Discordant Fetal Infection for Parvovirus B19 in a Dichorionic Twin Pregnancy

Dickinson, Jan E.; Keil, Anthony D.; Charles, Adrian

doi:10.1375/183242706777591353

Cited by 7 publications

(4 citation statements)

References 13 publications

(9 reference statements)

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“…Studying twins discordant for CP allows genetic and environmental components to be partitioned from each other and provides a unique opportunity to evaluate the importance of non-shared environmental factors such as umbilical cord or placental function during early development in isolation. It is possible that only twin of a pair may develop an infection or inflammation of the umbilical cord or placenta ([ 13 , 19 , 20 , 94 ]). Such non-shared environmental factors are known to influence the development of individual members of a twin pair.…”

Section: Discussionmentioning

confidence: 99%

“…Such within-pair variation can arise from differences in the length and morphology of the umbilical cord or placenta. This can affect growth rate and development of the individual twins leading to discordance in infection or inflammation, leading to disease discordance [ 13 , 19 , 20 ]. More generally, the study of phenotypically discordant MZ twins, matched for genetic variation, sex, gestational age and maternal factors, provides a great opportunity to examine the role of epigenetics in disease aetiology by allowing us to isolate the effect of such non-shared environmental factors [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Epigenome-wide analysis in newborn blood spots from monozygotic twins discordant for cerebral palsy reveals consistent regional differences in DNA methylation

et al. 2018

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BackgroundCerebral palsy (CP) is a clinical description for a group of motor disorders that are heterogeneous with respect to causes, symptoms and severity. A diagnosis of CP cannot usually be made at birth and in some cases may be delayed until 2–3 years of age. This limits opportunities for early intervention that could otherwise improve long-term outcomes. CP has been recorded in monozygotic twins discordant for the disorder, indicating a potential role of non-genetic factors such as intrauterine infection, hypoxia-ischaemia, haemorrhage and thrombosis. The aim of this exploratory study was to utilise the discordant monozygotic twin model to understand and measure epigenetic changes associated with the development of CP.MethodsWe performed a genome-wide analysis of DNA methylation using the Illumina Infinium Human Methylation 450 BeadChip array with DNA from newborn blood spots of 15 monozygotic twin pairs who later became discordant for CP. Quality control and data preprocessing were undertaken using the minfi R package. Differential methylation analysis was performed using the remove unwanted variation (RUVm) method, taking twin pairing into account in order to identify CP-specific differentially methylated probes (DMPs), and bumphunter was performed to identify differentially methylated regions (DMRs).ResultsWe identified 33 top-ranked DMPs based on a nominal p value cut-off of p < 1 × 10−4 and two DMRs (p < 1 × 10−3) associated with CP. The top-ranked probes related to 25 genes including HNRNPL, RASSF5, CD3D and KALRN involved in immune signalling pathways, in addition to TBC1D24, FBXO9 and VIPR2 previously linked to epileptic encephalopathy. Gene ontology and pathway analysis of top-ranked DMP-associated genes revealed enrichment of inflammatory signalling pathways, regulation of cytokine secretion and regulation of leukocyte-mediated immunity. We also identified two top-ranked DMRs including one on chromosome 6 within the promoter region of LTA gene encoding tumour necrosis factor-beta (TNF-β), an important regulator of inflammation and brain development. The second was within the transcription start site of the LIME1 gene, which plays a key role in inflammatory pathways such as MAPK signalling. CP-specific differential DNA methylation within one of our two top DMRs was validated using an independent platform, MassArray EpiTyper.ConclusionsOurs is the first epigenome-wide association study of CP in disease-discordant monozygotic twin pairs and suggests a potential role for immune dysfunction in this condition.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0457-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epigenome-wide analysis in newborn blood spots from monozygotic twins discordant for cerebral palsy reveals consistent regional differences in DNA methylation

et al. 2018

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“…Discordance in vertical transmission is not unique to ZIKV, as prior case series have reported inter-twin discordance for other antenatally acquired infections, including parvovirus B19 [15], toxoplasmosis [16], and cytomegalovirus [17]. The precise factors that contribute to discordant vertical transmission of congenital infections remain unknown but may include placental alterations that promote versus prevent acquisition of infection.…”

Section: Discussionmentioning

confidence: 98%

Discordant Zika Virus Findings in Twin Pregnancies Complicated by Antenatal Zika Virus Exposure: A Prospective Cohort

Sobhani

Avvad-Portari

Nascimento

et al. 2019

The Journal of Infectious Diseases

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Background There are limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding intertwin concordance of prenatal, placental, and infant outcomes. Methods This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. Polymerase chain reaction (PCR) testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment. Results Among 244 pregnancies, 4 twin gestations without coinfection were identified. Zika virus infection occurred at 16–33 weeks gestation. Zika virus PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the 8 infants, 3 (38%) had an abnormal neonatal outcome. Of 6 infants with long-term follow-up, 3 (50%) have demonstrated ZIKV-related abnormalities. Conclusions Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission.

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“…To date, transplacental transfer of drugs in twin pregnancies has been neglected. Discordant vertical transmission of pathogens has been described for parvovirus (16,17), cytomegalovirus (18), zika (19) toxoplasmosis (20) and HIV (21). Differential placental transfer in twin pairs has been studied for immunoglobulins, with lower levels of antibodies in cord blood reported in case of monochorionic, compared to dichorionic twins (20).…”

Section: Findings In the Context Of What Is Knownmentioning

confidence: 99%

Frequency of differential placental transfer to twins of maternal antiretroviral medications

Louchet

Peytavin

Didelot

et al. 2021

European Journal of Obstetrics & Gynecology and Reproductiv

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Discordant Fetal Infection for Parvovirus B19 in a Dichorionic Twin Pregnancy

Cited by 7 publications

References 13 publications

Epigenome-wide analysis in newborn blood spots from monozygotic twins discordant for cerebral palsy reveals consistent regional differences in DNA methylation

Epigenome-wide analysis in newborn blood spots from monozygotic twins discordant for cerebral palsy reveals consistent regional differences in DNA methylation

Discordant Zika Virus Findings in Twin Pregnancies Complicated by Antenatal Zika Virus Exposure: A Prospective Cohort

Frequency of differential placental transfer to twins of maternal antiretroviral medications

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