Top 10 research priorities for congenital diaphragmatic hernia in Australia: James Lind Alliance Priority Setting Partnership.

OBJECTIVES: The Gaps in the Congenital Diaphragmatic Hernia (CDH) Journey Priority Setting Partnership (PSP) was developed in collaboration with CDH Australia, James Lind Alliance (JLA) and the Murdoch Children's Research Institute to identify research priorities for people with CDH, their families and healthcare workers in Australasia. DESIGN: Research PSP in accordance with the JLA standardised methodology. SETTING: Australian community and institutions caring for patients with CDH and their families. PATIENTS: CDH survivors, families of children born with CDH (including bereaved) and healthcare professionals including critical care physicians and nurses (neonatal and paediatric), obstetric, surgical, allied health professionals (physiotherapists, speech pathologists and speech therapists) and general practitioners. MAIN OUTCOME MEASURE: Top 10 research priorities for CDH. RESULTS: 377 questions, from a community-based online survey, were categorised and collated into 50 research questions. Through a further prioritisation process, 21 questions were then discussed at a prioritisation workshop where they were ranked by 21 participants (CDH survivors, parents of children born with CDH (bereaved and not) and 11 multidisciplinary healthcare professionals) into their top 10 research priorities. CONCLUSION: Stakeholders' involvement identified the top 10 CDH-related research questions, spanning from antenatal care to long-term functional outcomes, that should be prioritised for future research to maximise meaningful outcomes for people with CDH and their families.

Developmental care education in Australian surgical neonatal intensive care units: A cross-sectional study of nurses' perceptions.

Background: Nurse perceptions of developmental care practices have been researched globally for almost 30 years. Yet, there is a lack of research exploring this subject in the specialised setting of the surgical neonatal intensive care unit (sNICU). This research explores the effect of developmental care education programs on sNICU nurses' perceptions of developmental care. Objective: To determine perceptions and attitudes towards developmental care in a specialty neonatal setting. Design: Cross-sectional study. Settings: Two surgical neonatal intensive care units in Australia. Participants: Registered nurses permanently employed at the study sites between May 2021 to April 2022. Methods: A modified electronic survey explored sNICU nurse perceptions of developmental care organised around three themes: effects of developmental care on parents and infants, application of developmental care, and unit practices. Associations between site, nurse characteristics, developmental care education and nurses' perceptions were explored using logistic regression [odds ratios (OR) and 95 % confidence intervals (CI)]. Results: Of 295 sNICU nurses, 117 (40 %) participated in the survey. Seventy-five percent of respondents had attended a formal developmental care education program. High levels of agreement (>90 %) were reported regarding the benefits of developmental care for parents and infants. Exposure to developmental care education influenced perceptions of its application. Nurses without formal developmental care education were more likely to agree that it was consistently applied [OR:3.3, 95%CI:1.3-8.6], developmental care skills are valued [OR:2.7, 95%CI:1.1-6.8], and that their nursing peers offered support in its application ([OR:2.5, 95%CI:1.1-6.2]. Conclusions: The results from our research suggest sNICU nurses have a high level of awareness of developmental care and its positive impacts. Despite differences between the surveyed units' developmental care education programs, the value of developmental care in reducing stress for infants and supporting families was collectively recognised. Future research in this setting should focus on evaluating the application of developmental care in this setting.

360-degree phenomenology: A qualitative approach to exploring the infant experience of hospitalisation in neonatal intensive care.

This paper describes the development and justification of a qualitative methodology aimed at exploring the infant's personal experience of hospitalisation in the neonatal intensive care unit (NICU). We begin by briefly reviewing existing methods for documenting and recording infant experiences. These methods focus on the clinical needs of the infant predominantly through quantifiable medical outcome data. Research understanding their experience of receiving clinical care is lacking. By exploring newborn infant behaviour, cues, and communication strategies we assert the infant as a capable participant in neonatal research. We then describe the methodology and methods which we have named 360-degree phenomenology that draws directly from the capabilities and knowledge of the infants themselves. We propose this methodology will address the gap in the literature by enabling a rich and comprehensive overview of the early life experiences of infants hospitalised in NICU.

Growth from infancy to adulthood and associations with cardiometabolic health in individuals born extremely preterm.

