ABSTRACT

Diffuse white matter abnormalities and post-hemorrhagic ventricular dilation are common at term and seem to correlate with reduced developmental quotients. Early lesions, except for cerebellar hemorrhage and major destructive lesions, do not show clear relationships with outcomes.

BackgroundWe postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment.Methods and FindingsWe analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25–1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth.ConclusionsHuman brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

This study provides objective evidence that DEHSI represents diffuse white matter abnormality.

Intrauterine infection has been frequently linked with preterm labor before 30 wk of human pregnancy. Many different species of organisms have been detected, leading to the suggestion that infection-induced preterm labor is a generic inflammatory response to organisms rather than a specific response to a limited number of pathogens. The detection of organisms by microbiological culture is a laborious and unreliable process, so the aim of this study was to harness modern molecular techniques to detect organisms in tissues from human pregnancy. A DNA probe specific for conserved regions of bacterial 16S ribosomal RNA sequence was designed and labeled with fluorescein for fluorescence in situ hybridization. Organisms were detected in the great majority (Ͼ80%) of fetal membranes after prolonged premature rupture of the fetal membranes and after preterm labor, which was consistent with previous data. Organisms were also detected in fetal membranes after preterm delivery without labor and in term deliveries (with or without labour). Inflammatory cells were found frequently in the amnion or chorion of preterm fetal membranes but not in term tissues. Our primary finding is that fluorescence in situ hybridization is an appropriate method to detect organisms in human fetal membranes. In addition, our data show that bacteria may be present in fetal membranes without necessarily causing an inflammatory response, so the mere presence of bacteria may not be sufficient to cause preterm labor. Human labor at all gestational ages involves an inflammatory response, being characterized by increased levels of prostaglandins and cytokines (1,2). This inflammation is presumed to be initiated by physiological mediators, including corticotrophin-releasing hormone (3) or platelet-activating factor (4), or by pathological processes (5-7).At 23-32 wk of pregnancy, preterm labor is most frequently associated with micro-organisms within the uterus (8). These organisms are thought to activate inflammatory responses within intrauterine tissues and cause the recruitment of leukocytes to the fetal membranes (chorioamnionitis) (9,10). This is so thoroughly accepted that in some studies, chorioamnionitis has been used as being diagnostic of intrauterine infection, without determination of the presence of bacteria (11). However, the precise relation between the presence of bacteria and an inflammatory response has not been clearly defined. This is an important issue as it is not known whether the presence of bacteria always causes chorioamnionitis or whether chorioamnionitis is always linked to infection.Many different organisms have been identified from intrauterine tissues after preterm labor using various sampling and culture techniques (12-14), but no clear pattern has emerged from these studies, so it has not been possible to implicate one particular organism or family of organisms as the main causes of preterm labor. Furthermore, it has not been proved that the bacteria present in the vagina are those that have caused chorioamnionitis in pre...