Risk of congenital heart defects in offspring exposed to maternal diabetes mellitus: an updated systematic review and meta-analysis

2019 ◽  
Vol 300 (6) ◽  
pp. 1491-1506 ◽  
Author(s):  
Letao Chen ◽  
Tubao Yang ◽  
Lizhang Chen ◽  
Lesan Wang ◽  
Tingting Wang ◽  
...  
Author(s):  
Ali Ghanchi ◽  
Neil Derridj ◽  
Damien Bonnet ◽  
Nathalie Bertille ◽  
Laurent J. Salomon ◽  
...  

Newborns with congenital heart defects tend to have a higher risk of growth restriction, which can be an independent risk factor for adverse outcomes. To date, a systematic review of the relation between congenital heart defects (CHD) and growth restriction at birth, most commonly estimated by its imperfect proxy small for gestational age (SGA), has not been conducted. Objective: To conduct a systematic review and meta-analysis to estimate the proportion of children born with CHD that are small for gestational age (SGA). Methods: The search was carried out from inception until 31 March 2019 on Pubmed and Embase databases. Studies were screened and selected by two independent reviewers who used a predetermined data extraction form to obtain data from studies. Bias was assessed using the Critical Appraisal Skills Programme (CASP) checklist. The database search identified 1783 potentially relevant publications, of which 38 studies were found to be relevant to the study question. A total of 18 studies contained sufficient data for a meta-analysis, which was done using a random effects model. Results: The pooled proportion of SGA in all CHD was 20% (95% CI 16%–24%) and 14% (95% CI 13%–16%) for isolated CHD. Proportion of SGA varied across different CHD ranging from 30% (95% CI 24%–37%) for Tetralogy of Fallot to 12% (95% CI 7%–18%) for isolated atrial septal defect. The majority of studies included in the meta-analysis were population-based studies published after 2010. Conclusion: The overall proportion of SGA in all CHD was 2-fold higher whereas for isolated CHD, 1.4-fold higher than the expected proportion in the general population. Although few studies have looked at SGA for different subtypes of CHD, the observed variability of SGA by subtypes suggests that growth restriction at birth in CHD may be due to different pathophysiological mechanisms.


The Lancet ◽  
2012 ◽  
Vol 379 (9835) ◽  
pp. 2459-2464 ◽  
Author(s):  
Shakila Thangaratinam ◽  
Kiritrea Brown ◽  
Javier Zamora ◽  
Khalid S Khan ◽  
Andrew K Ewer

2020 ◽  
Author(s):  
Dongmei Su ◽  
Yanhua Li ◽  
Lina Guan ◽  
Qian Li ◽  
Cuige Shi ◽  
...  

Abstract Background:Gestational diabetes mellitus is a risk factor for congenital heart defects. The article aimed to investigate the expression and roles of Mst1, Yap1, Last1/2 and Survivin in modulating HG-induced cardiomyocyte apoptosis and maternal diabetes-induced heart abnormality. Methods:The gene and protein expression were assessed by quantitative PCR, western blot, and immunohistochemical staining. The protein phosphorylation level were analyzed by western blot .Knockdown of gene expression were assessed by RNA interference. Hoechst 33342 staining assay were performed to explore H9C2 apoptosis. Diabetes mellitus was induced in rats using streptozotocin.Results:Our results revealed that increased MST1 protein levels in the heart tissues of the offspring of diabetic rats in vivo occurred concomitantly with HG-induced apoptosis in H9C2 cardiomyocytes in vitro. Knockdown and overexpression experiments showed that MST1 played a key role in mediating HG-induced apoptosis in cardiomyocytes. Downregulation of YAP1 was associated with HG-induced, MST1-mediated cardiomyocyte apoptosis. Further study showed that MST1 downregulated the protein level of YAP1 through mediation of YAP1 phosphorylation on Ser127 and Ser397; this process also required LATS1/2 participation. MST1 overexpression increased the phosphorylation levels of LATS1/2, which were also shown to be increased in the heart tissues of diabetic offspring. We also found that YAP1 mediated the expression of Survivin during HG-induced apoptosis, and the Survivin-inhibitor YM155 partially inhibited the role of YAP1 in suppressing apoptosis induced by HG in cardiomyocytes. Conclusion:These findings reveal a regulatory mechanism of MST1/YAP1/Survivin signaling in modulating cardiomyocyte apoptosis in vitro and maternal diabetes-induced congenital heart defects in vivo.


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