Association Between Diaphragm Ultrasound Measures and Extubation Outcomes in Neonates: A Systematic Review and Meta‐Analysis

ABSTRACT

Objective

We conducted a systematic review and prognostic meta‐analysis to evaluate the association between ultrasound‐derived measures of diaphragm structure and contractile activity with the risk of extubation failure in mechanically ventilated neonates.

Data Sources

MEDLINE, Embase, the Cochrane Library, CINAH, Scopus, and ClinicalTrials.gov were systematically searched from inception to January 12, 2026, without using language restrictions.

Study Selection

Observational studies including mechanically ventilated neonates (≤ 28 days old) undergoing planned extubation in whom diaphragmatic thickness, thickening fraction, or excursion were measured by ultrasound and extubation outcome were reported. Studies involving congenital diaphragmatic or neuromuscular disorders were excluded. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Random‐effects meta‐analyses were conducted using mean differences (MD) with 95% confidence intervals (CI).

Results

Of 1,522 records identified, 110 full‐text articles were assessed, and seven prospective cohort studies (n = 255 neonates) met the inclusion criteria. Extubation failure occurred in 90 neonates (35%). Neonates who failed extubation had significantly lower diaphragm thickening fraction compared with those successfully extubated (MD = −9.51%; 95% CI: −14.73 to −4.29; p = 0.0004; I² = 0%). Differences in diaphragm thickness and excursion were not statistically significant. Overall risk of bias was moderate to high, primarily due to inadequate adjustment for confounding and variability in outcome definitions.

Conclusions

Lower diaphragm thickening fraction is associated with extubation failure in mechanically ventilated neonates. Standardization of measurement protocols and prospective validation studies are needed before diaphragm ultrasound can be incorporated into routine extubation decision‐making.

REGISTRATION

PROSPERO CRD420251045024.

1. Introduction

Mechanical ventilation is a cornerstone of care for critically ill neonates with respiratory distress, prematurity, or congenital abnormalities [1, 2, 3, 4]. However, the management of mechanical ventilation in neonates is still a clinical challenge, particularly regarding the timing and safety of extubation [1, 5]. Extubation failure, typically defined as the need for reintubation within 48–72 h after planned extubation, is associated with increased morbidity and longer neonatal intensive care unit (NICU) stays [5, 6, 7].

Current prediction of extubation readiness in neonates remains largely subjective, with a clear need for more precise and objective approaches [5]. In this context, ultrasound has increasingly been used for respiratory assessment in the NICU, and early evidence supports that lung ultrasound scores may help identify neonates at higher risk of extubation failure [8, 9]. However, a frequently overlooked component is diaphragm function. In adult and pediatric critical care, diaphragm ultrasound has emerged as a promising tool for assessing diaphragm structure, displacement, and activity. Several studies [10, 11, 12, 13] in older populations have suggested that diaphragm ultrasound improves prediction of weaning success, offering a bedside assessment that is both repeatable and easily accessible [14, 15].

In neonatology, however, evidence remains limited [16, 17]. The neonatal diaphragm differs structurally and functionally from that of older children and adults [18, 19, 20], and factors such as gestational age at birth (degree of prematurity), sedation, and underlying conditions may influence ultrasound interpretation [21]. As such, the role of diaphragm ultrasound in supporting extubation decisions in neonates is still unclear. Therefore, we conducted a systematic review and prognostic factor meta‐analysis evaluating the association between diaphragm ultrasound measures obtained prior to planned extubation and subsequent extubation outcome. Specifically, we evaluated three key ultrasound‐based parameters: diaphragm thickness, diaphragm thickening fraction, and diaphragm excursion.

2. Methods

2.1. Protocol and Registration

We conducted a systematic review and meta‐analysis using frequentist methods, following a prespecified protocol registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251045024). This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 guideline [22]. As all the included data were previously published, institutional review board approval was not required.

