Periventricular Leucomalacia Research Articles

Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial

One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth. 1858 women at 25-32 weeks' gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148. Infants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216 g vs 2330 g, p=0.0026), were shorter (44.5 cm vs 45.4 cm, p<0.001), and had a smaller head circumference (31.1 cm vs 31.7 cm, p<0.001). Multiple courses of antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes, and are associated with a decreased weight, length, and head circumference at birth. Therefore, this treatment schedule is not recommended. Canadian Institutes of Health Research.

Inhaled nitric oxide to prevent bronchopulmonary dysplasia in preterm neonates

Bronchopulmonary dysplasia is a chronic lung disease that affects premature infants and contributes to their morbidity and mortality. With the advent of prenatal steroids and postnatal exogenous surfactant and less aggressive respiratory support, premature infants can develop chronic oxygen dependency without even acute respiratory distress. This 'new bronchopulmonary dysplasia' could be the result of impaired postnatal growth. Several experimental studies have suggested a possible role of the vascular endothelial growth factor/nitric oxide (VEGF/NO) pathway in restoring pulmonary angiogenesis and enhancing distal lung growth. The results of the clinical studies are, however, inconclusive, and it is currently unclear which subsets of premature infants might benefit from inhaled nitric oxide. Besides, severe intracranial haemorrhage and/or cystic periventricular leucomalacia may affect the most immature babies, many of whom are spared from severe initial respiratory disease. Recently, inhaled nitric oxide was shown to significantly decrease the incidence of these neurological events, and to improve the long-term outcome in a few clinical trials. At times neuroprotective, at times neurotoxic, nitric oxide is capable of divergent effects depending upon the extent of cerebral damage, the redox state of the cell, and the experimental model used. Recently, our group found that inhaled nitric oxide had remote effects including angiogenesis and maturation on the developing brain in rodent pups. Thus, we await the results of the recently completed randomised clinical trial of inhaled nitric oxide to prevent bronchopulmonary dysplasia (the European Nitric Oxide or 'EUNO' trial) where, besides the primary endpoint of chronic oxygen dependency reduction at 36 weeks' postconceptional age, long-term lung and brain will be followed-up until 7 years of age.

Cranial imaging in very low birth weight babies: a review

Introduction: Periventricular-intraventricular haemorrhage is the most common, well known acute perinatal brain injury in low birth weight infants (LBWI). It is the major cause of death and disability in this group of babies. The other major lesion is periventricular leucomalacia (PVL). The non-invasive technique of cranial ultrasound clarified the diagnosis and assisted in documenting the decline in the 1980's from 34-39%

Chest physiotherapy for reducing respiratory morbidity in infants requiring ventilatory support

Chest physiotherapy (CPT) has been used in many neonatal nurseries around the world to improve airway clearance and treat lung collapse; however, the evidence to support its use has been conflicting. Despite the large number of studies there is very little evidence of sufficiently good quality on which to base current practice. To assess the effects of active CPT techniques, such as percussion and vibration followed by suction compared with suction alone, on the respiratory system in infants receiving mechanical ventilation. Additionally, differences between types of active CPT techniques were assessed. Our search included The Cochrane Library (Issue 2, 2007), MEDLINE (1966 to 2007), EMBASE (1988 to 2007), CINAHL, Science Citation Index, previous reviews including cross-references, abstracts, conference proceedings and grey literature. Trials in which ventilated newborn infants up to four weeks of age were randomly or quasi-randomly assigned to receive active CPT or suction alone. Infants receiving CPT for the extubation period were excluded. Two review authors independently conducted quality assessments and data extraction for included trials. We analysed data for individual trial results using relative risk (RR) and mean difference (MD). Results are presented with 95% confidence intervals (CI). Due to insufficient data, we could not undertake meta-analysis. Three trials involving 106 infants were included in this review. In one trial (n = 20) CPT was no better than standard care in clearing secretions. No increase in the risk of intraventricular haemorrhage was noted. Two trials compared different types of active CPT. One trial (n = 56) showed that non-resolved atelectasis was reduced in more neonates receiving the lung squeezing technique (LST) when compared to postural drainage, percussion and vibration (PDPV) (RR 0.25; 95% CI 0.11 to 0.57). No difference in secretion clearance or in the rate of intraventricular haemorrhage or periventricular leucomalacia was demonstrated. The other trial (n = 30) showed that the use of percussion or 'cupping' resulted in an increased incidence of hypoxaemia (RR 0.53; 95% CI 0.28 to 0.99) and increased oxygen requirements (MD -9.68; 95% CI -14.16 to -5.20) when compared with contact heel percussion. There was insufficient information to adequately assess important short and longer-term outcomes, including adverse effects. The results of this review do not provide sufficient evidence on which to base clinical practice. There is a need for larger randomised controlled trials to address these issues.

