A longitudinal study of fatty acid profiles, macronutrient levels, and plasmin activity in human milk.

Introduction: Human milk provides nutrients essential for infant growth and health, levels of which are dynamic during lactation. Methods: In this study, changes in macronutrients, fatty acids, and plasmin activities over the first six months of lactation in term milk were studied. Results: There was a significant influence of lactation stage on levels of protein and plasmin activities, but not on levels of fat and carbohydrate in term milk. Concerning fatty acids in term milk, levels of caproic acid and α-linolenic acid increased significantly (p < 0.05), whereas those of arachidonic acid and docosahexaenoic acid decreased, in the six months after birth. Significant impacts of maternal pre-pregnancy BMI and infant gender on fatty acid profiles were also found. Multivariate statistical analysis showed that protein level, plasmin activity, and several fatty acids (α-linolenic acid, lignoceric acid, and docasadienoic acid) contributed strongly to discrimination of milk from different lactational stages. Discussion: The study demonstrates that not all but some fatty acids were influenced by lactation, whereas protein and protease levels showed clear decreasing trends during lactation, which may help in understanding the nutritional requirements of infants.

Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: a multicentre experience.

OBJECTIVE: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres. METHODS: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server. RESULTS: Of 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9-51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11-32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED. CONCLUSIONS: Our results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat. OBERSERVATION STUDY NUMBER: NCT02160171.

Corrective ventilation strategies in delivery room resuscitation of preterm infants.

AIM: Corrective ventilation strategies (CVS) during neonatal resuscitation and stabilisation (R&S) are taught through the MRSOPA mnemonic: Mask adjustment, Repositioning airway, Suctioning, Opening the mouth, Increasing inspiratory Pressure, and Alternative airway. The aim was to examine the use of CVS and to investigate the relationship between MRSOPA strategies and intubation of very preterm infants <32 weeks' gestation in the delivery room. METHODS: Retrospective review of video recordings of R&S of preterm infants born in Cork University Maternity Hospital, Ireland. RESULTS: In 46 resuscitation recordings, mask adjustment was observed in almost all (95.6%), followed by suctioning, (23.9%), opening the mouth (100%), increasing inspiratory pressure (81.0%) and intubation (32.6%). The most frequently used mask holds were: one-handed (95.6%), two-handed (63.0%), stem hold (23.8%), and modified spider hold (6.5%). There were no significant associations between individual mask holds and intubation. The more CVS employed the greater the need for intubation. CONCLUSION: The greater the number of MRSOPA strategies used in the delivery room, the more likely intubation occurred. Further studies may identify the effect of these CVS on short- and long-term outcomes, in order to enhance R&S training and clinical practice.

A Randomized Controlled Trial of End-Tidal Carbon Dioxide Detection of Preterm Infants in the Delivery Room.

OBJECTIVE: To compare the ability of qualitative versus quantitative methods of end-tidal carbon dioxide (EtCO2) detection to maintain normocarbia during face mask ventilation (FMV) of preterm infants (<32 weeks) in the delivery room. STUDY DESIGN: Preterm infants <32 weeks were randomly assigned to the use of a disposable PediCap EtCO2 detector (Covidien, Dublin, Ireland) (qualitative) or a Microstream side stream capnography device (Covidien) (quantitative) for FMV in the delivery room, via a NeoPuff T-piece resuscitator (Fisher and Paykel, Auckland, New Zealand). The primary outcome was the presence of normocarbia, based on partial pressure of CO2 (PaCO2) readings obtained in the neonatal intensive care unit within an hour of birth. Normocarbia was defined as a PaCO2 measure between 37.5 and 60 mm Hg (5-8 kPa). RESULTS: Of the 59 infants included, 59% (35/59) were within the PaCO2 target range within an hour of birth. There was no difference in the primary outcome; 64% (21/33) of infants in the quantitative group were within the PaCO2 range compared with 54% (14/26) in the qualitative group (P = .594); and 93% of participants <28 weeks' gestation were within the PaCO2 normocarbic range (90% [9/10] in quantitative group and 100% [5/5] in the qualitative group [P = 1]). There was no difference in the intubation rate, days of ventilation, or bronchopulmonary dysplasia rates between the 2 groups. CONCLUSIONS: Quantitative or qualitative EtCO2 detection methods are both feasible for FMV in the delivery room. Although there was no difference in the incidence of normocarbia, the use of either form of EtCO2 monitoring should be considered during newborn stabilization, especially in infants less than 28 weeks' gestation. TRIAL REGISTRATION: ISRCTN: ISRCTN10934870.

