Major Neurosensory Disability Research Articles

Neurosensory, cognitive and academic outcomes at 8 years in children born 22–23 weeks’ gestation compared with more mature births

Despite providing intensive care to more infants born <24 weeks’ gestation, data on school-age outcomes, critical for counselling and decision-making, are sparse.ObjectiveTo compare major neurosensory, cognitive and academic impairment among...

Systemic corticosteroids for the prevention of bronchopulmonary dysplasia, a network meta-analysis.

Systemic corticosteroids for the prevention of bronchopulmonary dysplasia, a network meta-analysis.

Late (> 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Many preterm infants who survive go on to develop bronchopulmonary dysplasia, probably as the result of persistent inflammation in the lungs. Corticosteroids have powerful anti-inflammatory effects and have been used to treat individuals with established bronchopulmonary dysplasia. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. To examine the relative benefits and adverse effects of late systemic postnatal corticosteroid treatment (> 7 days) for preterm infants with evolving or established bronchopulmonary dysplasia. For the 2017 update, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1); MEDLINE via PubMed (January 2013 to 21 February 2017); Embase (January 2013 to 21 February 2017); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; January 2013 to 21 February 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We selected for inclusion in this review randomised controlled trials (RCTs) comparing systemic postnatal corticosteroid treatment versus placebo or nothing initiated more than seven days after birth for preterm infants with evolving or established bronchopulmonary dysplasia. We used the GRADE approach to assess the quality of evidence.We extracted and analysed data regarding clinical outcomes including mortality, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, failure to extubate, complications during primary hospitalisation, and long-term health outcomes. Twenty-one RCTs enrolling a total of 1424 participants were eligible for this review. All were RCTs, but methods used for random allocation were not always clear. Allocation concealment, blinding of the intervention, and blinding of outcome assessments most often were satisfactory. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days) but no reduction in mortality at 36 weeks, at discharge, or at latest reported age. Benefits of delayed steroid treatment included reductions in failure to extubate by 3, 7, or 28 days; bronchopulmonary dysplasia both at 28 days of life and at 36 weeks' postmenstrual age; need for late rescue treatment with dexamethasone; discharge on home oxygen; and death or bronchopulmonary dysplasia both at 28 days of life and at 36 weeks' postmenstrual age. Data revealed a trend towards increased risk of infection and gastrointestinal bleeding but no increase in risk of necrotising enterocolitis. Short-term adverse affects included hyperglycaemia, glycosuria, and hypertension. Investigators reported an increase in severe retinopathy of prematurity but no significant increase in blindness. Trial results showed a trend towards reduction in severe intraventricular haemorrhage, but only five studies enrolling 247 infants reported this outcome. Trends towards an increase in cerebral palsy or abnormal neurological examination findings were partly offset by a trend in the opposite direction involving death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability and the combined rate of death or major neurosensory disability were not significantly different between steroid and control groups. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure, or growth, although there were fewer participants with a clinically important reduction in forced expired volume in one second (FEV1) on respiratory function testing in the dexamethasone group.GRADE findings were high for all major outcomes considered, but review authors degraded the quality of evidence by one level because we found evidence of publication bias (bronchopulmonary dysplasia at 36 weeks). Benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. This review of postnatal systemic corticosteroid treatment for bronchopulmonary dysplasia initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of studies determining long-term outcomes is limited in some cases (some studies assessed surviving children only before school age, when some important neurological outcomes cannot be determined with certainty), and no studies were sufficiently powered to detect increased rates of important adverse long-term neurosensory outcomes. Evidence showing both benefits and harms of treatment and limitations of available evidence suggests that it may be prudent to reserve the use of late corticosteroids for infants who cannot be weaned from mechanical ventilation, and to minimise both dose and duration for any course of treatment.

Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Postnatal Corticosteroids to Treat or Prevent Bronchopulmonary Dysplasia in Preterm Infants

Background: The lungs of particularly newborn are fragile and can be easily damaged. With injury, scarring may follow which is translated into difficult breathing and increased oxygen needs, a condition called bronchopulmonary dysplasia (BPD) or Chronic Lung Disease (CLD). Since inflammation plays an important role in the pathogenesis of CLD, corticosteroids, especially dexamethasone, have been extensively used to avert or treat CLD. Thus, several studies suggest that systemic corticosteroids decrease the duration of ventilator dependence. Aim of the Study: investigate the beneficial and harmful effects of the use of steroid in the prevention and treatment of BPD. Methods: A systematic review and meta-analysis of observational studies and randomized controlled trials was conducted. A review of the scientific literature. Pubmed, Embase and Central were searched to identify randomized controlled trials that investigated postnatal corticosteroids treatment for BPD were the primary endpoints. Identification of papers and data extraction were performed by two independent researchers. We searched for relevant trials in the Cochrane Library, MEDLINE (from 1955), Embase (from 1970), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to September 2017.Results: The search yielded seven RCTs which enrolled a total of 1862 participants eligible for inclusion in the present review. There were significant beneficial outcomes such as lower rates of failure to extubate and decreased risks of chronic lung disease at both 28 days (RR 0.84, 95% CI 0.83 to 0.87) and 36 weeks' postmenstrual age (RR 0.77, 95% CI 0.72 to 0.84), death or chronic lung disease at 28 days (RR 0.9, 95% CI 0.85 to 0.96) and 36 weeks' postmenstrual age (RR 0.91, 95% CI 0.87 to 0.96). Nevertheless, there were no significant differences in the rates of neonatal mortality (RR= 1.06, 95% CI 0.93, 1.26), periventricular leukomalacia (RR 1.16, 95% CI 0.9 to 1.46), necrotizing enterocolitis or pulmonary haemorrhage (RR 1.21, 95% CI 0.83 to 1.62). In contrast, gastrointestinal bleeding (RR 2.13, 95% CI 1.41 to 2.84) and intestinal perforation (RR 1.77, 95% CI 1.46 to 2.1) were imperative adverse effects. Moreover, many adverse neurological effects were found at follow-up examinations, including developmental delay (RR 1.72, 95% CI 1.4 to 2.05) and cerebral palsy (RR 1.56, 95% CI 1.03 to 2.1). Additionally, the rates of the combined outcomes of death or cerebral palsy (1.92, 95% CI 1.18 to 2.67), or of death or major neurosensory disability (RR 1.25, 95% CI 0.98 to 1.53), were not significantly increased. In subgroup analyses by type of corticosteroid, most of the advantageous and disadvantageous effects were related chiefly to dexamethasone whilst hydrocortisone had slight effect on any of the outcomes except for an increase in intestinal perforation and a borderline reduction in patent ductus arteriosus. The overall risk for bias was low as all were RCTs using robust methods. Conclusion: despite the fact that early corticosteroid treatment can have beneficial outcome for BPD management through facilitation of extubation and decreasing the risk of chronic lung disease and patent ductus arteriosus, it ,on the other hand, results in short-term adverse effects including gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure. Clinicians should carefully assess the risks of a short course of glucocorticoid therapy to mitigate BPD for premature neonates such that an individualized decision should be made in conjunction with the infant's parents.

Early surgery and neurodevelopmental outcomes of children born extremely preterm

ObjectivesTo (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...

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

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. 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. 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. 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.

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants.

