Discussion
There was no significant difference in LGA rate and adverse neonatal outcomes, such as neonatal hypoglycemia or hyperbilirubinemia, between the treatment from early pregnancy group and the treatment from mid-pregnancy group. On the other hand, although there was no significant difference in birth weight, the SGA rate was higher in the group where all cases were intervened from early pregnancy.
Between the treatment from early pregnancy group and the treatment from mid-pregnancy group, there was no difference in the LGA rate and adverse neonatal outcome, such as neonatal hypoglycemia and hyperbilirubinemia. Liu et al15 conducted a prospective cohort study of low-risk pregnant women in China, where 75 g OGTT was performed in early pregnancy and mid-pregnancy, and the therapeutic intervention for GDM was based on the mid-pregnancy 75 g OGTT results. They stated that, even in low-risk pregnant women, GDM diagnosed at 18–20 weeks of gestation is associated with a poor outcome, and that diagnosing and managing GDM from early pregnancy may improve the outcomes. On the other hand, Harper et al16 reported that there was no significant difference in the LGA rate and neonatal outcome between obese American pregnant women who were diagnosed with early-onset GDM and started treatment in early pregnancy and those who were only followed up during early pregnancy and diagnosed with GDM in mid-pregnancy and started treatment from mid-pregnancy. Even in the obese population, the authors reported that they did not find any differences in pregnancy outcomes by screening and treating GDM from early pregnancy, which contradicts the findings of Liu et al.15 Our findings in Japanese pregnant women at a high risk for GDM showed no improvement in pregnancy outcomes with therapeutic intervention from early pregnancy for those diagnosed with GDM in early pregnancy by IADPSG thresholds. However, in a subanalysis limited to BMI >25 kg/m2, LGA was significantly reduced in the intervention group that was treated from early pregnancy as compared with the follow-up group until second 75 g OGTT, suggesting that intervention from early pregnancy may be beneficial only for obese pregnant women. The differences between our results and those of Harper et al may be due to differences in the diagnostic criteria for GDM.
Although there was no significant difference in birth weight, the SGA rate was higher in the group receiving interventions from early pregnancy. The rate of SGA in women with GDM is 4.4%–11.6%,17–21 and in Japanese women with GDM, the rate of SGA is reported to be almost 7%,17 18 which is lower than that of the general population of pregnant women. However, even in GDM cases, it is reported that strict glycemic control leads to SGA.22–24 Among the early-onset GDM group receiving interventions from early pregnancy as GDM, the median weight gain of pregnant women with SGA was 4.7 kg, whereas that of pregnant women without SGA was 7.7 kg. Thus, the lesser weight gain in the group with higher SGA rate suggests that excessive interventions for GDM may have resulted in an increase in SGA births. The increase in the number of low birthweight babies is a concern in Japan, and it is reported that a nationwide effort to raise awareness of this issue and an immediate response to the matter in question are needed, as a decrease in birth weight may pose a risk of long-term health problems, such as diabetes and hypertension.25 Therefore, in this context, it is necessary to reconsider the diagnosis and therapeutic intervention of GDM from early pregnancy.
This study has some limitations. First, this is not a prospective randomized controlled trial, but a retrospective study comparing a prospective cohort of one arm with historical controls. Second, in this study, there was no significant difference in pregnancy outcomes between the two groups, but we were not able to verify equivalence. Third, although the women in the treated from mid-pregnancy group did not receive active GDM treatment until after a mid-pregnancy OGTT, and only if the second test was positive, they were aware of the early diagnosis of GDM and some may have modified lifestyle from early pregnancy as a result. In addition, it has been reported that maternal hyperglycemia during pregnancy can affect future pediatric health,26 but in this study, we were only able to examine the short-term outcomes. As it is known that the profile of 75 g OGTT and subsequent pregnancy outcomes vary according to ethnicity,27 the advantage of this study is that it is the first to report whether therapeutic intervention from early pregnancy for early-onset GDM is effective for pregnant women in Japan.
In conclusion, diagnosing GDM by IADPSG thresholds in early pregnancy and providing therapeutic intervention to all patients with early-onset GDM did not improve the pregnancy outcomes, but rather increased the SGA rate. The Japanese treatment strategy, which recommends that all pregnant women with impaired glucose tolerance by IADPSG thresholds in early pregnancy should be treated from early pregnancy, needs to be revisited.