Comparison of early postnatal hemodynamics in neonates born at high-altitude or low-altitude using USCOM: a pilot study

Abstract

This study’s purpose is to compare early postnatal hemodynamics between neonates from high- and low-altitude regions using Ultrasound Cardiac Output Monitor (USCOM) measurements. We prospectively enrolled hemodynamically stable neonates from Shanghai Children’s Hospital (low-altitude group, sea level) and People’s Hospital of Shigatse City (high-altitude group, 3850 m) between January and June 2024. Hemodynamic parameters derived from USCOM and clinical data (including oxygen saturation, heart rate, blood pressure, and hemoglobin levels) were obtained on postnatal day 7. The Mann–Whitney U test was employed to compare the differences between groups. The analysis included 80 neonates (40 per group) with comparable baseline characteristics, including gender, gestational age, weight, length, hemoglobin, oxygen carrying capacity, heart rate, and diastolic and mean blood pressure (p > 0.05). Compared to low-altitude group, high-altitude group demonstrated significantly higher stroke volume index (SVI), cardiac output (CO), cardiac index (CI), Smith-Madigan inotropy index (SMII), and systolic blood pressure (p < 0.05). Subgroup analysis indicated that preterm infants in the high-altitude group showed increased SVI, CO, CI, and SMII with lower systemic vascular resistance index (SVRI) (p < 0.05), whereas term infants in the group exhibited elevated CI, SMII, and systolic and mean blood pressure, compared to infants in the low-altitude group, respectively (p < 0.05).

Conclusion: Neonates born at high altitude may maintain circulatory adaptation through enhanced myocardial contractility and cardiac performance, while the compensatory responses seem to differ between preterm infants (Frank-Starling mechanism) and term infants (sympathetic-driven regulation).

What is Known: • Neonates born at high altitude demonstrate lower SpO2 and cardiovascular adaptations to hypobaric hypoxia. • While USCOM enables non-invasive hemodynamic monitoring in neonates, physiological differences at different altitude levels may affect the interpretation of USCOM measurements.

What is New: • First USCOM-derived comparison reveals elevated cardiac efficiency (higher SVI, CI, and SMII) in neonates born at high-altitude. • The compensatory mechanisms for hypobaric hypoxia differed according to cardiovascular maturity: preterm infants relied on the Frank-Starling mechanism, whereas term infants exhibited sympathetic activation.

Introduction

Neonates experience critical hemodynamic transitions as circulation shifts from fetal to neonatal patterns after birth. Research demonstrated that pulse oxygen saturation (SpO₂) levels decrease with rising altitude [1, 2]. Hypobaric hypoxia significantly impairs cardiovascular development and function, which may lead to incomplete cardiopulmonary transition, increased pulmonary arterial pressure, and polycythemia. These physiological changes elevate the risk of pulmonary hypertension, respiratory distress, pulmonary edema, and right heart failure [3]. The Ultrasound Cardiac Output Monitor (USCOM) enables non-invasive, real-time assessment of hemodynamic parameters (including stroke volume index (SVI), cardiac output (CO), cardiac index (CI), systemic vascular resistance index (SVRI), flow time corrected (FTC), and Smith-Madigan inotropy index (SMII)) in neonates [4, 5]. Although USCOM has been extensively validated in low-altitude environments, its reliability under hypobaric hypoxia conditions remains uncertain. This pilot study examines differences in early postnatal hemodynamic parameters between high- and low-altitude neonates to investigate altitude-related cardiovascular adaptations.

Materials and methods

Study subjects

This prospective study enrolled hemodynamically stable neonates admitted to Shanghai Children’s Hospital and People’s Hospital of Shigatse City between January and June 2024. Participants were stratified into the high-altitude group (Shigatse, 3850 m) and low-altitude group (Shanghai, sea level), with further classification by gestational age as the preterm group (gestational age < 37 weeks) or term group (gestational age ≥ 37 weeks).

