Variation between Clinician-Recorded and Downloaded Invasive Blood Pressure in Extremely Preterm Infants.

OBJECTIVE: This study aimed to examine the variation between clinician-recorded and continuously downloaded invasive blood pressure (BP). STUDY DESIGN: Prospective study where invasive BP data were downloaded every 10 seconds for the first week of life. Hourly clinician-recorded BP was recorded. Agreement between the two methods were examined. RESULTS: A total of 1,180 BP measurements were examined from 42 preterm infants with a mean (standard deviation [SD]) gestation and birthweight of 25.7 weeks (1.4) and 802 g (177) respectively. The mean (SD) bias was -0.11 mm Hg (3.17), but the 95% limits of agreement (LOA) varied between -6.3 and +6.1 mm Hg. Inotrope usage was significantly higher for BP measurements that fell in the 5% outliers when compared with those that fell within the 95% LOA (62.7 vs. 44.6%, p = 0.006). CONCLUSION: Clinicians showed no systematic bias to over- or underrecord BP, but some of the greatest differences were found in infants receiving inotropes. KEY POINTS: · BP is a commonly recorded cardiovascular parameter in the neonatal intensive care unit.. · Invasively measured BP remains the gold standard.. · Clinician-recorded BP showed no systematic bias in over-or underrecording invasive BP..

Common carotid artery blood flow volume in extremely preterm infants.

AIM: The aim of this study was to determine carotid blood flow volume, a surrogate for cerebral blood flow, using Doppler ultrasound in extremely preterm infants. METHODS: In infants <29 weeks, right common carotid artery flow volume (RCCAF) was calculated from vessel diameter and intensity-weighted mean velocity measured using Doppler ultrasound on days 1 and 3. In addition, left ventricular output (LVO), ductus arteriosus characteristics and invasive mean arterial blood pressure (MABP) were obtained. RESULTS: Sixty infants with mean gestation of 25.8 weeks were studied. The median RCCAF increased from 12 (IQR 9-15) mL/kg/min on day 1, to 14 (IQR 12-18) mL/kg/min on day 3 (p = 0.007). RCCAF was positively correlated with invasive MABP on days 1 and 3. RCCAF significantly correlated with LVO in infants with closing or closed ductus arteriosus on day 1. Using multiple regression analysis, RCCAF was significantly associated with invasive MABP on day 1 and to inotropic treatment on day 3. CONCLUSION: Doppler ultrasound can be used to measure RCCAF in extremely preterm infants receiving intensive care. RCCAF increased during the first three days and was positively related to invasive MABP on day 1. Values were lower than previously described in more mature infants. CLINICAL TRIAL REGISTRATION: ISRCTN 83507686.

Seasonal Influenza Vaccination During Pregnancy and the Risk of Major Congenital Malformations in Live-born Infants: A 2010-2016 Historical Cohort Study.

BACKGROUND: Available evidence indicates that seasonal inactivated influenza vaccination during pregnancy protects both the mother and her newborn and is safe. Nevertheless, ongoing safety assessments are important in sustaining vaccine uptake. Few studies have explored safety in relation to major congenital malformations (MCMs), particularly in the first trimester when most organogenesis occurs. METHODS: Anonymized UK primary care data (the Clinical Practice Research Datalink), including a recently developed Pregnancy Register, were used to identify live-born singletons delivered between 2010 and 2016. Maternal influenza vaccination was determined using primary care records and stratified by trimester. Ascertainment of MCMs from infant primary care records was maximized by linkage to hospitalization data and death certificates. The relationship between vaccination and MCMs recorded in the year after delivery and in early childhood was then assessed using multivariable Cox regression. RESULTS: A total of 78 150 live-birth pregnancies were identified: 6872 (8.8%) were vaccinated in the first trimester, 11 678 (14.9%) in the second, and 12 931 (16.5%) in the third. Overall, 5707 live births resulted in an infant with an MCM recorded in the year after delivery and the adjusted hazard ratio when comparing first-trimester vaccination to no vaccination was 1.06 (99% CI, .94-1.19; P = .2). Results were similar for second- and third-trimester vaccination and for analyses considering MCMs recorded beyond the first birthday. CONCLUSIONS: In this large, population-based historical cohort study there was no evidence to suggest that seasonal influenza vaccine was associated with MCMs when given in the first trimester or subsequently in pregnancy.

