Introduction: The complex biopsychosocial pathways linking maternal mental health with preterm birth (PTB) are not well understood. This study aimed to explore allostatic load (AL) as a mediator and perceived chronic stress as a moderator in the pathway linking maternal mental health and PTB. Methods: A cohort study of pregnant women (n = 1,567) recruited at clinic visits within 10–19 weeks of gestation was assessed for maternal mental health (i.e., pregnancy-related anxiety, state anxiety, depressive symptoms) and perceived chronic stress. Blood pressure and levels of cortisol, total cholesterol, C-reactive protein, and glycosylated hemoglobin were used to create a composite measure of AL. Results: AL had the most significant effect on PTB (odds ratio (OR) = 1.84, 95% CI = 1.26–12.67, p = 0.001), while systolic blood pressure emerged as the only significant individual marker using variable selection (OR = 22%, 95% CI = 1.06–1.40, p < 0.001) in multiple logistic regression analysis. A mediation analysis revealed that maternal mental health did not have a significant direct effect on PTB (p = 0.824), but its indirect effect mediated by AL was significant (z = 2.33, p < 0.020). Low and high levels of perceived chronic stress, relative to the mean, moderated this indirect effect (z = 3.66, p < 0.001). Conclusions: AL has a significant direct influence on PTB and mediates the effect of maternal mental health on PTB; however, the indirect effect of AL is indistinguishable between women with higher or lower levels of perceived chronic stress than normal.

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