It happened Tuesday morning on Interstate 10 in Houston.
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The freeway is shut down and is expected to be closed for at least another few hours.
According to Lynn Nguyen, Chief of Vehicular Crimes, a white truck stopped in a moving lane of traffic because a water bottle was stuck underneath the driver's brake and gas pedals.
The driver put on his hazard lights as he tried to remove the bottle.
A second and third car were both able to stop and did not hit him. However, a fourth vehicle, a silver pickup truck, couldn't stop in time and crashed into them.
An 18-wheeler that was unable to avoid the wreck also hit the silver truck, causing it to spin.
The 3-year-old and 9-year-old were in the back of the silver pickup. Both children were flown to the hospital and taken into surgery.
The 3-year-old has a brain hemorrhage and the 9-year-old has a skull fracture.
The drivers are okay. They have not shown signs of intoxication, according to authorities.
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An investigation will determine if the driver of the silver truck was speeding.
Officials did see a car seat, but they don't know if either of the children were restrained.
Charges are possible, pending the outcome of the investigation.