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ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 4  |  Page : 235-241

Status of pulmonary artery pressures on echocardiography among high-risk newborns


Department of Pediatrics, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Date of Submission07-Mar-2019
Date of Decision05-Aug-2020
Date of Acceptance09-Aug-2020
Date of Web Publication01-Oct-2020

Correspondence Address:
Dr. Shaad Abqari
Assistant Professor, Division of Pediatric Cardiology, Department of Pediatrics, J.N Medical College AMU, Aligarh - 202 002, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_24_19

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  Abstract 


Background: There is a paucity of data about the outcome of newborns who have one or more risk factors for persistent pulmonary hypertension of newborn (PPHN) and have some degrees of pulmonary hypertension not significant enough to cause hypoxemia and desaturation to be labeled as PPHN. Objective: Status of pulmonary artery pressures in high risk newborns. Materials and Methods: This was a prospective observational study, in which newborns up to 1 month of age having risk factors for PPHN were included and pulmonary hypertension was identified on echocardiography in neonates more than 48 h of life. Second screening was done at 6 weeks of life independent of subjects having PAH or not at the first screening. Results: Out of 400 cases, 26 patients were lost to follow-up, 2 cases left against medical advice, and 18 patients expired after first screening. Finally, a total of 354 cases came for follow-up at 6 weeks and repeat echocardiography was done in all cases. PAH was found in 54 cases on first screening, 12 neonates had reversal of shunt at the level of patent ductus arteriosus or patent foramen ovale, and only 2 cases had persistence PAH on second screening at 6 weeks. Perinatal asphyxia (43.9%), respiratory distress (31%), and meconium-stained amniotic fluid (30%) have shown a significant association with the development of PAH in these neonates. Development of PAH worsens the prognosis in newborns with asphyxia and sepsis. Conclusion: Newborns with risk factors have some degree of PAH, which can have an adverse impact on outcome.

Keywords: Respiratory distress syndrome, Meconium-stained amniotic fluid, PAH, perinatal asphyxia, persistent pulmonary hypertension of newborn, risk factors


How to cite this article:
Ahmed T, Abqari S, Firdaus U, Shahab T, Ali SM. Status of pulmonary artery pressures on echocardiography among high-risk newborns. J Clin Neonatol 2020;9:235-41

How to cite this URL:
Ahmed T, Abqari S, Firdaus U, Shahab T, Ali SM. Status of pulmonary artery pressures on echocardiography among high-risk newborns. J Clin Neonatol [serial online] 2020 [cited 2020 Nov 28];9:235-41. Available from: https://www.jcnonweb.com/text.asp?2020/9/4/235/297000




  Introduction Top


Persistent pulmonary hypertension of newborn (PPHN) can be defined as a failure of normal fall in pulmonary vascular resistance (PVR) at or shortly after birth, leading to shunting of unoxygenated blood into the systemic circulation across foramen ovale or ductus arteriosus.[1]

PPHN is suspected when the newborn has persistent desaturation and validated pulmonary hypertension on echocardiography or cardiac catheterization. There are many studies which have found various risk factors associated with PPHN.[2],[3],[4] However, there is a paucity of data about the outcome of newborns who have one or more risk factors for PPHN and have some degrees of PAH not significant enough to cause hypoxemia and desaturation. There are no clear cutoff limits to label a newborn as having pulmonary artery (PA) hypertension unlike in adults where the mean PA pressure (PAP) of >25 mmHg at rest is labeled as PAH, besides its not feasible to subject a newborn to cardiac catheterization for documentation of PAPs. There is also no data about the trends of fall of PAPs, especially in newborns with risk factors over a period of time especially during the first few weeks of life and likewise it is not clear what are the normal PAPs with regard to the post gestational age of the child since we are lacking in data on trends and cutoff of PAPs with respect to the age of the child. The present study was undertaken to measure the PAPs in newborns prone to develop PAH utilizing a less invasive method of measurement, i.e., echocardiography and look for prevalence of PAH in these newborns.

