Introduction

Infantile hypertrophic pyloric stenosis (IHPS) is caused by hypertrophy of the pyloric sphincter muscle.

Objectives

Since previous reports have implicated lipid metabolism, we aimed to (1) investigate associations between IHPS and a wide array of lipid-related metabolites in newborns, and (2) address whether detected differences in metabolite levels were likely to be driven by genetic differences between IHPS cases and controls or by differences in early life feeding patterns.

Methods

We used population-based random selection of IHPS cases and controls born in Denmark between 1997 and 2014. We randomly took dried blood spots of newborns from 267 pairs of IHPS cases and controls matched by sex and day of birth. We used a mixed-effects linear regression model to evaluate associations between 148 metabolites and IHPS in a matched case–control design.

Results

The phosphatidylcholine PC(38:4) showed significantly lower levels in IHPS cases (P = 4.68 × 10⁻⁸) as did six other correlated metabolites (four phosphatidylcholines, acylcarnitine AC(2:0), and histidine). Associations were driven by 98 case–control pairs born before 2009, when median age at sampling was 6 days. No association was seen in 169 pairs born in 2009 or later, when median age at sampling was 2 days. More IHPS cases than controls had a diagnosis for neonatal difficulty in feeding at breast (P = 6.15 × 10⁻³). Genetic variants known to be associated with PC(38:4) levels did not associate with IHPS.

Conclusions

We detected lower levels of certain metabolites in IHPS, possibly reflecting different feeding patterns in the first days of life.

中文翻译：

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婴儿肥厚性幽门狭窄的遗传学与新生儿代谢组学的整合

介绍

婴儿肥厚性幽门狭窄 (IHPS) 是由幽门括约肌肥大引起的。

目标

由于之前的报告涉及脂质代谢，我们旨在 (1) 研究 IHPS 与新生儿中广泛的脂质相关代谢物之间的关联，以及 (2) 解决检测到的代谢物水平差异是否可能是由之间的遗传差异驱动的。 IHPS 病例和对照或早期喂养模式的差异。

方法

我们使用基于人群随机选择 1997 年至 2014 年出生在丹麦的 IHPS 病例和对照。我们从 267 对 IHPS 病例和对照中随机抽取新生儿的干血斑，这些病例和对照按性别和出生日期匹配。我们使用混合效应线性回归模型来评估匹配病例对照设计中 148 种代谢物与 IHPS 之间的关联。

结果

磷脂酰胆碱 PC(38:4) 在 IHPS 病例中显示出显着较低的水平 ( P  = 4.68 × 10 ^-8 )，其他六种相关代谢物（四种磷脂酰胆碱、酰基肉碱 AC(2:0) 和组氨酸）也是如此。相关性是由 2009 年之前出生的 98 对病例-对照对驱动的，当时采样的中位年龄为 6 天。在 2009 年或之后出生的 169 对中没有发现相关性，当时采样的中位年龄为 2 天。与对照组相比，更多的 IHPS 病例被诊断为新生儿母乳喂养困难（P  = 6.15 × 10 ^-3）。已知与 PC(38:4) 水平相关的遗传变异与 IHPS 无关。

结论

我们在 IHPS 中检测到较低水平的某些代谢物，这可能反映了生命最初几天的不同喂养模式。