In our study which aimed to evaluate the association between pregestational maternal glucose level and singleton neonatal outcome, we found that pregestational maternal diabetic hyperglycemia was associated with an increased risk for macrosomia and pregestational IFG seemed to be associated with lower rates of LBW and SGA, and even with PTB and VPTB.
To our knowledge, the association between GDM or PGDM and pregnancy outcomes have been well studied, regardless of in the population [26, 27], or at the molecular level [28-30]. And in recent years, researchers began to focus on the association of IFG during the pregnancy with adverse perinatal outcomes and later diabetes mellitus. While the HAPO study has established the relationship of glycose levels below the diagnostic of diabetes during the pregnancy with GDM and increased birth weight [6, 31, 32], few projects studied on the pre-pregnancy maternal glucose among women without overt diabetes mellitus, and its association with later pregnancy or delivery was still uncertain. In our study, we found a significant association between diabetic glucose level within one year before pregnancy and macrosomia, indicating that diabetic hyperglycemia in once fasting glucose test during the preconception examination might also be an early sign of macrosomia.
This finding was compatible with similar but different studies. In previous studies as we know, women with GDM, PGDM, first-trimester hyperglycemia, or mild hyperglycemia at the late trimester, were all proved to be associated with increased risk of macrosomia or LGA [6, 31, 33-35]. And then, our finding indicated that the existing insulin resistance prior to pregnancy might also have an influence on the mothers and their fetuses during the pregnancy or at the delivery, although its degree was under the current diagnostic of diabetes. As a result, the current standard diagnostic criteria of diabetes might be a little strict for women who prepared for pregnancy. Earlier prejudge and proper intervention needs to be taken into consideration for hyperglycemia women in the absence of overt diabetes during the period of preparing for pregnancy.
In addition, there was an interesting finding that the possible effect of maternal diabetic hyperglycemia before pregnancy on macrosomia appeared to be somewhat greater in male fetus than the female fetus. This difference also existed in LGA, which suggested that it cannot just be interpreted by gender or gestational age. A previous study in Spain has shown a similar result that GDM was only a predictor of macrosomia in male fetuses [36]. According to their interpretation, the difference by fetal sex might due to the higher frailty of male fetuses to external influences during the pregnancy, which means male fetuses would be more affected by maternal hyperglycemia and then to be overweight.
Questions have been raised for the possible benefits of pregestational IFG in neonatal outcomes among pregnant women. In our study, the “mild hyperglycemia” prior to the pregnancy might be a protective factor to some adverse birth outcomes including LBW, SGA, PTB and VPTB. Moreover. it did not increase the risks of macrosomia and LGA as diabetic hyperglycemia did. However, this finding was inconsistent with one similar study in Guangdong province of China, which suggested that maternal pre-pregnancy IFG increased the risk of PTB (aRR, 1.07; 95%CI, 1.02-1.12) and LGA (aRR, 1.10; 95%CI, 1.06-1.14) [37]. Another study focusing on the pre-pregnancy IFG found that there was no significant difference in neonatal outcome in women with IFG from the normoglycemia group, but it might be associated with increased risks for maternal outcomes including gestational diabetes and mild preeclampsia [38]. Based on their finding that pregestational maternal IFG was associated with GDM and the guideline of diabetes management for pregnant women in China, we guessed that the protective effect of IFG in our study might be influenced by the intervention such as healthy diet, exercise or insulin taking during the pregnancy to some certain, for there was some evidence showing that treating women with “mild” gestational diabetes mellitus could improve birth outcome [39], but it should be interpreted with caution due to the insufficient data. It also inspired us that the analysis of associations between pregestational hyperglycemia and maternal outcomes, such as GDM, pregnancy hypertension and mild preeclampsia, which information was lacking in NFPHEP database, should be considered in our further study.
As we know, this is one of the few studies with large sample size addressing the impact of glucose level prior to pregnancy on neonatal outcomes among the general women at childbearing age. The strength of our study is the large cohort based on an unselected population covering almost the whole Chongqing Municipality of China, which supports good generalizability of our finding. Our study also has some limitations. Since it is a retrospective cohort study design, our database lacks some important information during the pregnancy period which cannot be collected again. We do not know if the diabetic hyperglycemia women also had a high glucose level during their pregnancies, or whether they had any treatment or intervention to fight with the insulin resistance after their preconception health examinations. Therefore, the findings of our study should be interpreted with caution, since the lack of information might have an impact on the final associations of pregestational glucose level with birth outcomes. Although the lack of information brought uncertainty and possible bias, we inclined to think that the significant risk of macrosomia in pregestational diabetic hyperglycemia women might be underestimated, due to their higher probabilities of developing GDM [10, 38], and the possible subsequent intervention. The aRR of macrosomia might be higher if there was not any intervention before and during pregnancy.
In this retrospective cohort from preconception to delivery, we suggested that pregestational diabetic hyperglycemia is associated with a higher risk of macrosomia. Diabetic hyperglycemia in just one fasting blood glucose testing within one year before the pregnancy might be considered as an early sign of overweight neonates. As no uniform guidelines for pre-pregnancy care on blood glucose management in China and many other developing countries currently, such evidence could count towards justification of official guidelines for maternal blood glucose testings and related interventions during pre-pregnancy care to improve pregnancy outcomes. Further high-quality prospective studies, which included the information of the mothers during the pregnancy, are needed to investigate the effect of pregestational glucose level on the maternal outcome and the metabolic-related variables during the pregnancy.