2.2. Eligibility Criteria

We included observational studies (prospectives or retrospective cohort or case‐control designs) evaluating mechanically ventilated neonates (≤ 28 days of age) undergoing planned extubation in whom diaphragm ultrasound measurements were performed prior to extubation and extubation outcomes were reported. Our exposures of interest were diaphragm end‐expiratory thickness, representing diaphragm macroscopic structure, and diaphragm thickening fraction and excursion, which reflect contractile activity and cranio‐caudal displacement during inspiration, respectively. The primary outcome was extubation failure, as defined by individual studies.

We excluded studies including congenital or pre‐existing neuromuscular disorders or congenital diaphragm abnormalities. Case reports and case series with fewer than five participants were also excluded.

2.3. Information Sources and Search Strategy

A comprehensive search strategy was developed in consultation with a health sciences librarian (ML), using controlled vocabulary and keywords related to the diaphragm, ultrasound, and the neonatal population, without using language restrictions. Electronic databases searched included MEDLINE (Ovid), Embase (Ovid), Scopus, CINAHL (EBSCO), the Cochrane Library (Wiley), and ClinicalTrials.gov from inception to April 15, 2025, and updated on January 12, 2026. Searches incorporated controlled vocabulary and keywords related to diaphragm ultrasound and neonatal populations, including the Cochrane Neonatal Population Filter. Full search strategies are provided in the Supplemental Digital Content and publicly accessible at: https://doi.org/10.5683/SP3/OCVSSD. The search strategy was reported in accordance with the PRISMA‐S extension.

2.4. Study Selection and Data Collection

All records were imported into Covidence (Melbourne, Australia) for deduplication and screening. Two reviewers (TD, AACC, GA, or MLAS) independently evaluated titles/abstracts and full texts according to predefined eligibility criteria, with disagreements resolved through discussion or, when needed, adjudication by a third reviewer.

Data extraction followed the same two‐reviewer process using a standardized data collection form. Extracted data included study design, population characteristics, ventilatory parameters, ultrasound measurement protocols, exposure definitions, extubation outcomes, and secondary clinical outcomes (e.g., duration of mechanical ventilation and mortality).

2.5. Risk of Bias Assessment and Certainty of Evidence

Risk of bias was assessed independently by two reviewers using the Quality in Prognosis Studies (QUIPS) tool, which evaluates six domains: study participation, study attrition, prognostic factor measurement, outcome measurement, confounding, and statistical analysis/reporting. Each domain was rated as low, moderate or high risk of bias. An overall risk of bias judgment was derived based on domain‐level assessments, with particular emphasis on confounding and statistical analysis.

The certainty of evidence for each diaphragm ultrasound parameter was assessed using the GRADE approach adapted for prognostic factor research [23], with the body of evidence initially rated as high and downgraded considering the domains of risk of bias, inconsistency, indirectness, imprecision, and publication bias.

2.6. Data Synthesis and Analysis

Due to anticipated clinical and methodological heterogeneity, random‐effects meta‐analysis using restricted maximum likelihood (REML) estimation was performed using mean differences (MD) with 95% confidence interval (CI) comparing extubation failure versus success group. Statistical heterogeneity was quantified using Cochran's Q, I², and τ² statistics.

When studies reported measurements from both hemidiaphragms, data from the right hemidiaphragm were preferentially extracted due to superior acoustic window and greater reproducibility in neonatal ultrasound assessment. Descriptive data, including ultrasound protocols, were summarized in structured tables to characterize methodological variability across studies. Continuous outcomes reported as medians with interquartile ranges were converted to means and standard deviation using established methods [24, 25].

Because of observed between‐study variability, meta‐regression (mixed‐effects model) was performed to evaluate whether gestational age at birth, birth weight, or proportion of male neonates modified the associations between diaphragm ultrasound metrics and extubation outcomes. Multivariable meta‐regression was not performed due to the limited number of studies per outcome. We attempted to obtain missing or unpublished data directly from study authors; when these efforts were unsuccessful, we did not impute missing values. Sensitivity analyses were performed using the trim‐and‐fill method and, when applicable, by repeating the meta‐analysis after excluding studies judged to have a high risk of bias in more than one domain.

