Low Birth Weight Raises PH Risk in Premature Infants Needing Oxygen

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by Steve Bryson, PhD |

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Low birth weight has been linked to an increased risk of pulmonary hypertension (PH) in premature infants needing oxygen therapy for at least 28 days, an analysis revealed.

Additionally, the failure, after birth, of the blood vessels of the heart to close — before birth, they’re normally open to allow blood flow to bypass the lungs — also was associated with a greater PH risk among these premature infants, according to researchers.

Noting that “the diagnosis of PH depended entirely on echocardiography” — a non-invasive heart scan not done until “at least 28 days after birth” among the more than 80 infants in this study — the investigators said implementing additional screening could help in treating premature babies with PH.

“We suggest that a more active screening echocardiogram may be needed for diagnosing PH” in very low birth-weight, premature infants with blood vessel problems, the team wrote.

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The study, “Risk factors and clinical characteristics for bronchopulmonary dysplasia associated pulmonary hypertension in very-low-birth-weight infants,” was published in the journal BMC Cardiovascular Disorders.

Due to advances in oxygen therapy and other treatment approaches for premature babies, their survival rate — especially among those with very low or extremely low birth weights — has increased.

Bronchopulmonary dysplasia or BPD, characterized by damage to the airways and the tiny air sacs (alveoli) of the lung, is a chronic lung disease that can affect these newborns. In some cases, BPD can thicken the arteries that supply the lungs, resulting in high blood pressure or pulmonary hypertension.

While women ages 20–40 are most at risk for pulmonary hypertension, the disease can occur at any age, even among newborns.

To date, few studies exploring the clinical characteristics and outcomes of PH in infants with very low birth weights with BPD have been conducted.

“Little is known about the risk factors for PH in [very low birth weight infants] with BPD, making it difficult to formulate screening strategies to identify PH in these infants,” the researchers wrote.

To learn more, scientists at Shanghai Children’s Hospital, in China, examined the medical records of very low birth weight infants with BPD treated in the neonatal intensive care unit during a four-year period. They aimed to determine the characteristics of PH associated with BPD in these infants, with a goal of establishing risk factors for pulmonary hypertension in this patient population.

The definition of BPD severity the team used was based on that proposed by the National Institute of Child Health and Human Development, with at least 28 days of oxygen therapy in all cases.

Data was collected and analyzed from 83 premature infants with BPD, 55% of them male, with a mean gestational age of 28.3 weeks or about 6.5 months. Of note, gestational age is the term commonly used during pregnancy to describe how far along the usual 40 weeks duration the expectant parent is.

The infants were then divided into two groups: 18 with PH and 65 without the disease, based on the echocardiogram screens. Additional information collected was data on birth history, prenatal characteristics, maternal medical history, postpartum medical history, and various complications.

The analysis revealed that the birth weight of BPD infants with PH was significantly lower than that of premature infants without PH.

There were, however, no significant differences related to sex, duration of gestation, small size for gestational age, and Apgar score after five minutes. The Apgar score is a global measure of newborn health based on breathing, heart rate, muscle tone, reflexes, and skin color.

An examination of maternal medical history found no significant differences between the two groups regarding the birth parent’s age, cesarean sections, gestational high blood pressure or diabetes, placental separation from the uterus, and preterm premature rupture of membranes.

Compared with non-PH infants, the proportion of babies with moderate to severe BPD and PH did not increase significantly. Still, these babies had a longer duration of oxygen therapy and mechanical ventilation, both invasive and non-invasive. The proportion of those with a below-normal oxygen level in their blood did not differ between the two groups.

After the PH diagnosis, two infants with the disease died versus one from the non-PH group. This difference was not found to be statistically significant.

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Patent ductus arteriosus or PDA is a condition in which the opening between the two major blood vessels leading from the heart fails to close shortly after birth, as it should. PDA is normal in the womb, and allows blood to bypass the unborn baby’s developing lungs. However, the incidence of PDA among the infants in this study was found to be significantly higher among those with PH as compared with babies without the disease.

Surgical treatment of PDA to close the opening was performed in four study participants, all of whom were in the PH group. Of the 22 patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) for PDA, nine were in the PH group.

There were no significant differences in other echocardiogram results for the PH group as compared with the non-PH group.

Statistical analysis including individual clinical characteristics found an increased risk of PH due to low birth weight, longer duration of oxygen therapy, longer duration of mechanical ventilation, and the presence of PDA.

When all clinical characteristics were combined in the analysis, low birth weight and the presence of PDA were specific risk factors PH in premature infants with BPD.

“In conclusion, we found that [birth weight], PDA, duration of oxygen therapy and duration of mechanical ventilation were risk factors for BPD-PH,” the scientists concluded, suggesting that “a more active screening echocardiogram” may be needed to improve diagnoses.

“Further large cohort studies will be required to identify other risk factors for the development of PH in [very low birth weight infants] with BPD,” they added.

As for study limitations, the researchers noted a lack of confirmation of PH by the gold standard method — right heart catheterization — because it was not practical in this patient population. The researchers also pointed out that echocardiography was not done until the infants were past either 36 weeks’ corrected gestation or before discharge to home.