Noise exposure exceeded safe limits during neonatal care and road transport but was reduced by active noise cancelling.

AIM: Noise levels above 45 dB in a neonatal intensive care unit (NICU) and 60 dB during neonatal transport are recognised hazards, but protective equipment is not standard. We measured noise levels in both settings, with and without noise protection. METHODS: Peak sound and equivalent continuous sound levels were measured in a NICU and during road transport, at a mannequin's ear and inside and outside the incubator. Recordings were made without protective earwear, with noise protecting earmuffs and with active noise cancelling headphones. RESULTS: In the NICU, the peak levels at the ear, and inside and outside the incubator, were 61, 68 and 76 dB. The equivalent continuous sound levels were 45, 54 and 59 dB. During road transport, the respective levels were 70, 77 and 83 dB and 54, 62 and 68 dB. In the NICU, 80% of environmental peak noise reached the ear and this was reduced to 78% with earmuffs and 75% with active noise cancelling. The respective figures during transport were 87% without protection and 72% with active noise cancelling, with an unexpected increase for ear muffs. CONCLUSION: Noise levels exceeded safe limits in the NICU and during transport, but active noise cancelling reduced exposure.

Hypotension in Preterm Infants (HIP) randomised trial.

OBJECTIVE: To determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation. DESIGN: Double-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment. SETTING: 10 sites across Europe and Canada. PARTICIPANTS: Infants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage. INTERVENTION: Participants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management). PRIMARY OUTCOME: Survival to 36 weeks of PMA without severe brain injury. RESULTS: The trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038). CONCLUSION: Though this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area. TRIAL REGISTRATION NUMBER: NCT01482559, EudraCT 2010-023988-17.

A Pilot Randomized Controlled Trial of Early Targeted Patent Ductus Arteriosus Treatment Using a Risk Based Severity Score (The PDA RCT).

OBJECTIVES: To evaluate the feasibility of recruiting preterm infants to a randomized controlled trial of patent ductus arteriosus (PDA) treatment based on a PDA severity score (PDAsc) and to characterize challenges in obtaining consent, compliance with the protocol, and PDA closure rates. STUDY DESIGN: This single-center, randomized control pilot study of 60 infants <29 weeks of gestation with a high PDAsc (≥5.0) at 36-48 hours of age receiving either ibuprofen or placebo intravenously. The study protocol did not allow for additional PDA therapy within the first 2 weeks. We reported the rate of consent, open label treatment, and PDA closure rates. The primary outcome was chronic lung disease or death. RESULTS: We approached 83 families for enrollment with 73 (88%) providing consent; 13 infants had a PDAsc of <5; of the remaining infants, 30 were assigned ibuprofen and 30 received placebo. Eight infants received open label treatment in the first 2 weeks (12%). The overall PDA closure rate after treatment was 57% in the intervention group and 17% in the control group (P < .01). There was no difference in the primary clinical outcome (OR, 0.8; 95% CI, 0.3-2.1). CONCLUSIONS: Using a PDAsc for infant recruitment to a PDA treatment randomized controlled trial is feasible. There is a high rate of consent and relatively low rate of open-label PDA treatment. The overall PDA closure rate in the intervention arm was low placing the emphasis on devising more effective PDA closure strategies in future randomized controlled trials. TRIAL REGISTRATION: ISRCTN (13281214) and European Union Drug Regulating Authorities Clinical Trials Database (2015-004526-33).

Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT).

A patent ductus arteriosus (PDA) in preterm infants is associated with increased ventilator dependence and chronic lung disease, necrotizing enterocolitis, intraventricular haemorrhage, and poor neurodevelopmental outcome. Randomised controlled trials of early PDA treatment have not established a drop in the aforementioned morbidities. Those trials did not physiologically categorise PDA severity. Incorporating the specific physiological features of a haemodynamic significant PDA may evolve our understanding of this phenomenon, allowing accurate triaging using echocardiography and targeted treatment.  Our group has recently demonstrated that a PDA severity score (PDAsc) derived at 36-48 hours of age can accurately predict the later occurrence of chronic lung disease or death (CLD/Death). Using echocardiography, we assessed PDA characteristics, as well as left ventricular diastolic function and markers of pulmonary overcirculation, and from this formulated a PDAsc. Gestation was also incorporated into the score. We hypothesise that in preterm infants at high risk of developing CLD/Death based on a PDAsc, early treatment with Ibuprofen compared with placebo will result in a reduction in CLD/Death. This is a single centre double-blind two arm randomised controlled trial conducted in the neonatal intensive care unit in the Rotunda Hospital, Dublin. Echocardiogram is carried out in the first 36-48 hours of life to identify preterm infants with a PDAsc ≥ 5.0 and these infants are randomised to Ibuprofen or placebo. Primary outcomes are assessed at 36 weeks post menstrual age. This pilot study's purpose is to assess the feasibility of performing the trial and to obtain preliminary data to calculate a sample size for a definitive multi-centre trial of early PDA treatment using a PDAsc. We aim to recruit a total of 60 infants with a high risk PDA over three years. Trial Registration: ISRCTN ISRCTN13281214 (26/07/2016) and the European Union Drug Regulating Authorities Clinical Trials Database 2015-004526-33 (03/12/2015).

