Shimokawa Shoko, Sakata Akiko, Suga Yukio, Isoda Kazuya, Itai Shingo, Nagase Katsuhiko, Shimada Tsutomu, Sai Yoshimichi
1Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
2Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
J Pharm Health Care Sci. 2019 Apr 16;5:7. doi: 10.1186/s40780-019-0137-3. eCollection 2019.
Ritodrine hydrochloride (RD), a β2-adrenergic agonist, is widely used as a tocolytic medication to suppress premature labor, but can cause neonatal hypoglycemia, a potentially severe side effect. We examined the incidence and risk factors of neonatal hypoglycemia following maternal intravenous administration of RD.
This was a retrospective study of neonates, who had birth weight of ≥2000 g and were delivered at 36 weeks gestation or later in Kanazawa University Hospital from August 2013 to July 2016. We defined neonatal hypoglycemia as blood glucose level < 50 mg/dL. Neonates who were delivered without maternal intravenous RD or who were delivered 8 days or more after stopping maternal RD or who received oral RD were defined as the RD non-administration group, while those delivered within 7 days after stopping maternal RD were defined as the RD intravenous administration group. We examined the incidence and risk factors of RD-induced neonatal hypoglycemia by comparing these two groups.
We enrolled 603 neonates in this study; 504 (83.6%) showed no neonatal hypoglycemia, while 99 (16.4%) exhibited neonatal hypoglycemia. The incidence of neonatal hypoglycemia was significantly higher (61.7%; 58/94) in the RD intravenous administration group than in the RD non-administration group (8.1%; 41/509) ( < 0.001). Binomial logistic regression analysis in the RD intravenous administration group showed that maternal age over 35 years (AOR: 3.385; 95% CI, 1.082-10.588, = 0.036) and the interval to delivery from stopping intravenous administration of RD (AOR: 0.974; 95% CI, 0.953-0.996, = 0.020) were independent factors associated with neonatal hypoglycemia. The cut-off value of the interval to predict the incidence of neonatal hypoglycemia was about 6 h (sensitivity 82.8%, specificity 63.9%).
The incidence of neonatal hypoglycemia was significantly increased by maternal intravenous administration of RD. We newly identified maternal age (over 35 years) and the interval to delivery from stopping intravenous administration of RD (within 6 h) as independent risk factors for neonatal hypoglycemia following maternal intravenous administration of RD. In cases with these risk factors, careful blood glucose monitoring is recommended for early detection and treatment of neonatal hypoglycemia.
盐酸利托君（RD）是一种β2肾上腺素能激动剂，被广泛用作抑制早产的宫缩抑制剂，但可导致新生儿低血糖，这是一种潜在的严重副作用。我们研究了母亲静脉注射RD后新生儿低血糖的发生率及危险因素。
这是一项对2013年8月至2016年7月在金泽大学医院出生体重≥2000g且孕36周或更晚出生的新生儿的回顾性研究。我们将新生儿低血糖定义为血糖水平<50mg/dL。未接受母亲静脉注射RD分娩的新生儿、母亲停止使用RD后8天或更长时间分娩的新生儿或接受口服RD的新生儿被定义为RD未给药组，而母亲停止使用RD后7天内分娩的新生儿被定义为RD静脉给药组。通过比较这两组，我们研究了RD诱导的新生儿低血糖的发生率及危险因素。
本研究共纳入603例新生儿；504例（83.6%）未出现新生儿低血糖，而99例（16.4%）出现新生儿低血糖。RD静脉给药组新生儿低血糖的发生率（61.7%；58/94）显著高于RD未给药组（8.1%；41/509）（<0.001）。RD静脉给药组的二项逻辑回归分析显示，母亲年龄超过35岁（比值比：3.385；95%置信区间，1.082 - 10.588，P = 0.036）以及停止静脉注射RD至分娩的间隔时间（比值比：0.974；95%置信区间，0.953 - 0.996，P = 0.020）是与新生儿低血糖相关的独立因素。预测新生儿低血糖发生率的间隔时间的截断值约为6小时（敏感性82.8%，特异性63.9%）。
母亲静脉注射RD显著增加了新生儿低血糖的发生率。我们新确定母亲年龄（超过35岁）以及停止静脉注射RD至分娩的间隔时间（6小时内）是母亲静脉注射RD后新生儿低血糖的独立危险因素。对于存在这些危险因素的病例，建议进行仔细的血糖监测以早期发现和治疗新生儿低血糖。
