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J Nutr. 2017 Jul;147(7):1392-1400. doi: 10.3945/jn.117.250589. Epub 2017 Jun 7.

Higher Maternal Protein Intake during Pregnancy Is Associated with Lower Cord Blood Concentrations of Insulin-like Growth Factor (IGF)-II, IGF Binding Protein 3, and Insulin, but Not IGF-I, in a Cohort of Women with High Protein Intake.

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Friedman School of Nutrition Science and Policy,
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA.
Friedman School of Nutrition Science and Policy.
Jean Mayer-USDA Human Nutrition Research Center on Aging, and.
Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, MA.
Pediatric Endocrinology and Diabetes, Maine Medical Center, and Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Scarborough, ME.
Environmental Influences on Child Health Outcomes (ECHO) Program, Office of the Director, NIH, Bethesda, MD; and.
Department of Nutrition, Harvard School of Public Health, Boston, MA.


Background: Prenatal exposure to dietary protein may program growth-regulating hormones, consequently influencing early-life growth patterns and later risk of associated chronic diseases. The insulin-like growth factor (IGF) axis is of particular interest in this context given its influence on pre- and postnatal growth and its sensitivity to the early nutritional environment.Objective: Our objective was to examine associations of maternal protein intake during pregnancy with cord blood concentrations of IGF-I, IGF-II, IGF binding protein-3 (IGFBP-3), and insulin.Methods: We studied 938 mother-child pairs from early pregnancy through delivery in the Project Viva cohort. Using multivariable linear regression models adjusted for maternal race/ethnicity, education, income, smoking, parity, height, and gestational weight gain and for child sex, we examined associations of second-trimester maternal protein intake [grams per kilogram (weight before pregnancy) per day], as reported on a food frequency questionnaire, with IGF-I, IGF-II, IGFBP-3, and insulin concentrations in cord blood. We also examined how these associations may differ by child sex and parity.Results: Mothers were predominantly white (71%), college-educated (64%), and nonsmokers (67%). Mean ± SD protein intake was 1.35 ± 0.35 g ⋅ kg-1 ⋅ d-1 Each 1-SD increment in second-trimester protein intake corresponded to a change of -0.50 ng/mL (95% CI: -2.26, 1.26 ng/mL) in IGF-I and -0.91 μU/mL (95% CI: -1.45, -0.37 μU/mL) in insulin. Child sex and parity modified associations of maternal protein intake with IGF-II and IGFBP-3: protein intake was inversely associated with IGF-II in girls (P-interaction = 0.04) and multiparous mothers (P-interaction = 0.05), and with IGFBP-3 in multiparous mothers (P-interaction = 0.04).Conclusions: In a cohort of pregnant women with relatively high mean protein intakes, higher intake was associated with lower concentrations of growth-promoting hormones in cord blood, suggesting a pathway that may link higher protein intake to lower fetal growth. This trial was registered at as NCT02820402.


IGF axis; Project Viva; cohort; fetal growth; growth-promoting hormones; prenatal nutrition; protein

[Indexed for MEDLINE]
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Conflict of interest statement

Author disclosures: KMS, PFJ, AM, M-FH, AF, MWG, SR-S, and EO, no conflicts of interest.

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