Neonatal hypoglycaemia, a common condition, can be associated with brain injury. It is frequently managed by providing infants with an alternative source of glucose, given enterally with formula or intravenously with dextrose solution. This often requires that mother and baby are cared for in separate environments and may inhibit breast feeding. Dextrose gel is simple and inexpensive and can be administered directly to the buccal mucosa for rapid correction of hypoglycaemia, in association with continued breast feeding and maternal care. To assess the effectiveness of dextrose gel in correcting hypoglycaemia and in reducing long-term neurodevelopmental impairment. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science from inception of the database to February 2016. We also searched international clinical trials networks and handsearched proceedings of specific scientific meetings. Randomised and quasi-randomised studies comparing dextrose gel versus placebo, no treatment or other therapies for treatment of neonatal hypoglycaemia. Two review authors independently assessed trial quality and extracted data and did not assess publications for which they themselves were study authors. We included two trials involving 312 infants. No data were available for correction of hypoglycaemia for each hypoglycaemic event. We found no evidence of a difference between dextrose gel and placebo gel for major neurosensory disability at two-year follow-up (risk ratio (RR) 6.27, 95% confidence interval (CI) 0.77 to 51.03; one trial, n = 184; quality of evidence very low). Dextrose gel compared with placebo gel or no gel did not alter the need for intravenous treatment for hypoglycaemia (typical RR 0.78, 95% CI 0.46 to 1.32; two trials, 312 infants; quality of evidence very low). Infants treated with dextrose gel were less likely to be separated from their mothers for treatment of hypoglycaemia (RR 0.54, 95% CI 0.31 to 0.93; one trial, 237 infants; quality of evidence moderate) and were more likely to be exclusively breast fed after discharge (RR 1.10, 95% CI 1.01 to 1.18; one trial, 237 infants; quality of evidence moderate). Estimated rise in blood glucose concentration following dextrose gel was 0.4 mmol/L (95% CI -0.14 to 0.94; one trial, 75 infants). Investigators in one trial reported no adverse outcomes (n = 237 infants). Treatment of infants with neonatal hypoglycaemia with 40% dextrose gel reduces the incidence of mother-infant separation for treatment and increases the likelihood of full breast feeding after discharge compared with placebo gel. No evidence suggests occurrence of adverse effects during the neonatal period or at two years' corrected age. Oral dextrose gel should be considered first-line treatment for infants with neonatal hypoglycaemia.

What are we telling the parents of extremely preterm babies?

Parent counselling and decision-making regarding the management of preterm labour and birth are influenced by information provided by healthcare professionals regarding potential infant outcomes. The aim of this study was to determine whether perinatal healthcare providers had accurate perceptions of survival and major neurosensory disability rates of very preterm infants born in non-tertiary hospitals ('outborn') and tertiary perinatal centres ('inborn'). A web-based survey was distributed to midwives, nurses, obstetricians and neonatologists working in non-tertiary and tertiary maternity hospitals, and the perinatal/neonatal emergency transport services in Victoria, Australia. Estimates of survival rates at 24 and 28-weeks' gestation were compared with actual survival rates of a population-based cohort of 24 and 28-weeks' gestation infants, born free of lethal anomalies in Victoria in 2001-2009. Estimates of major neurosensory disability rates in 24 and 28-week survivors were compared with actual disability rates in 24 and 28-week children born in Victoria averaged over three eras: 1991-1992, 1997 and 2005. Response rates varied as follows: 83% of non-tertiary midwives, 4% of obstetricians, 55% of tertiary centre staff and 68% of transport team staff responded (total of 30%). Overall, respondents underestimated survival and overestimated major neurosensory disability rates in both outborn and inborn 24 and 28-week infants. Outborn infants were perceived to have much worse prospects for survival and for survival with major disability compared with inborn peers. Many clinicians overestimated rates of adverse outcomes. These clinicians may be misinforming parents about their child's potential for a favourable outcome.

Late (> 7 days) postnatal corticosteroids for chronic lung disease in preterm infants.

