If you want something specific to Mathematica then I don't know, but in general:
Let σ=ρAD=TrBC(ρ). ρ is an operator on four subsystems, so it has four inputs and four outputs making it a rank 8 tensor. Let i,i′ be the indices corresponding to the input and output of ρ on subsystem A, let j,j′ correspond to B, etc. The components of σ are then σii′ll′=∑jkρii′jjkkll′.
If ρ is sparse you only need to sum the entries which are nonzero. If ρ is Hermitian then σ will be Hermitian and it is enough to only compute the upper triangle (the lower triangle is then the conjugate of that). I don't believe there are any other optimizations available unless you know of further structure on ρ. The sum is trivially parallelizable - each combination ii′ll′ is completely independent of the others.
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