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 late-onset 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.
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。