Vitamin C supplementation in very preterm infants: a randomised controlled trial

OBJECTIVE: To determine whether regulating vitamin C (ascorbic acid: AA) intake to achieve higher or lower plasma concentrations was associated with improved clinical outcome. DESIGN: A double blind, randomised controlled trial. SETTING: Neonatal intensive care unit at Christchurch Women's Hospital. PATIENTS: Infants with birth weight <1500 g or gestation <32 weeks, admitted to the unit within 48 hours of birth. INTERVENTION: Infants were randomised to one of three protocols with regard to AA supplementation for the first 28 days of life: group LL received low supplementation throughout; group LH received low until day 10 and then high: group HH received high throughout. MAIN OUTCOME MEASURES: Primary outcome measures were oxygen requirement at 28 days and 36 weeks postmenstrual age, total days supplemental oxygen, and retinopathy of prematurity. AA concentrations were measured at study entry (day 2), and days 10, 21, and 28. RESULTS: A total of 119 infants were enrolled over 24 months (mean gestation 28.4 weeks; birth weight 1161 g). Six infants died, and these had significantly higher AA concentrations before randomisation than surviving infants (116 micromol/l (95% confidence interval 90 to 142) v 51 micromol/l (45 to 58), p<0.0001). There were no significant differences in primary outcomes between the groups. However, the proportion of surviving infants with an oxygen requirement at 36 weeks postmenstrual age in group HH (19%) was half that in group LL (41%) (p=0.06). CONCLUSIONS: In a randomised controlled trial, no significant benefits or harmful effects were associated with treatment allocation to higher or lower AA supplementation throughout the first 28 days of life.     

Follow up of a randomised trial of two different courses of dexamethasone for preterm babies at risk of chronic lung disease

OBJECTIVES: To report 18 month outcome of a randomised trial of two courses of dexamethasone to prevent chronic lung disease of prematurity. STUDY DESIGN: Babies of birth weight 1250 g or less ventilated at 7 days of age were randomised to a 42 day reducing course (long) or a 3 day pulsed (pulse) course of dexamethasone. Growth, cardiovascular status, and respiratory and neurodevelopmental outcomes were assessed at 18 months. RESULTS: Seventy six babies were enrolled. Nine died and three were lost to follow up. Babies receiving the long course were weaned off oxygen more quickly than those receiving the pulse course (47% v 69% on oxygen at 28 days; p = 0.01), but there were no differences in 18 month outcomes. However, children averaged -1 SD for growth parameters, half had moderate or severe disability, and 35% and 19% respectively required oxygen at 36 weeks and discharge. CONCLUSIONS: The dexamethasone course used did not influence long term outcome. However, entry criteria for this study selected a group of babies at high risk of poor long term outcome.     

Reduced lighting does not improve medical outcomes in very low birth weight infants

OBJECTIVE: To objectively assess the effect of light reduction as an isolated environmental intervention on neonatal morbidity. STUDY DESIGN: Randomized multicenter trial. Neonates < 1251 g birth weight and < 31 weeks gestational age were randomly assigned to receive goggles or to a control group. Goggles that reduced visible light by 97% were placed within 24 hours of birth and remained in use until 31 weeks postmenstrual age or for a minimum of 4 weeks. RESULTS: Four hundred nine infants were enrolled, and outcome data are reported for 359 surviving infants. There were no significant differences between the groups in weight gain, duration of oxygen therapy, mechanical ventilation, or hospital stay either in the unadjusted analyses or in the analyses adjusted for birth weight, gestational age, race, sex, and inborn (born in study hospital) status. There was no difference between the groups in the incidence of intracranial hemorrhage. CONCLUSIONS: This randomized trial of continuous light reduction in the first few weeks of life for very low birth weight infants showed no effect on medical outcomes.     

