A National Review of Neonatal Jaundice Identification.

Background Physiological neonatal hyperbilirubinemia is a normal transitional phenomenon, however bilirubin encephalopathy can develop due to exposure to very high bilirubin levels. A systematic approach to early detection of high levels can prevent this outcome. Methods We designed a questionnaire to assess local jaundice management practices in Irish maternity units. Results All 19 units responded to our clinical questionnaire. Early discharge (<48 hours) occurs in 12 units (63%). Six units universally screen all babies with a transcutaneous bilirubinometer (TCB) (32%) while 12 units only do so if clinically jaundiced (83%). 12 units follow up <5% of their babies for jaundice monitoring after discharge (67%), which is lower than expected for optimal jaundice management. Conclusion Our survey responses show a high degree of variability in jaundice identification and follow up practices around the country. As maternity units trend towards earlier discharge of mothers due to resource constraints, we need to develop national systems to stratify risk before discharge and monitor jaundice in the out-patient setting. Introduction

Staff Attitudes towards Patient Safety Culture and Working Conditions in an Irish Tertiary Neonatal Unit

Introduction There is little published research evaluating attitudes towards patient safety culture and working conditions in neonatal units. This study aimed to explore this within a Level III Irish neonatal unit setting. Methods This was a quantitative, cross-sectional study performed in the Rotunda Hospital, Dublin. A 30-item safety attitudes questionnaire (SAQ) was utilized to analyze staff perceptions in areas including job satisfaction, working conditions and stress recognition. Results The 'Stress Recognition' domain received the highest score (75.3) followed by 'Job Satisfaction' domain with a mean score of 74.4. The lowest mean scale score in the neonatal unit was for 'Perceptions of Management', with a mean score of 50.7. Collaboration and Communication scores were high across all disciplines. Conclusion This SAQ has highlighted a number of important areas for quality improvement and staff satisfaction in our neonatal unit.

The utility of routine echocardiography in newborn infants with a persistent oxygen requirement

In the era of antenatal screening for congenital heart disease (CHD), infants presenting with an undiagnosed significant CHD are rare. However, term infants admitted with an initial diagnosis of TTN and a prolonged oxygen requirement often undergo an echocardiogram. We aimed to assess whether this practice yields any additional cases of undiagnosed CHD. We performed a retrospective chart review over a three year period [2013 ­ 2015] of term (> 36 weeks) infants admitted to the NICU for ≥ 5 days with a diagnosis of TTN and received an echocardiogram. The presence of CHD on the echocardiogram was assessed. Forty-seven infants were enrolled. The median age of echocardiogram was day four [2 ­ 8]. No infant had a diagnosis of significant CHD on the postnatal echocardiogram. A small muscular VSD was identified in two infants. Routine echocardiography for this cohort of infants to rule out major CHD appears to be unwarranted.

Longitudinal Assessment of Left and Right Myocardial Function in Preterm Infants Using Strain and Strain Rate Imaging.

BACKGROUND: There is a paucity of longitudinal data on left ventricular (LV) and right ventricular (RV) function in preterm infants of less than 29 weeks' gestation. OBJECTIVE: The aim of this study was to describe changes in tissue Doppler-derived basal longitudinal strain (BLS) and systolic (SRs), early (SRe) and late (SRa) diastolic strain rates in extremely premature infants from birth to 36 weeks postmenstrual age (PMA). METHODS: Echocardiographic assessments were carried out on days 1, 2, 5-7 and at 36 weeks PMA. We assessed the following associations: correlation with systemic vascular resistance (SVR) on day 1, influence of a patent ductus arteriosus (PDA) during days 5-7, and the effect of chronic lung disease (CLD). RESULTS: In total, 105 infants with a median gestation of 27.1 weeks (IQR 26.0-28.1) and a birthweight of 965 g (IQR 785-1,153) were included. There was an increase in most of the measurements across the four time points. On day 1, there was a weak negative correlation between SVR and LV BLS (r = -0.3, p = 0.01), SVR and septal BLS (r = -0.4, p < 0.001) and SVR and LV SRe (r = -0.4, p = 0.005). On days 5-7, infants with a PDA >1.5 mm had higher LV BLS [-13.0 (2.4) vs. -11.9 (1.9)%, p = 0.03]. At 36 weeks, infants with CLD (n = 28/47) had lower RV BLS [-26.4 (5.0) vs. -30.7 (5.5)%, p = 0.01] and lower RV SRa [4.2 (1.3) vs. 5.3 (1.9) s-1, p = 0.04]. CONCLUSION: Myocardial function undergoes important longitudinal changes in preterm infants. Left heart strain measurements appear to be weakly influenced by changes in preload and afterload. CLD appears to leave a negative impact on RV function.