Short-Term Effects of Phenobarbitone on Electrographic Seizures in Neonates.

BACKGROUND: Phenobarbitone is the most common first-line anti-seizure drug and is effective in approximately 50% of all neonatal seizures. OBJECTIVE: To describe the response of electrographic seizures to the administration of intravenous phenobarbitone in neonates using seizure burden analysis techniques. METHODS: Multi-channel conventional EEG, reviewed by experts, was used to determine the electrographic seizure burden in hourly epochs. The maximum seizure burden evaluated 1 h before each phenobarbitone dose (T-1) was compared to seizure burden in periods of increasing duration after each phenobarbitone dose had been administered (T+1, T+2 to seizure offset). Differences were analysed using linear mixed models and summarized as means and 95% CI. RESULTS: Nineteen neonates had electrographic seizures and met the inclusion criteria for the study. Thirty-one doses were studied. The maximum seizure burden was significantly reduced 1 h after the administration of phenobarbitone (T+1) [-14.0 min/h (95% CI: -19.6, -8.5); p < 0.001]. The percentage reduction was 74% (IQR: 36-100). This reduction was temporary and not significant within 4 h of administrating phenobarbitone. Subgroup analysis showed that only phenobarbitone doses at 20 mg/kg resulted in a significant reduction in the maximum seizure burden from T-1 to T+1 (p = 0.002). CONCLUSIONS: Phenobarbitone significantly reduced seizures within 1 h of administration as assessed with continuous multi-channel EEG monitoring in neonates. The reduction was not permanent and seizures were likely to return within 4 h of treatment.

Delivery room end tidal CO2 monitoring in preterm infants <32†weeks.

OBJECTIVES: To determine the feasibility of end tidal (EtCO2) monitoring of preterm infants in the delivery room, to determine EtCO2 levels during delivery room stabilisation, and to examine the incidence of normocapnia (5-8 kPa) on admission to the neonatal intensive care unit in the EtCO2 monitored group compared with a historical cohort without EtCO2 monitoring. PATIENTS AND METHODS: Preterm infants (<32 weeks) were eligible for inclusion in this observational study. The evolution of EtCO2 values immediately after delivery was assessed and linear least-squares methods were used to fit a line to EtCO2 recordings. The partial pressure of CO2 in blood (PCO2) from the infants who received EtCO2 monitoring was compared with a historical cohort without EtCO2 monitoring. RESULTS: EtCO2 monitoring was feasible in the delivery room. EtCO2 values were successfully obtained in 39 (88.7%) of the 44 infants included in the study. EtCO2 gradually increased over the first 4 min. Intubated infants had higher EtCO2 values compared with infants who were not intubated, with median (IQR) values of 4.7 (3.3-8.4) kPa versus 3.2 (2.6-4.2) kPa (p=0.05). No difference was found between the proportions of PCO2 values within the range of normocapnia among infants who received EtCO2 monitoring compared with those who did not (56.8% vs 47.9%, p=0.396). CONCLUSIONS: Delivery room EtCO2 monitoring is feasible and safe. EtCO2 values obtained after birth reflect the establishment of functional residual capacity and effective ventilation. The potential short-term and long-term consequences of EtCO2 monitoring should be established in randomised controlled trials.

Standardised formal resuscitation training programmes for reducing mortality and morbidity in newborn infants.

