Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants

Carmel T. Collins, Maria Makrides, Andrew J. McPhee, Thomas R. Sullivan, Peter G. Davis, Marta Thio, Karen Simmer, Victor S. Rajadurai, Javeed Travadi, Mary J. Berry, Helen G. Liley, Gillian F. Opie, Kenneth Tan, Kei Lui, Scott A. Morris, Jacqueline Stack, Michael J. Stark, Mei Chien Chua, Pooja A. Jayagobi, James Holberton & 4 others Srinivas Bolisetty, Ian R. Callander, Deborah L. Harris, Robert A. Gibson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. Methods: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. Results: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P = 0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P = 0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P = 0.06). Conclusions: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk.

Original languageEnglish
Pages (from-to)1245-1255
Number of pages11
JournalNew England Journal of Medicine
Volume376
Issue number13
DOIs
Publication statusPublished - 30 Mar 2017

Cite this

Collins, C. T., Makrides, M., McPhee, A. J., Sullivan, T. R., Davis, P. G., Thio, M., ... Gibson, R. A. (2017). Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants. New England Journal of Medicine, 376(13), 1245-1255. https://doi.org/10.1056/NEJMoa1611942
Collins, Carmel T. ; Makrides, Maria ; McPhee, Andrew J. ; Sullivan, Thomas R. ; Davis, Peter G. ; Thio, Marta ; Simmer, Karen ; Rajadurai, Victor S. ; Travadi, Javeed ; Berry, Mary J. ; Liley, Helen G. ; Opie, Gillian F. ; Tan, Kenneth ; Lui, Kei ; Morris, Scott A. ; Stack, Jacqueline ; Stark, Michael J. ; Chua, Mei Chien ; Jayagobi, Pooja A. ; Holberton, James ; Bolisetty, Srinivas ; Callander, Ian R. ; Harris, Deborah L. ; Gibson, Robert A. / Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 13. pp. 1245-1255.
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title = "Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants",
abstract = "Background: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. Methods: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. Results: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1{\%} by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9{\%}) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95{\%} confidence interval [CI], 1.02 to 1.25; P = 0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3{\%} of the infants in the DHA group and in 46.4{\%} of the infants in the control group (adjusted relative risk, 1.11; 95{\%} CI, 1.00 to 1.23; P = 0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2{\%} of the infants in the DHA group and in 49.7{\%} of the infants in the control group (P = 0.06). Conclusions: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk.",
author = "Collins, {Carmel T.} and Maria Makrides and McPhee, {Andrew J.} and Sullivan, {Thomas R.} and Davis, {Peter G.} and Marta Thio and Karen Simmer and Rajadurai, {Victor S.} and Javeed Travadi and Berry, {Mary J.} and Liley, {Helen G.} and Opie, {Gillian F.} and Kenneth Tan and Kei Lui and Morris, {Scott A.} and Jacqueline Stack and Stark, {Michael J.} and Chua, {Mei Chien} and Jayagobi, {Pooja A.} and James Holberton and Srinivas Bolisetty and Callander, {Ian R.} and Harris, {Deborah L.} and Gibson, {Robert A.}",
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Collins, CT, Makrides, M, McPhee, AJ, Sullivan, TR, Davis, PG, Thio, M, Simmer, K, Rajadurai, VS, Travadi, J, Berry, MJ, Liley, HG, Opie, GF, Tan, K, Lui, K, Morris, SA, Stack, J, Stark, MJ, Chua, MC, Jayagobi, PA, Holberton, J, Bolisetty, S, Callander, IR, Harris, DL & Gibson, RA 2017, 'Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants' New England Journal of Medicine, vol. 376, no. 13, pp. 1245-1255. https://doi.org/10.1056/NEJMoa1611942

Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants. / Collins, Carmel T.; Makrides, Maria; McPhee, Andrew J.; Sullivan, Thomas R.; Davis, Peter G.; Thio, Marta; Simmer, Karen; Rajadurai, Victor S.; Travadi, Javeed; Berry, Mary J.; Liley, Helen G.; Opie, Gillian F.; Tan, Kenneth; Lui, Kei; Morris, Scott A.; Stack, Jacqueline; Stark, Michael J.; Chua, Mei Chien; Jayagobi, Pooja A.; Holberton, James; Bolisetty, Srinivas; Callander, Ian R.; Harris, Deborah L.; Gibson, Robert A.

In: New England Journal of Medicine, Vol. 376, No. 13, 30.03.2017, p. 1245-1255.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants

AU - Collins, Carmel T.

AU - Makrides, Maria

AU - McPhee, Andrew J.

AU - Sullivan, Thomas R.

AU - Davis, Peter G.

AU - Thio, Marta

AU - Simmer, Karen

AU - Rajadurai, Victor S.

AU - Travadi, Javeed

AU - Berry, Mary J.

AU - Liley, Helen G.

AU - Opie, Gillian F.

AU - Tan, Kenneth

AU - Lui, Kei

AU - Morris, Scott A.

AU - Stack, Jacqueline

AU - Stark, Michael J.

AU - Chua, Mei Chien

AU - Jayagobi, Pooja A.

AU - Holberton, James

AU - Bolisetty, Srinivas

AU - Callander, Ian R.

AU - Harris, Deborah L.

AU - Gibson, Robert A.

PY - 2017/3/30

Y1 - 2017/3/30

N2 - Background: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. Methods: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. Results: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P = 0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P = 0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P = 0.06). Conclusions: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk.

AB - Background: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. Methods: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. Results: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P = 0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P = 0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P = 0.06). Conclusions: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk.

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DO - 10.1056/NEJMoa1611942

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Collins CT, Makrides M, McPhee AJ, Sullivan TR, Davis PG, Thio M et al. Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants. New England Journal of Medicine. 2017 Mar 30;376(13):1245-1255. https://doi.org/10.1056/NEJMoa1611942