Inclusion criteria comprised (1) hospitalization within 24 h post-birth; (2) hemodynamic stability (blood pressure, heart rate, temperature, and urine output within normal ranges); and (3) completion of cardiac ultrasound evaluation 3–4 days after birth.

Exclusion criteria included (1) complex congenital heart disease; (2) arrhythmia; (3) shock of any etiology; (4) multiple malformations; (5) severe birth asphyxia (Apgar score $<$ 5 at 5th minute); (6) hemodynamically significant patent ductus arteriosus (ductus diameter $>$ 1.5 mm, left atrial diameter to aortic root ratio $\ge$ 1.4, audible precordial murmur, or vasoactive drug requirement); and (7) death or discharge within 7 postnatal days.

This study protocol received approval from the Ethics Review Committee of Shanghai Children’s Hospital (2020R155), with written informed consent obtained from all participants’ legal guardians.

Research methods

Data collection

Patient demographics and clinical parameters were recorded, including gender, gestational age, birth weight, body length, hemoglobin, oxygen carrying capacity (OCC), SpO₂, heart rate, and blood pressure (systolic, diastolic, and mean). Hemodynamic parameters comprised SVI, CO, CI, SVRI, FTC, and SMII.

USCOM measurement

On postnatal day 7, hemodynamic parameters were assessed using the Ultrasound Cardiac Output Monitor 1 A (USCOM Ltd, Sydney, Australia). The USCOM system was initialized with the infant’s gender, birth weight, body length, blood pressure, SpO₂, and hemoglobin values. Infants were placed supine with shoulders elevated to optimize suprasternal fossa exposure. A 2.2 MHz probe was positioned perpendicular to the skin over the fossa and gently rotated until optimal alignment with the aortic valve was achieved. Measurements at both sites were performed each by two well-trained neonatologists following standardized protocols. Data acquisition required ultrasound spectral waveforms meeting predefined criteria: triangular morphology with sharp apex, smooth contours, and complete filling. Each measurement lasted 30–60 s, with at least five consecutive qualified waveforms per cardiac cycle. Three measurements were averaged for final analysis.

Statistical methods

The sample size was determined using G-Power 3.1 with an independent t-test calculation, based on an anticipated effect size of 0.67 for cardiac index differences between altitude groups, as reported in previous pediatric studies [6]. For a power of 80%, two-tailed α of 0.05, and 1:1 group allocation, this yielded 36 participants per group (72 total), which we increased to 40 per group (80 total) to account for a projected 10% attrition rate.

Analyses were conducted using SPSS 26.0 software (IBM Corp). Normally distributed continuous variables with homogeneous variance are reported as mean ± standard deviation (x̄ ± s) and compared using independent t-tests. Non-normally distributed variables appear as median (Q1, Q3) with Mann–Whitney U tests for group comparisons. Categorical data are presented as percentages (%) and analyzed using χ² or Fisher’s exact tests, as appropriate.

Results

Basic characteristics of neonates in high- and low-altitude regions (Tables 1 and 2)

Table 1.

Basic characteristics of neonates in high- and low-altitude regions

Region	High-altitude group (n = 40)	Low-altitude group (n = 40)	z/χ2	p
Male, n (%)	21 (52.50)	21 (52.50)	0.00	1.000
GAa (w)	37.00 (33.96, 39.29)	36.72 (33.39, 38.75)	− 0.55	0.580
BWa (g)	2500.00 (1900.00, 3177.50)	2455.00 (1845.00, 3012.50)	− 0.65	0.516
Lengtha (cm)	46.00 (42.75, 50.00)	45.00 (42.00, 48.25)	− 1.87	0.061
SpO2a (%)	92.50 (90.00, 94.25)	99.00 (97.50, 100.00)	− 6.62	<.001*
HRa (n/min)	143.00 (136.00, 151.25)	141.66 (131.26, 154.21)	− 0.21	0.836
HBa (g/L)	185.00 (168.25, 195.25)	173.00 (156.00, 193.25)	− 0.89	0.373
OCCa (mL O2/dL)	24.79 (22.55, 26.16)	23.18 (20.90, 25.90)	− 0.89	0.373
SBPa (mmHg)	68.00 (64.00, 74.00)	62.00 (57.75, 66.50)	− 3.13	0.002*
DBPa (mmHg)	37.50 (33.50, 44.00)	38.00 (32.00, 42.00)	− 0.30	0.765
MAPa (mmHg)	47.00 (42.75, 53.00)	46.00 (40.00, 51.42)	− 0.85	0.397