The Use of Inhaled Nitric Oxide in a Tertiary Neonatal Intensive Care Unit.

There is currently insufficient evidence to create a standardised protocol for the use and weaning of inhaled nitric oxide (iNO). We aimed to determine our application of iNO in this patient cohort. We performed a retrospective chart review on patients receiving iNO therapy for persistent pulmonary hypertension of the newborn (PPHN) from a single tertiary neonatal centre in 2014. The data was entered into the European Inhaled Nitric Oxide Registry. Thirty two babies were treated with iNO during this period, 9 of which were less than 32 weeks gestation. The median time to initiation of iNO treatment was 4-5 hours and the median duration of treatment was 74 hours for term and 66 hours for preterm infants. We recommend that further use of the European Inhaled Nitric Oxide Registry across more neonatal units in the Republic of Ireland could lead to the development of national guidelines on iNO use and weaning in this cohort.

The effect of antenatal magnesium sulfate on left ventricular afterload and myocardial function measured using deformation and rotational mechanics imaging.

OBJECTIVE: Assess the effect of antenatal magnesium sulfate (MgSO4) on left ventricular function measured using deformation and rotational mechanics imaging. STUDY DESIGN: Infants who received MgSO4 were matched for gestation, birth weight and mode of delivery with controls. Echocardiography was carried out on days 1 and 2 to measure left ventricle longitudinal strain (LV LS), twist, untwist rate, ejection fraction (EF), and systemic vascular resistance (SVR). RESULTS: Thirty-eight infants with a median gestation and birth weight of 27.1 weeks and 923 g were included. On day 1, the MgSO4 group (n=19) had a lower SVR and higher LV LS, EF, twist and untwist rate than the Control group (n=19) (all P<0.05). There were no differences between the groups on day 2. CONCLUSION: Antenatal MgSO4 administration is associated with a lower SVR and higher myocardial function on day 1 in preterm infants <29 weeks gestation.

The Bhutani Nomogram Reduces Incidence of Severe Hyperbilirubinaemia in Term and Near Term Infants.

Very high bilirubin levels can have devastating neurodevelopmental effects on infants including hearing loss and cerebral palsy. A previous study in our institution determined the rate of, and factors associated with, bilirubin values above exchange transfusion level. Since this study the Bhutani nomogram was introduced to help identify infants at risk of severe hyperbilirubinaemia. In our study we looked at the initial serum bilirubin taken in infants 36 weeks and 2.5 kgs. Our results show that since this nomogram was introduced there has been a significant reduction in the number of infants reaching exchange transfusion levels. We also showed that the Bhutani nomogram could successfully be used in a population of unknown direct Coombs status.

Treatment of premature infants with pulmonary hypertension and right ventricular dysfunction with milrinone: a case series.

OBJECTIVE: Milrinone has been proposed as an effective treatment for pulmonary hypertension (PH) and right ventricular (RV) dysfunction. We aimed to determine the effect of milrinone therapy on clinical and echocardiography parameters of PH in preterm infants with elevated pulmonary pressures. STUDY DESIGN: A retrospective case review was conducted on infants <32 weeks gestation who received milrinone for the treatment of PH and reduced RV function. Echocardiographic data were collected before and after treatment with milrinone, and serial clinical parameters were recorded over a 72h period. RESULT: Seven infants met the inclusion criteria with a median gestation and birth weight of 27.3 weeks and 1140 g, respectively. Four infants had a diagnosis of pulmonary hypoplasia with PH, and three infants were recipients in twin-to-twin transfusion syndrome who also developed PH. Nitric oxide was used in six infants before commencement of milrinone. Milrinone was commenced at a dose of 0.33 µg kg(-1) min(-1) to 0.5 µg kg(-1) min(-1) and continued for a median duration of 70 h. Use of milrinone was associated with a fall in oxygenation index and inhaled nitric oxide dose. Following an initial fall in blood pressure over the first 6 h, there was an increase in blood pressure over the subsequent 72 h. Echocardiographic data demonstrated an increase in indicators of myocardial performance and PH. One infant died before discharge. CONCLUSION: This case series suggests that milrinone may be a useful therapy for premature infants with echocardiography findings of PH and/or RH dysfunction. This data support the need for a randomised control trial to confirm its efficacy.

