Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: A follow-up of a randomised controlled trial

C.T. Collins; R.A. Gibson; P.J. Anderson; A.J. Mcphee; T.R. Sullivan; J.F. Gould; P.F. Ryan; L. Doyle; P.G. Davis; J.E. Mcmichael; Noel French; P.B. Colditz; Karen Simmer; S.A. Morris; M. Makrides

doi:10.1136/bmjopen-2014-007314

Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: A follow-up of a randomised controlled trial

C.T. Collins, R.A. Gibson, P.J. Anderson, A.J. Mcphee, T.R. Sullivan, J.F. Gould, P.F. Ryan, L. Doyle, P.G. Davis, J.E. Mcmichael, Noel French, P.B. Colditz, Karen Simmer, S.A. Morris, M. Makrides

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Abstract

Objective

To determine if improvements in cognitive outcome detected at 18 months’ corrected age (CA) in infants born <33 weeks’ gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood.

Design

Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital.

Setting

Five Australian tertiary hospitals from 2008 to 2013.

Participants

626 of the 657 participants randomised between 2001 and 2005 were eligible to participate.

Interventions

High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2–4 days until term CA.

Primary outcome

Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted.

Results

604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital −0.3, 95% CI −2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet.

Conclusions

Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years’ CA.

Original language	English
Pages (from-to)	1-12
Journal	BMJ Open
Volume	5
Issue number	3
DOIs	https://doi.org/10.1136/bmjopen-2014-007314
Publication status	Published - 18 Mar 2015

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Collins, C. T., Gibson, R. A., Anderson, P. J., Mcphee, A. J., Sullivan, T. R., Gould, J. F., Ryan, P. F., Doyle, L., Davis, P. G., Mcmichael, J. E., French, N., Colditz, P. B., Simmer, K., Morris, S. A., & Makrides, M. (2015). Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: A follow-up of a randomised controlled trial. BMJ Open, 5(3), 1-12. https://doi.org/10.1136/bmjopen-2014-007314

@article{ab8dd9ec7cda44868203cf4722f5934e,

title = "Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: A follow-up of a randomised controlled trial",

abstract = "Objective To determine if improvements in cognitive outcome detected at 18 months{\textquoteright} corrected age (CA) in infants born <33 weeks{\textquoteright} gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood. Design Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital. Setting Five Australian tertiary hospitals from 2008 to 2013. Participants 626 of the 657 participants randomised between 2001 and 2005 were eligible to participate. Interventions High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2–4 days until term CA. Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted. Results 604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital −0.3, 95% CI −2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet. Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years{\textquoteright} CA. ",

author = "C.T. Collins and R.A. Gibson and P.J. Anderson and A.J. Mcphee and T.R. Sullivan and J.F. Gould and P.F. Ryan and L. Doyle and P.G. Davis and J.E. Mcmichael and Noel French and P.B. Colditz and Karen Simmer and S.A. Morris and M. Makrides",

year = "2015",

month = mar,

day = "18",

doi = "10.1136/bmjopen-2014-007314",

language = "English",

volume = "5",

pages = "1--12",

journal = "BMJ Open",

issn = "2044-6055",

publisher = "John Wiley & Sons",

number = "3",

}

Collins, CT, Gibson, RA, Anderson, PJ, Mcphee, AJ, Sullivan, TR, Gould, JF, Ryan, PF, Doyle, L, Davis, PG, Mcmichael, JE, French, N, Colditz, PB, Simmer, K, Morris, SA & Makrides, M 2015, 'Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: A follow-up of a randomised controlled trial', BMJ Open, vol. 5, no. 3, pp. 1-12. https://doi.org/10.1136/bmjopen-2014-007314

TY - JOUR

T1 - Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: A follow-up of a randomised controlled trial

AU - Collins, C.T.

AU - Gibson, R.A.

AU - Anderson, P.J.

AU - Mcphee, A.J.

AU - Sullivan, T.R.

AU - Gould, J.F.

AU - Ryan, P.F.

AU - Doyle, L.

AU - Davis, P.G.

AU - Mcmichael, J.E.

AU - French, Noel

AU - Colditz, P.B.

AU - Simmer, Karen

AU - Morris, S.A.

AU - Makrides, M.

PY - 2015/3/18

Y1 - 2015/3/18

N2 - Objective To determine if improvements in cognitive outcome detected at 18 months’ corrected age (CA) in infants born <33 weeks’ gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood. Design Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital. Setting Five Australian tertiary hospitals from 2008 to 2013. Participants 626 of the 657 participants randomised between 2001 and 2005 were eligible to participate. Interventions High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2–4 days until term CA. Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted. Results 604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital −0.3, 95% CI −2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet. Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years’ CA.

AB - Objective To determine if improvements in cognitive outcome detected at 18 months’ corrected age (CA) in infants born <33 weeks’ gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood. Design Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital. Setting Five Australian tertiary hospitals from 2008 to 2013. Participants 626 of the 657 participants randomised between 2001 and 2005 were eligible to participate. Interventions High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2–4 days until term CA. Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted. Results 604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital −0.3, 95% CI −2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet. Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years’ CA.

U2 - 10.1136/bmjopen-2014-007314

DO - 10.1136/bmjopen-2014-007314

M3 - Article

C2 - 25787990

SN - 2044-6055

VL - 5

SP - 1

EP - 12

JO - BMJ Open

JF - BMJ Open

IS - 3

ER -

Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: A follow-up of a randomised controlled trial

Abstract

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