Doppler Assessment of Fetal Pulmonary Artery as a Predictor in Neonatal Respiratory Distress

Abstract

Background:

Respiratory distress (RD) in newborns is a major cause of neonatal morbidity and mortality. Evaluating fetal lung maturity before labor is therefore essential, particularly in high-risk pregnancies where early termination may be considered. A key clinical challenge is identifying fetuses at risk for respiratory distress syndrome (RDS) to optimize the timing of delivery.

Methods:

This prospective study included pregnant women between 28 and 40 weeks of gestation. Doppler ultrasound was performed within 72 hours of delivery, assessing the fetal main pulmonary artery (MPA) parameters including resistance index (RI), pulsatility index (PI), and the acceleration-to-ejection time (At/Et) ratio. Scans were conducted using advanced ultrasound systems equipped with modern obstetric and fetal echocardiography software. After birth, neonates were evaluated for RD based on birth weight, APGAR score, clinical signs (such as tachypnea, chest retractions, grunting, and wheezing), and need for neonatal intensive care unit (NICU) admission.

Results:

The At/Et ratio of the fetal pulmonary artery showed significant predictive value for the occurrence of neonatal RDS. Among the Doppler indices assessed, the At/Et ratio demonstrated the highest sensitivity and specificity in predicting fetal lung maturity and the risk of neonatal respiratory distress.

Conclusion:

The At/Et ratio measured in the fetal pulmonary artery is a promising non-invasive marker for assessing fetal lung maturity and predicting the development of neonatal RDS. Larger studies are warranted to validate its clinical utility and potential as an alternative to amniocentesis in the prevention of neonatal RDS.

INTRODUCTION

Respiratory distress (RD) is the leading cause of neonatal intensive care unit (NICU) admissions and significantly affects neonatal outcomes. It occurs in about 15% of full-term and 29% of late preterm infants, with rates increasing in those born before 34 weeks due to immature lungs and low surfactant levels. RD usually appears within hours of birth, showing signs such as tachypnea, nasal flaring, grunting, and chest retractions. Common causes include respiratory distress syndrome (RDS), TTN, MAS, and neonatal pneumonia, all requiring prompt care. Imaging tools, such as B-mode ultrasound and Gray-level histogram analysis, have improved early diagnosis and assessment of lung maturity. These noninvasive methods are especially useful for identifying at-risk fetuses and guiding treatment in preterm infants. Timely diagnosis and management are key to improving survival and long-term health outcomes.[1,2,3]

RDS has a high mortality rate of 40%–60%, especially in preterm and low-birth-weight infants. Despite advances like surfactant therapy, ventilation, and antenatal steroids, RDS remains a leading cause of neonatal death. Early diagnosis and better access to NICU care, especially in resource-limited areas, are critical. As noted by Bhutta and Yusuf,[4] improving prenatal care is key, while Gregg and Bernstein[5] highlight that understanding RDS histopathology, like hyaline membrane formation, can help improve outcomes.

As fetal growth progresses, lung maturation and the development of the respiratory vasculature occur. Vessel diameter increases, smooth muscle matures, and pulmonary vascular resistance decreases, resulting in a steady rise in blood flow. Ultrasonography remains a vital, noninvasive tool for routine prenatal assessments. With advances in computing power and image resolution, more quantitative ultrasound techniques have emerged. Studies by Palacio et al.[6] and Palacio et al.[7] showed that the Quantus FLM method provides a noninvasive alternative for assessing lung maturity, with accuracy comparable to invasive tests.

Abbreviations

AFI Amniotic Fluid Index

APGAR Appearance, Pulse, Grimace, Activity, and Respiration

At Acceleration Time

BMI Body Mass Index

Et Ejection Time

GA Gestational Age

MPA Main Pulmonary Artery

NICU Neonatal Intensive Care Unit

PI Pulsatility Index

RI Resistance Index

This study hypothesizes that a noninvasive technique can provide critical insights into functional pulmonary maturity. Evaluating its effectiveness in predicting RDS across term, preterm, and early-term neonates, along with analyzing the outcomes of main pulmonary artery (MPA) abnormalities and their impact on neonatal survival, is essential for enhancing clinical management.[8]

In addition, Doppler velocimetry has been used to assess fetal pulmonary circulation, with MPA acceleration time (At) and ejection time (Et) serving as predictors of RD.

MATERIALS AND METHODS

This was a prospective observational study conducted over 1 year 6 months from August 2023 to February 2025 and included 60 subjects during this time frame, who had attended the outpatient department or were admitted to tertiary care Hospital attached to Sri Guru Ram Das Institute of Medical Sciences and Research, Sri Amritsar. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Research and Ethical Committee, Sri Guru Ram Das University of Health Sciences, Sri Amritsar, under Ref No. SGRD/CONT/THESIS/24-533 dated 27/07/2023. Informed consent was obtained from the patients undergoing examination.

