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1.  L-citrulline provides a novel strategy for treating chronic pulmonary hypertension in newborn infants 
Acta paediatrica (Oslo, Norway : 1992)  2014;103(10):1019-1026.
Effective therapies are urgently needed for infants with forms of pulmonary hypertension that develop or persist beyond the first week of life. The L-arginine nitric oxide (NO) precursor, L-citrulline, improves NO signalling and ameliorates pulmonary hypertension in newborn animal models. In vitro studies demonstrate that manipulating L-citrulline transport alters NO production.
Strategies that increase the supply and transport of L-citrulline merit pursuit as novel approaches to managing infants with chronic, progressive pulmonary hypertension.
PMCID: PMC4209175  PMID: 24862864
pulmonary hypertension; bronchopulmonary dysplasia; premature infants; nitric oxide; oxidative stress
2.  The association between 5-min Apgar score and mortality disappears after 24 h at the borderline of viability 
Acta paediatrica (Oslo, Norway : 1992)  2011;101(6):e243-e247.
To quantify the relationship between 5-min Apgar scores and infant mortality for infants at the borderline of viability.
Cohort study of 7008 infants 23–25 weeks' gestation using 2002 US National Center for Health Statistics data. Using Cox proportional-hazards models, we quantified the relationship between Apgar score and infant mortality for all infants, and then infants surviving their first 24 h. Models were adjusted for gestational age, birth weight, gender, delivery method, plurality, maternal race, marital status and education.
Within one year, 46% of infants died. Of the non-survivors, deaths within 24 h were more common among infants with Apgar scores 0–3 (83%) than among infants with Apgar scores 7–10 (13%). When including all infants and adjusting for potential confounders, each 1-point increase in Apgar score decreased the hazard of mortality by 0.82. However, after excluding infants who died within 24 h, the hazard ratio increased to 0.95; although statistically significant, the practical impact was negated.
For 23–25 week gestation infants surviving the first 24 h, the Apgar score loses clinical significance. Clinicians should be aware of the limitations of clinical assessments in the delivery room.
PMCID: PMC4547603  PMID: 21535125
Apgar score; Epidemiology; Neonatology; Prematurity
3.  The nonimpact of gestational age on neurodevelopmental outcome for ventilated survivors born at 23–28 weeks of gestation 
It has long been known that survival of preterm infants strongly depends upon birth weight and gestational age. This study addresses a different question – whether the gestational maturity improves neurodevelopmental outcomes for ventilated infants born at 23–28 weeks who survive to neonatal intensive care unit (NICU) discharge.
We performed a prospective cohort study of 199 ventilated infants born between 23 and 28 weeks of gestation. Neurodevelopmental impairment was determined using the Bayley Scales of Infant Development-II at 24 months.
As expected, when considered as a ratio of all births, both survival and survival without neurodevelopmental impairment were strongly dependent on gestational age. However, the percentage of surviving infants who displayed neurodevelopmental impairment did not vary with gestational age for any level of neurodevelopmental impairment (MDI or PDI <50, <60, <70). Moreover, as a higher percentage of ventilated infants survived to NICU discharge at higher gestational ages, but the percentage of neurodevelopmental impairment in NICU survivors was unaffected by gestational age, the percentage of all ventilated births who survived with neurodevelopmental impairment rose – not fell – with increasing gestation age.
For physicians, parents and policy-makers whose primary concern is the presence of neurodevelopmental impairment in infants who survive the NICU, reliance on gestational age appears to be misplaced.
PMCID: PMC4528368  PMID: 22277021
Prematurity; Neurodevelopmental disability; Gestational age; Neonatal outcomes research; Neonatal ethics
4.  The Prediction and Cost of Futility in the NICU 
To quantify the cost and prediction of futile care in the Neonatal Intensive Care Unit (NICU).
We observed 1813 infants on 100 000 NICU bed days between 1999 and 2008 at the University of Chicago. We determined costs and assessed predictions of futility for each day the infant required mechanical ventilation.
Only 6% of NICU expenses were spent on nonsurvivors, and in this sense, they were futile. If only money spent after predictions of death is considered, futile expenses fell to 4.5%. NICU care was preferentially directed to survivors for even the smallest infants, at the highest risk to die. Over 75% of ventilated NICU infants were correctly predicted to survive on every day of ventilation by every caretaker. However, predictions of ‘die before discharge’ were wrong more than one time in three. Attendings and neonatology fellows tended to be optimistic, while nurses and neonatal nurse practitioners tended to be pessimistic.