Many preterm infants who survive go on to develop chronic lung disease. This is probably due to persistent inflammation in the lungs. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established chronic lung disease. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. To determine the relative benefits and adverse effects associated with late (> 7 days) postnatal systemic corticosteroid treatment compared with control (placebo or nothing) in the preterm infant with evolving or established chronic lung disease. We sought randomised controlled trials (RCTs) of postnatal corticosteroid therapy from the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 8), MEDLINE (1966 through August 2013), handsearching paediatric and perinatal journals, and by examining previous review articles and information received from practising neonatologists. When possible, we contacted authors of all studies to confirm details of reported follow-up studies or to obtain any information about long-term follow-up where none had been reported. We selected RCTs of postnatal corticosteroid treatment initiated after seven days after birth in preterm infants with evolving or established chronic lung disease for this review. We extracted and analysed data regarding clinical outcomes including mortality, chronic lung disease, death or chronic lung disease, failure to extubate, complications in the primary hospitalisation, and long-term health outcomes Twenty-one RCTs enrolling a total of 1424 participants were eligible for this review. All were randomised controlled trials, but the methods for random allocation were not always clear. Allocation concealment, blinding of the intervention and blinding of the outcome assessments were mostly satisfactory. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days), but not mortality at discharge or latest reported age. Benefits of delayed steroid treatment included reductions in failure to extubate by three, seven or 28 days, chronic lung disease at both 28 days and 36 weeks' postmenstrual age, need for late rescue treatment with dexamethasone, discharge on home oxygen, and death or chronic lung disease at both 28 days and 36 weeks' postmenstrual age. There was a trend towards an increase in risk of infection and gastrointestinal bleeding, but not necrotising enterocolitis. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, but no significant increase in blindness. There was a trend towards a reduction in severe intraventricular haemorrhage, but only 247 infants were enrolled in five studies reporting this outcome. The trends to an increase in cerebral palsy or abnormal neurological examination were partly offset by a trend in the opposite direction in death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability, and the combined rate of death or major neurosensory disability, were not significantly different between steroid and control groups. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure or growth, although there were fewer with a clinically important reduction in the forced expired volume in one second (FEV1) on respiratory function testing. The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. Although there continues to be concern about an increased incidence of adverse neurological outcomes in infants treated with postnatal steroids, this review of postnatal corticosteroid treatment for chronic lung disease initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of the studies determining the long-term outcome is limited in some cases; in some studies the surviving children have only been assessed before school age, when some important neurological outcomes cannot be determined with certainty, and no study was sufficiently powered to detect increased rates of important adverse long-term neurosensory outcomes. Given the evidence of both benefits and harms of treatment, and the limitations of the evidence at present, it appears prudent to reserve the use of late corticosteroids for infants who cannot be weaned from mechanical ventilation and to minimise the dose and duration of any course of treatment.

Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.

Chronic lung disease remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to either prevent or treat chronic lung disease because of their potent anti-inflammatory effects. To examine the relative benefits and adverse effects of postnatal corticosteroids commenced within the first seven days of life to preterm infants at risk of developing chronic lung disease. We sought randomised controlled trials (RCTs) of postnatal corticosteroid therapy from the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 8), MEDLINE (1966 to August 2013), handsearching paediatric and perinatal journals, and by examining previous review articles and information received from practising neonatologists. We contacted authors of all studies, where possible, to confirm details of reported follow-up studies, or to obtain any information about long-term follow-up where none had been reported. We selected RCTs of postnatal corticosteroid treatment within the first seven days of life (early) in high-risk preterm infants for this review. Most studies evaluated the use of dexamethasone but we also included studies that assessed hydrocortisone, even if it was used primarily to manage hypotension. We extracted and analysed data regarding clinical outcomes that included mortality, chronic lung disease, death or chronic lung disease, failure to extubate, complications during the primary hospitalisation, and long-term health outcomes. Twenty-nine RCTs enrolling a total of 3750 participants were eligible for inclusion in this review. The overall risk for bias was probably low as all were randomised controlled trials, and most trials have used rigorous methods. There were significant benefits for the following outcomes: lower rates of failure to extubate and decreased risks of chronic lung disease at both 28 days and 36 weeks' postmenstrual age, death or chronic lung disease at 28 days and 36 weeks' postmenstrual age, patent ductus arteriosus and ROP, including severe ROP. There were no significant differences in the rates of neonatal or subsequent mortality, infection, severe intraventricular haemorrhage, periventricular leukomalacia, necrotising enterocolitis or pulmonary haemorrhage. Gastrointestinal bleeding and intestinal perforation were important adverse effects. The risks of hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure were also increased. In the 12 trials that reported late outcomes, several adverse neurological effects were found at follow-up examinations, including developmental delay (not defined), cerebral palsy and abnormal neurological examination. However, major neurosensory disability was not significantly increased, either overall in the seven studies where this outcome could be determined, or in the two individual studies where the rates of cerebral palsy or abnormal neurological examination were significantly increased. Moreover, the rates of the combined outcomes of death or cerebral palsy, or of death or major neurosensory disability, were not significantly increased. Dexamethasone was used in most studies (n = 20); only nine studies used hydrocortisone. In subgroup analyses by type of corticosteroid, most of the beneficial and harmful effects were attributable to dexamethasone; hydrocortisone had little effect on any outcomes except for an increase in intestinal perforation and a borderline reduction in patent ductus arteriosus. The benefits of early postnatal corticosteroid treatment (≤ 7 days), particularly dexamethasone, may not outweigh the adverse effects of this treatment. Although early corticosteroid treatment facilitates extubation and reduces the risk of chronic lung disease and patent ductus arteriosus, it causes short-term adverse effects including gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure. Long-term follow-up studies report an increased risk of abnormal neurological examination and cerebral palsy. However, the methodological quality of the studies determining long-term outcomes is limited in some cases; the surviving children have been assessed predominantly before school age, and no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes. There is a compelling need for the long-term follow-up and reporting of late outcomes, especially neurological and developmental outcomes, among surviving infants who participated in all randomised trials of early postnatal corticosteroid treatment. Hydrocortisone in the doses and regimens used in the reported RCTs has few beneficial or harmful effects and cannot be recommended for the prevention of chronic lung disease.

