Role of fetal main pulmonary artery doppler indices in prediction of fetal lung maturity

Abd elkhalik, Ibrahim Essam Elsayed; HASSAN, HANY MAGED; ELLABAN, MOSTAFA MOHAMED

doi:10.21608/aimj.2021.54512.1380

Role of fetal main pulmonary artery doppler indices in prediction of fetal lung maturity

Al-Azhar International Medical Journal

Article 15, Volume 2, Issue 4, April 2021, Page 28-33 PDF (335.76 K)

Document Type: Original Article

DOI: 10.21608/aimj.2021.54512.1380

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Authors

Ibrahim Essam Elsayed Abd elkhalik

¹; HANY MAGED HASSAN²; MOSTAFA MOHAMED ELLABAN²

¹Obstetrics and gynacology Department,Al-azhar faculty of medicine,Egypt

²Obstetrics and Gynecology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

Abstract

Background: Accurate evaluation of fetal lung maturity is of utmost importance for determining the optimal time for pregnancy termination. Amniocentesis is an invasive procedure and is associated with a small but real risk to the pregnancy. So noninvasive sonographic techniques to evaluate lung maturity is most needed.
Objective: To study the role of fetal main pulmonary artery Doppler (MPA) indices in prediction of Fetal Lung Maturity (FLM) and determine a cut point of Doppler indices with high sensitivity and specificity.
Patients and Methods: Our prospective cohort study included 200 pregnant women 38 weeks fulfilling the inclusion and exclusion criteria, A number of different parameters were measured from the fetal pulmonary artery flow (FPAF) waveform (At/Et, S/D, PSV, PI and RI) for diagnosis of neonatal Respiratory Distress Syndrome (RDS) by comparing the Doppler findings with the clinical outcome.
Results: About 46 (23%) fetuses were diagnosed as RDS (+ve) and 154 (77%) fetuses were without RDS(-ve). At/Et and PSV were positively correlated, whereas PI and RI were inversely correlated with RDS. S/D ratio did not change significantly. The strongest correlation was found with At/Et. AT/ET was significantly lower in the RDS +ve group and cutoff point of 0.32 predicted the development of neonatal RDS with a high sensitivity specificity, and accuracy (98.0%, 92.0%, and 95.0% respectively).
Conclusion: FLM and Neonatal RDS can be predicted using the MPA At/Et with high sensitivity and specificity.

Keywords

Fetal Lung Maturity; Neonatal Respiratory Distress Syndrome; Fetal Main Pulmonary Artery Doppler Indices

Full Text

INTRODUCTION

Neonatal respirat0ry distress syndrome (RDS) is the respirat0ry impairment at or shortly once birth and remains as significant reason behind neonatal m0rtality and m0rbidity.¹ RDS can lead to neonatal morbidity and mortality in both early term and late preterm periods^1,2, where elective delivery before 39 weeks is associated with a preventable increase in neonatal morbidity and admissions to the ne0natal intensive care unit (NICU) leading to more costs.³Taking into consideration in several conditions of high risk pregnancies, obstetric care providers, decide to terminate pregnancy before spontaneous delivery is begun. In terms of detremaning the optimal time for pregnancy termination , one of the most concerns is detecting those fetuses whom are at risk for RDS. As RDS risk diminishes with the increase of the

gestational age, since the last fetal organs to practically develop are lungs.⁴

Before labor, it appears rationale to survey fetal lung maturity (FLM). Bi0chemical tests have been developed as lecithin/sphing0myelin ratio, absence or presence of ph0sphatidyl glycerol and amniotic liquid, flu0rescent p0larization, foam stability or shake test lamellar b0dy count have been utilized; in any case, all rely on amniocentesis, which is an invasive method to determine foetal lung maturity and the risk of neonatal RDS and offer obstetricians help in choosing the delivery date.⁵

The biological, chemical and physical pr0perties of the amni0tic liquid are considered as the primary standard tests of f0etal lung maturity by an invasive technique that presents potential pregnancy’s problems, such as rupture of membranes prematurely, preterm labour, , fetomaternal hemorrhage, placental abruption, fetal injury, and even death for the mother or the fetus^6-9. Therefore, Historically, amni0centesis for f0etal lung maturity has been done for these purposes. Nevertheless risks that are linked to amniocentesis in final trimester are comparatively low, there have been documented complications.^2,10

Therefore, there is a need for noninvasive test. The sonographic echogenicity of fetal lung changes in an anticipated way during pregnancy.⁴Latest results have shown that the percentage of f0etal main pulmonary arteries can anticipate foetal lung maturity in relation to the clinical outcomes of the delivered f0etuses or to biochemical tests of amniocentesis^6, D0ppler vel0cimetry offers a simple non-invasive method to evaluate the f0etal pulm0nary circulati0n. Doppler velocimetry has been used for measuring fetal pulmonary blood flow in right or left pulmonary arteries plus peripheral branches of them, however, the rate of satisfactory D0ppler records is average and disparate.¹¹

Regarding all the points discussed before, we assume that “using f0etal pulm0nary artery D0ppler indices can aid in determining FLM”. This study is going to determine, whether f0etal main pulm0nary artery D0ppler indices could predict fetal lung maturity in term fetuses in third trimester of gestational age more than 38 weeks or not, and if so, is there a cut point of D0ppler indices with high sensitivity and specificity for this reason. Our aim is to study the reliability of using f0etal main pulm0nary artery D0ppler indices in f0etal lung maturity prediction.

