Diabetes and Congenital Heart Defects

Abstract

Context Maternal pregestational diabetes (PGDM) is a risk factor for development of congenital heart defects (CHDs). Glycemic control before pregnancy reduces the risk of CHDs. A meta-analysis was used to estimate summary ORs and mathematical modeling was used to estimate population attributable fractions (PAFs) and the annual number of CHDs in the U.S. potentially preventable by establishing glycemic control before pregnancy. Evidence acquisition A systematic search of the literature through December 2012 was conducted in 2012 and 2013. Case–control or cohort studies were included. Data were abstracted from 12 studies for a meta-analysis of all CHDs. Evidence synthesis Summary estimates of the association between PGDM and CHDs and 95% credible intervals (95% CrIs) were developed using Bayesian random-effects meta-analyses for all CHDs and specific CHD subtypes. Posterior estimates of this association were combined with estimates of CHD prevalence to produce estimates of PAFs and annual prevented cases. Ninety-five percent uncertainty intervals (95% UIs) for estimates of the annual number of preventable cases were developed using Monte Carlo simulation. Analyses were conducted in 2013. The summary OR estimate for the association between PGDM and CHDs was 3.8 (95% CrI=3.0, 4.9). Approximately 2670 (95% UI=1795, 3795) cases of CHDs could potentially be prevented annually if all women in the U.S. with PGDM achieved glycemic control before pregnancy. Conclusions Estimates from this analysis suggest that preconception care of women with PGDM could have a measureable impact by reducing the number of infants born with CHDs.

Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis

“…Among the non-genetic factors that influence the fetal heart, maternal hyperglycemia is the most common medical condition, associated with a 2–5-fold increase in CHD independent of genetic contributors ( Centers for Disease Control, 1990 ; Simeone et al, 2015 ; Yogev and Visser, 2009 ). Diabetic pregnancy is often accompanied by maternal complications including vasculopathy, neuropathy, and insulin resistance, which potentially affect fetal cardiac formation indirectly.…”

Proportion of selected congenital heart defects attributable to recognized risk factors

“…Hypoplastic left heart syndrome (HLHS) and Tetralogy of Fallot (TOF) are two relatively common critical CHDs, estimated to occur in 2.3 per 10,000 live births and 3.4 per 10,000 live births in the United States, respectively, each year [17]. There are several recognized risk factors for HLHS and TOF, which include pregestational diabetes [18–20], maternal prepregnancy obesity [21–23], family history of a CHD [24–28], and use of certain medications during early pregnancy [29–31]. Although HLHS and TOF are considered etiologically distinct, we focused the current analysis on these two CHDs because they are relatively common, critical, and have several recognized risk factors.…”

Investigating the Mechanism of Hyperglycemia-Induced Fetal Cardiac Hypertrophy

“…Pregnant women with either pre-gestational diabetes mellitus (PGDM) or gestational diabetes mellitus are at high risk (2–5 times higher than non-diabetic pregnancies) of carrying a fetus with congenital anomalies, such as phocomelia, cardiac malformations, macrosomia and central nervous system malformations [ 1 , 2 ]. Among those congenital malformations induced by hyperglycemia, congenital heart disease [ 3 ] and anomalies of the nervous system are prominent [ 4 ] because both the cardiovascular and nervous systems start to develop during the early embryonic developmental stage, the period that is vulnerable to external harmful factors. Hyperglycemia is hypothesized to be the most important teratogen affecting cardiovascular formation by generating excess reactive oxygen species (ROS) [ 5 , 6 ].…”