GA gestational age, BW body weight, SpO₂ pulse oxygen saturation, HB hemoglobin, HR heart rate, OCC oxygen carrying capacity, SBP systolic blood pressure, DBP diastolic blood pressure, MAP mean blood pressure

^aData are presented as n (%), mean ± standard deviation (x ± s), and median (P25, P75)

^*p < 0.05 indicates a statistically significant difference

Table 2.

Basic characteristics between term and preterm infants in high- and low-altitude regions

	High-altitude group (n = 40)		Low-altitude group (n = 40)		p 1	p 2
	Term infants (n = 20)	Preterm infants (n = 20)	Term infants (n = 20)	Preterm infants (n = 20)
Male, n (%)	10 (50.00)	11 (55.00)	11 (55.00)	10 (50.00)	0.752	0.752
GAa (w)	39.43 (38.32, 40.04)	33.93 (30.86, 35.82)	38.78 (37.86, 39.34)	33.34 (31.53, 34.57)	0.239	0.715
BWa (g)	3125.00 (2500.00, 3420.00)	1950.00 (1700.00, 2327.50)	3025.00 (2705.00, 3242.50)	1900.00 (1575.00, 2270.00)	0.636	0.387
Lengtha (cm)	49.00 (46.50, 50.25)	43.50 (42.00, 46.00)	49.00 (46.00, 49.00)	42.50 (39.75, 44.00)	0.318	0.053
SpO2a (%)	91.50 (89.75, 94.25)	93.00 (92.00, 94.25)	98.00 (96.00, 100.00)	99.50 (98.00, 100.00)	<.001*	<.001*
HRa (n/min)	144.50 (136.75, 151.25)	142.50 (135.00, 149.75)	134.39 (127.47, 149.36)	147.82 (138.20, 158.43)	0.091	0.199
HBa (g/L)	174.50 (153.25, 193.50)	187.00 (176.25, 199.25)	178.50 (158.00, 190.75)	169.00 (156.00, 195.50)	1.000	0.323
OCCa (mL O2/dL)	23.38 (20.54, 25.93)	25.06 (23.62, 26.70)	23.92 (21.17, 25.56)	22.65 (20.90, 26.20)	1.000	0.323
SBPa (mmHg)	74.00 (69.00, 78.25)	64.00 (59.50, 67.25)	65.50 (59.50, 70.00)	60.00 (56.75, 64.25)	<.001*	0.243
DBPa (mmHg)	43.00 (36.00, 48.25)	35.50 (30.25, 38.00)	40.50 (35.00, 44.00)	36.00 (31.00, 42.00)	0.171	0.432
MAPa (mmHg)	52.50 (47.75, 58.50)	43.00 (37.75, 45.50)	50.17 (43.08, 52.17)	45.17 (39.42, 47.83)	0.025*	0.330

p¹: comparison between high-altitude versus low-altitude in term neonates; p²: comparison between high-altitude versus low-altitude in preterm neonates

GA gestational age, BW body weight, SpO₂ pulse oxygen saturation, HB hemoglobin, HR heart rate, OCC oxygen carrying capacity, SBP systolic blood pressure, DBP diastolic blood pressure, MAP mean blood pressure

^aData are presented as n (%), mean ± standard deviation (x ± s), and median (P25, P75)

