Low-grade inflammation from prenatal period to age 6-8 years in a Vitamin D trial.

Background: Low-grade systemic inflammation measured as high sensitivity C-reactive protein (hs-CRP) has been associated with non-communicable disease risk. We assessed whether prenatal inflammation and early-childhood vitamin D are associated with inflammation until age 6-8.

Methods: We analyzed blood hs-CRP and 25-hydroxy vitamin D [25(OH)D] in pregnancy, at birth from umbilical cord blood (UCB), from offspring at ages 1, 2, and 6-8 years in the Vitamin D Intervention in Infants (VIDI) study. VIDI was a randomized-controlled trial of vitamin D supplementation of 10 μg/day or 30 μg/day from age 2 weeks until 2 years in 975 infants recruited in 2013-14, with follow-up at age 6-8 in 2019-21 (n = 283).

Results: Pregnancy hs-CRP was associated with UCB hs-CRP (r = 0.18, p < 0.001) but not independently with childhood hs-CRP (Estimate [95% CI] 0.04 [<-0.00, 0.09]). Higher UCB hs-CRP was associated independently with higher hs-CRP until 6-8 years (0.20 [0.12, 0.29]). Infant vitamin D dose had no effect on longitudinal hs-CRP (6-8 years, 0.11 [-0.04, 0.25]). Childhood 25(OH)D were associated positively with hs-CRP until age 6-8 (0.01 [>0.00, 0.01]).

Conclusion: Our results indicate that in children, inflammation, assessed by hs-CRP, persists from birth until 6-8 years. We observed positive associations between 25(OH)D and hs-CRP in vitamin D-sufficient children.

Impact: High sensitivity C-reactive protein (hs-CRP) concentrations tract from birth to age 8 years Our novel finding suggests a long-lasting pro-inflammatory phenotype in the child Higher vitamin D concentration - but not dose - is associated with higher childhood hs-CRP Chronic disease risk related to inflammation may in part originate from the prenatal period or early childhood Further studies are needed to investigate the effects of inflammation on long-term clinical health outcomes.