Changes in perinatal management and outcomes of extremely preterm infants born below 26 weeks of gestation in a tertiary referral hospital in Sweden: Comparison between 2004-2007 and 2012-2016.

INTRODUCTION: Perinatal management of extremely preterm births in Sweden has changed toward active care from 22-23 gestational weeks during the last decades. However, considerable regional differences exist. This study evaluates how one of the largest perinatal university centers has adapted to a more active care between 2004-2007 and 2012-2016 and if this has influenced infant survival. MATERIAL AND METHODS: In this historical cohort study, women admitted with at least one live fetus and delivered at 22-25 gestational weeks (stillbirths included) at Karolinska University Hospital Solna during April 1, 2004-March 31, 2007, and January 1, 2012-December 31, 2016, were compared regarding rates of obstetric and neonatal interventions, and infant mortality and morbidity. Maternal, pregnancy and infant data from 2004-2007 were obtained from the Extreme Preterm Infants in Sweden Study while data from 2012-2016 were extracted from medical journals and quality registers. The same definitions of interventions and diagnoses were used for both study periods. RESULTS: A total of 106 women with 118 infants during 2004-2007 and 213 women with 240 infants during 2012-2016 were included. Increases between the study periods were seen regarding cesarean delivery (overall rate 14% [17/118] during 2004-2007 vs. 45% [109/240] during 2012-2016), attendance of a neonatologist at birth (62% [73/118] vs. 85% [205/240]) and surfactant treatment at birth in liveborn infants (60% [45/75] vs. 74% [157/211]). Antepartum stillbirth rate decreased (13% [15/118] vs. 5% [12/240]) and the proportion of live births increased (80% [94/118] vs. 88% [211/240]) while 1-year survival (64% [60/94] vs. 67% [142/211]) and 1-year survival without major neonatal morbidity (21% [20/94] vs. 21% [44/211]) among liveborn infants did not change between the study periods. At 22 gestational weeks, interventions rates were still low during 2012-2016, most obvious regarding antenatal steroid treatment (23%), attendance of a neonatologist (51%), and intubation at birth (24%). CONCLUSIONS: Both obstetric and neonatal interventions at births below 26 gestational weeks increased between 2004-2007 and 2012-2016 in this single center study; however, at 22 gestational weeks they were still at a low level during 2012-2016. Despite more infants being born alive, 1-year survival did not increase between the study periods.

Alpha-1-acid glycoprotein and its potential impact on local anesthetic dose in neonates.

BACKGROUND: Alpha-1-acid glycoprotein is an acute-phase protein with a high affinity for amide local anesthetics. Compared to adults, neonates have lower concentrations of this glycoprotein in plasma, and are therefore at higher risk of developing local anesthetic toxicity. Alpha-1-acid glycoprotein concentrations rise in adults after surgery as a response to stress as well as in inflammatory conditions. Previous studies have shown that concentrations of alpha-1-acid-glycoprotein in neonates vary postpartum, influenced by gestational age and mode of delivery. AIM: This study aims to determine the concentrations of alpha-1-acid glycoprotein pre- and postoperatively in neonates undergoing major surgery. This information is important for determining safe and effective dosage of local anesthetic in this vulnerable group of patients. METHODS: In this prospective observational study, 25 neonates (median 3 days of age) undergoing major surgery were included. Blood sampling was performed preoperatively and at four occasions postoperatively. Alpha-1-acid-glycoprotein plasma concentrations were analyzed using an immunoturbidimetric assay. Mann-Whitney U test, Kruskal-Wallis and Spearman ranking correlation test were used for the statistical analysis. RESULTS: Higher plasma concentrations of alpha-1-acid-glycoprotein were found 48 h postoperatively compared to preoperatively [median (inter-quartile range) 0.815 g L-1 (0.663-0.983 g L-1 ) vs. 0.300 g L-1 (0.205-0.480 g L-1 p < 0.001)], respectively. It was not possible to detect any influence of sex, postnatal age, gestational age, or delivery mode on alpha-1-acid-glycoprotein concentrations in our data. CONCLUSIONS: Alpha-1-acid-glycoprotein concentrations increase in neonates as a response to surgery regardless of gestational age, sex, or mode of delivery.

