Electrical Cardiometry during transition and short-term outcome in very preterm infants: a prospective observational study.

The purpose of this study is to evaluate the association of Electrical Cardiometry (EC)-derived cardiac output indexed to weight (CO) and its changes during the first 48 h in relation to adverse short-term outcome in very preterm infants. In this prospective observational study of preterm infants < 32 weeks gestational age (GA), the combined adverse outcome was defined as mortality or abnormal cranial ultrasound (any grade intracranial hemorrhage (ICH) or periventricular leukomalacia) within the first 2 weeks postnatally. Logistic regression models were used to investigate the association between median CO and outcome and mixed-effects models for the time trajectory of CO. In the absence of device-specific thresholds for low or high CO, no thresholds were used in our analysis. Fifty-three infants (median (IQR) GA 29.0 (25.4-30.6) weeks, birthweight 1020 (745-1505) g) were included in the analysis. Median CO was 241 (197-275) mL/kg/min for the adverse outcome and 198 (175-227) mL/kg/min for normal outcome (odds ratio (OR) (95% confidence interval (95% CI)), 1.01 (1.00 to 1.03); p = 0.028). After adjustment for GA, the difference was not significant (adjusted OR (95% CI), 1.01 (0.99 to 1.02); p = 0.373). CO trajectory did not differ by outcome (p = 0.352). A post hoc analysis revealed an association between CO time trajectory and ICH ≥ grade 2.          Conclusions: EC-derived CO estimates within 48 h postnatally were not independently associated with brain injury (any grade) or mortality in the first 14 days of life. CO time trajectory was found to be associated with ICH ≥ grade 2. What is Known: • Bioreactance-derived cardiac output indexed to bodyweight (CO) in the transitional period has been associated with adverse short-term outcome in preterm infants. What is New: • Electrical Cardiometry (EC)-derived CO measurements in very preterm infants during the transitional period are not independently associated with adverse outcome (death or ultrasound detected brain damage) within 2 weeks postnatally. • In the first 48 h EC-derived CO increases over time and is higher in extremely preterm infants compared to very preterm and differs from previously reported bioreactance-derived CO values.

Influence of innate immune activation on endocrine and metabolic pathways in infancy.

Prematurity is the leading cause of neonatal morbidity and mortality worldwide. Premature infants often require extended hospital stays, with increased risk of developing infection compared with term infants. A picture is emerging of wide-ranging deleterious consequences resulting from innate immune system activation in the newborn infant. Those who survive infection have been exposed to a stimulus that can impose long-lasting alterations into later life. In this review, we discuss sepsis-driven alterations in integrated neuroendocrine and metabolic pathways and highlight current knowledge gaps in respect of neonatal sepsis. We review established biomarkers for sepsis and extend the discussion to examine emerging findings from human and animal models of neonatal sepsis that propose novel biomarkers for early identification of sepsis. Future research in this area is required to establish a greater understanding of the distinct neonatal signature of early and late-stage infection, to improve diagnosis, curtail inappropriate antibiotic use, and promote precision medicine through a biomarker-guided empirical and adjunctive treatment approach for neonatal sepsis. There is an unmet clinical need to decrease sepsis-induced morbidity in neonates, to limit and prevent adverse consequences in later life and decrease mortality.

Antimicrobial stewardship in the neonatal unit reduces antibiotic exposure.

AIM: Antimicrobial stewardship plays an important role in ensuring that the appropriate drug, dose, route and duration are employed to provide adequate treatment while minimising the risks of unnecessary antibiotic use. Surveillance of antibiotic use with prescriber feedback is recommended as a high-impact stewardship intervention. The aim of this study was to reduce unnecessary antimicrobial use in a neonatal unit. METHODS: A prospective audit was performed to assess compliance with antimicrobial guidelines. Following this, educational interventions were applied, electronic prescribing was introduced to the neonatal unit, and re-audit was performed. The primary outcome was a reduction in days of therapy (DOT). RESULTS: There were 312 neonatal admissions. There was a significant overall reduction in the primary outcome of DOT/1000 patient days from 572 to 417 DOT. This represents a 27% reduction in total antibiotic use. Prolonged antibiotic treatment courses >36 hours in negative sepsis evaluations were reduced from 82 DOT to 7.5 DOT. Similarly, treatment courses greater than five days for culture-negative sepsis were reduced from 46.5 DOT to 7 DOT. CONCLUSION: Monitoring antibiotic prescribing data can provide useful insights into the trends of antibiotic use and also inform clinicians of potential areas where antibiotic use may be safely reduced.