Laboratory coagulation parameters in extremely premature infants born earlier than 27 gestational weeks upon admission to a neonatal intensive care unit.

BACKGROUND: Few published data exist to guide interpretation of coagulation times in extremely premature infants. OBJECTIVE: To determine coagulation reference ranges on day 1 of life in extremely premature infants. METHODS: A retrospective review of day 1 coagulation tests was performed in 144 infants <27 weeks' gestation between 2004 and 2010 in a tertiary neonatal unit. Samples were drawn through a non-heparinized umbilical or peripheral venous catheter as part of routine clinical care. RESULTS: Mean (SD) and median (range) prothrombin times (PT) of 21.5 (5.3) and 20.2 (13.3-39) s, respectively, activated partial thromboplastin times (APTT) of 75.2 (27.8) and 67.4 (34.9-191.6) s, respectively, and plasma fibrinogen levels of 1.9 (1.1) and 1.4 (0.5-4.8) g/l, respectively, were reported. Using reference intervals derived from the 2.5th to 97.5th centiles, ranges of 14.4-36.7 s, 40.5-158.5 s and 0.7-4.8 g/l were determined for PT, APTT and plasma fibrinogen levels, respectively. In a subcohort with grade 0-2 intraventricular haemorrhage (n = 92), mean PT and APTT were 20.9 and 71.3 s, respectively, versus mean PT and APTT of 23.1 and 88.4 s (p = 0.06 and p = 0.03), respectively for those with grade 3-4 intraventricular haemorrhage. Mean PT and APTT in a cohort of infants defined to be small for gestational age were 22 and 76.8 s. These results did not differ significantly from non-small for gestational age infants, with a mean PT and APTT of 19.5 and 73.4 s (p = 0.09 and p = 0.7). CONCLUSIONS: Reference ranges based on retrospective data were determined for PT, APTT and fibrinogen in a large cohort of extremely preterm infants.

Myocardial assessment using tissue doppler imaging in preterm very low-birth weight infants before and after red blood cell transfusion.

OBJECTIVE: To investigate myocardial velocities in anemic very low-birth weight (VLBW) preterm infants, pre and post red blood cells transfusion using tissue Doppler imaging echocardiography. STUDY DESIGN: Forty-eight VLBW preterm infants34 weeks and>2 weeks old were prospectively divided: Transfused symptomatic infants (Hematocrit (Hct)<0.30 (n=32)) and non transfused asymptomatic controls (control 1, Hct >0.30 (n=9) and control 2, Hct <0.30 (n=7)). Echocardiography was performed before and 3-5 days after transfusion in the transfused, and the controls were studied at similar intervals. Non parametric tests were used for statistical analysis. RESULT: Left ventricular (LV) systolic velocity increased (transfused (4.6±0.70 vs 6.0±0.65, P<0.01)) as did LV diastolic velocities (P<0.01) without significant difference over time in each control. The percentage change in LV velocity following transfusion correlated negatively (ρ=0.36) with pre transfusion Hct. CONCLUSION: There is a significant increase in myocardial performance following transfusion, which is related to the severity of the anemia.

Initial assessment of jaundice in otherwise healthy infants--a comparison of methods in two postnatal units.

Transcutaneous bilirubin (TcB) has the potential to reduce total serum bilirubin (TS) sampling. The principal aim of this study was to determine and compare the number of initial TSB samples (TSBs) in two postnatal units (hospitals A & B) whereby hospital A used TcB and hospital B did not. A secondary aim was to determine the clinical factors that led to initial TSBs exceeding exchange transfusion level in both hospitals. Results demonstrated both hospitals had similar populations and patient numbers following selection criteria. 1645 neonates (10.4%) had one or more TSBs performed in hospital A, versus 2373 neonates (15.1%) in hospital B (p < 0.01). Fourteen neonates in hospital A and 3 neonates in hospital B had initial TSBs above exchange transfusion level. For neonates with TSBs above exchange, preventable factors related to earlier testing and follow up. In routine clinical practice, TcB is associated with a significantly reduced number of TSB measurements. TSB levels above exchange transfusion are linked to preventable factors, in otherwise healthy neonates.

