Early-Pregnancy Glucose May Best Oral Glucose Tolerance as Congenital Disease Predictor

Patrice Wendling

November 29, 2016

NEW ORLEANS, LA — A new study suggests that elevated early maternal plasma glucose predicts the risk of offspring congenital heart disease (CHD) and is superior to a later 1-hour oral glucose tolerance test (OGTT), the current method to risk-stratify women for echocardiographic screening[1].

For every 10-mg/dL (0.6-mmol/L) increase in blood sugar at 4 weeks before conception to the end of the first trimester, the risk of delivering a baby with CHD rose 8%.

This phenomenon was seen even after researchers controlled for known maternal CHD risk factors such as prepregnancy body-mass index, maternal age, and pregestational diabetes (adjusted odds ratio [OR] 1.08, 95% CI 1.02–1.13; P=0.003). The results were virtually indistinguishable after diabetic mothers were also excluded from the model.

In contrast, an abnormal OGTT at 24 to 28 weeks did not reach statistical significance between pregnancies with and without CHD (adjusted OR 1.03, 95% CI 0.98–1.07).

"I think there's potential for this to change the practice model, although we need to confirm this finding using a population-based sample," senior investigator Dr James R Priest (Stanford University School of Medicine, Stanford, CA) told heartwire from Medscape.

He added, "A random serum glucose where a woman doesn't have to fast or drink any awful orange-juice glucose load is one of the cheapest and most available lab tests there is."

Maternal pregestational diabetes is long known to significantly increase an infant's risk for CHD, but emerging evidence suggests higher glucose values even in nondiabetic mothers may also increase CHD risk. The investigators recently reported an association between elevated glucose values in the second trimester in nondiabetic mothers and risk of tetralogy of Fallot[2] and speculated a similar association with CHD would be present when measuring glucose metabolism in early pregnancy, when the most important cardiac structures develop.

The investigators, led by Dr Emmi Helle (Stanford University School of Medicine), analyzed a convenience sample of 19,107 pregnant women from Stanford Healthcare and Geisinger Health System, of whom 74 had prepregnancy diabetes and 811 had CHD. Pregnancies where the offspring had trisomy 21, 18, or 13 or 22q11.2-deletion syndrome were excluded.

The mean early glucose value was 96 mg/dL (5.3 mmol/L) in pregnancies without CHD vs 107 mg/dL (95.9 mmol/L) in pregnancies with CHD. The respective mean 1-hour OGTT values were 117 mg/dL (6.5 mmol/L) and 122 mg/dL (6.8 mmol/L).

Dr Michael Portman (Seattle Children's and University of Washington) commented at the American Heart Association (AHA) 2016 Scientific Sessions, where the study was formally presented, that the findings were very important and "hopefully we can change our guidelines and make it more scientific for identifying mothers who should undergo fetal echocardiography."

He observed that several studies have shown making a prenatal diagnosis with fetal echocardiography improves general surgical outcomes of CHD in newborns, but how to get these patients to cardiologists is less clear. The OGTT, which is conducted during late second or early third trimester, is one of the screening tools, but "it's not really a guideline, it's just suggested," he said at a trending topics in clinical science session.

Priest said it is not yet known whether random glucose testing is uniquely beneficial for identifying individual malformations or for CHD risk across the board but that a recent nationwide Danish cohort study[3] showed all types of congenital heart defects were associated with maternal type 1 and type 2 pregestational diabetes.

"The question of whether there is something about having a high glucose level that changes cardiac development or is just a marker for something else that's going on we still don't know, but I have a strong suspicion that glucose is the causative agent," he said.

A major limitation of the present study is the potential for sampling bias inherent in the retrospective design. First-trimester glucose measurements were available for only 13% of mothers and as the reason for the measuring glucose was random, the population may not represent average pregnancies.

The investigators are planning to use Finnish-population–based healthcare registries and early pregnancy serum samples to examine glucose values in a more unbiased population, Priest noted.

He added, "So few of the fetuses, thankfully, ever end up having congenital heart disease, but if we can find a way to really pick up the women who are at higher risk, we can have a much better pickup rate on our fetal echocardiography."

Priest, Helle, and Portman reported no financial relationships. Disclosures for the coauthors are listed in the abstract.

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org, follow us on Twitter and Facebook.

 

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