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.