Investigations into a possible immunological origin of idiopathic non‐immune hydrops fetalis and initial results of prophylactic immune treatment of subsequent pregnancies

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Abstract
The cause of the non‐immune hydrops fetalis (NIHF) remains unsettled despite all efforts. From the immunological point of view of pregnancy as a successful course of an allograft, it would seem possible that the idiopathic NIHF can be caused by an immunologic disorder in the meaning of a host‐versus‐graft reaction. Of 324 cases of prenatally diagnosed NIHF, 49 (15,1%) could be classified after exclusion of all other causes as idiopathic and in 38 patients, as well as in 38 age‐ and parity‐paired controls, a differentiation of HLA‐antigens and a determination of lymphocytotoxic antibodies using the NIH Prolonged Incubations and Cold‐Complement‐Dependent Cytotoxicity Test (CoCoCy Test) were performed. In cases of idiopathic NIHF, the proportion of parents sharing 4 or 5 HLA antigens was increased significantly (p<0.05) compared with the control group. In women with idiopathic NIHF, the incidence of lymphocytotoxic antibodies was decreased, due to the test system used; between 28 and 68% in the NIHF group and 24‐80% in the control group. The proportion of women without lymphocytotoxic antibodies was increased in the NIHF group by 72% to 52%, whereas in the control group, in none of the patients could a higher cytotoxicity with a lysing rate of more than 75% be detected. In 8 cases of idiopathic NIHF, where an increased paternal histocompatibility and a decreased incidence and percentage of lymphocytotoxic antibodies were determined, an immunotherapy was performed in order to induce maternal blocking antibodies. Treatment was given as an intradermal injection of paternal lymphocytes before and from the 6th‐8th week of pregnancy every 4 weeks until the 26th week. In all patients, an induction of lymphocytotoxic antibodies could be achieved, giving six successful pregnancies so far. These results fulfilled the requirement of an immunologic diagnosis in all patients with an “idiopathic” NIHF and the carrying out of immunotherapy on appropriate indications.