The non-genetic paternal factors for congenital heart defects: A systematic review and meta-analysis.
ABSTRACT: BACKGROUND:Advances have been made in identifying genetic etiologies and maternal risk factors of congenital heart defects (CHDs), while few literatures are available regarding paternal risk factors for CHDs. Thus, we aim to conduct a meta-analysis and systematic review about the non-genetic paternal risk factors for CHDs. METHODS:We searched the PubMed, MEDLINE, and Cochrane Library online databases and identified 31 studies published between 1990 and 2018 according to the inclusion criteria. Paternal risk factors were divided into subgroups, and summarized odd ratios (OR) were calculated. RESULTS:Paternal age between 24 and 29 years decreased the risk of CHDs in the offspring (OR = 0.90 [0.82, 0.98]), while paternal age ≥ 35 years old increased the risk of CHDs (35-39 years old: OR = 1.14 [1.09, 1.19], and ≥ 40 years: OR = 1.27 [1.14, 1.42]). Paternal cigarette smoking increased the risk of CHDs in a dose-dependent way. Paternal wine drinking (OR = 1.47 [1.05, 2.07]) and exposure to chemical agents or drugs (OR = 2.15 [1.53, 3.02]) also increased the risk of CHDs. Some specific paternal occupations were also associated with increased risk for CHDs or CHD subtypes including factory workers, janitors, painters, and plywood mill workers. CONCLUSIONS:This meta-analysis and systematic review suggested that advanced paternal age, cigarette smoking, wine drinking, exposure to chemical agents or drugs and some specific occupations were associated with an increased risk of CHDs. More measures should be taken to reduce occupational and environment exposures. At the same time, fertility at certain age and establishment of healthy life habits are strongly recommended.
Project description:Paternal age has been associated with offspring congenital heart defects (CHDs), which might be caused by increased mutations in the germ cell line because of cumulated cell replications. Empirical evidences, however, remain inconclusive. Furthermore, it is unknown whether all subtypes of CHDs are affected by paternal age. We aimed to explore the relationship between paternal age and the risk of offspring CHDs and its five common subtypes using national register data in Denmark. A total of 1,893,899 singletons born in Denmark from 1977 to 2008 were included in this national-based cohort study. Cox's proportion hazards model with robust sandwich estimate option was used to estimate the hazards ratio (95% confidence interval) for the associations between paternal age and all CHDs, as well as subtypes of CHDs (patent ductus arteriosus (PDA), ventricular septal defect (VSD), atrial septal defect (ASD), tetralogy of fallot (TOF) and coarctation of the aorta (CoA)). We did not observe an overall association between paternal age and offspring CHDs. However, compared to the paternal age of 25-29 years, paternal age of older than 45 years was associated with a 69% increased risk of PDA (HR45+ = 1.69, 95%CI:1.17-2.43). We observed similar results when subanalyses were restricted to children born to mothers of 27-30 years old. After taking into consideration of maternal age, our data suggested that advanced paternal age was associated with an increased prevalence of one subtype of offspring congenital heart defects (CHDs), namely patent ductus arteriosus (PDA).
Project description:The study aims to explore the associations between various occupations and thyroid cancer risk.A population-based, case-control study involving 462 histologically confirmed incident cases and 498 controls was conducted in Connecticut in 2010 to 2011.A significantly increased risk of thyroid cancer, particularly papillary microcarcinoma, was observed for those working as the health care practitioners and technical workers, health diagnosing and treating practitioners, and registered nurses. Those working in building and grounds cleaning, maintenance occupations, pest control, retail sales, and customer service also had increased risk for papillary thyroid cancer. Subjects who worked as cooks, janitors, cleaners, and customer service representatives were at an increased risk of papillary thyroid cancer with tumor size more than 1?cm.Certain occupations were associated with an increased risk of thyroid cancer, with some tumor size and subtype specificity.
Project description:Paternal occupational exposures have been proposed as a risk factor for childhood leukaemia. This study investigates possible associations between paternal occupational exposure and childhood leukaemia in Great Britain.The National Registry of Childhood Tumours provided all cases of childhood leukaemia born and diagnosed in Great Britain between 1962 and 2006. Controls were matched on sex, period of birth and birth registration subdistrict. Fathers' occupations were assigned to 1 or more of 33 exposure groups. Social class was derived from father's occupation at the time of the child's birth.A total of 16 764 cases of childhood leukaemia were ascertained. One exposure group, paternal social contact, was associated with total childhood leukaemia (odds ratio 1.14, 1.05-1.23); this association remained significant when adjusted for social class. The subtypes lymphoid leukaemia (LL) and acute myeloid leukaemia showed increased risk with paternal exposure to social contact before adjustment for social class. Risk of other leukaemias was significantly increased by exposure to electromagnetic fields, persisting after adjustment for social class. For total leukaemia, the risks for exposure to lead and exhaust fumes were significantly <1. Occupationally derived social class was associated with risk of LL, with the risk being increased in the higher social classes.Our results showed some support for a positive association between childhood leukaemia risk and paternal occupation involving social contact. Additionally, LL risk increased with higher paternal occupational social class.