Neonatal catecholamine levels and neurodevelopmental outcome: a cohort study

AIMS: To determine whether neonatal plasma catecholamine concentrations can be used to predict (a) death plus disability and (b) motor and cognitive impairment at 5 years of age. METHODS: A cohort comprised 136 preterm infants from two randomised controlled trials of neonatal sedation (1989-1992). Adrenaline (epinephrine) and noradrenaline (norepinephrine) were measured at baseline (first day) and 24 hours later. Intelligence and motor ability were assessed at 5-6 years. RESULTS: Infants who died or sustained disability had significantly higher plasma noradrenaline levels on the second day of life. Noradrenaline levels above 9.0 nmol/l were most predictive of death (likelihood ratio 3.27; 95% confidence interval 1.48 to 7.23) and death plus disability (likelihood ratio 3. 55; 95% confidence interval 1.77 to 7.10). There was no correlation between neonatal catecholamine levels and cognitive or motor impairment at 5-6 years. CONCLUSIONS: Elevated noradrenaline levels are associated with adverse outcome in preterm infants; however, the power to predict death or disability is limited and they are not predictive of later motor or cognitive impairment.     

Developmental outcome of the use of etamsylate for prevention of periventricular haemorrhage in a randomised controlled trial

OBJECTIVE: To compare neurodevelopmental outcome of survivors of the multicentre trial of etamsylate (the iRNN for ethamsylate) for prevention of periventricular haemorrhage in very low birthweight infants. DESIGN: Double blind, single observer, prospective follow up of placebo controlled study. SETTING: Six neonatal intensive care units in the United Kingdom. Neurodevelopmental outcome was assessed in health premises or children's homes. SUBJECTS: 268 of 276 survivors of the original study were seen between 3.5 and 4.2 years of age. All were inborn and weighed 1500 g or less at birth. INTERVENTION: Etamsylate 12.5 mg/kg or placebo six hourly from within one hour of delivery for four days. MAIN OUTCOME MEASURES: McCarthy scales of children's abilities, standardised neurological examination, full physical examination, functional assessment, seven letter Stycar vision test, and audiometry. RESULTS: There was no difference between the groups in neuromotor outcome (cerebral palsy) or in the general cognitive index (GCI) of the McCarthy scales (mean GCI was 93.3 for the etamsylate group (n = 133) and 89.7 for the placebo group (n = 131); p = 0.10). There were more children with GCI < 70 (9 v 19; p = 0.047) or 相似文献   

Randomised trial of parental support for families with very preterm children: outcome at 5 years

AIMS: To test the effectiveness of a home based developmental education intervention in improving outcome at 5 years for very preterm infants. METHODS: The Avon Premature Infant Project (APIP) is a randomised controlled trial in which the parents of 284 babies born <33 weeks gestational age received a developmental education programme, a social support intervention, or standard care. A term reference population was also recruited. This study reports outcomes at 5 years (mean age 58 months 15 days) for 187 (66%) of these children without disability. Outcomes were assessed using the British Ability Scales II for cognitive development, the Movement ABC for motor impairment, and the Child Behavior Checklist for behavioural problems. RESULTS: Preterm infants showed poorer cognitive performance than their term peers. Mean (SD) general conceptual ability (GCA) scores were: Portage 99.2 (15.7); parent adviser 100.3 (14.8); preterm control 101.1 (15.0); term reference 107.2 (13.4). There were no significant differences between preterm groups in GCA scores indicating no effect of either intervention. Similarly, there was no significant effect of intervention on behavioural or motor outcomes. Further analyses, in which outcome data were adjusted for social factors, did not reveal any differences between the three preterm groups or by subgroups classified by a range of perinatal variables. CONCLUSION: The small advantage shown at 2 years of age is no longer detectable at 5 years. These results question the effectiveness of early intervention in enhancing cognitive, behavioural, and motor function at 5 years.     

Improving compliance with pulse oximetry alarm limits for very preterm infants?

