Principal Investigator: Liisa Lehtonen, Helena Lapinleimu, Leena Haataja
Researchers:,Eeva Ekholm, Pentti Kero, Riikka Korja, Harry Kujari, Hanna Manninen, Annika Lind, Jonna Maunu, Petriina Munck, Pekka Niemi, Pertti Palo, Riitta Parkkola, Jorma Piha, Liisa Rautava, Päivi Rautava, Milla Reiman, Hellevi Rikalainen, Elina Savonlahti, Matti Sillanpää, Suvi Stolt, Tuula Äärimaa
Department of Pediatrics, Turku University Hospital
Background
The brain of a preterm infant is prone to biological injuries due to prematurity and related treatments. The final functional outcome is further modified by later environmental factors. Research of mechanisms causing and compensating these injuries opens an interesting view into brain development.
Objectives
Centralized care of very preterm infants (<32 weeks of gestation or birth weight <1501 g) provides a solid foundation for our multidisciplinary long-term follow-up study of the preterm infants. We follow a cohort of 232 very preterm infants who survived in Turku University Hospital during the years 2001-2006 and a group of 246 full term healthy control infants. The follow-up is carried out using standardized methods starting from fetal assessments and ending up to the functional outcome at school-age. As successful functioning at school is a sum of different skills and abilities, we have coordinated different approaches to get a full picture of the outcome, the risk factors for later functional deficits and also to find early diagnostic features of an abnormal development in preterm infants.
Key findings by March, 2008
One of our focuses is to study antenatal causes for brain injury. Of the harmful antenatal processes, placental insufficiency manifested as a redistribution of the blood flow in a fetus was shown to relate to reduced brain volumes at term (3). Inflammation itself, although a common cause for a preterm delivery, did not relate to brain pathology (7). However, differences in the genetic predisposition of an individual to mount inflammation related to the risks of both placental inflammation and neonatal infections (11). Genetic polymorphisms of IL-6 promoter region also seemed to affect regional brain volumes (Reiman et PIPARI Group, submitted). We will evaluate the predictive value of regional brain volumes as a tool to screen the infants with later neuropsychological problems.
The quality of early parent-child interaction has a central role in the overall development of a child. Our results show that the quality of mother-infant interaction in preterm group as a whole is comparable to that in the full term infants (5). However, we identified protective factors such as physical contact (carrying the infant) and, on the other hand, risk factors, such as maternal depression (6). The later correlates of early mother-child interaction will be evaluated after the follow-up is completed.
Multidisciplinary clinical research with a long follow-up is necessary to learn to understand the causes and compensating mechanisms of brain injuries related to prematurity. Our aim is also to find early diagnostic predictors of abnormal development to focus the follow-up. We have been able to demonstrate that the size of the receptive lexicon at 1 year of age predicts the language skills at 2 years of age providing a potential way to screen a risk group for a delayed language development among preterm infants (Stolt et al, submitted). Diagnostic predictors can help to target rehabilitation in a cost-effective way for those who benefit of it most.
Understanding the primary origins of injuries and the potential ways to support the compensating mechanisms of the developing brain are crucial to improve the care and to achieve better developmental outcomes. The final goal is to learn to use treatments preventing brain injuries, and when this is not possible, to maximize the recruitment the compensatory mechanisms of the brain.
Contact: liisa.lehtonen(at)utu.fi, tel.: +358 2 3130 253
Original publications:
1. Maunu J, Kirjavainen J, Rikalainen, H, Parkkola R, Rikalainen H, Lapinleimu H, Haataja L, Lehtonen L and the PIPARI Study Group: Relation of prematurity and brain injury to crying in infancy. Pediatrics 2006;118:e57-e65.
2. Rautava L, Lempinen A, Ojala S, Parkkola R, Rikalainen H, Lapinleimu H, Helena Lapinleimu, Leena Haataja, Liisa Lehtonen and PIPARI Study Group. Acoustic quality of cry in very-low-birth-weight infants at the age of 1 1/2 years. Early Human Development. 2007/1;83(1):5-12.
