Maternal occupational exposure and congenital heart defects in offspring

Objectives Congenital heart defects (CHD) are the most prevalent congenital anomalies. This study aims to examine the association between maternal occupational exposures to organic and mineral dust, solvents, pesticides, and metal dust and fumes and CHD in the offspring, assessing several subgroups of CHD. Methods For this case-control study, we examined 1174 cases with CHD from EUROCAT Northern Netherlands and 5602 controls without congenital anomalies from the Lifelines cohort study. Information on maternal jobs held early in pregnancy was collected via self-administered questionnaires, and job titles were linked to occupational exposures using a job exposure matrix. Results An association was found between organic dust exposure and coarctation of aorta [adjusted odds ratio (OR adj) 1.90, 95% confidence interval (CI) 1.01-3.59] and pulmonary (valve) stenosis in combination with ventricular septal defect (OR adj2.68, 95% CI 1.07-6.73). Mineral dust exposure was associated with increased risk of coarctation of aorta (OR adj2.94, 95% CI 1.21-7.13) and pulmonary valve stenosis (OR adj1.99, 95% CI 1.10-3.62). Exposure to metal dust and fumes was infrequent but was associated with CHD in general (OR adj2.40, 95% CI 1.09-5.30). Exposure to both mineral dust and metal dust and fumes was associated with septal defects (OR adj3.23, 95% CI 1.14-9.11). Any maternal occupational exposure was associated with a lower risk of aortic stenosis (OR adj0.32, 95% CI 0.11-0.94). Conclusions Women should take preventive measures or avoid exposure to mineral and organic dust as well as metal dust and fumes early in pregnancy as this could possibly affect foetal heart development

Meckel-Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe

Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3?2.6 (range 11-36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies

Maternal occupational exposure and congenital heart defects in offspring

Objectives Congenital heart defects (CHD) are the most prevalent congenital anomalies. This study aims to examine the association between maternal occupational exposures to organic and mineral dust, solvents, pesticides, and metal dust and fumes and CHD in the offspring, assessing several subgroups of CHD. Methods For this case-control study, we examined 1174 cases with CHD from EUROCAT Northern Netherlands and 5602 controls without congenital anomalies from the Lifelines cohort study. Information on maternal jobs held early in pregnancy was collected via self-administered questionnaires, and job titles were linked to occupational exposures using a job exposure matrix. Results An association was found between organic dust exposure and coarctation of aorta [adjusted odds ratio (OR adj) 1.90, 95% confidence interval (CI) 1.01-3.59] and pulmonary (valve) stenosis in combination with ventricular septal defect (OR adj2.68, 95% CI 1.07-6.73). Mineral dust exposure was associated with increased risk of coarctation of aorta (OR adj2.94, 95% CI 1.21-7.13) and pulmonary valve stenosis (OR adj1.99, 95% CI 1.10-3.62). Exposure to metal dust and fumes was infrequent but was associated with CHD in general (OR adj2.40, 95% CI 1.09-5.30). Exposure to both mineral dust and metal dust and fumes was associated with septal defects (OR adj3.23, 95% CI 1.14-9.11). Any maternal occupational exposure was associated with a lower risk of aortic stenosis (OR adj0.32, 95% CI 0.11-0.94). Conclusions Women should take preventive measures or avoid exposure to mineral and organic dust as well as metal dust and fumes early in pregnancy as this could possibly affect foetal heart development

Meckel–Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe

Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11-36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies

Holt Oram syndrome: a registry-based study in Europe

Background: Holt-Oram syndrome (HOS) is an autosomal dominant disorder characterised by upper limb anomalies and congenital heart defects. We present epidemiological and clinical aspects of HOS patients using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. Methods:The study was based on data collected during 1990–2011 by 34 registries. The registries are population based and use multiple sources of information to collect data on all types of birth using standardized definitions,methodology and coding. Diagnostic criteria for inclusion in the study were the presence of radial ray abnormalities and congenital heart disease (CHD), or the presence of either radial ray anomaly or CHD, with family history of HOS. Results: A total of 73 cases of HOS were identified, including 11 (15.1%) TOPFA and 62 (84.9%) LB. Out of 73 HOS cases, 30.8%(20/65) were suspected prenatally, 55.4% (36/65) at birth, 10.7% (7/65) in the first week of life, and 3.1%(2/65) in the first year of life. The prenatal detection rate was 39.2% (20/51), with no significant change over the study period. In 55% (11/20) of prenatally detected cases, parents decided to terminate pregnancy. Thumb anomalies were reported in all cases. Agenesis/hypoplasia of radius was present in 49.2% (30/61), ulnar aplasia/ hypoplasia in 24.6% (15/61) and humerus hypoplasia/phocomelia in 42.6% (26/61) of patients. Congenital heart defects (CHD) were recorded in 78.7% (48/61) of patients. Isolated septal defects were present in 54.2 (26/48), while 25% (12/48) of patients had complex/severe CHD. The mean prevalence of HOS diagnosed prenatally or in the early years of life in European registries was 0.7 per 100,000 births or 1:135,615 births. Conclusions: HOS is a rare genetic condition showing regional variation in its prevalence. It is often missed prenatally, in spite of the existence of major structural anomalies. When discovered, parents in 45% (9/20) of cases opt for the continuation of pregnancy. Although a quarter of patients have severe CHD, the overall first week survival is very good, which is important information for counselling purposes