A realistic flow phantom model of the carotid artery in preterm infants for training and research.

INTRODUCTION: Cerebral blood flow is increasingly monitored in preterm infants. Doppler ultrasound of the carotid artery is a widely available method but is operator dependent. Our aim was to design and produce a realistic flow phantom model of the carotid artery of preterm infants. METHODS: Data from cerebral blood flow measurements using Doppler ultrasound of the right common carotid artery from 21 premature newborn infants were used to produce a Doppler flow phantom model with three different vessel diameters. Vessel diameter, continuous and pulsatile flow volume measurements were performed by two blinded observers (with more than eight and 20 years of experience). RESULTS: Vessel diameter measurements using the phantom were underestimated by 7%. Continuous flow volume measurements were overestimated by 7% by both observers (observer 1 mean difference 1.5 ± 1.96 SD -3.3 to 6.3 ml/min versus observer 2, 1.9 ± 1.96 SD -3.6 to 7.4 ml/min). Pulsatile flow measurements were overestimated by 12.6% by observer 1 (2.7 ± 1.96 SD -0.6 to 5.9 ml/min) and by 7.8% by observer 2 (1.7 ± 1.96 SD -1.6 to 4.9 ml/min). There was good interobserver and intraobserver reliability for the majority of measurements using continuous and pulsatile flow. CONCLUSION: It is feasible to produce a realistic flow phantom model of the neonatal carotid artery of preterm infants. Diameter measurements were underestimated and flow measurements were overestimated. These errors fell within acceptable limits for in vivo measurements. If these limitations were related to materials, this could be explored using a wall-less model. The flow phantom could be utilised for research and training clinicians in measuring cerebral blood flow using the carotid artery in this vulnerable group of infants.

Blood pressure intervention levels in preterm infants: pilot randomised trial.

OBJECTIVE: To examine the feasibility of a trial allocating different blood pressure (BP) intervention levels for treatment in extremely preterm infants. DESIGN: Three-arm open randomised controlled trial performed between February 2013 and April 2015. SETTING: Single tertiary level neonatal intensive care unit. PATIENTS: Infants born <29 weeks' gestation were eligible to participate, if parents consented and they did not have a major congenital malformation. INTERVENTIONS: Infants were randomised to different levels of mean arterial BP at which they received cardiovascular support: active (<30 mm Hg), moderate (

Does antibiotic choice for the treatment of suspected late-onset sepsis in premature infants determine the risk of developing necrotising enterocolitis? A systematic review.

BACKGROUND: Necrotising enterocolitis (NEC) is a significant cause of infant morbidity and mortality, disproportionately affecting those of extreme prematurity and/or very low birth weight. A number of risk factors have been identified, including an association between the use of antibiotics, and the subsequent development of NEC. AIM: This review sought to address whether the choice of antibiotic(s) used to treat infants with suspected late-onset sepsis (LOS) influences the risk of developing NEC. METHODS: A systematic review was performed across Web of Knowledge, Cochrane Library, Ovid Medline, EMBASE and CINAHL databases, up to February 2018, assessing the primary outcome of NEC occurrence, as extracted directly from the published articles. Studies were included if they were randomised control trials (or featured adequate adjustment for confounders); included clear criteria for defining LOS/NEC; and assessed occurrence of NEC in premature infants treated for LOS with intravenous antibiotics. Studies were excluded if non-original, not exclusively featuring premature infants, or where treatment was given for early-onset sepsis only. FINDINGS: 2291 titles and abstracts were identified, of which one study (81 subjects) was suitable for analysis, following screening against eligibility criteria. This suggested a decreased risk of developing definite NEC following treatment with a vancomycin/aztreonam combination, versus a vancomycin/gentamicin regimen (OR = 0·08, 95%CI = 0·00-1·45). CONCLUSION: This systematic review identified one study where the occurrence of NEC was reported in the context of comparing different antibiotic regimens for late onset sepsis and highlights that the type of antibiotic used to treat LOS in preterm infants might be a determinant of the risk of developing NEC. Although it is known that different antibiotic combinations impact the enteric microbiome and that antibiotic exposure is a risk factor for NEC, there is a paucity of well-designed studies that look at the relationship between NEC risk and specific antibiotic exposures.

