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Background: Given that pregnant women taking medications are excluded from clinical trials, real-world evidence is essential. We aimed to build a Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO) and compare frequency of prematurity, low-birth-weight (LBW), major malformations, multiplicity, and gestational medication use across four provinces., Methods: CAMCCO is a collaborative research infrastructure that uses real-world data from large provincial health care databases in Canada; developed with standardized methods to similarly construct population-based pregnancy/child cohorts with longitudinal follow-up by linking administrative/hospital/birth databases. CAMCCO also includes a common repository to i) share algorithms and case definitions based on diagnostic and procedural codes for research/training purpose, and ii) download aggregate data relevant to primary care providers, researchers, and decision makers. For this study, data from Quebec (1998-2015), Manitoba (1995-2019), Saskatchewan (1996-2020), and Alberta (2005-2018) are compared (Chi-square tests, p-values), and trends are calculated using Cochran-Armitage trend tests., Results: Almost two-thirds (61%) of women took medications during pregnancy, mostly antibiotics (26%), asthma drugs (8%), and antidepressants (4%). Differences in the prevalence of prematurity (5.9-6.8%), LBW (4.0-5.2%), and multiplicity (1.0-2.5%) were statistically significant between provinces (p<0.001). Frequency of major malformations increased over time in Quebec (7-11%; p<0.001), Saskatchewan (5-11%; p<0.001), and Alberta (from 7-8%; p<0.001), and decreased in Manitoba (5-3%; p<0.001). Cardiovascular and musculoskeletal malformations were the most prevalent., Interpretation: Medications are often used among Canadian pregnancies but adverse pregnancy outcomes vary across provinces. Digitized health data may help researchers and care providers understand the risk-benefit ratios related to gestational medication use, as well as province-specific trends., Competing Interests: The authors have declared that no competing interests exist.