Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years

The objective of the series was to study the effect of prenatal dexamethasone therapy on the growth and neurological development of preterm children until the age of 2 years. Eighty-two children with a mean gestational age of 30 (24–33) weeks and a mean weight of 1291 (530–2360) g at birth, treated antenatally with either dexamethasone ( n = 50) or placebo ( n = 32), were examined at the adjusted age of 24 months by a paediatric neurologist, a neuropsychologist and a speech therapist. Neurological development was defined as normal if all scores of neuropaediatric, neuropsychological and verbal tests were within the normal range. Normal neurological development was found in 52% of the dexamethasone-treated and in 34% of the placebo-treated children. The incidence of cerebral palsy was 10% in the dexamethasone group and 22% in the placebo group. Minor developmental delay was found in 42% of dexamethasone-treated and in 53% of placebo-treated children. Our follow-up results indicate that the beneficial effect of prenatal glucocorticoid treatment on cerebral complications I intraventricular haemorrhage or periventricular leucomalacia) demonstrated during the neonatal period may be followed by a lower incidence of cerebral palsy in surviving premature children.     

Neonatal antecedents for cerebral palsy in extremely preterm babies and interaction with maternal factors

BACKGROUND: Preterm delivery is associated with an increased risk of cerebral palsy (CP). The greatest risk is for infants born <28 weeks' gestation. AIMS: To identify significant neonatal risk factors for CP and explore the interactions between antenatal and neonatal risk factors, among extremely preterm infants of 27 weeks' gestation or less. STUDY DESIGN: Nested case control design. METHODS: Infants born between 1989 and 1996, at 24-27 weeks' gestation, were evaluated: 30 with CP at 2 years corrected age and 120 control infants matched for gestation age. Neonatal variables were compared using matched analyses with the interaction between antenatal and neonatal factors being examined using logistic regression analyses. RESULTS: Risk factors for CP on matched analyses included patent ductus arteriosus requiring surgical ligation, peri-intraventricular haemorrhage, moderate to severe ventricular dilatation, periventricular leukomalacia (PVL) and need for home oxygen. Independent neonatal predictors were ventricular dilatation (OR 7.3; 95% CI 1.6, 32.3), PVL (OR 29.8; 95% CI 5.6, 159.1) and home oxygen use (OR 3.4; 95% CI 1.2, 9.4). No interaction terms in the logistic models were significant between the previously identified pregnancy risk factors of absence of antenatal steroids and intrauterine growth restriction and the neonatal risk factors. CONCLUSIONS: PVL is the most powerful independent predictor of CP in extremely preterm infants of 27 weeks' gestation or less and appears to be uninfluenced by antenatal factors.     

Ultrasound and necropsy study of periventricular haemorrhage in preterm infants.

The diagnostic accuracy of cerebral ultrasound for periventricular haemorrhage was determined by comparing this with necropsy findings in 30 preterm neonates of 30 weeks'' gestation or less and birthweight under 1500 g. Ultrasound gave an accurate diagnosis of 85% in infants with germinal layer haemorrhage, 92% in intraventricular haemorrhage, and 97% in intracerebral haemorrhage. False positive errors were caused by vascular congestion; false negative errors occurred when the maximum dimension of haemorrhage was less than 3 mm. Cerebral ultrasound gave a diagnostic accuracy of 63% for periventricular leucomalacia. False negative errors occurred when periventricular leucomalacia was microscopic or when it was out of range of the scanner. The maximum width of the germinal layer was measured in 77 neonates of gestational age 23 to 36 weeks who died and had no periventricular haemorrhage at necropsy. The progressive involution of the germinal layer with increasing gestational age paralleled the steady decrease in incidence of periventricular haemorrhage diagnosed over the same gestational age range. Neonates of the youngest gestational age who had the most extensive germinal layers also had the highest risk for periventricular haemorrhage.     

Reduction in periventricular haemorrhage in preterm infants.

