Novel Approaches to the Studyof Risk Factors for CerebralPalsy

Abstract

Despite long-standing research, the knowledge of causes and risk factors of cerebral palsy (CP) is limited, and only a few of the risk factors can be prevented. Alternative hypotheses, novel data analyses and more comprehensive studies are therefore needed. One such new hypothesis is that CP is the result of a cascade of causes, rather than one single cause. Furthermore, it may be necessary to study the prevalence of CP in conjunction with perinatal and neonatal mortality. The aim of this thesis was to study the relationship between the prevalence of CP and perinatal mortality rates, the effect of combinations of risk factors on the prevalence of CP, and the probable timing of events leading to CP in singletons born small for gestational age (SGA) at term taking neonatal death into consideration.

The thesis is based upon data relating to Norwegian infants born during 1996-2003. In paper I, all infants were included, whereas in paper III only live born infants were included. For paper II, only those born during 1996-98 and surviving the neonatal period were considered. Clinical data on a number of potential antenatal and perinatal risk factors for CP were available in the Medical Birth Registry of Norway. For children with CP, detailed clinical data were available in the Cerebral Palsy Register of Norway. Furthermore, Apgar scores at five minutes, antenatal and intrapartum risk factors, magnetic resonance imaging (MRI)-findings and CP-subtypes were used to assess the probable timing of events leading to CP or neonatal death.

Prevalence of CP, neonatal mortality rates (NMR) and preterm birth varied significantly between the 19 counties. After adjustment for differences in prematurity rates between the counties, the correlation coefficient between prevalence of CP and NMR was -0.48 (p = 0.04), suggesting that higher survival in the neonatal period may be achieved at the cost of a higher proportion of children with CP. Very few children shared the same combination of risk factors both for children born at term and preterm. The majority of children born at term CP most likely had an antenatal or single cause, suggesting individual susceptibility to an injury. The majority of children born preterm had combinations or sequences of antenatal and perinatal risk factors as the most likely cause of CP. Among 69 children with CP born SGA, intrapartum origin of CP was considered in five children (7%; CI: 3-16), compared with 31 of 263 (12%; CI: 8-16) non-SGA children (p = 0.28). The low proportion of SGA children with CP following a probable intrapartum event was not outweighed by a higher neonatal mortality rate when congenital malformations were excluded. Despite increased risk of both low Apgar score and CP among children born SGA, our findings suggest that in nine out of ten children born SGA the event leading to CP is of antenatal origin. The higher risk of CP among SGA than non-SGA children is probably due to an overall higher prevalence of antenatal risk factors leading to CP and neonatal death (p < 0.001).