Julie-Clare Becher

Neonatal research: the parental perspective

Objectives: To investigate the recollections of parents consenting for their infants to be research subjects and determine their views about the need for consent. Subjects: Parents of 154 sick newborn infants enrolled in a randomised trial in the early neonatal period. All parents had given written consent and received printed information. Methods: A questionnaire and accompanying letter was sent to the parental home 18 months later. Non-responders were sent a further questionnaire and letter. Results: Response rate was 64% (99/154). Some respondents (12%) did not remember being asked to consent to their baby joining a study, and a further 6% were unsure. Most of the respondents (79%) were happy, 13% neutral, and 8% unhappy with their decision to give consent. None felt heavy pressure to agree. Entering the trial caused 24% of respondents to feel more anxious, 56% neutral, and 20% less anxious about their baby. Most of the respondents (83%) would be unhappy to forgo the consent process for trials passed by the institutional ethics committee. Conclusions: A significant proportion of parents who give written consent for a trial in the early neonatal period do not later remember having done so. Parents who have had experience of neonatal research would be unhappy for their baby to be enrolled in a study that had ethics committee approval without their consent being obtained.

Clinical Diagnosis of Pneumothorax Is Late: Use of Trend Data and Decision Support Might Allow Preclinical Detection

Pneumothorax in the newborn has a significant mortality and morbidity. Early diagnosis would be likely to improve the outlook. Forty-two consecutive cases of pneumothorax that developed after admission to a tertiary referral neonatal medical intensive care unit over 4 y from 1993 to 1996 were reviewed. The time of onset of the pneumothorax was determined by retrospective evaluation of the computerized trend of transcutaneous carbon dioxide (tcpCO2) and oxygen tensions. The timing of the occurrence in the notes and x-rays determined the time of clinical diagnosis noted at the time. The difference was the time the condition was undiagnosed. The overall mortality before discharge was 45% (19cases), four patients succumbing within 2 h. The median time (range) between onset of pneumothorax and clinical diagnosis was 127 min (45–660 min). In most cases, the endotracheal tube was aspirated and the transcutaneous blood gas sensor was repositioned, and in at least 40% of the cases, the baby was reintubated before the diagnosis was made. Reference centiles were constructed for level of tcpCO2 and slope of the trended tcpCO2 over various time intervals (in minutes) from 729 infants from 23 to 42 wk gestation who needed intensive care during the first 7 d of life from the same time period. The 5-min tcpCO2 trend slopes were compared in index and matched control infants. The presence of five consecutive and overlapping 5-min slopes greater than the 90th centile showed good discrimination for a pneumothorax (area under the receiver operating characteristic curve, 89%). We concluded that 1) the clinical diagnosis of pneumothorax was late, occurring when infants decompensate;2) trend monitoring of tcpCO2 might allow the diagnosis to be made earlier if used properly; and 3) use of reference centiles of the trended slopes of tcpCO2 might be used for automatic decision support in the future.

Unexpected collapse in apparently healthy newborns--a prospective national study of a missing cohort of neonatal deaths and near-death events.

Background Sudden and unexpected postnatal collapse (SUPC) of a healthy newborn infant is a rare event, which carries a high risk of mortality and significant neurodisability in survivors. An underlying condition can be found in 60% of cases who undergo detailed postmortem but in the remainder there are important associations with prone position, breast feeding and primiparous status. The authors undertook a prospective study to ascertain the population incidence of SUPC in the UK. Methods Cases were referred through the British Paediatric Surveillance Unit reporting scheme over a 13-month period. Infants were at ≥37 weeks of gestation, had an Apgar score of ≥8 at 5 min, collapsed within 12 h in hospital requiring positive pressure ventilation and either died or received ongoing intensive care. Data were collected on maternal and infant characteristics, clinical investigations and 1-year outcome. Findings 45 cases were reported, an incidence of 0.05/1000 live births of whom 12 infants died. In 15/45 infants, an underlying disease/abnormality was determined. In 30/45 cases (0.035/1000 live births), no such cause was found, but in 24, the clinical/pathological diagnosis was airway obstruction during breast feeding or in prone position. Mothers were commonly primiparous and unattended by clinical staff before collapse was recognised. Approach to investigation was highly disparate and frequently very limited. Of the 30 infants with no underlying disease/abnormality, 22 (73%) developed a postasphyxial encephalopathy and 10 had a poor outcome (33%) – 5 died and 5 had neurological sequelae at 1 year. Interpretation SUPC is rare in any one centre and there is no standard approach to investigation. In those cases where collapse is not due to an underlying abnormality, breast feeding and prone position are important associations. Guidelines for safe postnatal care of infants should include appropriate vigilance of infants particularly where mothers are primiparous or where ability to assess the baby may be impaired.

