Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk.

Luling Lin, Greg D Gamble, Caroline A Crowther, Frank H Bloomfield, Massimo Agosti, Stephanie A Atkinson, Augusto Biasini, Nicholas D Embleton, Mary S Fewtrell, Fernando Lamy-Filho, Christoph Fusch, Maria L Gianni, H Gozde Kanmaz Kutman, Winston Koo, Ita Litmanovitz, Colin Morgan, Kanya Mukhopadhyay, Erica Neri, Jean-Charles Picaud, Niels Rochow, Paola Roggero, Atul Singhal, Kenneth Stroemmen, Maw J Tan, Francesco M Tandoi, Claire L Wood, Gitte Zachariassen, Jane E Harding

Journal: Nutrients 2022;14(3):418

PMID: 35276786

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Abstract

Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, = 438; aRR 0.94 [0.76, 1.17]; = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, = 1406; aRR 0.76 [0.60, 0.97]; = 0.03), and improved motor scores overall (13 trials, = 1406; adjusted mean difference 1.57 [0.14, 2.99]; = 0.03) and in girls not boys ( = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.

Address: Liggins Institute, University of Auckland, Auckland 1023, New Zealand.; Neonatal Intensive Care Unit, Woman and Child Department, Ospedale Del Ponte, Insubria University, 21100 Varese, Italy.; Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.; Donor Human Milk Bank Italian Association (AIBLUD), 20126 Milan, Italy.; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE2 4AX, UK.; Childhood Nutrition Research Centre, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.; Departamento de Medicina, Universidade Federal do Maranhão (UFMA), São Luís 65080-805, MA, Brazil.; Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.; Department of Pediatrics, Nuremberg General Hospital, Paracelsus Medical University, 90471 Nuremberg, Germany.; Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy.; Department of Clinical Sciences and Community Health, University of Milan, Via Commenda 19, 20122 Milan, Italy.; Department of Neonatology, Bilkent City Hospital, Ankara 06800, Turkey.; Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA.; Department of Neonatology, Meir Medical Center, Kfar Saba 44281, Israel.; Department of Neonatology, Liverpool Women's Hospital, Liverpool L8 7SS, UK.; Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India.; Department of Psychology, University of Bologna, 40100 Bologna, Italy.; Division of Neonatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 69004 Lyon, France.; CarMen Laboratory, INSERM, INRA, Claude Bernard University Lyon 1, 69677 Pierre Benite, France.; Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy.; Department of Nutrition, Institute of Child Health, London WC1N 1EH, UK.; Department of Neonatal Intensive Care, Division of Paediatric and Adolescent Medicine, Rikshospitalet, Oslo University Hospital, 0310 Oslo, Norway.; Department of Developmental Paediatrics, Alder Hey Children's NHS Foundation Trust, Liverpool L12 2AP, UK.; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.; H.C. Andersen Children's Hospital, Odense University Hospital and University of Southern Denmark, 5000 Odense, Denmark.

DOI: 10.3390/nu14030418

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MeSH Terms: Cognition, Cognitive Dysfunction, Dietary Supplements, Female, Humans, Infant, Infant, Newborn, Infant, Small for Gestational Age, Male, Parturition, Pregnancy