Maternal and perinatal complications according to maternal age: a systematic review and meta-analysis

Objective: To evaluate the risk levels for maternal and perinatal complications at >=40, >=45, >50 years old compared to younger controls METHODS: Electronic databases were searched from their inception until March 2021. We included studies reporting pregnancy outcome in pregnant women 40, 45 and 50 years or older compared with controls at the time of delivery. Case reports, and case series were excluded. The primary outcome was the incidence of stillbirth. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of either a relative risk (RR) with 95% confidence interval (CI). Heterogeneity was measured using I-squared (Higgins I2 ). Subgroup analyses in women older than 45 years and in those older than 50 years were performed. Results: 27 studies, including 31,090,631, were included in the meta-analysis. The overall quality of the included studies was moderate to high. The vast majority of the included studies were retrospective cohort studies (21/27), four were population-based studies, and two were cross sectional studies. Women ≥ 40 years had significantly higher risk of stillbirth (RR 2.16, 95% CI 1.86 to 2.51), perinatal mortality, IUGR, neonatal death, admission to NICU, preeclampsia, preterm delivery, cesarean delivery, and maternal mortality compared to <40 yo women (RR 3.18, 95% CI 1.68 to 5.98). The increased risk for maternal mortality was 42.76 and 11.60 for women older than 50 years and for those older than 45 years, respectively, while those for stillbirth was 3.72 and 2.32. The risk of stillbirth and cesarean delivery was significantly higher in women >45 years compared to those aged 40-45, and in those >50 years compared to those aged 45-50. The risk of maternal mortality was significantly higher in women >50 years compared to those aged 40-45 (RR 60.40, 95% CI 13.28 to 274.74). Conclusions: The risk of stillbirth, cesarean delivery, and maternal mortality increases with advancing maternal age. The risk ratio for maternal mortality was 3.18, 11.60, and 42.76 in women older than 40, older than 45, and older than 50 years, respectively. These data should be used when women with advanced maternal age are counselled regarding their risk in pregnancy.