目的 探索孕母产前糖皮质激素（antenatal corticosteroid, ACS）的使用对极早产儿（very premature infant, VPI）结局及婴儿期神经发育的影响。 方法 回顾性选取2020年1月—2022年12月安徽医科大学第一附属医院儿科收治的190例VPI为研究对象，按照孕母是否使用ACS及使用剂量分为未使用组（n=18）、单疗程组（n=88）、多疗程组（n=40）和部分疗程组（n=44）。比较4组VPI临床结局、矫正胎龄40周时新生儿神经行为评分、矫正年龄1岁时格塞尔发育量表评分的差异，分析特定胎龄VPI的ACS不同使用时机对矫正年龄1岁时婴幼儿格塞尔发育量表评分的影响。 结果 临床结局方面，部分疗程组、单疗程组及多疗程组新生儿呼吸窘迫综合征、支气管肺发育不良、新生儿肺炎及新生儿湿肺的发生率低于未使用组（P<0.008），而部分疗程组、单疗程组及多疗程组间比较差异无统计学意义（P>0.008）。未使用组、部分疗程组、单疗程组矫正胎龄40周时新生儿神经行为评分（行为能力、主动肌张力、原始反射和一般评估）、矫正年龄1岁时神经发育正常比例高于多疗程组（P<0.008）。不同ACS使用时机对不同胎龄VPI矫正年龄1岁时神经发育无显著影响（P>0.05）。 结论 ACS对VPI的呼吸系统发育具有重要价值，但多疗程ACS可能会造成VPI出现一定程度的神经发育异常，而对神经发育的影响与胎龄及ACS的使用时机无关。
Abstract
Objective To explore the effects of antenatal corticosteroids (ACS) on the outcomes of very premature infants (VPIs) and neurodevelopment during infancy. Methods A retrospective study was conducted on 190 VPIs admitted to the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University from January 2020 to December 2022. The infants were categorized into four groups based on ACS usage and dosage: no ACS group (n=18), single-course group (n=88), multi-course group (n=40), and partial-course group (n=44). The clinical outcomes, Neonatal Behavioral and Neurological Assessment (NBNA) scores at 40 weeks of corrected age, and Gesell Developmental Schedule (Gesell) scores at 1 year of corrected age were compared among the four groups. The impact of timing of ACS use on the Gesell scores of infants at 1 year of corrected age in VPIs with specific gestational ages was analyzed. Results The incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia, transient tachypnea of the newborn, and neonatal pneumonia were significantly lower in the partial-course, single-course, and multiple-course groups compared with the no ACS group (P<0.008). However, there was no significant difference among the partial-course, single-course, and multiple-course groups (P>0.008). The NBNA scores (behavioral ability, active muscle tone, primitive reflexes, and general assessment) at 40 weeks of corrected age were significantly higher in the no ACS, partial-course, and single-course groups than in the multiple-course group (P<0.008). The proportion of VPIs with normal neurodevelopment at 1 year of corrected age was significantly higher in the no ACS, partial-course, and single-course groups than in the multiple-course group (P<0.008). The timing of ACS use had no significant effect on neurodevelopment at a corrected age of 1 year in infants with various gestational ages (P>0.05). Conclusions ACS is crucial for the development of the respiratory system in VPIs, but multiple courses of ACS may cause neurodevelopmental abnormalities. The impact of ACS use on neurodevelopment is independent of gestational age and the timing of ACS use.
关键词
产前糖皮质激素 /
临床结局 /
神经发育 /
极早产儿
Key words
Antenatal corticosteroid /
Clinical outcome /
Neurodevelopment /
Very premature infant
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
1 黄列, 郭宁, 程美乐. 极低出生体质量儿支气管肺发育不良发生的高危因素分析[J]. 宁夏医科大学学报, 2023, 45(2): 151-154. DOI: 10.16050/j.cnki.issn1674-6309.2023.02.007.
2 Deng K, Liang J, Mu Y, et al. Preterm births in China between 2012 and 2018: an observational study of more than 9 million women[J]. Lancet Glob Health, 2021, 9(9): e1226-e1241. PMID: 34416213. PMCID: PMC8386289. DOI: 10.1016/S2214-109X(21)00298-9.
3 冯叶, 戴立英. 极早产儿神经发育远期结局的研究进展[J]. 中国当代儿科杂志, 2023, 25(10): 1066-1071. PMID: 37905765. PMCID: PMC10621061. DOI: 10.7499/j.issn.1008-8830.2305072.
4 Lee HS, Kim SY. Histological chorioamnionitis, antenatal steroids, and neonatal outcomes in very low birth weight infants: a nationwide study[J]. PLoS One, 2019, 14(10): e0224450. PMID: 31661511. PMCID: PMC6818766. DOI: 10.1371/journal.pone.0224450.
5 茹喜芳, 冯琪. 新生儿呼吸窘迫综合征的防治——欧洲共识指南2022版[J]. 中华新生儿科杂志（中英文）, 2023, 38(3): 191-192. DOI: 10.3760/cma.j.issn.2096-2932.2023.03.016.
6 李宇丹, 李冬. 产前应用糖皮质激素对子代神经发育影响的研究进展[J]. 发育医学电子杂志, 2022, 10(2): 156-160. DOI: 10.3969/j.issn.2095-5340.2022.02.014.
7 Dagklis T, Sen C, Tsakiridis I, et al. The use of antenatal corticosteroids for fetal maturation: clinical practice guideline by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine foundation[J]. J Perinat Med, 2022, 50(4): 375-385. PMID: 35285217. DOI: 10.1515/jpm-2022-0066.