Our previous cerebral ultrasound study of antecedents of periventricular haemorrhage in infants weighing 1250 g or less at birth suggested that neonatal events that caused increased or fluctuating cerebral blood flow lead to periventricular haemorrhage. As the risk period for this type of haemorrhage was the first four days of life strict guidelines were introduced to avoid the previously identified neonatal risk factors. No attempt was made to modify obstetric practice. Over the next two years, although the obstetric risk profile, the frequency and severity of hyaline membrane disease, and the gestation, birth weight, and sex distributions of a similar cohort of infants did not change, the incidence of periventricular haemorrhage decreased significantly from 60% to 36%. Significant antecedents of haemorrhage similar to those found in the previous study included severe bruising, low arterial:fractional inspiratory oxygen ratio and low packed cell volume on admission, hyaline membrane disease, hypercarbia, and hypoxaemia. Assisted ventilation, pneumothorax, treatment with tubocurarine, and hypotension were no longer significant risk factors for periventricular haemorrhage. A multivariate discriminant analysis correctly predicted haemorrhage in 86% of the study group when bruising, hypercarbia, hypoxaemia, hyaline membrane disease, and low gestation were considered. These results suggest that changes in neonatal practices can reduce the incidence of periventricular haemorrhage and that drug studies indicating similar reduction in haemorrhage need to be evaluated carefully to ensure that placebo and treated groups are in fact comparable.     

Periventricular leucomalacia and intraventricular haemorrhage in the preterm neonate.

Two hundred very low birthweight infants were prospectively scanned to ascertain the incidence of periventricular leucomalacia (PVL) and haemorrhage. Before collection of data, clear definitions of ultrasound abnormalities believed to represent PVL and intraventricular haemorrhage were described. These referred to small and moderate intraventricular haemorrhage, paenchymal haemorrhage, and PVL, including prolonged flare (echoes in the periventricular region lasting for two weeks or more and not becoming cystic). Sixty nine infants (34%) had no abnormality on ultrasound scans. Intraventricular haemorrhage occurred in 107 babies (37 grade I and 62 grade II), and only eight infants were thought to have true parenchymal haemorrhage. Ultrasound appearances of PVL were seen in 27 infants, 19 of whom developed cysts and eight died in the precystic stage. Prolonged flare occurred in another 25 babies. Unilateral parenchymal haemorrhage occurred in four infants who subsequently developed cystic PVL in the contralateral hemisphere. Twenty one infants developed ventricular dilatation, 12 of whom had associated parenchymal lesions. Haemorrhage, PVL, and flare occurred commonly in infants of 30 weeks'' gestation and below and became markedly less common in more mature infants. We believe prolonged flare represents a form of PVL, and in this study a total of 52 (26%) infants had an ultrasound appearance of periventricular leucomalacia, an incidence considerably higher than previously reported.     

Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive cystic periventricular leucomalacia

AIMS: To compare the ultrasound (US) evolution and neurodevelopmental outcome of infants with localised (grade II) and extensive (grade III) cystic periventricular leucomalacia (c-PVL). METHODS: Over a nine year period, c-PVL was diagnosed in 96/3451 (2.8%) infants in two hospital cohorts. Eighteen were excluded from the study. Thirty nine infants with grade II PVL were compared with 39 infants with grade III PVL. RESULTS: The two populations were comparable for gestational age and birth weight. In infants with grade II PVL, cysts were noted to develop more often after the first month of life (53%) in contrast with grade III PVL (22%) (odds ratio (OR) 3.81 (95% confidence interval (CI) 1.19 to 12.63)). Cysts were also more often unilateral in grade II (54%) than in grade III PVL (0%) (OR indefinite; RR 3.17 (95% CI 2.16 to 4.64)). At 40 weeks postmenstrual age (PMA), cysts were no longer seen on US in 13/38 infants with grade II PVL, with ventriculomegaly being the only visible sequel in nine cases. In grade III PVL, cysts were still present in 25 of the 27 surviving infants. Nine infants with grade II PVL were free of motor sequelae at follow up compared with one infant with grade III PVL (OR 8.07 (95% CI 0.92 to 181.66)). Twenty two out of 29 children with grade II PVL who developed cerebral palsy achieved independent walking compared with 3/26 with grade III PVL (OR 75 (95% CI 11.4 to 662)). CONCLUSIONS: In the cohort studied, 50% of the infants with c-PVL had a more localised form (grade II). In grade II PVL, the cysts developed beyond the first month of life in more than half of the cases and were often no longer visible, on US, at 40 weeks PMA. In order not to miss this diagnosis, sequential US should also be performed beyond the first month of life. Mild ventriculomegaly noted at term can sometimes be due to grade II c-PVL. Cerebral palsy was slightly less common and tended to be less severe in infants with grade II PVL than in those with grade III PVL.     