^*p < 0.05 indicates a statistically significant difference

The study included 80 neonates (40 per group, 20 preterm and 20 term; 42 males, 38 females) with a mean gestational age of 36.13 ± 3.41 weeks and mean body weight of 2473.70 ± 709.17 g. Diagnoses comprised neonatal respiratory distress syndrome (n = 14), transient tachypnea of the newborn (n = 16), neonatal pneumonia (n = 15), and hyperbilirubinemia (n = 35). No significant differences were observed between groups in gender, gestational age, weight, length, hemoglobin, oxygen-carrying capacity, heart rate, diastolic blood pressure, or mean blood pressure (p > 0.05). However, high-altitude neonates exhibited lower SpO₂ (p < 0.001) and higher systolic blood pressure (p = 0.002).

Term infants

Term infants in the high-altitude group had significantly lower SpO₂ (p < 0.001) and elevated systolic and mean blood pressure compared to the low-altitude group (p < 0.05), with no differences in other baseline parameters (p > 0.05).

Preterm infants

Preterm infants in the high-altitude group also showed reduced SpO₂ (p < 0.001) but no significant differences in other baseline characteristics (p > 0.05).

Hemodynamic parameters of neonates in high- and low-altitude regions (Tables 3 and 4)

Table 3.

Hemodynamic parameters of neonates in high- and low-altitude regions

Region	High-altitude group (n = 40)	Low-altitude group (n = 40)	z/χ2	p
SVIa (ml/m2)	23.00 (20.00, 26.25)	19.12 (15.70, 23.42)	− 3.08	0.002*
COa (L/min)	0.58 (0.47, 0.78)	0.49 (0.36, 0.66)	− 2.16	0.031*
CIa (L/min/m2)	3.30 (2.98, 3.60)	2.62 (2.40, 3.20)	− 3.58	<.001*
SVRIa (dyn·s·cm−5·m2)	1243.50 (1091.25, 1367.25)	1362.47 (1139.83, 1553.40)	− 1.87	0.061
FTCa (ms)	375.00 (353.50, 396.25)	360.42 (338.70, 383.04)	− 1.63	0.103
SMIIa (W/m2)	0.63 (0.51, 0.74)	0.51 (0.43, 0.62)	− 2.74	0.006*

SVI stroke volume index, CO cardiac output, CI cardiac index, SVRI systemic vascular resistance index, FTC flow time corrected, SMII Smith-Madigan inotropy index

^aData are presented as n (%), mean ± standard deviation (x ± s), and median (P25, P75)

^*p < 0.05 indicates a statistically significant difference

Table 4.

Hemodynamic parameters between term and preterm infants in high- and low-altitude regions

	High-altitude group (n = 40)		Low-altitude group (n = 40)		p 1	p 2
	Term infants (n = 20)	Preterm infants (n = 20)	Term infants (n = 20)	Preterm infants (n = 20)
SVIa (ml/m2)	26.00 (22.75, 27.00)	21.00 (19.00, 23.00)	23.49 (21.23, 25.48)	15.77 (14.72, 18.00)	0.133	<.001*
COa (L/min)	0.78 (0.60, 0.80)	0.49 (0.39, 0.58)	0.66 (0.57, 0.73)	0.36 (0.29, 0.44)	0.229	0.002*
CIa (L/min m2)	3.45 (3.20, 3.73)	3.00 (2.80, 3.32)	3.22 (3.02, 3.47)	2.41 (2.24, 2.59)	0.024*	<.001*
SVRIa (dyn·s·cm−5·m2)	1283.50 (1168.50, 1348.25)	1200.50 (1091.25, 1449.00)	1174.05 (1067.05, 1361.77)	1455.01 (1362.46, 1625.46)	0.640	0.003*
FTCa (ms)	381.00 (354.00, 406.75)	369.00 (352.00, 396.00)	361.49 (342.85, 393.76)	358.34 (337.39, 378.28)	0.337	0.189
SMIIa (W/m2)	0.75 (0.69, 0.82)	0.54 (0.44, 0.61)	0.62 (0.54, 0.74)	0.44 (0.37, 0.49)	0.022*	0.017*

p¹: comparison between high-altitude versus low-altitude in term neonates; p²: comparison between high-altitude versus low-altitude in preterm neonates