Need for the study

PAH is a disease fairly common in neonatal period and leads to significant morbidity and mortality. Various risk factors are associated with the development of PAH and identification of these risk factors with early detection of PAH and proper management can decrease morbidity and mortality. Hence, this study was undertaken with the aim of studying the prevalence of PAH in neonates with certain maternal and neonatal risk factors.


  Materials and Methods Top


This was a prospective observational study done from January 2015 to October 2016 in the neonatal high dependency unit and neonatal intensive care unit (NICU) of the Department of Pediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh. Newborns up to 1 month of age were included in the study. We had done first a pilot study in 100 patients who had one or more of these risk factors for PPHN and we found the prevalence of pulmonary hypertension as 16% in neonates with risk factors. Hence, considering 16% prevalence, 95% confidence interval, and 4% precision, a minimum of 323 cases were needed for the study. However, we had screened a total of 410 cases, but ten cases were excluded as they have one or other heart defect and finally 400 newborns with one or more risk factor of PPHN were included in the study.

Methodology

After obtaining informed consent from parents or guardian, a detailed history including antenatal history and examination of newborn was done to identify various risk factors (both maternal and neonatal). Newborn with either risk factor or both was taken up for the study. The echocardiography was done in the NICU and the neonatal ward with Aloka echo machine by a trained resident, and the findings were confirmed by the pediatric cardiologist, and in case of doubt, a repeat echocardiography was done on Vivid S6 GE machine. The average of three values was taken as final measurement. Initial echocardiography was done after 48 h of birth for inborn neonates and at first presentation for out born neonates (age more than 48 h of life). Repeat echocardiography was done for patients who showed clinical deterioration or no improvement during hospital stay. The child received the standard treatment for the PAH as per the NICU protocol which includes nonpharmacological measures such as sedation, minimal stimulation, and drugs such as sildenafil. Second echocardiographic evaluation was done in all neonates at 6 weeks to know the persistence of PAH or development of PAH in cases initially having normal scan.

Inclusion criteria

Risk factors in newborn

Preterm, very low birth weight (VLBW), history of meconium-stained amniotic fluid (MSAF), respiratory distress syndrome (RDS), sepsis, perinatal asphyxia, intrauterine growth retardation/small for gestational age (SGA), postterm, metabolic derangements (hypoglycemia and hypocalcemia), and polycythemia.

Risk factors in mother

Asthma, diabetes mellitus, urinary tract infection (UTI), maternal drug intake (such as selective serotonin reuptake inhibitors), cesarean section, twin delivery, pregnancy-induced hypertension (PIH), and oligohydramnios.

Exclusion criteria

Congenital heart disease and pulmonary vein stenosis.

Echocardiographic criteria for the diagnosis of PAH

Tricuspid regurgitation jet

The jet of blood leaking through the tricuspid valve was interrogated with Doppler. The peak velocity of the tricuspid regurgitation (TR) jet which is a direct indicator of the right ventricular (RV) pressure (and therefore PA pressure [PAP]) plus right atrial (RA) pressure (assumed) was taken as systolic PAP.

PAH - Pulmonary artery systolic pressure ([RV systolic pressure + RA pressure]) >50% of systolic blood pressure (SBP). We had assumed RA pressure as 5 mm of Hg.

SBP was measured from noninvasive blood pressure.

Grading of PAH:

  • Mild: 25–40 mm of Hg
  • Moderate: 40–60 mm of Hg
  • Severe: >60 mm of Hg.


Patent ductus arteriosus/patent foramen ovale flow

Pure right-to-left flow indicates that PAP is higher than aortic pressure throughout the cardiac cycle and newborn has PPHN.

Interventricular septum flattening

In the absence of TR jet, end-systolic ventricular septal flattening was considered to diagnose PAH, which indicates that the RV pressure is more than left ventricular systolic pressure.


