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ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 2  |  Page : 63-66

Prevalence and outcome of pulmonary arterial hypertension in newborns with perinatal asphyxia


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

Date of Web Publication10-Apr-2018

Correspondence Address:
Dr. Tauqueer Ahmed
Department of Pediatrics, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_85_17

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  Abstract 


Background: Pulmonary arterial hypertension (PAH) in adults is usually described as mean pulmonary artery pressures of 25 mmHg or more at rest. However, clear cutoff value is not well defined in neonatal age group. Persistent pulmonary hypertension of newborn (PPHN) can be defined as a failure of normal fall in pulmonary vascular resistance at or shortly after birth, leading to shunting of unoxygenated blood into the systemic circulation across foramen ovale or ductus arteriosus. Objective: To study the prevalence and outcome of Pulmonary arterial Hypertension in newborns with perinatal asphyxia. Materials and Methods: This was a prospective observational study in which newborns up to 1 month of age having a history and clinical/laboratorial features of perinatal asphyxia were included in the study. Both inborn and outborn newborns admitted in our Neonatal Intensive Care Unit/neonatal high dependency unit were enrolled in the study. Relevant investigations as and when required for management were done. Echocardiography was done after 48 h of birth, and the findings were noted for the presence of PAH. Second echocardiographic screening was done at 6 weeks of life in all cases. Results: A total number of neonates screened were 41, of which 18 (43.9%) cases had PAH. Out of 18 cases, 8 (44.4%) had a reversal of shunt at the level of patent ductus arteriosus/patent foramen ovale and hence were cases of PPHN. Eleven neonates expired before 6 weeks of age and rest seven cases were screened at 6 weeks. Only one case showed the persistence of PAH at 6 weeks. Conclusion: Perinatal asphyxia was found to have a significant association with the development of PAH, and the mortality was high in neonates with perinatal asphyxia once it is complicated by the development of PAH.

Keywords: Neonates, perinatal asphyxia, pulmonary arterial hypertension, pulmonary hypertension of newborn


How to cite this article:
Ahmed T, Abqari S, Shahab T, Ali SM, Firdaus U, Khan IA. Prevalence and outcome of pulmonary arterial hypertension in newborns with perinatal asphyxia. J Clin Neonatol 2018;7:63-6

How to cite this URL:
Ahmed T, Abqari S, Shahab T, Ali SM, Firdaus U, Khan IA. Prevalence and outcome of pulmonary arterial hypertension in newborns with perinatal asphyxia. J Clin Neonatol [serial online] 2018 [cited 2018 Jun 25];7:63-6. Available from: http://www.jcnonweb.com/text.asp?2018/7/2/63/229671




  Introduction Top


Perinatal asphyxia refers to a condition during the first and second stage of labor in which impaired gas exchange leads to fetal hypoxemia and hypercarbia. The frequency of perinatal asphyxia is approximately 1%–1.5% of live births in developed countries with advanced obstetrics/neonatal care and is inversely related to gestational age and birth weight. It also contributes to 20% of perinatal death.[1] Various factors increase the risk of perinatal asphyxia and include impaired maternal oxygenation, decreases blood flow from mother to placenta, and increased fetal oxygen requirement. Etiology of perinatal asphyxia may be multiple and include maternal factors such as hypertension, hypotension, infection, hypoxia from cardiac/pulmonary disorder, and drug exposure. Perinatal asphyxia affects mainly brain, kidneys, and heart and may manifest as multiorgan dysfunction. It also affects pulmonary system causing increased pulmonary vascular resistance (PVR), leading to persistent pulmonary hypertension of newborn (PPHN), pulmonary hemorrhage, and pulmonary edema.

PPHN can be defined as a failure of PVR to fall at or shortly after birth, leading to shunting of unoxygenated blood into the systemic circulation across foramen ovale or ductus arteriosus.[2] PPHN results from failure of transition of fetal to neonatal circulation that occurs after first breath of newborn (in this disorder, there is sustained PVR which normally falls after newborn starts breathing). With the first breath along with clamping of umbilical cord, there is a marked increase in systemic vascular resistance (SVR) along with fall in pulmonary artery pressure. Circulating biochemical mediators, increased pH, low Co2, and increased arterial oxygen content cause constriction of ductus arteriosus and vasorelaxation of pulmonary circulation. These physiological events raise SVR relative to PVR and cause functional closure of foramen ovale. PPHN physiology mimics the fetal circulation in which PVR exceeds SVR and right to left hemodynamic shunting occurs through foramen ovale and/or ductus arteriosus. Failure to cry or breath at birth may lead to maladaptation of these physiological changes increase the risk of PAH/PPHN.[2] PPHN is suspected when the newborn has persistent desaturation and validated pulmonary hypertension on echocardiography or cardiac catheterization. The burden of PAH in asphyxiated neonates as well as their outcome and long-term prognosis is largely unknown and hence this study was undertaken to find this burden of PAH in asphyxiated newborns.


