Prostanoids in pulmonary hypertension of the newborn

Review question

Are prostanoids or their derivatives effective in the treatment of pulmonary hypertension in the newborn?

Background

Persistent pulmonary hypertension of the neonate (PPHN) is a life-threatening condition. Before birth, a baby’s nourishment and oxygen are obtained through the placenta, hence blood circulates differently within the uterus. The baby with PPHN does not change over from fetal to normal newborn circulation. Blood flow is diverted from the lungs due to abnormally high blood pressure in the arteries that go to the lungs. This decreases the body’s supply of oxygen, causing significant injury to the brain and other organs.

The primary problem for newborns is that normal exchange of oxygen in the lung does not occur, so oxygen cannot be delivered to the body. Prostanoids are metabolites of fatty acid called 'arachidonic acid'. They have been shown to relax the lung bed blood vessels, improving blood flow to the lungs and helping with oxygenation in humans and animals. (Prostanoids are a class of drugs that dilate lung blood vessels and may help babies with PPHN. Prostacyclin (PGI₂) and prostaglandin E₁ (PGE₁) are two classes of prostanoids that have been used to treat PPHN in newborn babies.) The safety and effectiveness of these medicines have not been established.

Study characteristics

We searched the literature for studies that used prostanoids or their derivatives for the treatment of PPHN by injection or inhalation. We found no ongoing or completed randomized controlled studies. We found one small study that ended prematurely due to poor enrolment. Currently, no evidence for or against the use of prostanoids in newborn PPHN is available, and we recommend future studies to establish the safety and efficacy of these medicines.

Key results

We found no randomized controlled studies in our search. We found no ongoing studies that may answer our question when their results become available.

Quality of evidence

We could not assess this review question due to lack of eligible trials.

Authors' conclusions: 

Implications for practice

Currently, no evidence shows the use of prostanoids or their analogues as pulmonary vasodilators and sole therapeutic agents for the treatment of PPHN in neonates (age 28 days or less).

Implications for research

The safety and efficacy of different preparations and doses and routes of administration of prostacyclins and their analogues in neonates must be established. Well-designed, adequately powered, randomized, multi-center trials are needed to address the efficacy and safety of prostanoids and their analogues in the treatment of PPHN. These trials should evaluate long-term neurodevelopmental and pulmonary outcomes, in addition to short-term outcomes.

Read the full abstract...
Background: 

Persistent pulmonary hypertension of the newborn (PPHN) is a disease entity that describes a physiology in which there is persistence of increased pulmonary arterial pressure. PPHN is characterised by failure to adapt to a functional postnatal circulation with a fall in pulmonary vascular resistance. PPHN is responsible for impairment in oxygenation and significant neonatal mortality and morbidity. Prostanoids and their analogues may be useful therapeutic interventions due to their pulmonary vasodilatory and immunomodulatory effects.

Objectives: 

Primary objective

• To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing mortality and the need for extracorporeal membrane oxygenation (ECMO) among neonates with PH

Secondary objective

• To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing neonatal morbidity (necrotizing enterocolitis (NEC), chronic lung disease (CLD), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), length of hospital stay, and duration of mechanical ventilation) and improving neurodevelopmental outcomes among neonates with PH

Comparisons

• Prostanoids and their analogues at any dosage or duration used to treat PPHN versus ‘standard treatment without these agents’, placebo, or inhaled nitric oxide (iNO) therapy

• Prostanoids and their analogues at any dosage or duration used to treat refractory PPHN as an ‘add-on’ therapy to iNO versus iNO alone

Search strategy: 

We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9), MEDLINE via PubMed (1966 to 16 September 2018), Embase (1980 to 16 September 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 16 September 2018). We also searched clinical trials databases, conference proceedings of the Pediatric Academic Societies (1990 to 16 September 2018), and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. We contacted authors who have published in this field as discerned from the reference lists of identified clinical trials and review authors' personal files.

Selection criteria: 

Randomized and quasi-randomized controlled trials evaluating prostanoids or their analogues (at any dose, route of administration, or duration) used in neonates at any gestational age less than 28 days' postnatal age for confirmed or suspected PPHN.

Data collection and analysis: 

We used the standard methods of Cochrane Neonatal to conduct a systematic review and to assess the methodological quality of included studies (neonatal.cochrane.org/en/index.html). Three review authors independently assessed the titles and abstracts of studies identified by the search strategy and obtained full-text versions for assessment if necessary. We designed forms for trial inclusion or exclusion and for data extraction. We planned to use the GRADE approach to assess the quality of evidence.

Main results: 

We did not identify any eligible neonatal trials evaluating prostanoids or their analogues as sole agents in the treatment of PPHN.

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