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中华妇幼临床医学杂志(电子版) ›› 2024, Vol. 20 ›› Issue (01) : 89 -96. doi: 10.3877/cma.j.issn.1673-5250.2024.01.012

论著

网织红细胞百分比/未成熟网织红细胞指数联合胆红素与白蛋白比值对新生儿溶血病的病情评估意义
马海月1, 南晓琴2,†()   
  1. 1. 山西医科大学儿科医学系，太原　030001
    2. 山西医科大学第三医院（山西白求恩医院　山西医学科学院　同济山西医院），太原　030032
  • 收稿日期:2023-11-07 修回日期:2024-01-05 出版日期:2024-02-01
  • 通信作者: 南晓琴

The significance of reticulocyte percentage/immature reticulocyte fraction combined with the ratio of bilirubin to albumin in the assessment of the condition of hemolytic disease of newborns

Haiyue Ma1, Xiaoqin Nan2,†()   

  1. 1. Faculty of Pediatrics, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
    2. The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
  • Received:2023-11-07 Revised:2024-01-05 Published:2024-02-01
  • Corresponding author: Xiaoqin Nan
  • Supported by:
    NHC Open Fund of the Key Laboratory of Neonatal Diseases(NHC-XSRJB-2021-01)
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引用本文：

马海月, 南晓琴. 网织红细胞百分比/未成熟网织红细胞指数联合胆红素与白蛋白比值对新生儿溶血病的病情评估意义[J]. 中华妇幼临床医学杂志(电子版), 2024, 20(01): 89-96.

Haiyue Ma, Xiaoqin Nan. The significance of reticulocyte percentage/immature reticulocyte fraction combined with the ratio of bilirubin to albumin in the assessment of the condition of hemolytic disease of newborns[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(01): 89-96.

目的

探讨网织红细胞百分比(Retic%)、未成熟网织红细胞指数(IRF)分别联合胆红素与白蛋白比值(B/A)，对新生儿溶血病(HDN)患儿发生新生儿高胆红素血症(NHB)的预测价值。

方法

选择2020年6月至2023年12月于山西白求恩医院住院治疗的63例就诊时龄≤72 h的HDN患儿为研究对象。采用回顾性分析方法，根据生后时龄与血清总胆红素(TSB)水平在Bhutani曲线中对应的百分位区间，将患儿分为NHB高危组(n＝43，对应高危区)和NHB非高危组(n＝20，对应高中危、低中危及低危区)。采用多因素非条件logistic回归分析法，对本研究HDN患儿发生NHB的独立影响因素进行分析。绘制受试者工作特征(ROC)曲线，并采用曲线下面积(AUC)评估Retic%、IRF及二者分别联合B/A，对HDN患儿发生NHB的预测效果，不同预测模型之间诊断NHB效能(AUC)比较，采用DeLong检验。对入院时Retic%、IRF分别与HDN患儿就诊时龄相关性分析，采用Pearson相关分析法。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》的要求。所有患儿监护人签署临床知情同意书。

结果

①单因素分析结果显示：出生胎龄，入院时TSB水平、B/A、Retic%、网织红细胞(RET)计数绝对值及IRF，以及患儿母亲孕产史，为HDN患儿发生NHB的可能影响因素。②多因素非条件logistic回归分析结果显示：B/A升高(OR＝2.496，95%CI：1.236～5.042，P＝0.011)，Retic%升高(OR＝1.710，95%CI：1.088～2.688，P＝0.020)，IRF升高(OR＝1.682，95%CI：1.176～2.407，P＝0.004)，均为HDN患儿发生NHB的独立危险因素。③ROC曲线分析显示：Retic%与IRF分别联合B/A，对预测HDN患儿发生NHB的ROC-AUC分别为0.790、0.906，敏感度分别为66.7%、71.4%，特异度分别为80.0%、95.0%，阳性预测值分别为86.4%、92.9%，阴性预测值分别为73.7%、81.0%。④入院时Retic%、IRF与HDN患儿就诊时龄，均呈负相关关系(r＝－0.584、－0.703，均为P<0.001)。