BACKGROUND: Approximately 10% of all newborns require resuscitation at birth. Training healthcare providers in standardised formal neonatal resuscitation training (SFNRT) programmes may improve neonatal outcomes. Substantial healthcare resources are expended on SFNRT. OBJECTIVES: To determine whether SFNRT programmes reduce neonatal mortality and morbidity, improve acquisition and retention of knowledge and skills, or change teamwork and resuscitation behaviour. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PREMEDLINE, EMBASE, CINAHL, Web of Science and the Oxford Database of Perinatal Trials, ongoing trials and conference proceedings in April 2014 and updated in March 2015. SELECTION CRITERIA: Randomised or quasi-randomised trials including cluster-randomised trials, comparing a SFNRT with no SFNRT, additions to SFNRT or types of SFNRT, and reporting at least one of our specified outcomes. DATA COLLECTION AND ANALYSIS: Two authors extracted data independently and performed statistical analyses including typical risk ratio (RR), risk difference (RD), mean difference (MD), and number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH) (all with 95% confidence intervals (CI)). We analysed cluster-randomised trials using the generic inverse variance and the approximate analysis methods. MAIN RESULTS: We identified two community-based and three manikin-based trials that assessed the effect of SFNRT compared with no SFNRT. Very low quality evidence from one study suggested improvement in acquisition of knowledge (RR 5.96, 95% CI 3.60 to 9.87) and skills (RR 170, 95% CI 10.8 to 2711) and retention of knowledge (RR 3.60, 95% CI 2.43 to 5.35) and the other study suggested improvement in resuscitation and behavioural scores.We identified three community-based cluster-randomised trials in developing countries comparing SFNRT with basic resuscitation training (Early Newborn Care). In this setting, there was moderate quality evidence that SFNRT decreased early neonatal mortality (typical RR 0.88, 95% CI 0.78 to 1.00; 3 studies, 66,162 neonates) and when analysed by the approximate analysis method (typical RR 0.85, 95% CI 0.75 to 0.96; RD -0.0044, 95% CI -0.0082 to -0.0006; NNTB 227, 95% CI 122 to 1667). Low quality evidence from one trial showed that SFNRT may decrease 28-day mortality (typical RR 0.55, 95% CI 0.33 to 0.91) but the effect on late neonatal mortality was more uncertain (typical RR 0.47, 95% CI 0.20 to 1.11). None of our a priori defined neonatal morbidities were reported. We did not identify any randomised studies in the developed world.We identified two trials that compared SFNRT with team training to SFNRT. Teamwork training of physician trainees with simulation may increase any teamwork behaviour (assessed by frequency) (MD 2.41, 95% CI 1.72 to 3.11) and decrease resuscitation duration (MD -149.54, 95% CI -214.73 to -84.34) but may lead to little or no difference in Neonatal Resuscitation Program (NRP) scores (MD 1.40, 95% CI -2.02 to 4.82; 98 participants, low quality evidence).We identified two trials that compared SFNRT with booster courses to SFNRT. It is uncertain whether booster courses improve retention of resuscitation knowledge (84 participants, very low quality evidence) but may improve procedural and behavioural skills (40 participants, very low quality evidence).We identified two trials on decision support tools, one on a cognitive aid that did not change resuscitation scores and the other on an electronic decision support tool that improved the frequency of correct decision making on positive pressure ventilation, cardiac compressions and frequency of fraction of inspired oxygen (FiO2) adjustments (97 participants, very low quality evidence). AUTHORS' CONCLUSIONS: SFNRT compared to basic newborn care or basic newborn resuscitation, in developing countries, results in a reduction of early neonatal and 28-day mortality. Randomised trials of SFNRT should report on neonatal morbidity including hypoxic ischaemic encephalopathy and neurodevelopmental outcomes. Innovative educational methods that enhance knowledge and skills and teamwork behaviour should be evaluated.

Effects of Fractional Inspired Oxygen on Cerebral Oxygenation in Preterm Infants following Delivery.