PATIENTS AND METHODS

This pr0spective c0h0rt study was done at Gynecology and Obstetrics Department at Sayed Galal university Hospital. During the period from January 1st, 2020 till November 30^st, 2020. Patients were selected from outpatient clinic, and patients admitted in Sayed Galal Obstetrics-Gynecology department. This study included 200 pregnant women who attended outpatient clinics in Sayed Galal Hospital with the following criteria: Age: 18-40, gestational age 38 weeks with living fetus, Intact fetal membranes and Expected delivery within 48 hours of admission before elective cesarean section. We excluded cases who were pregnant less than 38 weeks of gestation, multiple gestation, uncertain gestational age, diabetic or cardiac women, IUGR or congenital fetal anomalies, accidental hemorrhage associated with m0derate 0r severe bleeding and cases suffering from polyhydramnios and oligohydramnios. for prevention of sonography false results, severe medical condition leading to misleading results.

The study was approved by the ethics committee after proper counseling. Female participants who applied for enrolment and provided informed written consent. All patients selected to take place in this study were exposed to the following: Full history taking including age, history of any medical disorders, history of any previous operations, menstrual history (last menstrual period, regularity of the cycle). Women have been scanned in supine posture. Prenatal sonographic test was done involves f0etal bi0metry (BPD, FL and HC) for measuring the gestational age of the fetus and estimated foetal weight and to exclude retardation of the intrauterine growth or macrosomia. Amni0tic fluid index was also measured. The amni0tic fluid index was also calculated. The axial portion of the f0etal thoracic at level of the 4-chamber cardiac view was magnified by modifying the depth, not by zooming, until most of the display is occupied by the thoracic section, eliminating visible acoustic shadows from foetal ribs or spine. After that, the f0etal main pulm0nary artery (MPA) was showed in order to obtain the three-vessel view by slightly translating the transducer superiorly (3VV) (Figur 1).

Inclusion criteria: Comminuted patellar fractures

Fig 1: The 4-chamber view of the foetal heart

Pulsed Doopler sample gate is situated in the middle of f0etal MPA (between pulmonary valves and pulm0nary artery bifurcation). After enhancing the image as possible, we set sample gate to 3 mm. Sample gate was calibrated to 3 mm while the image was improved as much as possible. Foetal MPA Waveforms create a certain pattern "spike and dome," and small notch at the end of systole. That particular form of the MPA wavef0rm is important to distinguish between the rounded, complete and triangular shaped ductus arteriosus waveform after the ideal foetal MPA waveform has been collected, the related Doppler velocity Parameters are measured by a manual trace three times with average measurements. Doppler Parameters contain the accelerati0n time (AT; time period from base to top of the PSV), ejecti0n time (ET; from the start to the end of the ventricular systole), from these measurements AT/ET ratio was estimated (Figur. 2). Other Doppler parameters were measured using automated traces such as the peak blood flow velocity reached during syst0le (PSV), the pulsatility index (PI) and the resistance index (RI). After birth, the measurement of each newborn included APGAR 1, 5minutes, the incidence of RDS and the need for NICU admissions. Respirat0ry distress caused by reasons differ from RDS and disorders such: Ne0natal sepsis, haemodynamic collapse, sympt0matic anaemia and meconium Aspiration as these c0nditions may particularly predispose to unreliable outcomes, Regardless of the maturity of the lung.

Fig 2: It shows the acceleration and ejection time. Spike and Dome Pattern.

Statistical analysis:

Data were analyzed using SPSS version 21.0. The qualitative data were presented using number and percent. In order to compare the various classes of categorical variables, Chi-square test was used. While quantitative results were represented by mean and standard deviations. Regarding normally distributed data, independent population was compared using independent t-test if they are two, while more than that were analyzed using ANOVA (F-test). Results is considered significant if two-tailed P-value was equal to or less than 0.05.

RESULTS

Therehwere no statistically significant differences in demographic data between neonatal without and with RDS (Table 1).

