Foetal Pulmonary Artery Derived Doppler Parameters for Foetal Lung Maturity Assessment: An Observational Study

1. Assistant Professor, Department of Radiodiagnosis, AIIMS, Gorakhpur, Uttar Pradesh, India. 2. Junior Resident, Department of Pathology, BRD Medical College, Gorakhpur, Uttar Pradesh, India.

Abstract

Introduction: Neonatal Respiratory Distress Syndrome (RDS) is a major cause of foetal mortality and morbidity, especially in preterm labour because of concerns about foetal lung maturity. One of the method to assess foetal lung maturity is the Doppler assessment of the foetal Pulmonary Artery.

Aim: To assess the accuracy of Doppler findings of the foetal Main Pulmonary Artery (MPA) in foetal lung maturity assessment and prediction of the development of neonatal RDS in preterm deliveries.

Materials and Methods: A prospective observational study was conducted in the Department of Radiology, along with the Departments of Obstetrics and the Department of Paediatrics of Rama Medical College, Hospital, and Research Institute in Kanpur, India from May 2022 to December 2022. A total of 76 pregnant women with singleton pregnancies and gestational age <37 weeks were included. Clinical history and relevant clinical examination data were collected from the patients. Ultrasound examination began with a general survey of the gestational sac, foetal biometry, detailed anatomical evaluation for any evident anomalies, and then cardiac evaluation. The Doppler waveform of the MPA was confirmed by its characteristic ‘spike and dome pattern’. It was distinguished from the ductus arteriosus waveform, as it shows a triangular waveform with increased diastolic flow. Acceleration Time (AT) was measured from the start of the systolic wave to the first systolic peak. Ejection Time (ET) measurement included the entire systolic wave. The diagnosis of RDS was made by the paediatrician, who was blinded to the Doppler findings. Receiver Operating Characteristic (ROC) curves were drawn using Statistical Package for the Social Sciences (SPSS) software to assess the diagnostic ability of the Doppler findings and to find the cut-off values with maximum sensitivity and specificity.

Results: Out of the 76 pregnant women included in this study, 14 were excluded due to inadequate Doppler measurements and not being able to give birth within one week of Doppler evaluation. The study assessed a total of 62 pregnant females who underwent preterm delivery following the Doppler study. In total, 28 neonates developed RDS. Doppler parameters of both groups were compared (the first group included pregnant women whose neonates developed RDS after birth, and the second group included pregnant women whose neonates didn’t develop RDS after birth) with the help of the ROC curve. The AT/ET ratio achieved the highest sensitivity and specificity, both at 82%.

Conclusion: The AT/ET ratio has produced the best results among all foetal pulmonary artery-derived Doppler parameters and is a promising non invasive method for assessing foetal lung maturity.

Acceleration time, Ejection time, Neonatology, Ultrasonography

Respiratory Distress Syndrome (RDS) in neonates, also called hyaline membrane disease, is a relatively common cause of morbidity and mortality in newborn babies, specifically in preterm deliveries (1). It occurs because of the deficient secretion of surfactant in the pulmonary alveoli by type 2 pneumocytes. The main function of surfactant is to reduce alveolar surface tension, hence, preventing alveolar collapse during expiration. Surfactant deficiency leads to inadequate functional transition of the lungs from foetal to neonatal life (1). RDS remains a common cause of Neonatal Intensive Care Unit (NICU) admission in preterm-born neonates and continues to be associated with significant mortality and morbidity, despite significant advances in perinatal care (2). Hence, assessment of foetal lung maturity is extremely important in obstetrical management. Traditionally, mainstay methods of foetal lung maturity assessment include lecithin sphingomyelin ratio, phosphatidylglycerol test, and foam stability test, among others. However, these tests are invasive, requiring amniocentesis, and have only moderate specificity (3),(4). Traditional non invasive methods of foetal lung maturity assessment include gestational age estimation, age of epiphyseal centers appearance, placental grading, comparison of foetal lung/liver echogenicity, and foetal weight estimation; however, these methods have proven to be less useful in clinical practice (5),(6).

Foetal lung maturity assessment holds great importance in clinical practice as it contributes significantly to mortality and morbidity in preterm deliveries (2). Determination of foetal lung maturity status is one of the most challenging tasks for a radiologist as well as for an obstetricians because there is still no validated optimal strategy developed for it. Conventional methods such as the foam stability test, L/S ratio, fluorescence polarisation test, phosphatidylglycerol test, and lamellar body count test are invasive in nature and have not been able to prove the superiority of one another in controlled studies (6).