Objective: To determine if participation in a randomised controlled trial of different oxygen saturation targets improved compliance with oximeter alarm limit guidelines. Design: Eligible infants were born after the commencement of the BOOST II trial. Data on alarm limits were collected on all infants <32 weeks' gestational age or birth weight <1500 g, who were born at The Royal Women's Hospital, Melbourne between February and June 2007, and receiving supplemental oxygen at the time of the audit. The proportions of infants in oxygen with correct alarm limits (upper 94%; lower 85% or 86%) were compared, between those in the BOOST II trial and those who were not, and with an earlier audit. Results: Of 100 infants surveyed, 56 had received oxygen (mean gestational age at birth 26.7 weeks, mean birth weight 913 g). Compliance with lower limits was good in both periods, irrespective of post‐menstrual age or participation in the trial. Compliance with upper limits improved after trial commencement, but only for infants enrolled in the trial and only whilst they were <36 weeks' post‐menstrual age. Conclusions: Starting a clinical trial of oxygen targeting was associated with improved compliance with upper alarm limits for participants receiving supplemental oxygen, but only whilst they were <36 weeks; with little effect outside the trial.     

Hemorrhagic shock and encephalopathy syndrome – the markers for an early HSES diagnosis

Background

Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis.

Methods

The study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and/or oxygen requirement and chronic lung disease. Trial registration Current Controlled Trials ISRCTN89493983     

Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life

BACKGROUND: Ventilation with higher PaCO(2) goals may reduce lung injury and bronchopulmonary dysplasia (BPD). The effect may be enhanced by using a higher PaCO(2) goal than in previous trials. OBJECTIVE: To determine the clinical benefits and safety of higher PaCO(2) goals for ventilated preterm infants. STUDY DESIGN: Preterm infants with a gestational age between 23 and 28 completed weeks receiving mechanical ventilation within 6 h of birth were randomized to be managed with either a PaCO(2) target between 55 and 65 mm Hg (7.3- 8.7 kPa, minimal ventilation) or 35 and 45 mm Hg (4.7- 6.0 kPa, routine ventilation) for the first 7 days of life. The primary outcome measure was BPD, defined as need for mechanical ventilation or supplemental oxygen at 36 weeks postmenstrual age, or death. The neurodevelopmental status was assessed at 18-22 months corrected age. RESULTS: The trial was stopped early after enrolling 31% of the projected sample size. Enrolled infants had a median birth weight of 640 g. BPD or death occurred in 21/33 (64%) infants after minimal ventilation and 19/32 (59%) infants after routine ventilation. Minimal ventilation was associated with trends towards higher mortality and higher incidence of neurodevelopmental impairment, and a significantly increased combined outcome of mental impairment or death (p < 0.05). CONCLUSION: Minimal ventilation as performed in this study did not improve clinical outcome, and may have been associated with a worse neurodevelopmental outcome.     

Cost effectiveness analysis of neonatal extracorporeal membrane oxygenation based on four year results from the UK Collaborative ECMO Trial

OBJECTIVE: To assess the cost effectiveness of extracorporeal membrane oxygenation (ECMO) for mature newborn infants with severe respiratory failure over a four year time span. DESIGN: Cost effectiveness analysis based on a randomised controlled trial in which infants were individually allocated to ECMO (intervention) or conventional management (control) and then followed up to 4 years of age. SETTING: Infants were recruited from 55 approved recruiting hospitals throughout the United Kingdom. Infants allocated to ECMO were transferred to one of five specialist regional centres. Follow up of surviving infants was performed in the community. SUBJECTS: A total of 185 mature (gestational age at birth >or= 35 weeks, birth weight >or= 2000 g) newborn infants with severe respiratory failure (oxygenation index >or= 40). MAIN OUTCOME MEASURES: Incremental cost per additional life year gained; incremental cost per additional disability-free life year gained. RESULTS: Over four years, the policy of neonatal ECMO was effective at reducing known death or severe disability (relative risk = 0.64; 95% confidence interval 0.47 to 0.86; p = 0.004). After adjustment for censoring and discounting at 6%, the mean additional health service cost of neonatal ECMO was pound 17367 (95% confidence interval pound 12072 to pound 22224) per infant ( pound UK, 2001 prices). Over four years, the incremental cost of neonatal ECMO was pound 16707 ( pound 9828 to pound 37924) per life year gained and pound 24775 ( pound 13106 to pound 69690) per disability-free life year gained. These results remained robust after variations in the values of key variables performed as part of a sensitivity analysis. CONCLUSIONS: The study provides rigorous evidence of the cost effectiveness of ECMO at four years for mature infants with severe respiratory failure.     