Duration of the study

The duration of the study was August 01, 2023–February 28, 2025.

Study design

This study involves prospective observational study.

All Doppler measurements were performed in the department of radiodiagnosis on patients who had GAs between 28 and 40 weeks using a Voluson E8 ultrasound machine and a C1-5-RS convex probe (2–5 MHz; General Electric Healthcare). Ultrasound was performed within 72 h of delivery. Fetal biometry, including biparietal diameter, femur length, abdominal circumference, and head circumference, was measured to assess for Intrauterine Growth Restriction (IUGR) or macrosomia. In addition, the amniotic fluid index (AFI) was evaluated.

Maternal data, such as age, parity, last menstrual period, body mass index, gestational age at the time of the scan, diabetic status, and history of preeclampsia, were recorded, as shown in Table 1.

Table 1.

Maternal data and statistics showing parameters such as maternal age, gestational age by last menstrual period, diabetic status, and body mass index

Maternal data	RDS positive (n=14)	RDS negative (n=46)	P
Age	25.42±4.42	25.73±4.16	0.7025
DM
Yes	1	2	0.688
No	13	44
GA (LMP)	36.35±2.47	38.02±1.27	0.0013
BMI	22.43±0.69	22.67±0.66	0.7112

BMI: Body mass index, LMP: Last menstrual period, RDS: Respiratory distress syndrome, DM: Diabetes mellitus, GA: Gestational age

The inclusion criteria for the study required informed consent, a gestational age between 28 and 40 weeks, an ultrasound performed within 72 h of delivery, and a singleton pregnancy. Exclusion criteria included pregnant women with a gestational age of <28 weeks or more than 40 weeks, multiple pregnancies, uncertain gestational age, and fetuses with congenital malformations. In addition, patients with maternal hypertension and those who had received antenatal steroid therapy were excluded from the study to reduce confounding effects on neonatal respiratory outcomes.

The MPA was visualized by shifting the transducer from the four-chamber cardiac view to the three-vessel view. Measurements were taken at the midpoint of the MPA, between the valves and bifurcation, with the sample gate set to 3 mm. Doppler waveforms displayed a “spike and dome” pattern [Figure 1]. The MPA waveform was key for distinguishing it from the ductus arteriosus, which showed two peaks: a higher systolic peak and a lower diastolic peak, forming narrow, base-aligned isosceles triangles, likely due to vessel wall characteristics.[9]

Figure 1.

Shows Doppler waveform representing typical “spike and dome pattern” suggestive of fetal pulmonary artery

Doppler measurements of the fetal MPA were captured, with key variables (At, Et) measured three times and averaged. The At/Et ratio was calculated, and additional parameters (peak systolic volume [PSV], end-diastolic volume [EDV], pulsatility index [PI], and resistance index [RI]) were traced automatically, as shown in Table 2.

Table 2.

Fetal pulmonary artery Doppler indices, including the acceleration/ejection time, pulsatility index, and resistive index

Fetal pulmonary artery Doppler indices
	RDS positive (n=14)	RDS negative (n=46)	P
AT/ET	0.27±0.03	0.33±0.04	0.0001*
PI	2.16±0.50	2.36±0.45	0.1612
RI	1.01±0.18	0.91±0.23	0.1415

*P< 0.05 was considered statistically significant. RDS: Respiratory distress syndrome, AT: Acceleration time, ET: Ejection time, PI: Pulsatility index, RI: Resistance index

At the time of delivery, neonatal parameters such as birth weight and APGAR scores at 1 and 5 min were recorded to assess the newborn’s immediate health. The diagnosis of RDS was made based on clinical signs, including tachypnea, intercostal/subcostal retractions, audible grunting, and abnormal respiratory sounds such as wheezing, gurgling, or stridor. These signs, along with the need for NICU admission, were crucial in confirming the diagnosis. Additional diagnostic support, including radiographic imaging and oxygen saturation monitoring, was also considered; however, the primary focus remained on clinical presentation and the need for specialized respiratory care.[10,11]

Statistical analysis

Data were entered into Excel and analyzed with SPSS-PC-25. Normality was tested using the Anderson–Darling test. Parametric data were compared with a t-test and nonparametric data with the Pearson Chi-square test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, with significance set at P < 0.05.

RESULTS

A total of 84 patients were examined, with 24 excluded: 18 delivered more than 72 h after the ultrasound, 3 had RDS from other causes, 2 had missing neonatal data, and 1 had suboptimal ultrasound data. This left 60 fetuses, with 14 diagnosed with RDS (RDS positive group) and 46 without (RDS negative group).

