Chicago Fire Department officials said she had to be revived several times - once at the scene of the horrific two-car crash, another time in an ambulance and again at Comer Children's Hospital.
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She and a 6-year-old boy were listed in critical condition at Comer, according to fire officials.
The crash occurred around 6:15 a.m. near the intersection of East 49th Street and South King Drive in the city's Bronzeville neighborhood. Police said a 2017 Hyundai Elantra carrying the two small children was T-boned by a Dodge Charger driven by a 23-year-old man.
Neighbors heard the loud crash and ran to the scene.
"The man that hit the oncoming car, he went running over and pulled the children out of the back seat," said Lauren Armour, a neighbor. "There were no car seats. There were no seatbelts, from what it looked like. When he pulled them out, both of their bodies were limp."
Authorities said both children were traveling in the backseat of the Hyundai and were not properly restrained.
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A 23-year-old woman was driving the Hyundai. Fire officials said her injuries were not life threatening. Chicago police said she was listed in serious condition at University of Chicago Medical Center.
The driver of the Dodge Charger refused medical treatment at the scene, authorities said.
Police have not confirmed if the mother or a relative was driving, or if it was a caregiver behind the wheel. Both drivers have accused each other of running the red light.
Detectives from the Major Accident Investigation Unit are investigating. They planned to look for any possible video nearby that may shed light on who was at fault.
Authorities said there were no city cameras at that intersection.