So, non invasive, novel methods are needed for determining foetal lung maturity. Foetal pulmonary artery pressure can be indirectly evaluated by Doppler indices measurement, which can be used to predict neonatal RDS occurrence as inadequate surfactant raises pulmonary impedance, leading to high pulmonary arterial pressure (7). Raised foetal pulmonary arterial pressure has been shown to correlate with gestational age, foetal lung maturity, and neonatal outcomes (7),(8). Limited studies have been performed on this concept (7),(8),(9). Thus, investigating the relationship between foetal pulmonary artery doppler indices and neonatal outcomes has been considered. The current study aimed to assess the accuracy of doppler findings of foetal MPA in foetal lung maturity assessment and prediction of the development of neonatal RDS in preterm deliveries.

Material and Methods

A prospective observational study included a total of 76 pregnant women during a period from May 2022 to December 2022 in the Department of Radiology, along with the Departments of Obstetrics and Paediatrics at Rama Medical College, Hospital, and Research Institute in Kanpur, Uttar Pradesh, India. Approval from the university Research Ethics Committee was obtained (certificate number RMCHRC/Ethics/2022/1990-A). All mothers included in this research were above 18 years old and gave written informed consent.

Inclusion criteria: Pregnant women, irrespective of parity, with singleton pregnancies and gestational age <37 weeks, who delivered within one week of the ultrasound scan were included in the study.

Exclusion criteria: Pre-existing maternal medical conditions like diabetes, renal diseases, cardiac diseases, and hypertensive disorders, among others. Major foetal anomalies identified during the scan or after delivery, chromosomal anomalies, intrauterine foetal growth restriction were all excluded from the study.

Sample size estimation: The Cochrane formula was used for sample size determination.

n=Z²p(1-p)/e²

Where,

‘Z’ is called the z-score.
‘p’ is the expected percentage of the population with the desired attribute.
‘e’ is the desired precision or margin of error.

The z-score was taken as 1.96, the p-value as 0.5, and the e-value as 0.13.

Before proceeding to the ultrasound examination, clinical history and relevant clinical examination data were collected from the patient. All ultrasound tests were performed by two radiologists, using a Samsung V7 ultrasound machine using a 3.5 MHz transabdominal probe.

The ultrasound examination started with a general survey of the gestational sac, biometry of the foetus, detailed anatomical evaluation of the foetus for any evident anomaly, and then the cardiac evaluation. All cardiac views were properly assessed, and then the pulmonary artery was focused on in axial sections, showing the pulmonary valve, MPA and its bifurcation into the right and left divisions (Table/Fig 1). The angle of insonation was kept below 30°, and the doppler sample gate was kept at 3 mm. Doppler gain and scale were adjusted such that the Peak Systolic Velocity (PSV) and early diastolic notch were clearly visualised. The Doppler waveform of the MPA was confirmed by its characteristic ‘spike and dome pattern’ and was distinguished from the ductus arteriosus wave, which later showed a triangular waveform with increased diastolic flow (Table/Fig 2). Acceleration Time (AT) was measured from starting of the systolic wave to the first systolic peak. Ejection Time (ET) measurement included the entirety of the systolic wave (Table/Fig 3).

The diagnosis of RDS was made by the paediatrician, who was blinded to the Doppler findings, by: 1) clinical history; 2) Not maintain oxygen saturation/increased oxygen requirement; 3) Low lung volume/reticulogranular pattern/whiteout on chest X-ray.

The cases were divided into two groups-those who developed RDS and those who did not develop RDS. The clinical, demographic, and doppler characteristics of these two groups were compared.

Statistical Analysis

Statistical analysis was done using SPSS for Windows version 11.0. A two-tailed Independent sample t-test and Student’s t-test was used. ROC curves were drawn, using SPSS software to assess the diagnostic ability of doppler findings and to find the cut-off values with maximum sensitivity and specificity. A significance level of p<0.05 was considered statistically significant.

Results

Out of the 76 pregnant women included in this study, 14 were excluded due to inadequate Doppler measurements and not being able to give birth within one week of Doppler evaluation. The mean maternal age of the study population was 25.0±3.6 years, and the mean gestational age was 33.52±1.56 (30-36 weeks).

Data from a total of 62 pregnant females who underwent preterm delivery (before the 37th week of pregnancy) following the doppler study were analysed in this study. Cases were divided into two groups: a) neonates with RDS (n=28); and b) neonates without RDS (n=34). A significant difference was found in the mean birth weight of the two groups (2043 g in RDS positives and 2212 g in the RDS negative group, with p-value=0.0001) (Table/Fig 4).

Among doppler parameters, a statistically significant difference was found in the mean values of AT, ET ratio of AT/ET, PSV, Mean Velocity (MV), and Resistive Index (RI) (Table/Fig 5).

