POSTPARTUM DEPRESSION AND TIMING OF SARS-COV-2 VACCINATION
Authors: Perez-Rodriguez *M Mercedes , Prakash Sahana , Moore Kendall , Camacho-Castro Juliana , Lieb Whitney , Jessel Rebecca , Gigase Frederieke , Lesseur Corina , Janevic Teresa , Dolan Siobhan , Stone Joanne , De Witte Lotje , Bergink Veerle , Rommel Anna-Sophie 
Published: February 2025

Abstract

Background
The SARS-CoV-2 vaccine is a key tool for protection against severe COVID-19 disease during pregnancy (1). However, the brief strong inflammatory reaction that occurs after vaccination may impact postpartum depressive symptoms as proposed by the neuroinflammatory hypothesis of depression (2).

Aims and Objectives
This study aims to examine the potential association between SARS- CoV-2 vaccination during pregnancy and postpartum depression.

Method
Participants (n=627) were enrolled in the CDC-funded Generation C (n=564) or the NIH-funded Generation C-SF (n=63) prospective pregnancy cohorts at the Mount Sinai Health System (MSHS) in New York City between April 2020 and September 2023. Edinburgh Postnatal Depression Scale Scores (EPDS) were measured between 1-9 months postpartum. SARS-CoV-2 vaccination status and timing were determined from vaccination records. We used quantile regression analysis to examine the relationship between SARS-CoV-2 vaccination timing (categorical predictor variable) and EPDS scores (continuous outcome variable), adjusting for gestational SARS-CoV-2 infection, race/ethnicity, pre-pregnancy BMI, education level, parity, gestational age at delivery, timing of EDPS assessment, maternal age, lifetime history of depression or anxiety, insurance type, and time elapsed from the start of the pandemic to delivery. Participants were categorized based on the timing of vaccination: 1) SARS-CoV-2 vaccinated with at least one dose during pregnancy, 2) SARS-CoV-2 vaccinated with all doses prior to pregnancy, 3) SARS- CoV-2 vaccinated with at least one dose between delivery and completion of EPDS assessment but not during pregnancy, and 4) no history of SARS-CoV-2 vaccination before EPDS assessment (reference group).

Results
61 (9.7%) participants had an EPDS score of 11 or higher, which indicates clinical levels of postpartum depression symptoms (3). For SARS-CoV-2 vaccination status, 94 (15%) of participants were vaccinated before pregnancy, 100 (16%) during pregnancy, 57 (9%) after delivery, and 376 (60%) were not vaccinated (reference group). In the quantile regression analysis, among participants who received SARS-CoV-2 vaccination during or prior to pregnancy, there were no significant associations between vaccination and EPDS scores in any quantile. Those who were vaccinated after delivery but before EPDS administration showed no association between vaccination and EPDS at the 25% quantile (Coefficient=-0.30, CI= -1.03; 0.18) or the 50% quantile (Coefficient= -1.16, CI= -1.85; 0.03), but did show a significant negative association at the 75% quantile (Coefficient= -1.41, CI= -2.46; -0.48).

Discussion & Conclusion
SARS-CoV-2 vaccination before and during pregnancy were not significantly associated with postpartum depression symptoms. Postpartum SARS-CoV-2 vaccination before the EPDS assessment was associated with slightly lower EPDS scores in those with more depressive symptoms. Enhanced access to health care, social support, physician follow up, or trust of medical institutions may account for this finding. Alternatively, those with lower EPDS scores (i.e., less severe depression) may be more likely to seek medical care (e.g., vaccination).

References
1.Piekos SN, Hwang YM, Roper RT, Sorensen T, Price ND, Hood L, Hadlock JJ. Effect of COVID-19 vaccination and booster on maternal-fetal outcomes: a retrospective cohort study. Lancet Digit Health. 2023 Sep;5(9):e594-e606. doi: 10.1016/S2589-7500(23)00093-6. Epub 2023 Aug 1. PMID: 37537121; PMCID: PMC10473855.
2.Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, Pariante CM, Howes OD. Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls. Brain Behav Immun. 2020 Jul;87:901-909. doi: 10.1016/j.bbi.2020.02.010. Epub 2020 Feb 27. PMID: 32113908; PMCID: PMC7327519
3.Levis, B., Negeri, Z., Sun, Y., Benedetti, A., Thombs, B. D., &DEPRESsionScreening Data (DEPRESSD) EPDS Group (2020). Accuracy of the Edinburgh Postnatal Depression Scale (EPDS) for screening to detect major depression among pregnant and postpartum women: systematic review and meta-analysis of individual participant data. BMJ (Clinical research ed.), 371, m4022. https://doi.org/10.1136/bmj.m4022