Department of Neonatology, All India Institute of Medical Sciences (AIIMS), Jodhpur, India.
Department of Clinical Sciences Lund, Paediatrics, Lund University, Skåne University Hospital, Lund, Sweden.
Cochrane Database Syst Rev. 2021 Feb 18;2(2):CD011466. doi: 10.1002/14651858.CD011466.pub2.
Transient tachypnea of the newborn (TTN) is caused by delayed clearance of lung fluid at birth. TTN typically appears within the first two hours of life in term and late preterm neonates and is characterized by tachypnea and signs of respiratory distress. Although it is usually a self-limited condition, admission to a neonatal unit is frequently required for monitoring and providing respiratory support. Restricting intake of fluids administered to these infants in the first days of life might improve clearance of lung liquid, thus reducing the effort required to breathe, improving respiratory distress, and potentially reducing the duration of tachypnea.
To evaluate the efficacy and safety of restricted fluid therapy as compared to standard fluid therapy in decreasing the duration of oxygen administration and the need for noninvasive or invasive ventilation among neonates with TTN.
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 12), in the Cochrane Library; Ovid MEDLINE and electronic ahead of print publications, in-process & other non-indexed citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on December 6, 2019. We also searched clinical trial databases and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.
We included randomized controlled trials (RCTs), quasi-RCTs, and cluster trials on fluid restriction in term and preterm neonates with the diagnosis of TTN or delayed adaptation during the first week after birth.
For each of the included trials, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy, need for continuous positive airway pressure [CPAP], need for mechanical ventilation, duration of mechanical ventilation) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcome considered in this review was the duration of supplemental oxygen therapy in hours or days. We used the GRADE approach to assess the certainty of evidence.
Four trials enrolling 317 infants met the inclusion criteria. Three trials enrolled late preterm and term infants with TTN, and the fourth trial enrolled only term infants with TTN. Infants were on various methods of respiratory support at the time of enrollment including room air, oxygen, or nasal CPAP. Infants in the fluid-restricted group received 15 to 20 mL/kg/d less fluid than those in the control group for varying durations after enrollment. Two studies had high risk of selection bias, and three out of four had high risk of performance bias. Only one study had low risk of detection bias, with two at high risk and one at unclear risk. The certainty of evidence for all outcomes was very low due to imprecision of estimates and unclear risk of bias. Two trials reported the primary duration of supplemental oxygen therapy. We are uncertain whether fluid restriction decreases or increases the duration of supplemental oxygen therapy (mean difference [MD] -12.95 hours, 95% confidence interval [CI] -32.82 to 6.92; I² = 98%; 172 infants). Similarly, there is uncertainty for various secondary outcomes including incidence of hypernatremia (serum sodium > 145 mEq/L, risk ratio [RR] 4.0, 95% CI 0.46 to 34.54; test of heterogeneity not applicable; 1 trial, 100 infants), hypoglycemia (blood glucose < 40 mg/dL, RR 1.0, 95% CI 0.15 to 6.82; test of heterogeneity not applicable; 2 trials, 164 infants), endotracheal ventilation (RR 0.73, 95% CI 0.24 to 2.23; I² = 0%; 3 trials, 242 infants), need for noninvasive ventilation (RR 0.40, 95% CI 0.14 to 1.17; test of heterogeneity not applicable; 2 trials, 150 infants), length of hospital stay (MD -0.92 days, 95% CI -1.53 to -0.31; test of heterogeneity not applicable; 1 trial, 80 infants), and cumulative weight loss at 72 hours of age (%) (MD 0.24, 95% CI -1.60 to 2.08; I² = 89%; 2 trials, 156 infants). We did not identify any ongoing trials; however, one trial is awaiting classification.
AUTHORS' CONCLUSIONS: We found limited evidence to establish the benefits and harms of fluid restriction in the management of TTN. Given the very low certainty of available evidence, it is impossible to determine whether fluid restriction is safe or effective for management of TTN. However, given the simplicity of the intervention, a well-designed trial is justified.
