DHA fails to prevent BPD in preterm infants

Docosahexaenoic acid (DHA) is an n-3 long-chain polyunsaturated fatty acid known to modulate inflammation, and that is essential for the healthy growth and functional development of numerous organs and systems in infants including the brain. Previous studies conducted in animals and in humans have suggested that DHA might be helpful in reducing the risk of bronchopulmonary dysplasia (BPD).

However, the results of a very recent study demonstrated that the supplementation of an emulsion containing DHA did not reduce the risk of preterm infants developing BPD compared with infants who received a control emulsion without DHA. On the contrary, those infants who received the DHA-containing emulsion appeared to be at a higher risk of developing BPD compared with controls.

Bronchopulmonary dysplasia is a common disorder seen in preterm infants, and previously it was believed that its incidence could be reduced with the supplementation of DHA in this patient population. In a recent multicenter controlled study,¹ Carmel T. Collins, PhD, South Australian Health and Medical Research Institute, Adelaide, and fellow colleagues aimed to determine the degree to which DHA supplementation reduces the incidence of BPD in preterm infants, as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks’ postmenstrual age.

Related: Broncopulmonary dysplasia, a consequence of survival

The 2-armed study included 1273 infants, born before 29 weeks of gestation, who 72 hours after their first enteral feeding were randomly assigned to receive either an enteral tuna oil emulsion containing 120 mg/mL of DHA to provide 60 mg/kg of body weight per day of DHA (0.17 mL/kg 3 times a day; intervention arm), or a soy oil control emulsion with no additional DHA given at 0.17 mL/kg 3 times a day (prevention arm). Both the intervention and prevention study arms received treatment until the primary outcome of the study, BPD, was achieved, which was defined on a physiologic basis (with the use of oxygen-saturation monitoring in selected infants) at 36 weeks’ postmenstrual age, or discharge home, whichever occurred first. All the patients were stratified according to sex, gestational age (either <27 weeks or 27 to <29 weeks), and center. The baseline characteristics were similar between both treatment study arms.

After imputation and excluding deaths, the results of 1205 infants were available for evaluation, of which 592 and 613 were in the interventional and prevention study groups, respectively. Data showed that a higher percentage of infants who were administered the enteral emulsion containing DHA (291 of 592, or 49.1% by multiple imputation) developed physiologic BPD on a physiologic basis, as compared with those infants who received the control soy emulsion without DHA (269 of 613, or 43.9%). The researchers found that the risk of developing BPD was significantly higher in the DHA interventional study arm compared with the control prevention arm (adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02).

Secondary outcomes of the study included a composite outcome of physiologic BPD or death prior to 36 weeks of postmenstrual age. The researchers found that although the risk was significantly higher among those infants in the DHA study group compared with the control group (52.3% versus 46.4%, respectively; adjusted relative risk [RR], 1.08; 95% CI, 1.00-1.18; P=0.045), this was attributed to the higher risk of BPD. However, data also showed that the risk of death did not differ significantly between groups: death prior to 36 weeks’ postmenstrual age (6.2% DHA vs 4.5% controls; adjusted RR, 1.33; 95% CI, 0.84-2.12; P=0.23) versus death prior to first discharge home (7.9% DHA vs 5.9% controls; adjusted RR, 1.31; 95% CI, 0.88-1.96; P=0.19). Results also showed that BPD based on a clinical definition occurred in 53.2% of the infants in the DHA study arm and in 49.7% of the infants in the control arm (P=0.06). In total, 9 deaths in the DHA group and 8 in the control group were classified as resulting from BPD.

It is believed that diets enriched in DHA can change the inflammatory balance, modulate cell function, and suppress inflammatory responses. Previous studies have suggested that DHA might be helpful in reducing the risk of preterm infants for developing BPD. However, according to Collins and fellow researchers, these studies achieved inconsistent results because they were underpowered to do so, underscoring the importance of conducting adequately powered, randomized clinical trials when investigating novel therapeutic approaches.

Next: Broncopulmonary dysplasia as a complication of prematurity

The researchers concluded that enteral administration of a DHA-containing emulsion dosed at 60 mg/ kg per day does not lower the risk of physiologic BPD when compared with a control emulsion without DHA in preterm infants born before 29 weeks’ gestation. Moreover, DHA supplementation may increase the risk of BPD, begging the need for clinicians to rethink optimal treatment and management in this patient population.

Study limitations included the absence n-6 fatty acid arachidonic acid in the DHA preparation used in this trial, and that BPD is often difficult to define in extremely preterm infants.

REFERENCE

1. Collins CT, Makrides M, McPhee AJ, et al. Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants. N Engl J Med. 2017;376(13):1245-1255.