Rees Philippa, Gale Chris, Battersby Cheryl, Williams Carrie, Carter Ben, Sutcliffe Alastair
Population Policy and Practice, Great Ormond Street UCL Institute of Child Health, London, United Kingdom.
Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom.
JAMA Netw Open. 2025 Jan 2;8(1):e2452883. doi: 10.1001/jamanetworkopen.2024.52883.
Intraventricular hemorrhage (IVH) has proven to be a challenging and enduring complication of prematurity. However, its association with neurodevelopment across the spectrum of IVH severity, independent of prematurity, and in the context of contemporary care remains uncertain.
To evaluate national trends in IVH diagnosis and the association with survival and neurodevelopmental outcomes at 2 years of age.
DESIGN, SETTING, AND PARTICIPANTS: This whole-population cohort study was conducted using data from the UK National Neonatal Research Database. Infants born at less than 29 weeks' gestation with any grade of IVH between January 2013 and December 2019 in England were included and matched with controls. Data analysis occurred from November 2023 to June 2024.
IVH grades 1 to 4 (Papile classification).
The primary outcome was survival without severe neurodevelopmental impairment (NDI) at 2 years' corrected age including severe delays (inability to understand or use >5 words or signs; being unable to walk, sit, or use hands; blindness; or uncorrectable hearing impairment). Secondary outcomes included gross and fine motor function, receptive and expressive communication, vision, hearing, and overall developmental progress. Outcomes were derived from clinician-entered data and analyzed using multiple logistic regression.
Between 2013 and 2019, of 26 756 infants born at less 29 weeks' gestation in England, 8461 received a diagnosis of IVH (5570 low-grade and 2891 high-grade, and 8328 were included in the study. Overall, 5519 included infants had low-grade IVH with a median [IQR] gestational age of 26 (25-27) weeks, of which 2477 (48.88%) were male. Of the 2809 included infants with high-grade IVH, the median (IQR) gestational age was 25 (24-26) weeks and 1710 (60.88%) were male. The mean (SD) incidence of high-grade IVH (108 [6.7] per 1000 live extremely preterm births) and low-grade IVH (208 [10.4] per 1000 live extremely preterm births) increased between 2013 and 2019, although this did not reach statistical significance for high-grade IVH. Survival without severe NDI decreased significantly after high-grade IVH (a 74% reduction; aOR, 0.26; 95% CI, 0.22-0.31), and to a lesser extent after low-grade IVH (a 12% reduction; aOR, 0.88; 95% CI, 0.79-0.98). Although low-grade IVH was associated with functional impairments, most survivors, 2283 of 4379 infants (52.15%), had no NDI, and the association with NDI was accounted for by grade 2 IVH. Decreased survival without severe NDI was observed with increasing grade of IVH, decreasing gestation, bilateral compared to unilateral injuries, and increasing morbidity count (severe retinopathy of prematurity, bronchopulmonary dysplasia, and surgical necrotizing enterocolitis). Impairments in gross motor function and communication were common, especially among those with high-grade IVH (with prevalences of 44.55% [715 of 1605 infants] and 48.91% [784 of 1603 infants], respectively).
In this cohort study, IVH was highlighted as a persistent issue with substantial neurodevelopmental implications despite advances in care. This study offers useful data for counseling families; however, follow-up to school age is necessary to grasp the full impact of these injuries on children's lives.
脑室内出血(IVH)已被证明是早产的一种具有挑战性且长期存在的并发症。然而,在当代护理背景下,其在IVH严重程度范围内与神经发育的关联(独立于早产因素)仍不确定。
评估IVH诊断的全国趋势以及与2岁时生存和神经发育结局的关联。
设计、设置和参与者:这项全人群队列研究使用了英国国家新生儿研究数据库的数据。纳入了2013年1月至2019年12月在英格兰出生、孕周小于29周且患有任何级别的IVH的婴儿,并与对照组进行匹配。数据分析于2023年11月至2024年6月进行。
1至4级IVH(Papile分类)。
主要结局是在2岁矫正年龄时无严重神经发育障碍(NDI)存活,包括严重发育迟缓(无法理解或使用超过5个单词或手势;无法行走、坐立或使用双手;失明;或无法矫正的听力障碍)。次要结局包括粗大和精细运动功能、接受性和表达性沟通、视力、听力以及整体发育进展。结局数据来自临床医生录入的数据,并使用多因素逻辑回归进行分析。
2013年至2019年期间,在英格兰26756名孕周小于29周出生的婴儿中,8461名被诊断为IVH(5570例低级别和2891例高级别),其中8328名被纳入研究。总体而言,5519名纳入研究的婴儿患有低级别IVH,中位(四分位间距)孕周为26(25 - 27)周,其中2477名(48.88%)为男性。在2809名纳入研究的高级别IVH婴儿中,中位(四分位间距)孕周为25(24 - 26)周,1710名(60.88%)为男性。2013年至2019年期间,高级别IVH(每1000例极早早产活产中有108例[6.7%])和低级别IVH(每1000例极早早产活产中有208例[10.4%])的平均(标准差)发病率有所增加,尽管高级别IVH未达到统计学显著性。高级别IVH后无严重NDI存活显著降低(降低74%;调整后比值比,0.26;95%置信区间,0.22 - 0.31),低级别IVH后降低程度较小(降低12%;调整后比值比,0.88;95%置信区间,0.79 - 0.98)。尽管低级别IVH与功能障碍相关,但大多数幸存者,即4379名婴儿中的2283名(52.15%)没有NDI,与NDI的关联由2级IVH导致。随着IVH级别增加、孕周减小、双侧损伤相比于单侧损伤以及发病率计数增加(严重早产儿视网膜病变、支气管肺发育不良和外科坏死性小肠结肠炎),无严重NDI存活降低。粗大运动功能和沟通障碍很常见,尤其是在高级别IVH患者中(分别占1605例婴儿中的4,4.55%[715例]和1603例婴儿中的48.91%[784例])。
在这项队列研究中,尽管护理有所进步,但IVH仍是一个具有重大神经发育影响的持续问题。本研究为向家庭提供咨询提供了有用数据;然而,有必要随访至学龄期以全面了解这些损伤对儿童生活的影响。