Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study
Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study
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DOI：
10.1007/s00467-019-04244-4
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发表时间：
2019-08-01
影响因子：
3
通讯作者：
Rozansky, David
中科院分区：
文献类型：
--
作者：
Jenkins, Randall;Tackitt, Shane;Rozansky, David
背景邻苯二甲酸酯与儿童血压升高有关。大量暴露于二-（2-乙基己基）邻苯二甲酸酯（DEHP）早产儿之间一直是一个令人担忧的causeforconcerns.Methods我们进行了一项前瞻性观察队列研究，以确定DEHP暴露是否与早产儿的收缩压（SBP），如果这种暴露与盐皮质激素受体（MR）的激活。婴儿从出生起纵向监测8个月。将发生特发性高血压的婴儿与血压正常的婴儿的DEHP暴露进行比较。记录暴露后尿液代谢产物的外观。线性回归评价了DEHP暴露与SBP指数之间的关系，以及尿皮质醇/可的松比率（11 β-HSD 2活性的替代标志物）是否介导了这些关系。尿外泌体进行定量钠转运蛋白/通道的表达和询问对SBP index.Results 18例患者符合研究标准，9个开发短暂的特发性高血压在月经后40.6 +/- 3.4周的年龄。尿中DEHP代谢物的存在与先前IV和呼吸管DEHP暴露相关（p < 0.05）。高血压婴儿的静脉注射和呼吸DEHP暴露量更大（p < 0.05）。SBP指数与IV液体中的DEHP暴露相关（p = 0.018），但与呼吸DEHP无关。尿皮质醇/可的松比值与静脉注射DEHP和收缩压指数相关（p < 0.05）。结论早产儿血压升高和高血压与出生后DEHP暴露有关。作用机制似乎是通过抑制11 β-HSD 2激活MR。
Background Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for concern.Methods We conducted a prospective observational cohort study to determine if DEHP exposures are related to systolic blood pressure (SBP) in premature infants, and if this exposure is associated with activation of the mineralocorticoid receptor (MR). Infants were monitored longitudinally for 8 months from birth. Those who developed idiopathic hypertension were compared with normotensive infants for DEHP exposures. Appearance of urinary metabolites after exposure was documented. Linear regression evaluated the relationship between DEHP exposures and SBP index and whether urinary cortisol/cortisone ratio (a surrogate marker for 11 beta-HSD2 activity) mediated those relationships. Urinary exosomes were quantified for sodium transporter/channel expression and interrogated against SBP index.Results Eighteen patients met the study criteria, nine developed transient idiopathic hypertension at a postmenstrual age of 40.6 +/- 3.4 weeks. The presence of urinary DEHP metabolites was associated with prior IV and respiratory tubing DEHP exposures (p < 0.05). Both IV and respiratory DEHP exposures were greater in hypertensive infants (p < 0.05). SBP index was related to DEHP exposure from IV fluid (p = 0.018), but not respiratory DEHP. Urinary cortisol/cortisone ratio was related to IV DEHP and SBP index (p < 0.05). Sodium transporter/channel expression was also related to SBP index (p < 0.05).Conclusions Increased blood pressure and hypertension in premature infants are associated with postnatal DEHP exposure. The mechanism of action appears to be activation of the MR through inhibition of 11 beta-HSD2.