Criticisms of the expense of NICU care find little support in these data. Rather, NICU care is remarkably well targeted to patients who will survive, particularly when contrasted with care in adult ICUs. We continue to search for better prognostic tools for individual infants.
PMCID: PMC4528369  PMID: 22150563
Futility; neonatal outcomes research; NICU economics; prediction; prematurity
5.  Raman spectroscopy provides a non-invasive approach for determining biochemical composition of the pregnant cervix in vivo 
The molecular changes that occur with cervical remodelling during pregnancy are not completely understood. This paper reviews Raman spectroscopy, an optical technique for detecting changes in the pregnant cervix, and reports preliminary studies on cervical remodelling in mice that suggest that the technique provides advantages over other methods. Conclusion: Raman spectroscopy is sensitive to biochemical changes in the pregnant cervix and has high potential as a tool for detecting premature cervical remodelling in pregnant women.
PMCID: PMC4048629  PMID: 24628401
cervix; pregnancy; parturition; preterm birth; cervical remodelling
6.  Ear drainage and the role of sepsis evaluations in the neonatal intensive care unit 
To design and implement an intervention to reduce ear drainage and subsequent sepsis evaluation and treatment in the neonatal intensive care unit.
From 2008 to 2011, we observed an increase in the rates of ear drainage warranting investigation. Data collection was performed from 1991 to 2013 on 50 cases. Preliminary analysis revealed an association between timing of endotracheal tube tape changes and onset of drainage. We speculated that pooling of anti-adhesive solution into the external auditory canal was precipitating an inflammatory process. Unit-wide education was conducted to protect the ears during tape removal. Post-initiative rates of drainage were collected and compared with pre-initiative rates.
Median gestational age and birth weight were 26 weeks and 754 grams. In 64% of cases, an anti-adhesive solution was used on the face within 48 hours of the onset of drainage. Sepsis evaluation was performed in 68% of cases. Rates of ear drainage peaked from 2008–2011 at 9.18 per 1,000 admissions when a new anti-adhesive product was used, declining to 0.66 post-initiative (rate difference: −8.52; 95% CI: −12.00, −5.03).
Protecting the ear from anti-adhesive solutions during tape removal may reduce rates of non-infectious ear drainage and limit unnecessary interventions.
PMCID: PMC4320968  PMID: 24635016
Neonate; ear drainage; sepsis evaluation
7.  Nordic pulse oximetry screening – implementation status and proposal for uniform guidelines 
Acta Paediatrica (Oslo, Norway : 1992)  2014;103(11):1136-1142.
Pulse oximetry screening of newborn infants increases early detection of critical congenital heart disease and minimises the risk of circulatory collapse before surgery. This study provides an update on the implementation of pulse oximetry screening in the Nordic countries and proposes standardised guidelines.
A questionnaire exploring pulse oximetry screening, clinical examination routines and availability of echocardiography was distributed to all 157 delivery units in the Nordic countries in June 2013.
We received responses from 156 of the 157 delivery units, and 116 (74%) were using pulse oximetry screening by September 2013. Preductal and postductal screening were both used in 59 of 116 units (51%), with just postductal screening in 51 of 116 (44%) and just preductal screening alone in 6 of 116 (5%). Screening was performed before 24 h in 105 of 116 units (91%). The implementation of screening was highest in Finland (29/30, 97%), Sweden (42/46, 91%) and Norway (43/48, 90%) and lowest in Denmark (2/24, 8%) and Iceland (0/8 units).
In Sweden, Norway and Finland, the implementation of pulse oximetry screening is currently the highest in the world and coverage will be close to 100% in 2014. We propose uniform Nordic guidelines using preductal and postductal screening before 24 h of age.
PMCID: PMC4480652  PMID: 25060211
Congenital heart disease; Guidelines; Newborn screening; Pulse oximetry
8.  Preterm born 9-year-olds have elevated IGF-1 and low prolactin, but levels vary with behavioural and eating disorders 
Acta Paediatrica (Oslo, Norway : 1992)  2014;103(11):1198-1205.
This study examined the relationship between hypothalamic-associated hormones and behavioural and eating disorders in children with low birthweight.
We included 100 children (mean age 9.7 years): 39 were born preterm at <32 gestational weeks, 28 were full-term, but small for gestational age, and 33 were full-term controls. Behavioural histories were analysed, together with fasting blood samples of leptin, insulin, insulin-like growth factor-1 (IGF-I), prolactin, glucagon and cortisol.