All analyses were conducted using R version v4.4.2 (R Foundation for Statistical Computing, Vienna, Austria).

3. Results

The search identified 1,522 studies, of which 110 full‐text articles were assessed for eligibility (Supplemental Figure 1). Seven prospective cohort studies published between 2021 and 2026 met the inclusion criteria [26, 27, 28, 29, 30, 31, 32], enrolling a total of 255 mechanically ventilated preterm and/or full‐term neonates without congenital abnormalities, as described in Table 1.

Table 1.

Main characteristics of the studies included in the analysis.

Study	Country	Study design	Sample size (N)	Inclusion criteria	Exclusion criteria	Gestational age at birth (weeks)	Birth weight (grams)	Sex male
Bahgat et al. 2021 (26)	Egypt	Prospective Cohort Study	43	< 32 weeks, IMV for RDS, planned for extubation	Chromosomal aberrations, hepatosplenomegaly, pleural effusion, congenital heart or lung disorders, congenital anomalies related to the diaphragm (diaphragmatic hernia and diaphragmatic paralysis)	29.4 ± 1.7	1186.1 ± 230.5	13 (30%)
Abd El‐Halim et al. 2022 (28)	Egypt	Prospective Cohort Study	48	Full and pre‐term neonates, IMV from the first day of NICU admission	Major congenital anomalies, need for surgical intervention, congenital diaphragmatic hernia, pleural effusion, hepato‐splenomegaly, weaned before 72 h	33.9 ± 4.0	2091.7 ± 913.0	27 (56%)
Mohsen et al. 2022 (27)	Canada	Prospective Cohort Study	45	< 28 weeks, IMV for at least 12 h for RDS, eligible for extubation	Congenital or chromosomal abnormalities, pneumothorax, pleural effusion at enrollment or scanning, intubated for non‐respiratory causes, on muscle relaxant, parents declined consent	25.3 ± 1.1	703.0 ± 195.3	24 (53%)
Nobile et al. 2023 (30)	Italy	Prospective Cohort Study	17	Preterm infants born < 37 weeks' gestation requiring IMV for at least 48 h during NICU admission	Chromosomal abnormalities, major malformations, gestational age < 23 weeks, need for palliative care	27.6 ± 3.6	796.5 ± 754.0	10 (59%)
Ibraheem et al. 2025 (29)	Saudi Arabia	Prospective Cohort Study	38	< 30 weeks, IMV within the first 24 h of life for RDS	IMV less than 24 h, failed NIV after first 24 h, congenital or chromosomal abnormalities, grade IV intraventricular hemorrhage, pneumothorax, pleural effusion, on sedation or muscle relaxant, parents declined consent	26.7 ± 1.8	844.2 ± 249.1	16 (42%)
Gautam et al. 2025 (31)	India	Prospective Cohort Study	45	< 34 weeks, IMV > 24 h, eligible for extubation	Major congenital anomalies, diaphragmatic paralysis or defects, chest deformities, prior extubation failure, intubation for neurological or hemodynamic etiology, and failure to obtain consent	29.8 ± 2.3	1184 ± 403	28 (62%)
de Alencar Nelo et al. 2025 (32)	Brazil	Prospective Cohort Study	38	Neonates*; IMV for respiratory conditions for at least 24 h; eligible for extubation	Pleural pathologies impairing diaphragmatic assessment; Zika virus or COVID‐19 infection, rhinorrhea, or abdominal pain at the time of evaluation; severe neurological disorders, significant hemodynamic congenital heart diseases, or genetic syndromes diagnosed during hospitalization; hemodynamic instability during SBT.	34.71 ± 4.35	N/A	10 (52%)

Note: *de Alencar Nelo et al. (2025) enrolled infants aged 0–2 years; neonatal‐only data were obtained directly from the study authors and included in this review.

