INTRODUCTION
Delaying motherhood is reported worldwide with the usage of assisted reproductive technologies, high education level and successful career in women (1-3). In China, with universal two child policy (announced in October 2015), the numbers of mother aged 35 and over have increased obviously (4). Previous studies have reported that advanced maternal age had a high risk of adverse obstetrical and perinatal outcomes (5). The tendency of advanced childbearing age draws our attention to the worse outcomes of the offspring in this particular risk group, trying to find the underlying mechanism.
Fetal macrosomia is defined as birthweight > 4000g, which is a crucial pregnancy outcome because of the maternal and neonatal adverse outcomes subsequently (6). The risk factors for fetal macrosomia include genetic, environmental and metabolic disorders (7). And one of the intriguing findings was that advanced maternal age was an independent predictor for macrosomia(8, 9). Comorbidities during pregnancy and reproductive aging may to some extent contribute to the poor pregnancy outcome of advanced maternal age (10-12). However, in older pregnant women irrespective of comorbidities there are still worse obstetric outcomes (13, 14). There remains unknown on mechanism why advanced maternal age has greater offspring birthweight.
On the other hand, previous studies found that advanced maternal age was significantly more likely to be diagnosed with diabetes mellitus or hyperglycemia during pregnancy (15-17), suggesting that the older pregnant women might have higher glucose level. Moreover, high glucose level before, during, and after pregnancy, is related to abnormal offspring birthweight (18-21). Notably, the preconception glucose level is recognised as the indicator of gestational diabetes (22). And it plays an important role in the preconception care to reduce the risk of the worse pregnancy outcome, since that hyperglycemia during pregnancy couldn’t be well controlled (23). Recently, Yumei Wei et.al reported the linear association between preconception fasting plasma glucose (FPG) level and macrosomia (24), suggesting that preconception glucose level initially affected offspring birthweight. Thus, it indirectly suggests that high glucose level before pregnancy might initially contribute potentially to the association between advanced maternal age and macrosomia. We assumed that preconception FPG level mediated the association between advanced maternal age and offspring birthweight, which prior studies have not been able to account for this.
Using prospective data from a population-based cohort study, we assessed preconception FPG level in advanced versus non-advanced pregnant women, investigating the association between maternal age and macrosomia. Furthermore, we studied for the first time the contribution of preconception FPG level to the effect of advanced maternal age on offspring birthweight by a mediation analysis.