Preterm children had lower prolactin (p = 0.01) and higher IGF-I than controls (p < 0.05, adjusted for confounders), despite being significantly shorter than the predicted target height (p < 0.001). More preterm children displayed behavioural disorders (38% versus 10%, p < 0.001) and eating disorders (26% versus 8%, p < 0.05) than full-term children. These disorders were associated with lower leptin (p < 0.01), insulin (p < 0.05) and IGF-I (p < 0.05), but correlations between these hormones and leptin were similar among the groups. Combined behavioural and eating disorders were only observed in preterm children, who were also the shortest in height.
Behavioural and eating disorders among preterm children were associated with low leptin, insulin and IGF-1. Low prolactin in all preterm children indicated an increased dopaminergic tonus, which might inhibit body weight incrementation. This raises speculation about IGF-I receptor insensitivity.
PMCID: PMC4480651  PMID: 25040495
Dopaminergic tonus; Insulin-like growth factor-1; Leptin; Prolactin; Target height deviation
9.  Sexual debut before the age of 14 leads to poorer psychosocial health and risky behaviour in later life 
This study investigated the relationship between sexual debut before 14 years of age and socio-demographics, sexual experience, health, experience of child abuse and behaviour at 18 years of age.
A sample of 3432 Swedish high school seniors completed a survey about sexuality, health and abuse at the age of 18.
Early debut was positively correlated with risky behaviours, such as the number of partners, experience of oral and anal sex, health behaviours, such as smoking, drug and alcohol use, and antisocial behaviour, such as being violent, lying, stealing and running away from home. Girls with an early sexual debut had significantly more experience of sexual abuse. Boys with an early sexual debut were more likely to have a weak sense of coherence, low self-esteem and poor mental health, together with experience of sexual abuse, selling sex and physical abuse. A multiple logistic regression model showed that a number of antisocial acts and health behaviours remained significant, but early sexual debut did not increase the risk of psychiatric symptoms, low self-esteem or low sense of coherence at 18 years of age.
Early sexual debut was associated with problematic behaviours during later adolescence, and this vulnerability requires attention from parents and healthcare providers.
PMCID: PMC4480657  PMID: 25213099
Child abuse; Drug use; Risky behaviour; Sexual behaviour; Sexual debut
10.  The incidence and aetiology of acute kidney injury in children in Norway between 1999 and 2008 
Acta Paediatrica (Oslo, Norway : 1992)  2014;103(11):1192-1197.
Primary acute kidney injury (AKI) is a direct cause of hospitalisation in children, but can also result from other conditions. There is limited information on the epidemiology of this condition. Our aim was to describe the national incidence rate and aetiology of acute kidney injury in children under the age of 16 in Norway from 1999 to 2008.
We carried out a retrospective study of medical records provided by all 18 of the paediatric hospital departments that specialise in treating paediatric patients with AKI.
We identified 315 cases of AKI (53% male), with an estimated average annual incidence rate of 3.3 cases per 100 000 children and a median annual occurrence of 33 cases. Most cases (43%) were in children under five. We identified 53 aetiologies and classified these into 30 aetiological groups: 24% of the cases were prerenal (n = 75), 74% were intrinsic/renal (n = 234) and 2% were postrenal (n = 5). Nephritic syndromes was the major cause (44%) of AKI, followed by haemolytic-uraemic syndrome (HUS) (15%).
Nephritic syndromes and HUS are the most common aetiologies of AKI in Norway. Although our results could indicate a low incidence of paediatric AKI in Norway, the lack of other national studies makes comparisons difficult.
PMCID: PMC4480659  PMID: 25039408
Acute kidney injury; Aetiology; Epidemiology; Haemolytic-uraemic syndrome; Nephritic syndrome
11.  Interactions among peripheral perfusion, cardiac activity, oxygen saturation, thermal profile and body position in growing low birth weight infants 
To investigate the correlation between the ‘perfusion index’ (PI) and other commonly used estimates of cutaneous blood flow [heart rate (HR), surface temperatures (ST) and central-to-peripheral thermal gradients (C-P grad)] and to use this new non-invasive tool to compare differences between prone and supine sleep position in low birth weight (LBW) infants.