The Scottish perinatal neuropathology study: clinicopathological correlation in early neonatal deaths

Background: A proportion of neonatal deaths from asphyxia have been shown to be associated with pre-existing brain injury. Objectives: (a) To compare the epidemiology of infants displaying signs of birth asphyxia with those not showing signs; (b) to examine the neuropathology and determine if possible the timing of brain insult comparing asphyxiated with non-asphyxiated infants; (c) to compare the clinical features of those born with birth asphyxia with and without pre-labour damage. Methods: Over a two year period, all 22 Scottish delivery units collected clinical details on early neonatal deaths. Requests for post mortem included separate requests for detailed neuropathological examination of the brain. Infants were classified into two groups: birth asphyxia and non-birth asphyxia. Clinicopathological correlation was used to attempt to define the time of brain insult. Results: Detailed clinical data were available on 137 of 174 early neonatal deaths that met the inclusion criteria. Seventy of 88 parents who had agreed to post mortem examination consented to a detailed examination of additional samples from the brain; in 53 of these cases the infant was born in an asphyxiated condition. All asphyxiated and encephalopathic infants, 38% of mature and 52% of preterm infants with features of birth asphyxia but without encephalopathy, and only one of 12 infants without any signs of birth asphyxia showed damage consistent with onset before the start of labour. Conclusions: In a large proportion of neonatal deaths, brain injury predates the onset of labour. This is more common in infants born in an asphyxiated condition.

Expertise and the interpretation of computerized physiological data: implications for the design of computerized monitoring in neonatal intensive care

This paper presents the outcomes from a cognitive engineering project addressing the design problems of computerized monitoring in neonatal intensive care. Cognitive engineering is viewed, in this project, as a symbiosis between cognitive science and design practice. A range of methodologies has been used: interviews with neonatal staff, ward observations and experimental techniques. The results of these investigations are reported, focusing specifically on the differences between junior and senior physicians in their interpretation of monitored physiological data. It was found that the senior doctors made better use of the different knowledge sources available than the junior doctors. The senior doctors were able to identify more relevant physiological patterns and generated more and better inferences than did their junior colleagues. Expertise differences are discussed in the context of previous psychological research in medical expertise. Finally, the paper discusses the potential utility of these outcomes to inform the design of computerized decision support in neonatal intensive care.

The Scottish Perinatal Neuropathology Study—clinicopathological correlation in stillbirths

Objective  To examine the neuropathology of fetuses dying before birth, to determine the timing of any brain damage seen and to ascertain clinical associations of pre‐existing brain damage.