新生儿暂时性呼吸急促(TTN)是由于出生时肺部液体清除延迟引起的。在足月和晚期早产儿中,TTN 通常在生命的头两个小时内出现,其特征是呼吸急促和呼吸窘迫的迹象。尽管它通常是一种自限性疾病,但通常需要入住新生儿病房进行监测和提供呼吸支持。限制这些婴儿在生命最初几天内给予的液体摄入量可能会改善肺液清除,从而减少呼吸所需的努力,改善呼吸窘迫,并可能减少呼吸急促的持续时间。
评估限制液体疗法与标准液体疗法相比,在减少 TTN 新生儿氧疗时间和需要无创或有创通气方面的疗效和安全性。
我们使用 Cochrane 新生儿中心的标准检索策略,检索 Cochrane 图书馆中的 Cochrane 对照试验注册库(CENTRAL;2019 年第 12 期)、Ovid MEDLINE 和电子预印本出版物、在处理中和其他非索引引文、每日和版本(R)以及 Cumulative Index to Nursing and Allied Health Literature(CINAHL),检索日期为 2019 年 12 月 6 日。我们还检索了临床试验数据库和检索文章的参考文献,以查找 TTN 或出生后第一周内延迟适应的足月和早产儿的液体限制随机对照试验和准随机试验。
我们纳入了关于 TTN 或出生后第一周内延迟适应的足月和晚期早产儿的液体限制的随机对照试验(RCT)、准随机试验和群组试验。
对于每个纳入的试验,两位综述作者独立提取数据(例如:参与者人数、出生体重、胎龄、氧疗持续时间、持续气道正压通气(CPAP)的需求、机械通气的需求、机械通气的持续时间)并评估偏倚风险(例如:随机化的充分性、盲法、随访的完整性)。本综述中考虑的主要结局是补充氧气治疗的持续时间(以小时或天数计)。我们使用 GRADE 方法评估证据的确定性。
四项试验共纳入 317 名婴儿符合纳入标准。三项试验纳入了 TTN 的晚期早产儿和足月儿,第四项试验纳入了仅 TTN 的足月儿。婴儿在入组时接受各种形式的呼吸支持,包括空气、氧气或鼻 CPAP。与对照组相比,液体限制组的婴儿在入组后不同时间接受的液体量减少了 15 至 20 毫升/公斤/天。两项研究存在选择偏倚的高风险,四项研究中有三项存在实施偏倚的高风险。只有一项研究存在检测偏倚的低风险,两项研究存在高风险,一项研究存在不明确风险。由于估计值不精确且偏倚风险不明确,所有结局的证据确定性都非常低。两项研究报告了主要的补充氧气治疗持续时间。我们不确定限制液体是否会减少或增加补充氧气治疗的持续时间(平均差异[MD]-12.95 小时,95%置信区间[CI]-32.82 至 6.92;I²=98%;172 名婴儿)。同样,对于各种次要结局也存在不确定性,包括高钠血症(血清钠>145 mEq/L,风险比[RR]4.0,95%CI0.46 至 34.54;不适用异质性检验;1 项试验,100 名婴儿)、低血糖(血糖<40 mg/dL,RR1.0,95%CI0.15 至 6.82;不适用异质性检验;2 项试验,164 名婴儿)、气管内通气(RR0.73,95%CI0.24 至 2.23;I²=0%;3 项试验,242 名婴儿)、无创通气的需求(RR0.40,95%CI0.14 至 1.17;不适用异质性检验;2 项试验,150 名婴儿)、住院时间(MD-0.92 天,95%CI-1.53 至-0.31;不适用异质性检验;1 项试验,80 名婴儿)和 72 小时龄时的累积体重损失(%)(MD0.24,95%CI-1.60 至 2.08;I²=89%;2 项试验,156 名婴儿)。我们没有发现任何正在进行的试验,但有一项试验正在等待分类。
我们发现限制液体疗法在 TTN 管理中的益处和危害的证据有限。鉴于现有证据的确定性非常低,无法确定限制液体是否安全或有效用于 TTN 的管理。然而,鉴于干预措施的简单性,进行一项精心设计的试验是合理的。