numerous stressful medical interventions, and for the parents to spend a lot of time in the Neonatal Intensive Care unit (NICU). This paper aims to outline the Swedish nursing approach to nurturing these infants and their families. The nursing care is structured so the parents are the primary caregivers supported by the staff and is based on: timely expression and provision of mother's own breast milk, early and prolonged skin-to-skin contact and close collaboration with the family. While this presentation is based on a single-center's experience, it well represents the general features of nursing provided to extremely preterm infants in Swedish NICUs.

Early extubation is associated with shorter duration of mechanical ventilation and lower incidence of bronchopulmonary dysplasia.

INTRODUCTION: Respiratory care of extremely preterm infants remains a challenge. The majority require invasive mechanical ventilation (MV), which is a contributing factor in developing bronchopulmonary dysplasia (BPD). It is important to keep MV to a minimum but there have been concerns that attempting extubation too early increases the risk for atelectasis, re-intubation, and further lung trauma. The aim of this study was to compare two different approaches to extubation. METHODS: Single-center, retrospective cohort study including infants born at 22 + 0-25 + 6 weeks during 2005-2009 and 2011-2015, before and after implementing guidelines recommending delayed extubation. Primary outcomes were BPD, duration of MV and length of hospital stay. RESULTS: Eighty-eight infants in the early era and 102 infants in the late era were included. Infants in the first period were younger at first extubation attempt, and a higher number of infants were extubated within 24 h, 72 h, and one week after birth. The number of infants re-intubated and postnatal age at re-intubation did not differ between the groups. The incidence of severe BPD was 28% in the early period compared to 48% in the later (p < 0.01). Infants in the late period had longer duration of MV (17 vs 27 days, p < 0.01) but similar length of hospital stay (118 vs 123, p = 0.21). CONCLUSION: After implementing guidelines recommending delayed extubation, the incidence of severe BPD was higher and the duration of MV was longer. This supports the strategy to attempt extubation early even in extremely preterm infants.

Established severe BPD: is there a way out? Change of ventilatory paradigms.

Improved survival of extremely preterm newborn infants has increased the number of infants at risk for developing bronchopulmonary dysplasia (BPD). Despite efforts to prevent BPD, many of these infants still develop severe BPD (sBPD) and require long-term invasive mechanical ventilation. The focus of research and clinical management has been on the prevention of BPD, which has had only modest success. On the other hand, research on the management of the established sBPD patient has received minimal attention even though this condition poses large economic and health problems with extensive morbidities and late mortality. Patients with sBPD, however, have been shown to respond to treatments focused not only on ventilatory strategies but also on multidisciplinary approaches where neurodevelopmental support, growth promoting strategies, and aggressive treatment of pulmonary hypertension improve their long-term outcomes. In this review we will try to present a physiology-based ventilatory strategy for established sBPD, emphasizing a possible paradigm shift from acute efforts to wean infants at all costs to a more chronic approach of stabilizing the infant. This chronic approach, herein referred to as chronic phase ventilation, aims at allowing active patient engagement, reducing air trapping, and improving ventilation-perfusion matching, while providing sufficient support to optimize late outcomes. IMPACT: Based on pathophysiological aspects of evolving and established severe BPD in premature infants, this review presents some lung mechanical properties of the most severe phenotype and proposes a chronic phase ventilatory strategy that aims at reducing air trapping, improving ventilation-perfusion matching and optimizing late outcomes.

Outcomes of a uniformly active approach to infants born at 22-24 weeks of gestation.

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.

When all I wanted was to hold my baby-The experiences of parents of infants who received therapeutic hypothermia.

AIM: The knowledge is limited about how parents experience the time when their infant is receiving therapeutic hypothermia (TH) after severe perinatal asphyxia. The aim of this study was to explore parents' experience of closeness and involvement in their infant's care while in the neonatal intensive care unit (NICU) with their newborn undergoing TH. METHODS: Face-to-face, semi-structured interviews were conducted with parents (n = 11) whose infants (n = 8, aged 3-5 years at the time of the study) underwent TH at a level III Swedish NICU during 2013-2016. The interviews were analysed using qualitative content analysis. RESULTS: All the parents shared the trauma of being both physically and psychologically separated from their infant. They all described a need for information and emotional support, and reported that the NICU staff had influenced the extent to which they as parents had been able to be near and actively participate in the care. Parents described the wish to be closer to their infant and to be more actively involved in their infant's care. CONCLUSION: Strategies to enable parent-infant closeness and active guidance from staff might help alleviate the emotional stress of parents and promote their participation during TH.