The distribution of apolipoprotein E alleles in Scottish perinatal deaths

Background: The apolipoprotein E (ApoE) polymorphism has been well studied in the adult human population, in part because the e4 allele is a known risk factor for Alzheimer’s disease. Little is known of the distribution of ApoE alleles in newborns, and their association with perinatal brain damage has not been investigated. Methods: ApoE genotyping was undertaken in a Scottish cohort of perinatal deaths (n = 261), some of whom had prenatal brain damage. The distribution of ApoE alleles in perinatal deaths was compared with that in healthy liveborn infants and in adults in Scotland. Results: ApoE e2 was over-represented in 251 perinatal deaths (13% v 8% in healthy newborns, odds ratio (OR) = 1.63, 95% confidence interval (CI) 1.13 to 2.36 and 13% v 8% in adults, OR = 1.67, 95% CI 1.16 to 2.41), both in liveborn and stillborn perinatal deaths. In contrast, the prevalence of ApoE e4 was raised in healthy liveborn infants (19%) compared with stillbirths (13%, OR = 1.59, 95% CI 1.11 to 2.26) and with adults (15%, OR = 1.35, 95% CI 1.04 to 1.76). However, no correlation was found between ApoE genotype and the presence or absence of perinatal brain damage. Conclusions: This study shows a shift in ApoE allelic distribution in early life compared with adults. The raised prevalence of ApoE e2 associated with perinatal death suggests that this allele is detrimental to pregnancy outcome, whereas ApoE e4 may be less so. However, ApoE genotype did not appear to influence the vulnerability for perinatal hypoxic/ischaemic brain damage, in agreement with findings in adult brains and in animal models.

Is intrapartum asphyxia preventable

The contribution of intrapartum events to asphyxia‐related mortality and morbidity and the degree to which it may be prevented are controversial. We examined trends in asphyxia‐related mortality and morbidity in a single large regional perinatal centre. Between 1994 and 2005, the rate of asphyxia fell from 2.86/1000 births in 1994 to 0.91/1000 births in 2005 (P < 0.001). Hypoxic‐ischaemic encephalopathy of all grades fell from 2.41 to 0.77/1000 live births (P < 0.001). This substantial and steady fall in the rate of asphyxia‐related mortality and morbidity over a 12‐year period suggests that a significant proportion of cases of intrapartum asphyxia may be preventable.

Provision of servo-controlled cooling during neonatal transport

Introduction Therapeutic hypothermia is a time critical intervention for infants who have experienced a hypoxic–ischaemic event. Previously reported methods of cooling during transport do not demonstrate the same stability achieved in the neonatal unit. The authors developed a system which allowed provision of servo-controlled cooling throughout transport, and present their first years experience. Methods Retrospective review of routinely collected patient data. Results 14 out-born infants were referred for cooling during a 12-month period. Nine infants were managed with the servo-controlled system during transport. Cooling was commenced in all infants before 6 h of life. Median time from team arrival to the infant having a temperature in the target range (33–34°C) was 45 min. Median temperature during transfer was 33.5°C (range 33–34°C). Temperature on arrival at the cooling centre ranged from 33.4°C to 33.8°C. Conclusion Servo-controlled cooling during transport is feasible and provides an optimal level of thermal control.

Who is blaming the baby

FIGURE 6. TRAILshort is both necessary and sufficient to cause TRAIL resistance. (A) Jurkat T cells, which constitutively express TRAILshort, were induced to die by the addition of sk-TRAIL, in the presence or absence of increasing amounts of anti-TRAILshort Ab. Cell death was measured by active caspase-3 staining. Control cells were treated with increasing anti-TRAILshort Ab alone. (B) HeLa cells, which do not express TRAILshort, were stimulated to die by the addition of sk-TRAIL in the absence or presence of increasing amounts of a fusion protein consisting of the extracellular domain of TRAILshort fused to Fc (TRAILshort-ECD:Fc) or with BSA control and analyzed as in (A). Additional control cells were treated with increasing TRAILshort-ECD:Fc alone. Data are representative of six independent experiments. p , 0.05 considered statistically significant (linear regression).Sudden unexplained collapse within the first 12 h of life is a rare but recognised event. Over a 2-year period, five infants, previously assessed as healthy, were found collapsed in our maternity unit in the care of their primiparous mothers. Two were found prone on their mother’s chest, and two were in their mother’s bed. The outcomes were poor, with four neonatal deaths and one death at 18 months. The rate of sudden unexplained neonatal collapse was 0.4 per 1000 live births. No cause for collapse was identified despite extensive investigations, which included postmortem in all the neonatal deaths. One infant, however, showed widespread antenatal brain damage at postmortem. It is postulated that some infants with an underlying vulnerability may maladapt to extrauterine life following an hypoxic stressor possibly caused by positional airway obstruction.