Background: Despite advances in neonatal intensive care, male infants born very or extremely preterm continue to show worse long-term outcomes compared to female counterparts. There is increasing evidence that preterm males respond differently to enteral nutrition interventions compared to females. As undernutrition and extrauterine growth restriction in preterm infants are known contributors to poor long-term outcomes and neurodevelopment, understanding the sex-specific differences in response to enteral feeding volume optimization would help address the differences in outcomes between sexes.
Objective: To determine the sex-specific response to an aggressive enteral feeding volume increase guideline initiated between 31 0/7 and 34 0/7 weeks postmenstrual age (PMA) in very and extremely preterm infants.
Methods: This is a single center retrospective analysis at the University of Massachusetts Medical Center neonatal intensive care unit (NICU) between the period of October 2017 and November 2020. All appropriate for gestational age and large for gestational age infants born less than or equal to 32 0/7 weeks who met criteria for and followed the nutrition guideline of increasing enteral feeding volumes from 150 – 160 to 170 – 180 millimeters per kilogram per day during 31 0/7 to 34 0/7 weeks PMA were included. Data including gender, race, necrotizing enterocolitis (NEC) rate, bronchopulmonary dysplasia (BPD) rate, weekly weight from birth to discharge before (20 months) and after (36 months) guideline implementation were collected on 373 infants. Changes in weight were reported by weekly z-score changes using PediTools. Retrospective analysis was conducted to analyze difference in sex-specific responses to the change in enteral feeding volumes.
Results: Implementation of a targeted volume nutrition guideline resulted in a reduction in infants with growth failure (22% vs. 12.4% p= 0.01), defined as weight for age < 10th %ile at discharge on the Fenton Growth Curve. There were 66 male's pre-volume increase guideline implementation and 129 male's post-implementation with an average change of Z-score during intervention weeks 31 0/7 through 34 0/7 weeks of -0.07 (standard deviation 0.12) and -0.00 (± 0.12) respectively (Figure 1). A total of 59 females were included pre-implementation and 119 female's post-implementation with an average change in z-score during intervention weeks of -0.09 (± 0.10) and -0.04 (± 0.13) respectively (Figure 2). NEC and BPD rates remained steady pre- and post-implementation for both sexes.
Conclusion: Male preterm infants benefited more from an increased enteral volume guideline compared to females. Males may have different metabolic needs at various stages and therefore may respond differently to nutritional regimens. More research and sex-specific analyses on nutrition interventions in preterm infants are therefore necessary to address gender specified differences in energy and macronutrient requirements.