结论

Retic%及IRF分别联合B/A，对就诊时龄≤72 h的HDN患儿发生NHB，均有一定预测价值，IRF联合B/A的预测价值更高。

关键词: 网状细胞, 网织红细胞百分比, 幼红细胞增多症，胎儿, 高胆红素血症，新生儿, 未成熟网织红细胞, 胆红素与白蛋白比值, 婴儿，新生
Objective

To investigate predictive value of reticulocyte percentage (Retic%) and immature reticulocyte fraction (IRF) in combination with the ratio of bilirubin to albumin (B/A), respectively, for the development of neonatal hyperbilirubinemia (NHB) in hemolytic disease of newborns (HDN).

Methods

A total of 63 aged ≤72 h neonates who were hospitalized and diagnosed with HDN in neonatology department of Shanxi Bethune Hospital from June 2020 to December 2023 were selected as subjects for this study. According to the percentile intervals of postnatal hourly age and serum total bilirubin (TSB) level in the Bhutani curve, the children were divided into the NHB high-risk group (n=43, corresponding to the high-risk zone) and the NHB non-high-risk group (n=20, corresponding to the high-mid-risk zone, low-mid-risk zone, and low-risk zone) by retrospective analysis method. The independent influencing factors of NHB in children with HDN were analyzed by multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve of the subjects was plotted, and the area under the curve (AUC) was used to assess the predictive effect of Retic%, IRF, and the combined B/A of the two, respectively, on the occurrence of NHB in children with HDN, and the comparison of NHB diagnostic efficacy between different predictive models was performed using the DeLong test. The correlation between Retic%, IRF, respectively, and the age of HDN children at admission was analyzed by Pearson correlation analysis. The procedure followed in this study meets the requirements of the World Medical Association Declaration of Helsinki revised in 2013. Informed consents were obtained from all guardians of the children.

Results

①The results of univariate analysis showed that birth gestational age, TSB level, B/A, Retic%, absolute reticulocyte (RET) count and IRF at admission, as well as maternal pregnancy history, were the possible influencing factors for the development of NHB in children with HDN. ② Multivariate unconditional logistic regression analysis showed that B/A was increased (OR=2.496, 95%CI: 1.236-5.042, P=0.011), Retic% was increased (OR=1.710, 95%CI: 1.088-2.688, P=0.020), and IRF was increased (OR=1.682, 95%CI: 1.176-2.407, P=0.004) were all independent risk factors for the development of NHB in children with HDN in this study. ③ ROC curve analysis showed that the ROC-AUC of Retic% combined with B/A and IRF combined with B/A to predict the occurrence of NHB in children with HDN were 0.790 and 0.906, with sensitivities of 66.7% and 71.4%, and specificities of 80.0% and 95.0%, and positive predictive values of 86.4% and 92.9%, and negative predictive values of 73.7% and 81.0%, respectively.④ Retic% and IRF at admission were negatively correlated with the age of neonates with HDN at admission (r=-0.584, -0.703, all with P<0.001).

Conclusions

Both Retic% combined with B/A and IRF combined with B/A have certain predictive value for the development of NHB in children with HDN and age ≤72 h at the time of admission, and IRF combined with B/A has higher predictive value.