Emergency uncross-matched blood transfusions in a tertiary neonatal unit.

AIM: To determine the neonatal incidence, indications and outcomes following transfusions with emergency uncross-matched O-negative blood. METHODS: A five-year retrospective review in a single tertiary neonatal unit was conducted. The blood transfusion laboratory's database was analysed for all infants who had received an emergency released blood transfusion (ERBT) between January 2010 and December 2014. RESULTS: We calculated a total ERBT rate of 0.91 per 1000 live births (39/42 657) and a rate of 0.43 per 1000 in infants >34 weeks' gestation (18/41 637). A rate of 0.14 per 1000 births (6/42 657) received an ERBT as part of newborn stabilisation despite almost half of our infant cohort having intrapartum haemorrhages (n = 18, 46%). One-third (13/39) of all infants who were transfused died. Outcome varied depending on underlying aetiology, gestation and birthweight. The highest mortality was in preterm infants weighing <1000 g, of whom 70% died. CONCLUSION: This study establishes an ERBT rate of <1 per 1000 births, and 0.14 per 1000 infants received an ERBT as part of newborn delivery room stabilisation. ERBTs are associated with a high mortality rate. This study highlights the need for further research and guidelines that clarify the role of ERBTs in newborn stabilisations.

Auscultate, palpate and tap: time to re-evaluate.

AIM: To determine the accuracy of current methods of heart rate (HR) assessment. METHODS: All participants palpated a simulated pulsating umbilicus (UMB), listened to a tapping rate (TAP) and auscultated a simulated HR (AUSC). A simulated HR of 54, 88 and 128 beats per minute (bpm) was randomised for all methods. RESULTS: Twenty-nine healthcare staff participated in this study. Correct assessment of HR of 54 bpm as being within the 0-59 range occurred in 17.2% UMB, 17.2% TAP and 31% AUSC and was obtained in <10 seconds by 48.3%, 65.5% and 62.1%, respectively. A rate of 88 bpm was correctly assessed as within the 60-100 range in 82.8% UMB, 79.3% TAP and 79.3% AUSC and was obtained in <10 seconds by 55.2%, 58.6% and 55.2%, respectively. A rate of 128 bpm was identified as >100 bpm by 96.6% UMB, 93.1% TAP, and 93.1% AUSC and was obtained in <10 seconds by 51.7%, 55.2% and 62.1%, respectively. CONCLUSION: Current methods in assessing rates below 60 bpm are inaccurate and may overestimate HR. We recommend that these methods alone should not be relied upon in neonatal resuscitation and objective assessment of heart rate should be readily available at all newborn resuscitations.

Timing of Therapeutic Hypothermia for Inborn and Outborn Infants with Neonatal Encephalopathy.

Therapeutic hypothermia is now the standard of care for infants with moderate to severe hypoxic ischaemic encephalopathy. Sixty-three infants received therapeutic hypothermia at Cork University Maternity Hospital (CUMH) from 2010-2014. Median gestational age was 40 weeks. Eighteen (29%) infants were Sarnat grade 3, 41(65%) grade 2 and 4(6%) grade 1. Nineteen outborn infants arrived in CUMH at a median (IQR) age of 310 (270, 420) minutes. Four (21%) outborn infants were within the target temperature range on arrival. Median (IQR) time (minutes) from birth to achieve target temperature was 136 (90, 195) for inborn and 300 (240, 360) for outborn infants (p < .01). Overall, 35 (56%) infants had electrical seizures, 42 (74%) had a normal MRI at a median (IQR) age of 7(6,9) days and the median(IQR) length of stay was 9 (7,11) days. Although no difference in seizures or MRI findings was seen, passive cooling does not achieve consistent temperature control for outborn infants.

Current research suggests that the future looks brighter for cerebral oxygenation monitoring in preterm infants.

UNLABELLED: Brain injuries remain a significant problem for preterm infants, despite extensive physiological monitoring. Near infrared spectroscopy (NIRS) monitoring in the neonatal intensive care unit has to date remained limited to research activities. CONCLUSION: This review highlights the increasing clinical application of NIRS in delivery suites and neonatal units. Four randomised controlled trials incorporating NIRS monitoring suggest that the future may indeed be brighter for this technology in the care of very preterm infants.