Early echocardiography does not predict subsequent treatment of symptomatic patent ductus arteriosus in extremely preterm infants.

AIM: To determine whether early echocardiographic ductal parameters identified infants who subsequently received medical or surgical treatment of the patent ductus arteriosus (PDA). METHODS: Infants <29 weeks had PDA size in 2D and colour, flow velocity and patterns obtained on days 1 and 3. Infants were followed up to identify those subsequently receiving treatment for symptomatic PDA by clinicians who were unaware of scan results. Receiver operator characteristics curves and logistic regression were performed. RESULTS: Sixty infants were studied. Mean (SD) gestation and birthweight were 25.8 (1.5) weeks and 817 (190) grams, respectively. Twenty-four (40%) infants received medical treatment, and nine (15%) infants received surgical ligation of PDA at a median age of 12 and 37 days, respectively. PDA size on days 1 and 3, change in ductal size between days 1 and 3, flow pattern/velocity did not predict whether infants subsequently received medical or surgical management of PDA. Using logistic regression, gestation (p = 0.006) was the only factor that predicted whether infants would subsequently receive medical or surgical treatment for PDA in this cohort. CONCLUSION: Echocardiographic ductal parameters on day 1 or 3 did not identify infants who received PDA treatment. Gestation was the most powerful predictor for receiving medical or surgical treatment of PDA.

Investigation of EEG Activity Compared with Mean Arterial Blood Pressure in Extremely Preterm Infants.

BACKGROUND: Cerebral electrical activity in extremely preterm infants is affected by various factors including blood gas and circulatory parameters. OBJECTIVE: To investigate whether continuously measured invasive mean arterial blood pressure (BP) is associated with electroencephalographic (EEG) discontinuity in extremely preterm infants. STUDY DESIGN: This prospective observational study examined 51 newborn infants born <29 weeks gestation in the first 3 days after birth. A single channel of raw EEG was used to quantify discontinuity. Mean BP was acquired using continuous invasive measurement and Doppler ultrasound was used to measure left ventricular output (LVO) and common carotid artery blood flow (CCAF). RESULTS: Median gestation and birthweight were 25.6 weeks and 760 g, respectively. Mean discontinuity reduced significantly between days 1 and 3. EEG discontinuity was significantly related to gestation, pH and BP. LVO and CCAF were not associated with EEG discontinuity. CONCLUSION: Continuously measured invasive mean arterial BP was found to have a negative relationship with EEG discontinuity; increasing BP was associated with lower EEG discontinuity. This did not appear to be mediated by surrogates of systemic or cerebral blood flow. Infants receiving inotropic support had significantly increased EEG discontinuity on the first day after birth.

Newborn infants with bilious vomiting: a national audit of neonatal transport services.

