Maternal Pre-Existing Diabetes: A Non-Inherited Risk Factor for Congenital Cardiopathies
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ABSTRACT:
SUBMITTER: Ibrahim S
PROVIDER: S-EPMC10671602 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:BackgroundAn understanding of the correlation between maternal immunity and congenital cytomegalovirus (CMV) infection is critical for informing the design and evaluation of an effective maternal vaccine. This study aimed to quantitatively measure the protective effect of pre-existing maternal immunity against congenital CMV (cCMV) infection.MethodsA mother-child cohort study was conducted in three maternal and child health hospitals in China from 2015 to 2018. Pregnant women were consecutively enrolled, and anti-CMV pp150 IgG concentration at early, middle and late gestational ages were evaluated. Their newborns were screened for cCMV infection by CMV-DNA testing of saliva and urine.FindingsIn total, 6729 pregnant women were enrolled, and 6602 of them (98·11%) were positive for CMV IgG at their early gestational age visit (median time: 13 gestational weeks (GW); time range: 6-25 GW). In total, 6228 live newborns were born to seropositive mothers, and 48 (0·77%) of these infants were diagnosed with cCMV infection. The geometric mean concentration (GMC) of CMV IgG at an early gestational age in the women who delivered cCMV-positive newborns (i.e., the transmitters) was 8·54 IU/mL; this was significantly lower than the GMC in the non-transmitters (11·01 IU/mL; P=0·04). In early gestation, the risk of cCMV infection decreased as maternal IgG antibody levels increased (P=0·020); however, the same was not true in middle or late gestation (P>0·05). Using receiver operating characteristic analysis, a CMV IgG concentration of 12·83 IU/mL was established as the optimal diagnostic threshold. Compared to lower levels of CMV IgG (<12·83 IU/mL) in seropositive pregnant women, higher maternal CMV IgG levels (≥12·83 IU/mL) were associated with a 50% reduction in cCMV infection risk in infants (relative risk=0·50; 95% confidence interval: 0·27-0·93; P=0·028).InterpretationFor seropositive women, a higher level of CMV IgG at an early gestational age is associated with a lower risk of cCMV infection in their newborns.FundingNational Natural Science Foundation of China; Science and Technology Key Project in Fujian Province; Merck Sharp & Dohme Corp., Kenilworth, NJ, USA; Fieldwork Funds for graduate students of Xiamen University.
| S-EPMC8861648 | biostudies-literature
Project description:Maternal hyperglycemia increases the risk of CHD and is further sensitized by haploinsufficiency of Notch1 supporting a gene-environment interaction model. To gain insights into chromatin accessible status by which hyperglycemia affects molecular pathways regulating cardiac development, we performed ATAC-seq on embryonic AV cushion mesenchymal cells maintained in normal and high glucose.
2017-10-03 | GSE104520 | GEO
Project description:BackgroundThe aims of this study are to investigate the impact of pre-existing diabetes and diabetes treatments on lung cancer prognosis.MethodsA total of 2484 women with confirmed incident lung cancer from the Women's Health Initiative were followed for an average of 2.9 years through the date of death or 29 August 2014.ResultsCompared with women with lung cancer but without diabetes, women with lung cancer and diabetes had significantly increased risk of overall mortality (HR=1.27, 95% CI: 1.07-1.50). Women with diabetes receiving insulin or metformin or women who had long duration of diabetes also had increased risk of overall mortality.ConclusionsOur large prospective study provides evidence that pre-existing diabetes is associated with poor overall survival among women with lung cancer, but do not support the hypothesis that metformin use may have a protective effect in women with lung cancer and diabetes.
| S-EPMC4931364 | biostudies-literature
Project description:Birth defects are the leading cause of infant mortality, and they are caused by a combination of genetic and environmental factors. Environmental risk factors may contribute to birth defects in genetically susceptible infants by altering critical molecular pathways during embryogenesis, but experimental evidence for gene-environment interactions is limited. Fetal hyperglycemia associated with maternal diabetes results in a 5-fold increased risk of congenital heart disease (CHD), but the molecular basis for this correlation is unknown. Here, we show that the effects of maternal hyperglycemia on cardiac development are sensitized by haploinsufficiency of Notch1, a key transcriptional regulator known to cause CHD. Using ATAC-seq, we found that hyperglycemia decreased chromatin accessibility at the endothelial NO synthase (Nos3) locus, resulting in reduced NO synthesis. Transcription of Jarid2, a regulator of histone methyltransferase complexes, was increased in response to reduced NO, and this upregulation directly resulted in inhibition of Notch1 expression to levels below a threshold necessary for normal heart development. We extended these findings using a Drosophila maternal diabetic model that revealed the evolutionary conservation of this interaction and the Jarid2-mediated mechanism. These findings identify a gene-environment interaction between maternal hyperglycemia and Notch signaling and support a model in which environmental factors cause birth defects in genetically susceptible infants.
