Targeting human milk fortification to improve very preterm infant growth and brain development: study protocol for Nourish, a single-center randomized, controlled clinical trial.

BACKGROUND: Human milk is recommended for very preterm infants, but its variable macronutrient content may contribute to undernutrition during a critical period in development. We hypothesize that individually targeted human milk fortification is more effective in meeting macronutrient requirements than the current standard of care. METHODS: We designed a single-center randomized, controlled trial enrolling 130 infants born < 31 completed weeks' gestation. Participants will receive fortified maternal and/or pasteurized donor milk but no formula. For participants in the intervention group, milk will be individually fortified with protein and fat modulars to achieve target levels based on daily point-of-care milk analysis with mid-infrared spectroscopy, in addition to standard fortification. The study diet will continue through 36 weeks' postmenstrual age (PMA). Clinical staff and parents will be masked to study group. Primary outcomes include: 1) body length and lean body mass by air displacement plethysmography at 36 weeks' PMA; 2) quantitative magnetic resonance imaging-based measures of brain size and microstructure at term equivalent age; and 3) Bayley-IV scales at 2 years' corrected age. DISCUSSION: We expect this trial to provide important data regarding the effectiveness of individually targeted human milk fortification in the neonatal intensive care unit (NICU). TRIAL REGISTRATION: NCT03977259 , registered 6 June, 2019.

Nutritional and immunological considerations relevant to infant nutrition.

Optimal nutrition during infancy is critical not only to support the dramatic growth and development that takes place during the first 12 months following birth but also for establishing a healthy immune response throughout childhood and across the life span. The normative standards for infant feeding and nutrition are breast-feeding and human breast milk. However, in cases in which human breast milk is not available, infant formula is substituted. Providing optimal patient care that results in the best clinical outcomes depends on understanding the unique attributes of the 3 main sources of nutrition for newborns. This state of the science review provides an update on the macronutrient and immunological content of human milk, donor milk, and infant formula and highlights the relevance of these sources of infant nutrition on the development of immune system.

Diffuse correlation spectroscopy blood flow monitoring for intraventricular hemorrhage vulnerability in extremely low gestational age newborns.

In premature infants with an extremely low gestational age (ELGA, < 29 weeks GA), dysregulated changes in cerebral blood flow (CBF) are among the major pathogenic factors leading to germinal matrix/intraventricular hemorrhage (GM/IVH). Continuous monitoring of CBF can guide interventions to minimize the risk of brain injury, but there are no clinically standard techniques or tools for its measurement. We report the feasibility of the continuous monitoring of CBF, including measures of autoregulation, via diffuse correlation spectroscopy (DCS) in ELGA infants using CBF variability and correlation with scalp blood flow (SBF, served as a surrogate measure of systemic perturbations). In nineteen ELGA infants (with 9 cases of GM/IVH) monitored for 6-24 h between days 2-5 of life, we found a strong correlation between CBF and SBF in severe IVH (Grade III or IV) and IVH diagnosed within 72 h of life, while CBF variability alone was not associated with IVH. The proposed method is potentially useful at the bedside for the prompt assessment of cerebral autoregulation and early identification of infants vulnerable to GM/IVH.

Association of early cerebral oxygen saturation and brain injury in extremely preterm infants.

OBJECTIVE: To assess the association between cerebral saturation (crSO2) using Near-Infrared Spectroscopy (NIRS) and brain injury in extremely preterm infants. STUDY DESIGN: This retrospective study includes 62 infants (<28 weeks gestation) who underwent continuous NIRS monitoring in the first 5 days after birth. Median crSO2 were compared in 12 h increments between infants with and without germinal matrix/intraventricular hemorrhage (GM/IVH). crSO2 was also compared by IVH severity, onset, and by grade of injury on term equivalent MRI. RESULTS: After 48 h of life (HOL), infants with GM/IVH had significantly lower crSO2 than those without GM/IVH in analysis adjusted for potential confounding e.g., at 49-60 HOL (69.5 (66.2, 72.8) vs. 74.7 (71.8, 77.6), p = 0.023). There were no significant differences in crSO2 by IVH subcategory or injury severity on MRI. CONCLUSION: Clinical use of NIRS has the potential to identify crSO2 patterns associated with development of GM/IVH.

The Effects of COVID-19 Hospital Practices on Breastfeeding Initiation and Duration Postdischarge.

Background: Early in the COVID-19 pandemic, many birth hospitals separated SARS-CoV-2-positive mothers from their newborn infants and advised against breastfeeding to decrease postnatal SARS-CoV-2 transmission. Information on how these practices impacted breastfeeding postdischarge is limited. Objectives: In a statewide sample of SARS-CoV-2-positive mothers, we aimed to determine the extent to which (1) mother-infant separation and (2) a lack of breastfeeding initiation in-hospital were associated with breast milk feeding postdischarge. Design/Methods: From 11 birthing hospitals in Massachusetts, we identified 187 women who tested positive for SARS-CoV-2 from 14 days before to 72 hours after delivery (March 1-July 31, 2020) and their newborn infants. We abstracted chart data from the delivery hospitalization on main exposure variables (mother-infant separation, in-hospital breast milk feeding [expressed milk feeding and/or direct breastfeeding]) and from outpatient visits until 30 days postdischarge. We evaluated associations of in-hospital practices with outcomes up to 30 days postdischarge, adjusting for confounders using multivariable logistic and linear regression. Results: Mother-infant separation in-hospital was associated with a shorter duration of any breast milk feeding (regression coefficient estimate -5.29 days, 95% confidence intervals [CI] [-8.89 to -1.69]). Direct breastfeeding in-hospital was associated with higher odds of any breast milk feeding (adjusted odds ratios [AOR] 5.68, 95% CI [1.65-23.63]) and direct breastfeeding (AOR 8.19, 95% CI [2.99-24.91]) postdischarge; results were similar for any breast milk feeding in-hospital. Conclusions: Perinatal hospital care practices implemented early in the COVID-19 pandemic, specifically mother-infant separation and prevention of breast milk feeding initiation, were associated with adverse effects on breast milk feeding outcomes assessed up to 1 month postdischarge.

Macronutrient Intake from Human Milk, Infant Growth, and Body Composition at Term Equivalent Age: A Longitudinal Study of Hospitalized Very Preterm Infants.

The variable macronutrient content of human milk may contribute to growth deficits among preterm infants in the neonatal intensive care unit (NICU). In a longitudinal study of 37 infants < 32 weeks gestation, we aimed to (1) determine the between-infant variation in macronutrient intake from human milk and (2) examine associations of macronutrient intake with growth outcomes. We analyzed 1626 human milk samples (median, 43 samples/infant) with mid infrared spectroscopy. Outcomes at term equivalent age were weight, length, head circumference, fat mass, and fat-free mass. Median (range) intakes from human milk were: protein 1.37 (0.88, 2.43) g/kg/day; fat 4.20 (3.19, 5.82) g/kg/day; carbohydrate 8.94 (7.72, 9.85) g/kg/day; and energy 82.5 (68.7, 99.3) kcal/kg/day. In median regression models adjusted for birth size and gestational age, and other covariates, greater intakes of fat and energy were associated with higher weight (0.61 z-scores per g/kg/day fat, 95% CI 0.21, 1.01; 0.69 z-scores per 10 kcal/kg/day, 95% CI 0.28, 1.10), whereas greater protein intake was associated with greater body length (0.84 z-scores per g/kg/day protein, 95% CI 0.09, 1.58). Higher fat intake was also associated with higher fat mass and fat-free mass. Macronutrient intakes from human milk were highly variable and associated with growth outcomes despite routine fortification.