Objectives To assess how the COVID outbreak in Brazil might have impacted birth defects in the State of São Paulo. Design Population-based cohort study. Setting The State of São Paulo, in Brazil. Population Births between 2017 and 2022. Methods Exposure was determined by the midpoint of the first trimester. We used a generalized linear model with Poisson distribution and log link, with clustered robust standard errors. Municipality was used for clustering. Main Outcome Measures The Relative Risk (RR) for any congenital anomaly and per each anatomical site. Results There were 2,961,741 cases in the analysis. The RR for congenital anomalies was 0.97 in the first wave (95% CI: 0.95-1.00, p = 0.029) due to a decrease in respiratory, genitourinary and central nervous system defects, a pattern previously associated with fever-induced anomalies. During the third wave, there was an RR of 1.08 (95% CI: 1.04-1.13, p < 0.001), with an increase in cleft lip and palate, digestive and circulatory defects, just as severe food insecurity rose. No change in risk was identified during the second wave, when both vaccines were introduced and the sales of ivermectin and hydroxychloroquine spiked. Conclusions The COVID-19 outbreak impacted birth defects differently during each wave. Considering concurrent conditions might provide insight into the underlying causes for this phenomenon. The true burden for pregnant individuals of food supply chain disruption, which is also threatened by climate change, might not yet be fully recognized.