Inequities in health occur across many facets of life. Life expectancy varies across countries1 and across communities within countries.2 In neonatology, racial disparities in preterm birth are the largest contributor to differences in outcomes that matter to families and society: mortality and long-term morbidity.3 Compared to White counterparts, Black infants are fifty percent more likely to be born preterm, and three times more likely to be born prior to 28 weeks of gestation.4 Extremely preterm infants are at highest risk of death and disability among survivors.5 Longstanding racial disparities in perinatal and infant outcomes remain incompletely understood.

One of the major limiting factors in understanding and resolving disparities in preterm birth is that the pathophysiology of preterm birth remains a mystery. In part, this is because preterm birth is a multifactorial adverse pregnancy outcome following a multitude of biologic processes. Spontaneous preterm birth occurs after labor or rupture of membranes prior to 37 completed weeks of gestation. Medically indicated preterm birth occurs when providers decide the maternal or fetal risks of continuing a pregnancy exceed the benefits of longer gestation (e.g., severe preeclampsia or profound growth restriction). The precise pathophysiology of each of these conditions, while active areas of research, remains elusive. However, risk factors for preterm birth have been identified. Prior spontaneous preterm birth, short cervical length, bacterial vaginosis, and maternal smoking are well-established risk factors for spontaneous preterm birth.6,7 Obesity, hypertension, and older maternal age are significant risk factors for medically indicated preterm birth.8, 9, 10 Black patients have significantly higher risk than white patients of each preterm subtype11 but given that we do not understand underlying the basic pathophysiologic processes, it should not be surprising that we do not understand why the disparity exists.

However, even in the absence of an exact delineation of the pathophysiology of preterm birth, investigators have searched for explanations for disparities by analyzing many factors including, but not limited to, genetics,12 nutrition,13 infection,14 cardiometabolic disorders (hypertension, diabetes, and obesity),11 as well as exposures to social stressors15 and physical environmental toxicants.16,17 Many epidemiologic studies, including some of our own, that attempt to find variables to explain disparities employ interaction terms and race-stratified analyses. However, in this piece, which largely focuses on physical environmental toxicant exposures, we propose that mediation analyses are underutilized and powerful models to interrogate disparities and may be more appropriate to identify targets for interventions to improve health equity.