Abbreviations: IMV, invasive mechanical ventilation; NICU, neonatal intensive care unit; NIV, non‐invasive ventilation; RDS, respiratory distress syndrome; SBT, spontaneous breathing trial.

Across the seven cohorts, mean gestational age at birth ranged from 25.3 ± 1.1 to 34.71 ± 4.35 weeks, while mean birth weight ranged from 703 ± 195 g to 2,092 ± 913 g, reflecting a predominantly preterm and very‐low‐birth‐weight population. The proportion of male neonates ranged from 30% to 62%.

Ultrasound assessment protocols are summarized in Table 2. Four studies [26, 27, 29, 32] measured diaphragm thickness, thickening fraction, and excursion, while three [28, 30, 31] assessed only selected parameters. Most studies used linear high‐frequency probes (5–20 MHz) for thickness and thickening assessments and microconvex or curvilinear probes (3–10 MHz) for excursion measurements. Only one study [26] reported using a micro‐convex probe for all measurements, and another study [28] used a linear probe for excursion assessment. Most studies obtained images from the right hemidiaphragm, and participants were generally positioned supine. The timing of ultrasound measurement varied from within 1 h of planned extubation to serial measurements throughout the entire period of mechanical ventilation. Ventilatory support settings also varied across studies, including pressure support ventilation (PSV) and continuous positive airway pressure (CPAP).

Table 2.

Diaphragm ultrasound assessment protocol in neonates.

Study	Measurement type	Probe type and frequency	Probe position	Patient position	Timing of measurement	Ventilatory support at time of ultrasound	Averaging method
Bahgat et al. 2021 (26)	Thickness, thickening fraction, excursion	Micro‐convex probe, 5–10 MHz	Right subcostal and lower intercostal spaces between anterior axillary and mid‐clavicular lines, with the probe directed cranially, dorsally, and medially	Supine	Within 1 h before extubation	PSV, PS of 4cmH2O, PEEP of 4cmH2O, for 1 h before assessment (but not more than 2 h)	Average of up to three respiratory cycles
Abd El‐Halim et al. 2022 (28)	Excursion	Linear probe, 5–8 MHz	Right costal margin at the mid‐clavicular line	Semi‐setting position (head of the bed at 30°)	During sleeping, 1 h after feeding	PSV, PEEP of 5cmH2O	Average of three respiratory cycles
Mohsen et al. 2022 (27)	Thickness, thickening fraction, excursion	Linear probe, 5–20 MHz (thickness) and curvilinear probe 3–10 MHz (excursion)	Thickness: above the 10th rib at the right midaxillary line Excursion: right subcostal hepatic window at the mid‐clavicular line	Supine	1 h before extubation	CPAP with PEEP equivalent to MAP	Average of three respiratory cycles
Nobile et al. 2023 (30)	Thickness, thickening fraction	Linear probe, 12 MHz, resolution limit 0.01 mm	Longitudinally on the right mid‐axillary line	Supine	Daily when intubated	N/A	Average of three respiratory cycles
Ibraheem et al. 2025 (29)	Thickness, thickening fraction, excursion	Linear probe, 6.7–18 MHz (thickness) and curvilinear probe of 4–10 MHz (excursion)	Thickness: above the 10th rib in the right anterior or mid‐axillary lines Excursion: lower intercostal spaces between the mid‐clavicular and anterior axillary lines	Supine	Within 24 h of initiating IMV, and then every 48–72 h until extubation	CPAP with PEEP equivalent to MAP ± 2 cmH2O	Average of three respiratory cycles
Gautam et al. 2025 (31)	Excursion, thickening fraction	Linear probe, 6–13 MHz (thickness) and curvilinear probe 4–8 MHz (excursion)	Thickness: above the 10th rib at the right midaxillary line Excursion: right subcostal area between the midclavicular and anterior axillary line	N/A	Within 1 h before extubation	CPAP with PEEP equivalent to MAP	Average of three respiratory cycles
de Alencar Nelo et al. 2025 (32)	Thickness, thickening fraction, excursion	Linear probe, 7.5 MHz (thickness) and curvilinear probe 3.5 MHz (excursion)	Thickness: perpendicular to the chest wall between the eighth and ninth intercostal spaces Excursion: right mid‐axillary line below the costal margin	Supine	The day of SBT, before extubation	N/A	Average of three respiratory cycles