  Results Top


Total numbers of cases screened in our study were 410. Out of 410 neonates, 10 cases were of congenital heart disease and hence excluded from the study (6 cases of ventricular septal defect, 3 cases of tetralogy of fallot, and one case of atrial septal defect). Out of 400 cases enrolled in the study, 26 patients lost to follow-up, 2 cases left against medical advice, and 18 patients expired after first screening. Finally, a total of 354 cases came for follow-up at 6 weeks and repeat echocardiography was done in all cases [Flowchart 1]. PAH was found in 13.5% (54 out of 400) of neonates screened. Out of those 54 neonates, 12 (22.2%) had reversal of shunt at the level of patent ductus arteriosus (PDA) or patent foramen ovale (PFO) and hence these were cases of PPHN. As shown in [Table 1], total 362 cases (90.5%) were screened within the first 2 weeks of life and 38 (9.5%) cases after 2 weeks and latter consisted of outborn deliveries. There were 265 males (66.3%) and 135 females (33.8%). Out of 400 neonates, 264 were delivered by cesarean section and 136 by vaginal route. 25 newborns (6.3%) were preterm, 5 were (1.3%) postterm, and 12 (3%) were VLBW [Figure 1]. The number of cesarean delivery was large as it was the most common maternal risk factor. Furthermore, most of the newborns with one or other risk factor were born through lower segment cesarean section (LSCS), which sometimes become an indication for doing it. There were no cases of asthma in the mother during the study period and only 2 mothers with UTI were screened since only those mothers with symptomatic bacteriuria with positive urine cultures were taken as risk factor for PAH. Thirteen newborns of mothers with PIH were screened. There were 40 cases (10%) of twins and 2 cases were having maternal history of drug intake and a total of 11 mothers (2.8%) were having oligohydramnios. As shown in [Table 2], the most common neonatal risk factor screened was respiratory distress (17.8%), followed by sepsis (15.7%), MSAF (12.3%), and perinatal asphyxia (10.3%), while 6.3%, 3%, and 1.3% cases of preterm, VLBW, and postterm neonates, respectively, were also screened. There were 5 cases who were either IUGR or SGA. A total 13 neonates had metabolic derangements, with 6 cases having hypocalcemia and 7 hypoglycemia.
Table 1: Demographic profile of newborns (n=400)

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Figure 1: Distribution of study subjects according to various maternal and neonatal risk factors studied (n = 400)

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Table 2: Association of various maternal and neonatal risk factors with PAH in neonates by univariate analysis

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Association with Pulmonary artery Hypertension (PAH)

As shown in [Table 3], perinatal asphyxia, MSAF, and respiratory distress were found to have significant association with PAH in our study. Out of 41 cases of perinatal asphyxia, 18 (43.9%) neonates had PAH; similarly, out of 49 neonates with a history of MSAF, 15 (30.6%) had developed PAH, whereas among neonates with respiratory distress, only 22 (31%) neonates developed PAH. The percentage of neonates with sepsis, preterm, VLBW, and hypocalcemia as risk factors who developed PAH was 14.3%, 20.5%, 25%, and 30.8%, respectively, but the association was not found to be significant as the numbers were small. Among neonates with one or other maternal risk factor, most cases screened were of LSCS, but only 18 newborns (6.8%) developed PAH, which was not significant (P = 0.108). Another risk factor showing association with PAH was twin delivery that too was found to be nonsignificant. Furthermore, out of 13 cases of PIH, only single newborn had PAH.
Table 3: Association of risk factors with PAH on logistic regression analysis

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On further follow-up, out of 54 cases of PAH, only two patients showed persistence of PAH at 6 weeks. One case was of twin pregnancy, delivered by LSCS, and had MSAF and respiratory distress, while the second case was having no maternal risk factor but had MSAF with birth asphyxia and respiratory distress as neonatal risk factor. Thus, on analyzing all these risk factors with logistic regression for the development of PAH, only three risk factors (neonatal) showed P < 0.05. These risk factors were RDS, MSAF, and perinatal asphyxia.

