Exposure to air and water pollution during pregnancy and risk of adverse perinatal outcomes in São Paulo State: protocol for a retrospective population-based cohort study.

Introduction: The fetus is highly susceptible to extrauterine environmental influences during its development. Exposure to air and water pollutants may compromise fetal growth, increasing risks of morbidity and mortality. Since such exposure can be mitigated through governmental interventions, it is necessary to deepen our understanding of pollution's potential impact in this context. This protocol proposes a study which aims to investigate the association between maternal exposure to air and water pollutants during pregnancy and adverse perinatal outcomes (preterm delivery, low birth weight, small-for-gestational-age births, congenital anomalies and stillbirth) in São Paulo State, Brazil, between 2015 and 2020. Methods and analysis: We will carry out a retrospective population-based cohort study to assess differences in rates of preterm delivery, low birth weight, small-for-gestational-age births, congenital anomalies and stillbirths. All births will be classified according to gestational exposure to air pollutants (particulate matter, nitrogen dioxide, sulfur dioxide, ozone) and water pollutants (nitrate-nitrogen, phosphorus, manganese, nickel, zinc, cadmium, mercury, lead, aluminium, iron and copper). Individual and environmental data will be retrieved from public databases. Inferential analysis will be conducted through a Mixed-Effects Model with prespecified sensitivity analysis. Furthermore, as a secondary objective, we will compare traditional statistical approaches with deep learning methods. Ethics and dissemination: The study will use publicly available, deidentified data. Formal ethical approval is not required, according to the Brazilian National Commission of Ethics in Research (CONEP). Findings will be disseminated through conferences and peer-reviewed publications.