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Maternal Serum Insulin-Like Growth Factor Binding Protein-1 in Pregnancy at High Altitude

From the Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, United Kingdom.

Address reprint requests to: Kypros H. Nicolaides, King’s College Hospital, Harris Birthright Research Centre for Fetal Medicine, Denmark Hill, London, SE5 9RS, United Kingdom; E-mail: kypros{at}fetalmedicine.com.

OBJECTIVE: To investigate the effect of environmental hypoxia at 4300-m altitude on the maternal serum concentration of insulin-like growth factor binding protein-1 (IGFBP-1).

METHODS: We conducted a cross-sectional study of 108 pregnant women in Peru, 62 from high altitude (4300 m, 14100 ft) and 46 from sea level at 14–42 weeks’ gestation. For comparison, 20 healthy nonpregnant women (ten from high altitude and ten from sea level) were also examined. Total and nonphosphorylated IGFBP-1 were measured in maternal serum.

RESULTS: Both total and nonphosphorylated IGFBP-1 were higher at high altitude than at sea level in the pregnant groups (ratio = 1.28, P = .008, and ratio = 1.45, P = .003, respectively), and there was significant interaction between high altitude and sea level (P = .037 and P = .043, respectively). The threshold model showed that the difference became significant from 25 weeks’ gestation onwards.

CONCLUSION: Before 25 weeks of pregnancy, there was no significant difference in IGFBP-1 between women living at high or low altitude, suggesting that the increased IGFBP-1 at high altitude is unlikely to be related to inadequate trophoblast invasion resulting in placental hypoxia. In the second half of pregnancy, the maternal and fetal demands increase dramatically, and low atmospheric oxygen with resulting maternal systemic hypoxemic hypoxia may cause placental hypoxia. This stimulates increased production of IGFBP-1, which in turn restricts the insulin-like growth factor-mediated fetal growth as an adaptive mechanism to prevent worsening of the fetoplacental hypoxia.

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				S. Kajimura, K. Aida, and C. Duan From the Cover: Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation PNAS, January 25, 2005; 102(4): 1240 - 1245. [Abstract] [Full Text] [PDF]