Growth of late preterm infants fed nutrient-enriched formula to 120 days corrected age-A randomized controlled trial

Karen P Best; Lisa N Yelland; Carmel T Collins; Andrew J McPhee; Geraint B Rogers; Jocelyn Choo; Robert A Gibson; Teresa Murguia-Peniche; Jojy Varghese; Timothy R Cooper; Maria Makrides

doi:10.3389/fped.2023.1146089

Growth of late preterm infants fed nutrient-enriched formula to 120 days corrected age-A randomized controlled trial

Front Pediatr. 2023 May 2:11:1146089. doi: 10.3389/fped.2023.1146089. eCollection 2023.

Authors

Karen P Best^{1

2}, Lisa N Yelland^{1

3}, Carmel T Collins^{1

2}, Andrew J McPhee¹, Geraint B Rogers^{4

5}, Jocelyn Choo^{4

5}, Robert A Gibson^{1

6}, Teresa Murguia-Peniche^{7

8}, Jojy Varghese⁹, Timothy R Cooper⁸, Maria Makrides^{1

2}

Affiliations

¹ Women and Kids Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
² Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
³ School of Public Health, The University of Adelaide, Adelaide, SA, Australia.
⁴ Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
⁵ Infection and Immunity, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia.
⁶ School of Agriculture, Food and Wine, University of Adelaide, Adelaide, SA, Australia.
⁷ School of Medicine, Indiana University, Evansville, IN, United States.
⁸ Medical Sciences, Mead Johnson Nutrition|Reckitt, Evansville, IN, United States.
⁹ Department of Neonatology, Lyell McEwin Hospital, Adelaide, SA, Australia.

Abstract

Objectives: We aimed to compare the effects of nutrient-enriched formula with standard term formula on rate of body weight gain of late preterm infants appropriately grown for gestational age.

Study design: A multi-center, randomized, controlled trial. Late preterm infants (34-37 weeks' gestation), with weight appropriate for gestational age (AGA), were randomized to nutrient enriched formula (NEF) with increased calories (22 kcal/30 ml) from protein, added bovine milk fat globule membrane, vitamin D and butyrate or standard term formula 20 kcal/30 ml (STF). Breastfed term infants were enrolled as an observational reference group (BFR). Primary outcome was rate of body weight gain from enrollment to 120 days corrected age (d/CA). Planned sample size was 100 infants per group. Secondary outcomes included body composition, weight, head circumference and length gain, and medically confirmed adverse events to 365 d/CA.

Results: The trial was terminated early due to recruitment challenges and sample size was substantially reduced. 40 infants were randomized to NEF (n = 22) and STF (n = 18). 39 infants were enrolled in the BFR group. At 120 d/CA there was no evidence of a difference in weight gain between randomized groups (mean difference 1.77 g/day, 95% CI, -1.63 to 5.18, P = 0.31). Secondary outcomes showed a significant reduction in risk of infectious illness in the NEF group at 120 d/CA [relative risk 0.37 (95% CI, 0.16-0.85), P = 0.02].

Conclusion: We saw no difference in rate of body weight gain between AGA late preterm infants fed NEF compared to STF. Results should be interpreted with caution due to small sample size.

Clinical trial registration: The Australia New Zealand Clinical Trials Registry (ACTRN 12618000092291). "mailto:maria.makrides@sahmri.com" maria.makrides@sahmri.com.

Keywords: infant feeding; infant growth; late preterm; nutrient enriched formula; nutrition; preterm.

Grants and funding

Mead Johnson & Company, LLC., 2400 West Lloyd Expressway, Evansville, Indiana 47721-000 funded the study, and monies were paid to the South Australian Health and Medical Research Institute (SAHMRI). Reckitt Benckiser LLC bought Mead Johnson during the study and continued to fund the study. The study was supported by the M.S. McLeod Research Fund, Women's and Children's Hospital Research Foundation (M.S. McLeod Post-Doctoral Fellowship to KPB), and by an NHMRC Fellowship (Principal Research Fellowship 1061704 to MM).