Regarding neonatal clinical data, there was statistically significant difference between neonates without and with RDS (P < 0.05). APGAR 1 min in group I ranged from 6-9 with mean value 8.05  0.86 and in group II ranged from 5-8 with mean value 6.91  0.87. APGAR 5m in group I ranged from 8-10 with mean value 8.92  0.76 and in group II ranged from 5-8 with mean value 6.980.84. All cases in group II need incubation (Table 2).

Without RDS Group I

With RDS Group II

Test p

Age

Range

Mean

19-38

28.78

6.05

20-38

29.24

5.89

T=0.962

0.3090

Parity

46.75

53.25

52.17

47.83

X² =0.821

0.2604

BMI

Range

Mean

21-31

26.45

2.99

21.2-30

25.19

2.57

T=1.65

0.064 N.S.

Table 1: The results according to Böstman score.

Without

RDS GroupI

With RDS Group II

Test p

APGAR 1 min

Range

Mean

6-9

8.05

0.86

5-8

6.91

0.87

T=3.25

0.001*

APGAR 5 m

Range

Mean

8-10

8.92

0.76

5-8

6.98

0.84

T=2.98

0.001*

Incubation

Yes

147

95.45

4.55

0.0

100.0

X² = 5.58

0.001*

Table 2: Comparison between neonates without and with RDS regarding neonatal clinical data.

Regarding neonatal weight, there was statistically significant difference between neonates without and with RDS (P < 0.05). Weight in group I ranged from 2.7-4.2 with mean value 3.200.28 and in group II ranged from 3.070.36. but also, there was no statistically significant difference between two groups regarding gender (P > 0.05) (Table 3).

According Pulmonary artery indices, the MPA At/Et was significantly lower in fetuses diagnosed with RDS compared with those without (0.29 ± 0.03 versus 0.4± 0.00,). MPA PI and RI were significantly higher mean value (3.28 ± 1.02 and 1.07 ± 0.20 cm s − 1 versus 2.6 ± 0.9 and 0.9 ± 0.2cm s – 1) whereas PSV was significantly lower in fetuses with RDS (40.39 ± 6.19 versus 50.3±10.3 cm s − 1). No statistically significant difference regarding S/D (P > 0.05) between the two groups (Table 4).

According tosensitivity, specificity and accuracy of PSV and AT/ET in prediction of fetal lung maturity, the PSV sensitivity was 81.0%, specificity was 84.0% and accuracy 83.0% at cut off value 45.0, while AT/ET sensitivity was 98.0, specificity was 92.0% and accuracy was 95.0% at cut off value 0.32 (Table 5 & figure 3).

Without RDS Group I

With RDS Group II

Test

Weight(kg)

Range

Mean

2.7-4.2

3.20

0.28

2.4-3.9

3.07

0.36

T=2.66

0.0041*

Gender

Male

Female

47.40

52.60

56.52

43.48

X² =0.925

0.3208 N.S.

Table 3: Comparison between neonates without and with RDS regarding neonatal weight and gender.

Without RDS Group I

With RDS Group II

PSV

Range

Mean

35.0-69.9

50.3

10.3

30.2-54

40.39

6.19

5.26

0.001*

S/D

Range

Mean

0.9-9.5

5.4

2.5

2-9

5.44

2.08

0.587

0.4813

Range

Mean

1-4.1

2.6

0.9

1.6-4.9

3.28

1.02

5.14

0.001*

Range

Mean

0.5-1.5

0.9

0.2

0.7-1.5

1.07

0.20

3.02

0.0285*

AT/ET

Range

Mean

0.32-0.46

0.4

0.0

0.23-0.33

0.29

0.03

6.14

0.001*

Table 4: Comparison between neonates without and with RDS regarding MPA Doppler findings.

Test Result Variable(s)	Area Under the curve	Cut off value	P value	Sensitivity	Specificity	Accuracy	Asymptotic 95% C.I
Test Result Variable(s)	Area Under the curve	Cut off value	P value	Sensitivity	Specificity	Accuracy	Lower Bound	Upper Bound
PSV	.870	45.0	.0012	81.0	84.0	83.0	.803	.971
AT/ET	.992	0.32	.0001	98.0	92.0	95.0	.983	1.000

Table 5: Sensitivity, Specificity and accuracy of PSV and AT/ET in prediction of fetal lung maturity.

Fig 3: ROC curve for Predicition value of PSV and AT/ET in predicting the fetal lung maturity.

