Nicola Austin

BACKGROUND: Very preterm infants are at high risk for adverse neurodevelopmental outcomes. Magnetic resonance imaging (MRI) has been proposed as a means of predicting neurodevelopmental outcomes in this population. METHODS: We studied 167 very preterm infants (gestational age at birth, 30 weeks or less) to assess the associations between qualitatively defined white-matter and gray-matter abnormalities on MRI at term equivalent (gestational age of 40 weeks) and the risks of severe cognitive delay, severe psychomotor delay, cerebral palsy, and neurosensory (hearing or visual) impairment at 2 years of age (corrected for prematurity). RESULTS: At two years of age, 17 percent of infants had severe cognitive delay, 10 percent had severe psychomotor delay, 10 percent had cerebral palsy, and 11 percent had neurosensory impairment. Moderate-to-severe cerebral white-matter abnormalities present in 21 percent of infants at term equivalent were predictive of the following adverse outcomes at two years of age: cognitive delay (odds ratio, 3.6; 95 percent confidence interval, 1.5 to 8.7), motor delay (odds ratio, 10.3; 95 percent confidence interval, 3.5 to 30.8), cerebral palsy (odds ratio, 9.6; 95 percent confidence interval, 3.2 to 28.3), and neurosensory impairment (odds ratio, 4.2; 95 percent confidence interval, 1.6 to 11.3). Gray-matter abnormalities (present in 49 percent of infants) were also associated, but less strongly, with cognitive delay, motor delay, and cerebral palsy. Moderate-to-severe white-matter abnormalities on MRI were significant predictors of severe motor delay and cerebral palsy after adjustment for other measures during the neonatal period, including findings on cranial ultrasonography. CONCLUSIONS: Abnormal findings on MRI at term equivalent in very preterm infants strongly predict adverse neurodevelopmental outcomes at two years of age. These findings suggest a role for MRI at term equivalent in risk stratification for these infants.

OBJECTIVES: Neurodevelopmental outcomes associated with preterm birth are of major health and educational concern. This study examined the neuromotor, cognitive, language and emotional/behavioural outcomes of a regional cohort of 4-year-old children born extremely preterm (EPT: 23-27 weeks' gestation), very preterm (VPT: 28-33 weeks) and full term (FT: 38-41 weeks). Of particular interest were children's risks of impairment across multiple neurodevelopmental domains. METHODS: Data were gathered as part of a prospective longitudinal study of 105 very preterm (< or = 33 weeks gestation) and 107 FT children born during 1998-2000. At 4 years corrected age, children underwent a comprehensive multidisciplinary assessment that included a paediatric neurological examination, cognitive and language testing, and an assessment of child emotional and behavioural adjustment. RESULTS: At age 4 years, compared to FT children, EPT and VPT children had increased risks of cerebral palsy (EPT 18%, VPT 15%, FT 1%), cognitive delay (EPT 33%, VPT 36%, FT 13%), language delay (EPT 29%, VPT 29%, FT 10%) and emotional/behavioural adjustment problems (EPT 37%, VPT 13%, FT 11%). EPT and VPT children were three times more likely to have multiple domain impairments than FT children (EPT 30%, VPT 29%, FT 10%). CONCLUSIONS: A substantial proportion of preschool children born very preterm show clinically significant problems in at least one neurodevelopmental domain, with impairment in multiple domains being common. There is a need to monitor preschool development across a range of functional domains and to consider the likely cascading effects of multiple impairments on later development.

BACKGROUND: Invasive fungal infection is an important cause of mortality and morbidity in very preterm and very low birth weight infants. Early diagnosis is difficult and treatment is often delayed. Systemically absorbed antifungal agents (usually azoles) are increasingly used as prophylaxis against invasive fungal infection in this population. OBJECTIVES: To assess the effect of prophylactic systemic antifungal therapy on mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 8), MEDLINE, EMBASE, and CINAHL (to May 2015), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic systemic antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. MAIN RESULTS: We identified 15 eligible trials enrolling a total of 1690 infants. Ten trials (1371 infants) compared systemic antifungal prophylaxis versus placebo or no drug. These trials were generally of good methodological quality. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio (RR) 0.43, 95% confidence interval (CI) 0.31 to 0.59; risk difference (RD) -0.09, 95% CI -0.12 to -0.06). The average incidence of invasive fungal infection in the control groups of the trials (16%) was much higher than that generally reported from large cohort studies. Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.79, 95% CI 0.61 to 1.02; typical RD -0.04, 95% CI -0.07 to 0.00). Very limited data on long-term neurodevelopmental outcomes were available. Three trials that compared systemic versus oral or topical non-absorbed antifungal prophylaxis did not detect any statistically significant effects on invasive fungal infection or mortality. Two trials that compared different dose regimens of prophylactic intravenous fluconazole did not detect any significant differences in infection rates or mortality. AUTHORS' CONCLUSIONS: Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very preterm or very low birth weight infants. This finding should be interpreted and applied cautiously since the incidence of invasive fungal infection was very high in the control groups of many of the included trials. Meta-analysis does not demonstrate a statistically significant effect on mortality. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.