Peter W Fowlie

Prophylactic indomethacin for preterm infants: a systematic review and meta-analysis

Background: Rates of long term morbidity remain unacceptably high in infants surviving after preterm birth. Prophylactic indomethacin has been shown to effectively reduce the rate of intraventricular haemorrhage in this group but there is the potential for unwanted side effects because of reduced organ perfusion. Objective: To examine the effect of prophylactic indomethacin on mortality and short and long term morbidity of preterm infants. Data sources: Medline (1966–2002), the Cochrane Controlled Trials Register and abstracts of the Society for Pediatric Research and the European Society for Pediatric Research were searched independently by both authors. Review methods: Trials were included if they used a randomised design, enrolled preterm infants given intravenous indomethacin within 24 hours of birth, and reported any of the prespecified outcome measures. Each author extracted data and assessed trial quality independently, according to the methods of the Cochrane Collaboration. Data were combined in a meta-analysis where appropriate. Results: Nineteen trials fulfilling the inclusion criteria were identified, of which four reported long term outcomes. Short term benefits of indomethacin were identified, including a reduction in the rate of severe intraventricular haemorrhage (relative risk (RR) 0.66 (95% confidence interval (CI) 0.53 to 0.82)) and the need for surgical ligation of a patent ductus arteriosus (RR 0.51 (95% CI 0.37 to 0.71)). No evidence of short term gastrointestinal or renal adverse effects was detected. There was no significant difference between indomethacin and control groups with respect to the important long term outcome of death or severe neurosensory impairment (RR 1.02 (95% CI 0.90 to 1.15)). Conclusions: Prophylactic indomethacin has a number of short term benefits for the preterm infant but there is no evidence to suggest that it results in an improvement in the rate of survival free of disability.

Communicating with parents on the neonatal unit

Should we be doing more than just talking?

Measurement properties of the Clinical Risk Index for Babies-Reliability, validity beyond the first 12 hours, and responsiveness over 7 days

OBJECTIVES Clinical Risk Index for Babies (CRIB) is a simple instrument used to measure clinical risk and illness severity in very low birth-weight infants. We assessed its reliability, validity beyond the first 12 hrs after birth, and responsiveness to individual change in condition after 7 days. DESIGN Cohort study. SETTING Three tertiary and three nontertiary UK hospitals. PATIENTS Three hundred ninety-eight infants whose birth weight was <1501 g or who were born before a 31-wk gestation period. INTERVENTIONS Inter- and intrarater reliability of data extraction were assessed by Pearson and intraclass correlation. To validate CRIB, we tested the correlation between clinical risk and illness severity with the risk of: a) death; b) prolonged treatment with supplemental oxygen; and c) disability at 2 yrs. Logistic regression models were fitted to assess validity and responsiveness. MEASUREMENTS AND MAIN RESULTS Reliability coefficients ranged from 0.76 (95% confidence interval, 0.71 to 0.81) to 0.97 (0.94 to 1.00). Throughout the first week, CRIB correlated with the risk of death (p < .001), prolonged treatment with oxygen (p < .001), and disability (p < .001 to p = .033). Improved condition, represented by a reduction in CRIB within the first week, was independently associated with lower risks of each adverse outcome, p < .05. CONCLUSIONS During the first week, CRIB was reliable, valid, and responsive. These properties support the use of CRIB in the stratification of infants by risk and illness severity in cohort studies, and they also indicate that CRIB may have the potential to be used in other ways in the future.

Predicting outcome in very low birthweight infants using an objective measure of illness severity and cranial ultrasound scanning

AIM To investigate the feasibility of developing an objective tool for predicting death and severe disability using routinely available data, including an objective measure of illness severity, in very low birthweight babies. METHOD A cohort study of 297 premature babies surviving the first three days of life was made. Predictive variables considered included birthweight, gestation, 3 day cranial ultrasound appearances and 3 day CRIB (clinical risk index for babies) score. Models were developed using regression techniques and positive predictive values (PPV) and likelihood ratios (LR) were calculated. RESULTS On univariate analysis, birthweight, gestation, 3 day CRIB score and 3 day cranial ultrasound appearances were each associated with death. On multivariate analysis, 3 day CRIB score and 3 day cranial ultrasound appearances remained independently associated. A 3 day CRIB score > 4 along with intraventricular haemorrhage (IVH) grade 3 or 4 was associated with a PPV of 64% and an LR of 9.8 (95% confidence limits 3.5, 27.9). Only 3 day CRIB score and 3 day cranial ultrasound appearances were associated with severe disability on univariate analysis. Both remained independently associated on multivariate analysis. A 3 day CRIB score > 4 along with an IVH grade of 3 or 4 was associated with a PPV of 60% and an LR of 24.2 (95% CI 4.4, 133.3). CONCLUSION Incorporating objective measures of illness severity may improve current prediction of death and disability in premature infants.

CRIB (clinical risk index for babies) in relation to nosocomial bacteraemia in very low birthweight or preterm infants.

Positive blood cultures in very low birthweight or preterm infants usually reflect bacteraemia, septicaemia, or failure of asepsis during sampling and lead to increased costs and length of stay. Rates of nosocomial, or hospital acquired, bacteraemia may therefore be important indicators of neonatal unit performance, if comparisons are adjusted for differences in initial risk. In a preliminary study the risk of nosocomial bacteraemia was related to initial clinical risk and illness severity measured by the clinical risk index for babies (CRIB). Nosocomial bacteraemia was defined as clinically suspected infection with culture of bacteria in blood more than 48 hours after birth. One or more episodes of nosocomial bacteraemia were identified retrospectively in 36 of 143 (25%) infants in a regional neonatal unit between 1992 and 1994. Biologically plausible models were developed using regression analysis techniques. After correcting for period at risk, nosocomial bacteraemia was independently associated with gestation at birth and CRIB. Death was independently associated with CRIB, but not with nosocomial bacteraemia. CRIB may contribute, with other explanatory variables, to more comprehensive predictive models of death and nosocomial infection. These may facilitate future risk adjusted comparative studies between groups of neonatal units.