A Multicountry Analysis of Prevalence and Mortality among Neonates and Children with Bladder Exstrophy

Q2Q1Recién nacidos y niñosObjective: Bladder exstrophy (BE) is a rare but severe birth defect affecting the lower abdominal wall and genitourinary system. The objective of the study is to examine the total prevalence, trends in prevalence, and age-specific mortality among individuals with BE. Study Design: We conducted a retrospective cohort study. Data were analyzed from 20 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research in 16 countries. Live births, stillbirths, and elective terminations of pregnancy for fetal anomaly (ETOPFA) diagnosed with BE from 1974 to 2014. Pooled and program-specific prevalence of BE per 100,000 total births was calculated. The 95% confidence intervals (CI) for prevalence were estimated using Poisson approximation of binomial distribution. Time trends in prevalence of BE from 2000 to 2014 were examined using Poisson regression. Proportion of deaths among BE cases was calculated on the day of birth, day 2 to 6, day 7 to 27, day 28 to 364, 1 to 4 years, and ≥5 years. Mortality analysis was stratified by isolated, multiple, and syndromic case status. Results: The pooled total prevalence of BE was 2.58 per 100,000 total births (95% CI = 2.40, 2.78) for study years 1974 to 2014. Prevalence varied over time with a decreasing trend from 2000 to 2014. The first-week mortality proportion was 3.5, 17.3, and 14.6% among isolated, multiple, and syndromic BE cases, respectively. The majority of first-week mortality occurred on the first day of life among isolated, multiple, and syndromic BE cases. The proportion of first-week deaths was higher among cases reported from programs in Latin America where ETOPFA services were not available. Conclusions: Prevalence of BE varied by program and showed a decreasing trend from 2000 to –2014. Mortality is a concern among multiple and syndromic cases, and a high proportion of deaths among cases occurred during the first week of life. Key Points: Total prevalence of BE was 2.58 per 100,000 births. Prevalence decreased from 2000 to 2014. The first-week mortality was 9.3%.https://orcid.org/0000-0002-0729-6866Revista Internacional - IndexadaA1N

Study of smell and reproductive organs in a mouse model for CHARGE syndrome

CHARGE syndrome is a multiple congenital anomaly syndrome characterised by Coloboma, Heart defects, Atresia of choanae, Retardation of growth and/or development, Genital hypoplasia, and Ear anomalies often associated with deafness. It is caused by heterozygous mutations in the CHD7 gene and shows a highly variable phenotype. Anosmia and hypogonadotropic hypogonadism occur in the majority of the CHARGE patients, but the underlying pathogenesis is unknown. Therefore, we studied the ability to smell and aspects of the reproductive system (reproductive performance, gonadotropin-releasing hormone (GnRH) neurons and anatomy of testes and uteri) in a mouse model for CHARGE syndrome, the whirligig mouse (Chd7(Whi/+)). We showed that Chromodomain Helicase DNA-binding protein 7 (Chd7) is expressed in brain areas involved in olfaction and reproduction during embryonic development. We observed poorer performance in the smell test in adult Chd7(Whi/+) mice, secondary either to olfactory dysfunction or to balance disturbances. Olfactory bulb and reproductive organ abnormalities were observed in a proportion of Chd7(Whi/+) mice. Hypothalamic GnRH neurons were slightly reduced in Chd7(Whi/+) females and reproductive performance was slightly less in Chd7(Whi/+) mice. This study shows that the penetrance of anosmia and hypogonadotropic hypogonadism is lower in Chd7(Whi/+) mice than in CHARGE patients. Interestingly, many phenotypic features of the Chd7 mutation showed incomplete penetrance in our model mice, despite the use of inbred, genetically identical mice. This supports the theory that the extreme variability of the CHARGE phenotype in both humans and mice might be attributed to variations in the fetal microenvironment or to purely stochastic events. European Journal of Human Genetics (2010) 18, 171-177; doi:10.1038/ejhg.2009.158; published online 7 October 200