Abbreviations: CPAP, continuous positive airway pressure; IMV, invasive mechanical ventilation; MAP, mean airway pressure; PEEP, positive end‐expiratory pressure; PSV, pressure support ventilation.

Diaphragm ultrasound parameters and reported clinical outcomes are summarized in Table 3. Overall, diaphragm thickening fraction was higher in neonates who were successfully extubated, ranging from 27% to 74%, whereas those who failed showed lower values, ranging from 17% to 64%. Similarly, when reported, diaphragm thickness and excursion were modestly greater among neonates who were successfully extubated.

Table 3.

Diaphragm ultrasound measurements, duration of mechanical ventilation, and mortality according to extubation outcome in the studies included.

Study	Extubation outcome	Diaphragm excursion (mm)	Expiratory diaphragm thickness (mm)	Thickening fraction (%)	Duration of IMV (days)	Mortality (%)
Bahgat et al. 2021(26)	Success – 34 (79%)	3.43 ± 0.41	1.29 ± 0.13	38.4 ± 9.4	6.5 (4–9)	N/A
	Failure – 9 (21%)	2.37 ± 0.37	1.19 ± 0.04	32.1 ± 7.5	10 (7.5–11.5)	N/A
Abd El‐Halim et al. 2022 (28)	Success – 23 (48%)	3.6 ± 0.8	N/A	N/A	7.2 ± 2.9	3 (13%)
	Failure – 25 (52%)	2.6 ± 0.55	N/A	N/A	9.4 ± 3.8	8 (32%)
Mohsen et al. 2022 (27)	Success – 36 (80%)	3.4 ± 1.5	0.8 ± 0.3	74 ± 38	4.5 (3–10)	N/A
	Failure – 9 (20%)	3.5 ± 1.2	0.7 ± 0.3	64 ± 40	5.0 (1.5–9.5)	N/A
Nobile et al. 2023 (30)	Success – 13 (76%)	N/A	0.11 ± 0.05	26.7 ± 19.8	N/A	N/A
	Failure – 4 (24%)	N/A	0.12 ± 0.05	17.2 ± 19.5	N/A	N/A
Ibraheem et al. 2025 (29)	Success – 20 (52%)	3.1 ± 0.8	0.9 ± 0.1	30.9 ± 11.8	N/A	N/A
	Failure – 18 (47%)	2.5 ± 0.6	0.7 ± 0.1	20.9 ± 10.2	N/A	N/A
Gautam et al. 2025 (31)	Success – 25 (56%)	4.3 (1.1–10.9)	N/A	26.6 (12.5–57.3)	28 (7–95)	6 (24%)
	Failure – 20 (44%)	4.2 (0–8.8)	N/A	26.4 (16.3–124.1)	34 (9–78)	5 (26.3%)
de Alencar Nelo et al. 2025 (32)	Success – 14 (74%)	7.75 ± 3.34	2.00 ± 1.26	27.86 ± 25.85	N/A	N/A
	Failure – 5 (26%)	10.50 ± 2.25	2.17 ± 0.85	24.79 ± 9.57	N/A	N/A

Note: Continuous data are reported as mean ± standard deviation or median (interquartile range), following the original format of the manuscript or author‐provided data. Categorical data are reported as proportions.

Abbreviations: IMV, invasive mechanical ventilation; N/A, not available.