OBJECTIVE: The precautionary approach to urgently investigate infants with bilious vomiting has increased the numbers referred to transport teams and tertiary surgical centres. The aim of this national UK audit was to quantify referrals and determine the frequency of surgical diagnoses with the purpose to inform the consequent inclusion of these referrals in the national 'time-critical' data set. METHODS: A prospective, multicentre UK-wide audit was conducted between 1 August, 2015 and 31 October, 2015. Term infants aged ≤7 days referred for transfer due to bilious vomiting were included. Data at the time of transport and outcomes at 7 days after transfer were collected by the local teams and transferred anonymously for analysis. RESULTS: Sixteen teams contributed data on 165 cases. Teams that consider such transfers as 'time-critical' responded significantly faster than those that do not classify bilious vomiting as time-critical. There was a surgical diagnosis in 22% cases, and 7% had a condition where delayed treatment may have caused bowel loss. Most surgical problems could be predicted by clinical and/or X-ray findings, but two infants with normal X-ray features were found to have a surgical problem. CONCLUSION: The results support the need for infants with bilious vomiting to be investigated for potential surgical pathologies, but the data do not provide evidence for the default designation of such referrals as 'time-critical.' Decisions should be made by clinical collaboration between the teams and, where appropriate, swift transfer provided.

Comparison of Passive and Servo-Controlled Active Cooling for Infants with Hypoxic-Ischemic Encephalopathy during Neonatal Transfers.

Objective The recent availability of servo-controlled cooling equipment on transport makes it possible to commence active cooling at the referral unit for infants with hypoxic-ischemic encephalopathy. This study aimed to compare the temperature and transfer variables in passively and actively cooled babies. Study Design This is a retrospective cohort study comparing two groups-passively cooled (July 2011 to August 2012) versus actively cooled group (September 2012 to June 2013), following introduction of active hypothermia using servo-controlled cooling mattress by the London Neonatal Transfer Service (NTS). Results Seventy-six infants were passively cooled and 69 were actively cooled. There was a significant difference between the temperatures of the two groups at each point in the transfer episode: on arrival of NTS, during stabilization, during transfer, and at the receiving hospital. Median time to achieve target temperature was 30 (95% confidence interval [CI]: 23-37) minutes in actively cooled, significantly shorter in comparison to 130 (95% CI: 83-177) minutes in passively cooled babies. Of the 69 newborns, 62 (90%) had temperature within target range at receiving center in actively cooled group as compared with 30/76 (40%) in passively cooled group. Conclusion The use of active cooling during neonatal transfer achieves target temperature in a shorter period and maintains better temperature stability.

Outcomes of full-term infants with bilious vomiting: observational study of a retrieved cohort.

UNLABELLED: Bilious vomiting in a neonate may be a sign of intestinal obstruction often resulting in transfer requests to surgical centres. The aim of this study was to assess the use of clinical findings at referral in predicting outcomes and to determine how often such patients have a time-critical surgical condition (eg, volvulus, where a delay in treatment is likely to compromise gut viability). METHODS: 4-year data and outcomes of all term newborns aged ≤7 days with bilious vomiting transferred by a regional transfer service were analysed. Specificity, sensitivity, likelihood ratios, correlations, prior and posterior probability of clinical findings in predicting newborns with surgical diagnosis were calculated. RESULTS: Of 163 neonates with bilious vomiting, 75 (46%) had a surgical diagnosis and 23 (14.1%) had a time-critical surgical condition. The diagnosis of a surgical condition in neonates with bilious vomiting was significantly associated with abdominal distension (χ(2)=5.17, p=0.023), abdominal tenderness (χ(2)=5.90, p=0.015) and abnormal abdominal X-ray findings (χ(2)=5.68, p=0.017) but not with palpation findings of a soft as compared with a tense abdomen (χ(2)=3.21, p=0.073). Abnormal abdominal X-ray, abdominal distension and tenderness had 97%, 74% and 62% sensitivity, respectively, with regard to association with an underlying surgical diagnosis. Normal abdominal X-ray reduced the posterior probability of surgical diagnosis from 50% to 16%. Overall, clinical findings at referral did not differentiate between infants with or without surgical or time-critical condition. CONCLUSIONS: We recommend that term neonates with bilious vomiting referred for transfer are prioritised as time critical.

Feeding infants below 29 weeks' gestation with abnormal antenatal Doppler: analysis from a randomised trial.

