Abstract
Background/Aims Septal hypertrophic cardiomyopathy (sHCM) is a characteristic anomaly of the infant of diabetic mother (IDM). Insulin-like growth factor-I (IGF-I) has been identified to contribute to the various tissue overgrowth in these infants. We have previously shown that maternal IGF-I levels were significantly elevated among neonates with sHCM. IGF-I does not cross the placenta and its physiologic action is mediated through the receptor, IGF-IR. IGF-IR are present in various tissues including the heart muscle. We have thus investigated whether there is an association between placental IGF-IR in IDMs with and without sHCM.
Methods A cohort of 50 diabetic and 50 normal pregnancies booked in the Hospital UKM, Kuala Lumpur, over a period of two years (Jan. 2001- Dec. 2002) were enrolled into a larger related study. The placentae of six diabetic pregnancies with neonatal sHCM and six randomly selected diabetic pregnancies without neonatal sHCM were compared to the placentae from six normal pregnancies for IGF-IR expression by immunohistochemistry. The staining for IGF-IR in the decidua, cytotrophoblast, syncytiotrophoblast and fetal endothelium for these 18 samples were assessed randomly by the pathologist who was blinded to the respective diagnoses. The intensities of IGF-IR staining were classified as 0 (negative), 1+ (weak), 2+ (medium), 3+ (strong).
Results Placental IGF-IR staining was negative in the fetal endothelium for all three groups. In the normal controls, and diabetic group without neonatal sHCM, IGF-IR were 3+ in decidua, 2+ in cytotrophoblast and 2+ in syncytiotrophoblast. In contrast, IGF-IR were all 2+ in the decidua, cytotrophoblast and syncytiotrophoblast from the diabetic group with neonatal sHCM.
Conclusions Reduced placental IGF-IR expression in the decidua of diabetic pregnancies suggests that IGF-IR is down-regulated in response to elevated maternal IGF or mediators of neonatal sHCM. Modulation of activity at the IGF-IR level may be a target for therapy against the development of fetal/neonatal sHCM in diabetic pregnancies.
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Hayati, A., Tan, G., Tan, A. et al. 65 Placental IGF-I Receptor and Septal Hypertrophic Cardiomyopathy in Infants of Diabetic Mothers. Pediatr Res 58, 365 (2005). https://doi.org/10.1203/00006450-200508000-00094
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DOI: https://doi.org/10.1203/00006450-200508000-00094