Clinical utility of right ventricular fractional area change in preterm infants.

INTRODUCTION: Right ventricular fractional area change (RV FAC) is a novel non-invasive quantitative measure of RV function. Reference values of RV FAC and RV end systolic and diastolic areas (RVEDA, RVESA) have recently been established in preterm infants, but their role as marker to assess the efficacy of patient management strategies in the first week of life is largely unknown. The aims of this study were to assess the relationship between RV FAC and gestational age/birthweight, assess the RV FAC on day one of age to predict the later evolution of peri/intraventricular haemorrhage (P/IVH), and assess the influence of a persistent patent ductus arteriosus (PDA) on RV FAC during the first week of age. METHODS: Preterm infants <29 weeks gestation underwent echocardiography assessments on days 1, 2 and 5-7. RVEDA and RVESA were traced in the RV-focused apical four-chamber view, and RV FAC was calculated using the formula [(RVEDA-RVESA)÷(RVEDA)] × 100. PDA treatment was not carried out during the study period. A cranial ultrasound was carried out on all infants on Days 5-7 of age. P/IVH was defined as IVH grades II to IV. RESULTS: One hundred and one infants with a mean gestation of 26.5 (1.4) weeks and a birthweight of 983 (240) grams were enrolled in the study. There was no relationship between RV FAC and birthweight (r=-0.02, p=0.86) but there was a negative correlation between RV FAC and echo-measured SVR (r=-0.57, p<0.001). On Day 1, RV FAC was lower in infants who developed P/IVH (24% [18-34] vs. 31% [25-40], p=0.04). On Days 5-7 infants with a PDA had a lower RV FAC compared with those without [42 (7) vs. 49 (9) %, p<0.001]. CONCLUSION: RV FAC may be a useful addition to the haemodynamic assessment of preterm infants during the first week of age.

Neuro-developmental outcome of a large cohort of growth discordant twins.

UNLABELLED: Our aims were to study the effect of birthweight growth discordance (≥20%) on neuro-developmental outcome of monochorionic and dichorionic twins and to compare the relative effects of foetal growth discordance and prematurity on cognitive outcome. We performed a cross-sectional multicentre prospective follow-up study from a cohort of 948 twin pregnancies. One hundred nineteen birthweight-discordant twin pairs were examined (24 monochorionic pairs) and were matched for gestational age at delivery with 111 concordant control pairs. Participants were assessed with the Bayley Scales between 24 and 42 months of age. Analysis was by paired t test for intra-twin pair differences and by multiple linear regression. Compared to the larger twin of a discordant pair, the smaller twin performed significantly worse in cognition (mean composite cognitive score difference = -1.7, 95% confidence interval (CI) = 0.3-3.1, p = 0.01) and also in language and motor skills. Prematurity prior to 33 weeks' gestation, however, had a far greater impact on cognitive outcomes (mean cognitive composite score difference = -5.8, 95% CI = 1.2-10.5, p = 0.008). CONCLUSION: Birthweight growth discordance of ≥20% confers an independent adverse effect on long-term neuro-development of the smaller twin. However, prior to 33 weeks' gestation, gestational age at birth adversely affects cognitive development to a greater extent than foetal growth discordance.

A Patent Ductus Arteriosus Severity Score Predicts Chronic Lung Disease or Death before Discharge.

OBJECTIVES: To test the hypothesis that a patent ductus arteriosus (PDA) severity score (PDAsc) incorporating markers of pulmonary overcirculation and left ventricular (LV) diastolic function can predict chronic lung disease or death before discharge (CLD/death). STUDY DESIGN: A multicenter prospective observational study was conducted for infants <29 weeks gestation. An echocardiogram was carried out on day 2 to measure PDA diameter and maximum flow velocity, LV output, diastolic flow in the descending aorta and celiac trunk, and variables of LV function using tissue Doppler imaging. Predictors of CLD/death were identified using logistic regression methods. A PDAsc was created and a receiver operating characteristic curve was constructed to assess its ability to predict CLD/death. RESULTS: We studied 141 infants at a mean (SD) gestation and birthweight of 26 (1.4) weeks and 952 (235) g, respectively. Five variables were identified that were independently associated with CLD/death (gestation at birth, PDA diameter, maximum flow velocity, LV output, and LV a' wave). The PDAsc had a range from 0 (low risk) to 13 (high risk). Infants who developed CLD/death had a higher score than those who did not (7.3 [1.8] vs 3.8 [2.0], P < .001). PDAsc had an area under the curve of 0.92 (95% CI 0.86-0.97, P < .001) for the ability to predict CLD/death. A PDAsc cut-off of 5 has sensitivity and specificity of 92% and 87%, and positive and negative predictive values of 92% and 82%, respectively. CONCLUSIONS: A PDAsc on day 2 can predict the later occurrence of CLD/death further highlighting the association between PDA significance and morbidity.