Background: Few studies have tracked growth in children born extremely preterm (EP, <28 weeks' gestation) beyond late adolescence. The relationships between growth parameters (including weight and BMI) through childhood and adolescence with later cardiometabolic health, are unclear in those born EP. We aimed to (i) compare growth from 2 to 25 years between EP and controls; and in the EP group (ii) determine the associations of growth parameters with cardiometabolic health. Methods: Prospective state-wide cohort of all EP livebirths in Victoria, Australia, in 1991-1992 and contemporaneous term-born controls. Z-scores for weight (z-weight), height (z-height) and BMI (z-BMI) at 2, 5, 8, 18 and 25 years, and cardiometabolic health at 25 years (body composition, glucose tolerance, lipid profiles, blood pressure, exercise capacity) were measured. Growth trajectories were compared between groups using mixed models. The relationships between z-BMI changes/year, and being overweight at different ages, with cardiometabolic health were explored using linear regression. Findings: Z-weight and z-BMI were lower in EP than controls, but the gap decreased with age due to a more rapid rate of rise in z-weight and a decrease in z-height in the EP group compared with controls. Greater increases in z-BMI/year in the EP group were associated with poorer cardiometabolic health [coefficient (95% CI) per 0.1 z-BMI increase/year: visceral fat volume (cm3) 217.8 (160.9, 274.7), triglycerides (mmol/L) 0.45 (0.20, 0.71), systolic blood pressure (mmHg) 8.9 (5.8, 12.0), and exercise capacity (BEEP test maximum level -1.2 (-1.7, -0.7)), all p < 0.001]. The association between being overweight with poorer cardiometabolic health strengthened with age. Interpretation: The catch-up in weight and BMI by young adulthood in survivors born EP may not be desirable as it is associated with poorer cardiometabolic health. The associations of being overweight from mid-childhood with poorer cardiometabolic health may provide a window for intervention. Funding: National Health and Medical Research Council of Australia.

Trends in survival, perinatal morbidities and two-year neurodevelopmental outcomes in extremely low-birthweight infants over four decades.

BACKGROUND: Although outcomes for infants born extremely low birthweight (ELBW; <1000 g birthweight) have improved over time, it is important to document survival and morbidity changes following the advent of modern neonatal intensive care in the 1990s. OBJECTIVE: To describe trends in survival, perinatal outcomes and neurodevelopment to 2 years' corrected age over time across six discrete geographic cohorts born ELBW between 1979 and 2017. METHODS: Analysis of data from discrete population-based prospective cohort studies of all live births free of lethal anomalies with birthweight 500-999 g in the state of Victoria, Australia, over 6 eras: 1979-80, 1985-87, 1991-92, 1997, 2005 and 2016-17. Perinatal data collected included survival, duration and type of respiratory support, neonatal morbidities and two-year neurodevelopmental outcomes. RESULTS: More ELBW live births were inborn (born in a maternity hospital with a neonatal intensive care unit) over time (1979-80, 70%; 2016-17, 84%), and more were offered active care (1979-80, 58%; 2016-17, 90%). Survival to 2 years rose substantially, from 25% in 1979-80 to 80% in 2016-17. In survivors, rates of any assisted ventilation rose from 75% in 1979-80 to 99% in 2016-17. Cystic periventricular leukomalacia, severe retinopathy of prematurity and blindness improved across eras. Two-year data were available for 95% (1054/1109) of survivors. Rates of cerebral palsy, deafness and major neurodevelopmental disability changed little over time. The annual numbers with major neurodevelopmental disability increased from 12.5 in 1979-80 to 30 in 2016-17, but annual numbers free of major disability increased much more, from 31 in 1979-80 to 147 in 2016-17. CONCLUSIONS: Active care and survival rates in ELBW children have increased dramatically since 1979 without large changes in neonatal morbidities. The numbers of survivors free of major neurodevelopmental disability have increased more over time than those with major disability.

Temporal Trends in Neurodevelopmental Outcomes to 2 Years After Extremely Preterm Birth.

