September 05, 2014
By Will Boggs MD
NEW YORK - A hemoglobin (Hb) A1c level of 5.9% or higher is optimal for detecting diabetes and for identifying women at increased risk of adverse pregnancy outcomes, according to researchers from New Zealand.
This is lower than the currently recommended 6.5% threshold, they note in Diabetes Care, online September 4.
"HbA1c is predictive of pregnancy outcomes in women with known diabetes, so we weren't that surprised," Dr. Ruth C. E. Hughes from University of Otago in Christchurch told Reuters Health by email. "However, the rates of adverse pregnancy outcomes were higher than anticipated in women with an HbA1c 5.9%-6.4% (41-46 mmol/mol) who did not meet New Zealand criteria for gestational diabetes on an early pregnancy oral glucose tolerance test."
Although several organizations recommend screening for diabetes in pregnancy at the first antenatal visit, the most appropriate test and threshold remain undefined.
Dr. Hughes's team studied a prospective cohort study of more than 16,100 pregnant women, who had blood drawn at a median 47 days' gestation. The mean HbA1c among all women tested was 5.3%. Only 33 women (0.2%) had HbA1c of 6.5% or higher.
Of the 974 women who had oral glucose tolerance tests (OGTTs) before 20 weeks' gestation, 15 met criteria for diabetes (median HbA1c, 6.5%) and 170 for gestational diabetes (GDM) (median HbA1c, 5.8%).
On receiver operating curve (ROC) analysis, an HbA1c of 5.9% emerged as the optimal screening threshold for detecting diabetes. It yielded 100% sensitivity, 97.4% specificity, 18.8% positive predictive value, and 100% negative predictive value.
The 5.9% cutoff was also highly specific (98.4%) for early GDM, with a positive predictive value of 52.9% and a negative predictive value of 92.8%.
About three-quarters of women with early HbA1c of 5.9% or higher who had an OGTT met GDM criteria at some stage in their pregnancy, and 10.4% of women at or above this cutoff met diabetes criteria.
Women whose HbA1c met or exceeded the 5.9% threshold had more than a two-fold increased risk of preeclampsia, shoulder dystocia, and major congenital anomaly; more than a three-fold increased risk of perinatal death; and more than 1.5-fold increased risk of delivery before 37 weeks' gestation, compared with women who had HbA1c below 5.9%.
An HbA1c threshold of 6.5% or more would have missed almost half of the women with diabetes, the researchers say.
"In New Zealand, HbA1c measurement costs one-third less than an OGTT, and costs would be even lower if the test was added routinely to the first antenatal screen," they note. "Thus an HbA1c measurement is likely to be a more cost-effective screening approach than an early pregnancy OGTT, as well as being a more acceptable test to women in early pregnancy."
"We believe that HbA1c should be measured in the first trimester as part of the first antenatal blood screen," Dr. Hughes said. "Management will then depend on local policy, but we hypothesize that all women with an HbA1c >= 5.9% (41mmol/mol) would benefit from dietary and weight gain advice as well as closer monitoring (which might include blood sugar monitoring as well as increased fetal surveillance)."
"Further studies are required to investigate whether blood sugar monitoring and treatment, beginning in the first trimester, will impact on reducing the risks for women with an HbA1c 5.9-6.4% (41-46mmol/mol)," she said.
"We hope that others will carry out similar research to confirm our results across diverse ethnic backgrounds," Dr. Hughes added. "We are planning a further study to examine whether early intervention can improve outcomes for these women. Certainly, in women with known pre-existing diabetes those who have the best outcomes have tight blood sugar control prior to, or from very early on in pregnancy and therefore it seems logical that early treatment could benefit women who have an elevated HbA1c at booking."
Dr. Florence Brown from Joslin Diabetes Center in Boston told Reuters Health by email, "It is not a surprise to me that higher levels of A1c predict worse pregnancy outcomes, but the finding of Hughes and others that worse outcomes occur when the threshold for A1c is 5.9% is important, as this value is considerably lower than the value of 6.5% used to diagnose patients with diabetes who are not pregnant."
"The A1c test done early in pregnancy may be a convenient and effective way to identify women with pre-existing diabetes or at greater risk of worse pregnancy outcomes," said Dr. Brown, who was not involved in the new work. "Women with A1c > 5.9% also have higher risk of gestational diabetes. A 75-gram oral glucose tolerance test should be done to confirm the diagnosis of pre-existing diabetes or gestational diabetes when the A1c is >= 5.9%."
She added, "Still, all women should undergo screening for gestational diabetes routinely at 24 to 28 weeks. I advocate the 1-step 75 gm 2-hour oral glucose tolerance test that is endorsed by the American Diabetes Association and the Endocrine Society."
Diabetes Care 2014.
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