A U-spin relation among four ratios of amplitudes for $D^0 to pi^+K^-$, $K^+pi^-$, $K^+K^-, pi^+pi^-$, including first, second and third order U-spin breaking, has been derived recently with a precision of $10^{-3}$. We study effects of new $|Delta C|=1$ operators on this relation. We find that it is not affected by U-spin scalar operators, including QCD penguin and chromomagnetic dipole operators occurring in supersymmetric and extra-dimensional models. The relation is modified by new $U=1$ operators with a sensitivity of a few percent characteristic of second order U-spin breaking. Combining this relation with CP asymmetries in $D^0to K^+K^-, pi^+pi^-$ leads to a more solid constraint on $U=1$ operators than from asymmetries alone.