SVI stroke volume index, CO cardiac output, CI cardiac index, SVRI systemic vascular resistance index, FTC flow time corrected, SMII Smith-Madigan inotropy index

^aData are presented as n (%), mean ± standard deviation (x ± s), and median (P25, P75)

^*p < 0.05 indicates a statistically significant difference

The high-altitude group displayed significantly higher SVI, CO, CI, and SMII (p < 0.05), with no differences in SVRI and FTC between groups (p > 0.05).

Term infants

Term infants in the high-altitude group exhibited elevated CI and SMII (p < 0.05), with no differences in SVI, CO, SVRI, or FTC (p > 0.05).

Preterm infants

Preterm infants in the high-altitude group demonstrated increased SVI, CO, CI, and SMII (p < 0.05), along with reduced SVRI (p < 0.05). No statistically significant difference was observed in FTC levels (p > 0.05).

Discussion

This study employed USCOM technology to identify significant differences in hemodynamic parameters between neonates from high- and low-altitude regions. Neonates exposed to hypobaric hypoxia maintained hemodynamic stability primarily through compensatory increases in CI and SMII, facilitating the transition from fetal to neonatal circulation. These findings contribute preliminary observational data on neonatal hemodynamic adaptations to high-altitude hypobaric hypoxia.

USCOM has become an established tool for neonatal hemodynamic monitoring. Ausrine et al. [7] validated its accuracy by comparing cardiac output measurements with echocardiography, supporting its utility for bedside monitoring. Doni et al. [5] further demonstrated its clinical value by establishing reference ranges for hemodynamically stable preterm infants. Liu et al. [8] extended these applications, showing that USCOM effectively guides fluid management and vasoactive drug use following patent ductus arteriosus ligation in preterm infants.

High-altitude hypobaric hypoxia substantially affects cardiovascular physiology. While most researches have examined chronic hypoxia in adults and children [9, 10], studies on neonatal hemodynamics at high-altitude remain scarce, with only isolated reports on infant pulmonary artery pressure changes [3, 11]. USCOM’s potential for neonatal hemodynamic assessment at high-altitude remains largely unexplored, despite its advantages as a noninvasive, real-time monitoring tool in resource-limited settings. Our study is the first to document altitude-related hemodynamic differences in neonates using USCOM, establishing its utility for investigating plateau environment effects on neonatal health. By implementing standardized measurement protocols and controlling for gestational age, weight, and length, we isolated the independent influence of altitude on hemodynamic parameters, ensuring robust conclusions.

Multiple studies confirm that altitude inversely correlates with postnatal SpO₂. Decreasing atmospheric oxygen partial pressure at higher elevations limits pulmonary oxygen diffusion, consistently producing lower SpO₂ values in high-altitude neonates—a finding our results corroborate. Li et al. [1] observed progressive SpO₂ increases in healthy term neonates during the first 2 postnatal hours at altitudes > 3500 m, contrasting with stable trends at lower elevations. Such physiological variations necessitate consideration in neonatal screening protocols to ensure appropriate clinical management [12]. Kannan et al. [13] reported elevated erythrocyte counts, hemoglobin, and hematocrit in neonates at high altitude, reflecting compensatory erythropoiesis triggered when arterial oxygen content falls below 60% of normal. Although our study detected higher hemoglobin and OCC levels in neonates at high altitude, the difference lacked statistical significance, potentially due to limited sample size.