OBJECTIVE: To describe feeding and gastrointestinal outcomes in growth-restricted infants <29 weeks' gestation and to determine the rate of feed advancement which they tolerate. DESIGN: Analysis of prospectively collected data from a randomised feeding trial, the Abnormal Doppler Enteral Prescription Trial (ADEPT). SETTING: 54 neonatal units in the UK and Ireland. PARTICIPANTS: 404 preterm, growth-restricted infants with abnormal antenatal Doppler studies from ADEPT. 83 infants <29 weeks and 312 infants ≥ 29 weeks' gestation were included in this analysis. INTERVENTIONS: In ADEPT, infants were randomised to start milk 'early' on day 2 after birth, or 'late' on day 6. Subsequent feed advancement followed a regimen, which should have achieved full feeds by day 16 in the early and day 20 in the late group. MAIN OUTCOME MEASURES: Full feeds were achieved later in infants <29 weeks; median age 28 days {IQR 22-40} compared with 19 days {IQR 17-23} in infants ≥ 29 weeks (HR 0.35, 95% CI 0.3 to 0.5). The incidence of necrotising enterocolitis was also higher in this group; 32/83 (39%) compared to 32/312 (10%) in those ≥ 29 weeks (RR 3.7, 95% CI 2.4 to 5.7). Infants <29 weeks tolerated very little milk for the first 10 days of life and reached full feeds 9 days later than predicted from the trial regimen. CONCLUSIONS: Growth-restricted infants born <29 weeks' gestation with abnormal antenatal Doppler failed to tolerate even the careful feeding regimen of ADEPT. A slower advancement of feeds may be required for these infants. TRIAL REGISTRATION NUMBER: ISRCTN87351483.

A toolkit for monitoring hospital-acquired bloodstream infection in neonatal intensive care.

OBJECTIVE: In neonatal intensive care units (NICUs), monitoring hospital-acquired bloodstream infection (BSI) is critical to alert clinicians to variations in the incidence of infection between units and over time. We demonstrate a toolkit of monitoring techniques that account for case mix and could be implemented using routinely available clinical data. This toolkit could enable quality of care comparisons between hospitals to facilitate the sharing of improved practices. DESIGN: Prospective study over 4 years. SETTING AND PATIENTS: Babies admitted to 2 tertiary London NICUs. METHODS: We derived expected numbers of BSI episodes using a Poisson regression risk model adjusting for variations in birth weight, transfers to the NICU from other hospitals, postnatal age, and days spent at each National Health Service level of care. We compared observed and expected numbers of BSI episodes using 2 monitoring techniques: standardized infection ratios (SIRs) and the sequential probability ratio test (SPRT). RESULTS: Using the SIR method, observed BSI incidence increased over expected incidence in 2002 at both NICUs, but this increase did not reach statistical significance at the 1% level. Using the SPRT method, neither unit showed a clinically important increase or decrease, defined as a 30% deviation from expected incidence. CONCLUSIONS: Risk-adjusted BSI monitoring can be performed using routine hospital data. NICUs could use SIRs for an annual look back at infection incidence and SPRTs for prospective, quarterly monitoring. The SIR and the SPRT methods have different strengths, and both could help clinicians improve infection control and patient care in NICUs.

Early or delayed enteral feeding for preterm growth-restricted infants: a randomized trial.

