Flank pain with fever during pregnancy is most concerning because it strongly suggests pyelonephritis, a serious upper urinary tract infection that can lead to maternal sepsis, preterm labor, and adverse fetal outcomes. Prompt diagnosis and treatment are critical to prevent complications. In contrast, mild frequency, nocturia, and mild dysuria are common, often benign urinary symptoms due to physiological changes in pregnancy. Therefore, the presence of systemic signs such as fever combined with flank pain necessitates urgent evaluation and management.

Reference: Williams Obstetrics, Cunningham et al., 25th Edition.