Adverse pregnancy outcomes and imbalance in angiogenic growth mediators and oxidative stress biomarkers is associated with advanced maternal age births: A prospective cohort study in Ghana

Abstract

Background Advanced maternal age (AMA) has been associated with negative pregnancy outcomes. Oxidative stress (OS) and defective placental dysfunction are contributing factors. This study determined the association between AMA and adverse pregnancy outcomes, OS biomarkers and angiogenic growth mediators (AGMs) in normal pregnancies. Methods This prospective cohort study conducted at the Obstetrics and Gynaecology (O&G) Department of the Komfo Anokye Teaching Hospital (KATH) finally included 175 normal pregnant women comprising, 58 AMA (35±45 years), 55 (30±34 years) and 62 optimal childbearing age (20±29 years). Venous blood samples were collected at 28±32 weeks for soluble fmslike tyrosine kinase-1 (sFlt-1), placental growth factor (PIGF), 8-epiprostaglandinF2-α (8- epi-PGF2α) and total antioxidant capacity (TAC) assays. Results Pregnancies of AMA had a significantly higher levels of sFlt-1, 8-epi-PGF2α and 8-epi- PGF2α: PIGF ratio but a reduced level of PIGF, TAC and PIGF: sFlt-1 ratio compared to 20±29 years (p<0.0001). A significant negative correlation between AMA and PIGF (r = -0.294; p = 0.038); TAC (r = -0.215; p = 0.001) and PIGF: sFlt-1 ratio (r = -0.457; p<0.0001) and a positive correlation with sFlt-1 (r = 0.269; p = 0.017), 8-epiPGF2α (r = 0.277; p = 0.029) and 8-epi-PGF2: PIGF ratio (r = 0.461; p<0.0001) levels were observed. The adjusted odds ratio (aOR), and 95% confidence interval, and p value for the significant independent adverse outcomes associated with AMA were emergency caesarean section [21.7 (5.9±121.3), p<00001], elective caesarean section [2.7(0.9±5.8), p = 0.0105], stillbirth [12.6 (1.4±82.1), p<0.0001], post-partum haemorrhage [4.3(1.1±18.5), p = 0.0094], preterm delivery [8.2(3.5±28.4), p<0.0001], low birth weight babies [9.7(2.8±29.3), p<0.0001], birth asphyxia [3.8(1.6±12.7), p = 0.0054], Apgar score 7 after 5 min for babies [10.1(4.7± 23.2), p<0.0001], placental abruption [3.5(1.3±8.4), p = 0.0117] and intrauterine growth restriction (IUGR) [4.6(2.3±12.9), p = 0.0001]. Conclusion AMA pregnancies correlate with adverse pregnancy outcomes and imbalance in OS biomarkers and AGMs. It is incumbent on health care givers to provide effective antenatal care among AMA mothers as early identification of these imbalance and treatment can prevent adverse pregnancy outcomes.