Importance: Survival of infants born extremely preterm (EP) (<28 weeks' gestation) has increased since the early 1990s. It is necessary to know whether increased survival is accompanied by increased neurodevelopmental disability. Objective: To examine changes in major (ie, moderate or severe) neurodevelopmental disability and survival free of major neurodevelopmental disability at 2 years in infants born EP. Design, Setting, and Participants: Four prospective longitudinal cohort studies comprising all EP live births at 22 to 27 weeks' gestation from April 1, 2016, to March 31, 2017, and earlier eras (1991-1992, 1997, and 2005), and contemporaneous term-born controls in the state of Victoria, Australia. Among 1208 live births during the periods studied, data were available for analysis of 2-year outcomes in 1152 children: 422 (1991-1992), 215 (1997), 263 (2005), and 252 (2016-2017). Data analysis was performed from September 17, 2020, to April 15, 2021. Exposures: Extreme preterm live birth. Main Outcomes and Measures: Survival, blindness, deafness, cerebral palsy, developmental delay, and neurodevelopmental disability at 2 years' corrected age. Developmental delay comprised a developmental quotient less than -1 SD relative to the control group means on the Bayley Scales for each era. Major neurodevelopmental disability comprised blindness, deafness, moderate to severe cerebral palsy, or a developmental quotient less than -2 SDs. Individual neurodevelopmental outcomes in each era were contrasted relative to the 2016-2017 cohort using logistic regression adjusted for gestational age, sex, birth weight z score, and sociodemographic variables. Changes in survival free of major neurodevelopmental disability over time were also assessed using logistic regression. Results: Survival to 2 years was highest in 2016-2017 (73% [215 of 293]) compared with earlier eras (1991-1992: 53% [225 of 428]; 1997: 70% [151 of 217]; 2005: 63% [170 of 270]). Blindness and deafness were uncommon (<3%). Cerebral palsy was less common in 2016-2017 (6%) than in earlier eras (1991-1992: 11%; 1997: 12%; 2005: 10%). There were no obvious changes in the rates of developmental quotient less than -2 SDs across eras (1991-1992: 18%; 1997: 22%; 2005: 7%; 2016-2017: 15%) or in rates of major neurodevelopmental disability (1991-1992: 20%; 1997: 26%; 2005: 15%; 2016-2017: 15%). Rates of survival free of major neurodevelopmental disability increased steadily over time: 42% (1991-1992), 51% (1997), 53% (2005), and 62% (2016-2017) (odds ratio, 1.30; 95% CI, 1.15-1.48 per decade; P < .001). Conclusions and Relevance: These findings suggest that survival free of major disability at age 2 years in children born EP has increased by an absolute 20% since the early 1990s. Increased survival has not been associated with increased neurodevelopmental disability.

Impact of an antimicrobial stewardship intervention in neonatal intensive care: Recommendations and implementation.

AIM: To (i) determine the appropriateness of antimicrobial prescribing in the neonatal intensive care unit (NICU) and (ii) assess the impact of a collaborative antimicrobial stewardship (AMS) intervention on prescribing practices. METHODS: The intervention was a weekly AMS audit-feedback joint ward round (6-month period) of Neonatology and Infectious Diseases clinicians in a tertiary neonatal intensive care unit in Melbourne, Australia. Antibiotic prescriptions were audited and recommendations delivered in real time. The proportion of recommendations implemented was used to assess acceptability of the intervention. RESULTS: During the study period, there were 23 AMS rounds, during which 249 patients were reviewed at 627 separate episodes. Of these, 233 (37%) episodes were for patients receiving antimicrobials. Of these, 147 (63%) received empirical antimicrobial treatment, 43 (18%) targeted antimicrobial treatment and 43 (18%) antimicrobial prophylaxis. There were 58 (25%) of 233 episodes of inappropriate antibiotic use, and 62 recommendations for improvement. Most common recommendations were to narrow (33/62, 53%) or stop (12/62, 19%) antimicrobials. The majority (45, 73%) of recommendations were accepted, resulting in significant improvement in the proportion of the 233 episodes that had completely appropriate antibiotic prescribing: 175 (75%) to 217 (93%) (relative risk 1.2, 95% confidence intervals 1.1-1.3, P < 0.001). CONCLUSIONS: A collaborative audit-feedback AMS intervention was effective in identifying inappropriate antimicrobial prescriptions and impacted positively on treatment plans. Ancillary benefits were improved communication between departments and the revision of antimicrobial prescribing guidelines.

Extreme prematurity, growth and neurodevelopment at 8 years: a cohort study.