As far as outcome is considered, we found that neonates with risk factors developing PAH have higher percentage of deaths as compared to non-PAH group. This can be clearly seen in [Table 4] as out of 15 cases of MSAF with PAH, 3 (20%) neonates expired, while in the non-PAH group, only 1 case (3%) was lost, though statistically not significant as the numbers were small. This observation becomes more obvious on analyzing the neonates with perinatal asphyxia as out of 18 cases with PAH, 12 (66.4%) neonates expired, while in the non-PAH group, only 1 (4.3%) newborn died out of total 23 cases of perinatal asphyxia.
Table 4: Comparison of outcome at 6 weeks in relation to initial PAH status in neonates with various risk factors

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As shown in [Table 5], the mean PAP in case of perinatal asphyxia, MSAF, and respiratory distress was relatively higher as compared to other risk factors and as expected mean PAP was highest in newborns with perinatal asphyxia with a mean value of 27.98 ± 20.061. At 6 weeks, the mean pressure had fallen to similar range as far as various risk factors are concerned.
Table 5: Risk factors and mean pulmonary artery pressures

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In our study, we have categorized newborns of PAH in three groups on the basis of values of PAPs. We found that 30 cases had PAPs <40 mm of Hg, but more than half of systemic pressure so were considered as cases of mild PAH. Eight cases of moderate PAH showed reversal of shunt and were categorized as cases of PPHN. This is an important observation as even with moderate PAH (as per absolute value of PA pressures) these neonates were having the reversal of shunt.

So its not the absolute value of PAP which is important but altered hemodynamics which can vary from one neonate to another and is dependent on various factors like gestational age. In the last category of severe PAH, only 4 cases had PAH >60 and all had reversal of shunts either at a level of PFO or PDA.


  Discussion Top


This is the first prospective study reporting data about the prevalence of PAH among high-risk neonates from Northern India. The prevalence of PAH was found to be 13% among high-risk neonates during early neonatal period. However, by 6 weeks of age, pulmonary hypertension was found to have resolved on its own among majority of high-risk neonates and persisted only in two neonates (3.7%) who were having multiple risk factors.

Although data on PAH are scarce in our country and globally, many researchers have reported data on PPHN. It was found to be 13.5% in our study. A prospective observational study done in Egypt, published in 2013 by Abdel Mohsen and Amin, found prevalence of PPHN as 5%.[5] Similarly, a study by Bakheet et al. found that PPHN represented nearly 3% (54/1801 cases) of total neonatal care unit admissions and 11% (54/486 cases) of NICU admission.[6]

The cases of PAH were more common among males. Out of 54 cases of PAH, 36 (66.7%) were male and 18 (33.3%) were female. Other studies also found higher prevalence among males. Studies by Razzaq et al. found that 61 out of 79 cases (77.2%) with PPHN were male.[4] Hernández-Díaz et al. also reported more cases of PPHN in males (63.4%) as compared to females (36.6%) in their study.[2]

Various maternal risk factors studied did not show any statistically significant association with PAH in this study. Around 6.8% (18 out of 264) of neonates who had undergone cesarean section had PAH. Overall, among 54 PAH cases, 18 (33.3%) were delivered by LSCS. It is an important observation since 33% of the children who developed PAH were product of cesarean delivery, pointing toward role of normal birth process in transition of PAPs. On the other hand, cesarean delivery can be a confounding factor for PAH as neonates with various other risk factors are likely to be born by cesarean section, as it becomes an indication in high-risk pregnancy with various maternal and neonatal risk factors. This is reflected in the result of logistic regression analysis in our study, in which cesarean delivery was not found to be an independent risk factor for PAH.