Key words: Reticulocytes, Reticulocyte percentage, Erythroblastosis, fetal, Hyperbilirubinemia, neonatal, Immature reticulocyte, The ratio of bilirubin to albumin, Infant, newborn
表1 2组HDN患儿一般临床资料及实验室检查结果比较
组别 例数 出生胎龄(周，±s) BW(g，±s) Hb值(g/L，±s) 就诊时龄(h，±s) 住院期内Hb最低值(g/L，±s) TSB水平(mg/dL，±s) 白蛋白水平(g/dL，±s)
NHB高危组 43 38.5±1.0 3 229±346 163.2±24.4 43.8±19.5 137.3±26.9 14.3±3.0 3.63±0.26
NHB非高危组 20 39.1±0.8 3 273±380 161.0±16.8 48.3±14.6 143.8±16.8 11.8±2.4 3.54±0.30
统计量   t＝－2.11 t＝－0.46 t＝0.68 t＝－1.02 t＝－1.15 t＝3.30 t＝1.25
P值   0.039 0.648 0.499 0.315 0.255 0.002 0.215
组别 例数 B/A (mg/g，±s) Retic%(±s) RET计数绝对值(×1012/L，±s) MCVr(fL，±s) IRF(±s) HFR%(±s) HFR计数绝对值(×1012/L，±s)
NHB高危组 43 3.9±0.9 5.5±2.1 0.23±0.07 131.3±9.4 0.73±0.06 3.6±1.7 0.15±0.06
NHB非高危组 20 3.3±0.7 4.2±1.1 0.18±0.04 131.3±9.3 0.67±0.06 2.8±1.0 0.12±0.04
统计量   t＝2.80 t＝2.54 t＝3.00 t<－0.01 t＝3.89 t＝1.92 t＝2.00
P值   0.007 0.014 0.004 0.999 <0.001 0.060 0.050
组别 例数 性别[例数(%)] 血型[例数(%)] DAT(＋)[例数(%)] 孕产史[例数(%)]
男 女 A，Rh(＋) B，Rh(＋) 有 无
NHB高危组 43 17(39.5) 26(60.5) 19(44.2) 24(55.8) 13(30.2) 37(86.0) 6(14.0)
NHB非高危组 20 9(45.0) 11(55.0) 11(55.0) 9(45.0) 8(40.0) 10(50.0) 10(50.0)
统计量   χ2＝0.17 χ2＝0.64 χ2＝0.59 χ2＝9.36
P值   0.682 0.424 0.444 0.002
表2 本研究HDN患儿发生NHB的多因素非条件logistic回归分析
影响因素 B SE Wald值 P值 OR值 OR值95%CI
出生胎龄(连续变量) －0.737 0.645 1.307 0.253 0.478 0.135～1.693
入院时TSB水平(连续变量) －3.361 2.319 2.101 0.147 0.035 0.000～3.266
B/A(连续变量) 0.915 0.359 6.504 0.011 2.496 1.236～5.042
Retic%(连续变量) 0.537 0.231 5.406 0.020 1.710 1.088～2.688
RET计数绝对值(连续变量) 0.440 0.243 3.290 0.070 1.553 0.965～2.499
IRF(连续变量) 0.520 0.183 8.103 0.004 1.682 1.176～2.407
有孕产史(vs无孕产史) 2.385 1.231 3.754 0.053 10.858 0.973～121.211
图1 相关影响因素单独或联合，预测HDN患儿发生NHB的ROC曲线分析注：HDN为新生儿溶血病，NHB为新生儿高胆红素血症，ROC曲线为受试者工作特征曲线，AUC为曲线下面积。Retic%为网织红细胞百分比，IRF为未成熟网织红细胞指数，B/A为胆红素与白蛋白比值
表3 相关影响因素单独或联合，对HDN患儿发生NHB的预测价值比较
影响因素 最佳临界值 AUC AUC 95%CI 敏感度(%) 特异度(%) 阳性预测值(%) 阴性预测值(%)
Retic% 4.44 0.681 0.544～0.818 65.1 75.0 82.4 48.3
IRF 0.73 0.779 0.663～0.895 55.8 95.0 90.0 51.5
B/A 4.20 0.708 0.578～0.839 47.6 95.0 87.5 43.6
Retic%联合B/A — 0.790 0.678～0.903 66.7 80.0 86.4 73.7
IRF联合B/A — 0.906 0.828～0.984 71.4 95.0 92.9 81.0
图2 HDN患儿入院时Retic%及IRF分别与其就诊时龄相关性分析的散点图注：HDN为新生儿溶血病。Retic%为网织红细胞百分比，IRF为未成熟网织红细胞指数
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