8 周宜洁, 余昕烊, 漆洪波. ACOG《产前胎儿监护实践指南（2021年版）》解读[J]. 中国实用妇科与产科杂志, 2022, 38(2): 186-190. DOI: 10.19538/j.fk2022020114.
9 邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学[M]. 5版. 北京: 北京人民卫生出版社, 2019.
10 魏燕云, 李艳民. 血清CASP2表达与缺氧缺血性脑病患儿NBNA评分及预后的关系[J]. 国际检验医学杂志, 2023, 44(24): 3006-3009. DOI: 10.3969/j.issn.1673-4130.2023.24.012.
11 周燕, 蔡荷飞, 汤行录. HINE联合Gesell对脑瘫高危儿早期识别的应用价值[J]. 中华全科医学, 2023, 21(10): 1706-1709. DOI: 10.16766/j.cnki.issn.1674-4152.003206.
12 Zhou C, Ye F, Wu H, et al. Recent advances in the study of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) inhibitors[J]. Environ Toxicol Pharmacol, 2017, 52: 47-53. PMID: 28366868. DOI: 10.1016/j.etap.2017.02.021.
13 王慧, 曹丽芳, 张雪峰. 产前糖皮质激素对晚期早产儿呼吸系统疾病的影响[J]. 临床儿科杂志, 2021, 39(6): 410-414. DOI: 10.3969/j.issn.1000-3606.2021.06.003.
14 van der Merwe JL, Sacco A, Toelen J, et al. Long-term neuropathological and/or neurobehavioral effects of antenatal corticosteroid therapy in animal models: a systematic review[J]. Pediatr Res, 2020, 87(7): 1157-1170. PMID: 31822018. DOI: 10.1038/s41390-019-0712-1.
15 Valencia M, Santander O, Torres E, et al. Environmental enrichment reverses cerebellar impairments caused by prenatal exposure to a synthetic glucocorticoid[J]. AIMS Neurosci, 2022, 9(3): 320-344. PMID: 36329900. PMCID: PMC9581733. DOI: 10.3934/Neuroscience.2022018.
16 Noorlander CW, Tijsseling D, Hessel EV, et al. Antenatal glucocorticoid treatment affects hippocampal development in mice[J]. PLoS One, 2014, 9(1): e85671. PMID: 24465645. PMCID: PMC3899077. DOI: 10.1371/journal.pone.0085671.
17 Tijsseling D, Wijnberger LD, Derks JB, et al. Effects of antenatal glucocorticoid therapy on hippocampal histology of preterm infants[J]. PLoS One, 2012, 7(3): e33369. PMID: 22457757. PMCID: PMC3311632. DOI: 10.1371/journal.pone.0033369.
18 Hung TH, Liu YC, Wu CH, et al. Antenatal low-intensity pulsed ultrasound reduces neurobehavioral deficits and brain injury following dexamethasone-induced intrauterine growth restriction[J]. Brain Pathol, 2021, 31(6): e12968. PMID: 33960564. PMCID: PMC8549022. DOI: 10.1111/bpa.12968.
19 Shaw JC, Crombie GK, Palliser HK, et al. Impaired oligodendrocyte development following preterm birth: promoting GABAergic action to improve outcomes[J]. Front Pediatr, 2021, 9: 618052. PMID: 33634057. PMCID: PMC7901941. DOI: 10.3389/fped.2021.618052.
20 洪昆峣, 郑直, 林新祝, 等. 胎盘炎症和产前糖皮质激素与早产儿生后早期脑损伤的关系[J]. 中华新生儿科杂志（中英文）, 2019, 34(3): 182-186. DOI: 10.3760/cma.j.issn.2096-2932.2019.03.005.
21 Norberg H, St?lnacke J, Diaz Heijtz R, et al. Antenatal corticosteroids for preterm birth: dose-dependent reduction in birthweight, length and head circumference[J]. Acta Paediatr, 2011, 100(3): 364-369. PMID: 21054513. DOI: 10.1111/j.1651-2227.2010.02074.x.
22 Li J, Wang ZN, Chen YP, et al. Late gestational maternal serum cortisol is inversely associated with fetal brain growth[J]. Neurosci Biobehav Rev, 2012, 36(3): 1085-1092. PMID: 22206902. DOI: 10.1016/j.neubiorev.2011.12.006.
23 Navalón P, Campos-Berga L, Buesa J, et al. Rescue doses of antenatal corticosteroids, children's neurodevelopment, and salivary cortisol after a threatened preterm labor: a 30-month follow-up study[J]. Am J Obstet Gynecol MFM, 2023, 5(7): 100918. PMID: 36882125. DOI: 10.1016/j.ajogmf.2023.100918.
24 Gentle SJ, Carlo WA, Tan S, et al. Association of antenatal corticosteroids and magnesium sulfate therapy with neurodevelopmental outcome in extremely preterm children[J]. Obstet Gynecol, 2020, 135(6): 1377-1386. PMID: 32459430. PMCID: PMC7278037. DOI: 10.1097/AOG.0000000000003882.
25 Sarid EB, Stoopler ML, Morency AM, et al. Neurological implications of antenatal corticosteroids on late preterm and term infants: a scoping review[J]. Pediatr Res, 2022, 92(5): 1225-1239. PMID: 35681094. DOI: 10.1038/s41390-022-02135-3.
26 李丽霞, 李海静, 蒋叶均, 等. 产前糖皮质激素疗程对早产儿并发症的影响[J]. 浙江医学, 2022, 44(4): 392-395. DOI: 10.12056/j.issn.1006-2785.2022.44.4.2021-3108.
基金
安徽省临床医学研究科研项目（202204295107020007）。
PDF(564 KB)
