PDF(Pubmed)
Abstract：
OBJECTIVE: Although recent discoveries regarding the biomarkers of newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) highlight the critical need to establish reference intervals (RIs) specifically for preterm infants, no such RIs has been formally published yet. This study addressed the gap by offering a comprehensive set of reference intervals (RIs) for preterm neonates, and illustrating the dynamic changes of each biomarker with age.
METHODS: The NBS data of 199,693 preterm newborns (< 37 weeks of gestation) who met the inclusion and exclusion criteria from the NNSCP database were included in study analysis. The birth weight stratified dynamic trend of each biomarker were captured by their concentrations over age. Reference partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated using a non-parametric rank approach.
RESULTS: Increasing birth weight is associated with an elevation in the levels of arginine, citrulline, glycine, leucine and isobarics, methionine, ornithine, phenylalanine, and valine, whereas the levels of alanine, proline and tyrosine decrease. Additionally, two short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and isovalerylcarnitine + methylbutyrylcarnitine) and a median-chain acylcarnitine (octenoylcarnitine) decrease, while four long-chain acylcarnitines (tetradecanoylcarnitine, palmitoylcarnitine, palmitoleylcarnitine and oleoylcarnitine) increase with increasing birth weight. Age impacts the levels of all MS/MS NBS biomarkers, while sex only affects the level of malonylcarnitine + 3-hydroxybutyrylcarnitine (C3-DC + C4-OH) in very low birth weight preterm neonates.
CONCLUSIONS: The current study developed reference intervals (RIs) specific to birth weight, age, and/or sex for 35 MS/MS biomarkers, which can help in the timely evaluation of the health and disease of preterm neonates.
METHODS: The NBS data of 199,693 preterm newborns (< 37 weeks of gestation) who met the inclusion and exclusion criteria from the NNSCP database were included in study analysis. The birth weight stratified dynamic trend of each biomarker were captured by their concentrations over age. Reference partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated using a non-parametric rank approach.
RESULTS: Increasing birth weight is associated with an elevation in the levels of arginine, citrulline, glycine, leucine and isobarics, methionine, ornithine, phenylalanine, and valine, whereas the levels of alanine, proline and tyrosine decrease. Additionally, two short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and isovalerylcarnitine + methylbutyrylcarnitine) and a median-chain acylcarnitine (octenoylcarnitine) decrease, while four long-chain acylcarnitines (tetradecanoylcarnitine, palmitoylcarnitine, palmitoleylcarnitine and oleoylcarnitine) increase with increasing birth weight. Age impacts the levels of all MS/MS NBS biomarkers, while sex only affects the level of malonylcarnitine + 3-hydroxybutyrylcarnitine (C3-DC + C4-OH) in very low birth weight preterm neonates.
CONCLUSIONS: The current study developed reference intervals (RIs) specific to birth weight, age, and/or sex for 35 MS/MS biomarkers, which can help in the timely evaluation of the health and disease of preterm neonates.
摘要：
目的：尽管最近关于通过串联质谱（MS/MS）进行的新生儿筛查（NBS）计划的生物标志物的发现突出了建立针对早产儿的参考区间（RI）的迫切需要，尚未正式发布此类RI。这项研究通过提供一组全面的早产儿参考间隔（RI）来解决这一差距，并说明各生物标志物随年龄的动态变化。
方法：将符合NNSCP数据库纳入和排除标准的199,693名早产新生儿（妊娠<37周）的NBS数据纳入研究分析。每个生物标志物的出生体重分层动态趋势由其随年龄的浓度捕获。通过Harris和Boyd的方法确定参考分区。RIs,对应于第2.5和97.5百分位数，以及第0.5个，25日,50岁，使用非参数排名方法计算第75和99.5百分位数。
结果：出生体重的增加与精氨酸水平的升高有关，瓜氨酸,甘氨酸,亮氨酸和等温线,蛋氨酸,鸟氨酸,苯丙氨酸,和缬氨酸,而丙氨酸的水平，脯氨酸和酪氨酸减少。此外,两个短链酰基肉碱（丁酰肉碱+异丁酰基肉碱和异戊酰基肉碱+甲基丁酰肉碱）和正中链酰基肉碱（辛烯酰基肉碱）减少，而四种长链酰基肉碱（十四烷酰肉碱，棕榈酰肉碱,棕榈酰基肉碱和油酰基肉碱）随着出生体重的增加而增加。年龄影响所有MS/MSNBS生物标志物的水平，而性别仅影响极低出生体重早产儿的丙二酰肉碱3-羟基丁酰肉碱（C3-DCC4-OH）水平。
结论：当前的研究开发了特定于出生体重的参考间隔（RI），年龄,和/或35MS/MS生物标志物的性别，这可以帮助及时评估早产儿的健康和疾病。
方法：将符合NNSCP数据库纳入和排除标准的199,693名早产新生儿（妊娠<37周）的NBS数据纳入研究分析。每个生物标志物的出生体重分层动态趋势由其随年龄的浓度捕获。通过Harris和Boyd的方法确定参考分区。RIs,对应于第2.5和97.5百分位数，以及第0.5个，25日,50岁，使用非参数排名方法计算第75和99.5百分位数。
结果：出生体重的增加与精氨酸水平的升高有关，瓜氨酸,甘氨酸,亮氨酸和等温线,蛋氨酸,鸟氨酸,苯丙氨酸,和缬氨酸,而丙氨酸的水平，脯氨酸和酪氨酸减少。此外,两个短链酰基肉碱（丁酰肉碱+异丁酰基肉碱和异戊酰基肉碱+甲基丁酰肉碱）和正中链酰基肉碱（辛烯酰基肉碱）减少，而四种长链酰基肉碱（十四烷酰肉碱，棕榈酰肉碱,棕榈酰基肉碱和油酰基肉碱）随着出生体重的增加而增加。年龄影响所有MS/MSNBS生物标志物的水平，而性别仅影响极低出生体重早产儿的丙二酰肉碱3-羟基丁酰肉碱（C3-DCC4-OH）水平。
结论：当前的研究开发了特定于出生体重的参考间隔（RI），年龄,和/或35MS/MS生物标志物的性别，这可以帮助及时评估早产儿的健康和疾病。