Respiratory distress was one of the most common neonatal risk factor, which showed association with development of PAH. In our study, we found that 31% (22 cases out of 71) of neonates with respiratory distress had PAH and while among total PAH cases 40.7% neonates had RDS, this percentage rose to 50% among neonates who developed PPHN. Bakheet et al. and Abdel Mohsen and Amin found that all the cases of PPHN were having respiratory distress (100%).[6],[5] However, Hernández-Díaz et al. and Razzaq et al. found a lower percentage of respiratory distress among PPHN cases (23.4% and 13.9%, respectively).[2],[4]

This is an important observation since some of the neonates were not having features of RDS but still had severe PAH so much, so that it was causing the reversal of shunt. This group of neonates are likely to be missed and can present later in a critical state. RDS can be a cause or manifestation of PAH in a neonates and in preterms there can be delayed physiological fall of pulmonary pressures. Another important aspect was the number of preterms in the RDS group (11.3%), which was much less, and it has been shown by other authors[7] that surfactant deficiency can affect the term and post term babies as well.

In our study, we found that 14.3% of cases of sepsis had PAH, out of which three cases had PPHN (25%). In a retrospective study, Mota et al. found that 8 (10.1%) PPHN cases had sepsis[8] while Hernández Díaz et al. and Razzaq et al. had 32.4% and 29.1% of septic patients among PPHN respectively.[2],[4] However Abdel Mohsen and Amin had higher percentage (43.7%) of septic patients.[5] Bakheet et al. (12.9%) and Roofthooft et al. (11.1%) had found a lower value.[6],[9] Sepsis is regarded as one of the complicating events in the natural history of patients with one or the other risk factor for PAH. The recovery in neonates without PAH was much higher as compared to those who developed PAH as 4 out 9 patients with sepsis with PAH had died.

MSAF is the most common risk factor studied for the development of PPHN. In a study by Choudhary et al., 19% of cases of MSAF developed PPHN.[10] In our study, we found a higher prevalence (30.6%), i.e., 15 out of 49 MSAF cases developed PAH and further two cases had PPHN (16.6%). Retrospective studies by Mota et al. found that out of 77 cases of PPHN, 9 (11.7%) were having MAS. Similarly, Rocha et al. (12.8%) and Roofthooft et al. (4.8%) found MSAF as an important risk factor for PPHN.[9],[11] However, Hernández-Díaz et al. (47.5%), Abdel Mohsen and Amin (50%), Razzaq et al. (35.4%), and Bakheet et al. (35.2%) found a higher percentage than our study.[2],[4],[5],[6] The outcome was poorer in those newborns with MSAF who developed PAH as 3 out 15 neonates did not recover.

Perinatal asphyxia just like sepsis is a complicating event in the natural history of fall in PAPs in a newborn. The patient with asphyxia can have multiple other risk factors such as RDS, sepsis, and electrolyte imbalances, which can complicate the spectrum. In our study, we found that 43.9% of cases of asphyxia had PAH and 8 out of 12 cases of PPHN had perinatal asphyxia (66.6%) and this percentage was highest as compared to other risk factors. Abdel Mohsen and Amin found a lower percentage of 43.7%.[5] Other studies by Hernández-Díaz et al. (21.2%), Bakheet et al. (18.5%), Roofthooft et al. (8.3%), Mota et al. (8%), and Rocha et al. (5.1%) found even a much lower percentage.[2],[6],[8],[9],[11] This has reflected as far as outcome is concerned as 11 out of 18 patients with PAH and asphyxia had expired. Development of PAH in an asphyxiated newborn complicates the picture and can affect the outcome also.

Preterm is also a common risk factor associated with PPHN as shown in many studies. Surfactant deficiency in these newborns causes RDS and complicates their normal fall in PVR causing high PAPs. In our study, we found PAH in 20.5% of preterm newborns and out of 54 PAH cases, 5 cases were preterm (9.25%); however, none of the cases developed reversal of shunt. Rocha et al. found a higher percentage (20.5%) of preterms developing PPHN.[11] Similarly, Razzaq et al. and Roofthooft et al. also found a higher risk of 22.8% and 18.8%, respectively.[4],[9] Preterms form a unique cohort since they tend to have surfactant deficiency and prone to develop RDS which can perpetuate and even delay the normal fall of PAPs. This has reflected in the outcome as preterms having PAH had a far worse outcome as compared to those without PAH though the numbers are less to arrive at significant conclusion. In our study, 25% of VLBW babies had PAH. None of the case developed PPHN. In our study, mortality was higher among PAH cases of VLBW (66.7%) as compared to non-PAH group (33.3%).


