Abstract: Transplacental enzyme replacement therapy (ERT) is disclosed for deficiency of a polypeptide such as a tissue-nonspecific alkaline phosphatase (TNSALP) by administering a pharmaceutical composition that comprises a water-soluble TNSALP portion, e.g., C-terminus-truncated TNSALP peptide-bonded to an IgG1 antibody Fc portion, to a pregnant animal whose fetus or embryo is in need of such therapy. Also contemplated is a method for treating a metabolic disorder, such as HPP, in a fetus or embryo where a fusion protein that comprises a Fc fragment of an IgG1 antibody peptide-bonded to TNSALP is administered to a pregnant mother. The protein crosses the placenta of the mother and enters the fetal blood stream. The protein is taken up into fetal tissue such that the TNSALP restores normal metabolic activity in the fetus.