BackgroundHigh feed osmolality (or osmolarity) is often suggested to be linked with adverse gastrointestinal events in preterm infants.AimTo systematically review the literature on milk feed osmolality and adverse gastrointestinal events in newborn and low birthweight infants and animals.MethodsMEDLINE, Embase, CAB Abstracts, Current Contents, BIOSIS Previews and SciSearch were searched from inception to May 2018 to identify potentially relevant studies. Inclusion criteria: randomised controlled or observational studies of newborn and low birthweight infants or animals investigating the effects of milk-based feeds with different osmolalities. Only full-text, English-language papers were included.ResultsTen human and six animal studies met the inclusion criteria. Of human studies, seven reported no differences in adverse events with varying feed osmolalities; one reported delayed gastric emptying with feed osmolarity of 539 mOsm/L compared with lower levels; one reported higher necrotising enterocolitis (NEC) incidence with feed osmolarity of 650 mOsm/L compared with 359 mOsm/L; one found higher NEC incidence with the lowest feed osmolality (326 mOsm/kg compared with 385 mOsm/kg). Of animal studies, two reported delayed gastric emptying with feed osmolarity >624 mOsm/L, one reported decreased survival due to dehydration with dietary osmolarities ≥765 mOsmol/L and none reported increased NEC incidence with differing feed osmolalities. No clear mechanisms were found, and diet composition differences limited the interpretations regarding the independent impact of osmolality.ConclusionsThere is no consistent evidence that differences in feed osmolality in the range 300–500 mOsm/kg are associated with adverse gastrointestinal symptoms in neonates.