Reply to “Exclusive human milk diet and severe intraventricular hemorrhage”

Abstract

Dr. Kumar brings up several interesting points in his review of our recent publication, “Exclusive human milk diet reduces incidence of severe intraventricular hemorrhage (IVH) in extremely low birth weight infants”, published earlier by the journal [1]. We would like to address his concerns and hope to provide more clarity to our discussion. Dr. Kumar points out the difference in the timing and pathophysiology between severe IVH and periventricular leukomalacia (PVL). Indeed, head ultrasound, the most widely used diagnostic modality, identifies IVH as an “early” event, while PVL is usually noticed later. IVH and PVL often cooccur in preterm infants, especially when the IVH is severe (grade 3 or 4), though a debate still exists as to whether IVH and PVL are two completely different entities or a continuum of the same pathophysiological processes [2]. We propose that colostrum oral care (COC) from the first 24 h of life confers the early protection against IVH and an ongoing exclusive human milk diet (EHM) exerts its beneficial protective effects against PVL. Both interventions stabilize the blood brain barrier by downregulating the inflammatory cascade, inhibiting effects of ischemic injury, and improving myelination and connectivity. We elected to assess the combined outcome of IVH/PVL due to the infrequency of the individual entities, due to the fact that IVH may be a trigger of brain changes which predispose to PVL and because of the significant impact both have on later neurodevelopmental outcome. We did not find a statistical difference in the individual incidence of IVH only, PVL only, or both IVH and PVL, likely due to the infrequency of these events. A larger sample size would be needed to evaluate this independent difference. The practice in our NICU is to perform HUS on day of life 1–3, day 7, day 30, prior to discharge and additionally for clinical concerns. The infants in the EHM and nonEHM group had severe IVH at similar times [median (IQR) DOL 6 (1–14) vs 2 (2–5), respectively]. All infants in the EHM group received COC with mothers’ own colostrum or PDHM starting in the first 24 h of life and continued until the first oral feed. Enteral feeds in both groups were started at similar times [median (IQR) DOL 2 (1–12) vs 2 (2–5), respectively]. Thus the only early difference in the management was COC in the EHM group. The observational, retrospective nature of our study did not allow us to determine the exact timing of PVL or if a dose response to human milk or bovine protein exposure existed. The protective factors in breast milk, such as VEGF, EGF, TGF-β, and mRNA, are potent biological molecules and highly concentrated in colostrum, which allows them to exert protective action despite minimal milk intake. In support of this, a Keller et al., found that VLBW infants who received drops of intranasal breast milk after IVH had less progressive hydrocephalus and less surgical interventions than infants who did not receive intranasal breast milk [3]. Dr. Kumar also noted concern that the large time frame in which our study was conducted may have inadvertently affected the observed outcome by time associated changes in practice. However, our NICU did not implement any other changes in clinical practice aside implementation of an EHM diet during this * Amanda Rahman [email protected]