Clinical associations of prenatal ischaemic white matter injury.

Neuropathological examinations were carried out at necropsy on 274 cases of intrauterine death or neonatal death at or before three days after birth. Fifty six (20.4%) subjects had evidence of prenatal ischaemic brain damage. On review of the maternal case notes to ascertain antenatal clinical associations there was an increased incidence of intrauterine growth retardation, either based on birth weight for gestational age (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.1 to 3.7) or diagnosed antenatally (OR 2.7; 95% CI 1.3 to 5.6). Oligohydramnios was also more common (OR 2.9; 95% CI 1.2 to 7.0). The association of intrauterine growth retardation and white matter damage remained after excluding fetuses with a major congenital anomaly (OR 2.4; 95% CI 1.1 to 5.1). The findings suggest that chronic intrauterine hypoxia may be associated with damage to cerebral white matter among fetuses and infants who die. The relation between ischaemic white matter damage and cerebral palsy among survivors remains speculative.     

Low neonatal cerebral oxygen delivery is associated with brain injury in preterm infants

Neonatal cerebral oxygen delivery was estimated in 93 preterm infants (gestational age < 34 weeks) who survived the neonatal period. Of these, 26 had developed neurological handicap at follow-up 1.7–4.6 years later. Neonatal cerebral oxygen delivery was dependent on gestational age, and was also related to the degree of intra-uterine growth retardation, carbon dioxide tension, and blood glucose concentration. Lower oxygen delivery was observed in infants who developed germinal layer haemorrhage or periventricular leucomalacia compared with infants with normal brains. However, as no information on cerebral metabolic demand or oxygen extraction is available, it is unclear whether decreased oxygen delivery is a contributing factor to brain damage or whether it is a marker of existing injury.     

A study of cerebral perfusion using single photon emission computed tomography in neonates with brain lesions

In this study we used a single photon emission computed tomography technique (SPECT) with radiolabelled ^99mTc HMPAO to assess cerebral perfusion in newborn infants with documented cerebral lesions and to determine to what extent brain SPECT might be useful in the neonatal period. A total of 15 newborn infants with the following cerebral pathologies were enrolled: severe parietal bilateral periventricular leucomalacia (PVL, n = 6); moderate parietal bilateral PVL ( n = 2); intraventricular haemorrhage grade II with unilateral parietal parenchymal extension (IHV + PE, n = 3); cerebral infarction (CI, n = 2) in the zone of middle cerebral artery; and post-haemorrhagic hydrocephalus ( n = 2). Follow-up was available in all infants. Alterations in cerebral perfusion were seen in only 12 of 15 infants and at the location of severe PVL, PE and CI. We have noted that the regions of diminished perfusion extended, beyond the apparent extent of cerebral pathology delineated by ultrasound or magnetic resonance imaging. Markedly diminished perfusion was seen in 1 infant with hydrocephalus, which recovered following placement of ventriculo-peritoneal shunt. Regarding outcome, SPECT data failed to provide additional information than that of neuroradiological investigations. We conclude that the use of SPECT, under these conditions, to assess alteration of cerebral perfusion in the neonatal period will not provide any additional information than that of neuroradiological investigations.     

Trends in incidence of cranial ultrasound lesions and cerebral palsy in very low birthweight infants 1982-93.