选择性头部亚低温治疗新生儿缺氧缺血性脑病临床多中心研究疗效阶段性分析

目的：通过临床多中心随机对照研究观察选择性头部亚低温治疗新生儿HIE的有效性。方法：收集2002年5月至2004年11月30日之前入选的至今已经完成18个月随访的新生儿HIE患儿共187（低温组104例，对照组83例）例进行初步疗效分析。低温组生后6h以内开始选择性头部低温联合全身轻度低温治疗，维持鼻咽部温度34±0.2℃，直肠温度维持在34.5℃以上；持续72h，然后自然复温。常温组维持直肠温度在36～37.5℃之间。生后 18个月进行神经发育评估（Gesell，s Development Diagnosis），主要观察严重伤残的发生率和死亡率。患儿存在脑瘫或智力发育迟滞中的任何一项定义为严重伤残。结果：187例中共失访30例（16％），实际有效病例157例（低温组88例，常温组69例）。低温组和常温组死亡和严重伤残的联合发生率分别为31.8％和50.7％（odds ratio：0.45，95％ CI 0.23－0.86，P=0.02）；其中死亡率分别为20.5％和31.9％（odds ratio：0.54，95％ CI 0.26－1.11，P=0.10）；严重伤残率分别为14.3％和27.7％（odda ratio：0.43，95％ CI 0.17－1.11，P=0.07）。进一步分析亚低温对不同严重程度的HIE的治疗效果，在中度HIE患儿中，低温治疗组死亡和严重伤残的联合发生率为24.2％，较对照组（52％）显著降低，(odds ratia:0.29,95% CI 0.10-0.9, P=0.03)；重度HIE患儿低温组和对照组的死亡和严重伤残的联合发生率分别为为55.6％和73.3％（P=0.13）。结论：选择性头部低温联合全身轻度低温72小时，可以显著降低HIE新生儿严重伤残率的发生,尤其是中度HIE患儿。     

Caffeine citrate for very preterm infants: Effects on development, temperament and behaviour

Aim: To compare two dosing regimens for caffeine citrate for neonates born less than 30 weeks gestation in terms of development, temperament and behaviour. Methods: A multi‐centre, randomised, controlled trial design was undertaken. A total of 287 infants with apnoea of prematurity or in the peri‐extubation period were randomised to receive one of two dosage regimens (20 vs. 5 mg/kg/day). The main outcome measure was cognitive development at 1 year of age on the Griffiths Mental Development Scales. Secondary outcome measures included neonatal morbidity, death and disability, temperament at 1 year and behaviour at 2 years of age. Results: Data on the primary outcome were available for 190 survivors at 12 months corrected for prematurity. A significantly greater mean general quotient was found in the high‐dose group (mean (standard deviation), 98.0 (13.8) vs. 93.6 (16.5), P= 0.048). On omission of two infants for whom cognitive assessment was not possible because of disability while the mean general quotient remained higher for infants in the high‐dose group, this was no longer statistically significant (P= 0.075). There was a non‐significant trend for benefit in the high‐dose caffeine group for death or major disability, 15.4% versus 24.2%; relative risk 0.75 (95% confidence interval 0.49–1.14). No differences in the mean values between the two groups were shown for temperament and behaviour. Conclusions: Caffeine citrate with a dosage regimen of 20 mg/kg/day did not result in adverse outcomes for development, temperament and behaviour. The borderline benefit in cognition with high‐dose caffeine needs further investigation.     