OBJECTIVES: To explore regional cerebral oxygen saturations (rcSO2) in preterm neonates initially stabilized with 0.3 fractionated inspired oxygen (FiO2) concentrations. We hypothesized that those infants who received >0.3 FiO2 during stabilization following delivery would have relatively higher rcSO2 postdelivery compared with those stabilized with a lower FiO2. STUDY DESIGN: A single center prospective observational study of 47 infants born before 32 weeks. Using near infrared spectroscopy, rcSO2 values were recorded immediately after birth. All preterm infants were initially given 0.3 FiO2 and were divided into 2 groups according to subsequent FiO2 requirements of either ≤0.3 or >0.3 FiO2. Using a mixed-effects model, we compared the difference between the groups over time. Also, the area measures below 55% (hypoxia) and above 85% (hyperoxia) were compared between the groups. RESULTS: The mean (SD) gestation was 29.4 (1.6) weeks and the mean (SD) weight was 1.3 (0.4) kg. Less than one-half of the infants (20/45; 43%) required ≤0.3 FiO2. In the delivery suite, the median (IQR) rcSO2 in the low and high FiO2 groups were 81% (66%-86%) and 72% (62%-86%), respectively. Patients in the high FiO2 group had a larger rcSO2 area below 55% (P = .01). There was a significant difference in rcSO2 between the groups (P < .05), with the low group having higher rcSO2 values initially, but this difference changed over time. In the neonatal intensive care unit (NICU), rcSO2 values were lower by 7.1% (CI 12.13 to 2.06%) P = .008 in the high FiO2 group. CONCLUSIONS: Infants given >0.3 FiO2 had more cerebral hypoxia than infants requiring ≤0.3 FiO2 but no difference in the degree of cerebral hyperoxia, both in the delivery suite and the NICU. This suggests that a more rapid increase in oxygen titration maybe be required initially for preterm infants.

Randomised controlled trial of a mobile phone infant resuscitation guide.

AIM: The aim of this study was to develop a mobile phone resuscitation guide (MPRG) and to evaluate its use during simulated resuscitation of a mannequin. METHODS: An MPRG was developed using EpiSurveyor. A randomised controlled trial was performed in school-going children aged 15-16 years. All subjects were taught infant CPR skills using the American Heart Association Infant CPR Anytime. Two weeks later, the students were randomised to use of MPRG or not, and their CPR skills were re-assessed. The assessment was conducted using previously validated checklists. RESULTS: Twenty-one students participated in this trial. The MPRG group performed notably better in the areas of calling emergency services (80% vs. 36.4%, P = 0.044), completing sufficient CPR cycles (90% vs. 45.5%, P = 0.047) and following the correct CPR sequence (60% vs. 9.1%, P = 0.013). No difference in resuscitation skills of participants was observed. CONCLUSIONS: We have shown that participants were more likely to call emergency services if they were using the MPRG. Further trials are needed to investigate the utility of mobile phone guides and whether or not they can reduce the time taken to contact emergency services as well as if they can sustain correct CPR sequence in an in-vivo setting.

Identification of aminoglycoside and ß-lactam resistance genes from within an infant gut functional metagenomic library.

The infant gut microbiota develops rapidly during the first 2 years of life, acquiring microorganisms from diverse sources. During this time, significant opportunities exist for the infant to acquire antibiotic resistant bacteria, which can become established and constitute the infant gut resistome. With increased antibiotic resistance limiting our ability to treat bacterial infections, investigations into resistance reservoirs are highly pertinent. This study aimed to explore the nascent resistome in antibiotically-naïve infant gut microbiomes, using a combination of metagenomic approaches. Faecal samples from 22 six-month-old infants without previous antibiotic exposure were used to construct a pooled metagenomic library, which was functionally screened for ampicillin and gentamicin resistance. Our library of ∼220Mb contained 0.45 ampicillin resistant hits/Mb and 0.059 gentamicin resistant hits/Mb. PCR-based analysis of fosmid clones and uncloned metagenomic DNA, revealed a diverse and abundant aminoglycoside and ß-lactam resistance reservoir within the infant gut, with resistance determinants exhibiting homology to those found in common gut inhabitants, including Escherichia coli, Enterococcus sp., and Clostridium difficile, as well as to genes from cryptic environmental bacteria. Notably, the genes identified differed from those revealed when a sequence-driven PCR-based screen of metagenomic DNA was employed. Carriage of these antibiotic resistance determinants conferred substantial, but varied (2-512x), increases in antibiotic resistance to their bacterial host. These data provide insights into the infant gut resistome, revealing the presence of a varied aminoglycoside and ß-lactam resistance reservoir even in the absence of selective pressure, confirming the infant resistome establishes early in life, perhaps even at birth.