AIM: To evaluate the effects of changing perinatal practice on outcome in terms of cranial ultrasound appearances and subsequent cerebral palsy rates in survivors. METHODS: A tertiary neonatal centre based prospective cohort study was undertaken of very low birthweight infants, in three 4 year periods: 1982-5, 1986-9, 1990-3. Rates of survival, parenchymal cerebral haemorrhage (PH), and leucomalacia on cerebral ultrasound scans, and cerebral palsy (CP) at the age of 3 years were compared. Antenatal steroid prophylaxis and postnatal surfactant use were also compared. RESULTS: VLBW infants (1722) were admitted over the 12 years, of whom 1268 (73.6%) were discharged home. Neonatal survival increased significantly over the three periods (69.2%, 72.9%, 79.7%; p < 0.0001). PH declined from 14.9% to 10.5% (p = 0.032) after 1990 as did CP rate (10.9% to 7.3%; p = 0.046). The use of antenatal steroids and postnatal surfactant greatly increased during this period. Steroid use was significantly associated with increased survival (OR 3.34, 2.31-4.79), decreased PH (OR 0.44, 0.28-0.71), and decreased risk of CP in survivors (OR 0.47, 0.27-0.81) after standardising for gestation, birthweight, sex, place and mode of delivery. Similar effects for surfactant did not remain significant after steroid use had been accounted for. CONCLUSION: Improved survival in VLBW infants since 1990 has been accompanied by a fall in PH and subsequent CP rates in survivors. This change is most likely to be due to the greater use of antenatal steroid prophylaxis.     

The sequelae of neonatal brain injury

The neonatal brain is very vulnerable to injury due to its relatively large size, rapid rate of development and immature immunological systems. Injury at this time often results in lifelong neuro-developmental sequelae such as cerebral palsy, learning difficulties and sensory deficits. In the term brain injury is most commonly due to hypoxia–ischaemia during labour, but hyperbilirubinaemia, trauma, thrombosis and infections remain important causes.In the preterm infant, because of immaturity, the pattern of injury is different with forms of white matter damage predominating. Germinal matrix haemorrhage, parenchymal infarction and forms of periventricular leucomalacia predominate. Preterm white matter damage often leads to altered or reduced development of cortical grey matter subsequently. All forms of cerebral palsy are seen in preterm children, but spastic cerebral diplegia is the commonest. Minor motor impairments in childhood are also very common as are behavioural disorders.Exact prognoses for infants with neonatal brain lesions are difficult to make owing to the fact that more than one lesion may co-exist in the same infant.     

Intraventricular haemorrhage and periventricular leucomalacia: ultrasound and autopsy correlation.

The brains of 30 infants who died after at least one real time ultrasound scan were examined after fixation. The ultrasound diagnosis of either periventricular haemorrhage or periventricular leucomalacia was compared with the macroscopic and histological appearances. Each hemisphere was considered separately for both periventricular haemorrhage and periventricular leucomalacia. The accuracy of ultrasound diagnosis for periventricular haemorrhage was 88%, with sensitivity of 91% and specificity of 85%. The accuracy for periventricular leucomalacia was 90%, with sensitivity of 85% and specificity of 93%. Ultrasound was shown to diagnose the entire range of periventricular leucomalacia lesions. Three hemispheres showed the appearance of prolonged flare, and this correlated with extensive spongiosis and microcalcification of the periventricular white matter, although no macroscopic lesion was seen.     

Effect of Dexamethasone Therapy on the Neonatal Ductus Arteriosus

Patent ductus arteriosus (PDA) is believed to be a contributing factor in the etiopathogenesis of bronchopulmonary dysplasia (BPD). We studied the effects of early dexamethasone therapy on persistent ductal patency and the role of PDA in the etiopathogenesis of BPD during the course of a randomized double-blind trial of dexamethasone to prevent BPD. Infants, who weighed between 700 and 999 g, had severe RDS, and had been given surfactant, were randomized to receive a 12-day course of dexamethasone (n= 13) or placebo (n= 17) starting within the first 12 hours of postnatal life. The diagnosis of PDA was made clinically and was confirmed by cardiac ultrasound. The incidence of clinically significant ductus in infants who weighed less than 1000 g was 23% in the dexamethasone-treated group, as compared with 59% in infants who were given placebo. This difference was marginally significant, p= 0.05, odds ratio 0.21, 95% confidence interval 0.04–1.05. None of the infants in the dexamethasone group had recurrence of PDA after indomethacin therapy as compared with three infants in the placebo group. Dexamethasone significantly reduced the number of days infants required ventilator and supplemental oxygen as compared with infants who received placebo. Dexamethasone, as compared with placebo, also reduced the incidence of BPD, p= 0.025, odds ratio 0.08, 95% confidence interval 0.01–0.58. Dexamethasone may reduce the incidence of PDA in premature infants who weigh less than 1000 g at birth and thereby reduce the incidence of BPD.     

