Noninherited Risk Factors Research Articles

Prevalence of Congenital Heart Defects and their Non-Inherited Risk Factors among Children through the Period 2019-2023: A Retrospective Comparative Study

Background: Congenital heart defects (CHD) are the most common types of congenital disabilities. The frequency of CHD among their patient populations also remains the leading cause of their increased mortality, accounting for an estimated 50% of all causes of death from abnormalities. Objectives: The study aimed to identify the prevalence of non-inherited risk factors among children with cardiac defects and compare the prevalence of congenital heart defects among children in different governorates in Iraq related to non-inherited risk factors. Materials and Methods: A retrospective study design was used to study congenital heart defects in children in Babylon Centre for Catheterization and Cardiac Surgery in Al-Imam Sadiq Hospital Babylon province, Iraq, from 15/10/2023 to 13/6/2024. A nonprobability convenience sample of 542 patients aged 0-18 years with CHD was collected by administering a constructed tool for the study. The data were collected from all Iraqi governorates, including the north, center, and south, as well as east and west countries. Result: The study shows the mean age of children was 2.2 ±9.2 years. The majority of children included were within infant age groups, almost equal in their sexes, giving girl to boy, 1.04:1. The age at screening and diagnosis of Echo was more than half in the first month, and the type of defect was Ventricular-septal-defect (VSD) and Tetralogy of Fallot (TOF). The study findings show that there is a statistically significant relationship between risk factors related to maternal medication history, including Folic acid Supplements. Maternal diseases such as Rubella, with CHD, and the highest recorded governorates for congenital heart defects are Baghdad, Mosul, and Diyala. Conclusions: The study concludes that most children included were within infant age groups, almost equal in their sexes, and the highest recorded governorates for congenital heart defects are Baghdad, Mosul, and Diyala. Also, the most frequent CHD is VSD and TOF, the history of maternal medication use, including folic acid supplements, and maternal diseases such as Rubella were significant factors in assessing the risk or outcome.

Assessment of Knowledge, Attitudes, and Practices Regarding Non-Inherited Risk Factors for Congenital Heart Disease Among Mothers in Al-Baha City, Saudi Arabia: A Cross-Sectional Study.

Background Despite advancements in healthcare, congenital heart disease (CHD) remains a global concern. It is crucial to understand non-inherited risk factors for CHD to develop effective prevention strategies. This study evaluates the awareness and impact of socio-economic factors on the knowledge and practices regarding CHD among mothers in Al-Baha City, Saudi Arabia. Methods A cross-sectional study was conducted using a structured questionnaire distributed among 300 mothers. This questionnaire collected demographic data and assessed the knowledge of non-inherited CHD risk factors, along with associated health practices. Chi-square tests were employed for categorical variables, and logistic regression was used to analyze the influence of socioeconomic factors on awareness levels. Results The study revealed a significant association between higher educational levels and increased awareness of CHD risk factors. About 75% of mothers with postgraduate education accurately identified major risk factors, compared to 30% of those with only a high school education. Additionally, income levels influenced health practices, with higher-income groups showing better adherence to recommended health behaviors. Conclusion Our findings highlight the need for targeted educational interventions tailored to diverse socio-economic backgrounds to enhance awareness of CHD risk factors and promote preventive health practices. The study emphasizes the importance of incorporating socioeconomic considerations into public health strategies to reduce the incidence of CHD.

Understanding the Genetic and Non-genetic Interconnections in the Aetiology of Isolated Congenital Heart Disease: An Updated Review: Part 1.

Congenital heart disease (CHD) is the most frequently occurring birth defect. Majority of the earlier reviews focussed on the association of genetic factors with CHD. A few epidemiological studies provide convincing evidence for environmental factors in the causation of CHD. Although the multifactorial theory of gene-environment interaction is the prevailing explanation, explicit understanding of the biological mechanism(s) involved, remains obscure. Nonetheless, integration of all the information into one platform would enable us to better understand the collective risk implicated in CHD development. Great strides in novel genomic technologies namely, massive parallel sequencing, whole exome sequencing, multiomics studies supported by system-biology have greatly improved our understanding of the aetiology of CHD. Molecular genetic studies reveal that cardiac specific gene variants in transcription factors or signalling molecules, or structural proteins could cause CHD. Additionally, non-hereditary contributors such as exposure to teratogens, maternal nutrition, parental age and lifestyle factors also contribute to induce CHD. Moreover, DNA methylation and non-coding RNA are also correlated with CHD. Here, we inform that a complex combination of genetic, environmental and epigenetic factors interact to interfere with morphogenetic processes of cardiac development leading to CHD. It is important, not only to identify individual genetic and non-inherited risk factors but also to recognize which factors interact mutually, causing cardiac defects.