OBJECTIVE: Infants born extremely preterm (EP, <28 weeks' gestation) exhibit poorer growth and neurodevelopmental impairment in early childhood compared with their term-born peers. Whether poor growth persists and whether associations of growth with neurodevelopmental functioning have changed in the decades since the introduction of surfactant are not well described. This study aims to (1) compare growth from birth to 2 years then 8 years in children born EP between three different eras, and (2) investigate the associations of growth from birth to 2 years then 8 years with cognitive, academic, executive and motor function at 8 years, and if associations have changed over time. DESIGN: Prospective observational cohort studies in the State of Victoria, Australia in three discrete eras: 1991-1992, 1997 and 2005. EP children had weight and head circumference measured at birth, and weight, head circumference and height at 2 and 8 years. Cognitive ability, academic performance, executive function and motor skills were assessed at 8 years, corrected for prematurity. RESULTS: 499/546 (91%) of surviving EP children were fully assessed at 8 years. Growth in children born EP did not differ substantially between eras and associations between growth and neurodevelopment did not change over time. Overall, better weight and head growth from birth to 2 years were associated with improved neurodevelopment at 8 years. CONCLUSIONS: Growth of children born EP has not improved in more recent eras. Better early head and weight growth are associated with improved neurodevelopment in mid-childhood.

Skin-to-skin care alters regional ventilation in stable neonates.

OBJECTIVE: Skin-to-skin care (SSC) has proven psychological benefits; however, the physiological effects are less clearly defined. Regional ventilation patterns during SSC have not previously been reported. This study aimed to compare regional ventilation indices and other cardiorespiratory parameters during prone SSC with supine and prone position cot-nursing. DESIGN: Prospective observational study. SETTING: Single quaternary neonatal intensive care unit in Australia. PATIENTS: 20 infants spontaneously breathing (n=17) or on non-invasive ventilation (n=3), with mean (SD) gestational age at birth of 33 (5) weeks. INTERVENTIONS: Thirty-minute episodes of care in each position: supine cot care, prone SSC and prone cot care preceding a 10 min period of continuous electrical impedance tomography measurements of regional ventilation. MAIN OUTCOME MEASURES: In each position, ventral-dorsal and right-left centre of ventilation (CoV), percentage of whole lung ventilation by region and percentage of apparent unventilated lung regions were determined. Heart and respiratory rates, oxygen saturation and axillary temperature were also measured. RESULTS: Heart and respiratory rates, oxygen saturation, temperature and right-left lung ventilation did not differ between the three positions (mixed-effects model). Ventilation generally favoured the dorsal lung, but the mean (95% CI) ventrodorsal CoV was -2.0 (-0.4 to -3.6)% more dorsal during SSC compared with prone. Supine position resulted in 5.0 (1.5 to 5.3)% and 4.5 (3.9 to 5.1)% less apparently unventilated lung regions compared with SSC and prone, respectively. CONCLUSIONS: In clinically stable infants, SSC generates a distinct regional ventilation pattern that is independent of prone position and results in greater distribution of ventilation towards the dorsal lung.

The lived experiences of critically ill infants hospitalised in neonatal intensive care: A scoping review.

BACKGROUND: Neonatal intensive care saves lives, but the environment in which this occurs is complex and has been shown to negatively disrupt some aspects of an infant's early development. Identifying these negative effects has relied on measuring physiological and behavioural responses. Little research has sought to understand and learn from what an individual infant can communicate about their lived experience. AIM: To examine what is known of the lived experiences of infants hospitalised in neonatal intensive care. STUDY DESIGN: A scoping review using the revised Arksey and O'Malley framework was undertaken. Relevant studies, exploring an infant's experience of hospitalisation were identified through a comprehensive, systematic literature search. RESULTS: 4955 articles were retrieved, 88 full texts reviewed, and 23 studies included. We identified no studies that assessed the experience from the infant's perspective. The infant experience was explored using quantitative methodology, characterising, and describing the experience in measurable physiological, behavioural, and neurodevelopmental terms or through the lens of medical outcomes. The environment is described as too loud and too bright and infants are exposed to high levels of medical handling, impacting on physiology, behaviour, sleep, feeding, and both short- and longer-term outcomes. CONCLUSION: The studies captured in this review focused on quantitative, measurable outcomes as a proxy for the experience as it might be felt, interpreted, and processed by an infant. Medical focus has been crucial to advance the field of neonatology, but the review highlights an important gap; the need to explore and better understand the infant's experience through their eyes.

Changing consumption of resources for respiratory support and short-term outcomes in four consecutive geographical cohorts of infants born extremely preterm over 25 years since the early 1990s.

