Parental age and the risk of bipolar disorder in the offspring: A systematic review and meta-analysis

Objectives Whether parental age, i.e., paternal or maternal, at childbirth is associated with the risk of bipolar disorder (BD) in offspring remains unclear. We conducted a meta-analysis of observational studies to address this gap. Methods PubMed, PsycINFO, Embase, and Web of Science were searched up to June 2021. Studies investigating the associations between parental age at childbirth (exposure) and the risk of BD in offspring (outcome) were eligible for inclusion in our study. Paternal and maternal age were examined separately. Odds ratio (OR) was used as the effect size index. Data were pooled through random-effects meta-analyses. Results Seven studies involving 3,183,539 participants and 23,253 individuals with BD were included in our meta-analyses. Meta-analyses indicated an increased risk of BD in the offspring of the older paternal age groups (35-44 years old [k = 5; OR = 1.09; 95% CI 1.05, 1.14; p < 0.0001] and >= 45 years old [k = 5; OR = 1.44; 95% CI 1.19, 1.14; p = 0.0001]) in comparison with the reference category (25-34 years old). Meta-analysis also indicated an increased risk of BD in the offspring of the older maternal age group (>= 40 years old [k = 3; OR = 1.20; 95% CI 1.10, 1.31; p < 0.0001]) in comparison with the reference category (20-29 years old). Conclusions Advanced paternal and maternal age were both associated with an increased risk of BD in offspring. Further studies are needed to investigate the mechanisms behind this association.