The crash happened in the southbound lanes in the 8400 block of I-45 near Veteran's Memorial Drive around 10:30 p.m. Sunday.
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The North Freeway was closed for several hours overnight as crews worked to clear the crash.
Video from the scene shows a black Honda crossover smashed up and surrounded by debris.
A witness told Houston police the Honda somehow lost control, slammed into the sidewall of the freeway, then flipped several times.
Inside the car were seven people total -- four children who are all siblings, two adult passengers, and the adult driver.
Two of the children and one adult were ejected from the car, according to HPD. A 1-year-old girl was killed, and a 3-year-old boy and a 29-year-old man are in critical condition, according to police.
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Investigators said the two other children -- a 10-year-old boy and a 5-year-old boy-- were taken to the hospital with minor injuries. The 33-year-old man who was driving and a 31-year-old woman -- the children's mother -- were not injured, police said.
The exact cause of the crash is still being investigated.
"We have a DRE and a DWI unit out here conducting field sobriety tests, doing that aspect of the investigation," Lt. J.P. Horelica said. "At this time, it's too early in the investigation to know if anybody was intoxicated or not, but we have to check all angles."
Investigators said none of the children were properly restrained. There was reportedly one car seat inside the vehicle, but it was in the trunk.
The driver was detained at the scene and a field sobriety test was conducted, police said. Investigators did not say whether or not the driver was intoxicated or if charges would be filed.
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