| S-EPMC5846898 | biostudies-literature
Project description:BackgroundPatients with previous stroke episodes tend to have poor outcomes after an endovascular treatment (EVT). Encephalomalacia (EM) is an objective indicator of previous strokes but has not been systematically investigated. The fundamental aim of this exploration is to investigate the effects of a pre-existing non-disabling EM on clinical outcomes after EVT.MethodsConsecutive patients undergoing an EVT due to the anterior circulation large vessel occlusion (LVO) strokes were enrolled in the study. The pre-existing EM was defined as the focal hypodense lesions (≥ 3 mm in maximum diameter) on a non-contrast cranial CT using axial images before EVT. The primary outcome was the 90-day functional assessment using the modified Rankin Scale (mRS) score. The safety outcome was the incidence of symptomatic intracranial hemorrhage (sICH) defined as any hemorrhage within 24 h after an EVT, which is responsible for an increase of ≥ 4 points in the score of National Institutes of Health Stroke Scale (NIHSS).ResultsOf the 433 patients analyzed in this investigation, a pre-existing non-disabling EM was observed in 106 (24.5%) patients. After adjusting for potential confounding factors, patients with contralateral EM (OR = 2.68, 95% CI = 1.13-6.31; P = 0.025) and with an EM+ > 20 mm in maximum diameter (OR = 2.21, 95% CI = 1.01-4.85; P =0.048) were substantially associated with unfavorable outcomes (mRS > 2). For the sICH, we did not observe any association with the pre-existing EM (P > 0.05).ConclusionsA pre-existing non-disabling EM is common and safe in patients undergoing EVT. However, a contralateral EM and the large size of EM may predict an unfavorable outcome at 90 days, which should receive more attention before EVT.
| S-EPMC8873094 | biostudies-literature
Project description:Women with pre-gestational diabetes have a higher risk of producing children with congenital heart defects (CHDs), caused predominantly by hyperglycemia-induced oxidative stress. In this study, we evaluated if exercise during pregnancy could mitigate oxidative stress and reduce the incidence of CHDs in the offspring of diabetic mice. Female mice were treated with streptozotocin to induce pre-gestational diabetes, then mated with healthy males to produce offspring. They were also given access to running wheels 1 week before mating and allowed to exercise voluntarily until E18.5. Heart morphology, gene expression, and oxidative stress were assessed in foetal hearts. Maternal voluntary exercise results in a significantly lower incidence of CHDs from 59.5% to 25%. Additionally, diabetes-induced defects in coronary artery and capillary morphogenesis were also lower with exercise. Myocardial cell proliferation and epithelial-mesenchymal transition at E12.5 was significantly lower with pre-gestational diabetes which was mitigated with maternal exercise. Cardiac gene expression of Notch1, Snail1, Gata4 and Cyclin D1 was significantly higher in the embryos of diabetic mice that exercised compared to the non-exercised group. Furthermore, maternal exercise produced lower reactive oxygen species (ROS) and oxidative stress in the foetal heart. In conclusion, maternal exercise mitigates ROS and oxidative damage in the foetal heart, and results in a lower incidence of CHDs in the offspring of pre-gestational diabetes. Exercise may be an effective intervention to compliment clinical management and further minimize CHD risk in mothers with diabetes.