What has the Cochrane Collaboration ever done for newborn infants

The Cochrane Library is a regularly-updated source of evidence-based reviews to guide clinical care practices. Over the past 15 years, clinicians and consumers have collaborated to generate several hundred Cochrane reviews of a range of therapies relevant to pregnancy and perinatal health. By meta-analysing data from several trials, Cochrane reviews generate more precise estimates of the benefit of important interventions. This technique has also proved useful for defining the harmful effect of interventions which individual trials were not powered to detect. Cochrane reviews have also been used to inform future research strategies- several recent large trials have been developed because a Cochrane review had highlighted the paucity of available evidence to guide practice. Over the next decade, on-going challenges for the Cochrane Collaboration include the need to develop more user-friendly interfaces and to extend the relevance of reviews to perinatal care practices in low-income settings.

Obstetric issues in preterm birth.

Predicting and preventing preterm labour and choosing the safest method of delivery are important challenges in reducing the number of preterm births and improving outcomes for mother and baby. This article covers the predictive tests, methods of prevention, maternal and fetal indications for preterm birth, and various approaches to delivery. Most preterm deliveries follow spontaneous onset of preterm labour or preterm prelabour rupture of the amniotic membranes (pPROM). Much work has been done (with limited success) to find diagnostic tests that predict accurately if a woman who is at risk of preterm delivery will go on to deliver preterm. For these women, who may have a history of preterm birth or clinical signs of preterm labour, such tests would allow early and targeted use of antenatal interventions. These interventions, especially antenatal corticosteroids, improve neonatal and long term outcomes for preterm infants. View this table: Antenatal corticosteroids The most common clinical tests used to determine the risk of preterm labour are transvaginal sonography (to measure the length of the endocervix) and the cervicovaginal fetal fibronectin test. These tests have high negative predictive values—that is, if results are negative then the women probably will not progress to preterm delivery. Although there does not seem to be a role for routine use of the fibronectin test or transvaginal sonography to screen women for preterm birth, women thought to be at high risk can be reassured by negative results. This may help women to avoid unnecessary interventions such as antenatal transfer to a distant perinatal unit. View this table: Cervicovaginal fetal fibronectin test Current medical approaches to preventing preterm labour include the use of tocolytic drugs, antibiotic treatment, and cervical cerclage. ### Tocolytic drugs Tocolytic drugs can delay the progress of preterm labour in the short term but maternal side effects include hypotension, …

Withdrawing and withholding treatment: comments on new guidelines

A new practice framework for clinicians has recently been issued by the Royal College of Paediatrics and Child Health through their Ethics Advisory Committee.1 It deals with babies and children for whom intensive treatment may not be in their best interest. These are difficult cases. Absolute certainty is rarely possible; there are inevitably issues of conscience and conflict, which add to the burden individuals carry. Do the RCPCH guidelines address the concerns of doctors and nurses at the cotside? Will they be of practical help? The guidelines are based on evidence from experts, and discussion by carefully selected focus groups, both useful ways to further thinking on a subject. But these methods lack the rigour of empirical data collected by scientific research. Does research evidence confirm expert opinion? If it does, the guidelines will carry greater weight. We looked at the RCPCH document in relation to the expressed concerns and stresses of staff who work in neonatal intensive care units. In a recent survey2 we carried out in depth interviews with 57 doctors and 119 nurses currently employed in six neonatal intensive care units in Scotland. The units were selected to reflect different geographical, cultural, and social factors; the sample was stratified to represent all grades and levels of experience. In principle, the RCPCH guidelines do address most of the issues that concern clinicians, but we highlight five areas that warrant further discussion. Time and again the RCPCH document refers to the need to listen carefully to all those participating in the care of the child. The …

Foot orthoses in children with juvenile idiopathic arthritis: a randomised controlled trial

Introduction There is limited evidence supporting the podiatric treatment of children with juvenile idiopathic arthritis (JIA). This multicentre randomised controlled trial aimed to determine whether preformed foot orthoses (FOs) impacted on pain and quality of life (QoL) in children with JIA. Methods Eligible children were randomised to receive either ‘fitted’ FOs with customised chair-side corrections or ‘control’ FOs made without corrections. Changes in pain and QoL were measured using a visual analogue scale and Paediatric Quality of Life questionnaire, respectively. JIA children were assessed at baseline, 3 months and 6 months. Results 60 children were recruited. 179 out of a possible 180 assessments (99.4%) were completed. A statistically significant greater difference in pain reduction (baseline—6 months) was seen between the two groups favouring fitted FOs (p=0.029). The reduction in pain in the fitted FOs group was clinically important (8 mm). Significant differences in QoL favouring fitted FOs were also identified as measured by the children and independently by their parents/carers. Conclusions Fitted FOs may reduce pain and improve QoL in selected children with JIA. Trial registration number NCT02001844.

Bridging the gaps: getting evidence into practice

See related research article by Lee and colleagues, page [469][1] During the early 1990s, adoption of key evidence-based interventions for the care of very preterm (< 32 weeks’ gestation) neonates substantially improved outcomes in this group. In particular, the use of antenatal corticosteroid