Hugo Lagercrantz

17 décembre 2012

Karolinska Institut, Dept. Women’s and Children’s Health, Stockholm, Sweden

The preterm brain - from birth to adolescence

Séminaire tutoré

invité par Julie Peyronnet-Roux

Abstract : The development of the human brain begins during the third week from conception and continues until about 25 years, when myelination is complete in the forebrain and the connectivity in the brain reaches its peak [1]. Gene-environment and epigenetic mechanisms seem to be particularly important during this long maturation process as compared with other organs. Being born preterm involves a dramatic change of environment which may disturb the developmental trajectory.

Ex-premies have been reported to have a number of neuropsychiatric problems. An inverse relationship between gestational age and IQ has been demonstrated in infants born below 32 weeks (see [2]). Attention deficit disorders and autism are more common among children born before 28 weeks [3]. Schizophrenia and more recently bipolar affective disorders have been reported to be more common among ex-premies [4]. These findings indicate that environmental factors play an important role to cause these diseases often regarded as typical neurogenetic disorders.

Some putative mechanisms will be discussed :

1. Birth and transition to the extrauterine environment has been found to cause a substantial release of neuroactive substances, trigger transcription factors and epigenetic mechanisms [5].

2. Synaptogenesis is probably also affected by the bombardement of sensory impressions in the extra-uterine environment.

3. The increased firing in the preterm brain in the extrauterine environment may disturb the normal spontaneous resting activity, which is probably of importance for the wiring [6].

4. Preterm birth disturbs the normal myelination, which has been demonstrated in adolescent ex-premies [7]. This may explain the cognitive deficits.

5. Preterm birth may affect the alignment of the neuronal columns which can affect the treatment of algoritms. Some ex-premies with autistic spectrum disorders seem to have an exceptional memory for figures etc. There are also some historic examples like Kepler and Newton who were born prematurely.

Some of these deficits can probably be ameliorated by neonatal developmental care, reducing environmental disturbances and stress by creating a more womb-like environment.

In conclusion neuroscientific studies of the preterm brain is not only important to improve neurodevelopment of these children but also to understand the cause of neuropsychiatric diseases in general.

References :

1. Lagercrantz H, Hanson M, Ment LR, Peebles D (eds) (2010) The newborn brain. Neuroscience and clinical applications. 2nd ed, Cambridge : Cambridge University Press.

2. Lagercrantz H (2008) The hard problem. Acta Paediatr 97 : p. 142-3.

3. Indredavik MS et al. (2008) Positive screening results for autism in ex-preterm infants. Pediatrics 122 : 222 ; author reply 222-3.

4. Nosarti C et al. (2012) Preterm birth and psychiatric disorders in young adult life. Arch Gen Psychiatry

5. Schlinzig T et al. (2009) Epigenetic modulation at brith - altered DNA -methylation in white blood cells after Caesarean section. Acta Paediatrica 98 : 1096- 1099

6. Fransson P et al. (2011) The functional architecture of the infant brain as revealed by resting-state fMRl. Cerebral Cortex 21 : 145-54

7. Nagy Z et al. (2003) Preterm children have disturbances of white matter at 11 years of age as shown by diffusion tensor imaging. Pediatr Res 54 : 672-9

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