Cerebral palsy and neonatal encephalopathy.

A retrospective cohort study was carried out to test the hypothesis that children born at term with cerebral palsy with signs of neurological dysfunction preceded by depression at birth (termed neonatal encephalopathy) differ from those without such signs in the frequency of antenatal and perinatal factors, and in the severity and characteristics of their impairment and disability. The study was carried out in the area covered by Oxford Regional Health Authority. Antenatal, intrapartum, neonatal factors, and the later clinical status of the two groups of children were used as the main outcome measures. Although most maternal and antenatal characteristics were similar in the two groups, the mothers of children with a history of neonatal encephalopathy were more likely to be primigravidae (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.0 to 4.3) and to have a pregnancy of greater than 41 weeks' gestation (OR 3.5; 95% CI 1.0 to 12.1). Intrapartum complications were more frequent in the neonatal encephalopathy group: meconium staining of the amniotic fluid (OR 3.5; 95% CI 1.5 to 7.8), an ominous first stage cardiotocograph (OR 10.2; 95% CI 2.9 to 36.4), with a longer median duration of abnormality (200 v 48 minutes). At 5 years of age those with neonatal encephalopathy were more likely to have developed spastic quadriplegia (OR 4.8; 95% CI 2.2 to 10.5), to have visual impairment (OR 3.0; 95% CI 1.0 to 8.6), and to be non-walking (OR 4.0; 95% CI 1.8 to 8.8) than those without neonatal encephalopathy. Children with cerebral palsy who were born at term and have neonatal encephalopathy are more likely to have had signs of intrapartum asphyxia and are more likely to have a more severe form of cerebral palsy than those without a history of neonatal encephalopathy. Although this group represents only one in 10 of all cases of cerebral palsy, some of these may be obstetrically preventable.     

Outcome of extremely low birth weight survivors at school age: the influence of perinatal parameters on neurodevelopment

Extremely low birth weight (ELBW) is associated with impaired neurodevelopmental outcome in infancy. Information on the long-term cognitive and neurological consequences of ELBW is scarce. We aimed to identify the perinatal and neonatal factors of ELBW infants associated with adverse cognitive and neurological outcome at school age. A regional cohort of 135 ELBW infants born between 1993 and 1998 was prospectively evaluated at 3, 6, 12, and 18 months postmenstrual age and at yearly intervals up to age 10 years. The comprehensive follow-up programme for high-risk infants included neurological examinations and psychometric evaluations. According to the overall results of these tests, children were classified as either being normal or having minor or major impairment. At a mean age of 8.4 (SD: 1.6) years, 43% of children had survived without any impairment. Minor impairment was diagnosed in 39% and major impairment in 18% of assessed children. The proportion of disabled school children rose with decreasing gestational age. The following neonatal complications were significant risk factors for developing major or minor impairment at school age: an increase in head circumference <6 mm per week (OR 4.0, 95% CI: 1.1–14.8), parenteral nutrition ≥6 weeks (OR 2.5, 95% CI: 1.1–6.0), and mechanical ventilation >14 days (OR 2.3, 95% CI: 1.0–5.1). High-grade intraventricular haemorrhage (IVH) and/or PVL (OR 13.3, 95% CI: 4.0–44.9), neonatal seizures (OR 5.2, 95% CI: 1.2–22.4) and bowel perforation, and/or necrotizing enterocolitis (OR 4.4, 95% CI: 1.1–17.0) were significant risk factors for developing major impairment. In spite of the relatively large proportion of normal children, ELBW remains an important risk factor for neurodevelopmental impairment at school age. Thus, measures to prevent complications such as necrotizing enterocolitis, cerebral haemorrhage, and undernutrition remain important goals for neonatal intensive care.     