Hypobaric hypoxia triggers multiple compensatory mechanisms in the neonatal cardiovascular system. We observed significantly higher CI and SMII values in high-altitude neonates, indicating enhanced myocardial contractility and pumping efficiency. These findings support the established paradigm of hypoxia-induced increases in SVI and heart rate to maintain tissue oxygenation [14]. Notably, preterm infants at high altitude in our study showed no significant heart rate elevation, instead relying primarily on increased SVI to elevate CI. This atypical response may stem from preterm sympathetic nervous system immaturity, limiting heart rate modulation and favoring Frank-Starling mechanism-mediated adaptations [11, 15]. The concurrent reduction in SVRI likely improves tissue perfusion, possibly through hypoxia-induced NO-mediated vasodilation. NO activates guanylate cyclase, relaxing vascular smooth muscle to decrease peripheral resistance and cardiac afterload, thereby augmenting cardiac output [16]. In contrast, term infants exhibited elevated systolic and mean blood pressures, reflecting mature sympathetic activation via carotid/aortic chemoreceptor stimulation. This mechanism increases SMII and SVI while inducing vasoconstriction to maintain perfusion. These responses may also be influenced by hypoxic pulmonary hypertension, which indirectly modulates the right ventricular afterload and consequently affects the left ventricular function [17, 18]. These divergent responses highlight gestational age-dependent cardiovascular adaptations of high-altitude neonates: preterm infants rely more on structural adaptations to meet the challenges of hypobaric hypoxia, while term infants utilize functional regulatory mechanisms.

The long-term cardiovascular consequences of neonatal hypobaric hypoxia require further investigation. Although we measured hemodynamics only on postnatal day 7, existing evidence suggests hypobaric hypoxia may induce lasting and irreversible cardiovascular changes that elevate disease risk [3]. Future studies should examine longitudinal hemodynamic patterns and their implications for cardiovascular health in high-altitude neonates.

While this study advances understanding of high-altitude neonatal hemodynamics, several limitations warrant consideration. The modest sample size and single-timepoint measurements preclude analysis of dynamic changes. Although we standardized clinical protocols across sites, including oxygen supplementation thresholds and respiratory support, unmeasured environmental variables may have influenced results. USCOM’s inability to assess right ventricular function or pulmonary pressures potentially omitted relevant hypertension data. Additionally, unaccounted factors like maternal altitude exposure and placental function may affect outcome interpretation. Future research should incorporate longitudinal designs and multifactorial analyses to comprehensively evaluate high-altitude neonatal cardiovascular adaptation.

Conclusion

Neonates born at high altitude may maintain circulatory adaptation through enhanced myocardial contractility and cardiac performance, while the compensatory responses seem to differ between preterm infants (Frank-Starling mechanism) and term infants (sympathetic-driven regulation).

Abbreviations

BW

Birth weight

CI

Cardiac index

CO

Cardiac output

DBP

Diastolic blood pressure

FTC

Flow time corrected

GA

Gestational age

HB

Hemoglobin

HR

Heart rate

MAP

Mean blood pressure

NO

Nitric oxide

OCC

Oxygen carrying capacity

SBP

Systolic blood pressure

SMII

Smith-Madigan inotropy index

SpO₂

Pulse oxygen saturation

SVI

Stroke volume index

SVRI

Systemic vascular resistance index

USCOM

Ultrasound Cardiac Output Monitor

Authors' Contributions

YY and ZG contributed equally to this study. YY, AX and CY contributed to the conception and design of this study. YY and ZG drafted the manuscript and revised it critically. ZG, WC and JW contributed to acquisition, analysis and interpretation of data. All authors read the manuscript and gave the permission to be published.

Funding

This study was funded by Natural Science Foundation of Tibet Autonomous Region, China [XZ2022ZR-ZY32(Z)] and Shanghai Children’s Hospital Clinical Research Project [2021YLYM11] and Shanghai Children’s Hospital Clinical Research Project [2022YLYM10].

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

All methods of this study were reviewed and approved by the ethics committee of Shanghai Children’s Hospital in accordance with the Declaration of Helsinki and its later amendments (approval number: 2020R155). All the parents of enrolled patients read and signed the informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.