Pulmonary hypertension linked to worse bronchopulmonary dysplasia outcomes in infants

Key takeaways:

• In the setting of bronchopulmonary dysplasia, pulmonary hypertension appeared associated with lengthier hypoxemic events.
• These prolonged events were linked to death in infants with pulmonary hypertension.

Among preterm infants with bronchopulmonary dysplasia, pulmonary hypertension appeared linked to extended intermittent hypoxemia events and death, according to results published in American Journal of Respiratory and Critical Care Medicine.

“Given the limited ability of clinicians to predict disease severity and monitor the impact of therapeutic strategies in limiting bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) severity, defining intermittent hypoxemia characteristics in individual infants may permit a range of applications for the detection and management of PH in this high-risk population on further validation in an independent cohort,” Samuel J. Gentle, MD, assistant professor in the division of neonatology in the department of pediatrics at The University of Alabama at Birmingham, and colleagues wrote.

In a retrospective, observational matched case-control study, Gentle and colleagues evaluated 40 extremely preterm infants with BPD-PH (median gestational age, 24.4 weeks; 53% boys; median birth weight, 589 g) — with PH determined based on ECG conducted 28 days after birth — and 40 extremely preterm infants with BPD and no PH (median gestational age, 24.6 weeks; 55% boys; median birth weight, 648 g) all born between 2018 and 2020 to assess differences in intermittent hypoxemia patterns between the two groups. Researchers studied the infants from 22 weeks 0 days to 28 weeks 6 days.

Further, researchers conducted receiver operating characteristic (ROC) analysis to determine whether various factors related to hypoxemia, such as cumulative hypoxemia, desaturation frequency and duration of intermittent hypoxemia events 1 week prior to ECG could distinguish those infants eventually diagnosed with PH.

Findings

Although the incidence of intermittent hypoxemia events and cumulative length of hypoxemia were comparable between the two groups, researchers found longer hypoxemic events for desaturations less than 80% among those with PH vs. those without PH (median, 7 seconds vs. 6 seconds; P = .03), as well as for desaturations less than 70% (median, 105 seconds vs. 58 seconds; P = .008).

Thirteen infants from the group with PH died, and these infants experienced prolonged hypoxemic events below 70% compared with survivors (145 seconds vs. 72 seconds; P = .01). Length of hypoxemic events below 80% did not significantly differ among those with PH who died and who survived, according to researchers.

Compared with infants without PH, infants with PH had double the likelihood for events longer than 1 minute, experiencing an average of seven such events a day compared with only 3.5 in the control group.

Notably, when including the length of hypoxemic events below 70%, researchers observed an area under the ROC curve of 0.71 for diagnosis of BPD-PH and 0.77 for survival in BPD-PH.

In a regression model that accounted for birth weight, patent ductus arteriosus, late-onset sepsis and FiO₂, the length of intermittent hypoxemia events for desaturations below 80% or 70% were not significant between those with and without PH; however, researchers did observe a significant difference between infants with PH who died and who survived when evaluating events below 70% (adjusted OR = 1.22; 95% CI, 1-1.47).

“The predictive use of intermittent hypoxemia characteristics was only retained within cases for the outcome of mortality following adjustment for baseline differences, suggesting that intermittent hypoxemia parameters may have greater use in predicting outcomes in infants with established BPD-PH rather than establishing the presence of BPD-PH,” Gentle and colleagues wrote.

Future studies

Even though more studies are required to evaluate how intermittent hypoxemia is related to PH in infants with BPD, a finding similar to one by Gentle and colleagues has been reported in prior work, according to an accompanying editorial by Thomas M. Raffay, MD, neonatologist at University Hospitals Rainbow Babies & Children’s Hospital and instructor of pediatrics at Case Western Reserve University School of Medicine, and Erik A. Jensen, MD, attending neonatologist at Children’s Hospital of Philadelphia.

“Gentle and colleagues found that infants with PH vs. those without PH were twice as likely to experience hypoxemic events lasting longer than 60 seconds,” Raffay and Jensen wrote. “This finding is noteworthy, as the authors indicate, because a post hoc analysis of data from COT (Canadian Oxygen Trial) suggested that exposure to hypoxemic events lasting longer than 1 minute, but not shorter events, during the first 2 to 3 months of age was associated with increased risk of death or developmental disability.

“Future studies will need to continue to investigate how the depth, duration and cumulative exposure to hypoxemia may relate to disease risk in preterm infants and optimal oximeter settings to reliably measure intermittent hypoxemia,” Raffay and Jensen added.

Reference:

• Raffay TM, et al. Am J Respir Crit Care Med. 2023;doi:10.1164/rccm.202212-2290ED.