Six-hour continuous recordings of pulse oximetry, cardiac activity and absolute ST from three sites (flank, forearm and leg), along with minute-to-minute assessment of behavioural states were performed in 31 LBW infants. Infants were randomly assigned to the prone or supine position for the first 3 h and then reversed for the second 3 h. PI data were correlated with HR and C-P grad, and compared across sleep positions during quiet sleep (QS) and active sleep (AS).
Perfusion index correlated significantly with HR (r2 = 0.40) and flank-to-forearm thermal gradient (r2 = 0.28). In the prone position during QS, infants exhibited higher PI (3.7 ± 0.9 vs. 3.1 ± 0.7), HR (158.4 ± 8.9 vs. 154.1 ± 8.8 bpm), SpO2 (95.8 ± 2.6 vs. 95.2 ± 2.6%), flank (36.7 ± 0.4 vs. 36.5 ± 0.4°C), forearm (36.1 ± 0.6 vs. 35.5 ± 0.4°C) and leg (35.4 ± 0.7 vs. 34.7 ± 0.7°C) temperatures and narrower flank-to-forearm (0.6 ± 0.4 vs. 0.9 ± 0.3°C) and flank-to-leg (1.3 ± 0.6 vs. 1.8 ± 0.7°C) gradients, compared to those of the supine position. Similar differences were observed during AS.
Perfusion index is a good non-invasive estimate of tissue perfusion. Prone sleeping position is associated with a higher PI, possibly reflecting thermoregulatory adjustments in cardiovascular control. The effects of these position-related changes may have important implications for the increased risk for sudden infant death syndrome in prone position.
PMCID: PMC4465210  PMID: 19785632
Active sleep; Prone; Quiet sleep; Sudden infant death syndrome; Supine
13.  Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain 
Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants.
We studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas.
Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant.
Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain.
PMCID: PMC4463763  PMID: 25358870
Brain; Cutaneous stimulation; Magnetic resonance imaging; Neonatal; Pain
14.  Delivering Perinatal Psychiatric Services in the Neonatal Intensive Care Unit 
Acta paediatrica (Oslo, Norway : 1992)  2013;102(9):e392-e397.
To describe characteristics of mothers who would likely benefit from on-site short-term psychiatric services while their infant is in the Neonatal Intensive Care Unit (NICU).
For 150 consecutive mothers who were referred for psychiatric evaluation and psychotherapeutic intervention in an innovative NICU mental health program, baseline information was collected. Data regarding their referrals, diagnosis, treatments, and their infants was analyzed.
Most mothers were referred because of depression (43%), anxiety (44%), and/ or difficulty coping with their infant's medical problems and hospitalization (60%). Mothers of VLBW infants were disproportionately more likely to be referred. A majority of mothers accepted the referral and were treated; most only required short-term psychotherapy. A minority resisted or refused psychiatric assessment; a quarter of these had more difficult interactions with staff or inappropriate behaviors. In these cases the role of the psychiatrist was to work with staff to promote healthy interactions and to foster maternal-infant bonding.
Overall, on-site psychiatric services have been accepted by a majority of referred NICU mothers, and most did not require long-term treatment. A considerable need exists for psychiatric services in the NICU to promote optimal parenting and interactions.
PMCID: PMC4420733  PMID: 23772977
depression; neonatal morbidity; anxiety; coping skills
15.  Children under the age of two are more likely to watch inappropriate background media than older children 
To establish whether young children watched foreground electronic media or background media that was not aimed at them or was inappropriate for their age.
We performed a longitudinal analysis of mother-infant dyads participating in a larger parenting study. The primary dependent variable was maternal reports of watching habits from media diaries at six, 14, 24 and 36 months. Independent variables were child age, programme content and whether the programme was turned on specifically for the child.
We analysed 3,570 programme exposures in 527 children, mostly from television. Children were significantly more likely to actually watch programmes if they were older, if the content was coded as “educational-young child” or if the parent tuned on the programme specifically so the child could watch it. Children under the age of two were more likely than older children to watch background media that featured age-inappropriate content or had not been turned on for them to watch (30% versus 16% of programmes; AOR = 2.19, [95%CI 1.82-2.65]).
Young children under the age of two frequently watch background media that has age-inappropriate content or has not been turned on for them to watch.
PMCID: PMC4067319  PMID: 24812713
Media; Young Child; Television
16.  Not the right time: why parents refuse to let their daughters have the human papillomavirus vaccination 
To explore why parents refused to allow their 10- to 12-year-old daughters to receive the human papillomavirus (HPV) vaccination from the Swedish school-based vaccination programme.
