Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Pediatr Res. 2018 Aug;84(2):272-278. doi: 10.1038/s41390-018-0023-y. Epub 2018 Jun 12.
There is an emerging evidence that pulmonary hypertension is associated with amino acid, carnitine, and thyroid hormone aberrations. We aimed to characterize metabolic profiles measured by the newborn screen (NBS) in infants with persistent pulmonary hypertension of the newborn (PPHN) METHODS: Nested case-control study from population-based database. Cases were infants with ICD-9 code for PPHN receiving mechanical ventilation. Controls receiving mechanical ventilation were matched 2:1 for gestational age, sex, birth weight, parenteral nutrition administration, and age at NBS collection. Infants were divided into derivation and validation datasets. A multivariable logistic regression model was derived from candidate metabolites, and the area under the receiver operator characteristic curve (AUROC) was generated from the validation dataset.
We identified 1076 cases and 2152 controls. Four metabolites remained in the final model. Ornithine (OR 0.32, CI 0.26-0.41), tyrosine (OR 0.48, CI 0.40-0.58), and TSH 0.50 (0.45-0.55) were associated with decreased odds of PPHN; phenylalanine was associated with increased odds of PPHN (OR 4.74, CI 3.25-6.90). The AUROC was 0.772 (CI 0.737-0.807).
In a large, population-based dataset, infants with PPHN have distinct, early metabolic profiles. These data provide insight into the pathophysiology of PPHN, identifying potential therapeutic targets and novel biomarkers to assess the response.
有证据表明，肺动脉高压与氨基酸、肉碱和甲状腺激素异常有关。我们旨在通过新生儿筛查（NBS）来描述持续性肺动脉高压（PPHN）患儿的代谢谱。
这是一项基于人群的数据库的巢式病例对照研究。病例为接受机械通气的患有 PPHN 的 ICD-9 编码患儿。接受机械通气的对照者按照胎龄、性别、出生体重、肠外营养和 NBS 采集时的年龄进行 2:1 匹配。将患儿分为推导数据集和验证数据集。从候选代谢物中推导出多变量逻辑回归模型，并从验证数据集中生成接收者操作特征曲线（AUROC）。
我们共确定了 1076 例病例和 2152 例对照。最终模型中有 4 种代谢物。精氨酸（OR 0.32，CI 0.26-0.41）、酪氨酸（OR 0.48，CI 0.40-0.58）和 TSH 0.50（0.45-0.55）与 PPHN 的患病几率降低有关；苯丙氨酸与 PPHN 的患病几率增加有关（OR 4.74，CI 3.25-6.90）。AUROC 为 0.772（CI 0.737-0.807）。
在一项大型、基于人群的数据集研究中，患有 PPHN 的患儿存在独特的早期代谢特征。这些数据为 PPHN 的病理生理学提供了深入了解，确定了潜在的治疗靶点和新的生物标志物，以评估反应。