Minocycline treatment following hypoxic/ischaemic injury attenuates white matter injury in a rodent model of periventricular leucomalacia

Periventricular white matter injury in premature infants occurs following hypoxia/ischaemia and systemic infection, and results in hypomyelination, as well as neuromotor and cognitive deficits later in life. Inflammatory infiltrates are seen within human cerebral white matter from periventricular leucomalacia (PVL) cases. In this study, we examine the time course of CD-68+ microglial cell responses relative to cell death within white matter following hypoxia/ischaemia in a rat model of PVL. We also tested the efficacy of the minocycline, an agent that suppresses microglial activation, in this model when administered as a post-insult treatment. We show that preoligodendrocyte injury in the post-natal day 6 begins within 24 h and continues for 48-96 h after hypoxia/ischaemia, and that microglial responses occur primarily over the first 96 h following hypoxia/ischaemia. Minocycline treatment over this 96 h time window following the insult resulted in significant protection against white matter injury, and this effect was concomitant with a reduction in CD-68+ microglial cell numbers. These results suggest that anti-inflammatory treatments may represent a useful strategy in the treatment of PVL, where clinical conditions would favour a post-insult treatment strategy.

West syndrome in extremely preterm infants: its relation to postnatal events

West syndrome (WS) is the epileptic encephalopathy caused by various brain disorders. Although severe periventricular leucomalacia in preterm infants is related to later development of WS,1 there have been no...

Eye movements and binocular function in low birthweight teenagers

To assess eye movements and binocular function in 14-year-olds with very low birthweight (VLBW: birthweight </= 1500 g) and 14-year-olds born at term but small for gestational age (SGA: birthweight < 10th percentile) in a population-based study. Ophthalmological examinations including measurements of heterophoria/tropia, near point of convergence, accommodative amplitude, stereopsis, nystagmus, saccades and smooth pursuit were performed in 51 adolescents with VLBW, 58 adolescents born SGA and in a control group consisting of 75 subjects of the same age. Latent or manifest strabismus, poor stereopsis, poor convergence and nystagmus were all more frequent in the VLBW group than in the control group. The VLBW group did not differ from the control group regarding accommodative amplitude or saccades and smooth pursuit. The SGA population did not differ from the control group in the measured variables. Premature birth with VLBW affects binocular visual functions negatively in adolescence, whereas birth small for date at term does not appear to be a risk factor for impaired eye movements and binocular function.

Severe retinopathy of prematurity and visual outcomes in British Columbia: a 10-year analysis

To describe the incidence trend and long-term visual outcomes of infants diagnosed with stages 3 to 4 retinopathy of prematurity (ROP) or laser-treated ROP born in British Columbia (Canada). Data from all (n=1384) neonates with birth weight (BW) <1250 g, admitted to British Columbia Children's Hospital between period 1 (January 1992 to December 1996) and period 2 (January 1997 to December 2001) were analyzed. Ophthalmologic records of infants with stages 3 to 4 ROP or laser-treated ROP were abstracted. chi(2)- and t-test were used to compare neonatal characteristics between periods. Logistic regression was used to identify risk factors associated with visual impairment (defined as visual acuity <or=20/60 or visual field restriction of 20 degrees binocularly). Of 1159 surviving infants, 887 were examined for acute ROP (473 in period 1, 414 in period 2). Stages 3 to 4 ROP or laser-treated ROP were present in 35 infants in period 1 (7%) and 59 in period 2 (14%), P<or=0001. Infants born in period 2 had lower mean BW and gestational age. Among infants who developed severe ROP or laser-treated ROP, binocular visual impairment was present in eight children in period 1 and seven in period 2. Refractive errors, including myopia and astigmatism, were increased in period 2. Children who developed periventricular leucomalacia had the highest risk of visual impairment at 4 to 6 years of age. During the 10-year study period, a significant increase in rates of stages 3 to 4 or laser-treated ROP was not associated with increases in visual impairment rates.

