Congenital anomalies and the severity of impairments for cerebral palsy.

AIM: To study the prevalence of congenital anomalies among children with cerebral palsy (CP) born at term or late preterm, and if CP subtypes and clinical manifestations differ between children with and without congenital anomalies. METHOD: This was a cross-sectional study using data from the Cerebral Palsy Register of Norway and the Medical Birth Registry of Norway. All children with congenital CP born at and later than 34 weeks' gestation in Norway from 1999 to 2009 were included. Anomalies were classified according to the European Surveillance of Congenital Anomalies classification guidelines. Groups were compared using Fisher's exact test, Kruskal-Wallis test, and the Mann-Whitney U test. RESULTS: Among 685 children with CP, 169 (25%) had a congenital anomaly; 125 within the central nervous system. Spastic bilateral CP was more prevalent in children with anomalies (42%) than in children without (34%; p=0.011). Children with anomalies less frequently had low Apgar scores (p<0.001), but more often had severe limitations in gross- and fine-motor function, speech impairments, epilepsy, severe vision, and hearing impairments than children without anomalies (p<0.03). INTERPRETATION: Although children with CP and anomalies had low Apgar scores less frequently, they had more severe limitations in motor function and more associated problems than children with CP without anomalies. WHAT THIS PAPER ADDS: One in four children with cerebral palsy (CP) born at term or late preterm has a congenital anomaly. The added value of neuroimaging to detect central nervous system anomalies in children with CP. Children with anomalies have more severe motor impairments. More severe clinical manifestations are not explained by perinatal complications as indicated by low Apgar scores.

Child apolipoprotein E gene variants and risk of cerebral palsy: estimation from case-parent triads.

OBJECTIVE: To use case-parent triad data to investigate if cerebral palsy (CP) is associated with variants of the APOE gene, the rs59007384 SNP of the TOMM40 gene or combined haplotypes of the two genes. STUDY DESIGN: DNA was analyzed in buccal swabs from 235 children with CP, their parents and a sibling. The relative risks (RR) with 95% confidence intervals (CI) that the children would have a distribution of APOE genotypes, rs59007384 variants or combined haplotypes deviating from Mendelian inheritance were estimated. RESULTS: Children with CP were more likely than expected to carry the APOEε3 allele (RR 7.5; CI: 0.99-53.7 for heterozygotes and 10.3; CI: 1.4-79.6 for homozygotes), and to have the haplotype of APOEε3 and rs59007384 G (RR 2.4; CI: 1-5.7 for heterozygotes, RR 3.7; CI: 1.4-9.5 for homozygotes) whereas the distribution was as expected for rs59007384 alone. In the subgroup analyses the findings were confined to children born preterm. Among siblings the distribution of these genes was as expected according to Mendelian inheritance. CONCLUSION: We speculate that children with APOEε2/APOEε4 alleles are more likely to die following cerebral injury in utero, resulting in a higher than expected proportion of children with CP carrying the APOEε3 allele.

Cerebral palsy and neonatal death in term singletons born small for gestational age.

BACKGROUND AND OBJECTIVES: To investigate the probable timing of events leading to cerebral palsy (CP) in singletons born small for gestational age (SGA) at term, taking neonatal death into consideration. METHODS: In this registry-based cohort study, data on 400 488 singletons born during 1996-2003 were abstracted from the Medical Birth and the CP registries of Norway. Among 36 604 SGA children (birth weight <10th percentile), 104 died in the neonatal period and 69 developed CP. Apgar scores at 5 minutes, risk factors, MRI findings, and CP subtypes were used to assess the timing of events leading to CP or neonatal death. RESULTS: Intrapartum origin of CP was considered in 5 SGA children (7%; 95% confidence interval: 3-16) in comparison with 31 of 263 (12%; 95% confidence interval: 8-16) non-SGA children (P = .28). The proportions of children who died in the neonatal period after a probable intrapartum event did not differ between the groups when children with congenital malformations were excluded. Probable antenatal events leading to CP and neonatal death were more common among SGA than non-SGA children (P < .001). CONCLUSIONS: In ~90% of children born SGA the event leading to CP is of probable antenatal origin. The low proportion of SGA children with CP after a probable intrapartum event was not outweighed by a higher neonatal mortality rate when congenital malformations were excluded. The higher risk of CP among SGA than among non-SGA children is probably due to a higher prevalence of antenatal risk factors.

The effects of multiple pre- and perinatal risk factors on the occurrence of cerebral palsy. A Norwegian register based study.

AIMS: To examine the effects of multiple risk factors on cerebral palsy (CP). MATERIALS/METHODS: For 176,591 Norwegian infants born 1996-98 and surviving the early neonatal period, data on a number of potential pre- and perinatal risk factors (RFs) for CP were available in the Medical Birth Registry of Norway. For 241 children with CP detailed clinical data were available in the Norwegian CP registry. RESULTS: In children born at term, 31% had no RF, and none had five or more, while in children born preterm, 9% had no RF in addition to prematurity (p < 0.001 vs. term), and 5% had five or more (p < 0.02 vs. term). In both groups, few children shared the same combination of RFs. Interdependent sequences were more often observed among children born preterm than at term (p < 0.001 vs. term). The most detrimental effect was observed for the combination of maternal disease and low 5-min Apgar score, registered in 11.2% of children with CP. The combination of maternal disease and premature birth had an interaction contrast ratio of 9.25 (CI: 3.56; 14.94), which may be consistent with biological interaction. CONCLUSIONS: The majority of children with CP born at term 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.