Individual interviews with 25 parents who had been offered, but not consented to, their daughters receiving the HPV vaccination.
Five themes emerged through the interviews: 1) she is just a little girl, 2) inadequate information, 3) not compatible with our way of life, 4) scepticism about the vaccination and 5) who can you trust? The parents made their decisions with their child's best interests in mind. This was not considered the right time, and the vaccine was perceived as unnecessary and different from other vaccines. Mistrust in Government recommendations and a lack of evidence or information were other reasons to decline.
The decision-making process was complex. These parents preferred to wait until their daughter was older and believed the information they received from the school health system was insufficient. The results indicate that a more flexible HPV vaccination schedule may improve vaccine uptake. This includes more transparent information about the virus and the vaccine and information about who to contact to get the daughter vaccinated at a later date.
PMCID: PMC4383348  PMID: 24460679
Decision-making; Human papillomavirus; Parents; School; Vaccination programmes
17.  Development and psychometric properties of the Swedish ALPS-Neo pain and stress assessment scale for newborn infants 
To validate and evaluate the psychometric properties of the ALPS-Neo, a new pain assessment scale created for the continuous evaluation of pain and stress in preterm and sick term infants.
A unidimensional scale for continuous pain, Astrid Lindgren Children's Hospital Pain Scale (ALPS 1), was developed further to assess continuous pain and stress in infants treated in the neonatal intensive care unit (NICU). The pain scale includes observations of five behaviours. A manual was created, clarifying the scoring criteria. An internal and an external panel assessed face validity. Psychometric properties were evaluated in three different steps. Inter-rater reliability was estimated from video-based assessments (n = 625) using weighted kappa statistics (test I). Inter-rater reliability was further evaluated in test II (n = 125) and test III (n = 96) by real-time assessments using the intraclass correlation coefficient (ICC) and Cronbach's alpha.
The final inter-rater reliability (test III) was assessed as good with ICC 0.91 for the total score and 0.62–0.81 for the five items. Cronbach's alpha showed 0.95 for the total score.
ALPS-Neo is a new assessment tool for optimising the management of pain and stress in newborn infants in the NICU. It has proved easy to implement and user-friendly, permitting fast, reliable observations with high inter-rater reliability.
PMCID: PMC4368370  PMID: 24813238
Developmental care; Pain; Pain assessment; Pain management; Stress
18.  Cerebral maturation on amplitude-integrated electroencephalography and perinatal exposures in preterm infants 
To determine the associations between perinatal exposures, cerebral maturation on amplitude-integrated encephalography (aEEG) and outcome.
During this prospective cohort study, 136 infants ≤30 weeks estimated gestational age received four hours of aEEG at four time points (between the first two weeks of life and term equivalent age) during hospitalisation. Perinatal factors were documented. Associations between perinatal exposures and Burdjalov-scores were investigated. Neurodevelopmental outcome was assessed at the age of two.
Immature cyclicity on the initial aEEG recording was associated with higher CRIB score (p=0.01), vaginal delivery (p= 0.02), male gender (p<0.01) and death (p=0.01). Perinatal factors associated with lower Burdjalov-scores included cerebral injury (p<0.01), sepsis (p<0.01), lower caffeine dose (p=0.006), prolonged mechanical ventilation (p=0.002) and death (p<0.01). Burdjalov-scores at 30 (β=2.62, p<0.01) and 34 weeks post-menstrual age (β=2.89, p=0.05) predicted motor scores.
aEEG measures of cyclicity and Burdjalov-scores in the first six weeks of life, with an emphasis on 30 and 34 weeks post-menstrual age, demonstrated associations with perinatal factors known to predict adverse neurodevelopmental outcome.
PMCID: PMC3945948  PMID: 24354724
neonatal intensive care; preterm infant; aEEG; cerebral maturation; perinatal exposure
19.  Parents and children's perceptions of distress related to oral mucositis during haematopoietic stem cell transplantation 
Oral mucositis is a common and debilitating side effect of haematopoietic stem cell transplantation. Our study investigated parents' and children's experiences of oral mucositis treatment and whether the parents' perceptions accurately reflected the children's views.
We analysed 71 questionnaires completed by the parents of children who had undergone haematopoietic stem cell transplantation, together with 38 questionnaires completed by children who were 7 years of age or over.
