In this prospective cohort study, we found that patients with first-trimester fasting hyperglycemia have a higher incidence of developing GDM which was diagnosed between 24 and 28 weeks of gestation. Importantly, we also found that first-trimester hyperglycemia is not associated with adverse pregnancy including macrosomia, preterm delivery primary cesarean delivery, premature rupture of membranes and pregnancy hypertension disorders, while subsequent GDM patients were excluded in the analysis.
It is established that overt or preexisting diabetes in early pregnancy is associated with an increase in several adverse maternal outcomes and women at risk may benefit from screening and treatment in early pregnancy,however, importance of detecting and regulating degrees of hyperglycemia less severe than “overt” diabetes from early pregnancy is controversial. Advocates argue that traditionally GDM screen which begin at the beginning of the third trimester provide only a brief period for intervention and result in little improvement for pregnancy outcomes. Critics points that mild hyperglycemia does not carry anything like the same degree of risk as overt diabetes. In addition, If IADPSG proposal is adopted, rates of diagnosis of gestational diabetes will increase enormously. Interventions and costs will increase without evident benefits.
Our results are consistent with the results of numerous studies which demonstrated that first-trimester FPG level was strongly correlated with GDM diagnosed at 24–28 gestational weeks. In a large retrospective study conducted by Riskin-mashihar et al, it is noted that first-trimester FPG level had a continuous associations with increased frequency of GDM development. The incidence of GDM in highest first-trimester hyperglycemia is 11.7% (adjusted odds ratio 11.92 [95% CI 5.39 − 26.37]). F. Corrado et al reported a study including a number (n = 738) of pregnant women in Italy with an 11.9% prevalence of GDM revealed by OGTT between 24 and 28 weeks of gestation. In this study 24(45.3%) women who have a first-trimester FPG greater or equal to 5.1 mmol/L progressed to GDM. In a study of 17,186 pregnancies among Chinese population, the incidences of GDM were 37.0, 52.7, and 66.2%, respectively, for women with FPG at the first prenatal visit between 5.10 and 5.59, 5.60 and 6.09, and 6.10–6.99 mmol/L. In light of the high prevalence of GDM in pregnant women with FPG (6.10–6.99 mmol/L), the authors suggested that the same interventions should be provided for them as for GDM.
Our results are inconsistent with three previous reports which found that fasting hyperglycemia in early pregnancy is associated with adverse pregnancy. J. Seth Hawkins et al described that women with an earlier diagnosis of diet-treated GDM were at increased risk of preeclampsia and the delivery of large infants compared with women who received the diagnosis at 24 weeks of gestation. Women with early diagnosis were more likely to be older, multiparous, and obese. When differences in maternal characteristics and glycemic control were adjusted, there is still a higher risk of preeclampsia in earlier diagnosis group (odds ratio, 2.4; 95% CI, 1.5, 3.8). Similar results were reported in the study of Maisa N et al. In contrast with women who received a diagnosis for GDM at or after 24 weeks, women diagnosed with GDM before 24 weeks were associated with an increased risk for macrosomia (OR 2, 95% 1-4.15, p = 0.0498), but relationship with other adverse outcomes was not found. Women diagnosed with GDM before 24 weeks were more likely to be obese and they were less likely to have excess gestational weight gain. A large multiethnic cohort study conducted by Sweeting et al showed that incidence of macrosomia, large for gestational age and neonatal intensive care admission in women in whom GDM was diagnosed at < 12 weeks of gestation was high and even comparable to women with pre-existing diabetes. Difference in definitions of gestational diabetes is a potential reason for differences in study findings. Ours have been described above, whereas their approach was based on the Carpenter-Coustan Criteria that if either a 50-g one-hour glucose challenge test (GCT) that exceeded 200 mg/dL, or if they had two or more abnormal values on a 3 hour, 100 gram oral glucose tolerance test (OGTT). Other important distinctions between the current study and that of prior reports include populations studied and study design. All of these studies were made retrospectively and in two of the three studies only patients with high risk was included in the analysis. Maternal baseline characteristics including pre-pregnancy weight, maternal age and parity, which have previously been reported to be associated with adverse pregnancy outcomes in these studies were not comparable and strategies to control the confounders was vague and poorly explained.
Our study has several strengths, to our knowledge, it is the first prospective study with regard to the association between first-trimester fasting hyperglycemia and adverse pregnancy outcomes while important confounder as subsequent GDM was excluded from the analysis, particularly all women were followed at a single university clinic and also delivered in the same institution warranting the consistency of results. Other strengths included the relatively large patient sample size compared to earlier studies and inclusion criteria which the HAPO Study has adopted. However, we acknowledge our study also has several limitations. First, Pre-pregnancy BMI, which is a known confounding factor for adverse pregnancy outcomes, was self-reported. Its accuracy depended on the participants’ ability of memory and evidences showed adults are willing to overestimate their height and underestimate their weight. Notwithstanding, we do not believe this will bias our study dramatically as pre-pregnancy BMI was comparable in the two groups. Another problem is the test of first-trimester FPG level which was performed in different community center. The measurement lacks a standardized protocol and laboratory quantity control is impossible. Finally, our results are exclusively from Chinese population and may not be generalizable to other ethnicities. However, as Asians are more inclined to develop GDM, and we supposed that fewer patients with first-trimester fasting hyperglycemia will suffer from GDM among other races.