Hyponatremia at the onset of necrotizing enterocolitis is associated with intestinal surgery and higher mortality.

It has previously been shown that hyponatremia reflects the severity of inflammation in pediatric gastrointestinal diseases. Interpretation of electrolyte disorders is a common, but not well studied challenge in neonatology, especially in the context of early detection of necrotizing enterocolitis and bowel necrosis. The aim of this study was to assess if hyponatremia, or a decrease in plasma sodium level, at the onset of necrotizing enterocolitis (NEC) is associated with intestinal ischemia/necrosis requiring bowel resection and/or NEC-related deaths. This was a retrospective cohort study including patients with verified NEC (Bell's stage ≥ 2) during the period 2009-2014. Data on plasma sodium 1-3 days before and at the onset of NEC were collected. The exposure was hyponatremia, defined as plasma sodium < 135 mmol/L and a decrease in plasma sodium. Primary outcome was severe NEC, defined as need for intestinal resection due to intestinal ischemia/necrosis and/or NEC-related death within 2 weeks of the onset of NEC. Generalized linear models were applied to analyze the primary outcome and presented as odds ratio. A total of 88 patients with verified NEC were included. Fifty-four (60%) of them had severe NEC. Hyponatremia and a decrease in plasma sodium at onset of NEC were associated with increased odds of severe NEC (OR crude 3.91, 95% CI (1.52-10.04) and 1.19, 95% CI (1.07-1.33), respectively). Also, a sub-analysis, excluding infants with pneumoperitoneum during the NEC episode, showed an increased odds ratio for severe NEC in infants with hyponatremia (OR 23.0, 95% CI (2.78-190.08)). CONCLUSIONS: The findings of hyponatremia and/or a sudden decrease in plasma sodium at the onset of NEC are associated with intestinal surgery or death within 2 weeks. WHAT IS KNOWN: • Clinical deterioration, despite optimal medical treatment, is a relative indication for surgery in infants with necrotizing enterocolitis. • Hyponatremia is a common condition in preterm infants from the second week of life. WHAT IS NEW: • Hyponatremia and a decrease in plasma sodium level at the onset of necrotizing enterocolitis are positively associated with need of surgery or death within 2 weeks. • In infants with necrotizing enterocolitis, without pneumoperitoneum, where clinical deterioration despite optimal medical treatment is the only indication for surgery, hyponatremia, or a decrease in plasma sodium level can predict the severity of the disease.

Usefulness of the Parental Electronic Diary During Medical Rounds in a NICU.

Parental involvement in the care of their baby in family rooms in neonatal intensive care units (NICUs) can be improved. This could be done with an electronic medical report completed by the parents, which is then linked to the patient record system. The parents selected for this study completed an electronic diary during their stay in the NICU, while the staff answered a questionnaire about their opinion on the usefulness of the parents' diary. The length of stay, length of time the baby spent in Kangaroo care, breastfeeding, time given to breastfeeding, feeling of tiredness, the capability of identifying the newborn's signals, and parents' opinion on the diary were variables in the study. The NICU staff's opinion about the usefulness of the diary in decision-making was sought using a questionnaire. Eleven mothers and three fathers completed the diary. The median time for staying in the ward was 20 hours/day. The median time in Kangaroo care was 3 hours/day. The majority of mothers were breastfeeding on average 5 times per day. The commonest length of time for breastfeeding was 1 to 2 hours/day. The parents felt somewhat tired during their stay. All parents recognized their child's signals mostly or all the time. Most parents were happy with the diary. The nursing staff's opinions on the usefulness of the diary too were uniformly positive, whereas the doctors' opinions varied from positive to critical in nature. In conclusion, the diaries provided us with new information about parents' perceptions in the NICU. The nurses found the diary useful whereas the doctors were more critical.

High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses.

Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic features of 34 affected individuals from 29 families with skeletal ciliopathies. Molecular diagnostic testing was performed using massively parallel sequencing (MPS) in combination with copy number variant (CNV) analyses and in silico filtering for variants in known skeletal ciliopathy genes. We identified biallelic disease-causing variants in seven genes: DYNC2H1, KIAA0753, WDR19, C2CD3, TTC21B, EVC, and EVC2. Four variants located in non-canonical splice sites of DYNC2H1, EVC, and KIAA0753 led to aberrant splicing that was shown by sequencing of cDNA. Furthermore, CNV analyses showed an intragenic deletion of DYNC2H1 in one individual and a 6.7 Mb de novo deletion on chromosome 1q24q25 in another. In five unsolved cases, MPS was performed in family setting. In one proband we identified a de novo variant in PRKACA and in another we found a homozygous intragenic deletion of IFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establish IFT74 as a new skeletal ciliopathy gene. In conclusion, combined single nucleotide variant, CNV and cDNA analyses lead to a high yield of genetic diagnoses (90%) in a cohort of patients with skeletal ciliopathies.

Preterm white matter injury: ultrasound diagnosis and classification.

White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will improve prediction of outcome in preterm infants with WMI still needs to be evaluated in prospective studies.

Low Splanchnic Oxygenation and Risk for Necrotizing Enterocolitis in Extremely Preterm Newborns.

OBJECTIVE: The aim of the study was to investigate whether splanchnic oxygenation (SrSO2), measured with near-infrared spectroscopy (NIRS), during the first week of life is associated with the risk of developing necrotizing enterocolitis (NEC) in extremely preterm infants. METHODS: This was a prospective observational cohort study including extremely preterm infants (<28 weeks of gestation) born at Karolinska University Hospital from September 2014 to December 2016. Using 1-hour NIRS monitoring during enteral feeding, mainly continuous enteral feeding, in the first week of life we measured both cerebral and splanchnic oxygenation. Primary outcome was risk of developing NEC (Bell stage ≥ II). Secondary outcome was the association between low mean SrSO2 during the first week of life and postnatal age at full enteral nutrition. RESULTS: We enrolled 52 extremely preterm newborns, but only 45 infants had complete NIRS data. One infant developed NEC within 1 day of NIRS monitoring and was excluded from the study. Median gestational age was 25.6 weeks (range 23.0-27.9) and median birth weight 698 g (range 485-1353). Eight infants developed NEC at the median postnatal age of 15 days (range 6-35). Median postnatal age at full enteral nutrition was 10 days (range 6-23). Infants with mean SrSO2 <30% had a higher risk for developing NEC compared with those with SrSO2 >30% (crude risk ratio 5.25; 95% CI [1.19-23.01]). Small for gestational age, gestational age, birth weight, postnatal age did not affect the results. We found no association between SrSO2 and age at full enteral nutrition. CONCLUSIONS: Low mean SrSO2 (<30%) during the first week of life is associated with an increased risk for developing NEC in extremely preterm infants on mainly continuous enteral nutrition.

Neonatal cortical perceptions of maternal breast odours: A fNIRS study.

AIM: The aim was to determine whether preterm and full-term newborn infants could process maternal breast odour at a cortical level. METHODS: Newborn infants were exposed to cloths containing their own mother's breast odour and freshly laundered control cloths for 10 seconds, while functional near-infrared spectroscopy measured cortical activation in their olfactory processing areas. We studied 45 newborn infants born at 28-41 weeks of gestation and divided them into three groups: full-term (37-41 weeks), late preterm (33-36 weeks) and very preterm (28-32 weeks). Cortical activation was defined as a regional increase of oxyhaemoglobin following maternal breast odour stimuli. RESULTS: Full-term infants demonstrated bilateral activation of their olfactory cortices following exposure to maternal breast odour. Late preterm infants and very preterm boys exhibited unilateral cortical activation, unlike very preterm girls. CONCLUSION: Infants born from 32 weeks, and possibly earlier, could process low concentration maternal odours at a cortical level, which suggests they were more aware of their environment. These findings could make a significant contribution to improving the sensory environment of preterm infants and improve bonding.

Cortical Responses to Alien Odors in Newborns: An fNIRS Study.