Data on maternal characteristics were collected, and the gestational age of participants ranged from 28 to 40 weeks, with all delivering within 72 h of the ultrasound. No significant differences in maternal age were found between groups. However, the RDS positive group had a significantly lower mean gestational age (36.41 ± 0.03 weeks) compared to the RDS negative group (37.99 ± 1.13 weeks) as shown in Table 1.

Significant differences were found between the groups for gestational age, AFI, neonatal weight, 5-minute APGAR score, and NICU admission. The RDS-positive group had a lower mean gestational age (36 weeks), AFI (7), and weight (2481.41 ± 593.09), and all neonates in this group required NICU admission. The 5-minute APGAR scores were also lower in the RDS-positive group, as shown in Table 3.

Table 3.

Neonatal data and statistics showing parameters such as gestational age by ultrasound, amniotic fluid index, weight, Apgar score at 1 min and 5 min, and neonatal intensive care unit admission

Neonatal data
	RDS positive (n=14)	RDS negative (n=46)	P
GA (US)	36.41±0.03	37.99±1.13	0.45
AFI	7.00	11.00	0.001*
Weight	2481.41±593.09	3394.22±342.24	0.032*
Apgar_score_1_min (<7)
Yes	11	46	0.001*
No	3	0
Apgar_score_5_min (<7)
Yes	14	46	0.001*
No	0	0
NICU admission
Yes	14	0	0.0001*
No	0	46

*P<0.05 was considered statistically significant. NICU: Neonatal intensive care unit, AFI: Amniotic fluid index, GA: Gestational age, RDS: Respiratory distress syndrome, US: Ultrasound

Doppler indices of the fetal MPA were analyzed, including the PI, RI, and the At/Et. The At/Et ratio was significantly lower in the RDS positive group (0.27) compared to the RDS negative group (0.34), with P < 0.001. The PI and RI showed no significant changes, as shown in Table 2.

The Doppler waveforms of the studied cases are shown in Figures 1-3. These images display the pulmonary circulation dynamics in neonates, highlighting key patterns such as the spike-and-dome pattern. Each image reflects different stages or conditions, providing insights into the progression of RDS and the role of Doppler ultrasonography in diagnosing and monitoring neonatal respiratory health.

Figure 3.

The clinical case involves a 29-year-old female at a gestational age of 37 weeks and 5 days. Doppler ultrasound of the fetal pulmonary circulation revealed the following: the acceleration time (At) was 73 ms, and the ejection time (Et) was 280 ms. The resulting At/Et ratio was 0.26. The neonate exhibited signs of respiratory distress postdelivery, suggesting impaired pulmonary function after birth

Figure 2.

The clinical case involves a 23-year-old female at a gestational age of 39 weeks and 3 days. Doppler ultrasound of the fetal pulmonary circulation revealed the following: the acceleration time (At) was 97 ms, and the ejection time (Et) was 277 ms. The resulting At/Et ratio was 0.35. Despite these values, the neonate showed no signs of respiratory distress after delivery, indicating stable pulmonary function postbirth

Using the At/Et ratio, RDS diagnosis had high sensitivity (85.70%), specificity (80.47%) positive predictive value (93.33%) negative predictive value (97.87%), and overall accuracy (96.77%), as shown in Table 4.

Table 4.

Result parameters such as sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, negative predictive value, and accuracy

Statistic	Value	95% CI
Sensitivity (%)	85.70	68.05–99.83
Specificity (%)	80.47	88.71–99.95
Positive likelihood ratio	43.87	6.28–306.40
Negative likelihood ratio	0.07	0.01–0.45
PPV* (%)	93.33	66.71–98.99
NPV* (%)	97.87	87.38–99.67
Accuracy* (%)	96.77	88.83–99.61

*Statistical parameters in above table show significant correlation between fetal pulmonary artery doppler At/Et Ratio and the likelihood of developing RDS. PPV: Positive predictive value, NPV: Negative predictive value, CI: Confidence interval

The receiver operating characteristic curve analysis [Figure 4] further confirmed the diagnostic accuracy of the AT/ET ratio in predicting neonatal RDS. The area under the curve was 0.92, indicating excellent discriminative ability. At an optimal cutoff value of ≤0.30, the AT/ET ratio demonstrated a sensitivity of 85.7% and specificity of 80.5%, supporting its utility as a reliable non-invasive predictor of fetal lung maturity and neonatal respiratory outcomes.

Figure 4.

The receiver operating characteristic curve shown demonstrates a strong correlation between the acceleration time/ejection time ratio and the prediction of neonatal respiratory distress syndrome

DISCUSSION

RDS is a critical condition that primarily affects premature infants, resulting from both structural and functional immaturity of the lungs. Accurate assessment of fetal lung maturity is essential for identifying fetuses at risk for RDS and determining the optimal timing for pregnancy termination, especially in high-risk pregnancies.