Association of fatty acid desaturase 2 gene polymorphism (rs28456) with susceptibility to bipolar disorder in the Turkish population: A case-control study

The FADS2 gene encodes a key, rate-limiting enzyme involved in polyunsaturated fatty acid (PUFA) metabolism. Recent studies suggest that changes in plasma PUFA levels can lead to disruptions in the neurotransmission system and increase the risk of mood disorders. FADS2 variations may contribute to the individual risk of developing bipolar disorder (BD). We investigated the association of regulatory FADS2 rs28456 with BD in the Turkish population. We performed TaqMan genotyping on 100 patients with BD and 91 healthy controls. Our results did not show significantly different genotype or allele frequencies of rs28456 in the BD cases compared to controls. However, we stratified the cases based on family history, which revealed that minor rs28456-G was observed more frequently (P=0.056) in cases without a family history of psychiatric illness compared to those with a family history of psychiatric illness. A marginally significant difference in the distribution of the ?G? allele (P=0.053) between male patients and healthy males without a family history was observed. Our findings did not provide strong evidence supporting the reported association between rs28456 and BD, yet they point to its potential gender-specific effect, which requires further investigation. Future studies are necessary to explore the impact of FADS2 variations on BD risk in larger study groups, considering their potential interaction with non-inherited risk factors.

Maternal Pre-Existing Diabetes: A Non-Inherited Risk Factor for Congenital Cardiopathies.

Congenital heart defects (CHDs) are the most common form of birth defects in humans. They occur in 9 out of 1000 live births and are defined as structural abnormalities of the heart. Understanding CHDs is difficult due to the heterogeneity of the disease and its multifactorial etiology. Advances in genomic sequencing have made it possible to identify the genetic factors involved in CHDs. However, genetic origins have only been found in a minority of CHD cases, suggesting the contribution of non-inherited (environmental) risk factors to the etiology of CHDs. Maternal pregestational diabetes is associated with a three- to five-fold increased risk of congenital cardiopathies, but the underlying molecular mechanisms are incompletely understood. According to current hypotheses, hyperglycemia is the main teratogenic agent in diabetic pregnancies. It is thought to induce cell damage, directly through genetic and epigenetic dysregulations and/or indirectly through production of reactive oxygen species (ROS). The purpose of this review is to summarize key findings on the molecular mechanisms altered in cardiac development during exposure to hyperglycemic conditions in utero. It also presents the various in vivo and in vitro techniques used to experimentally model pregestational diabetes. Finally, new approaches are suggested to broaden our understanding of the subject and develop new prevention strategies.

Noninherited Risk Factors of Congenital Heart Defects in Offspring: A Revi

Prognosis of children with congenital heart defects (CHDs) continues to improve with advancement in technology and training in pediatric cardiology and cardiac surgery; however, lack of information about risk factors for malformations in cardiovascular development impeded the prevention of CHDs. Etiology of CHDs are complex and possibly lies within the interaction of environmental exposures and inherited factors. Studies found multiple maternal environmental exposures, including living in newly renovated rooms, residential proximity to main traffic, smoking and maternal occupation as manual worker significantly associated with CHDs. Advanced maternal age, low socioeconomic status, maternal perinatal diseases including maternal fever, diabetes, influenza, maternal certain medication use and alcohol intake were also significantly associated with CHDs. Isolated CHDs and multiple defects have different profiles of risk factors, while subtype of CHDs share common risk factors. Because of differences in methods, these studies are only suggestive. Relatively less information has been reported on noninherited factors that may have an adverse effect on the cardiovascular development, which has made it difficult to create population-based strategies to reduce the burden of illness from CHDs and for couples to choose lifestyles to reduce the risk of delivering a child with CHDs.Bangladesh J Child Health 2017; VOL 41 (1) :40-52

Association between oral intake of dydrogesterone during early pregnancy and congenital heart disease: a case-control study