Risk factors and determinants of neurodevelopmental outcome in cystic periventricular leucomalacia

The aim of the study was to determine risk factors for the development of cystic periventricular leucomalacia (PVL) and to correlate ultrasound findings with neurodevelopmental outcome. By means of a retrospective case-control study (matched for gestational age, birth weight, sex, and year of birth) and a cohort analysis of all preterm infants with cystic PVL documented by ultrasound scans hospitalised at a local tertiary care centre between 1988 and 1998, 98 preterm infants with a gestational age ranging from 26 to 35 weeks were diagnosed as having cystic PVL. The mean day of diagnosis of periventricular echodensities was 3 ± 2 days (range 1–11 days), and of cystic PVL 21 ± 8 days (range 2–47 days). Of 79 infants (1988–1997) eligible for neurodevelopmental follow-up (91%), hemi-, di-, or tetraplegia was diagnosed in 61 (77%), normal mental outcome in 22 (28%), associated visual disorders in 41 (52%) and seizure disorders in 12 (15%) infants. Significant risk factors associated with the development of cystic PVL were premature rupture of membranes, chorioamnionitis, and hyperbilirubinaemia (odds ratios 4.665, 6.026, and 2.460 respectively). Subgroup analysis according to gestational age (26–28, 29–32, 33–35 weeks) revealed similar results despite spontaneous labour (26–28 weeks; odds ratio 4.808) and pre-eclampsia (33–35 weeks; odds ratio 3.517). Multiple pregnancy was associated with a twofold increased risk (odds ratio 2.075). The white matter damage probably accounted for the significantly higher prevalence of apnoeas (P < 0.001) and neonatal seizures (P < 0.001). Cysts located bilateral or parieto-occipital were associated with a higher risk of cerebral palsy (odds ratios 6.933 and 4.327 respectively). Solely anterior located cysts were associated with normal neurological outcome. Increasing size of the cysts was associated with increasing risk of cerebral palsy with a cut-off value of 10 mm (odds ratio 3.300 and above) and all infants with cysts of more than 20 mm diameter had cerebral palsy. Conclusion The high prevalence of premature rupture of the membranes and chorioamnionitis further supports the role of intra-uterine infection in the pathogenesis of periventricular leucomalacia. The overall prognosis of cystic periventricular leucomalacia is poor. Received: 30 September 1999 and in revised form: 28 February 2000 / Accepted: 17 March 2000     

Neurodevelopmental outcome of preterm infants with bronchopulmonary dysplasia.

The neurodevelopmental outcome of 78 infants with bronchopulmonary dysplasia (BPD) was compared with that of 78 control infants matched for birthweight. To determine the effect of the severity of BPD, 62 infants requiring oxygen at 36 weeks'' postmenstrual age (sBPD) were compared with their matched controls. Infants were followed up to 2 years of age, corrected for prematurity, and were classified for neurological impairment, developmental delay, and neurodevelopmental disability. Seventy six (98%) BPD infants and 71 (91%) controls had follow up data available to two years. Neurological impairment, developmental delay, and neurodevelopmental disability occurred more frequently in infants with BPD than in controls but this was not significant. For infants with sBPD, the increased incidence of neurological impairment and definite developmental delay was not significant when compared with the controls, though neurodevelopmental disability occurred more frequently (odds ratio (OR) 3.6: 95% confidence intervals (CI) 1.1-11.8). Predictors of disability in infants with sBPD included periventricular haemorrhage (OR 19.4: 95% CI 4.3-86.6), ventricular dilatation (OR 12.8: 95% CI 2.9-57.3), and sepsis (OR 5.0: 95% CI 1.3-19.4). Adjusting for the presence of these factors, the association between BPD and disability was no longer apparent (OR 0.9: 95% CI 0.2-3.6). The findings suggest that BPD is not independently associated with adverse neurodevelopmental outcome.     

Ultrasound appearance of the brain in very preterm infants and neurodevelopmental outcome at 18 months of age.

