Such continuous linear relationships between maternal glucose and adverse fetal outcomes were seen studywide for birth weight and other outcomes (N. Engl. J. Med. 2008;358:1991–2002).
Among the most striking findings was that a significant number of fat babies were born to women whose blood glucose levels were considered “normal.”
The question at this point became, What should we do about it? Should we allow these obese babies to be born without any intervention, or can we treat them before birth?
Insights on Treatment
Many experts have been doubtful that treatment of mothers with GDM would be effective in altering newborn outcomes. However, the Australian Carbohydrate Intolerance Study in Pregnant Women, published in 2005, concluded that early treatment of GDM reduces serious perinatal morbidity and may improve health-related quality of life. In this study, women with GDM were randomized to receive dietary advice, blood glucose monitoring, and insulin therapy as needed (the treatment group), or routine care (N. Engl. J. Med. 2005;352:2477–86).
In another randomized study published several years later, Dr. Mark B. Landon and his colleagues finally convinced many experts of the value of aggressive screening and early intervention for GDM. Dr. Landon focused on a subset of women who had an abnormal result on a 3-hour 100-g OGTT but a fasting glucose level below 95 mg/L. These women thus had only mild glucose intolerance. (An abnormal result was defined as two or three timed glucose measurements that exceeded certain thresholds: 1-hour, 180 mg/dL; 2-hour, 155 mg/dL; and 3-hour, 140 mg/dL.)
In 14 centers across the United States, 958 patients were randomized to receive treatment of their diabetes or nothing but usual prenatal care. Treatment included formal nutritional counseling and diet therapy, along with insulin if needed. The majority of the women (93%) needed only dietary counseling and education about blood glucose control, while the other 7% needed insulin as well.
Women receiving dietary counseling checked their blood glucose levels before they got up in the morning, and 2 hours after each major meal. In essence, they planned and adjusted their diet based on their blood glucose readings.
What did we learn from this trial? We learned that the incidence of large-for-gestational-age births (greater than the 90th percentile) was cut in half from approximately 14% in the untreated group to 7% in the treated group. There also was a 10%-14% reduction in fat mass in the babies born to the women who received treatment, as well as significant reductions in mean birth weight and birth weight greater than 4,000 g. Most importantly, treatment also reduced the number of injuries that occurred during birth, while the number of small-for-gestational-age infants did not increase (N. Engl. J. Med. 2009;361:1339–48).
With these two randomized studies demonstrating significantly reduced risks with early GDM treatment, the question shifted from the broader issue of whether it is worthwhile to treat women with GDM to the more specific question of who needs treatment the most.
A New Approach
Today, in most demographic and ethnic groups in the United States, the incidence of gestational diabetes is between 4% and 12%, with a national incidence of about 8%. These are the patients we are already treating.
The HAPO trial, however, has shown us that there are a significant number of babies whose mothers have mild hyperglycemia and who are not being treated for this condition. These babies have neonatal adiposity and subsequently are being injured during the birth process.
In addition, we now have multiple epidemiologic studies demonstrating that adiposity at birth markedly increases – by as much as 30%–40% – the risk of being fat as a child and as an adolescent. Studies also have shown that the risk of developing childhood and adolescent type 2 diabetes proportionately increases with increasing neonatal adiposity.
Thus, the goal is no longer just to prevent neonatal adiposity so that babies will not be injured during birth; it now includes helping mothers control their glucose profiles so that their babies will have better health during their childhood and adult years.
However, the answer to the current, pressing question of whether we should offer treatment to women who are not now defined as having gestational diabetes is not yet clearly answered.
In 2008, after the initial release of HAPO study findings, a group called the International Association of Diabetes and Pregnancy Study Groups (IADPSG) was created to discuss the definition of gestational diabetes in light of the new HAPO findings and other research demonstrating improved outcomes with treatment.
In 2010, the consensus group released revised recommendations for glucose tolerance testing, suggesting that everyone convert to the 2-hour 75-g OGTT and that we lower the cutoff points used for diagnosis to protect as many babies as possible from becoming obese.