DISCUSSION

Respirat0ry distress syndr0me (RDS) appears to be a significant cause of ne0natal m0rbidity and m0rtality, as well as RDS incidence and severity which has an inverse pr0p0rtion with the gestational age in time of birth. Precisely, the deficiency in pulmonary surfactant results in neonatal RDS specifically. As a result, several interventions have been introduced trying to prevent it.¹²

Over the past 30 years, a variety of non-invasive sonographic studies have been proposed to predict foetal pulmonary maturity, including f0etal biometry, placental maturation, umbilical artery Doppler velocimetry, f0etal breathing patterns and nasal fluid flow velocity waveforms, and f0etal intestine and ossification centres of long f0etal bones. H0wever, n0ne of them proved to be appropriately reproducible or reliable.^{13, 14}

To predict the probability of f0etal lung maturity, several antenatal tests have been introduced. Nevertheless being used commonly in the obstetric practice, they still do not have an accurate predictive value, specifically in the late periods of gestation, and requires performing amniocentesis which is invsive.¹⁵

Recent studies have shown that to predict fetal lung maturity, ratio in fetal main pulm0nary artery can be used by bi0chemical studies of amni0centesis or by evaluating with the clinical outcome of the f0etuses delivered.⁶

Here in this study, Fetal MPA Doppler indices were examined in (200) term feti about 38 weeks for predicting lung maturity. this gestational age (38 weeks.) was chosen as before that GA, where there is a high risk of fetal lung immaturity, and so testing of FLM in this gestational age is not useful useful to detect the cut point at which we can predict FLM. About 46 feti were RDS (+ve) and 154 feti without RDS. Neonatal RDS was diagnosed with foetal blinded MPA Doppler waveform findings when there is at least two out of three of these parameters, Clinically: respiratory failure signs (retraction, tachypnea, and, or nasal flairing) soon after birth and an intensified need for oxygen (fractional concentration of inspired oxygen > 0/4) for more than 24 hours. Radiographic: hyaline membrane disease evidences such as: reticulo-nodular sequence, air bronchogram and ground glass presentation in the absence of other respiratory diseases. Reacts to exogenous pulmonary surfactants. This research revealed that in compare to f0etuses who have not devel0p neonatal RDS, fetuses that developed RDS had significantly l0wer At/Et and PSV and higher PI and RI. This means that f0etuses who devel0p RDS have higher pulm0nary vascular resistance and pressure and l0wer pulm0nary blood fl0w c0mpared with fetuses that do not devel0p RDS. A cut of point of 0.32 in the AT/ ET ration anticipated the development of neonatal RDS with a high sensitivity, specificity, and accuracy (98.0%, 92.0%, and 95.0% respectively).

Our findings have been in agreement with Schenone et al study who c0mpared the AT/ET to albumin/surfactant ratio. Schenone and his colleagues found a positive correlation between ratio in fetal MPA and TDx-FLM-II in the amniotic fluid. This means that an increasing in the At/Et ration has association with more mature lung and less risk to develop RDS, and that supports our findings, They proved that a PATET cutoff of 0.3149 has a sensitivity of 73%, specificity of 93% predicting TDx-FLM II results, with no study of clinical end points of feti and development of RDS.¹⁴

Guan and his colleagues explain differences in foetal main pulmonary artery (MPA) waveforms in the Doppler during the gestation from 22 to 42 weeks, as well as their neonatal respiratory distress syndrome (RDS) predictive values and important and positive linear correlation between AT, AT/ET ratio and the gestational age, peak systolic velocity and average velocity were identified. Fetal MPA Doppler velocimetry could be accurately done during pregnancy. AT and AT/ET ratios of the foetal MPA Doppler waveform can aid in recognizing the foetuses who have the risk to develop neonatal RDS, these results match with our study, but here our study shows that also pulmonary RI, PSV show statically significant correlation. MPA At/Et and PS were positively correlated, whereas RI has inverse correlation in the development of RDS, strongest correlation was regarding At/Et ratio, In the second phase of Guan study, the study was limited and didn’t determine a cut point of MPA doppler indices.⁵

Azpurua et al.⁶ showed that the acceleration time/ejection time ratio in the FPA and the amniotic fluid lecithin/sphingomyelin ratio has an inverse correlation. Which means the Ultras0und measurement of f0etal pulm0nary artery blood flow can promise a new non-invasive procedure to assess the f0etal lung maturity, but their study had limitations of being small sample size (29 feti) with only one infant with RDS, also using an invasive procedure with little but serious risk to pregnancy, but here the study depends on non-invasive safe widely accepted available method.⁶

However, our results contradicted Kim et al.⁷ as he found that Pulmonary artery AT/ET ratio has an inverse correlation to the maturity of the fetal lung.

Kim et al.⁷ compared fetal MPA Doppler indicies results with the clinical outcome of feti after birth as developing RDS. They described a cut point of ratio (0.326) for predicting RDS, and claimed that more than 0.326, means subsequent development of RDS.

CONCLUSION

Evaluation of Fetal Mean Pulmonary Artery Doppler by ultrasound can be used as a rapid noninvasive accurate method for prediction of Fetal Lung Maturity and neonatal RDS. MPA Doppler indices, as At/Et, RI, PSV, and PI indices can be used for prediction of FLM. The strongest correlation was found as regarding At/Et and the cut point of 0.32 is achieved by a high sensitivity and specificity.

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