Extubation readiness was assessed using physiologic stability criteria, as described in Supplemental Table 1. Clinical indicators included spontaneous respiratory effort, adequate gas exchange, appropriate pH and PaCO₂ thresholds, hemodynamic stability, and acceptable ventilatory settings (typically MAP ≤ 8–12 cmH₂O or FiO₂ ≤ 0.30–0.40). Definitions of extubation failure varied but commonly included reintubation within 72 h (range: 72 h to 7 days), accompanied by recurrent apnea requiring stimulation or positive pressure ventilation, respiratory acidosis, or increasing oxygen requirements.

Risk of bias assessments are summarized in Figure 1. Overall risk of bias was moderate to high. The most frequent concern was bias due to confounding, as several studies did not adjust for gestational age, illness severity, ventilatory parameters or timing of ultrasound assessment.

Figure 1.

Risk of bias assessment by QUIPS. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2. presents the meta‐analysis results for the diaphragm ultrasound variables. For diaphragm thickening fraction, the random effects model showed a statistically significant reduction among neonates who failed extubation, with a pooled mean difference of −9.51% (95% CI −14.73 to −4.29%; p = 0.0004), and no detectable heterogeneity (I² = 0%, τ² = 0). In contrast, for end‐expiratory diaphragm thickness, the random effects model yielded a pooled mean difference of −0.09 mm (95% CI −0.22 to 0.04; p = 0.171), indicating no significant association after accounting for substantial heterogeneity (I² = 83.2%, τ² = 0.3474). Similar findings were found for diaphragm excursion (pooled mean difference of −0.56 mm (95% CI −1.17 to 0.05 mm; p = 0.0730), with substantial heterogeneity (I² = 70.4%, τ² = 0.1117). Meta‐regression analysis did not identify a statistically significant association between gestational age at birth or birth weight and the differences in diaphragm excursion, thickening fraction, or thickness across extubation success and failure groups (Supplemental Table 2). Results remained consistent across sensitivity analyses (Supplemental Figure 2 and 3).

Figure 2.

Forest plots for (A) Thickening Fraction, (B) End‐Expiratory Thickness, and (C) Diaphragm Excursion. [Color figure can be viewed at wileyonlinelibrary.com]

According to the GRADE assessment, the certainty of evidence was moderate for diaphragm thickening fraction and very low for diaphragm thickness and diaphragm excursion (Supplementary Table 3).

Data on secondary clinical outcomes, including duration of mechanical ventilation and mortality, were reported inconsistently across studies and by too few studies to permit quantitative synthesis. These findings are therefore presented narratively in Table 3.

4. Discussion

In this systematic review and meta‐analysis, diaphragm ultrasound identified measurable differences between neonates with successful and failed extubation. Neonates who failed extubation had significantly lower diaphragm thickening fraction (TFdi), whereas diaphragm excursion and end‐expiratory thickness showed non‐significant trends toward lower values.

Only seven studies met inclusion criteria, underscoring the limited evidence base in this population. The included cohorts were heterogeneous with respect to gestational age, birth weight, and sex distribution. These and other factors related to critical illness, including severity of illness, ventilatory settings (and their potential interruption during ultrasound measurements), duration of mechanical ventilation, and sedation, may influence the development of diaphragm dysfunction and extubation outcomes [33, 34, 35, 36] and therefore should have been controlled for or adjusted for in most analyses. Inadequate adjustment for these confounders was the primary source of bias across studies and limits causal interpretation of these findings.

Some aspects of the ultrasound protocols were consistent across most studies, including probe type and positioning, and the averaging method. However, there was substantial variability in the definition of extubation failure, the timing of measurements, and the ventilatory support used during image acquisition.

Among the ultrasound parameters, thickening fraction showed the most consistent discrimination between groups, with higher values in neonates who were successfully extubated. This finding is consistent with the adult literature [13], where thickening fraction frequently is often reported as the most accurate diaphragm ultrasound parameter for predicting extubation outcomes [37, 38]. Thickening fraction reflects the relative change in diaphragm thickness between end‐expiration and peak inspiration, providing an index of contractile activity expressed as a normalized percentage [15, 39, 40]. We believe that the greater uniformity observed in thickening fraction findings across neonatal studies likely reflects this normalization, as the measure inherently accounts for baseline thickness, thereby further reducing the influence of factors such as body size and developmental variability. As a result, the thickening fraction may represent a robust and comparable indicator of diaphragm activity in neonates.

