Yi Fang, Wang Ling, Wang Mei, Yuan Xue-Lian, Wan Hua-Jing, Li Jia-Yuan
West China School of Public Health, Sichuan University, Chengdu 610041, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2018 May;20(5):352-357. doi: 10.7499/j.issn.1008-8830.2018.05.003.
To study the combined effect of gestational age and birth weight on metabolites related to inherited metabolic diseases (IMD).
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.
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).
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.
研究胎龄和出生体重对遗传性代谢疾病（IMD）相关代谢物的联合影响。
从2014年至2016年参加新生儿IMD筛查的38931例新生儿中，随机选取3381例经随访排除IMD的样本。根据胎龄和出生体重将这3381例新生儿分为七组：极早早产适于胎龄（AGA）组（n = 12）、早产小于胎龄（SGA）组（n = 18）、早产AGA组（n = 219）、早产大于胎龄（LGA）组（n = 18）、足月SGA组（n = 206）、足月AGA组（n = 2677）和足月LGA组（n = 231）。在充分母乳喂养后，于出生后3 - 7天从每组采集足跟血样本。采用串联质谱法测定干血斑中17种关键IMD相关代谢指标的水平。采用Spearman秩相关分析研究17种IMD相关代谢指标与其影响因素之间的关系，同时采用协方差分析比较各组间的代谢指标。
在调整生理和病理状态等影响因素后，与足月AGA组相比，极早早产AGA组、早产SGA组和早产AGA组的亮氨酸/异亮氨酸/羟脯氨酸和缬氨酸水平显著降低（P < 0.05）；早产AGA组的鸟氨酸水平显著降低（P < 0.05）；极早早产AGA组和早产AGA组的脯氨酸水平显著降低（P < 0.05）。此外，极早早产AGA组和早产AGA组的苯丙氨酸水平、早产SGA组的蛋氨酸水平以及早产AGA组的酪氨酸水平均显著升高（P < 0.05）。早产SGA组和早产AGA组的游离肉碱、乙酰肉碱和丙酰肉碱水平升高。早产SGA组的油酰肉碱水平也显著升高（P < 0.05）。在早产和足月婴儿中，大多数肉碱指标在SGA组与AGA/LGA组之间均存在显著差异（P < 0.05）。
低胎龄和低出生体重可能导致IMD筛查结果异常。因此，应考虑胎龄和出生体重以综合判断IMD筛查中的异常结果。