BackgroundCongenital heart disease is the most frequent form of congenital anomaly in newborn infants and accounts for more than a quarter of all serious congenital abnormalities worldwide. A genetic cause is identified in less than 20% of cases of congenital heart disease and in most cases the cause remains unknown. In the context of the health burden of congenital heart disease, the contribution of non-inherited risk factors is important, especially if the disease is caused by a drug that can be avoided during pregnancy. We sought to determine whether maternal dydrogesterone treatment in early pregnancy is associated with congenital heart disease in the infant. MethodsA retrospective case-control study of birth defects and associated risk factors was conducted at Al Rantisi Specialist Paediatric Hospital in the Gaza Strip. Data were obtained and compared between 202 children born with congenital heart disease and a control group of 200 childrenwho did not have congenital heart disease and were randomly selected from the same geographical populations during their admission due to different medical reasons. All children were born in the period of 2010–2013. Data were collected from June, 2013, to December, 2013, by interview with mothers. Dydrogesterone exposure was defined as any reported use during the first trimester of pregnancy. Exclusion criteria included stillbirth, chromosomal abnormalities in the child, and maternal chronic medical illnesses such as diabetes. Binary logistic regression analyses were used to identify any association between drug exposure and congenital heart disease. The study was approved by the human research ethics committee, Ministry of Health, Gaza Strip. Verbal informed consent was obtained from the children's parents. FindingsExposure to dydrogesterone during the first trimester of pregnancy was more frequent among mothers of children born with congenital heart disease (75 of 202) than in mothers of children in the control group (36 of 200; adjusted odds ratio 2·71, 95% CI 1·54–4·24, p<0.001]. InterpretationWe identified a positive association between dydrogesterone use during early pregnancy and congenital heart disease in the offspring. Further studies are needed to confirm these findings. FundingNone.

Pedigree-based Analysis of Inherited and Noninherited Risk Factors of Congenital Heart Defects

BackgroundAlthough congenital heart defect (CHD) pedigrees are rare, they are generally taken as evidence of the existence of a genetic etiologic mechanism or environmental factors common to family members, or a combination of both. Therefore, the analysis of CHD pedigrees is important for bridging the gap in our knowledge of its etiology. AimsTo assess the prevalence of CHD and evaluate the nongenetic factors in the CHD patients and healthy controls in the pedigrees. Study designObservational retrospective study. SubjectsTwenty-three CHD pedigrees were involved in the prevalence statistics; thirty-nine CHD cases and fifty-two healthy controls in the CHD pedigrees were included in the family-based noninherited factors analysis. Outcome measuresThe three-degree relatives and overall CHD prevalence were calculated. Thirty-four noninherited risk factors were compared between the CHD and control groups, first by univariate analysis and later by multivariable logistic stepwise regression analysis. ResultsThe CHD prevalence of the probands’ relatives in all pedigrees was 8.0%, and it was 10.9%, 2.9% and 11.9% in first-, second- and third-degree relatives, respectively. The three risk factors, including maternal febrile illnesses (OR=14.2, 95%CI: [1.5 - 133.7]), influenza (OR=6.9 [2.0 - 23.6]) and air pollution (OR=13.5 [2.6 - 70.5]), were strongly associated with a higher risk of CHD in our sample. ConclusionsFor the cluster and high prevalence of CHD in the collected pedigrees, our study confirms that genetic factors play a major role in the pathogenesis of CHD, while environmental factors, such as maternal febrile illnesses, influenza and air pollution, may also increase the burden of risk for CHD pathogenesis.

The Impact of Oral Intake of Dydrogesterone on Fetal Heart Development During Early Pregnancy.

Congenital heart disease is the most frequent form of congenital anomaly in newborn infants and accounts for more than a quarter of all serious congenital afflictions worldwide. A genetic etiology is identified in <20 % of cases of congenital heart defects, and in most cases the etiology remains a mystery. In the context of the health burden caused by congenital heart disease, the contribution of non-inherited risk factors is important especially if it turns out to be caused by a drug which can be avoided during pregnancy. We sought to determine whether maternal dydrogesterone treatment in early pregnancy is associated with congenital heart disease in the infant. We conducted a retrospective case-control study of birth defects and associated risk factors. Data were obtained and compared between 202 children born with congenital heart disease and a control group consisting of 200 children. All children were born in the period of 2010-2013. Dydrogesterone exposure was defined as any reported use during the first trimester of pregnancy. Exclusion criteria included stillbirths, children with chromosomal abnormalities and infants of mothers with chronic medical illnesses, e.g., diabetes. Binary logistic regression analyses were used to analyze the data and attempt to identify a causal relationship between drug exposure and congenital heart disease. Mothers of children born with congenital heart disease received more dydrogesterone during first trimester of pregnancy than mothers of children in the control group [adjusted odds ratio 2.71; (95 % CI 1.54-4.24); P = 0.001]. We identified a positive association between dydrogesterone usage during early pregnancy and congenital heart disease in the offspring. Nevertheless, further studies are needed to confirm these results.