Neurodevelopmental outcomes of premature infants treated with l-arginine for prevention of necrotising enterocolitis

Aim:   This study aimed to compare the long-term neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birth weight ≤ 1250 gm) who received supplementation with l -arginine during the first 28 days of life with controls.
Methods:   Surviving infants enrolled in a randomised control study of l -arginine supplementation were prospectively followed longitudinally to determine their neurodevelopmental outcomes at 36 months of adjusted age. Neurologic examination and neurodevelopmental assessments were performed by examiners who were unaware of the original treatment assignments.
Results:   A total of 132 children (95% of survivors) were evaluated at 36 months adjusted age. In the group given l -arginine, 5 of 61 (8.1%) had major neurodevelopmental disabilities, defined as the presence of one or more of cerebral palsy, cognitive delay (cognitive index <70), bilateral blindness or bilateral hearing loss requiring hearing aids as compared with 9 of 71 (12.6%) in the placebo group (relative risk, 0.64; 95 % confidence interval, 0.22–1.82; P = 0.40).
Conclusions:   There is no increase in neurodevelopmental disability in preterm infants who received l -arginine supplementation.     

Effects of cognitive, motor, and sensory disabilities on survival in cerebral palsy.

BACKGROUND: Cerebral palsy presents with a range of severity of cognitive, motor, and sensory disabilities, which might affect survival. AIMS: To quantify the effects of motor, cognitive, and sensory disabilities, year of birth, birth weight, and gestational age on survival in cerebral palsy. METHODS: A cohort of children with cerebral palsy born between 1966 and 1989 to mothers resident in a defined geographical region was subdivided into early impairment (EICP: cerebral insult prenatally or within 28 days of birth) or late impairment (LICP: insult at least 28 days after birth). Deaths are notified by the National Health Service Central Register. Birth and disability details were obtained from clinical records. Survival analyses were carried out. RESULTS: Severe motor disability was associated with a 30 year survival of 42% and severe cognitive disability with a 30 year survival of 62%. Severe visual disability was associated with a 30 year survival of 38%, but the association of survival with hearing disability was weak. EICP had better survival than LICP but the difference was not significant after allowing for severity of functional disabilities. Normal birth weight infants (>/= 2500 g) showed no birth cohort effect, but the 10 year survival of low birth weight (<2500 g) infants declined from 97% for 1966 to 89% for 1989 births. CONCLUSIONS: Survival in cerebral palsy varies according to the severity and number of functional disabilities and by birth weight. Among low birth weight children, survival declined steadily from 1966 to 1989 after allowing for disability. The disabilities reported do not capture all the factors affecting survival of preterm infants.     

Radiological outcome of very prematurely born infants randomised to high frequency oscillatory or conventional ventilation

The appearance of the chest radiograph (CXR) at 28 days after birth or 36 weeks post-menstrual age (PMA) has been shown to be predictive of respiratory symptoms at follow-up. The aim of this study was to determine whether the CXR appearance at 28 days or 36 weeks PMA differed according to the ventilatory mode used in the perinatal period. CXRs were routinely obtained at 28 days and 36 weeks PMA from infants entered into a multicentre randomised trial (UKOS) comparing high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV); the ventilation allocation mode had been instituted within 60 min of birth. The CXRs were assessed using a scoring system (maximum score 8) for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation. A total of 487 infants, median gestational age 26+5 weeks (range 23–28+6 weeks) and birth weight 865 g (range 428–1459 g) who had had a CXR taken at 28 days and/or 36 weeks PMA. No significant differences were found between the total CXR scores of the two groups either at 28 days or 36 weeks PMA (mean scores 3.2 HFOV versus 3.5 CMV, 95%CI for difference –0.66 to 0.06, P=0.11 at 28 days and mean scores 3.5 HFOV versus 3.6 CMV, 95% for difference –0.49 to 0.29, P=0.61 at 36 weeks PMA). Conclusion:These results are consistent with high frequency oscillatory ventilation and conventional mechanical ventilation having similar effects on pulmonary function in very prematurely born infants.     

Foot length, an accurate predictor of nasotracheal tube length in neonates.