Very preterm (VPT) infants are exposed to odors released by healthcare products, triggering the trigeminal and olfactory subsystems. Irritation of the nasal mucosa induces pain in adults. We examined whether preterm and full-term (FT) newborns perceived trigeminal odors at different cortical levels, whether these odors elicit pain, and if oral glucose modulates this pain. We performed 44 recording sessions in newborn (15 VPT infants, 12 VPT infants at term-equivalent age, and 17 FT infants) following exposure to trigeminal/olfactory stimuli from the hospital environment. We repeated the exposure after oral glucose administration. We recorded cortical activation in the olfactory, frontal, and somatosensory cortices by functional near-infrared spectroscopy, and analyzed pain behaviors from videotaped recordings. Newborns integrated trigeminal/olfactory stimuli in trigeminal/olfactory and nociceptive processing areas beginning at 31 weeks postmenstrual age, and also exhibited pain behaviors. Pain scores were positively associated with the level of cortical activation. Oral glucose inhibited pain behaviors and cortical activation. There were developmental differences in cortical integration related to brain maturation and duration of the extra-uterine experience. In conclusion, VPT and FT infants showed trigeminal sensitivity after exposure to alien odors that induce pain, potentially affecting the wiring of the neuronal circuits of the newborn brain.

Extremely Preterm-Born Infants Demonstrate Different Facial Recognition Processes at 6-10 Months of Corrected Age.

OBJECTIVES: To compare cortical hemodynamic responses to known and unknown facial stimuli between infants born extremely preterm and term-born infants, and to correlate the responses of the extremely preterm-born infants to regional cortical volumes at term-equivalent age. STUDY DESIGN: We compared 27 infants born extremely preterm (<28 gestational weeks) with 26 term-born infants. Corrected age and chronological age at testing were between 6 and 10 months, respectively. Both groups were exposed to a gray background, their mother's face, and an unknown face. Cerebral regional concentrations of oxygenated and deoxygenated hemoglobin were measured with near-infrared spectroscopy. In the preterm group, we also performed structural brain magnetic resonance imaging and correlated regional cortical volumes to hemodynamic responses. RESULTS: The preterm-born infants demonstrated different cortical face recognition processes than the term-born infants. They had a significantly smaller hemodynamic response in the right frontotemporal areas while watching their mother's face (0.13 µmol/L vs 0.63 µmol/L; P < .001). We also found a negative correlation between the magnitude of the oxygenated hemoglobin increase in the right frontotemporal cortex and regional gray matter volume in the left fusiform gyrus and amygdala (voxels, 25; r = 0.86; P < .005). CONCLUSION: At 6-10 months corrected age, the preterm-born infants demonstrated a different pattern in the maturation of their cortical face recognition process compared with term-born infants.

Plasma concentrations of levobupivacaine associated with two different intermittent wound infusion regimens following surgical ductus ligation in preterm infants.

BACKGROUND: Administration of local anesthetics by a surgically placed wound catheter has recently been shown to reduce the need for postoperative morphine administration in extremely preterm infants undergoing ductus ligation. The primary aim of this randomized safety study was to define the plasma levels of levobupivacaine (LB) following two different intermittent infusion regimens. METHODS: Eighteen preterm infants 23-27 gestational weeks, median birthweight 721 g scheduled for ductus ligation were included in the study. All patients were anesthetized according to a standardized protocol based on high-dose fentanyl (25-50 µg·kg(-1) ). Before skin closure, a subcutaneous catheter was inserted into the wound. The patients were randomized to receive one of the two intermittent infusion regimens: Group BII: Initial bolus plus early start of the intermittent infusion or Group DII: No bolus plus delayed start (8 h) of the intermittent infusion. Blood samples for determination of LB plasma concentrations were obtained on six occasions during the 24-h postoperative observation period, as well as hourly postoperative pain assessments using the Echelle Douleur Inconfort Noveau (EDIN) pain scale. RESULTS: Plasma concentrations of LB ranged from 0.094 to 1.682 µg·ml(-1) and 0 to 0.549 µg·ml(-1) in group BII and DII, respectively. Both regimens were associated with low postoperative EDIN pain scores (24 h median of 0 and 1 in group BII and DII, respectively). No signs of systemic local anesthetic toxicity were noted. CONCLUSIONS: The two studied intermittent infusion regimens were associated with plasma levels below potentially toxic levels and were both associated with adequate postoperative pain scores.

