Orton Jane, Doyle Lex W, Tripathi Tanya, Boyd Roslyn, Anderson Peter J, Spittle Alicia
Royal Women's Hospital, Parkville, Australia.
Department of Physiotherapy, University of Melbourne, Parkville, Australia.
Cochrane Database Syst Rev. 2024 Feb 13;2(2):CD005495. doi: 10.1002/14651858.CD005495.pub5.
Infants born preterm are at increased risk of cognitive and motor impairments compared with infants born at term. Early developmental interventions for preterm infants are targeted at the infant or the parent-infant relationship, or both, and may focus on different aspects of early development. They aim to improve developmental outcomes for these infants, but the long-term benefits remain unclear. This is an update of a Cochrane review first published in 2007 and updated in 2012 and 2015.
Primary objective To assess the effect of early developmental interventions compared with standard care in prevention of motor or cognitive impairment for preterm infants in infancy (zero to < three years), preschool age (three to < five years), and school age (five to < 18 years). Secondary objective To assess the effect of early developmental interventions compared with standard care on motor or cognitive impairment for subgroups of preterm infants, including groups based on gestational age, birthweight, brain injury, timing or focus of intervention and study quality.
We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and trial registries in July 2023. We cross-referenced relevant literature, including identified trials and existing review articles.
Studies included randomised, quasi-randomised controlled trials (RCTs) or cluster-randomised trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age (GA). Interventions could commence as an inpatient but had to include a post discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. The control groups in the studies could receive standard care that would normally be provided.
Data were extracted from the included studies regarding study and participant characteristics, timing and focus of interventions and cognitive and motor outcomes. Meta-analysis using RevMan was carried out to determine the effects of early developmental interventions at each age range: infancy (zero to < three years), preschool age (three to < five years) and school age (five to < 18 years) on cognitive and motor outcomes. Subgroup analyses focused on GA, birthweight, brain injury, time of commencement of the intervention, focus of the intervention and study quality. We used standard methodological procedures expected by Cochrane to collect data and evaluate bias. We used the GRADE approach to assess the certainty of evidence.
Forty-four studies met the inclusion criteria (5051 randomly assigned participants). There were 19 new studies identified in this update (600 participants) and a further 17 studies awaiting outcomes. Three previously included studies had new data. There was variability in the focus and intensity of the interventions, participant characteristics, and length of follow-up. All included studies were either single or multicentre trials and the number of participants varied from fewer than 20 to up to 915 in one study. The trials included in this review were mainly undertaken in middle- or high-income countries. The majority of studies commenced in the hospital, with fewer commencing once the infant was home. The focus of the intervention programmes for new included studies was increasingly targeted at both the infant and the parent-infant relationship. The intensity and dosages of interventions varied between studies, which is important when considering the applicability of any programme in a clinical setting. Meta-analysis demonstrated that early developmental intervention may improve cognitive outcomes in infancy (developmental quotient (DQ): standardised mean difference (SMD) 0.27 standard deviations (SDs), 95% confidence interval (CI) 0.15 to 0.40; P < 0.001; 25 studies; 3132 participants, low-certainty evidence), and improves cognitive outcomes at preschool age (intelligence quotient (IQ); SMD 0.39 SD, 95% CI 0.29 to 0.50; P < 0.001; 9 studies; 1524 participants, high-certainty evidence). However, early developmental intervention may not improve cognitive outcomes at school age (IQ: SMD 0.16 SD, 95% CI -0.06 to 0.38; P = 0.15; 6 studies; 1453 participants, low-certainty evidence). Heterogeneity between studies for cognitive outcomes in infancy and preschool age was moderate and at school age was substantial. Regarding motor function, meta-analysis of 23 studies showed that early developmental interventions may improve motor outcomes in infancy (motor scale DQ: SMD 0.12 SD, 95% CI 0.04 to 0.19; P = 0.003; 23 studies; 2737 participants, low-certainty evidence). At preschool age, the intervention probably did not improve motor outcomes (motor scale: SMD 0.08 SD, 95% CI -0.16 to 0.32; P = 0.53; 3 studies; 264 participants, moderate-certainty evidence). The evidence at school age for both continuous (motor scale: SMD -0.06 SD, 95% CI -0.31 to 0.18; P = 0.61; three studies; 265 participants, low-certainty evidence) and dichotomous outcome measures (low score on Movement Assessment Battery for Children (ABC) : RR 1.04, 95% CI 0.82 to 1.32; P = 0.74; 3 studies; 413 participants, low-certainty evidence) suggests that intervention may not improve motor outcome. The main source of bias was performance bias, where there was a lack of blinding of participants and personnel, which was unavoidable in this type of intervention study. Other biases in some studies included attrition bias where the outcome data were incomplete, and inadequate allocation concealment or selection bias. The GRADE assessment identified a lower certainty of evidence in the cognitive and motor outcomes at school age. Cognitive outcomes at preschool age demonstrated a high certainty due to more consistency and a larger treatment effect.