Schenone et al. reported a positive correlation between the MPA At/Et ratio and the TDx-FLMII, suggesting that a higher ratio is linked to a reduced risk of developing RDS.[12]

Maternal age and parity showed no significant variation, but a significant correlation was found between lower gestational age and fetal weight with the incidence of RDS (P < 0.001). Briana et al.[13] shows that small for GA babies may have poorer lung function, challenging the belief that IUGR helps lung maturation. Studies in animals indicate that factors linked to IUGR – like limited nutrients, low oxygen, and high cortisol – can negatively affect lung development. These changes may lead to chronic breathing issues later in life.

In addition, our study highlighted the importance of monitoring AFI as part of a comprehensive approach to assessing fetal health. The reduction in AFI was found to be a reliable indicator of potential complications such as RDS, aligning with the research by Ghidini et al.,[14] who noted that lower AFI levels often correlate with increased risks of neonatal morbidity.

Due to challenges in obtaining a longitudinal section of the fetal MPA, we excluded PSV and EDV, focusing on the AT/ET ratio, PI, and RI. A significant correlation was found between the AT/ET ratio and RDS, with the RDS-positive group having a lower mean (0.27) than the RDS-negative group (0.33, P = 0.0001). No significant differences were found for PI or RI (P = 0.1612 and 0.1415), as shown in Table 2.

We found that RDS-positive cases had a significantly lower mean gestational age (36.41 weeks) compared to RDS-negative cases (37.99 weeks), suggesting a clear link between lower gestational age and RDS. The gestational age for RDS-negative cases ranged from 33.4 to 39.4 weeks, while RDS-positive cases ranged from 32.0 to 38.5 weeks, indicating more preterm cases in the RDS-positive group. These findings align with previous studies, showing that preterm infants are at higher risk for RDS due to underdeveloped lungs. The results emphasize the importance of gestational age in predicting neonatal respiratory outcomes.

Similarly, Guan et al. investigated the effect of increasing gestational age on the Doppler waveforms. Of the eight Doppler variables analyzed, five increased with gestational age (most dramatically At and At/Et ratio, but also PSV, EDV, and main volume; PI decreased with increasing gestational age, and Et and RI did not change significantly throughout gestation.[15]

In our study, we found a significant correlation between the fetal pulmonary artery Doppler At/Et ratio and the likelihood of developing RDS. Specifically, an AT/ET cutoff of ≤0.3 was highly predictive of neonatal outcomes, with 85.70% sensitivity, meaning all infants with a lower AT/ET ratio developed RDS. The specificity was 80.47%, indicating high accuracy in identifying those without RDS. The PPV was 93.33%, while the NPV was 97.87%. The overall accuracy of the test was 96%, demonstrating its utility as a reliable, noninvasive tool for assessing fetal lung maturity and identifying neonates at high risk for respiratory complications [Tables 4 and 5].

Table 5.

Graph illustrating the acceleration/ejection time ratio in patients with respiratory distress compared to those without distress

Abdelhamid et al. performed similar studies for comparing Doppler with clinical outcome and found a positive correlation between the At/Et ratio and fetal lung maturity which was explained by an elevated At/Et ratio representing a decrease in fetal pulmonary artery pressure which was expected in a mature fetal lung.[16]

In our study, similar to the literature, we observed that while Apgar scores were lower at 1 min, they improved by 5 min for three infants. McElrath et al.[17] found that low Apgar scores at 1 min, especially in preterm infants, typically improved by 5 min with appropriate interventions.

In our study, all 14 neonates with RDS were admitted to the NICU, supporting findings by Basnet et al.,[18] Fantz et al.,[19] Warren, and Anderson et al.,[11] who highlighted the need for specialized care and respiratory support for RDS infants.

However, the results were in contrast to those of Mohamed et al., who found that the At/Et ratio was inversely correlated with fetal lung maturity. This discrepancy may be attributed to variations in the ultrasound measurements and equipment used.[20]

This study’s sample size limited our ability to perform multivariate regression analysis to adjust for potential confounders such as gestational age and birth weight, which are known to influence the risk of neonatal RDS. While our univariate analyses demonstrated a strong association between the fetal pulmonary artery AT/ET ratio and RDS, future studies with larger cohorts are needed to conduct comprehensive multivariate analyses. Such analyses will help clarify the independent predictive value of Doppler parameters by accounting for key clinical variables.

CONCLUSION

Our study suggested that the AT/ET ratio of the fetal pulmonary artery is an important predictor of fetal lung maturity and the associated risk of neonatal RDS, showing high sensitivity and specificity. To confirm these results, larger prospective studies are needed.

In addition, it was important to explore whether this ratio could serve as a replacement for amniocentesis in assessing fetal lung maturity, potentially aiding in preventing neonatal RDS.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.