Evidence-based medicine in neonatology: time to re-think

Undoubtedly, evidence-based medicine has contributed substantially to improve the quality of medicine in general, and in neonatology in particular [2]. However, quite often clinical studies performed in neonatology fail to provide clear evidence that a particular intervention is beneficial for the premature infant [1]. Often, only a trend can be seen, or statistically significant changes can only be seen for shortterm outcome parameters (e.g. ventilated days) [3], but not for long-term outcome parameters (e.g. the incidence of death or chronic lung disease at 36 weeks, intraventricular haemorrhage grade 3 or 4 or periventricular leucomalacia) [4]. Unfortunately, it is then concluded that a particular intervention does not have a role in the field of neonatology. In our opinion this approach is often too crude and should be revisited. Being born as a very premature infant constitutes a medical emergency with numerous medical problems, possibly occurring simultaneously (surfactant deficiency, patent ductus arteriosus, metabolic dysfunction, intraventricular haemorrhage, etc.). Therefore, it is unlikely for a single intervention (e.g. use of diuretics or permissive hypercapnia to prevent chronic lung disease) to impact significantly on crude outcome parameters. Deducing that these interventions have no place in neonatology would be short-sighted as they may very well have shown a positive trend [3]. In the future, clinical studies in neonatology should also assess a “compound” interventional approach, e.g. a lung protective approach (e.g. permissive hypercapnia plus use of diuretics, plus fluid restriction) vs a conventional approach. These studies should combine two or more interventions that have proved to be partially beneficial (positive trend) and assess prospectively whether the combination of these interventions will improve outcome parameters in the premature infant. These studies will have the potential to contribute more substantially to our knowledge in the complex field of neonatology and impact more profoundly on our therapeutic approach than studies that assess single interventions alone.

What’s new in the other journals?

What’s new in the other journals?

Short-Term Outcome of Very Low Birth Weight Infants in a Developing Country: Comparison with the Vermont Oxford Network

To determine the outcome of very low birth weight infants (VLBWI) admitted to a level III NICU in UAE and compare the results to percentiles published by the Vermont Oxford Network (VON). Outcome data were collected retrospectively, using standard definitions, on a cohort of VLBWI 500-1500 g admitted between January 2004 and December 2006. Of the 173 infants weighing 501-1500 g at birth, 85.6% survived until discharge, which corresponds to the 50th percentile (P50) of VON. Chronic lung disease (CLD) occurred in 12.1% (<P25), death or CLD 26.6%, necrotizing enterocolitis (NEC) 5.8% (<P50), intraventricular hemorrhage (IVH) of any grade 17.5% (P25), grade III or IV IVH in 5% (P25), periventricular leucomalacia (PVL) 2.8% (P50), retinopathy of prematurity stage (ROP) 11.3% (<P10). The mortality and morbidity data for the subgroups of 501-1000 g and 1001-1500 g birth weight are also reported. We report the outcome of VLBWI born in a developing country with high resources. The rates of CLD, IVH and ROP were < or =25th percentile of the VON and mortality, NEC and PVL were in the 50th percentile.

Welchen Anteil haben ehemalige Frühgeborene an der Prävalenz von sonderpädagogischen Maßnahmen bei Schulkindern einer deutschen Großstadt (Frankfurt am Main)?

To compare infants, who were born prematurely, with all school beginners in a German city in terms of the need for special education over a 2 year period, and to evaluate the educational outcome of infants at age 6-7 years. Children, who were born premature with a gestational age of less than 30 weeks, were identified with the help of their personal health records (Gelbes Untersuchungsheft) among all school beginners of the years 2002 and 2003 in the city of Frankfurt/Main. Neonatal risk factors (intracranial bleeding, periventricular leucomalacia, retinopathy) were registered. All families and teachers of the identified children were contacted by telephone in 2005, and interviewed concerning the present school situation. In 2002 and 2003 a total of 10.743 children began school. 30 of them were identified as former premature infants (2.8 per 1000/year). They were treated after birth in various neonatal centres of the region. 11 of 30 infants were examined for a possible need for special education, and the others entered a regular school without any examination. 9 out of the 11 children were admitted to special schools, and in 2005 a further two children had special education. 18 children had a confirmed impairment as risk factor at discharge from neonatal unit, and 15 out of them were attending regular schools. In contrast, 6 out of 12 children with confirmed impairments could go to regular schools. The relative risk of need for special education in former premature born children was 30% whereas it was in whole population 10%. Ca. 70% of children, who were born with a gestational age less than 30 weeks, could attend normal school without any special education. Impairments, which were confirmed at the end of neonatal period, were of minor prognostic value for school outcome.

