ObjectiveAllostatic load refers to cumulative neuroendocrine burden and has been postulated to mediate and moderate physiological and psychological stress-related responses. This may have important implications for the risk of preterm birth. This systematic review examines the evidence on the association between prenatal allostatic load and preterm birth.Data sourcesA comprehensive search of seven electronic databases was conducted from inception to August 23, 2022 to identify all English-language observational and mixed methods studies examining allostatic load and preterm birth with no year or geographic restrictions.Study eligibility criteriaStudies were included if they measured allostatic load, evaluated as the cumulative effect of any combination of more than one allostatic load biomarker, during pregnancy. Studies must have observed preterm birth, defined as < 37 weeks' gestational age, as a primary or secondary outcome of interest.Study appraisal and synthesis methodsThe Quality In Prognosis Studies tool was used to evaluate risk of bias within included studies. A narrative synthesis was conducted to explore potential associations between allostatic load and preterm birth, and sources of heterogeneity.ResultsThree prospective cohort studies were identified and revealed mixed evidence for an association between allostatic load and preterm birth. One study reported a statistically significant association while the other two studies reported little to no evidence for an association. Heterogeneity in when and how allostatic load was measured, limitations in study design and cohort socio-demographics may have contributed to the mixed evidence.ConclusionsThis review provides insight into key individual-, community-, and study-level characteristics that may influence the association between allostatic load and preterm birth. Knowledge gaps are identified as foci for future research, including heterogeneity in allostatic load biomarkers and allostatic load index algorithms as well as pregnancy-specific considerations for allostatic load measurement. Further investigation of the allostatic load framework in the context of perinatal mental health is needed to advance understandings of maternal, infant, and child health.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020208990, PROSPERO, identifier: CRD42020208990.