  Materials and Methods Top


This prospective observational study was done from January 2015 to October 2016 in Neonatal Intensive Care Unit (NICU) and neonatal high dependency unit (HDU) in Department of Pediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh. In this study, newborns up to 30 days of life and having a history/clinical features of severe perinatal asphyxia were included in the safety. Both newborns delivered in our hospital (intramural) and neonates delivered outside our hospital (extramural) were enrolled in the study. Echocardiography was done after 48 h of life for both intramural infants and extramural infants. Second screening was done at 6 weeks for all enrolled neonates.

Methodology

After obtaining informed consent from parents or guardian, a detailed history of the mother and newborn was taken followed by examination of the newborn to identify neonates of perinatal asphyxia. The guidelines laid down by the American Academy of Pediatrics (AAP) and the American College of Obstetrics and Gynecology (ACOG) consider all of the following criteria in diagnosing asphyxia: (i) profound metabolic or mixed acidemia (pH <7.00) in umbilical artery blood sample, if obtained (ii) persistence of an Apgar score of 0–3 for longer than 5 min, (iii) neonatal neurologic sequelae (e.g., seizures, coma, and hypotonia), and (iv) multiple organ involvement (e.g., kidney, lungs, liver, heart, and intestines). For extramural infants, asphyxia was defined as a history of delayed cry, respiration beyond 5 min, seizures in the first 6 h of life, floppiness, and failure to feed. Newborns fulfilling ACOG defined criteria for perinatal asphyxia or history/a clinical feature suggestive of severe perinatal asphyxia was taken up for the study. Initial echocardiography was done after 48 h of birth for newborns of this hospital and at first presentation for outborn patients (age >48 h of life). Follow-up echocardiographic evaluation was done in all neonates at 6 weeks to know persistence of PAH or development of PAH in cases initially having normal scan.

Statistical analysis was done, using the Statistical Package for the Social Science (SPSS 23) for Windows Software. Continuous variables were expressed as means, standard deviation (SD), 95% confidence intervals, frequency, and range. P < 0.05 was considered statistically significant. The univariate analysis was done for computing factor association separately. Logistic regression analysis was done for finding association of dependent factor in relation to other factors.

Inclusion criteria:

  • Newborns with perinatal asphyxia as defined by AAP criteria or relevant history and clinical/laboratorial features of perinatal asphyxia.


Exclusion criteria:

  • Congenital heart disease.


Echocardiography criteria for diagnosis of pulmonary arterial hypertension

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 is a direct indicator of the right ventricular pressure (and therefore PAP) plus right atrial pressure (assumed) was taken as pulmonary artery pressure.

We have taken a newborn having PAH only if her pulmonary artery pressure was more than half of systemic blood pressure (NIBP was measured in every newborn taken for study). We had assumed RA pressure as 5 mmHg.

Grading of PAH:

  • Mild – 25–40 mmHg
  • Moderate – 40–60 mmHg
  • Severe – >60 mmHg.


Patent ductus arteriosus/patent foramen ovale flow

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

Interventricular septum flattening

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


  Results Top


A total number of neonates with severe birth asphyxia screened in our study were 41. Only one case was extramural while rest being intramural. Out of these, 13 (31.8%) cases were males and 28 (68.2%) were females. Eleven neonates expired before follow-up echocardiographic screening at 6 weeks. The mode of delivery was normal vaginal route for 39 (97.8%) cases, while 2 (2.2%) cases were born by LSCS. As far as gestation was concerned, 37 (95%) of the cases were term, 3 preterm, and 1 case was postterm. A total of 18 (43.9%) cases of perinatal asphyxia developed PAH, while out of 18 newborns of PAH, 8 (44.4%) cases had a reversal of shunt too and were designated as cases of PPHN. Oxygen support was required in almost all cases of PAH including ventilatory support in six cases with PPHN. Vasodilators such as oral sildenafil and intravenous milrinone (if cardiac dysfunction present) were given along with other supportive measures (dopamine, dobutamine, dextrose, and calcium infusion.) in these six cases. As far as outcome is considered, 11 of perinatal asphyxia developing PAH expired before follow-up at 6 weeks. On further analysis out of eight cases of PPHN, six cases expired. Only one case showed the persistence of PAH at 6 weeks of age. On comparing the outcome, mortality and morbidity was high in newborns of perinatal asphyxia developing PAH.


  Discussion Top


This prospective observational study was done from January 2015 to October 2016 in a tertiary care hospital of Western Uttar Pradesh, and we found a high prevalence of PAH in asphyxiated neonates. The presence of PPHN was in 8 out of 18 PAH cases. Neonates with PAH showed worse outcome than without PAH cases. This study was limited by its small number of cases enrolled in the study; moreover, the status of antenatal care was not included (which has overall impact on perinatal outcome). Similarly, the socioeconomic status and physical parameters (height and BMI) were not compared. Most studies on PAH or PPHN are retrospective, but we followed our case prospectively till 6 weeks of age, and this was the strength of our study.

