Cytomegalovirus and Epstein–Barr virus may be associated with some cases of cerebral palsy

McMichael, G.; MacLennan, Alastair H.; Gibson, Catherine; Alvino, E.; Goldwater, Paul N.; Haan, Eric; Dekker, Gustaaf A.

doi:10.3109/14767058.2012.666587

Cited by 20 publications

(19 citation statements)

References 27 publications

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“…The proportion of CP cases attributed to cCMV in this study was 1.5%. This is comparable to a state-based Australian study that retrospectively analyzed newborn screening cards 15 and estimates of severe neurological impairment from a recent European long-term follow up study. 10 This study utilized data available in an Australian CP register where cCMV was reported as the known cause and a requirement of laboratory confirmed evidence of CMV infection.…”

Section: Discussionsupporting

confidence: 73%

“…An Australian case-control study 14,15 identified cCMV DNA in 1.5% of newborn screening cards from CP cases in a revised estimate. 15 Clinical details of the children with CP and cCMV were not reported. Radiographic features [16][17][18] and/or neonatal 19 or early childhood signs 17,18 have also been described in a small case series of children with CP and confirmed cCMV, however the CP profile of these children was not well defined.…”

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confidence: 99%

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Congenital cytomegalovirus is associated with severe forms of cerebral palsy and female sex in a retrospective population‐based study

Smithers‐Sheedy

Raynes‐Greenow

Badawi

et al. 2014

Develop Med Child Neuro

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ACPR wk [4.4], range 24-41 wk) accounted for 1.5% of CP cases; 2.9 per 100 000 live births, (95% confidence intervals 1.9-3.9). When compared with CP cases where cCMV was not reported, proportionally, more CP cases with cCMV were born to younger mothers (p<0.001), were female (64% vs 43%, p=0.014), had spastic quadriplegia (73% vs 21%, p<0.001), required wheeled mobility i.e. GMFCS IV or V (78% vs 28%, p<0.001), had epilepsy (70% vs 30%, p<0.001), deafness (40% vs 2%, p<0.001), functional blindness (20% vs 5%, p<0.001), and severe communication impairment (71% vs 25%, p<0.001).

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Section: Discussionsupporting

confidence: 73%

mentioning

confidence: 99%

Congenital cytomegalovirus is associated with severe forms of cerebral palsy and female sex in a retrospective population‐based study

Smithers‐Sheedy

Raynes‐Greenow

Badawi

et al. 2014

Develop Med Child Neuro

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“…The increased prevalence of placental and cord abnormalities in children subsequently diagnosed with cerebral palsy underlines the importance of requesting placental histology and cord arterial gases in all caseswhere the baby is delivered in poor condition13 . spots from cerebral palsy cases and controls show increased cerebral palsy risk after both Cytomegalovirus and Epstein Barr virus infections during pregnancy40 .…”

mentioning

confidence: 99%

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

MacLennan

Thompson

Gécz

2015

American Journal of Obstetrics and Gynecology

372

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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“…Permanent physical sequelae include microcephaly, hearing loss, vision loss, and mental retardation. Furthermore, there is evidence that intrauterine CMV infection is significantly associated with cerebral palsy [11 ]. Between 20,000 and 40,000 children are born with congenital CMV infections in the USA each year, resulting in 100–200 deaths and 4,000–8,000 individuals developing permanent neurological sequelae [12, 13].…”

Section: Overt Danger: CMV Infection and Its Burden To Public Healthmentioning

confidence: 99%

Synthetic DNA Approach to Cytomegalovirus Vaccine/Immune Therapy

Villarreal

Shedlock

et al. 2015

Advances in Experimental Medicine and Biology

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There is no licensed vaccine or cure for human cytomegalovirus (CMV), a ubiquitous β-herpes virus that infects 60–95 % of adults worldwide. Infection is a major cause of congenital abnormalities in newborns, contributes to development of childhood cerebral palsy and medulloblastoma, can result in severe disease in immunocompromised patients, and is a major impediment during successful organ transplantation. While CMV has been increasingly associated with numerous inflammatory diseases and cancers, only recently has it been correlated with increased risk of heart disease in adults, the number-one killer in the USA. These data, among others, suggest that subclinical CMV infection, or microinfection, in healthy individuals may play more of a causative role than an epiphenomenon in development of CMV-associated pathologies. Due to the myriad of diseases and complications associated with CMV, an efficacious vaccine would be highly valuable in reducing human morbidity and mortality as well as saving billions of dollars in annual health-care costs and disability adjusted life years (DALY) in the developing world. Therefore, the development of a safe efficacious CMV vaccine or immune therapy is paramount to the public health. This review aims to provide a brief overview on aspects of CMV infection and disease and focuses on current vaccine strategies. The use of new synthetic DNA vaccines might offer one such approach to this difficult problem.

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Cytomegalovirus and Epstein–Barr virus may be associated with some cases of cerebral palsy

Abstract: Evidence of congenital viral infection was uncommon in cases of cerebral palsy and controls. However, CMV and EBV were significantly associated with cerebral palsy.

Cited by 20 publications

References 27 publications

Congenital cytomegalovirus is associated with severe forms of cerebral palsy and female sex in a retrospective population‐based study

Congenital cytomegalovirus is associated with severe forms of cerebral palsy and female sex in a retrospective population‐based study

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

Synthetic DNA Approach to Cytomegalovirus Vaccine/Immune Therapy

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