However, it should be noted that the thickening fraction measured during quiet breathing is effort‐dependent [41], albeit with some variability [42]. A low thickening fraction may simply reflect low inspiratory effort, whereas a high thickening fraction may reflect increased effort, rather than true differences in muscle function [41, 42, 43]. Thus, interpreting lower thickening fractions in neonates who failed extubation is not straightforward, as it does not necessarily imply worse diaphragm function per se. In the absence of standardized ventilatory conditions, a lower thickening fraction may instead reflect a more favourable load‐capacity balance (i.e., the ability to sustain a given respiratory load with relatively low effort) [41, 42, 43].

Diaphragm excursion, on the other hand, did not reach significance in the random‐effects model. Diaphragm excursion reflects the cranio‐caudal displacement of the diaphragm during inspiration and has a moderate correlation with transdiaphragmatic pressure [13, 39, 43], the gold standard for assessing diaphragm function. Thus, lower excursion in neonates, similarly to what has been observed in adults, may reflect reduced or impaired muscle function, contributing to unsuccessful weaning. However, excursion can be measured either during quiet breathing, where it primarily reflects tidal inspiratory effort, or during maximal inspiratory effort, which better reflects diaphragm function and strength. Excursion is also influenced by passive displacement generated by ventilatory support [43], which may partially explain the moderate heterogeneity across studies and the absence of between‐group differences in one study [27]. Although several studies reported the ventilatory mode and some support settings at the time of ultrasound assessment, reporting was incomplete and lacked sufficient detail. Most studies did not report the complete ventilatory settings (e.g., inspiratory pressure, delivered tidal volume), whether these settings were comparable between groups, or whether neonates remained connected to the ventilator during image acquisition. These limitations impact the interpretability of the findings and limit their full applicability to predicting extubation outcomes. Finally, unlike adults – whose normal tidal breathing excursions range around 1.6–1.8 ± 0.3 cm [44] and clearly separate normal from abnormal patterns – neonatal excursions are extremely small (approximately six‐fold lower), making it challenging to visually discern meaningful differences and therefore more susceptible to intrinsic, method‐related measurement errors.

Notably, one included study [32] reported markedly higher diaphragm excursion values than the others, with a mean of 7.75 mm in the successful extubation group and 10.5 mm in the failure group, whereas most studies reported mean values in the range of approximately 2–4 mm. This discrepancy may be partly explained by the older average age of neonates in that study and by the lack of standardized ventilatory settings during image acquisition, which may have affected diaphragm displacement, as explained previously.

End‐expiratory diaphragm thickness was also not statistically significant in the random‐effects model. Diaphragm thickness represents the absolute distance between the pleural and peritoneal diaphragmatic boundaries and is primarily a structural measure, commonly used to identify atrophy [15, 30]. Similar to excursion, this parameter is not normalized and also demonstrated substantial between‐study heterogeneity. Several patient characteristics and study‐level factors may have influenced the results; for example, the only study (26) that reported a significant difference between groups also had the largest proportion of failures (n = 18, 47%), which may have increased its power to detect group differences. In addition, the same limitations discussed for excursion apply to an even greater extent to thickness: in some studies, reported values were as low as 0.7–0.8 mm, making visual discrimination challenging and increasing susceptibility to intrinsic, technique‐related measurement error. These findings suggest that diaphragm thickness alone may be more susceptible to confounding and less reliable as an isolated predictor of extubation readiness in neonates.