The brains of 158 consecutively admitted very preterm infants were repeatedly examined with real time ultrasound. Abnormalities, most commonly periventricular haemorrhage, were detected in 79 (50%). The 109 infants who survived were followed up until they were 16-23 months old. Major or minor neurological or developmental sequelae were found in 5 of 62 infants (8%) with normal ultrasound scans and in an identical proportion, 2 of 25 infants (8%), with uncomplicated periventricular haemorrhage. By contrast, 15 of 21 infants (71%) whose ventricles became enlarged (with or without periventricular haemorrhage) had abnormalities at follow up. The proportion with sequelae depended on the cause and extent of the enlargement. Three of 8 infants (38%) with mild (usually transient) ventricular distension had sequelae, compared with 3 of 4 (75%) with hydrocephalus and 9 of 9 (100%) with cerebral atrophy (2 of whom also had hydrocephalus). Adverse neurodevelopmental sequelae at follow up appeared more often to be attributable to cerebral ischaemia and infarction than to periventricular haemorrhage.     

Short-term outcome after active perinatal management at 23-25 weeks of gestation. A study from two Swedish perinatal centres. Part 3: neonatal morbidity

Aim: To determine major neonatal morbidity in surviving infants born at 23-25 weeks, and to identify maternal and infant factors associated with major morbidity. Methods: The medical records of 224 infants who were delivered at two tertiary care centres in 1992-1998 were reviewed retrospectively. At these centres, policies of active perinatal and neonatal management were universally applied. Of the 213 liveborn infants, 140 (66%) survived to discharge. Data were analysed by gestational age and considered in three time periods. Logistic regression models were used to identify factors associated with morbidity. Results: Of the survivors, 6% had intraventricular haemorrhage grade ≥3 (severe IVH) or periventricular leukomalacia (PVL), 15% retinopathy of prematurity ≥stage 3 (severe ROP) and 36% bronchopulmonary dysplasia (BPD). On logistic regression analysis, severe IVH or PVL was associated with duration of mechanical ventilation (odds ratio, OR: 1.53 per 1-wk increment in duration; 95% confidence interval, CI: 1.01-2.33). Severe ROP was associated with the presence of a patent ductus arteriosus (PDA) (OR: 3.31; 95% CI: 1.11-9.90) and birth in time period 3 versus time periods 1 and 2 combined (OR: 6.28; 95% CI: 2.10-18.74). BPD was associated with duration of mechanical ventilation (OR: 2.71 per 1-wk increment in duration; 95% CI: 1.76-4.18) and with the presence of any obstetric complication (OR: 2.67; 95% CI: 1.07-6.65). Gestational age and birthweight were not associated with major morbidity. Of all survivors, 81% were discharged home without severe IVH, PVL or severe ROP.

Conclusions: Increased survival as a result of active perinatal and neonatal management was associated with favourable morbidity rates compared with those in recent studies. Among survivors born at 23-25 weeks, neither gestational age nor birthweight was a significant determinant of major morbidity.     

A study of periventricular haemorrhage, post-haemorrhagic ventricular dilatation and periventricular leucomalacia in Chinese preterm infants

Serial cranial ultrasound scans were performed in 178 preterm Chinese infants (gestation less than 35 weeks, birthweight less than 2000 g) to study the incidence, age of onset and associating risk factors of periventricular haemorrhage (PVH), and also the occurrence of post-haemorrhagic ventricular dilatation and periventricular leucomalacia (PVL). Sixty-four infants developed haemorrhage, giving an incidence of 36%. Among infants of birthweight less than 1500 and less than 1000 g the respective incidence was 52 and 69%. Seventy-two per cent (46 of 64) of haemorrhages were initially detected within the first 3 days of life, but delayed haemorrhage occurring after 1 week of age occurred in nine infants. In eight of these infants PVH had been shortly preceded by a major clinical disaster. Eleven perinatal factors were found to be significantly associated with PVH but only systemic hypotension showed a significant independent association. Post-haemorrhagic ventricular dilatation developed in 17 (46%) of the 37 infants who survived for more than 1 month after PVH. This was transient in 41%, persistent but stable in 29% and progressive in 29%. PVL was detected in eight infants who survived the initial period following PVH.