Association between age at first birth and postpartum depression: A two-sample mendelian randomization analysis

Area of Science:

• Reproductive Health
• Psychiatric Genetics
• Epidemiology

Background:

• Observational studies suggest a link between age at first childbirth (AFB) and postpartum depression (PPD).
• The causal nature of this association requires further investigation.
• Mendelian randomization (MR) offers a robust approach to explore causality.

Purpose of the Study:

• To investigate the causal effect of age at first childbirth (AFB) on the risk of postpartum depression (PPD).
• To utilize a two-sample Mendelian randomization analysis for assessing this relationship.

Main Methods:

• Employed two-sample Mendelian randomization (MR) using genetic instrumental variables from large-scale genome-wide association studies (GWAS).
• Utilized summary statistics from UK Biobank, Neale Lab, and Finngen consortium (13,657 PPD cases, 236,178 controls).
• Applied various MR methods including Inverse Variance Weighted (IVW) and Weighted Median, alongside heterogeneity and pleiotropy tests.

Main Results:

• A significant causal effect was observed, indicating that increased age at first childbirth is associated with a reduced risk of postpartum depression.
• The Inverse Variance Weighted (IVW) method showed an odds ratio (OR) of 0.59 (95% CI 0.36-0.96, p=0.03).
• Weighted median analysis corroborated these findings (OR 0.59, 95% CI 0.37-0.95, p=0.03), with no significant heterogeneity or horizontal pleiotropy detected.

Conclusions:

• Mendelian randomization analysis supports a causal relationship where a later age at first childbirth confers a protective effect against postpartum depression.
• Identified major depressive disorders, family income, and marital stress as potential mediating factors.
• Findings reinforce the importance of considering reproductive timing in the context of maternal mental health.