Diastolic ventricular function improves during the first 48-hours-of-life in infants weighting <1250 g.

AIM: Few studies have focused on cardiac ventricular diastolic function in preterm neonates in the immediate post-natal period. This study evaluated Doppler-derived parameters of diastolic ventricular function in infants with birth weights of <1250 g during the transitional period. METHODS: This was a prospective observational study conducted in the Coombe Women and Infants University Hospital in Dublin, Ireland. Flow patterns on the mitral and tricuspid valve, isovolumic relaxation time (IVRT), left and right ventricular output and superior vena cava flow were measured in 22 infants with a birth weight of below 1250 g at six, 12, 24 and 48 h of age. RESULTS: Early filling peak velocity of the left and right ventricle increased significantly from 30.3 to 39.5 cm/sec and 26.6 to 32.1 cm/sec, respectively. IVRT of the right ventricle decreased from 70 to 57 ms, and there was a nonsignificant decrease in IVRT of the left ventricle from 61.6 to 54 ms over the first 48 h. CONCLUSION: We have demonstrated that parameters of diastolic ventricular function change significantly over the first 48 h of life in preterm infants <1250 g and that these changes may represent early diastolic dysfunction during the transitional period.

Quantitative or qualitative carbon dioxide monitoring for manual ventilation: a mannequin study.

AIM: To compare the effectiveness of an in-line EtCO2 detector (DET) and a quantitative EtCO2 detector (CAP), both attached to a t-piece resuscitator, during PPV via a face mask. METHODS: Paediatric trainees were randomly assigned to determine the method of PPV they commenced with (No device (ND), DET or CAP). Participants used each method for 2 min. Participants were video-recorded to determine the amount of effective ventilations delivered with each method. RESULTS: Twenty-three paediatric trainees provided a total of 6035 ventilations, and 91.2% were deemed effective. The percentages of median effective ventilations with the ND, the DET and the CAP were 91.0%, 93.0% and 94.0%, respectively. Fourteen (61%) of the trainees indicated a preference for the DET method, 8 (35%) for the CAP method, and 1 (4%) of the trainees indicated a preference for the ND method. Capnography was the most effective method per patient. CONCLUSION: There was no adverse effect with the addition of EtCO2 detectors. Trainees favoured methods of EtCO2 monitoring during ventilation. The NeoStat device was the preferred device by the majority. The greatest efficacy was achieved with the capnography device. Capnography may enhance face mask ventilation.

Who are the PDCO?

In January 2007, the Paediatric Regulation entered into force and established the Paediatric Committee (PDCO) within the European Medicines Agency. The goal of the PDCO is to improve the health of the children of Europe by increasing high-quality research for medicinal products and promoting the development and authorization of such medicines at the EU level. A major function of the PDCO is to formulate and authorize Paediatric Investigation Plans and Paediatric Use Marketing Authorisations. The EU's Seventh Framework Programme for Research has facilitated the establishment of consortia whose ultimate goal is to answer important clinical questions involving medicines commonly used "off-label", in children. The benefits of these consortia include enhanced collaboration amongst paediatricians, scientists and small to medium enterprises whose ultimate goal is to obtain an authorization for a new indication or formulation for use in the paediatric population. It will be interesting in a number of years time to measure the success of this very important European initiative.

Your diagnosis? Congenital foot drop.

A term infant was noted to have right-sided foot drop. We discuss the role of neurophysiology and diagnostic imaging.

Efficacy and user preference of two CO2 detectors in an infant mannequin randomized crossover trial.

Assessment of effective ventilation in neonatal mask ventilation can be difficult. This study aims to determine whether manual ventilation with a T-piece resuscitator containing an inline CO2 detector (either a Pedi-Cap® CO2 detector or a Neo-StatCO2

Association of nucleated red blood cells and severity of encephalopathy in normothermic and hypothermic infants.

