Florio Pasquale, Marinoni Emanuela, Di Iorio Romolo, Bashir Moataza, Ciotti Sabina, Sacchi Renata, Bruschettini Matteo, Lituania Mario, Serra Giovanni, Michetti Fabrizio, Petraglia Felice, Gazzolo Diego
Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Siena, Italy.
Pediatrics. 2006 Sep;118(3):e747-54. doi: 10.1542/peds.2005-2875. Epub 2006 Aug 21.
Intrauterine growth retardation is one of the major causes of perinatal mortality and morbidity. To date, there are no reliable methods to detect brain damage in these patients.
We conducted a case-control study in tertiary NICUs from December 2001 to December 2003 with 42 intrauterine growth retardation infants and 84 controls. Routine laboratory variables, neurologic outcome at 7-day follow-up, ultrasound imaging, and urine concentrations of S100B protein were determined at 5 time points. Urine S100B levels were measured by an immunoluminometric assay at first urination, 24, 48, and 72 hours, and 7 days after birth. Routine laboratory parameters and neurologic patterns were assessed at the same time as urine sampling.
S100B protein was significantly higher at all of the monitoring time points in urine taken from intrauterine growth retardation newborns than in control infants. When intrauterine growth retardation infants were corrected for the presence of abnormal (group A) or normal (group B) neurologic examination 7 days after birth, S100B was significantly higher at all of the predetermined monitoring time points in group A infants than in group B or controls. At a cutoff of 7.37 multiples of median at first urination, S100B achieved a sensitivity of 95% and a specificity of 99.1% as a single marker for predicting an adverse neurologic outcome. Twenty of 126 patients had neurologic abnormalities, making an overall prevalence of the disease in our population of 15.9% (pretest probability). With respect to the performance of S100B in predicting brain damage, its positive and negative predictive values were 91.0% and 99.0%, respectively.
Increased urine S100B protein levels in intrauterine growth retardation newborns in the first week after birth suggest the presence of brain damage reasonably because of intrauterine hypoxia. Longitudinal S100B protein measurements soon after birth are a useful tool to identify which intrauterine growth retardation infants are at risk of possible neurologic sequelae.
宫内生长受限是围产期死亡率和发病率的主要原因之一。迄今为止,尚无可靠方法来检测这些患者的脑损伤。
我们在2001年12月至2003年12月期间于三级新生儿重症监护病房开展了一项病例对照研究,纳入42例宫内生长受限婴儿和84例对照。在5个时间点测定常规实验室指标、7天随访时的神经学结局、超声成像以及尿S100B蛋白浓度。出生后首次排尿、24、48和72小时以及7天时,通过免疫发光分析法测定尿S100B水平。在采集尿液样本的同时评估常规实验室参数和神经学模式。
宫内生长受限新生儿尿液中所有监测时间点的S100B蛋白均显著高于对照婴儿。将出生后7天神经学检查异常(A组)或正常(B组)的宫内生长受限婴儿进行校正后,A组婴儿在所有预定监测时间点的S100B均显著高于B组或对照组。首次排尿时以中位数的7.37倍为临界值,S100B作为预测不良神经学结局的单一标志物,灵敏度为95%,特异度为99.1%。126例患者中有20例存在神经学异常,在我们的研究人群中该疾病的总体患病率为15.9%(检验前概率)。就S100B预测脑损伤的性能而言,其阳性预测值和阴性预测值分别为91.0%和99.0%。
出生后第一周宫内生长受限新生儿尿S100B蛋白水平升高合理提示因宫内缺氧存在脑损伤。出生后不久纵向测量S100B蛋白是识别哪些宫内生长受限婴儿有发生神经学后遗症风险的有用工具。