Plasma levels of levobupivacaine during continuous infusion via a wound catheter after major surgery in newborn infants: An observational study.

BACKGROUND: Epidurals may be challenging in neonatal patients due to technical difficulties relating to insertion and the risk of local anaesthesia toxicity. The use of wound catheters with an infusion of local anaesthetic has been shown to be well tolerated in adults and older children. There are few data concerning wound catheter techniques in neonatal patients. OBJECTIVES: The primary aim of this study was to analyse plasma levels of levobupivacaine associated with continuous wound infiltration via a catheter following neonatal surgical procedures. Secondary parameters, including the quality of postoperative analgesia and wound healing, were also noted. DESIGN: A prospective, observational study. SETTING: Paediatric ICU at the Karolinska University Hospital, Stockholm, Sweden, from March 2008 to December 2010. PATIENTS: Twenty newborn infants (median weight 3.48 kg) scheduled for major abdominal or thoracic surgery were included. Exclusion criteria were known or suspected hepatic dysfunction. Before skin closure, a subcutaneous catheter was inserted into the wound followed by a 0.5 mg kg(-1) bolus of levobupivacaine (0.125%, 0.4 ml kg(-1)) through the catheter. A continuous infusion was started 20 to 30 min later at a rate of 0.2 mg kg(-1)h(-1) (0.16 ml kg(-1) h(-1)). MAIN OUTCOME MEASURES: Plasma concentrations of levobupivacaine (total and unbound) at 12, 24, 48 and 72 h postoperatively. Morphine consumption, pain scores and wound healing were also analysed. RESULTS: Median concentrations of unbound and total levobupivacaine at 72 h were 0.018 and 1.305 µg ml(-1), respectively. In 18 out of 20 infants [90%; 95% confidence interval (CI) 68.3 to 98.8], the unbound plasma concentration of levobupivacaine remained relatively stable and below 0.05 µg ml(-1) throughout the 72 h observation period. Pain scores and morphine consumption levels were low. All wounds except one healed within 10 days. CONCLUSION: The studied infusion regimen was associated with plasma levels of levobupivacaine well below those associated with toxicity. Adequate wound healing, low pain scores and a reduced need for opioids were also noted.

SARS-CoV-2 Inactivation in Aerosol by Means of Radiated Microwaves.

Coronaviruses are a family of viruses that cause disease in mammals and birds. In humans, coronaviruses cause infections on the respiratory tract that can be fatal. These viruses can cause both mild illnesses such as the common cold and lethal illnesses such as SARS, MERS, and COVID-19. Air transmission represents the principal mode by which people become infected by SARS-CoV-2. To reduce the risks of air transmission of this powerful pathogen, we devised a method of inactivation based on the propagation of electromagnetic waves in the area to be sanitized. We optimized the conditions in a controlled laboratory environment mimicking a natural airborne virus transmission and consistently achieved a 90% (tenfold) reduction of infectivity after a short treatment using a Radio Frequency (RF) wave emission with a power level that is safe for people according to most regulatory agencies, including those in Europe, USA, and Japan. To the best of our knowledge, this is the first time that SARS-CoV-2 has been shown to be inactivated through RF wave emission under conditions compatible with the presence of human beings and animals. Additional in-depth studies are warranted to extend the results to other viruses and to explore the potential implementation of this technology in different environmental conditions.

Reply to Taylor et al. Comment on "Manna et al. SARS-CoV-2 Inactivation in Aerosol by Means of Radiated Microwaves. Viruses 2023, 15, 1443".