AIM: To determine whether hypothermia alters the discriminative ability of postnatal nucleated red blood cells (NRBCs) to distinguish between mild and moderate/severely encephalopathic infants. METHODS: A prospective cohort study recruited full-term neonates with hypoxic ischaemic encephalopathy (HIE) from 2003 to 2012 (prehypothermic and hypothermic eras). The NRBC count was analysed in the first 24 h in all infants and compared between normothermic and hypothermic cohorts. The severity of encephalopathy was categorized using both clinical Sarnat score and continuous multichannel EEG. RESULTS: Eighty-six infants with HIE were included: in the normothermic group, 19 were clinically mild, 24 moderate/severe; in the hypothermic group, 22 were mild, 21 moderate/severe encephalopathy. NRBC count discriminated between mild and moderate/severe Sarnat scores in the normothermic group (p = 0.03) but not in the hypothermic group (p = 0.9). This change was due to a decrease in NRBCs among moderately encephalopathic infants in the hypothermic cohort. CONCLUSION: Postnatal NRBCs distinguished between mild and moderate/severe encephalopathy in normothermic infants but not in infants undergoing therapeutic hypothermia. We advise caution when using postnatal blood samples to study diagnostic biomarkers for HIE without first analysing the potential impact of hypothermia upon these markers.

Life and death decisions for incompetent patients: determining best interests--the Irish perspective.

AIMS: To determine whether healthcare providers apply the best interest principle equally to different resuscitation decisions. METHODS: An anonymous questionnaire was distributed to consultants, trainees in neonatology, paediatrics, obstetrics and 4th medical students. It examined resuscitation scenarios of critically ill patients all needing immediate resuscitation. Outcomes were described including survival and potential long-term sequelae. Respondents were asked whether they would intubate, whether resuscitation was in the patients best interest, would they accept surrogate refusal to initiate resuscitation and in what order they would resuscitate. RESULTS: The response rate was 74%. The majority would wish resuscitation for all except the 80-year-old. It was in the best interest of the 2-month-old and the 7-year-old to be resuscitated compared to the remaining scenarios (p value <0.05 for each comparison). Approximately one quarter who believed it was in a patient best interests to be resuscitated would nonetheless accept the family refusing resuscitation. Medical students were statistically more likely to advocate resuscitation in each category. CONCLUSION: These results suggest resuscitation is not solely related to survival or long-term outcome and the best interest principle is applied differently, more so at the beginning of life.

Are fathers underused advocates for breastfeeding?

Fathers' knowledge base and attitudes influence breastfeeding practice. We aimed to evaluate if Irish fathers felt included in the breastfeeding education and decision process. 67 fathers completed questionnaires, which assessed their role in the decision to breastfeed, knowledge regarding the benefits of breastfeeding and attitude towards breastfeeding.Forty-two (62.7%) of their partners were breastfeeding. Antenatal classes were attended by 38 (56.7%); 59 (88.1%) discussed breastfeeding with their partners and 26 (38.8%) felt that the decision was made together. Twelve (48%) fathers of formula fed infants were unaware that breastfeeding was healthier for the baby. Most fathers (80.6%) felt that breastfeeding was the mother's decision and most (82.1%) felt that antenatal information was aimed at mothers only. Irish fathers remain relatively uninformed regarding the benefits of breastfeeding. This may contribute to their exclusion from the decision to breastfeed. Antenatal education should incorporate fathers more, and this may result in an improvement in our breastfeeding rates.

Nonstationary coupling between heart rate and perfusion index in extremely preterm infants in the first day of life.

Objective.Adaptation to the extra-uterine environment presents many challenges for infants born less than 28 weeks of gestation. Quantitative analysis of readily available physiological signals at the cotside could provide valuable information during this critical time. We aim to assess the time-varying coupling between heart rate (HR) and perfusion index (PI) over the first 24 h after birth and relate this coupling to gestational age (GA), inotropic therapy, and short-term clinical outcome.Approach.We develop new nonstationary measures of coupling to summarise both frequency- and direction-dependent coupling. These measures employ a coherence measure capable of measuring time-varying Granger casuality using a short-time information partial-directed coherence function. Measures are correlated with GA, inotropic therapy (yes/no), and outcome (adverse/normal).Main results.In a cohort of 99 extremely preterm infants (<28 weeks of gestation), we find weak but significant coupling in both the HR → PI and PI → HR directions (P< 0.05). HR → PI coupling increases with maturation (correlationr = 0.26;P = 0.011). PI → HR coupling increases with inotrope administration (r = 0.27;P = 0.007). And nonstationary features of PI → HR coupling are associated with adverse outcome (r = 0.27;P = 0.009).Significance.Nonstationary features are necessary to distinguish different coupling types for complex biomedical systems. Time-varying directional coupling between PI and HR provides objective and independent biomarkers of adverse outcome in extremely preterm infants.

