Causal relationship between Women's reproductive traits and postpartum depression: a multivariate Mendelian randomization analysis

Background: The relationship between women's reproductive traits and postpartum depression (PPD) has not been clarified. We reveal the association between genetically predicted modifiable women’s reproductive traits and PPD using two-sample Mendelian randomization (MR). Methods: : We used genome-wide association studies (GWASs) to obtain instrumental variables (IVs) of 10 women's reproductive traits. Univariate and multivariate MR analyses were used to examine the association between traits and the risk of PPD (13,657 cases and 236,178 controls). The primary causal effect assessment employed IVW method. Results: : In the UVMR result, genetic prediction showed that age at first sexual intercourse (AFS) (OR = 0.474, 95% CI 0.396-0.567; P = 4.6×10 -16 ), age at first birth (AFB) (OR = 0.865, 95% CI 0.805-0.930; P = 8.02×10 -5 ), and age at last live birth (ALLB) (OR = 0.296, 95% CI 0.138-0.636; P = 0.002) were significantly inversely associated with PPD, while a higher lifetime number of sexual partners (LNSP) (OR = 1.431, 95% CI 1.009-2.031; P = 0.045) and a greater number of spontaneous miscarriages (OR = 1.519, 95% CI 1.021-2.262; P = 0.039) are suggested associated with an increased risk of PPD. In the MVMR result, only AFB (OR = 0.804, 95% CI 0.661-0.978; P = 0.029) and spontaneous abortion (OR = 1.182; 1.036-1.348; P = 0.013) retained a direct causative relationship with PPD. Conclusions: : We confirmed that AFB and spontaneous abortion are high-risk factors for PPD. Our findings further support revising the diagnostic criteria (ICD-10) such that PPD is independent of major depressive disorder.