Considerable heterogeneity was observed across studies, likely reflecting variability in extubation failure definition (ranging from 72 h to 7 days), timing of ultrasound measurements, ventilatory support conditions during assessment, and differences in patient maturity and illness severity. Formal assessment of small‐study effects and publication bias was not performed because fewer than 10 studies were available per outcome. Trim‐and‐fill analyses were conducted only as exploratory sensitivity analyses, recognizing their limited reliability with such small numbers of studies.

The limited and inconsistent reporting of clinically relevant secondary outcomes, such mortality, duration of mechanical ventilation, and length of stay, precluded quantitative synthesis, highlighting an important gap in the current evidence base.

Our study has several limitations. First, the number of available studies was small; however, we used a comprehensive search strategy from database inception and followed established systematic review standards to ensure quality and minimize the risk of missing relevant evidence. Nonetheless, the limited evidence base underscores the need for larger, more robust, prospective studies in this population. Second, there was variability in both exposure and outcome measurements across studies, including ultrasound protocols, definitions of extubation failure, timing of assessment and ventilator settings during image acquisition. In particular, most studies did not report ventilator settings at the time of ultrasound examination or whether neonates were disconnected from the ventilator during measurements. Given the known influence of ventilatory assistance on diaphragm excursion and thickening fraction, this represents a major limitation for between‐study and between‐group comparability and restricts the physiological interpretability of the findings. Third, the extremely small absolute values of diaphragm excursion and thickness in neonates increase susceptibility to intrinsic, technique‐related measurement error, potentially amplifying variability and attenuating true associations. This limitation may particularly affect non‐normalized parameters and underscores the importance of standardized acquisition protocols and, where feasible, normalized or effort‐standardized measurements. Finally, all included studies excluded infants with pre‐existing or congenital abnormalities. While this approach reduces confounding, congenital anomalies represent a common indication for mechanical ventilation in the NICU. As a result, the generalizability of the findings to these high‐risk populations is limited, and dedicated studies are needed to understand diaphragm function and extubation readiness in these neonates.

Future studies should standardize: (1) timing of ultrasound relative to extubation (ideally within 30–60 min prior), (2) ventilatory mode and support level during measurements, (3) hemidiaphragm selection and number of breaths averaged, and (4) extubation failure definitions (preferably within 72 h and restricted reintubation criteria). Prospective multicenter studies incorporating adjustments for gestational age and illness severity are needed to determine clinically actionable TFdi thresholds.

5. Conclusion

Lower diaphragm thickening fraction is associated with extubation failure in mechanically ventilated neonates, supporting the potential role of diaphragm ultrasound in guiding extubation decisions. However, given methodological heterogeneity and limited adjustments for confounding, these findings should be interpreted cautiously. As diaphragm ultrasound becomes more widely adopted in neonatal care, the development and implementation of standardized acquisition and measurement protocols will be essential to enhance reproducibility, comparability, and clinical applicability.

Author Contributions

Mayson L. A. Sousa: conceptualization, methodology, data curation, visualization, writing – original draft, writing – review and editing, formal analysis. Eleonora Balzani: conceptualization, methodology, visualization, writing – original draft, writing – review and editing, formal analysis. Sebastian Dubo: conceptualization, methodology, visualization, writing – original draft, writing – review and editing, formal analysis. Amanda A. C. Coelho: data curation, writing – review and editing. Taylor Davidson: data curation, writing – review and editing. Glasiela Alcala: data curation, writing – review and editing. Me‐Linh Le: conceptualization, methodology, data curation, writing – review and editing, writing – original draft, software. Shyamala Dakshinamurti: conceptualization, writing – review and editing. Yasser Elsayed: conceptualization, writing – review and editing. Annia F. Schreiber: conceptualization, methodology, visualization, writing – review and editing, writing – original draft, formal analysis.

Funding

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting File

Sousa M. L. A., Balzani E., Dubo S., et al., “Association Between Diaphragm Ultrasound Measures and Extubation Outcomes in Neonates: A Systematic Review and Meta‐Analysis,” Pediatric Pulmonology 81 (2026): e71807, 10.1002/ppul.71807.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.