Concerns about oxidant–antioxidant balance of preterm breast milk: fortify early or lately?

ESPGHAN 54th Annual Meeting , Kobenhavn, Danimarka, 22 - 25 Haziran 2022, cilt.74, sa.36, ss.959-960

O. Aydemir1, Y. Aydemir2, O. Sürmeli Onay1, Z. Sekili1

1Eskisehir Osmangazi University Faculty of Medicine, Department of Paediatrics, Division of

Neonatology, Eskisehir, Turkey, 2Eskisehir Osmangazi University Faculty of Medicine, Department of

Paediatrics, Division of Paediatric Gastroenterology, Eskisehir, Turkey

Objectives and Study: The fast transition from intrauterine to relatively hyperoxic extrauterine

environment exposes newborns to oxidative stress (OS) at birth. Preterm newborns are particularly

vulnerable to OS because of their immature antioxidant defence mechanisms. Breast milk (BM)

contains several antioxidant constituents which may protect newborns from OS. Early in lactation BM

of mothers delivering prematurely has higher levels of protein and many bioactive molecules which are

in parallel to increased requirements of the preterm newborns. However, these levels decrease in the

first few weeks after delivery. Fortification of preterm BM is recommended to provide additional

protein, vitamins and minerals and improve growth in preterm infants. The effects of fortification on the

oxidant–antioxidant profile of BM have not been studied to date. We aimed to evaluate the changes in

oxidant–antioxidant balance of preterm BM after fortification with a commercially available bovine milkbased

fortifier by measuring total antioxidant capacity (TAC) and total oxidant status (TOS).

Methods: A prospective cohort study was conducted. Transitional milk (TM) (6–10 days postpartum)

and mature milk (MM) (>15 days postpartum) samples were collected from the mothers of preterm

infants who were fed with fortified BM. All samples were kept at -80°C until analysis. TAC and TOS

were measured after thawing using colorimetric and automated methods described by Erel before and

after addition of BM fortifier (Aptamil Eoprotin®). The TOS-to-TAC ratio was defined as the oxidative

stress index (OSI), an indicator of the degree of OS.

Results:

Seventy-six BM samples were collected from mothers of 59 preterm infants. Mean gestational age of

the infants were 31.4 ± 2.8 weeks. In TM both TAC (1.032±0.252 mmolTroloxeq/L vs. 2.486±0.729

mmolTroloxeq/L, p<0.001) and TOS (1.78 ± 1.26 μmolH2O2/L vs. 5.5±2.85 μmolH2O2/L, p<0.001)

increased significantly after fortification. OSI was higher in fortified TM (0.180±0.138 AU vs.

0.273±0.208 AU, p=0.032). TAC and TOS increased significantly also in MM after fortification (0.917±

0.221 mmolTroloxeq/L vs 2.804 ± 0.681 mmolTroloxeq/L, p<0.001 and 2.15 ± 1.76 μmolH2O2/L vs

7.02 ± 2.99 μmolH2O2/L, p<0.001, respectively). However, OSI did not change significantly after

fortification in MM (0.248 ± 0.215 AU vs. 0.253 ± 0.116 AU, p=0.39) (figure).

Conclusions: There is no consensus on the best time to introduce fortification, and clinical practice

varies widely. It is common to add fortifier to BM after full enteral feeds are reached which generally

corresponds to mature milk stage of lactation. Randomised controlled trials reported that early

fortification, at an enteral feed volume of ≤100 mL or < 7 days postnatal age, is safe in terms of

feeding intolerance, necrotizing enterocolitis, and sepsis, but does not improve growth outcomes

significantly. We showed that in mature preterm BM oxidant–antioxidant balance is preserved after

fortification. However, in TM increase in TOS was greater than TAC after fortification which resulted in

a higher OSI. Safety of fortification of transitional BM requires further investigation regarding the OS related morbidities in preterm newborns.