Modified therapy for gestational diabetes using high-risk and low-risk fetal abdominal circumference growth to select strict versus relaxed maternal glycemic targets

In the last decade, level I evidence from 484 pregnancies in four clinical trials supports modified therapy to reduce newborn somatic growth disturbances related to GDM and demonstrates three consistent findings. First, fetal AC measurements during the second and third trimester discriminate low risk and high risk for LGA newborns using fetal AC thresholds <75th and ≥75th percentile for gestational age. The fetal AC is a standard component of the basic fetal ultrasound examination. Its reproducibility in determining weights and growth patterns has been long established by studies and daily clinical use. Newer ultrasound machines calculate fetal AC percentiles using standard growth curves. Thus, the fetal AC is ideal as a simple and practical measurement for determining low- and high-risk fetal growth. Second, when high-risk fetal AC growth is identified, modified therapy using lower fasting/2-h postprandial glucose targets of 80/100-110 mg/dl has been shown to significantly reduce LGA growth by over 50%. The key intervention strategy is lowering glucose levels below the standard levels considered to be "normal range" and can be accomplished by either diet or insulin therapy. Modified therapy may be most effective in pregnancies with mild initial hyperglycemia and excessive growth. When both moderate maternal glycemia and excessive growth are present, and insulin is prescribed regardless of therapy protocol, the LGA rates appear less responsive to glycemic therapy, possibly because high-risk growth may be well established before the traditional time of diagnosis of GDM. Third, when low-risk growth is identified, relaxing glycemic targets can decrease the risk of SGA infants (24). Larger studies are needed to address how best to reduce SGA risk, whether it is by lowering fetal AC percentiles or deciding which relaxed glucose targets should be used. Preventing SGA growth should be an equally important therapeutic goal as preventing LGA growth, since low birth weight and growth restriction have also been strongly associated with later life increased risk of hypertension and type 2 diabetes (26-28). From these four trials has emerged a modified therapy approach that is illustrated in Fig. 2. Shortly after the diagnosis of GDM, ultrasound measurement of fetal AC percentile should be performed. In pregnancies manifesting high-risk fetal growth, lower glycemic targets (80/100-110 mg/dl) should be used, starting insulin as needed. In pregnancies manifesting low-risk fetal growth, relaxed glycemic targets can be used. Currently, there is not a clear basis for recommending either 100/140 or 120/200 mg/dl. However, in the three trials where serial AC measures were performed, insulin therapy was started primarily for high-risk AC growth, not for exceeding either relaxed glycemic target. Current studies do not examine how frequently fetal AC measures should be evaluated. Bonomo et al. (24) attributed their success in reducing both LGA and SGA rates to their protocol of assessing fetal AC growth every 2 weeks and modulating therapy in "real-time." This permitted early and flexible therapy to reduce excessive growth or unnecessarily lowering glucose levels to avoid fetal undergrowth. More studies comparing management strategies that address optimal timing, frequency of ultrasound examinations, and glycemic targets will continue to improve modified therapy. Future studies are needed that examine whether other ultrasonic growth parameters (e.g., head-abdomen ratios or subcutaneous fat) are better able to discriminate between accelerated or restricted growth due to maternal, genetic, fetal, or diabetic mediated factors. However, by far, the most important outcome of all future therapeutic trials involving GDM pregnancies will be to examine the effects of in utero treatment on childhood and lifetime risks for developing obesity or impaired glucose tolerance. © 2007 by the American Diabetes Association.