The 5 min Apgar score of <3 is a poor indication of cerebral injury. Perinatal asphyxia is a complicating event in the natural history of fall in PA pressures in a newborn. The patient with asphyxia can have multiple other risk factors such as respiratory distress syndrome, sepsis, and electrolyte imbalances which can complicate the spectrum. Birth asphyxia is a common problem in our Indian setups with approximately 1–2 admissions every day in our NICU or neonatal HDU. In our hospital, the total number of deliveries in the year 2016 was 5538, while in month of January, a total of 449 deliveries occurred. Out of total 449 neonates, 11 (2.4%) had severe birth asphyxia. A study published in February 1995 by Rajesh Kumar, “Birth Asphyxia in a Rural Community of North India” found the prevalence of birth asphyxia in 2% cases with case fatality of 74% in asphyxiated cases [Table 1], [Table 2], [Table 3].[3]
Table 1: Demographic profile of newborns

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Table 2: Outcome of neonates with perinatal asphyxia in relation to persistent pulmonary hypertension of newborn

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Table 3: Comparison of outcome in newborns of perinatal asphyxia with and without pulmonary arterial hypertension

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In our study, we found that, out of 41 cases of perinatal asphyxia, 18 (43.9%) had PAH, while 8 (19.5%) neonates developed PPHN. There is a lack of data where prospectively people have studied the development of PAH in neonates with asphyxia, majority of studies were retrospective in which investigators have retrospectively analyzed the risk factors in neonates with PPHN. A study by Abdel Mohsen and Amin found that 43.7% cases of PPHN had severe birth asphyxia.[4] 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%) had found similar incidence.[5],[6],[7],[8],[9] We have prospectively followed a cohort of patients with severe birth asphyxia to look for the development of PAH (a stage before PPHN) and study whether the development of PAH affects the overall outcome in terms of survival. On analyzing the outcome of these neonates, 11 out of 18 patients with PAH and asphyxia had expired, while there was no mortality in the group who did not develop PAH, which was highly significant. A study published in 2013 from Johannesburg, South Africa by N Padayachee and Ballot analyzing the outcome of neonates with perinatal asphyxia found that, out of 447 cases, three had PPHN, but none of the neonate expired on follow-up.[10] In the end, we can say that perinatal asphyxia continues to be a major health problem at birth in neonates, and the prognosis is worsened by the development of PAH and more so by PPHN. Hence, to improve outcome promotion of good antenatal care and institutional delivery may decrease the burden of this problem. In addition, it is desirable to have strategies for early treatment of PAH so that outcome may be improved. At last, further studies are required to substantiate these findings and to make better management strategies in such neonates.


  Conclusion Top


Perinatal asphyxia has a significant association with the development of PAH, and mortality is high in neonates with perinatal asphyxia after the development of PPHN. Neonates of birth asphyxia and having persistence desaturation should have echocardiographic screening to rule out PAH.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hansen AR, Soul JS. Perinatal asphyxia and hypoxic-ischemic encephalopathy. In: Cloherty JP, Eichenwald EC, Hansen AR, Stark AR, editors. Manual of Neonatal Care. 7th ed. New Delhi: Wolter Kluwer; 2012. p. 712.  Back to cited text no. 1
    
2.
Marter LJ. Persistent pulmonary hypertension of the newborn. In: Cloherty JP, Eichenwald EC, Hansen AR, Stark AR, editors. Manual of Neonatal Care. 7th ed. New Delhi: Wolter Kluwer; 2012. p. 435-7.  Back to cited text no. 2
    
3.
Kumar R. Birth asphyxia in a rural community of North India. J Trop Pediatr 1995;41:5-7.  Back to cited text no. 3
[PUBMED]    
4.
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. 4
[PUBMED]  [Full text]  
5.
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. 5
    
6.
Bakheet MA, Metwalley KA, Abdel-Raheem AS. Evaluation of persistent pulmonary hypertension of the newborn (PPHN) in Upper Egypt. Egypt Pediatr Assoc Gazette 2013;61:96-9.  Back to cited text no. 6
    
7.
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. 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 Pediatr Neonatal Individualized Med 2016;5:e050119.  Back to cited text no. 8
    
9.
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. 9
    
10.
Padayachee N, Ballot DE. Outcomes of neonates with perinatal asphyxia at a tertiary academic hospital in Johannesburg, South Africa. South Afr J Child Health 2013;7:89-94.  Back to cited text no. 10
    



 
 
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  [Table 1], [Table 2], [Table 3]



 

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