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 as their neonatal survival has dramatically increased. In a national, prospective, population-based birth cohort, EPIPAGE-2, we observed that amino-acid intakes greater than 3.5 g/kg/day at day 7 after birth were independently associated with higher intelligence quotient at 5 years. As the association between high early amino-acid intake and later HBP in this population is debated, we assessed blood pressure (BP) at 5 years. METHODS This cohort was initiated in 2011, and approved by ethics committees. Eligible infants were those born between 24 and 29 weeks of gestation and alive on day7 after birth. Infants were distributed in two groups of 717 infants matched on propensity score on whether or not they were exposed to high amino-acid intake (>3.5 g/kg/d at Day7); 455 control term infants were also enrolled. Assessment at 5-year occurred from September 2016 to December 2017. A value > 95 th percentile of reference values for age and height defined systolic and/or diastolic HBP. RESULTS BP at five years of age was assessed for 389 and 385 children in exposed and non-exposed groups. Rates (%) of systolic HBP were 18.0% (95%CI, 14.5 to 22.2), 13.3% (95%CI, 10.3 to 17.0), and 8.5% (95%CI, 6.5 to 11.1) in exposed, non-exposed preterm infants, and term infants, respectively; and 9.0% (95%CI, 6.6 to 12.3), 10.2% (95%CI, 7.5 to 13.6), 5.4% (95%CI, 3.8 to 7.6) % for diastolic HBP, in exposed, non-exposed and term-born groups, respectively. Perinatal characteristics of exposed and non-exposed infants were similar, except for nutrition intake at day3 and day7 after birth. Exposure to high early amino-acid intake, and maximal serum creatinine between day3 and day7 were two independent risk factors for systolic HBP (aOR, 1.60 [95% CI, 1.05 to 2.43] and aOR, 1.59 [95% CI, 1.12 to 2.26] by 50 µmol/L, respectively) but not for diastolic HBP (aOR, 0.84 [95% CI, 0.50 to 1.39] and aOR, 1.09 [95% CI, 0.71 to 1.67] by 50 µmol/L, respectively). CONCLUSIONS These observations confirm the risk for HBP in young children born very preterm. Higher amino-acid intake and creatinine values in the first week of life were associated with childhood systolic HBP. These results suggest that mechanisms to childhood systolic HBP involves neonatal renal challenge by high amino-acid intake or dysfunction.