SARS-CoV-2 is inactivated in aerosol (its primary mode of transmission) by means of radiated microwaves at frequencies that have been experimentally determined. Such frequencies are best predicted by the mathematical model suggested by Taylor, Margueritat and Saviot. The alignment between such mathematical prediction and the outcomes of our experiments serves to reinforce the efficacy of the radiated microwave technology and its promise in mitigating the transmission of SARS-CoV-2 in its naturally airborne state.

Efficacy of topical lidocaine-prilocaine (EMLA®) for management of infant pain during pneumococcal vaccination: A randomized controlled trial.

Few studies have evaluated whether topical anesthetic cream reduces pain during pneumococcal vaccination. This is crucial, since effective pain management should be evidence-based. Previous studies have shown that topical lidocaine-prilocaine (EMLA®) reduces vaccination-related pain, measured using pain-rating instruments and observation of crying time. This intervention study aimed to compare the efficacy of topical lidocaine-prilocaine cream with that of the standard of care on the expression of pain during the first pneumococcal vaccination administered at age 3 months under the Swedish national vaccination program. A randomized controlled trial included 72 infants receiving their first pneumococcal vaccination (Prevenar 13®). The study showed that topical lidocaine-prilocaine before pneumococcal vaccination significantly reduced infants' expression of pain according to the Face, Legs, Activity, Cry, Consolability (FLACC) score (P = .006) and increased latency to cry (P = .001). There were no statistically significant differences in the total crying time (P = .146) between the groups. Topical lidocaine-prilocaine cream reduced pain expression and increased latency to cry in infants receiving their first pneumococcal vaccine. Systematic efforts are needed to successfully implement the use of topical anesthetic cream and other effective non-pharmacological pain-relieving strategies during infant vaccination procedures.

Early N-Terminal Pro B-Type Natriuretic Peptide (NTproBNP) Plasma Values and Associations with Patent Ductus Arteriosus Closure and Treatment-An Echocardiography Study of Extremely Preterm Infants.

The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012-2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760-6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120-19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740-28,100 ng/L); or surgery, 32,300 ng/L (29,100-35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001-18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54-0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.

Comparison of Respiratory Support After Delivery in Infants Born Before 28 Weeks' Gestational Age: The CORSAD Randomized Clinical Trial.

Importance: Establishing stable breathing is a key event for preterm infants after birth. Delivery of pressure-stable continuous positive airway pressure and avoiding face mask use could be of importance in the delivery room. Objective: To determine whether using a new respiratory support system with low imposed work of breathing and short binasal prongs decreases delivery room intubations or death compared with a standard T-piece system with a face mask. Design, Setting, and Participants: In this unblinded randomized clinical trial, mothers threatening preterm delivery before week 28 of gestation were screened. A total of 365 mothers were enrolled, and 250 infants were randomized before birth and 246 liveborn infants were treated. The trial was conducted in 7 neonatal intensive care units in 5 European countries from March 2016 to May 2020. The follow-up period was 72 hours after intervention. Interventions: Infants were randomized to either the new respiratory support system with short binasal prongs (n = 124 infants) or the standard T-piece system with face mask (n = 122 infants). The intervention was providing continuous positive airway pressure for 10 to 30 minutes and positive pressure ventilation, if needed, with the randomized system. Main Outcomes and Measures: The primary outcome was delivery room intubation or death within 30 minutes of birth. Secondary outcomes included respiratory and safety variables. Results: Of 246 liveborn infants treated, the mean (SD) gestational age was 25.9 (1.3) weeks, and 127 (51.6%) were female. A total of 41 infants (33.1%) receiving the new respiratory support system were intubated or died in the delivery room compared with 55 infants (45.1%) receiving standard care. The adjusted odds ratio was statistically significant after adjusting for stratification variables (adjusted odds ratio, 0.53; 95% CI, 0.30-0.94; P = .03). No significant differences were seen in secondary outcomes or safety variables. Conclusions and Relevance: In this study, using the new respiratory support system reduced delivery room intubation in extremely preterm infants. Stabilizing preterm infants with a system that has low imposed work of breathing and binasal prongs as interface is safe and feasible. Trial Registration: ClinicalTrials.gov Identifier: NCT02563717.

Effect of oral naloxone hydrochloride on gastrointestinal transit in premature infants treated with morphine.