Project description:Acute myeloid leukemia (AML) is the most common type of leukemia found in adults. Identifying jobs that pose a risk for AML may be useful for identifying new risk factors. A matched case-control analysis was conducted using California Cancer Registry data from 1988 to 2007. This study included 8999 cases of AML and 24 822 controls. Industries with a statistically significant increased AML risk were construction (matched odds ratio [mOR] = 1.13); crop production (mOR = 1.41); support activities for agriculture and forestry (mOR = 2.05); and animal slaughtering and processing (mOR = 2.09). Among occupations with a statistically significant increased AML risk were miscellaneous agricultural workers (mOR = 1.76); fishers and related fishing workers (mOR = 2.02); nursing, psychiatric and home health aides (mOR = 1.65); and janitors and building cleaners (mOR = 1.54). Further investigation is needed to confirm study findings and to identify specific exposures responsible for the increased risks.
Project description:Background:Congenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown. Higher prenatal body mass index (BMI), smoking and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear. Methods and Results:Seven European birth cohorts including 232,390 offspring (2,469 CHD cases [1.1%]) were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression and combined estimates using a fixed-effects meta-analysis. Analyses of BMI categories resulted in similar increased odds of CHD in overweight (mothers OR: 1.15 (1.01, 1.31) and fathers 1.10 (0.96, 1.27)) and obesity (mothers OR: 1.12 (0.93, 1.36) and fathers 1.16 (0.90, 1.50)). The association of mean BMI with CHD was null. Maternal smoking was associated with increased odds of CHD (OR: 1.11 (0.97, 1.25)) but paternal smoking was not (OR: 0.96 (0.85, 1.07)). The difference increased when removing offspring with genetic/chromosomal defects (mothers OR: 1.15 (1.01, 1.32) and fathers 0.93 (0.83, 1.05)). The positive association with maternal pregnancy smoking appeared to be driven by non-severe CHD cases (OR: 1.22 (1.04, 1.44)). Associations with maternal (OR: 1.16 (0.52, 2.58)) and paternal (OR: 1.23 (0.74, 2.06)) moderate/heavy pregnancy alcohol consumption were similar. Conclusions:We found evidence of an intrauterine effect for maternal smoking on offspring CHDs, but no evidence for higher maternal BMI or alcohol consumption. Our findings provide further support for why smoking cessation is important during pregnancy.
Project description:INTRODUCTION: Advanced paternal age (APA) is a reported risk factor for schizophrenia in the offspring. We performed a meta-analysis of this association, considering the effect of gender and study design. METHODS: We identified articles by searching Pub Med, PsychInfo, ISI, and EMBASE, and the reference lists of identified studies. Previously unpublished data from the Northern Finland 1966 Birth Cohort (NFBC 1966) study were also included. RESULTS: There were 6 cohort studies and 6 case-control studies that met the inclusion criteria. In both study designs, there was a significant increase in risk of schizophrenia in the offspring of older fathers (?30) compared to a reference paternal age of 25-29, with no gender differences. The relative risk (RR) in the oldest fathers (?50) was 1.66 [95% confidence interval (95% CI): 1.46-1.89, P < 0.01]. A significant increase in risk was also found for younger fathers (<25) in males (RR = 1.08, 95% CI: 1.02-1.14, P = 0.01) but not females (RR = 1.04, 95% CI: 0.97-1.14, P = 0.28). The population attributable risk percentage (PAR%) was 10% for paternal age ?30 and 5% for paternal age <25. DISCUSSION: Both APA (?30) and younger paternal age (<25) increase the risk of schizophrenia; younger paternal age may be associated with an increased risk in males but not females. This risk factor increases the risk of schizophrenia as much as any single candidate gene of risk. The mechanism of these associations is not known and may differ for older and younger fathers.
Project description:Employers play a vital role in promoting and supporting tobacco use cessation among tobacco-using workers. Cigarette smoking during pregnancy is a preventable cause of complications in pregnancy and adverse infant health outcomes.To estimate cigarette smoking prevalence and attempts to quit among working women of reproductive age in different industries and occupations using a nationally representative survey.The 2009-2013 National Health Interview Survey data for women of reproductive age (18-49 years) who were working in the week prior to the interview (n = 30855) were analyzed. Data were adjusted for nonresponse and weighted to produce nationally representative estimates.During 2009-2013, among working women of reproductive age, an estimated 17.3% (95% confidence interval [CI]: 16.7-17.8) and 12.9% (95% CI: 12.4-13.4) were current and former cigarette smokers, respectively. Of women who smoke daily, 44.5% (95% CI: 42.5-46.5) had made a quit attempt for more than 1 day in the year before the interview. Cigarette smoking prevalence was highest among women working in the construction industry (29.2%; 95% CI: 22.8-35.7) and in construction and extraction occupations (34.6%; 95% CI: 23.4-45.9). Among working women who were pregnant at the time of the interview, 6.8% (95% CI: 4.4-9.2) and 20.4% (95% CI: 16.9-24.0) were current and former cigarette smokers, respectively.Cigarette smoking prevalence varies by industry and occupation. Intensifying tobacco control efforts in high prevalence industries and occupations could result in higher cessation rates and improvements in health among women of reproductive age.This study identified discrepancies in cigarette smoking among women of reproductive age across industries and occupations. In the absence of smoke-free local and state laws, employer-established smoke-free policies and workplace cessation programs are important for achieving reduction of tobacco use among women and for protecting other workers' health. Results in this report may assist in developing educational campaigns targeting women in industries and occupations with high prevalence of cigarette smoking and low percentage of ever-smokers who had quit.
