Objective: To study the combined effect of gestational age and birth weight on metabolites related to inherited metabolic diseases (IMD).
Methods: A total of 3 381 samples ruled out of IMD by follow-up were randomly selected from 38 931 newborns who participated in the neonatal IMD screening during 2014-2016. The 3 381 neonates were categorized into seven groups according to their gestational age and birth weight: extremely preterm appropriate-for-gestational age (AGA) group (n=12), preterm small-for-gestational age (SGA) group (n=18), preterm AGA group (n=219), preterm large-for-gestational age (LGA) group (n=18), full-term SGA group (n=206), full-term AGA group (n=2 677), and full-term LGA group (n=231). Heel blood samples were collected from each group on postnatal days 3-7 after adequate breastfeeding. Levels of 17 key IMD-related metabolic indices in dried blood spots were measured using tandem mass spectrometry. Spearman′s correlation analysis was used to investigate the relationships between 17 IMD-related metabolic indices and their influencing factors, while covariance analysis was used to compare the metabolic indices between these groups.
Results: After adjusting the influencing factors such as physiological and pathological status, compared with the full-term AGA group, the extremely preterm AGA, preterm SGA, and preterm AGA groups had significantly reduced levels of leucine\isoleucine\hydroxyproline and valine (P<0.05); the preterm AGA group had a significantly decreased ornithine level (P<0.05); the extremely preterm AGA and preterm AGA groups had a significantly reduced proline level (P<0.05). Besides, the phenylalanine level in the extremely preterm AGA and preterm AGA groups, the methionine level in the preterm SGA group, and the tyrosine level in the preterm AGA group all significantly increased (P<0.05). The increased levels of free carnitine, acetylcarnitine, and propionylcarnitine were found in the preterm SGA and preterm AGA groups. The oleylcarnitine level also significantly increased in the preterm SGA group (P<0.05). Most carnitine indices showed significant differences between the SGA group and the AGA/LGA group in both preterm and full-term infants (P<0.05).
Conclusions: Low gestational age and low birth weight may result in abnormal results in IMD screening. Therefore, gestational age and birth weight should be considered to comprehensively judge the abnormal results in IMD screening.
目的: 探讨胎龄联合出生体重对遗传代谢病（IMD）相关代谢物的影响。
方法: 从2014~2016年间参加IMD筛查的38 931名新生儿中，随机抽取3 381例经随访排除IMD疾病的新生儿样本，按胎龄联合出生体重分为极早产适于胎龄儿组（n=12）、早产小于胎龄儿组（n=18）、早产适于胎龄儿组（n=219）、早产大于胎龄儿组（n=18）、足月小于胎龄儿组（n=206）、足月适于胎龄儿组（n=2 677）、足月大于胎龄儿组（n=231）。采集各组新生儿出生3~7 d充分哺乳后的足跟血，采用串联质谱检测干血斑中17种IMD关键代谢指标水平。利用Spearman秩相关分析各影响因素与代谢指标的相关性，采用协方差分析各组代谢指标水平差异。
结果: 在控制了新生儿生理及病理状态等相关因素后，与足月适于胎龄儿组相比，亮氨酸\异亮氨酸\羟基脯氨酸、缬氨酸在极早产适于胎龄儿、早产小于胎龄儿、早产适于胎龄儿组，鸟氨酸在早产适于胎龄儿组，脯氨酸在极早产、早产适于胎龄儿组中水平明显下降（P < 0.05）；苯丙氨酸在极早产、早产适于胎龄儿组，甲硫氨酸在早产小于胎龄儿组，酪氨酸在早产适于胎龄儿组中水平则明显升高（P < 0.05）；游离肉碱、乙酰肉碱、丙酰肉碱在早产小于胎龄儿、早产适于胎龄儿组，十八碳烯酰肉碱在早产小于胎龄儿组中水平明显升高（P < 0.05）。大部分肉碱指标在早产和足月的小于胎龄儿分别与适于胎龄儿、大于胎龄儿组间比较中差异有统计学意义（P < 0.05）。
结论: 胎龄不足和低出生体重均会造成IMD筛查指标异常，故在判读IMD筛查指标异常时应结合胎龄和体重情况综合判断。