BACKGROUND: Opioids are common drugs for pain treatment in preterm newborn infants, in spite of several adverse effects. Constipation is a frequent problem when opioids are used in both adults and neonates. Although several studies indicate that the oral administration of naloxone hydrochloride (NH) improves intestinal motility during opioid therapy, there is still a lack of evidence in newborns. AIM: The aim of this study was to assess the efficacy of NH against reduced intestinal motility during opioid treatment. METHODS: A retrospective cohort study was performed. We analysed the medical records of fifteen infants (Group 1) treated with continuous morphine (MO) infusion and fourteen infants (Group 2) treated with both oral NH (3 microg/kg 4 times daily) and MO. RESULTS: There was no statistically significant difference in the total MO dose. Infants treated both with NH and MO had a tendency to improve their mean stool frequency/day. A statistically significant improvement was observed in the mean total food intake (mL/kg/day) of the infants treated with NH (p = 0.014). No difference in the mean food retention between the two groups was observed. CONCLUSION: Orally administrated NH seems to improve intestinal motility resulting in increased food intake/day and improved stool frequency/day in premature newborn infants treated with MO. Further studies are needed to corroborate these findings.

The effect of gestational age on clinical and radiological presentation of necrotizing enterocolitis.

BACKGROUND/PURPOSE: To test the hypothesis that clinical and radiological features of necrotizing enterocolitis vary with gestational age in all neonates with NEC and in subgroup of surgically treated patients. METHODS: This was a retrospective study case series. NEC cases treated in Stockholm County from 2009 to 2014 were identified in the National Quality Register. Patients were included in the study if they had a verified NEC diagnosis and they were divided into 2 groups according to the gestational age. RESULTS: A total of 89 patients were included. Of these 60 (67.4%) neonates had a gestational age <28 and 29 (32.6%) infants ≥28weeks. Surgical NEC patients were 57 (64%). Pneumatosis intestinalis at the abdominal radiographs was noted significantly more often in neonates born at ≥28weeks of gestation (86.2%) compared to extremely preterm newborns (60.0%). Neonates born at ≥28weeks of gestation presented more often bloody stools (58.6%) compared to extremely preterm newborns (20.0%). In surgical NEC patients gasless abdomen was detected in 35.6% of the neonates born <28weeks compared to 6.7% of the more mature neonates. CONCLUSIONS: Extremely preterm neonates with NEC show less specific clinical and radiological signs of NEC compared to more mature neonates. This suggests that Bell's classification is not adequate for the diagnosis and staging of NEC in extremely preterm neonates. LEVEL OF EVIDENCE: III.

Complex Fluid Collection on Abdominal Ultrasound Indicates Need for Surgery in Neonates with Necrotizing Enterocolitis.

Aim The aim of this study was to determine whether a correlation exists between the sonographic findings and the clinical outcomes, defined as surgery or death, in neonates with radiographically and/or histopathologically confirmed necrotizing enterocolitis (NEC). Material and Methods In this retrospective study, the case notes of 58 patients admitted to Karolinska University Hospital, Stockholm, Sweden, with radiographically confirmed NEC from September 2010 to August 2013, were reviewed. We included all newborns who underwent both plain abdominal radiographs and an abdominal ultrasound on the same day. The images were reviewed retrospectively. Patients' characteristics, clinical data, and histopathological data were recorded from the case notes. We excluded newborns who developed free gas before surgery. Abdominal ultrasound images were reviewed for free intraperitoneal gas, peritoneal fluid, pneumatosis intestinalis, portal gas, bowel vascularity, bowel wall thickness, and peristalsis. We correlated the sonographic features with the clinical outcomes; defined as the need for surgery or death. Results Overall, 25 neonates were included. Out of these, 11 patients underwent surgery and 5 patients died. The sonographic finding of complex fluid collection was statistically significant, predicting severe NEC that needed surgery. No other sonographic features were related to the need for surgery or death. Conclusion Complex fluid collection shown with abdominal ultrasound appears to be strongly correlated to the need for surgery in newborn infants with severe NEC.