Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Ansh Labs, Webster, TX, USA.
Metabolism. 2019 Nov;100:153959. doi: 10.1016/j.metabol.2019.153959. Epub 2019 Aug 8.
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.
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.
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.
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.
新生儿的出生体重与其胎龄提供了有关其胎儿生长和健康的重要信息。虽然调节胎儿生长的潜在机制尚未完全阐明，但 IGF 轴起着重要作用。该轴的一些组成部分已在脐血中得到很好的描述，但其他部分尚未进行研究。我们测量了蛋白酶 PAPP-A 和 PAPP-A2 及其切割的结合蛋白（IGFBP-4 和 -5），以及脐血中的既定分子 IGF-I 和 -II，以更好地描述与出生体重和长度相关的 IGF 轴。
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。为了最大限度地提高效力，我们以 1:3:1 的比例招募了婴儿，其中 37 名 SGA、111 名 AGA 和 37 名 LGA 婴儿按胎龄、性别和分娩方式匹配。通过 ELISA 测量脐血中的 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，分析出生体重和出生长度 Z 分数与上述分子的 Z 分数之间的相关性。
出生体重和长度 Z 分数与 IGF-I、IGF-II、总 IGFBP-4 和 IGFBP-5 的 Z 分数呈正相关，其中 IGF-I 相关性最强。出生体重和长度 Z 分数与完整 IGFBP-4、PAPP-A 和 PAPP-A2 水平的 Z 分数呈负相关。
我们证实了先前发现的脐血中 IGF 与新生儿大小之间存在显著相关性，并且首次显示脐血总 IGFBP-4 和 -5 与出生体重呈正相关，与完整 IGFBP-4 与出生体重呈负相关。我们还首次显示 PAPP-A 和 PAPP-A2 与新生儿大小之间存在相反的关系。这些发现的意义需要在大型纵向研究中进一步研究，并且可能具有诊断和治疗潜力。