BACKGROUND: Existing guidelines for optimal positioning of endotracheal tubes in neonates are based on scanty data and relate to measurements that are either non-linear or poorly reproducible in sick infants. Foot length can be measured simply and rapidly and is related to a number of external body measurements. OBJECTIVES: To evaluate the relation of foot length to nasotracheal length in direct measurements at post mortem examinations, and then compare its clinical relevance with traditional weight based estimates in a randomised controlled trial. METHODS: The dimensions of the upper airway were measured at autopsy in 39 infants with median (range) postmenstrual age and birth weight of 32 (24-43) weeks and 1630 (640-3530) g. The regression equations with 95% prediction intervals were calculated to estimate the optimal nasotracheal length from foot length. In a randomised trial, 59 neonates were nasally intubated according to foot length and body weight based estimates to assess the achievement of "optimal" and "satisfactory" tube placements. RESULTS: In the direct measurements of the airway at autopsy, foot length was a better predictor of nasotracheal distances (r(2) = 0.79) than body weight, gestational age, and head circumference (r(2) = 0.67, 0.58, and 0.60 respectively). Measurement of foot length was easy and highly reproducible. In the randomised controlled trial, there were no significant differences between the foot length and body weight based estimates in the rates of optimal (44% v 56%) and satisfactory (83% v 72%) endotracheal tube placements. CONCLUSIONS: Foot length is a reliable and reproducible predictor of nasotracheal tube length and is at least as accurate as the conventional weight based estimation. This method may be particularly valuable in sick unstable infants.     

Randomised trial of fluid restriction in ventilated very low birthweight infants

BACKGROUND: Fluid restriction has been reported to improve survival of infants without chronic lung disease (CLD), but it remains unknown whether it reduces CLD in a population at high risk of CLD routinely exposed to antenatal steroids and postnatal surfactant without increasing other adverse outcomes. AIM: To investigate the impact of fluid restriction on the outcome of ventilated, very low birthweight infants. STUDY DESIGN: A randomised trial of two fluid input levels in the perinatal period was performed. A total of 168 ventilated infants (median gestational age 27 weeks (range 23-33)) were randomly assigned to receive standard volumes of fluid (60 ml/kg on day 1 progressing to 150 ml/kg on day 7) or be restricted to about 80% of standard input. RESULTS: Similar proportions of infants on the two regimens had CLD beyond 28 days (56% v 51%) and 36 weeks post conceptional age (26% v 25%), survived without oxygen dependency at 28 days (31% v 27%) and 36 weeks post conceptional age (58% v 52%), and developed acute renal failure. There were no statistically significant differences between other outcomes, except that fewer of the restricted group (19% v 43%) required postnatal steroids (p < 0.01). In the trial population overall, duration of oxygen dependency related significantly to the colloid (p < 0.01), but not crystalloid, input level; after adjustment for specified covariates, the hazard ratio was 1.07 (95% confidence interval 1.02 to 1.13). CONCLUSIONS: In ventilated, very low birthweight infants, fluid restriction in the perinatal period neither reduces CLD nor increases other adverse outcomes. Colloid infusion, however, is associated with increased duration of oxygen dependency.     

Exposure to repeat doses of antenatal glucocorticoids is associated with altered cardiovascular status after birth

OBJECTIVE: To determine if exposure to more than one course of antenatal glucocorticoids is associated with changes in infant blood pressure and myocardial wall thickness in the first month after birth. DESIGN: Prospective cohort study. SETTING: Tertiary neonatal intensive care unit. PARTICIPANTS: Mothers who were eligible for but declined to enter a randomised trial of repeated doses of antenatal glucocorticoids (ACTORDS)-that is, who had a singleton, twin, or triplet pregnancy at <32 weeks gestation, had received an initial course of glucocorticoids seven or more days previously, and were considered to be at continued risk of preterm birth. MAIN OUTCOME MEASURES: Blood pressure daily for the first week then weekly until 4 weeks of age. End diastolic interventricular septal and left ventricular posterior wall (EDIVS and EDLVPW) thickness at 48-72 hours after birth. RESULTS: Thirty seven women were enrolled and delivered 50 infants. Thirty mothers (39 infants) were exposed to one course of glucocorticoids, and seven mothers (11 infants) to more than one course. Blood pressures were higher in the first week after birth in infants exposed to multiple courses of glucocorticoids, and in infants with a latency between last exposure and delivery of less than seven days. Systolic blood pressure on day 1 was >2SD above published normal ranges in 67% of babies exposed to multiple courses and 24% of babies exposed to a single course of glucocorticoids (p = 0.04). There was no difference between groups in thickness of the EDIVS or EDLVPW. However, 44/50 (88%) babies had EDIVS and 49/50 (98%) babies had EDLVPW thickness >2 SD above the expected mean for birth weight and gestation. EDIVS but not EDLVPW thickness increased with increasing latency (mean 0.02 mm/day, p = 0.03). CONCLUSION: Future randomised trials should assess the long term effects of exposure to antenatal glucocorticoids, particularly multiple courses, on the cardiovascular status of the infant.     