BACKGROUND: Growth-restricted preterm infants are at increased risk of developing necrotizing enterocolitis (NEC) and initiation of enteral feeding is frequently delayed. There is no evidence that this delay is beneficial and it might further compromise nutrition and growth. METHODS: Infants with gestation below 35 weeks, birth weight below the 10th centile, and abnormal antenatal umbilical artery Doppler waveforms were randomly allocated to commence enteral feeds "early," on day 2 after birth, or "late," on day 6. Gradual increase in feeds was guided by a "feeding prescription" with rate of increase the same for both groups. Primary outcomes were time to achieve full enteral feeding sustained for 72 hours and NEC. RESULTS: Four hundred four infants were randomly assigned from 54 hospitals in the United Kingdom and Ireland (202 to each group). Median gestation was 31 weeks. Full, sustained, enteral feeding was achieved at an earlier age in the early group: median age was 18 days compared with 21 days (hazard ratio: 1.36 [95% confidence interval: 1.11-1.67]). There was no evidence of a difference in the incidence of NEC: 18% in the early group and 15% in the late group (relative risk: 1.2 [95% confidence interval: 0.77-1.87]). Early feeding resulted in shorter duration of parenteral nutrition and high-dependency care, lower incidence of cholestatic jaundice, and improved SD score for weight at discharge. CONCLUSIONS: Early introduction of enteral feeds in growth-restricted preterm infants results in earlier achievement of full enteral feeding and does not appear to increase the risk of NEC.

Identification of bacteria and potential sources in neonates at risk of infection delivered by Caesarean and vaginal birth.

Neonatal gastric aspirates (NGA) are routinely screened in UK hospitals to investigate fetal/neonatal infections associated with cases of adverse pregnancy outcome (APO). The aim of this study was to describe and compare the microbiology of NGA from Caesarean and vaginal deliveries using molecular methods, and to evaluate other possible clinical and non-clinical variables that may have determined the presence of the bacteria in the samples. The value of using NGA and molecular methods to investigate potential pathogens associated with the risk of early infection was also evaluated. Bacteria were identified by a combined molecular approach on the basis of the 16S rRNA gene using both clone analysis and denaturing gradient gel electrophoresis. A total of 43 and 34 different species were identified in the vaginal (n = 121) and Caesarean (n = 119) deliveries, respectively; 26 of the species observed (51 %) were common to both modalities, although usually less prevalent in the Caesarean cases. Multivariate analysis confirmed an association between infection and prolonged rupture of membranes in vaginal deliveries (odds ratio = 5.7, 95 % confidence interval = 1.1-29.0). Various associations between infection and given variables were also shown, including labour, intrapartum antibiotic prophylaxis, and time and place of sample collection. The molecular methods allowed identification of a range of bacteria and potential sources not previously observed in NGA, including possible genito-urinary, gastrointestinal and oral pathogens. NGA represents a valuable sample for investigating potential pathogens associated with APO and the risk of early infection in neonates using molecular methods.

The use of molecular techniques for bacterial detection in the analysis of gastric aspirates collected from infants on the first day of life.

UNLABELLED: Prospective service evaluation of the utility of molecular methods to analyse neonatal gastric aspirate specimens in a single neonatal unit and associated maternity unit. 43 newborn infants investigated for sepsis with median gestational age of 39 weeks (range 31-41 weeks) and median birth weight 3050 grams (range 1250-4220 g). Gastric aspirates routinely collected within 12h of birth were analysed using conventional and molecular methods for bacterial detection, bacterial DNA load and sequencing to identified bacterial species. RESULTS: Bacterial DNA loads varied from 0.03 to 1736 pg/microl of DNA extract (1 microl of DNA extract equivalent to 4 microl gastric aspirate). Bacteria were identified in 30/43 (70%) of samples by molecular methods and 10/43 (23.3%) of samples by culture. Cultures were only positive when the bacterial DNA exceeded 4.5 pg/microl of extract. Infants with prolonged rupture of membranes (>24h prior to delivery) had a DNA load on average 23 times higher than those without (95%CI 3.7 to 141; p=0.001). Additional bacteria detected by molecular methods included many species that are fastidious and potentially pathogenic including Leptotrichia spp., Serratia spp., Ureaplasma spp., Veillonella spp., Haemophilus influenzae and Group B Streptococcus. Due to a low rate of adverse outcomes it was not possible to correlate bacterial identifications or DNA load with infant outcome. CONCLUSIONS: Molecular methods can identify bacteria from a greater proportion of gastric aspirate specimens that conventional culture. Further work is required to establish whether this information can be used to improve infant outcomes.