Antenatal management of the expectant mother and extreme preterm infant at the limits of viability.

We explored the opinions of healthcare providers on the antenatal management and outcome of preterm delivery at less than 28 weeks gestation. An anonymous postal questionnaire was sent to health care providers. The response rate was 55% (74% Obstetrician, 70% neonatologist). Twenty four weeks is the limit at which most would advocate intervention. At 23 weeks 67% of neonatologists advocate antenatal steroids. 50% of all health care providers advocate cardiotocographic monitoring at 24 weeks gestation. Written information on survival and long-term outcome is provided by 8% of the respondents. Neonatologists (50%) were more likely than obstetrician (40%) to advocate caesarean section at 25 weeks. We conclude that 24 weeks is the limit at which most would advocate intervention. Significant variation exists both between and within each health care group at less than 25 weeks. Establishment and provision of national outcome data may aid decision making at the limits of viability.

Bedside detection of low systemic flow in the very low birth weight infant on day 1 of life.

We aimed to assess the relationship between the clinical and biochemical parameters of perfusion and superior vena cava (SVC) flow in a prospective observational cohort study of very low birth weight (VLBW) infants. Newborns with congenital heart disease were excluded. Echocardiographic evaluation of SVC flow was performed in the first 24 h of life. Capillary refill time (forehead, sternum and toe), mean blood pressure, urine output and serum lactate concentration were also measured simultaneously. Thirty-eight VLBW infants were examined. Eight patients (21%) had SVC flow less than 40 ml/kg/min. There was a poor correlation between the capillary refill time (in all sites), mean blood pressure, urine output and SVC flow. The correlation coefficient for the serum lactate concentration was r = -0.28, p = 0.15. The median serum lactate concentration was 3.5 (range 2.8-8.5) vs. 2.7 (range 1.2-6.9) mmol/l (p = 0.01) in low flow versus normal flow states. A serum lactate concentration of >2.8 was 100% sensitive and 60% specific for detecting a low flow state. Combining a capillary refill time of >4 s with a serum lactate concentration of >4 mmol/l had a specificity of 97% for detecting a low SVC flow state. Serum lactate concentrations are higher in low SVC flow states. A capillary refill time of >4 s combined with serum lactate concentrations >4 mmol/l increased the specificity and positive and negative predictive values of detecting a low SVC flow state.

Cerebral tissue oxygenation index and superior vena cava blood flow in the very low birth weight infant.

BACKGROUND: Superior vena cava (SVC) flow assesses blood flow from the upper body, including the brain. Near infrared spectroscopy (NIRS) provides information on brain perfusion and oxygenation. AIM: To assess the relationship between cerebral tissue oxygenation index (cTOI) and cardiac output measures in the very low birth weight (VLBW) infant in the first day of life. METHODS: A prospective observational cohort study. Neonates with birth weight less than 1500 g (VLBW) were eligible for enrollment. Newborns with congenital heart disease, major congenital malformations and greater than Papile grade1 Intraventricular Haemorrhage on day 1 of life were excluded. Echocardiographic evaluation of SVC flow was performed in the first 24 h of life. Low SVC flow states were defined as a flow less than 40 mL/kg/min. cTOI was measured using NIRO 200 Hamamatsu. RESULTS: Twenty-seven VLBW neonates had both echocardiography and NIRS performed. The median (range) gestation was 29/40 (25 + 3 to 31 + 5 weeks) and median birth weight was 1.2 kg (0.57-1.48 kg). The mean (SD) TOI was 68.1 (7.9)%. The mean (SD) SVC flow was 70.36(39.5) mLs/kg/min. The correlation coefficient of cerebral tissue oxygenation and SVC flow was r = 0.53, p-value 0.005. There was a poor correlation between right and left ventricular output and cTOI which is not surprising considering the influence of intra- and extracardiac shunts. CONCLUSION: There is a positive relationship between cerebral TOI values and SVC flow in the very low birth infant on day one of life.