Ayane Sakura, who voices Yotsuba, previously played all 5 of the Nakano Quintuplets in a Commercial for the Manga prior to the Show's creation.
The First Season was animated by Tenzuka Productions, while the Second Season Moved to Bibury Animation.
Yotsuba wears a shirt with the Numbers "428" written on it. Spelling these Numbers in Japanese spells her Name.
The final Episode of Season 2 has the Quintuples attempting to make the Perfect Date between Fuutaro & Miku. In the Manga, this is told out of Order, 1 Chapter seeing it from Fuutaro & Miku's Perspective & the Following Chapter from the Other Quintuplets. In the Anime, to save on time, they happen Concurrently, breaking a lot of the Mystery as to what's going on, you didn't have the Context for such things as to who pushed Fuutaro & Miku into the River until the Following Chapter; here, you get the Answer right away.
The Animation change between the First & Second Seasons are so drastically different that Flashbacks to the Pervious Season had to be reanimated to match the Newer Seasons style; unlike shows like, for Instance, the 4th Season of Attack on Titan where Studio Mappa simply reused Studio Wit's Animation whenever it could be used for Flashbacks.