3. Maunu J, Ekholm E, Parkkola R, Palo P, Rikalainen H, Lapinleimu H, Haataja L, Lehtonen L and the PIPARI Study Group: Antenatal doppler measurements and early brain injury in very low birth weight infants. J Pediatrics 2007;150:51-56.
4. Stolt S, Klippi A, Launonen K, Munck P, Lehtonen L, Lapinleimu H, Haataja L and the PIPARI Study Group: Size and composition of the lexicon in prematurily born very-low-birth-weight and full-term Finnish children at two years of age. J Child Language 2007;34:283-310.
5. Korja R, Maunu J, Kirjavainen J, Savonlahti E, Haataja L, Lapinleimu H, Manninen H, Piha J, Lehtonen L and the PIPARI Study Group: Mother-Infant Interaction is influenced by the Amount of Holding in Preterm Infants. Early Human Development 2008;84(4): 257-267.
6. Korja R, Savonlahti E, Ahlqvist-Björkruth S, Stolt S, Haataja, L, Lapinleimu H, Piha J, Lehtonen L and the PIPARI Study Group. Maternal depression is associated with mother-infant interaction in preterm infants. Acta Paediatrica 2008:2;97(6):724-730.
7. Reiman M, Kujari H, Maunu J, Parkkola R, Rikalainen H, Lapinleimu H, Lehtonen L, Haataja L and the PIPARI Study Group: Does placental inflammation relate to brain lesions and volume in very low birth weight infants? J Pediatrics 2008;152:642-7.
8. Munck P; Maunu J, Kirjavainen J, Lapinleimu H, Haataja L, Lehtonen L and the PIPARI Study Group: Crying Behavior in Early Infancy is Associated with developmental outcome at two years of age in very low birth weight infants. Acta Paediatrica 2008;97:332-336.
9. Stolt S, Haataja L, Lapinleimu, H. and Lehtonen L. Early lexical development of Finnish children – a longitudinal study. First language 2008; 28(3): 259-279.
10. Ekblad M, Maunu J, Munck P, Ekblad S, Matomäki J, Lapinleimu H, Haataja L, Lehtonen L ja PIPARI-tutkimusryhmä: Keskosten äidit tupakoivat raskausaikana muita yleisemmin. Suomen Lääkärilehti 2008; 11: 1047-51.
11. Reiman M, Kujari H, Ekholm E, Lapinleimu H, Lehtonen L, Haataja L and the PIPARI Study Group: Interleukin-6 polymorphism is associated with histological chorioamnionitis and neonatal infections in preterm infants. J Pediatrics 2008;153(1):19-24.
12. Stolt S, Haataja L, Lapinleimu H and Lehtonen L. Associations between lexicon and grammar at the end of the second year in Finnish children. J of Child Language 2009;36(4):779-806.
13. Stolt S, Haataja L, Lapinleimu H and Lehtonen L. Early lexical development of prematurely born very-low-birth-weight children, and its relations to language skills at 2;0. J of Communication Disorders 2009; 42:107-123.
14. Maunu J, Parkkola R, Rikalainen H, Lehtonen L, Haataja L, Lapinleimu H and the PIPARI Study Group: Brain and ventricles in very low birth weight infants at term: a comparison among head circumference, ultrasound and magnetic resonance imaging. Pediatrics 2009;123(2):617-26.
15. Korja R, Savonlahti E, Haataja L, Lapinleimu H, Manninen H, Piha J, Lehtonen L and the PIPARI Study Group: Attachment representations in mothers of preterm infants. Infant Behavior and Development 2009;32(3):305-11.
16. Reiman M, Parkkola R, Lapinleimu H, Lehtonen L, Haataja L and the PIPARI Study Group: Interleukin-6-174 and -572 genotypes and the volume of deep gray matter in preterm infants. Ped Res 2009;65:90-6.
17. Reiman M, Parkkola R, Johansson R, Jääskeläinen S, Kujari H, Lehtonen L, Haataja L, Lapinleimu H and PIPARI Study Group: Diffusion tensor imaging of the inferior colliculus and brainstem auditory-evoked potentials in preterm infants. Pediatr Radiol 2009;39:804-9.