Project description:Congenital heart defects (CHDs) arise through various combinations of genetic and environmental factors. Our study explores how polymorphisms in the glutathione S-transferase (GST) genes affect the association between cigarette smoke exposure and CHDs. We analysed 299 mothers of children with CHDs and 284 mothers of children without any abnormalities who were recruited from six hospitals. The hair nicotine concentration (HNC) was used to quantify maternal smoke exposure, and the maternal GSTT1, and GSTM1 and GSTP1 genes were sequenced. We found a trend of higher adjusted odds ratios with higher maternal HNC levels, suggesting a dose-response relationship between maternal smoke exposure and CHDs. The lowest HNC range associated with an increased risk of CHDs was 0.213-0.319 ng/mg among the mothers with functional deletions of GSTM1 or GSTT1and 0.319-0.573 ng/mg among the mothers with normal copies of GSTM1 and GSTT1. In addition, the adjusted odds ratio for an HNC of >0.573 ng/mg was 38.53 among the mothers with the GSTP1 AG or GG genotype, which was 7.76 (χ(2) = 6.702, p = 0.010) times greater than the AOR in the mothers with GSTP1 AA genotype. Our study suggests that polymorphisms of maternal GST genes may modify the association of maternal smoke exposure with CHDs.
Project description:We investigated the effects of paternal characteristics, including age, body mass index (BMI), and semen parameters on chromosomal aberration-related miscarriages in couples that underwent treatment with assisted reproductive technology (ART). Single nucleotide polymorphism (SNP) array analysis showed chromosomal aberrations in 60.2% (557/925) of miscarried fetuses, including trisomy in 73.1% (407/557) of cases. There were higher chromosomal aberration rates in fetuses for men aged 20-24 years and ?30 years compared with controls. After adjusting for age and BMI of the female partners, and the BMI and semen parameters of the males, there was no statistically significant effect of paternal age ?30 years on the risk of chromosomal aberrations-related miscarriages. However, the odds of chromosomal abnormality-related miscarriage were 148% higher for the youngest fathers (age: 20-24 years) than fathers aged 25-29 years [adjusted odds ratio (OR): 2.48, 95% confidence interval (CI): 1.03-5.96; P=0.042]. Furthermore, high male BMI (adjusted OR: 1.56, 95% CI: 1.14-2.14; P=0.005) and low semen volume (adjusted OR: 2.09, 95% CI: 1.06-4.11; P=0.034) were associated with increased risk of chromosomal aberration-related miscarriages. These findings demonstrate that very young paternal age, high BMI, and low semen volume are associated with increased risk of chromosomal aberration-related miscarriages in couples undergoing ART treatment.
Project description:Staphylococcus aureus is an important cause of infection, and brings additional concern with methicillin resistance. In addition, nasal methicillin-resistant Staphylococcus aureus (MRSA) colonization rates among health care workers are higher than that for general population. To determine the prevalence rate and risk factors for the colonization of S. aureus, including MRSA, among janitors working in hospitals in northern Taiwan, we conducted this study.Between June and August, 2014, a total of 186 janitors, 111 working in hospitals and 75 working in non-medical institutions, were recruited. Specimens were obtained from the nares of the subjects for the detection of S. aureus, with a questionnaire completed for each subject. All the S. aureus isolates, including MRSA and methicillin-susceptible S. aureus (MSSA), were further molecularly characterized.The nasal carriage rate of S. aureus was 15.3% for hospital janitors and 13.3% for non-medical janitors. The carriage rate of MRSA was 3.6% for hospital janitors and 1.3% for non-medical janitors. No statistically significant difference was found in the nasal carriage rate of S. aureus (p = 0.707) and MRSA (p = 0.65) between hospital janitors and non-medical janitors. Hospital janitors working in hospital more than 6 years and cleaning microbiologic laboratories were significantly associated with nasal S. aureus colonization. All 5 MRSA isolates carried either staphylococcal cassette chromosome type IV or V and three of them belonged to sequence type (ST) 59, the community clone prevailing in Taiwan. Of the 22 MSSA isolates, six pulsotypes were identified, with one major type for 14 isolates (shared by five STs) and another type for 4 isolates (all belonged to ST 188).Exposure to the hospital environment may not increase the nasal carriage rate of S. aureus, including MRSA, among janitors in hospitals in Taiwan. However, for janitors in the hospital setting, working for more than six years in hospital and cleaning laboratories may be risks factors for carrying S. aureus.