Underweight infants with PH at high risk for eye disease: Study
Inhaled nitric oxide may have 'protective effect,' researchers say
Underweight infants with pulmonary hypertension (PH) are at increased risk of developing retinopathy of prematurity (ROP), a leading cause of childhood blindness, according to a study.
However, the prevalence of severe ROP was 18% lower in PH infants who received treatment with inhaled nitric oxide (iNO). “While iNO is not a treatment for ROP, these findings suggest it may have a protective effect against severe ROP in the context of PH,” the researchers wrote.
The study, “Pulmonary hypertension, inhaled nitric oxide, and retinopathy of prematurity: evidence from the U.S. national database,” was published in Pediatric Research.
When the umbilical cord is clamped after birth, body-wide blood vessel resistance increases, helping the blood flow toward the lungs. Persistent pulmonary hypertension of the newborn, a serious breathing problem, occurs when a baby’s circulatory system doesn’t adapt to breathing outside of the uterus.
In PH, the pressure in the vessels that supply blood to the lungs increases abnormally. Treatment for PH often involves vasodilators, or agents that relax blood vessels. This allows blood to flow more freely to the lungs, potentially decreasing pressure and easing PH symptoms.
Oxygen fluctuations may influence risk
ROP occurs because of abnormal growth in the blood vessels that supply oxygen to the retina, a light-sensitive layer at the back of the eye. It primarily affects preterm infants born before their retinal blood vessels fully develop. Fluctuations in oxygen levels may increase the likelihood of severe ROP.
The researchers said that because infants with PH may experience oxygen fluctuations, they may be at higher risk of ROP. Treatment with iNO, a vasodilator, improves oxygen levels in the lungs and throughout the body, while also controlling vascular activity and blood circulation associated with blood vessel growth. However, “there is very limited data on the association between ROP and PH, and to our knowledge, no studies have specifically investigated the association between iNO and ROP,” the team wrote.
Cleveland Clinic Children’s researchers investigated these relationships in infants weighing less than 1,500 g (3.3 lbs) at birth. Using the U.S. National Inpatient Sample database, the team identified more than one million infants hospitalized with very low birth weight from 2003 through 2020.
Of these, 3% had PH. Several features corresponded to significantly higher odds of infant PH, such as delivery before 28 weeks, being male, and having lung anomalies, congenital heart disease, pulmonary bleeding, and postnatal sepsis (an improper reaction to infection that impairs organ functioning).
PH was a significant risk factor for ROP, corresponding to about 32% higher risk. Severe ROP was more than twice as common in the PH group as in the non-PH group (prevalence of 5.21% vs 1.48%). “This association may be attributed to the overall poorer health and clinical instability of infants with PH, who often also present with additional factors that increase the risk of ROP,” the researchers wrote.
Looking at the study population as a whole, the risk of ROP was higher with iNO treatment, but when looking specifically at the PH group, the prevalence of ROP was not significantly affected by iNO treatment. Severe ROP in infants with PH who received iNO was significantly less common than in PH infants not treated with iNO (4.33% vs. 5.35%).
Similar trends were seen in extremely low birth weight infants, meaning those weighing less than 1,000 g (2.2 lbs).
“While iNO is not a treatment for ROP, these findings suggest it may have a protective effect against severe ROP in the context of PH,” the scientists wrote. “Future prospective studies are needed to evaluate the efficacy and optimal dosing of iNO in mitigating the risk of ROP in infants with PH.”
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