  Conclusion Top


Among various risk factors studied, perinatal asphyxia, MSAF, and respiratory distress were found to have significant association with the development of PAH. The PAH can persist beyond 6 weeks if the newborn have multiple risk factors.

Limitations of study

  1. The prevalence of PAH found in our study cannot be used for general population as we had taken selected patients with particular risk factors in our study
  2. The pulmonary pressures mentioned in our study cannot be the true representative of PAP as we had measured this with TR jet and not through invasive method. Furthermore, we had assumed RA pressure as equal to 5 mm of Hg.


What is already known

Risk factors associated with PPHN.

What the study added

The prevalence of PAH in newborn with risk factors and whether development of PAH (a stage prior to PPHN) affects the outcome of these neonates.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Marter LJ. Persistent pulmonary hypertension of the newborn. In: Cloherty JP, Eichenwald EC, Hansen AR, Stark AR. Manual of Neonatal Care. 7th ed. New Delhi: Wolter Kluwer; 2012. p. 435-7.  Back to cited text no. 1
    
2.
Hernández-Díaz S, Van Marter LJ, Werler MM, Louik C, Mitchell AA. Risk factors for persistent pulmonary hypertension of the newborn. Pediatrics 2007;120:e272-82.  Back to cited text no. 2
    
3.
Delaney C, Cornfield DN. Risk factors for persistent pulmonary hypertension of the newborn. Pulm Circ 2012;2:15-20.  Back to cited text no. 3
    
4.
Razzaq A, Iqbal Quddusi A, Nizami N. Risk factors and mortality among newborns with persistent pulmonary hypertension. Pak J Med Sci 2013;29:1099-104.  Back to cited text no. 4
    
5.
Abdel Mohsen AH, Amin AS. Risk factors and outcomes of persistent pulmonary hypertension of the newborn in neonatal intensive care unit of Al-minya university hospital in egypt. J Clin Neonatol 2013;2:78-82.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Bakheet MA, Metwalley KA, Abdel-Raheem AS. Evaluation of persistent pulmonary hypertension of the newborn (PPHN) in Upper Egypt. Egypt Pediatric Assoc Gazette 2013;61:96-9.  Back to cited text no. 6
    
7.
Liu J, Shi Y, Dong JY, Zheng T, Li JY, Lu LL, et al. Clinical characteristics, diagnosis and management of respiratory distress syndrome in full-term neonates. Chin Med J (Engl) 2010;123:2640-4.  Back to cited text no. 7
    
8.
Mota R, Rocha G, Flor-de-Lima F, Guimarães H. Persistent pulmonary hypertension-the neonatal period and evaluation at 2 years of age. J Pediatric Netl Individualized Med (JPNIM) 2016;5:e050119.  Back to cited text no. 8
    
9.
Roofthooft MT, Elema A, Bergman KA, Berger RM. Patient characteristics in persistent pulmonary hypertension of the newborn. Pulm Med 2011;2011:858154.  Back to cited text no. 9
    
10.
Choudhary M, Meena MK, Chhangani N, Sharma D, Choudhary JS, Choudhary SK. To study prevalence of persistent pulmonary hypertension in newborn with meconium aspiration syndrome in western Rajasthan, India: A prospective observational study. J Matern Fetal Neonatal Med 2016;29:324-7.  Back to cited text no. 10
    
11.
Rocha G, Baptista MJ, Guimarães H. Persistent pulmonary hypertension of non cardiac cause in a neonatal intensive care unit. Pulm Med 2012;2012:818971.  Back to cited text no. 11
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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