Extremely preterm (EP) infants have high rates of respiratory morbidity and correspondingly high healthcare resource utilization. Data from the PHARMO Perinatal Research Network were analyzed to quantify the burden of EP birth in the Netherlands. A retrospective analysis included infants <28 weeks gestational age with a birth record in the Perinatal Registry (1999–2015) and data in the PHARMO Database Network. Outcomes of interest included select comorbidities, hospital readmissions, and costs of hospitalization and medication up to 1- and 2-years corrected age. Outcomes were stratified by birth period (1999–2005, 2000–2009, 2010–2015) and by diagnosis of bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD). The cohort included 168 EP infants (37 born 1999–2005, 51 born 2006–2009, 80 born 2010–2015). Median (Q1–Q3) birth weights decreased by birth period from 970 (840–1,035) g in 1999–2005 to 853 (695–983) g in 2010–2015. Overall, BPD and CLD were reported during the birth hospitalization in 40% and 29% of infants, respectively; rates of BPD increased and rates of CLD decreased by birth period. Eighty-four percent of EP infants had an additional comorbidity. Mean (standard deviation) costs of birth hospitalization were €110,600 (€73,000) for 1999–2005, €119,350 (€60,650) for 2006–2009, and €138,800 (€130,100) for 2010–2015. Birth hospitalization and total costs for up to 1- and 2-years corrected age were higher for infants with BPD and/or CLD than for those without either complication. Healthcare resource utilization and costs for EP infants, especially for those with respiratory morbidities, increased between 1999 and 2015. Future cost-effectiveness analyses are essential to determine the economic impact of this change and underscore the need for new therapeutic interventions to decrease clinical sequelae in this vulnerable population.