N-terminal pro-B-type natriuretic peptide: a measure of significant patent ductus arteriosus.

BACKGROUND: B-type natriuretic peptide (BNP) is a marker for ventricular dysfunction secreted as a pre-prohormone, pro-B-type natriuretic peptide (proBNP), and cleaved into BNP and a biologically inactive fragment, N-terminal pro-B-type natriuretic peptide (NT-proBNP). Little is known about the clinical usefulness of NT-proBNP in preterm infants. OBJECTIVE: To evaluate the usefulness of plasma NT-proBNP in diagnosing haemodynamically significant patent ductus arteriosus (hsPDA) in neonates and examine some factors that might affect this. METHODS: Infants born at <34 weeks' gestational age (GA) and <2 kg birth weight (BW) were prospectively enrolled within 6-12 hours of birth. Plasma NT-proBNP levels were measured on days 1, 3, 5 and 10 with simultaneous echocardiography done to detect hsPDA and assess ventricular function. Significant PDA was diagnosed by large ductal flow with left to right shunt on colour Doppler, measuring >1.6 mm on two-dimensional echocardiography, along with clinical features of PDA. RESULTS: Forty-nine infants were analysed. Median GA was 30 weeks (range 24-33) and median BW 1220 g (range 550-1950). Eighteen infants with hsPDA had higher day 3 plasma NT-proBNP values (median 32 907 pg/ml; range 11 396-127 155) (p<0.001) than controls (median 3147 pg/ml; range 521-10 343). Infants who developed sepsis had higher day 10 plasma NT-proBNP levels. Area under receiver operator characteristic curve for detection of hsPDA, by day 3 NT-proBNP value, was significant 0.978 (95% CI 0.930 to 1.026). NT-proBNP was predictive of hsPDA (sensitivity 100%; specificity 95%) at a cut-off value of 11 395 pg/ml. CONCLUSION: Plasma NT-proBNP level on day 3 is a good marker for hsPDA in preterm infants. Serial measurements of NT-proBNP may be useful in assessing the clinical course of PDA.

SNAP-II and SNAPPE-II: Simplified newborn illness severity and mortality risk scores.

OBJECTIVES: Illness severity scores for newborns are complex and restricted by birth weight and have dated validations and calibrations. We developed and validated simplified neonatal illness severity and mortality risk scores. The primary outcome was in-hospital mortality. STUDY DESIGN: Thirty neonatal intensive care units in Canada, California, and New England collected data on all admissions during the mid 1990s; patients moribund at birth or discharged to normal newborn care in <24 hours were excluded. Starting with the 34 data elements of the Score for Neonatal Acute Physiology (SNAP), we derived the most parsimonious logistic model for in-hospital mortality using 10,819 randomly selected Canadian cases. SNAP-II includes 6 physiologic items; to this are added points for birth weight, low Apgar score, and small for gestational age to create a 9-item SNAP-Perinatal Extension-II (SNAPPE-II). We validated SNAPPE-II on the remaining 14,610 cases and optimized the calibration. RESULTS: In all birth weights, SNAPPE-II had excellent discrimination and goodness of fit. Area under the receiver operator characteristic curve was .91 +/- 0.01. Goodness of fit (Hosmer-Lemeshow) was 0.90. CONCLUSIONS: SNAP-II and SNAPPE-II are empirically validated illness severity and mortality risk scores for newborn intensive care. They are simple, accurate, and robust across populations.

Lyso-phosphatidylcholine and outcome of preterm babies with respiratory distress syndrome treated with surfactant.

Phosphatidylcholine (PC) is the predominant phospholipid in natural surfactant preparations. A metabolic intermediate, lyso-PC, is potentially injurious to the lungs. In the present study, tracheal aspirates from preterm babies with respiratory distress syndrome treated with surfactant were examined for the presence of lyso-PC to determine if there was any correlation with outcome. Eighteen babies were assigned to receive initially either 100 or 200 mg/kg Curosurf followed by up to three further 100-mg/kg doses if required. Lyso-PC was present in aspirates taken 12-24 h after the last treatment from nine of 11 infants who initially received 200 mg/kg but in only one from seven receiving 100 mg/kg initially, and was dependent on the total dose of phospholipid administered. Three babies in the low-dose group developed bronchopulmonary dysplasia, whereas two in the high-dose group were non-survivors, however we could not correlate the presence of lyso-PC with adverse long-term outcome in this group of preterm infants.

