BACKGROUND A newborn's birth weight for gestational age provides important insights into his or her fetal growth and well-being. While the underlying mechanisms regulating fetal growth remain to be fully elucidated, the IGF axis plays an important role. Some components of this axis have been well-characterized in umbilical cord blood, but others have not yet been studied. We measured the proteases PAPP-A and PAPP-A2, the binding proteins they cleave (IGFBP-4 and -5), and the established molecules IGF-I and -II in umbilical cord blood to better characterize the IGF axis in relation to birth weight and length. METHODS We performed a case-control study of 180 neonates born at a tertiary teaching hospital in Boston. To maximize power, infants were recruited in a 1:3:1 ratio with 37 SGA, 111 AGA, and 37 LGA infants matched by gestational age, sex, and delivery mode. IGF-I, IGF-II, IGFBP-4, IGFBP-5, PAPP-A, and PAPP-A2 were measured in umbilical cord blood by ELISA. Associations between birth weight and birth length Z-scores and the Z-scores of the above molecules were analyzed using linear regression models and analysis of covariance. RESULTS Birth weight and length Z-scores were positively associated with Z-scores of IGF-I, IGF-II, total IGFBP-4, and IGFBP-5, with IGF-I having the strongest association. Birth weight and length Z-scores were negatively associated with Z-scores of intact IGFBP-4, PAPP-A, and PAPP-A2 levels. CONCLUSIONS We confirm previous findings of significant associations between the IGFs in cord blood and newborn size and for the first time show positive associations between cord blood total IGFBP-4 and -5 and birth weight and a negative association between intact IGFBP-4 and birth weight. We also show for the first time a reciprocal relationship between cord blood levels of PAPP-A and PAPP-A2 and newborn size. The implications of these findings need to be further examined in large longitudinal studies and likely have diagnostic and therapeutic potential.

中文翻译：

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胎盘蛋白酶PAPP-A和PAPP-A2，它们裂解的结合蛋白（IGFBP-4和-5）以及IGF-I和IGF-II：脐带血中的水平以及与出生体重和身长的关系。

背景技术针对胎龄的新生儿的出生体重为他或她的胎儿生长和健康提供了重要的见识。尽管调节胎儿生长的基本机制尚待充分阐明，但IGF轴起着重要的作用。该轴的某些组件在脐带血中已被很好地表征，但其他组件尚未进行研究。我们测量了蛋白酶PAPP-A和PAPP-A2，它们裂解的结合蛋白（IGFBP-4和-5）以及脐带血中已建立的分子IGF-I和-II，以更好地表征与出生有关的IGF轴重量和长度。方法我们对波士顿一家三级教学医院出生的180名新生儿进行了病例对照研究。为了最大程度地发挥力量，我们以1：3：1的比例招募了37名SGA，111名AGA和37名LGA婴儿，并按胎龄，性别，和投放方式。通过ELISA测量脐带血中的IGF-I，IGF-II，IGFBP-4，IGFBP-5，PAPP-A和PAPP-A2。使用线性回归模型和协方差分析来分析出生体重和出生长度Z分数与上述分子的Z分数之间的关联。结果出生体重和身长Z评分与IGF-I，IGF-II，总IGFBP-4和IGFBP-5的Z评分呈正相关，其中IGF-I关联最强。出生体重和身长Z评分与完整IGFBP-4，PAPP-A和PAPP-A2水平的Z评分呈负相关。结论我们证实先前发现脐带血IGFs与新生儿大小之间存在显着关联，并且首次显示脐带血总IGFBP-4和-5与出生体重之间呈正相关，而完整IGFBP-4与出生体重之间呈负相关。 。我们还首次显示了脐带血PAPP-A和PAPP-A2与新生儿大小之间的相互关系。这些发现的含义需要在大型纵向研究中进一步检查，并且可能具有诊断和治疗潜力。