The mediating effects of gestational diabetes mellitus and hypertensive disorders of pregnancy between maternal advanced age, previous caesarean section and the risk of small- or large-for-gestational-age newborns: a multicentric prospective cohort study in southern China

Background: Maternal obstetric characteristics have a key role in determining the occurrence of pregnancy-related disorders and subsequent neonatal outcomes. We aimed to investigate the mediating impact of gestational diabetes mellitus (GDM) and hypertensive disorder of pregnancy (HDP) on the relationship between maternal advanced age, previous caesarean section, and the risk of either large for gestational age (LGA) or small for gestational age (SGA) infants.

Methods: We used data from a prospective multicentre cohort study conducted through China's National Maternal Near-miss Surveillance System from January 2012 to December 2021. We performed univariate and multivariate logistic regression analyses to examine the connections between maternal advanced age, previous caesarean section, GDM and HDP, and the risks of LGA and SGA, as well as mediation analyses to assess the mediating effect of GDM and/or HDP on the relationship between maternal advanced age, previous caesarean section, and the risks of LGA and SGA.

Results: We included 482 458 women in our study, of whom13.5% were classified as advanced age, 51.4% as multipara, and 16.3% had a history of uterine scarring. Following adjustments for covariates, we found statistically significant associations between maternal advanced age and GDM (adjusted odds ratio (aOR) = 1.79; 95% confidence interval (CI) = 1.75, 1.83), maternal advanced age and HDP (aOR = 1.93; 95% CI = 1.86, 2.01), previous caesarean section and GDM (aOR = 1.13, 95% CI = 1.11, 1.16), previous caesarean section and HDP (aOR = 1.24; 95% CI = 1.20, 1.28), GDM and LGA (aOR = 1.32; 95% CI = 1.30, 1.35), and HDP and SGA (aOR = 3.93; 95% CI = 3.75, 4.12). The influence of maternal advanced age on SGA was significantly mediated by HDP, accounting for 68.96% of the mediation effect. Furthermore, GDM and HDP served as significant mediators in the relationship between previous caesarean section and the risks of LGA and SGA, with mediation proportions of 5.62% and 4.49%, respectively.

Conclusions: We found HDP has a mediating role in the impact of maternal advanced age and previous caesarean section individually on SGA risk, while GDM acts as a mediator in the connection between previous caesarean section and LGA risk.