OBJECTIVES: It is unclear how newer methods of respiratory support for infants born extremely preterm (EP; 22-27 weeks gestation) have affected in-hospital sequelae. We aimed to determine changes in respiratory support, survival and morbidity in EP infants since the early 1990s. DESIGN: Prospective longitudinal cohort study. SETTING: The State of Victoria, Australia. PARTICIPANTS: All EP births offered intensive care in four discrete eras (1991-1992 (24 months): n=332, 1997 (12 months): n=190, 2005 (12 months): n=229, and April 2016-March 2017 (12 months): n=250). OUTCOME MEASURES: Consumption of respiratory support, survival and morbidity to discharge home. Cost-effectiveness ratios describing the average additional days of respiratory support associated per additional survivor were calculated. RESULTS: Median duration of any respiratory support increased from 22 days (1991-1992) to 66 days (2016-2017). The increase occurred in non-invasive respiratory support (2 days (1991-1992) to 51 days (2016-2017)), with high-flow nasal cannulae, unavailable in earlier cohorts, comprising almost one-half of the duration in 2016-2017. Survival to discharge home increased (68% (1991-1992) to 87% (2016-2017)). Cystic periventricular leukomalacia decreased (6.3% (1991-1992) to 1.2% (2016-2017)), whereas retinopathy of prematurity requiring treatment increased (4.0% (1991-1992) to 10.0% (2016-2017)). The average additional costs associated with one additional infant surviving in 2016-2017 were 200 (95% CI 150 to 297) days, 326 (183 to 1127) days and 130 (70 to 267) days compared with 1991-1992, 1997 and 2005, respectively. CONCLUSIONS: Consumption of resources for respiratory support has escalated with improved survival over time. Cystic periventricular leukomalacia reduced in incidence but retinopathy of prematurity requiring treatment increased. How these changes translate into long-term respiratory or neurological function remains to be determined.

Changes in long-term prognosis with increasing postnatal survival and the occurrence of postnatal morbidities in extremely preterm infants offered intensive care: a prospective observational study.

BACKGROUND: Decisions regarding provision of intensive care and post-discharge follow-up for infants born extremely preterm (<28 weeks' gestation) are based on the risks of mortality and neurodevelopmental disability. We aimed to elucidate the changes in probability of three outcomes (death, survival with major disability, and survival without major disability) with postnatal age in extremely preterm infants offered intensive care, and the effect of postnatal events on the probability of survival without major disability. METHODS: In this prospective observational study, we used data from three geographical cohorts composed of all extremely preterm livebirths offered intensive care at birth during three distinct periods (1991-92, 1997, and 2005) in Victoria, Australia. Participants were assessed at 8 years' corrected age for major neurodevelopmental disability, defined as moderate or severe cerebral palsy, general intelligence more than 2 SDs below term-born control means, blindness, or deafness. Probabilities of outcomes conditional on survival to different postnatal ages were calculated by logistic regression. Multivariable logistic regression was used to assess factors predictive of survival with major disability. FINDINGS: 751 (82%) of 915 extremely preterm livebirths free of lethal anomalies were offered intensive care, of whom 546 (73%) survived to age 8 years. Of the 499 survivors assessed, 86 (17%) had a major disability. With increasing gestational age at birth or days of postnatal survival, the probability of death decreased and of survival without major disability increased. By contrast, the probability of survival with major disability varied little with gestational age or postnatal survival. In survivors, major disability was associated with the occurrence of four important postnatal events: grade 3 or 4 intraventricular haemorrhage (odds ratio 2·61 [95% CI 1·11-6·15]), cystic periventricular leukomalacia (9·17 [3·57-23·53]), postnatal corticosteroid use (1·99 [1·03-3·85]), and surgery (2·78 [1·51-5·13]). 241 survivors (48%) had no major postnatal events during the newborn period, and had the lowest prevalence of major disability (17 participants [7%]). The probability of survival without major disability decreased with increasing number of major events (0·93 [0·89-0·96] for no events vs 0·31 [0·11-0·59] for three or more events). INTERPRETATION: Long-term prognosis in terms of death and major neurodevelopmental disability changes rapidly after birth for extremely preterm infants. Counselling of families and post-discharge planning should be individualised to changing circumstances following birth. FUNDING: National Health and Medical Research Council of Australia.

Early surgery and neurodevelopmental outcomes of children born extremely preterm.

