单疗程或多疗程产前使用皮质类固醇预防早产并发症后的两岁婴儿神经发育结局

Two-year infant neurodevelopmental outcome after single or multiple antenatal courses of corticosteroids to prevent complications of prematurity.

作者信息

Spinillo Arsenio, Viazzo Franco, Colleoni Rossella, Chiara Alberto, Maria Cerbo Rosa, Fazzi Elisa

机构信息

Department of Obstetrics and Gynecology, University of Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy.

出版信息

Am J Obstet Gynecol. 2004 Jul;191(1):217-24. doi: 10.1016/j.ajog.2003.12.023.

DOI:10.1016/j.ajog.2003.12.023

PMID:15295369

Abstract

OBJECTIVE

This study was undertaken to evaluate the effect of exposure to multiple antenatal steroid courses on short-term neonatal morbidity and 2-year infant neurodevelopmental outcome.

STUDY DESIGN

This was a prospective observational study of 201 preterm singleton infants who received 1 or more courses of corticosteroids to prevent complications of prematurity and were delivered between 24 and 34 weeks' gestation at a single institution. Neurodevelopmental outcome of the infants was evaluated at 2 years corrected age. Logistic regression analysis was used to perform multivariate analyses of associations and trends.

RESULTS

One hundred thirty-eight subjects (68.7%) received at least 1 complete course of betamethasone, whereas 63 (31.3%) patients were treated with dexamethasone. The prevalence of multiple steroid doses exposure was 26.8% (37/138) in betamethasone and 52.4% (33/63) in dexamethasone group. The prevalence of infant leukomalacia, including both prolonged echogenicity and cystic leukomalacia, was 25.9% (34/131) after a complete corticosteroid course, 40% (6/15) after 1, 42.3% (12/28) after 2, and 44.4% (12/27) after more than 2 additional courses, respectively (adjusted P for trend=.011). In the same categories of steroid exposure, the corresponding prevalences of 2-year infant neurodevelopmental abnormalities were 18% (20/111), 21.4% (3/14), 29.2% (7/24), and 34.8% (8/23), respectively (adjusted P for trend=.038). Multivariate study of first grade interaction suggested that the risk of leukomalacia and 2-year infant neurodevelopmental abnormalities associated with multiple doses exposure was confined to dexamethasone. In fact, compared with betamethasone, exposure to multiple doses of dexamethasone was associated with an increased risk of leukomalacia (19/33 compared with 11/37; odds ratio [OR]=3.21, 95% CI=1.07-9.77) and overall 2-year infant neurodevelopmental abnormalities (12/28 compared with 6/35; OR=3.63, 95% CI=1.03-13.58).

CONCLUSION

In this study, multiple antenatal courses of dexamethasone but not betamethasone were associated with an increased risk of leukomalacia and 2-year infant neurodevelopmental abnormalities.

摘要

目的

本研究旨在评估多次产前使用类固醇疗程对新生儿短期发病率和2岁婴儿神经发育结局的影响。

研究设计

这是一项前瞻性观察性研究，对201名单胎早产婴儿进行了研究，这些婴儿接受了1个或更多疗程的皮质类固醇以预防早产并发症，并在单一机构于孕24至34周分娩。在矫正年龄2岁时评估婴儿的神经发育结局。采用逻辑回归分析对关联和趋势进行多变量分析。

结果

138名受试者（68.7%）接受了至少1个完整疗程的倍他米松，而63名（31.3%）患者接受了地塞米松治疗。倍他米松组多次类固醇剂量暴露的患病率为26.8%（37/138），地塞米松组为52.4%（33/63）。在完成一个完整的皮质类固醇疗程后，包括延长的强回声和囊性脑白质软化在内的婴儿脑白质软化患病率为25.9%（34/131），在接受1个额外疗程后为40%（6/15），2个额外疗程后为42.3%（12/28），超过2个额外疗程后为44.4%（12/27）（趋势校正P值=0.011）。在相同的类固醇暴露类别中，2岁婴儿神经发育异常的相应患病率分别为18%（20/111）、21.4%（3/14）、29.2%（7/24）和34.8%（8/23）（趋势校正P值=0.038）。一级交互作用的多变量研究表明，与多次剂量暴露相关的脑白质软化和2岁婴儿神经发育异常风险仅限于地塞米松。事实上，与倍他米松相比，多次剂量地塞米松暴露与脑白质软化风险增加相关（19/33对比11/37；优势比[OR]=3.21，95%置信区间=1.07 - 9.77）以及2岁婴儿总体神经发育异常风险增加相关（12/28对比6/35；OR=3.63，95%置信区间=1.03 - 13.58）。