Left Ventricular Rotational Mechanics in Preterm Infants Less Than 29 Weeks' Gestation over the First Week after Birth.

BACKGROUND: There is a paucity of data on left ventricular (LV) rotational physiology, twist, and torsional mechanics in preterm infants. The principal aims of the present study were to assess the feasibility and reproducibility of measuring LV rotation, twist, and torsion in preterm infants (<29 weeks' gestation) using two-dimensional speckle-tracking echocardiography and to examine the changes in those parameters over the first week after birth. METHODS: This was a prospective observational study involving preterm infants <29 weeks' gestation. Echocardiographic evaluations were performed on days 1, 2, and 5 to 7 after delivery. LV basal and apical rotation, LV twist, LV twist rate (LVTR), and LV untwist rate (LVUTR) were measured from the basal and apical short-axis parasternal views and calculated using two-dimensional speckle-tracking echocardiography. Torsion was also calculated by normalizing LV twist to LV end-diastolic length. One-way repeated-measures analysis of variance was used to compare values across the three time points. Intra- and interobserver reproducibility were assessed using Bland-Altman analysis and the intraclass correlation coefficient. RESULTS: Fifty-one infants with a mean ± SD gestational age of 26.8 ± 1.5 weeks and a mean birth weight of 945 ± 233 g were included. There was high intra- and interobserver reproducibility for basal and apical rotation, LV twist, and LV torsion, with intraclass correlation coefficients ranging from 0.78 to 0.96 (P < .001 for all). Intra- and interobserver intraclass correlation coefficients for LVTR and LVUTR ranged from 0.70 to 0.88 (P < .001 for all). Apical rotation remained constant over the first week of age in a positive counterclockwise fashion (11.8 ± 5.0° vs 12.1 ± 6.1° vs 11.7 ± 8.3°, P = .92). Basal rotation changed from counterclockwise on day 1 to clockwise on day 7 (median, 5.5° [interquartile range, -0.3° to 8.3°] vs 4.0 [interquartile range, -4.7° to 7.2°] vs -4.5° [interquartile range, -5.8° to -2.3°], P < .001), with resultant net increases in twist and torsion (P < .05). There was no change in LVTR (P = .60), but LVUTR increased across the same time period (P = .01). CONCLUSIONS: Assessment of twist, LVTR, and LVUTR is feasible in preterm infants, with acceptable reproducibility. There are increases in LV twist and torsion in addition to LVUTR, suggesting changes in LV mechanics during the first week of age.

Serial changes in myocardial function in preterm infants over a four week period: the effect of gestational age at birth.

BACKGROUND: Myocardial performance is impaired in the first days of life in preterm infants but improves by day 5. Tissue Doppler imaging (TDI) is a novel and reliable means of assessing myocardial performance. OBJECTIVE: To investigate myocardial performance using TDI and shortening fraction (SF) in preterm infants of different gestational age groups and serial changes in these parameters in first four weeks of life. Study design Infants less than 36 weeks of gestation were divided into group 1 (24-27 weeks, n=8), group 2 (28-31 weeks, n=12) and group 3 (32-35 weeks, n=13). Infants with severe congenital malformations, a hypoxic insult at birth, and those on inotropic support were excluded. Echocardiograms were performed at 36-48 hours, 2 weeks and 4 weeks of life. Left ventricular (LV) SF, systolic (S'), early diastolic (E') and late diastolic (A') TDI velocities were assessed. We analyzed the data using a repeated-measures ANOVA. RESULTS: Thirty three infants underwent serial TDI and SF measurements. There was an increase in LV S' (p=.02) and E' (.01) velocities in group 2 , and in group 3 (p=.03 for S' and p=.04 for E'), but no significant increase in group 1 (p=.48 for S' and .32 for E'). At each study point, there was significant difference in myocardial performance between group 1 and 3 for each of the parameters (p<.05). There was no significant increase in SF over time in any of the groups. CONCLUSION: We describe a serial increase in myocardial performance in infants of 28 weeks gestation and above. While there was no change in myocardial performance among the most extremely preterm infants, this may have been the result of small sample size of the group.