Mediation Analysis to Untangle Opposing Associations of High-Dose Docosahexaenoic Acid With IQ and Bronchopulmonary Dysplasia in Children Born Preterm.

Autor:	Sullivan TR; SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; School of Public Health, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia., Gould JF; SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; School of Psychology, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.; Discipline of Paediatrics, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia., Bednarz JM; SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia., McPhee AJ; SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; Neonatal Services, Women's and Children's Hospital, North Adelaide, South Australia, Australia., Gibson R; SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; School of Agriculture, Food and Wine, Waite Campus, University of Adelaide, Adelaide, South Australia, Australia., Anderson PJ; School of Psychological Sciences, Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, Australia.; Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Best KP; SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; Discipline of Paediatrics, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia., Sharp M; King Edward Memorial Hospital, Subiaco, Western Australia, Australia.; Newborn Medicine, Centre for Neonatal Research and Education, University of Western Australia, Perth, Western Australia, Australia., Cheong JLY; Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Newborn Research, Royal Women's Hospital, Parkville, Victoria, Australia.; Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia., Opie GF; Neonatal Services, Mercy Hospital for Women, Melbourne, Victoria, Australia., Travadi J; Department of Child Health, Neonatal Intensive Care Unit, Waikato Hospital, Waikato, Hamilton, New Zealand.; Newborn Services, John Hunter Children's Hospital, Newcastle, New South Wales, Australia.; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia., Davis PG; Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Newborn Research, Royal Women's Hospital, Parkville, Victoria, Australia.; Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia., Simmer K; Newborn Medicine, Centre for Neonatal Research and Education, University of Western Australia, Perth, Western Australia, Australia., Collins CT; SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; Discipline of Paediatrics, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia., Doyle LW; Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Newborn Research, Royal Women's Hospital, Parkville, Victoria, Australia.; Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia., Makrides M; SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; Discipline of Paediatrics, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2023 Jun 01; Vol. 6 (6), pp. e2317870. Date of Electronic Publication: 2023 Jun 01.
DOI:	10.1001/jamanetworkopen.2023.17870
Abstrakt:	Importance: High-dose omega-3 docosahexaenoic acid (DHA) supplementation of children born at less than 29 weeks' gestation has been shown to improve IQ despite increasing the risk of bronchopulmonary dysplasia (BPD). Given that BPD is associated with poorer cognitive outcomes, it is unclear whether the increased risk of BPD with DHA supplementation is associated with decreased benefit to IQ. Objective: To investigate whether the increased risk of BPD with DHA supplementation was associated with diminished IQ benefit. Design, Setting, and Participants: This cohort study used data collected from a multicenter, blinded, randomized controlled trial of DHA supplementation in children born at less than 29 weeks' gestation. Participants were recruited from 2012 to 2015 and followed up until 5 years' corrected age. Data were analyzed from November 2022 to February 2023. Interventions: Enteral DHA emulsion (60 mg/kg/d, to match the estimated in-utero requirement) or a control emulsion from the first 3 days of enteral feeds until 36 weeks' postmenstrual age or discharge home. Main Outcomes and Measures: Physiological BPD was assessed at 36 weeks' postmenstrual age. IQ was assessed at 5 years' corrected age using the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition; children from the 5 highest-recruiting Australian hospitals were assessed. The total effect of DHA supplementation on IQ was divided into direct and indirect effects using mediation analysis, with BPD as the presumed mediating variable. Results: Among 656 surviving children from hospitals involved in IQ follow-up (mean [SD] gestational age at birth, 26.8 [1.4] weeks; 346 males [52.7%]), there were 323 children with DHA supplementation and 333 children in the control group. Mean IQ was 3.45 points (95% CI, 0.38 to 6.53 points) higher in the DHA group than the control group, despite an increase in the risk of BPD (160 children [49.7%] vs 143 children [42.8%] with BPD). The indirect effect of DHA on IQ via BPD was not statistically significant (-0.17 points; 95% CI, -0.62 to 0.13 points), with most of the effect of DHA on IQ occurring independently of BPD (direct effect = 3.62 points; 95% CI, 0.55 to 6.81 points). Conclusions and Relevance: This study found that associations of DHA with BPD and IQ were largely independent. This finding suggests that if clinicians supplement children born preterm with high-dose DHA, any resulting increase in BPD risk would not be associated with meaningful reductions in the IQ benefit.
Databáze:	MEDLINE
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