Study protocol for multicentre randomized controlled trial of HeLP (Heat Loss Prevention) in the delivery room

IntroductionImmediate postnatal hypothermia is an independent risk factor for death in premature newborns. Three randomized controlled trials (RCTs) and five historical controlled trials show statistically significant differences in admission temperature between infants wrapped in occlusive skin wrap and unwrapped infants. This paper presents a study protocol for The Vermont Oxford Network (VON) Heat Loss Prevention (HeLP) Trial, a multicentre RCT of two interventions (standard of care vs. occlusive wrap) that investigates the effect of polyethylene occlusive wrap applied immediately after birth on mortality in infants born 24+0/7 to 27+6/7week gestation. MethodsInclusion criteria include: infants 24+0/7 to 27+6/7weeks gestational age and a firm decision prior to birth to provide full resuscitative measures. Exclusion criteria comprise infants born with blistering skin conditions or congenital anomalies that are not covered by skin. The primary outcome measure is all-cause mortality until discharge from the hospital or at six months corrected gestational age. The secondary outcome measures include baseline and post-stabilization axillary temperatures, acidosis, hypotension, hypoglycaemia, seizures in the first 12h, patent ductus arteriosus, and respiratory distress syndrome. Long-term follow-up at 18 to 24months corrected age will be assessed with the combined risk of death and major neurosensory disability as the primary outcome. DiscussionKey covariates and protocol deviations are addressed and steps to monitor these are described. Wrapping may prove an inexpensive and easy method to benefit premature newborns in level I and II nurseries, in both developed and developing countries, as well as large tertiary care centres. REB approvalSunnybrook Health Sciences Centre, Toronto, Ontario, Canada—355-2003University of Alberta, Edmonton, Alberta, Canada—Pro00003810Vermont Oxford Network, Burlington, Vermont, USA—CHRMS: M04-295