OBJECTIVES: To (1) compare the neurodevelopmental outcomes at 8 years of age of children born extremely preterm (EP) who underwent surgical procedures during the course of their initial hospital admission with those who did not and (2) compare the outcomes across eras, from 1991 to 2005. DESIGN: Prospective observational cohort studies conducted over three different eras (1991-1992, 1997 and 2005). Surviving EP children, who required surgical intervention during the primary hospitalisation, were assessed for general intelligence (IQ) and neurosensory status at 8 years of age. Major neurosensory disability comprised any of moderate/severe cerebral palsy, IQ less than -2 SD relative to term controls, blindness or deafness. RESULTS: Overall, 29% (161/546) of survivors had surgery during the newborn period, with similar rates in each era. Follow-up rates at 8 years were high (91%; 499/546), and 17% (86/499) of survivors assessed had a major neurosensory disability. Rates of major neurosensory disability were substantially higher in the surgical group (33%; 52/158) compared with those who did not have surgery (10%; 34/341) (OR 4.28, 95% CI 2.61 to 7.03). Rates of disability in the surgical group did not improve over time. After adjustment for relevant confounders, no specific surgical procedure was associated with increased risk of disability. IMPLICATIONS AND RELEVANCE: Major neurosensory disability at 8 years was higher in children born EP who underwent surgery during their initial hospital admission compared with those who did not. The rates of major neurosensory disability in the surgical cohort are not improving over time.

Changing Neurodevelopment at 8 Years in Children Born Extremely Preterm Since the 1990s.

BACKGROUND AND OBJECTIVE: Survival of extremely preterm (EP; <28 weeks' gestation) infants has increased over the last 2 decades. Equivalent reductions in developmental morbidity in early childhood have not been consistently reported. The aim of this study was to determine trends in neurodevelopmental outcomes at 8 years of age of children born EP (22-27 completed weeks' gestation) over the past 2 decades. METHODS: Population-based cohorts of all EP survivors born in the state of Victoria, Australia in 1991-1992, 1997, and 2005 were recruited at birth. At 8 years of age, general intelligence (IQ), academic achievement, and neurosensory status were assessed. Major neurosensory disability was defined as any of moderate or severe cerebral palsy, IQ <-2 SD relative to term controls, blindness, or deafness. RESULTS: Rates of major neurosensory disability were similar in all eras (1991-1992, 18%; 1997, 15%; 2005, 18%), as were rates of IQ <-2 SD, cerebral palsy, blindness, and deafness. Mean z scores for IQ were similar across eras, but there was some evidence that scores for academic achievement were lower in 2005 than in 1997, and the odds of having academic problems were higher in 2005 than in both earlier eras. These outcomes were not explained by differences in known perinatal care or sociodemographic variables between eras. CONCLUSIONS: Contrary to expectations, rates of major neurosensory disability have not improved, and academic performance is poorer at early school age in 2005 than in earlier eras for EP children born in the state of Victoria, Australia.

Probiotics, prematurity and neurodevelopment: follow-up of a randomised trial.

OBJECTIVE: To determine the impact of one probiotics combination on the neurodevelopment of very preterm children at 2-5 years corrected gestational age (CA). DESIGN: Follow-up study of survivors of a double-blinded, placebo-controlled, randomised trial of probiotic effects on late-onset sepsis in very preterm infants that found reduced necrotising enterocolitis. SETTING: 10 tertiary perinatal centres in Australia and New Zealand. PATIENTS: 1099 very preterm infants born <32 weeks' gestation and weighing <1500 g. INTERVENTION: Probiotics (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis) or placebo administered from birth until discharge home or term CA, whichever came sooner. MAIN OUTCOME MEASURES: Major neurodevelopmental impairment comprised any of moderate/severe cerebral palsy (Gross Motor Function Classification System score 2-5), motor impairment (Bayley-III Motor Composite Scale <-2SD or Movement Assessment Battery for Children <15th centile if >42 months' CA), cognitive impairment (Bayley-III Composite Cognitive or Language Scales <-2SD or Wechsler Preschool and Primary Scale of Intelligence Full Scale Intelligence Quotient <-2SD if >42 months' CA), blindness or deafness. RESULTS: Outcome data were available for 735 (67%) participants, with 71 deaths and 664/1028 survivors assessed at a mean age of 30 months. Survival free of major neurodevelopmental impairment was comparable between groups (probiotics 281 (75.3%) vs placebo 271 (74.9%); relative risk 1.01 (95% CI 0.93 to 1.09)). Rates of deafness were lower in probiotic-treated children (0.6% vs 3.4%). CONCLUSION: Administration of the probiotics combination Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis to very preterm babies from soon after birth until discharge home or term CA did not adversely affect neurodevelopment or behaviour in early childhood. TRIAL REGISTRATION NUMBER: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN012607000144415.