A different view: there is value in grading intraventricular hemorrhage

The traditional 1-4 grading system for intra-ventricular haemorrhage (IVH) has been criticized on several points. Grade 1 IVH is not really intra-ventricular at all but all neurosonographers have recognized this for many years. Grade 3 IVH is criticized as it includes ventricular dilatation but grade 3 IVH is a haemorrhage large enough to distend the ventricle with blood not cerebrospinal fluid (CSF). The distinction between small and large IVH is valuable as the prognosis is very different. Grade 4 IVH is criticized as it is not an 'extension' but authors have described this as parenchymal haemorrhagic infarction for decades. Grade 4 IVH has different risk factors, prognosis and prophylaxis from periventricular leucomalacia. The shorthand category of 'severe IVH', meaning grades 3 and 4, is not adequate for individual patient assessment but is certainly useful for annual statistics, comparisons over time and between hospitals. Despite limitations, grading IVH has value.

Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight

Very low birth weight (VLBW) children are at high risk of perinatal white matter injury, which, when subtle, may not be seen using conventional magnetic resonance imaging. The relationship between clinical findings and fractional anisotropy (FA) measurements in white matter of adolescents born prematurely with VLBW was studied in 34 subjects (age = 15 years, birth weight </=1500 g) and 47 age-matched controls born at term, who were examined both clinically and with diffusion tensor imaging (DTI). Perceptual and cognitive functions were evaluated by visual motor integration (VMI) with supplementary tests and sub-tests from WISC-III, motor function by movement ABC and Grooved Pegboard test and psychiatric symptoms by the schedule for affective disorders and schizophrenia for school-age children semistructured interview, the Autism Spectrum Screening Questionnaire and attention deficit hyperactivity disorder (ADHD) rating scale IV. Overall functioning was scored on the children's global assessment scale. DTI scans were performed for calculation of FA maps and areas of significant differences in mean FA values between subjects and controls were compared with their clinical data. The VLBW children had reduced FA values in the internal and external capsule, corpus callosum and superior, middle superior and inferior fasciculus. Within this group of children, visual motor and visual perceptual deficits were associated with low FA values in the external capsule, posterior part of the internal capsule and in the inferior fasciculus. Children with low IQ had low FA values in the external capsule and inferior and middle superior fasciculus. Fine motor impairment was related to low FA values in the internal and external capsule and superior fasciculus. Eight VLBW children with inattention symptoms or a diagnosis of ADHD had significantly lower FA values in several areas. Mild social deficits correlated with reduced FA values in the external capsule and superior fasciculus. We conclude that DTI was able to detect differences in FA between VLBW adolescents and controls in several white matter areas at risk of periventricular leucomalacia in VLBW newborns. Our results show that low FA values in these areas were associated with perceptual, cognitive, motor and mental health impairments. These conclusions indicate that perinatal injury of white matter tracts persist with clinical significance in adolescence.

Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants

Observational studies have shown an association between transiently low thyroid hormone levels in preterm infants in the first weeks of life (transient hypothyroxinaemia) and abnormal neurodevelopmental outcome. Thyroid hormone replacement might prevent this. To determine whether prophylactic thyroid hormones given to preterm infants without congenital hypothyroidism result in clinically important changes in neonatal and long term outcomes. The standard search strategy of the Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - March 2006), EMBASE, PREMEDLINE, and searches of abstracts of conference proceedings, citations of published articles and expert informants. All trials using random or quasi-random patient allocation in which prophylactic thyroid hormone treatment was compared to control in premature infants. Assessment of trial quality, data extraction and synthesis of data, using relative risk (RR) and weighted mean difference (WMD), were performed using standard methods of the Cochrane Collaboration and its Neonatal Review Group. Four studies enrolling 318 infants were included. All studies enrolled preterm infants on the basis of gestational age criteria. All studies commenced treatment in the first 48 hours, but used different regimens, dose and durations of treatment. All four studies used thyroxine (T4). Valerio 2004 incorporated one arm with an early short course of T3, then T4 for 6 weeks. Only two studies with neurodevelopmental follow-up were of good methodology (van Wassenaer 1997; Vanhole 1997). All studies were small with the largest (van Wassenaer 1997) enrolling 200 infants.No significant difference was found in neonatal morbidity, mortality or neurodevelopmental outcome in infants who received thyroid hormones compared to control. van Wassenaer 1997 reported no significant difference in abnormal mental development at 6, 12, 24 months (RR 0.67, 95% CI 0.28, 1.56) or five years (RR 0.66, 95% CI 0.22, 1.99) or cerebral palsy assessed at five years (RR 0.72, 95% CI 0.28, 1.84). Meta-analysis of two studies (van Wassenaer 1997, Vanhole 1997) found no significant difference in the Bayley MDI (WMD -1.14, 95% CI -5.46, 3.19) and PDI (WMD 0.22, 95% CI -4.80, 5.24) at 7 - 12 months. van Wassenaer 1997 reported no significant difference in the Bayley MDI (MD -3.50, 95% CI -11.21, 4.21) and PDI (MD 3.10, 95% CI -3.31, 9.51) at 24 months, IQ scores at 5 years (MD -2.10, 95% CI -7.91, 3.71) and children in special schooling at 10 years (RR 0.88, 95% CI 0.43, 1.83). Meta-analysis of all four trials found no significant difference in mortality to discharge (typical RR 0.76, 95% CI 0.46 to 1.24). van Wassenaer 1997 reported no significant difference in death or cerebral palsy at five years (RR 0.70, 95% CI 0.43 to 1.14). No significant differences were reported for neonatal morbidities, including the need for mechanical ventilation, duration of mechanical ventilation, air leak, CLD in survivors at 28 days or 36 weeks, intraventricular haemorrhage, severe intraventricular haemorrhage, periventricular leucomalacia, patent ductus arteriosus, sepsis, necrotising enterocolitis or retinopathy of prematurity. This review does not support the use of prophylactic thyroid hormones in preterm infants to reduce neonatal mortality, neonatal morbidity or improve neurodevelopmental outcomes. An adequately powered clinical trial of thyroid hormone supplementation with the goal of preventing the postnatal nadir of thyroid hormone levels seen in very preterm infants is required.

The effect of inotropes on morbidity and mortality in preterm infants with low systemic or organ blood flow

Low systemic blood flow (SBF) is common in extremely premature infants in the first day after birth and has been associated with peri / intraventricular haemorrhage (PIVH), necrotising enterocolitis (NEC), mortality and developmental impairment. To determine the effect of specific inotropes on morbidity and mortality in preterm infants with low systemic blood flow Searches were made of The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006 ), MEDLINE (1966 - April 2006), EMBASE (1980 - April 2006) and CINAHL (1982 - April 2006), supplemented by searches of abstracts of conference proceedings, citations of reviews and expert informants. Random and quasi-random controlled trials of inotropes enrolling preterm infants with low systemic or organ blood flow in the neonatal period. Independent assessment of trial eligibility, quality and data extraction by each review author. Synthesis of data using relative risk (RR) and weighted mean difference (WMD) using standard methods of the Cochrane Collaboration. No studies that compared an inotrope to no treatment in preterm infants with low SBF were found. One study (Osborn 2002a) was found that compared dobutamine versus dopamine. The study was of adequate methodology. It enrolled 42 infants < 30 weeks gestation and < 12 hours after birth with low SVC flow. The trial compared the effect of dobutamine versus dopamine titrated 10 to 20 mug/kg/min with the goal of increasing and maintaining SVC flow > 40 ml/kg/min. No significant difference was reported in mortality to discharge (RR 1.41, 95% CI 0.79, 2.52), PIVH (RR 1.01, 95% 0.52, 1.97), grade 3 or 4 PIVH (RR 0.39, 95% CI 0.12, 1.31) or NEC. At three years, there was no significant difference in cerebral palsy, deafness, Developmental quotient > 2 sd below norm or combined disability (RR 0.10, 95% CI 0.01, 1.56). Surviving infants treated with dobutamine had a significantly higher development quotient (MD 35.00, 95% CI 17.68, 52.32). There was no significant difference in death or disability at the latest time reported (RR 0.95, 95% CI 0.66, 1.38). For secondary outcomes, there was no significant difference in periventricular leucomalacia, renal impairment, pulmonary haemorrhage, retinopathy of prematurity or CLD at 36 weeks. There was no significant difference in treatment failure. Dobutamine produced a significantly greater increase in SVC flow at the highest dose reached (MD 13.10, 95% CI 2.87, 23.33), whereas dopamine produced a significantly greater increase in mean BP at 10 and 20 mug/kg/min and at the highest dose reached (MD -7.20, 95% CI -11.41, -2.99). In preterm infants with low systemic blood flow, there is some evidence that dobutamine is better than dopamine at increasing and maintaining systemic blood flow. The only eligible trial did not demonstrate any consistent differences in clinical outcomes. However, this study was not sufficiently powered to prove or disprove effects on clinical outcomes. It is unclear what is the most effective strategy for improving the cardiovascular status of immature infants in the first day. Further trials are needed to determine effective strategies for preventing and improving low systemic and organ blood flow.

