Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses

Abstract

Background The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. Methods We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. Results We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR , MTRR and MTR , GATA4 , NKX2-5 , SRD5A2 , CFTR, and 1p22 and 20q12 anomalies. Conclusion This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.

Prevalence of Congenital Anomaly and Its Relationship with Maternal Education and Age According to Local Development in the Extreme South of Brazil

“…Although in medium and high development regions there is greater income diversity in households, which makes this indicator more disperse, very high development regions are characterized by having almost exclusively high-income families [20], which may explain the difference between the observed frequencies. We can assume that women from regions with very high development have greater gestational planning with better preconception and gestational conditions, such as better prenatal coverage, healthy lifestyle habits, greater access to quality food and in sufficient quantity, which reduces the risk of CA considered preventable [3][4][5]36].…”

Assessment of evidence on reported non-genetic risk factors of congenital heart defects: the updated umbrella review

“…Although there have been published two umbrella reviews, Zhang’s study lacked of not only some important factors, maternal DM for instance, but also assessment of robustness based on sensitivity analysis [ 7 ]; while Lee’s review focused on both environmental and genetic risk factors of all kinds of congenital anomalies rather than only about CHD which seem unreasonable because different types of congenital anomalies occurred based on different pathogenesis [ 8 ]. Furthermore, the evidence was not graded in Lee’s review.…”

“…Compared with the results of published umbrella reviews, most of the summary results are consistent and grade of factors stay the same. Regarding the inconsistent results, partly because we chose latest published largest MA for specific association, in which the component individual studies were different from articles of Zhang’s and Korean research groups [ 7 , 8 ]. On the other hand, since some included MA did not provide the reference list or the complete data for analysis in this umbrella review so that we could not confirm the accuracy of the data in SR after careful consideration, even though we attempted to contact the corresponding author.…”

“…All studies that included the search terms in the titles or abstracts were identified. To supplement the database searches, we further hand-searched the additional potential eligible studies according to the references of the published umbrella reviews as a supplementary search [ 7 , 8 ].…”

“…Although the genetic algorithms for cardiac defects have been constructed, the risk assessment of CHD based on non-genetic risk factors is still imperative because non-genetic risk factors can be prevented more easily [ 6 ]. In order to clarify clear hierarchies of evidence between types of environmental factors and birth defect, especially for CHD, two umbrella reviews based on published systematic reviews and meta-analysis were performed [ 7 , 8 ]. However, with the accumulation of new significant evidence on risk factors of CHD, including maternal diabetes mellitus (DM) [ 9 ], parental smoking [ 10 ], maternal air pollution exposure [ 11 ], maternal caffeinated products [ 12 ], and antidepressant classes and individual antidepressants [ 13 ], it was found that some associations of specific subgroup of CHD had not been contained and analyzed in the published reviews.…”