Probiotics in neonatology.

Probiotics are micro-organisms that confer health benefits on the host. Postulated mechanisms include: increasing resistance of the mucosal barrier to migration of bacteria and their toxins by strengthening intestinal cell junctions, modification of host response to microbial products, augmentation of immunoglobulin A mucosal responses, enhancement of enteral nutrition to inhibit the growth of pathogens; production of antimicrobial proteins; and competitive exclusion of potential pathogens. Published meta-analyses and systematic reviews report the effects of probiotics on important clinical outcomes in neonates. This paper will review the evidence for probiotic supplementation in neonatology, with a focus on preterm infants.

The value of neonatal autopsy.

BACKGROUND AND OBJECTIVE: Neonatal autopsy rates were in decline internationally at the end of the last century. Our objective was to assess the current value of neonatal autopsy in providing additional information to families and healthcare professionals. METHODS: We conducted a review of neonatal autopsies performed in a tertiary perinatal centre over an 11-year period. Primary outcomes measured were the annual neonatal autopsy rates and concordance rates between clinical and autopsy diagnoses of the primary cause of death. Secondary outcomes were the clinical, genetic and audit value of the examinations. Findings were used to inform the consent process, and the effect this had on institutional post-mortem rates was assessed over the subsequent 5-year period. RESULTS: There was a marked decline in the annual neonatal autopsy rate from 73% in 1994 to 48% in 2004. 164 cases met the inclusion criteria for review. Complete concordance for cause of death was reached in 91% of cases. Previously unsuspected or unconfirmed clinical conditions, other than the primary cause of death, were uncovered at autopsy in 85 cases. Detailed information on inheritable conditions was obtained in 45 cases. Findings with perceived 'audit value' for clinical practice were identified in 29 cases. The dissemination of this information to staff and families contributed to the stabilisation of the consent rate in the following 5-year period. CONCLUSION: Neonatal autopsy remains a valuable diagnostic tool as it provides critical clinical and audit information for healthcare professionals and families.

The ProPrems trial: investigating the effects of probiotics on late onset sepsis in very preterm infants.

BACKGROUND: Late onset sepsis is a frequent complication of prematurity associated with increased mortality and morbidity. The commensal bacteria of the gastrointestinal tract play a key role in the development of healthy immune responses. Healthy term infants acquire these commensal organisms rapidly after birth. However, colonisation in preterm infants is adversely affected by delivery mode, antibiotic treatment and the intensive care environment. Altered microbiota composition may lead to increased colonisation with pathogenic bacteria, poor immune development and susceptibility to sepsis in the preterm infant.Probiotics are live microorganisms, which when administered in adequate amounts confer health benefits on the host. Amongst numerous bacteriocidal and nutritional roles, they may also favourably modulate host immune responses in local and remote tissues. Meta-analyses of probiotic supplementation in preterm infants report a reduction in mortality and necrotising enterocolitis. Studies with sepsis as an outcome have reported mixed results to date.Allergic diseases are increasing in incidence in "westernised" countries. There is evidence that probiotics may reduce the incidence of these diseases by altering the intestinal microbiota to influence immune function. METHODS/DESIGN: This is a multi-centre, randomised, double blinded, placebo controlled trial investigating supplementing preterm infants born at < 32 weeks' gestation weighing < 1500 g, with a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis). A total of 1,100 subjects are being recruited in Australia and New Zealand. Infants commence the allocated intervention from soon after the start of feeds until discharge home or term corrected age. The primary outcome is the incidence of at least one episode of definite (blood culture positive) late onset sepsis before 40 weeks corrected age or discharge home. Secondary outcomes include: Necrotising enterocolitis, mortality, antibiotic usage, time to establish full enteral feeds, duration of hospital stay, growth measurements at 6 and 12 months' corrected age and evidence of atopic conditions at 12 months' corrected age. DISCUSSION: Results from previous studies on the use of probiotics to prevent diseases in preterm infants are promising. However, a large clinical trial is required to address outstanding issues regarding safety and efficacy in this vulnerable population. This study will address these important issues. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN012607000144415The product "ABC Dophilus Probiotic Powder for Infants®", Solgar, USA has its 3 probiotics strains registered with the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ--German Collection of Microorganisms and Cell Cultures) as BB-12 15954, B-02 96579, Th-4 15957.