Impacto de la reanimación cardiopulmonar avanzada en recién nacidos pretérmino de extremado bajo peso

To examine whether extremely low birth weight (ELBW) infants who undergo Cardiopulmonary Resuscitation (CPR) in the delivery room present poorer survival and greater short-term neurological and general morbidity than those who do not.In a retrospective cohort of 150 ELBW infants born at our hospital between 2000 and 2004, those who needed CPR and those who did not were compared for mortality and short-term general and neurological morbidity. Infants with major birth defects, suspicion of genetic disease and those without a proactive perinatal attitude in the delivery room were excluded. CPR was defined as the administration of chest compressions and/or epinephrine in the delivery room.150 infants were included, with gestational ages of 23-27 weeks (mean 25.6+/-1.2), birth weight of 425-995 grams (mean 745.2+/-132). Delivery room CPR was given to 32 infants (21.4%). No differences in perinatal characteristics were found except for lower pH and Apgar score and a higher SNAPPE score in infants who underwent CPR. Survival at discharge was similar (62.5% vs 76.3% for those without CPR). Infants who received CPR needed more surfactant, oxygen and higher median airway pressure than infants who did not. Air leaks and coagulopathy were more frequent in CPR infants (p<0.01). Prevalence of bronchopulmonary dysplasia, necrotizing enterocolitis and retinopathy was similar in the two groups. No statistical differences between ELBW infants who needed CPR and those who did not were found in prevalence of intraventricular haemorrhage (IVH) (62.5% vs 52.5%), IVH III (31.2% vs 17.7%), periventricular haemorrhagic infarction (PHI) (18.7% vs 11%) or cystic periventricular leucomalacia (PVL) (15.6% vs 11%). However, in a combined analysis of neurological morbidity (IVH III and/or PVL and/or PHI), significant differences between the two groups were found (46.7% vs 21.6%; p=0.01).This study does not support poorer survival or significant non-neurological morbidity during the neonatal period in ELBW infants who receive CPR. Although the prevalence of individual neurological problems was similar in the two groups, CPR was associated with a clear increase in general neurological morbidity, with a three-times greater risk of brain damage.

Incidence and risk factors for cerebral palsy in infants with perinatal problems: A 15-year review

