晚期新生儿中性粒细胞减少症的危险因素分析

Risk factors for neutropenia of late newborns

摘要:

目的 分析晚期新生儿中性粒细胞减少症（NLN）的危险因素及诊治过程。方法 回顾性收集新生儿重症监护室2019年7月至2020年1月收治的早产儿及危重新生儿的临床资料。新生儿出生第2~4周连续2次血中性粒细胞绝对值（ANC）< 1.5×10⁹/L者纳入NLN组（n=46）。按照1：2比例匹配血ANC一直≥ 1.5×10⁹/L的晚期新生儿纳入对照组（n=92）。收集可能与NLN相关的临床因素及诊治过程，并对NLN的危险因素进行logistic回归分析。结果 46例NLN组患儿中，胎龄 < 32周29例、32~37周14例、> 37周3例。两组孕母妊娠高血压比例、胎膜早破 > 18 h比例、宫内窘迫比例、5 min Apgar评分、正压通气天数、早发败血症比例和初始使用抗生素种类等差异均无统计学意义（P > 0.05）。NLN组晚发败血症比例和累计使用抗生素天数均高于对照组（P < 0.05）。晚发败血症和累计使用抗生素天数延长是发生NLN的独立危险因素（P < 0.05）。存在晚发败血症时，新生儿发生NLN的危险性增加了1.537倍；累计使用抗生素每增加3 d，新生儿发生NLN的危险性增加了76.9%。46例NLN患儿诊断日龄为（21±6）d；其中7例胎龄 < 32周或伴有严重疾病，6例ANC < 0.5×10⁹/L，均给予1~2次重组人粒细胞集落刺激因子（G-CSF）10 μg/kg，ANC可暂时恢复至1.0×10⁹/L以上，未发现明确药物相关不良反应。诊断NLN后有2例发生新生儿败血症，其余患儿未发生其他常见的化脓性感染。结论 发生晚发败血症和累计使用抗生素时间越长，越有可能发生NLN。NLN一般呈良性过程，对于伴有严重疾病或ANC严重减少的NLN患儿，使用G-CSF安全有效。

Abstract:

Objective To study the risk factors and treatment for neutropenia of late newborns(NLN). Methods Related clinical data were collected from the preterm infants and critically ill neonates who were admitted to the neonatal intensive care unit from July 2019 to January 2020. A total of 46 newborns with a blood absolute neutrophil count(ANC) of <1.5×10⁹/L for two consecutive times at weeks 2-4 after birth were enrolled as the NLN group. A total of 92 late newborns with a blood ANC of ≥1.5×10⁹/L, matched at a ratio of 1:2, were enrolled as the control group. Possible risk factors associated with NLN and the treatment process were recorded. A logistic regression analysis was performed to identify the risk factors for NLN. Results Among the 46 neonates in the NLN group, 29 had a gestational age of <32 weeks, 14 had a gestational age of 32-37 weeks, and 3 had a gestational age of >37 weeks. There was no significant difference between the two groups in the incidence rates of gestational hypertension, premature rupture of membranes >18 hours and intrauterine distress, 5-minute Apgar score, the duration of positive pressure ventilation, the incidence rate of early-onset sepsis, and the type of initially used antibiotics(P>0.05). Compared with the control group, the NLN group had a higher incidence rate of late-onset sepsis and a longer duration of antibiotic use(P<0.05). Late-onset sepsis and prolonged duration of antibiotic use were independent risk factors for NLN(P<0.05). With the presence of lateonset sepsis, the risk of NLN was increased by 1.537 times in neonates, and the risk of NLN was increased by 76.9% for every 3-day increase in the duration of antibiotic use. The mean age at the diagnosis of NLN was(21±6) days for the 46 neonates in the NLN group. Thirteen neonates with NLN were administered with recombinant human granulocyte colony-stimulating factor(G-CSF, 10 μg/kg) once or twice. O the 13 neonates, 6 had an ANC of <0.5×10⁹/L and 7 had a gestational age of <32 weeks or severe disease conditions. After treatment the ANC returned to >1.0×10⁹/L in the 13 neonates. No drug-related adverse reactions were found. After the diagnosis of NLN, 2 neonates developed sepsis, and the remaining 44 neonates did not develop any common purulent infections. Conclusions The risk of NLN increases with the presence of late-onset sepsis and the increase in the duration of antibiotic use. NLN is generally a benign process. G-CSF appears to be safe and effective for NLN with severe disease conditions or severe reduction in ANC.