This randomized trial showed that although treatment of mild gestational diabetes mellitus did not reduce the frequency of the composite primary perinatal outcome, it did lower the risks of fetal overgrowth, shoulder dystocia, cesarean delivery, and preeclampsia. Overall, consistent with findings from the ACHOIS trial, the findings from our trial confirm a modest benefit from the identification and treatment of women with mild carbohydrate intolerance during pregnancy.8
The ACHOIS trial, however, included an ethnically homogeneous group of women who had a greater degree of hyperglycemia than that in our more diverse study population. In addition, we used a 100-g diagnostic oral glucose-tolerance test, whereas a 75-g oral glucose-tolerance test was used in the ACHOIS trial. The ACHOIS trial included a health status survey that showed that there were lower rates of postpartum depression in the intervention group, whereas we did not assess quality-of-life measures.
Our composite primary outcome included perinatal mortality (stillbirth or neonatal death) and complications that have been linked to maternal carbohydrate intolerance: neonatal hypoglycemia, hyperbilirubinemia, and birth trauma. The results of the ACHOIS trial showed that treatment did not reduce the rates of symptomatic neonatal hypoglycemia or jaundice requiring phototherapy.8
The lack of treatment effect in reducing metabolic abnormalities of the newborn in our study as well as in the ACHOIS trial may be due in part to the fact that these adverse outcomes are most consistently associated with more severe glucose elevations than those that were present in these two study populations. The results from the HAPO study suggested that a threshold for an increased risk of clinical neonatal hypoglycemia may not be apparent until fasting maternal glucose levels exceed 100 mg per deciliter (5.6 mmol per liter).6
Associations among macrosomia, shoulder dystocia, and the increased risk of brachial plexus injury in the offspring of women with diabetes are well documented.26
Consistent with the results of our trial, the ACHOIS trial also showed a reduction in the rate of shoulder dystocia when women with mild gestational diabetes mellitus received treatment (1%, vs. 3% in the untreated group).8
However, both trials lacked sufficient power to detect significant differences in uncommon adverse outcomes such as injury to the brachial plexus. Increased birth weight and neonatal fat mass may have long-term health implications for the offspring of mothers with gestational diabetes mellitus, including an increased risk of impaired glucose tolerance and childhood obesity.27,28
Long-term follow-up studies are needed to determine whether treatment of gestational diabetes mellitus can reduce the risk of these complications.
The diagnosis of gestational diabetes mellitus, or the knowledge that it is present, has been reported to be associated with an increase in several adverse maternal outcomes.29
Rates of cesarean delivery have been consistently higher in pregnancies in which gestational diabetes mellitus has been diagnosed.24,30
Naylor and colleagues suggested that simply the recognition that the mother has gestational diabetes mellitus may lead to a lower threshold for operative delivery, thus mitigating the potential benefits of treatment in reducing fetal overgrowth.24
We found that there was a significant reduction in the rate of cesarean delivery among the women who were treated for mild gestational diabetes mellitus, as compared with the rate among the women in the control group, and a rate of labor induction that was similar in the two groups. The extent to which a reduction in fetal size and in the frequency of large-for-gestational-age infants as a result of treatment may have contributed to the lower rate of cesarean deliveries is unknown. Labor induction and cesarean delivery may be less commonly performed in academic medical centers, including the centers that participated in this study.
Insulin resistance, a characteristic of gestational diabetes mellitus, has been associated with the development of preeclampsia.31
The HAPO study showed a continuous linear association between the results of glucose-tolerance tests and rates of preeclampsia.6
Hypertensive disorders of pregnancy are associated with an increased rate of maternal complications and are a major contributor to preterm delivery among women with gestational diabetes mellitus.30
Consistent with findings from the ACHOIS trial,8
we found a significant reduction in the rates of preeclampsia among women who received treatment for gestational diabetes mellitus. The overall rate of preeclampsia in our study was substantially lower than that in the ACHOIS study, which is probably explained by our use of more stringent diagnostic criteria.
In contrast with previous randomized trials involving women with gestational diabetes mellitus, we verified compliance with glycemic monitoring and documented whether target glucose thresholds were achieved. We did not disclose the results of oral glucose-tolerance tests to caregivers or subjects in the control group in order to minimize the likelihood of self-treatment, which has been a limitation in pilot studies of treatment of gestational diabetes mellitus.22,23
However, as a result, we could not assess glycemia in women in the control group, and thus it is not known whether intensive treatment of gestational diabetes mellitus reduced glycemic levels relative to standard obstetrical care.
The ACHOIS study reported that “serious” perinatal complications were reduced by treatment of gestational diabetes mellitus. The majority of outcomes included in the composite outcome of the ACHOIS trial were cases of shoulder dystocia, which is considered by many to be an intermediate health outcome.8,9
Although the primary composite outcome in our trial was not significantly reduced with treatment, the results of our study provide further compelling evidence that among women who have gestational diabetes mellitus and normal fasting glucose levels, treatment that includes dietary intervention and insulin therapy, as necessary, reduces rates of fetal overgrowth, cesarean delivery, and preeclampsia. These findings complement the ongoing analysis of the HAPO study data, which is focused on developing an international consensus for the diagnosis and treatment of carbohydrate intolerance during pregnancy.32