Objective Cerebral palsy (CP) is associated with prenatal, perinatal and postnatal factors. This is a retrospective case-control study aiming to determine the frequency of CP and examine risk factors for CP among infants cared for in the Neonatal Intensive Care Unit (NICU) covering Northwest Greece. Design and patients All neonates who were admitted to the NICU during the period 1989–2003 inclusive, and subsequently developed CP, were enrolled in the study, with matched controls. The incidence of CP was evaluated according to gestational age (GA): GA < 34 weeks (group A) and GA > 34 (group B), and study period: 1989–1996 (period I) and 1997–2003 (period II, during which intrauterine transfer and prenatal steroids were used). Results CP was diagnosed in 78 children, 55 in group A and 23 in group B. The incidence of CP increased significantly with decreasing GA. Survival without CP increased significantly in children of GA < 34 weeks during period II. The main factors associated with CP, identified by multivariate analysis, were (odds ratios, confidence interval), for group A: being small for gestational age (SGA) (2.5, 1.2–4.5) and patent ductus arteriosus (PDA) (3.4, 1.3–9.2) in period I, periventricular leucomalacia (PVL) (27, 4.8–209), prolonged rupture of membranes (PROM) (5.6, 1.8–18) and duration of mechanical ventilation (1.1, 1.05–1.2) in period II, and for group B: SGA (3.6, 1.3–9.9), neonatal transfer (3.06, 1.2–7.6), duration of mechanical ventilation (1.1, 1.06–1.25) and sepsis–meningitis (4.3, 1.2–16). Conclusion Improvement in survival without CP was observed in infants of GA < 34 weeks during the later period of the study, and risk factors for CP in preterm infants depended on the study period. PVL, PROM and PDA were the most powerful independent predictors of CP in children of GA < 34 weeks and SGA, neonatal transfer and sepsis/meningitis in children of GA > 34 weeks.

Use of tocolytics: what is the benefit of gaining 48 hours for the fetus?

Preterm birth remains one of the serious problems in perinatal medicine and is associated with an increased risk of neonatal complications and long-term morbidity. Although each day that delivery is delayed between 22 and 28 weeks of gestation increases survival by 3%, since most spontaneous preterm labour occurs between 28 and 34 weeks of gestation, this is of secondary concern; the primary goal of delay is to improve the function of certain systems in the fetus and to balance the risks of a hostile intrauterine environment with the complications of extrauterine preterm life. Although there is a lack of definitive evidence that tocolytic drugs improve outcome following spontaneous preterm labour and preterm birth, there is ample evidence that tocolysis delays delivery for long enough to permit administration of a complete course of antepartum glucocorticoids and to facilitate in utero transfer to a tertiary care unit where neonatal care will be optimal. Both these measures have been associated with improved outcomes; antepartum glucocorticoids reduce the incidence of respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia and necrotising enterocolitis, and in utero transfer is associated with decreased morbidity and mortality and less hospital-based intervention compared with postnatal transportation. Consequently, women who are more likely to benefit from tocolysis are those at early gestational ages, those needing transfer to a hospital that can provide neonatal intensive care and those who have not yet received a full course of antepartum glucocorticosteroids. In these cases, delaying labour for at least 48 hours with drugs such as atosiban should be considered, since it offers clear advantages for the fetus.

Use of tocolytics: what is the benefit of gaining even more time?

Today's dogma states that tocolytics can be used to prolong pregnancy for just 48 hours, allowing corticosteroids to be administered and transportation of the mother to a tertiary care centre. Surveys have shown that up to 30% of practitioners use maintenance tocolysis. Theoretically, maintenance tocolysis should be able to improve neonatal outcome by avoiding preterm birth and allowing delivery in the community maternity hospital or even at home, minimising social difficulties created by long distances between the mother and/or her baby and the rest of the family. This should result in fewer neonatal intensive care unit admissions, less respiratory distress syndrome and fewer long-term neurological sequelae. Such an effect has never been proven, probably because we do not know which women benefit from treatment, which do not require treatment because they are not in labour and which babies would better be born because chorioamnionitis and other insults jeopardize intrauterine development. Most studies on long-term tocolysis have been performed with beta-agonists. No improvement has been shown. On the contrary, a trend towards fetal harm with an increased risk for periventricular leucomalacia exists. Results from studies of one tocolytic should not be generalised; one published study on maintenance therapy with atosiban showed prolonged uterine quiescence and prolonged gestation, but was too small to detect differences in neonatal outcome. In the future, we need larger studies, not only to detect whether long-term tocolysis with newer tocolytics (oral oxytocin antagonists, prostaglandin receptor blockers) results in better neonatal outcome, especially at the lower gestational ages but also to discover methods that allow us to identify those women who will benefit from treatment and those for whom prolongation of pregnancy may cause harm.