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Objective To evaluate whether magnesium sulphate (MgSO 4 ) given to women at risk of very-preterm birth would be neuroprotective in preterm newborns and would prevent neonatal mortality and severe white-matter injury (WMI).Design A randomised study. Setting Eighteen French tertiary hospitals.Population Women with fetuses of gestational age < 33 weeks whose birth was planned or expected within 24 hours were enrolled from July 1997 to July 2003 with follow up of infants until hospital discharge.Methods Five hundred and seventy-three mothers were randomly assigned to receive a single 40-ml infusion of 0.1 g/ml of MgSO 4 (4 g) solution or isotonic 0.9% saline (placebo) over 30 minutes. This study is registered as an International Standard Randomised Controlled Trial, number 00120588.Main outcome measures The primary endpoints were rates of severe WMI or total mortality before hospital discharge, and their combined outcome. Analyses were based on intention to treat.Results After 6 years of enrolment, the trial was stopped. Data from 688 infants were analysed. Comparing infants who received MgSO 4 or placebo, respectively, total mortality (9.4 versus 10.4%; OR: 0.79, 95% CI 0.44-1.44), severe WMI (10.0 versus 11.7%; OR: 0.78, 95% CI 0.47-1.31) and their combined outcomes (16.5 versus 17.9%; OR: 0.86, 95% CI 0.55-1.34) were less frequent for the former, but these differences were not statistically significant. No major maternal adverse effects were observed in the MgSO 4 group. ConclusionAlthough our results are inconclusive, improvements of neonatal outcome obtained with MgSO 4 are of potential clinical significance. More research is needed to assess the protective effect of MgSO 4 alone or in combination with other neuroprotective molecules.

IPHIntraparenchymal haemorrhage IVH Intraventricular haemorrhage PPROM Preterm premature rupture of membranes PTL Preterm labour PVL Periventricular leucomalacia AIM The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population-based cohort of very preterm infants.METHOD As part of EPIPAGE, a population-based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997. RESULTSThe study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2wks; range 24-32wks) and a mean birthweight of 1367g (SD 393g; range 450-2645g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7-10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2wks; range 24-32wks) and a mean birthweight of 1305g (SD 386g; range 500-2480g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03-2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; were predictors of the development of CP in very preterm infants.INTERPRETATION Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.Very preterm infants (born before 33wks of gestation) are at high risk of developing motor deficiencies during childhood, particularly cerebral palsy (CP). 1 Cerebral lesions and several other neonatal and obstetric risk factors for CP have been described in the literature.2-4 These factors include, in particular, gestational age, low birthweight, multiple gestation, intrauterine infection, placental abruption, preterm labour or pre-labour rupture of membranes, respiratory distress syndrome, and neonatal sepsis.Since the early 1990s, advances in perinatal and neonatal care have improved the survival of very preterm infants. 5Although the incidence of severe cerebral lesions (i.e. white matter disease) has decreased significantly, 6,7 that of CP has not. 1,8 Indeed, in half of very preterm children who develop CP, no severe cerebral lesion is apparent on neonatal cranial ultrasound scans.9 Nevertheless, it is still strongly recommended that ultrasonography be performed in all infants born at a gestational age of less than 30 weeks and that it be used to p...

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