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

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


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 clinicaltrials.gov as NCT02820402.

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

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cohort Studies
  • Dietary Proteins*
  • Female
  • Fetal Blood / chemistry*
  • Gene Expression Regulation, Developmental
  • Humans
  • Insulin / chemistry
  • Insulin / metabolism*
  • Insulin-Like Growth Factor Binding Protein 3 / chemistry
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Insulin-Like Growth Factor I / chemistry
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor II / chemistry
  • Insulin-Like Growth Factor II / metabolism*
  • Pregnancy
  • Prenatal Nutritional Physiological Phenomena


  • Dietary Proteins
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II

Associated data

  • ClinicalTrials.gov/NCT02820402
  • ClinicalTrials.gov/NCT02820402