High Amino Acid Intake in Early Life Is Associated With Systolic but Not Diastolic Arterial Hypertension at 5 Years of Age in Children Born Very Preterm

Abstract

Background The life course of individuals born very premature is a topic of increasing concern. The association between high early amino acid intake and later high blood pressure (HBP) in preterm neonates is debated. Methods and Results In a national, prospective, population‐based birth cohort, EPIPAGE‐2 (Etude Epidémiologique sur Petits Ages Gestationnels), we assessed blood pressure at 5 years. Eligible infants were those born between 24 and 29 weeks of gestation. Infants were distributed in 2 groups of 717 infants matched on propensity score on whether or not they were exposed to high amino acid intake (>3.5 g/kg per day at day 7); 455 control term infants were also enrolled. A value ≥95th percentile of reference values for age and height defined systolic or diastolic HBP. Blood pressure at 5 years of age was assessed for 389 and 385 children in the exposed and nonexposed groups, respectively. Rates (in percent) of systolic and diastolic HBP were 18.0% (95% CI, 14.5%–22.2% ) , 13.3% (95% CI, 10.3%–17.0%), 8.5% (95% CI, 6.5%–11.1%), and 9.0% (95% CI, 6.6%–12.3%), 10.2% (95% CI, 7.5%–13.6%), and 5.4% (95% CI, 3.8%–7.6%) in exposed, nonexposed, and term‐born groups, respectively. Exposure to high early amino acid intake and maximal serum creatinine (by 50 μmol/L) between day 3 and day 7 were 2 independent risk factors for systolic HBP (adjusted odds ratio [aOR], 1.60 [95% CI, 1.05–2.43] and aOR, 1.59 [95% CI, 1.12–2.26], respectively) but not for diastolic HBP (aOR, 0.84 [95% CI, 0.50–1.39] and aOR, 1.09 [95% CI, 0.71–1.67], respectively). After adjustment for 5‐year weight Z score, the aOR between high early amino acid intake and systolic HBP was 1.50 [95% CI, 0.98–2.30]. Conclusions These results suggest that mechanisms of childhood systolic HBP involve neonatal renal challenge by high amino acid intake or dysfunction.