Elsevier

Early Human Development

Volume 89, Issue 9, September 2013, Pages 643-648
Early Human Development

Cerebral volume at term age: Comparison between preterm and term-born infants using cranial ultrasound

https://doi.org/10.1016/j.earlhumdev.2013.04.012Get rights and content

Abstract

Background and aims

Very preterm infants are at particular risk of neurodevelopmental impairments. This risk can be anticipated when major lesions are seen on cerebral ultrasound (cUS). However, most preterm infants do not have such lesions yet many have a relatively poor outcome. Our study aims were to describe a tri-dimensional cUS model for measuring cranial and brain volume and to determine the range of brain volumes found in preterm infants without major cUS lesions at term equivalent age (TEA) compared to term-born control infants. We also aimed to evaluate whether gestational age (GA) at birth or being small for gestational age (SGA) influenced estimated brain size.

Methods

We scanned a cohort of very preterm infants at TEA and term-born controls. Infants with major cerebral lesions were excluded. Measurements of intracranial diameters (bi-parietal, longitudinal, cranial height), brain structures, ventricles and extracerebral space (ECS) were made. A mathematical model was built to estimate from the cUS measurements the axial area and volumes of the cranium and brain. Appropriate statistical methods were used for comparisons; a p-value under 0.05 was considered significant. SGA infants from both groups were analysed separately.

Results

We assessed 128 infants (72 preterms and 56 controls). The preterms' head was longer (11.5 vs. 10.5 cm, p < 0.001), narrower (7.8 vs. 8.4 cm, p < 0.001) and taller (8.9 vs. 8.6 cm, p < 0.01) than the controls'. Estimated intracranial volume was not statistically different between the groups (411 vs. 399 cm3, NS), but preterms had larger estimated ECS volume (70 vs. 22 cm3, p < 0.001), lateral ventricular coronal areas (33 vs. 12 mm2, p < 0.001) and thalamo-occipital distances (20 vs. 16 mm, p < 0.001), but smaller estimated cerebral volume (340 vs. 377 cm3, p < 0.001). Smaller brain volumes were associated with being of lower gestational age and birth weight and being small-for-gestational age.

Conclusions

We have developed a model using cranial ultrasound for measuring cranial and brain volumes. Using this model our data suggest that even in the absence of major cerebral lesions, the average extrauterine cerebral growth of very preterm infants is compromised. Our model can help in identifying those preterm infants with smaller brains. Later follow-up data will determine the neurodevelopmental outcome of these preterm infants in relation to their estimated brain volumes.

Introduction

Preterm infants are at significant risk of developmental disability. This risk increases with decreasing gestational age (GA) at birth [1]. Focal cerebral lesions identified on cranial ultrasound (cUS) are helpful in predicting types and severity of adverse outcomes, particularly motor deficits [2], [3], [4]. However, most preterm infants born at the present time do not have identifiable focal lesions on cUS [5] yet many have a relatively poor global outcome [6], [7], [8]. Determining which of these infants is at most risk of such neurodevelopmental disability remains a challenge for neonatologists.

Studying brain growth and development in preterm infants without focal brain lesions has been actively researched in recent years, almost exclusively using different magnetic resonance imaging (MRI) techniques, notably not only by defining smaller volumes of different cerebral structures at term equivalent age (TEA), but also by the use of advanced MRI techniques [9], [10], [11], [12], [13], [14] that allow identification of poor cortical development [9], quantification of deep gray matter [12] and white matter maturation issues [14]. However, most of the above studies have been used to show group differences rather than giving information applicable to the individual infant. Also MRI is not widely available for clinical purposes in lower risk preterm infants, since it involves high costs, needs sedation in most cases, interpretation of more subtle findings is difficult and the relationship of such findings to outcome is not so well defined [10].

Some preterm infants without major central nervous system (CNS) lesions have smaller brains at TEA than term controls, even in the absence of overt brain injury [8], [15], [16]. It has been postulated that such infants may be at increased risk of neurodevelopmental disability [16], [17], [18]. Smaller brain volumes at TEA may not be a direct consequence of prematurity itself, but related to postnatal complications, e.g. prolonged oxygen requirement [19], high Clinical Risk Index for Babies (CRIB) score, high C reactive protein and time to achieve full enteral feeds [20].

A qualitative cUS approach detecting poorer brain growth at TEA has been related to poorer outcomes [18], but to the best of our knowledge quantitative approaches using cUS have not been used to address this issue.

We aim to (1) develop a model for estimating cranial and brain volumes using measurements made from cranial ultrasound imaging, (2) assess the reliability of our measurements and (3) determine whether using this model would allow us to find expected differences in brain volumes between preterm infants at TEA and newborn full-term control infants and between appropriate and small-for-gestational age infants at TEA.

Section snippets

Methods

We assessed prospectively during a 28 month period (May 2008–August 2010): (1) a consecutive cohort of preterm infants born at < 32 weeks GA and scanned using cUS at TEA; and (2) a group of term-born control infants scanned during the first postnatal week.

The study was performed at the Hospital de Santa Maria in Lisbon, a tertiary Neonatal Intensive Care Unit (NICU) and main referral centre for south Portugal. Written informed parental consent was obtained for each case and control infant; the

Results

We assessed 128 infants, 72 preterms at TEA and 56 term infants during their first postnatal week (Table 2). The preterm infants were of significantly lower birth weight, were more often born by caesarean section, had lower Apgar scores and higher CRIB scores than the control group. No infant in the control group was invasively ventilated or had culture-proven sepsis. In contrast 44% of the preterm infants were invasively ventilated, and 28% of them had at least one episode of culture-proven

Discussion

We studied a relatively low risk cohort of very preterm infants, excluding any infant with major CNS lesions detected on cUS. This choice was intentional, as the outcome of preterm infants with brain lesions on cUS is relatively well defined [3], [30], and these infants are natural candidates for diagnostic MR to characterize further their brain lesions. On the other hand, neonatologists increasingly care for very preterm infants surviving to term age without any major cUS lesion, and in most

Conflict of interest statement

None to declare.

Acknowledgements

We thank Prof. Ana Isabel Lopes and Prof. Jorge Campos for manuscript reviewing.

References (33)

  • C. Nosarti et al.

    Neonatal ultrasound results following very preterm birth predict adolescent behavioral and cognitive outcome

    Dev Neuropsychol

    (Jan 2011)
  • O. Kapellou et al.

    Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth

    PLoS Med

    (Aug 2006)
  • L. Srinivasan et al.

    Quantification of deep gray matter in preterm infants at term-equivalent age using manual volumetry of 3-tesla magnetic resonance images

    Pediatrics

    (2007 Apr)
  • L. Srinivasan et al.

    Smaller cerebellar volumes in very preterm infants at term-equivalent age are associated with the presence of supratentorial lesions

    AJNR Am J Neuroradiol

    (Mar 2006)
  • B.J.M. van Kooij et al.

    Neonatal tract-based spatial statistics findings and outcome in preterm infants

    AJNR Am J Neuroradiol

    (Jan 2012)
  • A.U.J. Mewes et al.

    Regional brain development in serial magnetic resonance imaging of low-risk preterm infants

    Pediatrics

    (Jul 2006)
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