Effects of cognitive, motor, and sensory disabilities on survival in cerebral palsy

Background: Cerebral palsy presents with a range of severity of cognitive, motor, and sensory disabilities, which might affect survival. Aims: To quantify the effects of motor, cognitive, and sensory disabilities, year of birth, birth weight, and gestational age on survival in cerebral palsy. Methods: A cohort of children with cerebral palsy born between 1966 and 1989 to mothers resident in a defined geographical region was subdivided into early impairment (EICP: cerebral insult prenatally or within 28 days of birth) or late impairment (LICP: insult at least 28 days after birth). Deaths are notified by the National Health Service Central Register. Birth and disability details were obtained from clinical records. Survival analyses were carried out. Results: Severe motor disability was associated with a 30 year survival of 42% and severe cognitive disability with a 30 year survival of 62%. Severe visual disability was associated with a 30 year survival of 38%, but the association of survival with hearing disability was weak. EICP had better survival than LICP but the difference was not significant after allowing for severity of functional disabilities. Normal birth weight infants (≥2500 g) showed no birth cohort effect, but the 10 year survival of low birth weight (<2500 g) infants declined from 97% for 1966 to 89% for 1989 births. Conclusions: Survival in cerebral palsy varies according to the severity and number of functional disabilities and by birth weight. Among low birth weight children, survival declined steadily from 1966 to 1989 after allowing for disability. The disabilities reported do not capture all the factors affecting survival of preterm infants.     

Early neonatal dexamethasone treatment for prevention of bronchopulmonary dysplasia. Randomised trial and meta-analysis evaluating the duration of dexamethasone therapy

The aim of the aborted trial was to determine whether the short early dexamethasone (DX) given after the birth improves the early outcome. We also reviewed the evidence (meta-analysis) to determine whether the duration of early DX treatment influences the early outcome, particularly in terms of bronchopulmonary dysplasia (BPD). The participants of the randomised multicentre, double-blinded placebo-controlled trial had a birth weight 500-999 g, gestation < or = 31.0 weeks, and respiratory failure by the age of 4 h. The infants received either four doses of DX (0.25 mg/kg at 12 h intervals) or placebo. The meta-analysis was performed to determine the beneficial and adverse effects of early short (<96 h duration) versus early prolonged (>96 h) DX treatment. The trial was discontinued after 109 infants had been enrolled. There was a non-significant improvement in the outcome (survival without BPD, severe intracranial haemorrhage or periventricular leukomalacia; RR 1.27; 95% CI 0.87-1.85). The risks for gastrointestinal perforation and hyperglycaemia tended to increase. A total of 15 trials were included in the meta-analysis: 10 involved prolonged (i.e. >96 h; 1594 infants) and five short interventions (1069 infants). Early prolonged DX decreased the RR for BPD to 0.72 (95% CI 0.61-0.87), whereas early short DX course did not significantly decrease the risk (RR 0.82; 95% CI 0.64-1.05). Gastrointestinal haemorrhages and perforations were significantly increased only in the early prolonged DX group. CONCLUSION: The dosage and duration of early corticosteroid given to small premature infants influences the risk of the side-effects and the early outcome.