Comparison of surface properties and physiological effects of a synthetic and a natural surfactant in preterm rabbits.

AIMS: To compare the physical and physiological properties of a synthetic surfactant (Exosurf, Wellcome Foundation) and a natural surfactant (Curosurf, Chiesi Farmaceutici). METHODS: Surface properties of the surfactant suspensions (10 mg phospholipid/ml) were evaluated using the pulsating bubble surfactometer. Lung-thorax compliance was determined in 47 immature newborn rabbits with a gestational age of 27 days, treated with recommended clinical doses of either surfactant (Exosurf 67.5 mg/kg; Curosurf 200 mg/kg). The lungs were examined histologically. RESULTS: The mean (SD) contractile forces of the surface at maximum and minimum bubble size were significantly lower for Curosurf than for Exosurf: 31 (2) and 0 (0) mN/m v 53 (5) and 29 (4) mN/m, respectively. Mean (SD) lung-thorax compliance after one hour of ventilation was significantly higher in rabbits treated with Curosurf compared with animals receiving Exosurf or those serving as controls: 0.60 (0.15) ml/cm H2O.kg v 0.44 (0.03) and 0.34 (0.18) ml/cm H2O.kg, respectively. Both surfactants increased alveolar volume density compared with results for control animals, but only Curosurf significantly reduced the incidence of moderate or severe bronchiolar epithelial disruption. CONCLUSIONS: The natural surfactant, Curosurf, reduced the contractile force at an air-liquid interface to a greater extent than the synthetic surfactant, Exosurf, and led to a greater improvement in compliance and less airway epithelial damage when given in clinical treatment doses to immature rabbits.

Antenatal intraventricular haemorrhage.

Germinal matrix-intraventricular haemorrhage (IVH) is a well described complication of premature birth. We present two infants with severe IVH in the absence of other serious neonatal illness. These lesions probably occurred antenatally and prior to the onset of labour. Unrecognised intrauterine stresses may cause intraventricular haemorrhagic or ischaemic lesions in the immature brain. Timing of these lesions is important for both clinical and indeed medico-legal reasons.

Antenatal intraventricular haemorrhage.

Germinal matrix-intraventricular haemorrhage (IVH) is a well described complication of premature birth. We present two infants with severe IVH in the absence of other serious neonatal illness. These lesions probably occurred antenatally and prior to the onset of labour. Unrecognised intrauterine stresses may cause intraventricular haemorrhagic or ischaemic lesions in the immature brain. Timing of these lesions is important for both clinical and indeed medico-legal reasons.

Multicentre randomised trial comparing high and low dose surfactant regimens for the treatment of respiratory distress syndrome (the Curosurf 4 trial).

A randomised trial was conducted in 82 centres using the porcine surfactant extract, Curosurf, to compare two regimens of multiple doses to treat infants with respiratory distress syndrome and arterial to alveolar oxygen tension ratio < 0.22. Infants were randomly allocated to a low dosage group (100 mg/kg initially, with two further doses at 12 and 24 hours to a maximum cumulative total of 300 mg/kg; n = 1069) or a high dosage group (200 mg/kg initially with up to four further doses of 100 mg/kg to a maximum cumulative total of 600 mg/kg; n = 1099). There was no difference between those allocated low and high dosage in the rates of death or oxygen dependency at 28 days (51.1% v 50.8%; difference -0.3%, 95% confidence interval (CI) -4.6% to 3.9%), death before discharge (25.0% v 23.5%; difference -1.5%, 95% CI -5.1% to 2.2%), and death or oxygen dependency at the expected date of delivery (32.2% v 31.0%; difference -1.2%, 95% CI -5.2% to 2.7%). For 14 predefined secondary measures of clinical outcome there were no significant differences between the groups but the comparison of duration of supplemental oxygen > 40% did attain significance; 48.4% of babies in the low dose group needed > 40% oxygen after three days compared with 42.6% of those in the high dose group. The total amount of surfactant administered in the low dose regimen (mean 242 mg phospholipid/kg) was probably enough to replace the entire pulmonary surfactant pool. Adopting the low dose regimen would lead to considerable cost savings, with no clinically significant loss in efficacy.