Epidemiologic Associations With Cerebral Palsy

O’Callaghan, Michael; MacLennan, Alastair H.; Gibson, Catherine; McMichael, G.; Haan, Eric; Broadbent, J. L.; Goldwater, Paul N.; Dekker, Gustaaf A.

doi:10.1097/aog.0b013e31822ad2dc

Cited by 102 publications

(96 citation statements)

References 15 publications

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“…In particular, spastic cerebral palsy increases with the degree of fetal growth restriction. Our large epidemiological study of Australian children and normal controls clearly confirms intrauterine growth restriction as a major risk factor for cerebral palsy 27 Intrauterine growth restriction can be due to many known and unknown causes, but usually reflects poor implantation and poor placentation from genetic, anatomical (e.g. uterine fibroids, congenitally abnormal uterus, abnormal placental site) or pathological causes (e.g.…”

Section: Introductionmentioning

confidence: 65%

“…reports of fever or infection during pregnancy are significantly associated with an increased risk of cerebral palsy in our recent large Australian case-control study 27 . Evidence of intrauterine infection, evidenced by histological chorioamnionitis in the placenta and membranes or intrapartum pyrexia is associated with a 4-5 fold increase in cerebral palsy (RR 4.7, 95% CI 1.3-16.2) in term infants 28 .…”

Section: Introductionmentioning

confidence: 97%

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Cerebral palsy: causes, pathways, and the role of genetic variants

MacLennan

Thompson

Gécz

2015

American Journal of Obstetrics and Gynecology

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371

288

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Cerebral palsy (CP) is heterogeneous with different clinical types, comorbidities, brain imaging patterns, causes, and now also heterogeneous underlying genetic variants. Few are solely due to severe hypoxia or ischemia at birth. This common myth has held back research in causation. The cost of litigation has devastating effects on maternity services with unnecessarily high cesarean delivery rates and subsequent maternal morbidity and mortality. CP rates have remained the same for 50 years despite a 6-fold increase in cesarean birth. Epidemiological studies have shown that the origins of most CP are prior to labor. Increased risk is associated with preterm delivery, congenital malformations, intrauterine infection, fetal growth restriction, multiple pregnancy, and placental abnormalities. Hypoxia at birth may be primary or secondary to preexisting pathology and international criteria help to separate the few cases of CP due to acute intrapartum hypoxia. Until recently, 1-2% of CP (mostly familial) had been linked to causative mutations. Recent genetic studies of sporadic CP cases using new-generation exome sequencing show that 14% of cases have likely causative single-gene mutations and up to 31% have clinically relevant copy number variations. The genetic variants are heterogeneous and require function investigations to prove causation. Whole genome sequencing, fine scale copy number variant investigations, and gene expression studies may extend the percentage of cases with a genetic pathway. Clinical risk factors could act as triggers for CP where there is genetic susceptibility. These new findings should refocus research about the causes of these complex and varied neurodevelopmental disorders.

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Section: Introductionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 97%

Cerebral palsy: causes, pathways, and the role of genetic variants

MacLennan

Thompson

Gécz

2015

American Journal of Obstetrics and Gynecology

Self Cite

371

288

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“…23 Genetic susceptibility may also be triggered by environmental risk factors for CP such as prematurity and IUGR. 5 In some cases, it will be the combination of genetic and nongenetic risk factors that trigger the causal pathway to CP. Four out of our 10 cases were born prematurely and 2 of these carried two or more CNVs.…”

Section: Discussionmentioning

confidence: 99%

“…4 There are a number of known major epidemiological risk factors for CP, including preterm delivery, intrauterine growth restriction (IUGR), intrauterine infection, and multiple pregnancy. 5 There is evidence of genetic susceptibility to CP but little is known about possible mechanisms. 6 Monozygotic twins have a significantly higher (P ¼ 0.0026) concordance rate for CP compared with dizygotic twins.…”

Section: Introductionmentioning

confidence: 99%

Rare copy number variation in cerebral palsy

et al. 2013

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Recent studies have established the role of rare copy number variants (CNVs) in several neurological disorders but the contribution of rare CNVs to cerebral palsy (CP) is not known. Fifty Caucasian families having children with CP were studied using two microarray designs. Potentially pathogenic, rare (o1% population frequency) CNVs were identified, and their frequency determined, by comparing the CNVs found in cases with 8329 adult controls with no known neurological disorders. Ten of the 50 cases (20%) had rare CNVs of potential relevance to CP; there were a total of 14 CNVs, which were observed in o0.1% (o8/8329) of the control population. Eight inherited from an unaffected mother: a 751-kb deletion including FSCB, a 1.5-Mb duplication of 7q21.13, a 534-kb duplication of 15q11.2, a 446-kb duplication including CTNND2, a 219-kb duplication including MCPH1, a 169-kb duplication of 22q13.33, a 64-kb duplication of MC2R, and a 135-bp exonic deletion of SLC06A1. Three inherited from an unaffected father: a 386-kb deletion of 12p12.2-p12.1, a 234-kb duplication of 10q26.13, and a 4-kb exonic deletion of COPS3. The inheritance was unknown for three CNVs: a 157-bp exonic deletion of ACOX1, a 693-kb duplication of 17q25.3, and a 265-kb duplication of DAAM1. This is the first systematic study of CNVs in CP, and although it did not identify de novo mutations, has shown inherited, rare CNVs involving potentially pathogenic genes and pathways requiring further investigation.

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“…Infants under the third centile for weight have an increased risk of cerebral palsy (odds ratio 11.75, 95% confidence interval 6.22 to 12.08). 20 Gestational age is a stronger predictor of cerebral palsy than impaired growth. 20 Other neurodevelopmental consequences of prematurity Motor dysfunction Although many survivors of preterm birth show neuromotor abnormalities on examination, most do not have cerebral palsy.…”

Section: Incidencementioning

confidence: 99%

Preterm birth and the role of neuroprotection

Chang

2015

BMJ

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Preterm birth remains a common complication of pregnancy and causes substantial neonatal morbidity and mortality. As improvements in the care of preterm neonates have outpaced efforts to prevent preterm birth, the numbers of survivors with neurologic sequelae that affect quality of life have increased. The main strategies to reduce the impact of neurologic complications of prematurity include prevention of preterm birth and protection of the developing fetal brain through antenatal administration of drugs. These strategies rely on a basic understanding of the intertwined pathophysiology of spontaneous preterm labor and perinatal brain injury, which will be reviewed here. The review will outline current methods for the prevention of prematurity and neuroprotection. The use of magnesium sulfate as a neuroprotective compound will be discussed, including concerns over its association with increased pediatric mortality and abnormalities in bone density.

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Epidemiologic Associations With Cerebral Palsy

Abstract: II.

Cited by 102 publications

References 15 publications

Cerebral palsy: causes, pathways, and the role of genetic variants

Cerebral palsy: causes, pathways, and the role of genetic variants

Rare copy number variation in cerebral palsy

Preterm birth and the role of neuroprotection

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