The parent proxy and child self‐reports showed good to excellent agreement. For example, 86% of the parents and 83% of the children reported oral pain and 44% of the parents and 47% of the children reported difficulty swallowing often or very often. The majority of the parents (61%) were satisfied with the pain treatment that had been given to their child. However, the treatment provided for oral mucositis was not altogether consistent.
Oral mucositis affected the majority of the children undergoing haematopoietic stem cell transplantation, causing considerable pain and discomfort. The parent proxy reports proved to be reliable and are an important supplement to child self‐reports on symptoms related to oral mucositis. But there is a clear need to establish more evidence‐based care for children suffering from oral mucositis.
PMCID: PMC4286779  PMID: 24612395
Haematopoietic stem cell transplantation; Oral mucositis; Pain; Parent proxy; Questionnaire
20.  Factors Associated with Infant Feeding Difficulties in the Very Preterm Infant 
Acta paediatrica (Oslo, Norway : 1992)  2013;102(12):e539-e545.
To investigate early medical and family factors associated with later feeding risk in preterm infants.
For this longitudinal study, we enrolled 136 infants born ≤30 weeks gestation. Medical and social background factors were assessed at term equivalent age. Infants underwent magnetic resonance imaging, neurobehavioral evaluation, and feeding assessment. Parent involvement in the neonatal intensive care unit was tracked, and maternal mental health was assessed at discharge. At age two years, feeding outcome was assessed using the Eating Subscale of the Infant-Toddler Social Emotional Assessment (n=80). Associations between feeding problems at age two and 1) early medical factors, 2) neurobehavioral functioning and feeding at term equivalent age, 3) cerebral structure, and 4) maternal mental health were investigated using regression.
Eighteen (23%) children had feeding problems at age two years. Feeding problems were associated with early hypotonia (p=0.03; β=0.29) and lower socioeconomic status (p=0.046; β=−0.22). No associations were observed between early medical factors, early feeding performance, cerebral structure alterations or maternal well-being and feeding outcome.
Early hypotonia may disrupt the development of oral-motor skills. Hypotonia and poor feeding also may share a common etiology. Associations with lower socioeconomic status highlight the influence of family background factors in feeding problems in the preterm infant.
PMCID: PMC3873367  PMID: 23952198
feeding; hypotonia; NICU; outcome; preterm; socioeconomic status
21.  A randomised controlled trial of an automated oxygen delivery algorithm for preterm neonates receiving supplemental oxygen without mechanical ventilation 
Providing consistent levels of oxygen saturation (SpO2) for infants in neonatal intensive care units is not easy. This study explored how effectively the Auto-Mixer® algorithm automatically adjusted fraction of inspired oxygen (FiO2) levels to maintain SpO2 within an intended range in extremely low birth weight infants receiving supplemental oxygen without mechanical ventilation.
Twenty extremely low birth weight infants were randomly assigned to the Auto-Mixer® group or the manual intervention group and studied for 12 h. The SpO2 target was 85–93%, and the outcomes were the percentage of time SpO2 was within target, SpO2 variability, SpO2 >95%, oxygen received and manual interventions.
The percentage of time within intended SpO2 was 58 ± 4% in the Auto-Mixer® group and 33.7 ± 4.7% in the manual group, SpO2 >95% was 26.5% vs 54.8%, average SpO2 and FiO2 were 89.8% vs 92.2% and 37% vs 44.1%, and manual interventions were 0 vs 80 (p < 0.05). Brief periods of SpO2 < 85% occurred more frequently in the Auto-Mixer® group.
The Auto-Mixer® effectively increased the percentage of time that SpO2 was within the intended target range and decreased the time with high SpO2 in spontaneously breathing extremely low birth weight infants receiving supplemental oxygen.
PMCID: PMC4228757  PMID: 24813808
Auto-mixer; Extremely low birth weight infants; Oxygen administration; Oxygen saturation targets; Pulse oximeter
22.  Limited professional guidance and literature are available to guide the safe use of neuromuscular block in infants 
Acta Paediatrica (Oslo, Norway : 1992)  2014;103(9):e370-e373.
Neuromuscular blocking agents (NMBAs) are used in a range of critical illnesses in neonates and infants, despite a lack of guidelines and professional standards. This study reviewed the current evidence base and ascertained UK practice regarding the continuous use of these agents in this age range.
We reviewed the literature and carried out a telephone questionnaire of all tertiary units in England and specialist children's hospital neonatal units in the UK.