Maternal lifestyle factors in pregnancy and congenital heart defects in offspring: review of the current evidence.

The prognosis of children with congenital heart defects(CHDs) continues to improve with advancing surgical techniques; however, lack of information about modifiable risk factors for malformations in cardiovascular development impeded the prevention of CHDs. We investigated an association between maternal lifestyle factors and the risk of CHDs, because epidemiological studies have reported conflicting results regarding maternal lifestyle factors and the risk of CHDs recently. A review published on 2007 provided a summary of maternal exposures associated with an increased risk of CHDs. As part of noninherited risk factors, we conducted a brief overview of studies on the evidence linking common maternal lifestyle factors, specifically smoking, alcohol, illicit drugs, caffeine, body mass index and psychological factors to the development of CHDs in offspring. Women who smoke and have an excessive body mass index(BMI) during pregnancy are suspected to be associated with CHDs in offspring. Our findings could cause public health policy makers to pay more attention to women at risk and could be used in the development of population-based prevention strategies to reduce the incidence and burden of CHDs. However, more prospective studies are needed to investigate the association between maternal lifestyle factors and CHDs.

Noninherited Risk Factors and Congenital Cardiovascular Defects: Current Knowledge

Noninherited Risk Factors and Congenital Cardiovascular Defects: Current Knowledge

Noninherited Risk Factors and Congenital Cardiovascular Defects: Current Knowledge

Prevention of congenital cardiovascular defects has been hampered by a lack of information about modifiable risk factors for abnormalities in cardiac development. Over the past decade, there have been major breakthroughs in the understanding of inherited causes of congenital heart disease, including the identification of specific genetic abnormalities for some types of malformations. Although relatively less information has been available on noninherited modifiable factors that may have an adverse effect on the fetal heart, there is a growing body of epidemiological literature on this topic. This statement summarizes the currently available literature on potential fetal exposures that might alter risk for cardiovascular defects. Information is summarized for periconceptional multivitamin or folic acid intake, which may reduce the risk of cardiac disease in the fetus, and for additional types of potential exposures that may increase the risk, including maternal illnesses, maternal therapeutic and nontherapeutic drug exposures, environmental exposures, and paternal exposures. Information is highlighted regarding definitive risk factors such as maternal rubella; phenylketonuria; pregestational diabetes; exposure to thalidomide, vitamin A cogeners, or retinoids; and indomethacin tocolysis. Caveats regarding interpretation of possible exposure-outcome relationships from case-control studies are given because this type of study has provided most of the available information. Guidelines for prospective parents that could reduce the likelihood that their child will have a major cardiac malformation are given. Issues related to pregnancy monitoring are discussed. Knowledge gaps and future sources of new information on risk factors are described.

Inherited and noninherited risk factors in rheumatoid arthritis.

Rheumatoid arthritis (RA) is likely the result of a concerted action of several inherited and noninherited factors. Although there is a high suspicion that environmental factors are important, proof is missing. Most information has been collected on genetic risk factors. The inheritance pattern for RA is complex, and there is good evidence that HLA as well as non-HLA genes are involved. Almost all racial-ethnic groups share the association of RA with the HLA-DRB1-encoded sequence motif QKRAA or QRRAA. However, the completeness of the association varies significantly in different ethnic cohorts, as can be expected in a multigene model. The sequence motif translates into a pocket in the antigen-binding site of the HLA-DR molecule. The "rheumatoid pocket" accommodates peptide side chains and has distinct binding characteristics. Epidemiologic evidence points toward a role for non-HLA genes. Candidate genes, such as transporter in antigen processing (TAP) genes are currently explored. Major advances in defining and understanding the contribution of inherited and noninherited factors in RA may come from abandoning the concept of RA as a single entity and accepting a heterogeneity model for RA. Distributions of HLA-DR genes indicate that several subsets of RA patients exist. Seronegative (prognostically good) and seropositive (prognostically worse) patients can be distinguished by the arginine versus lysine substitution at position 71 of the HLA-DRB1 gene. A different dimension of disease, rheumatoid organ disease, appears to be reached in patients with two HLA-DRB1*0401 alleles. Identification of distinct RA subsets may allow us to stratify patients into categories that differ with respect to etiology, disease course, clinical pattern, and treatment response.