AUTHORS' CONCLUSIONS: Early developmental intervention programmes for preterm infants probably improve cognitive and motor outcomes during infancy (low-certainty evidence) while, at preschool age, intervention is shown to improve cognitive outcomes (high-certainty evidence). Considerable heterogeneity exists between studies due to variations in aspects of the intervention programmes, the population and outcome measures utilised. Further research is needed to determine which types of early developmental interventions are most effective in improving cognitive and motor outcomes, and in particular to discern whether there is a longer-term benefit from these programmes.
与足月儿相比,早产儿出现认知和运动障碍的风险更高。针对早产儿的早期发育干预针对的是婴儿本身或亲子关系,或两者兼顾,可能侧重于早期发育的不同方面。其目的是改善这些婴儿的发育结局,但长期益处仍不明确。这是对Cochrane系统评价的更新,该评价首次发表于2007年,2012年和2015年进行了更新。
主要目的是评估与标准护理相比,早期发育干预对早产儿在婴儿期(0至<3岁)、学龄前(3至<5岁)和学龄期(5至<18岁)预防运动或认知障碍的效果。次要目的是评估与标准护理相比,早期发育干预对早产儿亚组的运动或认知障碍的影响,这些亚组包括基于胎龄、出生体重、脑损伤、干预时间或重点以及研究质量的分组。
我们于2023年7月检索了Cochrane系统评价数据库、MEDLINE、Embase、CINAHL、PsycINFO以及试验注册库。我们交叉引用了相关文献,包括已识别的试验和现有的综述文章。
研究包括随机、半随机对照试验(RCT)或整群随机试验,这些试验是关于对孕周小于37周出生的婴儿在出生后12个月内开始的早期发育干预项目。干预可以在住院期间开始,但必须包括出院后部分才能纳入本综述。除了必须评估认知结局、运动结局或两者外,结局测量未预先指定。研究中的对照组可以接受通常提供的标准护理。
从纳入研究中提取有关研究和参与者特征、干预时间和重点以及认知和运动结局的数据。使用RevMan进行荟萃分析,以确定早期发育干预在每个年龄范围(婴儿期(0至<3岁)、学龄前(3至<5岁)和学龄期(5至<18岁))对认知和运动结局的影响。亚组分析侧重于胎龄、出生体重、脑损伤、干预开始时间、干预重点和研究质量。我们使用Cochrane期望的标准方法程序来收集数据并评估偏倚。我们使用GRADE方法评估证据的确定性。
44项研究符合纳入标准(5051名随机分配的参与者)。本次更新中识别出19项新研究(600名参与者),另有17项研究等待结果。三项先前纳入的研究有新数据。干预的重点和强度、参与者特征以及随访时间存在差异。所有纳入研究均为单中心或多中心试验,参与者数量从少于20人到一项研究中的多达915人不等。本综述中的试验主要在中高收入国家进行。大多数研究在医院开始,婴儿回家后开始的较少。新纳入研究的干预项目重点越来越多地针对婴儿和亲子关系。干预的强度和剂量在不同研究中有所不同,这在考虑任何项目在临床环境中的适用性时很重要。荟萃分析表明,早期发育干预可能改善婴儿期的认知结局(发育商(DQ):标准化均数差(SMD)0.27标准差(SD),95%置信区间(CI)0.15至0.40;P<0.001;25项研究;3132名参与者,低确定性证据),并改善学龄前的认知结局(智商(IQ);SMD 0.39 SD,95%CI 0.29至0.50;P<0.001;9项研究;1524名参与者,高确定性证据)。然而,早期发育干预可能不会改善学龄期的认知结局(IQ:SMD 0.16 SD,95%CI -0.06至0.38;P = 0.15;6项研究;1453名参与者,低确定性证据)。婴儿期和学龄前认知结局研究之间的异质性为中度,学龄期为高度。关于运动功能,23项研究的荟萃分析表明,早期发育干预可能改善婴儿期的运动结局(运动量表DQ:SMD 0.12 SD,95%CI 0.04至0.19;P = 0.003;23项研究;2737名参与者,低确定性证据)。在学龄前,干预可能不会改善运动结局(运动量表:SMD 0.08 SD,95%CI -0.16至0.32;P = 0.53;3项研究;264名参与者,中度确定性证据)。学龄期连续(运动量表:SMD -0.06 SD,95%CI -0.31至0.18;P = 0.61;三项研究;265名参与者,低确定性证据)和二分法结局测量(儿童运动评估量表(ABC)低分:RR 1.04,95%CI 0.82至1.32;P = 0.74;3项研究;413名参与者,低确定性证据)的证据表明,干预可能不会改善运动结局。主要的偏倚来源是实施偏倚,即参与者和工作人员缺乏盲法,这在这类干预研究中是不可避免的。一些研究中的其他偏倚包括失访偏倚(结局数据不完整)以及分配隐藏不足或选择偏倚。GRADE评估确定学龄期认知和运动结局的证据确定性较低。由于更多的一致性和更大的治疗效果,学龄前认知结局显示出高确定性。
早产儿的早期发育干预项目可能改善婴儿期的认知和运动结局(低确定性证据),而在学龄前,干预显示可改善认知结局(高确定性证据)。由于干预项目、所使用的人群和结局测量方面的差异,研究之间存在相当大的异质性。需要进一步研究以确定哪种类型的早期发育干预在改善认知和运动结局方面最有效,特别是要确定这些项目是否有长期益处。