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Experience with Intraamniotic Thyroxine Treatment in Nonimmune Fetal Goitrous Hypothyroidism in 12 Cases

Department of Pediatrics (V.R.), Clemenceau Hospital, Caen, France; Pediatric Endocrinology and Gynecology (V.R., M.C., M.P.), Centre des Maladies Endocriniennes Rares de la Croissance, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, and Institut National de la Santé et de la Recherche Médical Unité 845, Paris Descartes University, 75015 Paris, France; Department of Pediatrics (A.-M.B.), Saint-Jacques Hospital, 25000 Besançon, France; Department of Fetal Biochemistry (J.G.), Cochin Hospital, 75014 Paris France; Perinatal Center (E.V.), Robert Debré Hospital, 75019 Paris, France; and Department of Obstetrics and Gynecology (D.L.), Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Diderot University, 75015 Paris, France

Address all correspondence and requests for reprints to: Michel Polak, M.D., Ph.D., Pediatric Endocrinology and Gynecology, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015 Paris, France. E-mail: michel.polak{at}nck.aphp.fr.

Context: Nonimmune fetal goitrous hypothyroidism is a rare condition that can induce obstetrical and/or neonatal complications and neurodevelopmental impairments such as those still seen in some patients with congenital hypothyroidism. Prenatal treatment to prevent these adverse outcomes is appealing, but experience is limited and the risk to benefit ratio controversial.

Objective: The objective of the study was to evaluate the feasibility, safety, and effectiveness of intrauterine L-thyroxine treatment in a large cohort with nonimmune fetal goitrous hypothyroidism.

Design: This was a retrospective study of 12 prenatally treated fetuses diagnosed between 1991 and 2005 in France.

Methods: During pregnancy, goiter size and thyroid hormone levels were compared before and after prenatal treatment. At birth, clinical, laboratory, and ultrasound data were evaluated.

Results: Prenatal treatment varied widely in terms of L-thyroxine dosage (200–800 µg/injection), number of injections (one to six), and frequency (every 1–4 wk). No adverse events were recorded. During pregnancy, thyroid size decreased in eight of nine cases and amniotic-fluid TSH levels decreased in the six investigated cases, returning to normal in four. However, at birth, all babies had hypothyroidism, indicating that intraamniotic TSH levels did not reliably reflect fetal thyroid function.

Conclusion: Our data confirm the feasibility and safety of intraamniotic L-thyroxine treatment for nonimmune fetal goitrous hypothyroidism. Although goiter size reduction is usually obtained, thyroid hormone status remains deficient at birth. Amniocentesis seems inadequate for monitoring fetal thyroid function. Further studies are needed to determine the optimal management of this disorder.