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Community-based case-control study of childhood stroke risk associated with congenital heart disease.

ABSTRACT: A better understanding of the stroke risk factors in children with congenital heart disease (CHD) could inform stroke prevention strategies. We analyzed pediatric stroke associated with CHD in a large community-based case-control study.From 2.5 million children (aged <20 years) enrolled in a Northern California integrated healthcare plan, we identified children with ischemic and hemorrhagic strokes and randomly selected age- and facility-matched stroke-free controls (3 per case). We determined exposure to CHD (diagnosed before stroke) and used conditional logistic regression to analyze stroke risk factors.CHD was identified in 15 of 412 cases (4%) versus 7 of 1236 controls (0.6%). Cases of childhood stroke (occurring between ages 29 days to 20 years) with CHD had 19-fold (odds ratio, 19; 95% confidence interval 4.2-83) increased stroke risk compared to controls. History of CHD surgery was associated with >30-fold (odds ratio, 31; confidence interval 4-241) increased risk of stroke in children with CHD when compared with controls. After excluding perioperative strokes, the history of CHD surgery still increased the childhood stroke risk (odds ratio, 13; confidence interval 1.5-114). The majority of children with stroke and CHD were outpatients at the time of stroke, and almost half the cases who underwent cardiac surgery had their stroke >5 years after the most recent procedure. An estimated 7% of ischemic and 2% of hemorrhagic childhood strokes in the population were attributable to CHD.CHD is an important childhood stroke risk factor. Children who undergo CHD surgery remain at elevated risk outside the perioperative period and would benefit from optimized long-term stroke prevention strategies.

SUBMITTER: Fox CK

PROVIDER: S-EPMC4308424 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Community-based case-control study of childhood stroke risk associated with congenital heart disease.

Fox Christine K CK Sidney Stephen S Fullerton Heather J HJ

Stroke 20141216 2

<h4>Background and purpose</h4>A better understanding of the stroke risk factors in children with congenital heart disease (CHD) could inform stroke prevention strategies. We analyzed pediatric stroke associated with CHD in a large community-based case-control study.<h4>Methods</h4>From 2.5 million children (aged <20 years) enrolled in a Northern California integrated healthcare plan, we identified children with ischemic and hemorrhagic strokes and randomly selected age- and facility-matched str ...[more]

PMID: 25516197

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Project description:BackgroundMTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations.MethodsA case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association.ResultsMothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13-2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57-3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01-2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38-4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01-2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02-2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure.ConclusionsMaternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.Trial registrationRegistration number: ChiCTR1800016635 .

Project description:IntroductionThe Baby Hearts study aimed to investigate risk and protective factors for congenital heart disease (CHD), and to investigate the health behaviours of a representative sample of pregnant women in Northern Ireland.ObjectivesWe describe and evaluate the population-based case-control design enhanced with data linkage to administrative health data.MethodsCases (mothers of babies with CHD, n=286) were recruited following diagnosis prenatally or postnatally. Controls (mothers of babies without CHD, n=966) were recruited at 18-22 weeks gestation, from all women attending each maternity unit during a designated month. Hybrid data collection methods were used, including a self-administered iPad/postal questionnaire, and linkage to maternity and prescription records.ResultsRefusal rates were low (8%). iPad questionnaire completion at clinic or home visit had high acceptability whereas postal questionnaires were poorly returned leading to a further 9-10% loss of eligible cases/controls. In total, 61% of eligible cases and 68% of eligible controls were recruited, closely representative of the Northern Ireland population, with no evidence of selection bias. Of those recruited, 97% gave consent for linkage to medical records. Thirty-three percent of women had an unplanned pregnancy and 76% suspected they were pregnant by 5 weeks gestation, with no significant differences between cases and controls. There was considerable discordance between self-report, maternity and prescription records regarding medications obtained/taken in the first trimester, but no evidence of differences between cases and controls that would indicate substantial recall bias. Although there was high concordance between self-report and maternity records regarding folic acid supplementation, cases had significantly lower concordance than controls.ConclusionsOur results suggest hybrid data collection approaches are a useful way forward for aetiological studies to reduce responder burden and address and estimate recall bias, and that the Baby Hearts study protocol is suitable for replication in other populations, modified to the local context.

Dataset Information

Community-based case-control study of childhood stroke risk associated with congenital heart disease.

Publications

Community-based case-control study of childhood stroke risk associated with congenital heart disease.

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