Do healthy preterm children need neuropsychological follow‐up? Preschool outcomes compared with term peers

the aim of this study was to determine neuropsychological performance (possibly predictive of academic difficulties) and its relationship with cognitive development and maternal education in healthy preterm children of preschool age and age-matched comparison children born at term. a total of 35 infants who were born at less than 33 weeks' gestational age and who were free from major neurosensory disability (16 males, 19 females; mean gestational age 29.4wk, SD 2.2wk; mean birthweight 1257g, SD 327g) and 50 term-born comparison children (25 males, 25 females; mean birthweight 3459g, SD 585g) were assessed at 4 years of age. Cognition was measured using the Griffiths Mental Development scales while neuropsychological abilities (language, short-term memory, visual-motor and constructive spatial abilities, and visual processing) were assessed using standardized tests. Multivariable regression analysis was used to explore the effects of preterm birth and sociodemographic factors on cognition, and to adjust neuropsychological scores for cognitive level and maternal education. the mean total Griffiths score was significantly lower in preterm than in term children (97.4 vs 103.4; p<0.001). Factors associated with higher Griffiths score were maternal university education (β=6.2; 95% confidence interval [CI] 0.7-11.7) and having older siblings or a twin (β=4.0; 95% CI 0.5-7.6). At neuropsychological assessment, preterm children scored significantly lower than term comparison children in all tests except lexical production (Boston Naming Test) and visual-processing accuracy. After adjustment for cognitive level and maternal education, differences remained statistically significant for verbal fluency (p<0.05) and comprehension, short-term memory, and spatial abilities (p<0.01). neuropsychological follow-up is also recommended for healthy very preterm children to identify strengths and challenges before school entry, and to plan interventions aimed at maximizing academic success.

Neurodevelopmental Outcomes of Extremely Preterm Infants

Recently, advances in perinatal and neonatal intensive care during the last decades have led to a dramatic increased survival of extremely preterm and extremely low birth weight infants (ELBWI, <1,000 g). These have influenced the rates of neonatal morbidity and neurodevelopmental impairment. Neurodevelopmental outcome is being used as the most important measure of successful neonatal care and has to be assessed, not only in the short term, but also in the long term. Long-term follow-up of ELBWI is necessary to identify neurodevelopmental outcomes with a wide array from major neurosensory disability to high prevalence/ low severity dysfunction in early childhood, school age and young adulthood.

Neurodevelopmental sequelae of intraventricular haemorrhage at 8 years of age in a regional cohort of ELBW/very preterm infants

Background Major grades of intraventricular haemorrhage (IVH) are associated with adverse neurodevelopmental sequelae in early childhood but the extent of problems in specific cognitive areas, such as executive function, and the contribution of lesser grades of IVH to neurodevelopmental problems at school age are not well described. Aims To determine the neuromotor, cognitive and educational outcome of extremely low birthweight (ELBW, birthweight < 1000 g) or very preterm (< 28 weeks) infants at 8 years of age related to the severity of IVH diagnosed in the newborn period. Design Regional cohort study. Patients Consecutive surviving children of either birthweight < 1000 g or gestational age < 28 weeks born in the state of Victoria in 1991 or 1992. Main outcome measures Neurological impairments and disabilities, cognitive function and academic progress. Results Of 298 consecutive ELBW/very preterm survivors 270 (90.6%) with cranial ultrasound data were assessed at 8 years of age. Cerebral palsy, poor motor performance and major neurosensory disability were more prevalent with increasing severity of IVH. Cognitive functioning across domains was worse with increasing severity of IVH. Most of the differences were attributable to the few ( n = 6) survivors who had grade 4 IVH; there were few substantial differences between survivors with lesser grades of IVH. Conclusions Neurodevelopmental dysfunction at school age in ELBW/very preterm survivors varies little with increasing severity of IVH, with the exception of grade 4 IVH.

The Magpie Trial follow up study: outcome after discharge from hospital for women and children recruited to a trial comparing magnesium sulphate with placebo for pre-eclampsia [ISRCTN86938761

