Associations of Early-Life Nutritional Exposures, Growth-Promoting Hormones and Fetal and Childhood Growth: Analysis of Mother-Child Pairs in Project Viva.
Evidence from animal, epidemiologic, and intervention studies suggests that prenatal and
early postnatal nutritional exposures may program growth-regulating hormones, fetal and
childhood growth patterns, and ultimately risk of associated chronic diseases in later
life. Approaches to understanding and preventing unfavorable growth patterns and chronic
disease increasingly ... read moreemphasize a life-course perspective. Objective: The objective of
this dissertation was to explore the role of early-life exposure to dietary protein in
programming fetal and childhood growth, including evaluating the role of the
insulin-like growth factor (IGF) axis. Methods: We used data from Project Viva, a
Boston, MA-based cohort of mother-child pairs. We analyzed energy- and weight-adjusted
maternal and child protein intakes assessed by food frequency questionnaire. We used
multivariable linear regression models adjusted for covariates to assess the following
associations: Aim 1: Maternal 1st- and 2nd-trimester protein intake with offspring
length at birth and in infancy (~6mo), early childhood (~3y), and mid-childhood (~7y)
(N=1961); Aim 2: Maternal 2nd-trimester protein intake with cord blood IGF-I, IGF-II,
IGFBP-3 and insulin levels, including effect modification by child sex and parity
(N=938); and Aim 3: Early childhood protein intake with adiposity (BMI z-score, sum of
skinfolds and dual X-ray absorptiometry (DXA) fat mass), height and IGF-I levels in
mid-childhood (N=1058). Results: Mean 2nd-trimester protein intake was 1.4g/kg/d.
Mothers were predominantly white, college-educated, and non-smokers. Aim 1: In adjusted
models, each 1-SD (0.36g/kg/d) increment in 2nd-trimester protein intake corresponded to
changes of -0.10 (95% CI: -0.18, -0.03) in birth length z-score; -0.03cm/mo (95% CI:
-0.05, -0.01) in slope of length growth from birth to <6mo; and -0.09cm/y (95% CI:
-0.14, -0.05) in slope of length growth from 6mo to mid-childhood. Aim 2: In adjusted
models, each 1-SD (0.35g/kg/d) increment in 2nd-trimester protein intake corresponded to
changes of -0.71 (-2.48, 1.05) ng/mL in IGF-I, -12.2 (-19.3, -5.14) ng/mL in IGF-II,
-37.2 (-60.7, -13.6) ng/mL in IGFBP-3 and -0.89 (-1.44, -0.34) uU/mL in insulin.
Associations with IGF-II were stronger in girls (p for interaction =0.05) and
multiparous mothers (p for interaction =0.03), and associations with IGFBP-3 were
stronger in multiparous mothers (p for interaction=0.03). Aim 3: Mean early childhood
protein intake was 58.2g/d, well above the US recommendation of 13g/d for 1-3y. Early
childhood protein intake was not associated with any mid-childhood outcomes. In adjusted
models, the βs (95% CIs) for the difference in outcome corresponding to the
highest vs. lowest quartile of protein intake were: 0.13 (-0.05, 0.30) BMI z-score; 0.02
(-1.66, 1.69) for SS+TR skinfolds (mm); -0.04 (-0.72, 0.63) for DXA fat mass (kg); 0.05
(-0.11, 0.21) for height z-score; and -5.30 (-29.6, 19.0) for IGF-I (ng/mL).
Conclusions: In a cohort of pregnant women with relatively high average protein intake,
higher intake was associated with shorter offspring birth length, slower linear growth
into mid-childhood, and lower levels of growth-promoting hormones in cord blood. Results
suggest that high protein intake during pregnancy does not increase fetal and child
growth and may even reduce early length growth, possibly via effects on hormones.
Additionally, our results do not support a role for early childhood protein intake in
programming later adiposity or height growth in children with high average
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Nutritional Epidemiology.
Advisor: Paul Jacques.
Committee: Aviva Must, and Emily Oken.
Keywords: Nutrition, and Epidemiology.read less