No best practice guidelines or general consensus statements were found, and the only randomised trial to feature an NMBA protocol expressed concerns about its use in such young babies. Of the 56 units contacted, 54 (96.4%) shared information. Only three of the 56 (5.4%) used intermittent boluses of NMBAs, 91.1% used NMBA infusions, 11 (19.6%) routinely used regular neuromuscular blocker pause to assess depth, and only one (1.8%) used peripheral nerve stimulation monitoring. All the units carried out clinical assessments, but only one (1.8%) had a written protocol.
There is a paucity of literature and professional standards to guide the safe use of NMBAs in infants. Of the 54 units who participated in the survey, only one had a protocol for using NMBAs in babies.
PMCID: PMC4228760  PMID: 24813671
Critical care; Neonatology; Neuromuscular blockade; Neuromuscular monitoring; Pharmacology
23.  Feasibility and compliance in a nutritional primary prevention trial in infants at increased risk for type 1 diabetes 
The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) was launched to determine whether weaning to a highly hydrolysed formula in infancy reduces the incidence of type 1 diabetes in children at increased genetic disease susceptibility. We describe here the findings on feasibility and compliance from the pilot study.
The protocol was tested in 240 children. The diet of the participating children was assessed by self-administered dietary forms, a structured questionnaire and a food record. Blood samples were taken and weight and height measured at birth and at 3, 6, 9, 12, 18 and 24 months.
A majority of the subjects (84%) were exposed to the study formula at least for 2 months. Linear growth or weight gain over the first 2 years of life was similar in the two study groups. The levels of IgA and IgG antibodies to cow’s milk and casein were higher in the cow’s milk–based formula group than in the hydrolysed formula group during the intervention period (p < 0.05), reflecting the difference in the intake of cow’s milk protein.
This randomized trial on infant feeding turned out to be feasible, and dietary compliance was acceptable. Valuable experience was gained for the planning and sample size estimation of the study proper.
PMCID: PMC4225541  PMID: 21114527
Compliance; Feasibility; Hydrolysed infant formula; Infants; Primary prevention
24.  Safe oxygen saturation targeting and monitoring in preterm infants: can we avoid hypoxia and hyperoxia? 
Acta Paediatrica (Oslo, Norway : 1992)  2014;103(10):1009-1018.
Oxygen is a neonatal health hazard that should be avoided in clinical practice. In this review, an international team of neonatologists and nurses assessed oxygen saturation (SpO2) targeting in preterm infants and evaluated the potential weaknesses of randomised clinical trials.
SpO2 of 85–89% can increase mortality and 91–95% can cause hyperoxia and ill effects. Neither of these ranges can be recommended, and wider intermediate targets, such as 87–94% or 88–94%, may be safer.
PMCID: PMC4225465  PMID: 24838096
Hyperoxia; Oximetry; Oxygen saturation; Premature infant; Retinopathy of prematurity
25.  Serum fatty acid profile does not reflect seafood intake in adolescents with atopic eczema 
Long-chain polyunsaturated fatty acids (LCPUFAs) are immunomodulatory, but their role in allergy development is controversial. We investigated whether proportions of LCPUFAs in serum phospholipids were related to allergic diagnosis, seafood intake and LCPUFA proportions in cord blood.
Serum was obtained from 148 birth cohort children at 13 years of age. Forty had atopic eczema, 53 had respiratory allergy, and 55 were nonallergic. Proportions of LCPUFAs were determined in serum phospholipids; cord blood from 128 of the individuals was previously analysed. Seafood intake was estimated using questionnaires.
Allergic and nonallergic individuals did not differ significantly regarding individual LCPUFAs. However, arachidonic acid over docosahexaenoic acid (DHA) ratio was higher in allergic, compared with nonallergic, adolescents. In nonallergic individuals, LCPUFA proportions in cord serum and adolescent serum correlated weakly. In individuals with atopic eczema and respiratory allergy, these correlations were weak or absent. A moderate correlation between seafood intake and serum DHA was seen in nonallergic individuals and those with respiratory allergy, but not in those with atopic eczema.
Serum LCPUFA pattern was similar in allergic and nonallergic adolescents. Fatty acid metabolism may be altered in atopic eczema subjects, suggested by poor correlations between fatty acid intake and serum levels.
PMCID: PMC4225477  PMID: 24837739
Allergy; Asthma; Atopic eczema; Fatty acids; Polyunsaturated fatty acids

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