To compare the diagnostic abilities of different parameters, ROC curves were drawn. The highest Area Under Curve (AUC) was found for the AT/ET ratio (0.875), followed by the absolute AT value (0.833) (Table/Fig 6). The highest sensitivity and specificity of 82% each were achieved with the AT/ET ratio at a cut-off value of 0.29. For AT alone, the sensitivity and specificity were 76% and 72%, respectively, at a cut-off value of 48.5 (Table/Fig 7).

ROC was also drawn for PSV, End Diastolic Velocity (EDV) and MV (Table/Fig 8) as well as for Pulsatility Index (PI) and RI (Table/Fig 9).

Discussion

RDS is one of the leading causes of neonatal mortality and morbidity. The incidence of RDS increases with decreasing gestational age, with the maximum risk in very preterm (28- <32 weeks) and extremely preterm births (<28 weeks). It can also be seen in late preterm and early-term deliveries (10). Hence, the determination of foetal lung maturity is gaining importance in obstetrical management, particularly in elective caesarean cases planned because of obstetrical or medical indications (10). A clue to the doppler application in pulmonary circulation came by the study of Kitabatake A et al., which showed that the time to peak flow and Right Ventricular Ejection Time (RVET) were both decreased in patients with pulmonary hypertension, thus it may be helpful in the indirect evaluation of pulmonary artery pressure (11). Subsequently, Rasanen J et al., showed that pulmonary vasculature impedance decreases throughout gestation, which may be because of increased vessel wall elasticity, angiogenesis, and decreased pulmonary pressure related to growing lung tissue (12).

Furthermore, Fuke S et al., showed a lower pulmonary arterial AT/ET ratio in cases of pulmonary hypoplasia (13). Similarly, two separate studies were done by Kim SM et al., and Azpurua H et al., showed the increasing probability of lung maturity with a decreasing pulmonary arterial AT/ET ratio (14),(15). Kim SM et al., in their study, showed that the Pulmonary artery AT/ET ratio was significantly greater in foetuses that developed RDS after birth, compared with those who did not develop RDS. The AT/ET ratio in the group that developed RDS was 0.37 with a range of 0.26 to 0.41, whereas in the group that did not develop RDS, it was 0.30 with a range of 0.21 to 0.44. Their data showed that foetal pulmonary artery doppler velocimetry may provide a reliable non invasive technique to assess foetal lung maturity (14). Similarly, Azpurua H et al., studied the correlation between AT/ET ratio in the foetal pulmonary artery and amniotic fluid L/S ratio, and found an inverse relation between them. They showed that the AT/ET ratio of the foetal pulmonary artery was in a decreasing trend with increasing gestational age, and attributed this finding to a progressive decrease in pulmonary vascular resistance and an increase in pulmonary blood flow with increasing gestational age (15).

Hassan HGEMA et al., also conducted a similar study and showed that the mean AT/ET ratio of the foetal pulmonary artery was significantly lower in foetuses that subsequently developed RDS compared to those who did not throughout all gestational age periods (0.297 vs 0.352, p-value <0.001) and in the early preterm period (0.280 vs 0.312, p-value=0.002), late preterm period (0.311 vs 0.362, p-value <0.001), and early term period (0.345 vs 0.383, p-value <0.001). The optimal cut-off value of the AT/ET ratio in their study was 0.305 with sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of 76.9%, 84.1%, 74%, and 86%, respectively (16).

Taha HMG et al., found the sensitivity and specificity of the foetal pulmonary artery as 76.6% and 100% at a cut-off value of 0.25 (17). This value was a relatively smaller compared to the studies performed by Keshuraj V et al., Hassan HGEMA et al., and Schenone MH et al., (9),(16),(18). All these data have been summarised in (Table/Fig 10) (9),(16),(17),(18).

In current study, an inverse association was found between foetal pulmonary AT/ET ratio and the diagnosis of RDS in the neonatal period. Hence, using the AT/ET ratio, instead of AT alone, produces better screening results. We look forward to similar studies on a large scale to validate the results and establish foetal pulmonary artery doppler as a screening tool to predict the occurrence of neonatal RDS.

Limitation(s)

The limitation of this study was the relatively small study population and single-centre nature of the study.

Conclusion

Among all the foetal pulmonary artery-derived doppler indices, the AT/ET ratio can prove to be a game-changer in obstetrical management of preterm and high-risk deliveries. Present study shows the significant screening ability of the AT/ET ratio in predicting the development of neonatal RDS.

DOI and Others

DOI: 10.7860/JCDR/2024/70374.19711

Date of Submission: Feb 27, 2024
Date of Peer Review: Apr 01, 2024
Date of Acceptance: Jun 05, 2024
Date of Publishing: Aug 01, 2024

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

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ETYMOLOGY: Author Origin

EMENDATIONS: 7