BackgroundThe Magpie Trial compared magnesium sulphate with placebo for women with pre-eclampsia. 10,141 women were recruited, 8804 before delivery. Overall, 9024 children were included in the analysis of outcome at discharge from hospital. Magnesium sulphate more than halved the risk of eclampsia, and probably reduced the risk of maternal death. There did not appear to be any substantive harmful effects on the baby, in the short term. It is now important to assess whether these benefits persist, and to provide adequate reassurance about longer term safety.The main objective of the Magpie Trial Follow Up Study is to assess whether in utero exposure to magnesium sulphate has a clinically important effect on the child's chance of surviving without major neurosensory disability. Other objectives are to assess long term outcome for the mother, and to develop and assess appropriate strategies for following up large numbers of children in perinatal trials.Study designFollow up is only feasible in selected centres. We therefore anticipate contacting 2800–3350 families, for 2435–2915 of whom the woman was randomised before delivery. A further 280–335 children would have been eligible for follow up if they had survived. The total sample size for the children is therefore 3080–3685, 2680–3210 of whom will have been born to women randomised before delivery.Families eligible for the follow up will be contacted, and surviving children screened using the Ages and Stages Questionnaires. Children who screen positive, and a sample of those who screen negative, will whenever possible have a paediatric and neurodevelopmental assessment. When women are contacted to ask how their child is, they will also be asked about their own health. The primary outcome is a composite measure of death or neurosensory disability for the child at 18 months.DiscussionThe Follow Up Study began in 2002, and now involves collaborators in 19 countries. Data collection will close at the end of 2003.

Early postnatal (

Chronic lung disease (CLD) remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to either prevent or treat CLD because of their potent anti-inflammatory effects. To determine if postnatal corticosteroid treatment is of benefit in the prevention of chronic lung disease (CLD) in the preterm infant. This review examines the outcome of trials where preterm infants at risk of CLD were given postnatal steroids within 96 hours after birth. Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Controlled Trials Register, MEDLINE (1966 - October 2002), hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. Authors of all studies were contacted, where possible, to confirm details of reported follow-up studies, or to obtain any information about long-term follow-up where none had been reported. Randomised controlled trials of postnatal corticosteroid treatment within 96 hours of birth (early) in high risk preterm infants were selected for this review. Data regarding clinical outcomes including mortality, CLD (including late rescue with corticosteroids, and need for home oxygen therapy), death or CLD, failure to extubate, complications during the primary hospitalisation (including infection, hyperglycaemia, hypertension, pulmonary air leak, patent ductus arteriosus (PDA), severe intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL), necrotising enterocolitis (NEC), gastrointestinal bleeding, intestinal perforation, severe retinopathy of prematurity (ROP), and long-term outcome (including blindness, deafness, cerebral palsy and major neurosensory disability) were abstracted and analysed using RevMan 4.1. Twenty-one randomised controlled trials enrolling a total of 3072 participants were eligible for inclusion in this review. A meta-analysis of these trials demonstrated significant benefits as regards earlier extubation and decreased risks of CLD at both 28 days and 36 weeks, death or CLD at 28 days and 36 weeks, PDA and severe ROP. There were no significant differences in the rates of neonatal or subsequent mortality, infection, severe IVH, PVL, NEC or pulmonary haemorrhage. Gastrointestinal bleeding and intestinal perforation were important adverse effects and the risks of hyperglycaemia and hypertension were also increased. In the nine trials which have reported late outcomes, several adverse neurological effects were found at follow-up examinations of survivors treated with early steroids: developmental delay (not defined), cerebral palsy and abnormal neurological exam. However, major neurosensory disability was not significantly increased, either overall in the 4 studies where this outcome could be determined, or in the 2 individual studies where the rate of cerebral palsy and abnormal neurological exam were significantly increased. Moreover, the rate of the combined outcome of death or major neurosensory disability was not significantly increased. The benefits of early postnatal corticosteroid treatment (< 96 hours) may not outweigh the known or potential adverse effects of this treatment. Although early steroid treatment facilitates extubation and reduces the risk of chronic lung disease, it causes short-term adverse effects including gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure. Long-term follow-up studies report an increased risk of abnormal neurological exam and cerebral palsy. However, the methodological quality of the studies determining the long-term outcome is limited in some cases, the children have been assessed predominantly before school age, and no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes. There is a compelling need for the long term follow-up and reporting of late outcomes, especially neurological and developmental outcomes, among surviving infants who participated in all randomised trials of early postnatal corticosteroid treatment. The role of inhaled steroids remains to be elucidated.