| S-EPMC6653048 | biostudies-literature
Project description:AimsTo evaluate the effects of gestational diabetes and pre-existing diabetes on maternal morbidity and medical costs, using data from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service.MethodsDelivery cases in 2010, 2011 and 2012 (459 842, 442 225 and 380 431 deliveries) were extracted from the Health Insurance Review and Assessment Service database. The complications and medical costs were compared among the following three pregnancy groups: normal, gestational diabetes and pre-existing diabetes.ResultsAlthough, the rates of pre-existing diabetes did not fluctuate (2.5, 2.4 and 2.7%) throughout the study, the rate of gestational diabetes steadily increased (4.6, 6.2 and 8.0%). Furthermore, the rates of pre-existing diabetes and gestational diabetes increased in conjunction with maternal age, pre-existing hypertension and cases of multiple pregnancy. The risk of pregnancy-induced hypertension, urinary tract infections, premature delivery, liver disease and chronic renal disease were greater in the gestational diabetes and pre-existing diabetes groups than in the normal group. The risk of venous thromboembolism, antepartum haemorrhage, shoulder dystocia and placenta disorder were greater in the pre-existing diabetes group, but not the gestational diabetes group, compared with the normal group. The medical costs associated with delivery, the costs during pregnancy and the number of in-hospital days for the subjects in the pre-existing diabetes group were the highest among the three groups.ConclusionsThe study showed that the rates of pre-existing diabetes and gestational diabetes increased with maternal age at pregnancy and were associated with increases in medical costs and pregnancy-related complications.
| S-EPMC4407911 | biostudies-literature
Project description:Background and aimsA variety of maternal heart conditions are associated with abnormal placentation and reduced foetal growth. However, their impact on offspring's long-term cardiovascular health is poorly studied. This study aims to investigate the association between intrauterine exposure to pre-existing maternal cardiovascular disease (CVD) and offspring CVD occurring from infancy to early adulthood, using paternal CVD as a negative control.MethodsThis nationwide cohort study used register data of live singletons without major malformations or congenital heart disease born between 1992 and 2019 in Sweden. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for essential maternal characteristics. Paternal CVD served as a negative control for assessment of unmeasured genetic and environmental confounding.ResultsOf the 2 597 786 offspring analysed (49.1% female), 26 471 (1.0%) were born to mothers with pre-existing CVD. During a median follow-up of 14 years (range 1-29 years), 17 382 offspring were diagnosed with CVD. Offspring of mothers with CVD had 2.09 times higher adjusted HR of CVD (95% CI 1.83, 2.39) compared with offspring of mothers without CVD. Compared with maternal CVD, paternal CVD showed an association of smaller magnitude (HR 1.49, 95% CI 1.32, 1.68). Increased hazards of offspring CVD were also found when stratifying maternal CVD into maternal arrhythmia (HR 2.94, 95% CI 2.41, 3.58), vascular (HR 1.59, 95% CI 1.21, 2.10), and structural heart diseases (HR 1.48, 95% CI 1.08, 2.02).ConclusionsMaternal CVD was associated with an increased risk of CVD in offspring during childhood and young adulthood. Paternal comparison suggests that genetic or shared familial factors may not fully explain this association.
| S-EPMC11458151 | biostudies-literature
Project description:Epigenetic mechanisms underlying maternal diabetes-associated risk of congenital heart disease
| PRJNA412907 | ENA
Project description:BackgroundThe objective of this study was to assess the impact of pre-existing diabetes on breast cancer prognosis.MethodsWomen (n=2833) with centrally confirmed invasive breast cancer in the Women's Health Initiative, who were linked to Medicare claims data (CMS) were followed from the date of breast cancer diagnosis to date of death or 20 September 2013. Information on diabetes was identified through the CMS Chronic Condition Warehouse algorithm. Cox proportional hazard regression was used to estimate adjusted hazard ratios for overall mortality. A competing risks model (proportional subdistribution) model was used to estimate hazard ratios for breast cancer-specific mortality.ResultsWomen with diabetes were more likely to have factors related to delayed diagnosis (less recent mammograms, and more advanced cancer stage) and were less likely to receive radiation therapy. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR=1.57, 95% CI: 1.23-2.01) and had nonsignificantly increased risk for breast cancer-specific mortality (HR=1.36, 95% CI: 0.86-2.15) before adjustment for factors related to delayed diagnosis and treatment. Adjustment for these factors resulted in a little change in the association of diabetes with overall mortality risk, but further attenuated the point estimate for breast cancer-specific mortality.ConclusionsOur study provides additional evidence that pre-existing diabetes increases the risk of total mortality among women with breast cancer. Very large studies with data on breast cancer risk factors, screening and diagnostic delays, treatment choices, and the biological influence of diabetes on breast cancer will be needed to determine whether diabetes also increases the risk for breast cancer-specific mortality.
| S-EPMC4559825 | biostudies-literature