 After running to the southwest of Lehigh Valley Hospital at Muhlenberg, the freeway enters an interchange with US 22 (Lehigh Valley Thruway), PA 378 northbound traffic is directed onto US 22 westbound.The at-grade portion of PA 378 south of Bethlehem was originally designated in the 1928 numbering as an alignment of PA 12, a route crossing through Northampton and Monroe Counties.On April 17, 1961, PA 12 was decommissioned in favor of PA 191, a highway from Center Valley to the New York state line on the Delaware River.