Neonatal multimorbidity and the phenotype of premature aging in preterm infants.

Multimorbidity is the co-occurrence of multiple chronic health problems, associated with aging, frailty, and poor functioning. Children born preterm experience more multimorbid conditions in early life compared to term-born peers. Though neonatal multimorbidity is linked to poor health-related quality of life, functional outcomes, and peer group participation, gaps in our theoretical understanding and conceptualization remain.

Association between type of feeding at hospital discharge and nutritional status of Brazilian very preterm infants: a multicenter study.

Objectives: To examine trends over time in diet and size of very preterm infants, and associations of diet with size at hospital discharge/transfer.

Methods: The authors studied 4062 surviving very preterm infants born < 32 weeks' gestational age and < 1500 g between January 2012 and December 2020 from 12 Brazilian Neonatal Intensive Care Units. Diet type at discharge/transfer was classified as exclusive human milk, exclusive formula, or mixed.

Deciphering macronutrient information about human milk.

Clinicians caring for small, vulnerable newborns increasingly have access to specific nutritional information about human milk through point-of-care analyzers and labeled products. It is critical for clinicians to recognize that there is considerable variability in how human milk nutritional data are derived and reported, which impacts the interpretation of nutritional values, comparison of nutritional data between products, and ultimately the ability to deliver optimal nutritional care. This article distills key issues that will enable clinicians to interpret human milk nutritional labels/analysis more effectively, ultimately allowing them to make better decisions about dietary strategies.

Human Milk Oligosaccharides, Growth, and Body Composition in Very Preterm Infants.

Human milk oligosaccharides (HMOs) are bioactive factors that benefit neonatal health, but little is known about effects on growth in very preterm infants (<32 weeks' gestation). We aimed to quantify HMO concentrations in human milk fed to very preterm infants during the neonatal hospitalization and investigate associations of HMOs with infant size and body composition at term-equivalent age. In 82 human-milk-fed very preterm infants, we measured HMO concentrations at two time points.

Lactoferrin intake from maternal milk during the neonatal hospitalization and early brain development among preterm infants.

Background: Lactoferrin is an immuno-modulatory nutrient in human milk that may be neuroprotective.

Methods: In 36 infants born <32 weeks' gestation, we sampled human milk at 14 and 28 days of chronologic age and measured lactoferrin by electrochemiluminescence multiplex immunoassay. Using 3T quantitative brain magnetic resonance imaging scans obtained at term equivalent, we estimated total and regional brain volumes.

Growth Velocities Across Distinct Early Life Windows and Child Cognition: Insights from a Contemporary US Cohort.

Objective: To evaluate the relative importance of overall and period-specific postnatal growth and their interaction with fetal growth on cognition in a generally well-nourished population.

Study Design: We included 1052 children from Project Viva, a prospective cohort in Boston, Massachusetts. Using linear spline mixed-effects models, we modeled length/height and body mass index (BMI) trajectories from birth to 7 years and estimated standardized overall (0-7 years) and period-specific growth velocities ie, early infancy (0-4 months), late infancy (4-15 months), toddlerhood (15-37 months), and early childhood (37-84 months).

Human Milk Fortification for Very Preterm Infants: Toward Optimal Nutrient Delivery, Neonatal Intensive Care Unit Growth, and Long-Term Outcomes.

Human milk is the preferred diet for very preterm infants due to short-term and long-term benefits for health and neurodevelopment. Fortification of human milk is required to deliver sufficient nutrients to attain recommended growth targets during the neonatal hospitalization. Intrinsic variability in human milk composition poses a challenge in clinical practice because some infants fail to meet recommended nutrient intakes even with existing approaches of standard (fixed-dose) and adjustable fortification.

Infant factors that impact the ecology of human milk secretion and composition-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 3.

Infants drive many lactation processes and contribute to the changing composition of human milk through multiple mechanisms. This review addresses the major topics of milk removal; chemosensory ecology for the parent-infant dyad; the infant's inputs into the composition of the human milk microbiome; and the impact of disruptions in gestation on the ecology of fetal and infant phenotypes, milk composition, and lactation. Milk removal, which is essential for adequate infant intake and continued milk synthesis through multiple hormonal and autocrine/paracrine mechanisms, should be effective, efficient, and comfortable for both the lactating parent and the infant.

Novel metrics to characterize temporal lobe of very preterm infants on term-equivalent brain MRI.

Background: Preterm birth adversely impacts brain development and contributes to neurodevelopmental impairment; the temporal lobe may be particularly vulnerable to the impact of very preterm (VP) birth. Yet, no prior magnetic resonance imaging (MRI) scoring system incorporated a method to quantify temporal lobe size in VP infants.

Methods: We developed and applied three metrics (temporal lobe length, extra-axial space, and temporal horn width) to quantify temporal lobe structure on term-equivalent brain MRIs obtained from 74 VP and 16 term infants.

Human Milk Oligosaccharides and Infant Neurodevelopment: A Narrative Review.

The objective of this narrative review was to synthesize the literature on human milk oligosaccharides (HMOs) and neurodevelopmental outcomes in human milk-fed infants. We conducted a scoping review of the literature indexed in PubMed reporting observational or interventional studies on HMO exposure in relation to psychometric measures in infants. Studies were characterized based on study design and definitions of HMO exposure and neurodevelopmental outcomes.

Association of Primary Language with Provision of Mother's Milk Among Very-Low-Birthweight Infants in Massachusetts.

Racial/ethnic inequities in mother's milk provision for hospitalized preterm infants persist. The extent to which primary language contributes to these racial/ethnic inequities is unknown. Examine associations of maternal race/ethnicity and primary language with (1) any/exclusive mother's milk at hospital discharge and (2) the time to cessation of mother's milk provision during the hospitalization.

Body composition measurement for the preterm neonate: using a clinical utility framework to translate research tools into clinical care.

Body composition analysis to distinguish between fat mass and fat-free mass is an established research approach to assess nutritional status. Within neonatal medicine, preterm infant body composition is linked with later health outcomes including neurodevelopment and cardiometabolic health. Mounting evidence establishing fat-free mass as an indicator of nutritional status, coupled with the availability of testing approaches that are feasible to use in preterm infants, have enhanced interest in measuring body composition in the neonatal intensive care unit (NICU) setting.

Health inequities start early in life, even before birth: Why race-specific fetal and neonatal growth references disadvantage Black infants.

Clinicians and researchers use published standards to assess and classify the size and growth of the fetus and newborn infant. Fetal growth is slower on average in Black fetuses as compared with White fetuses, and existing standards differ in whether they are race-specific or not. Here, we apply a health equity lens to the topic of fetal and newborn growth assessment by critically appraising two widely available growth standards.

Associations of cord blood leukocyte telomere length with adiposity growth from infancy to adolescence.

Objective: Leukocyte telomere length (LTL) may be a biomarker for chronic disease susceptibility, but no work has tested this hypothesis directly. Our study investigated associations of LTL at birth with markers of adiposity growth that are linked with cardiometabolic health later in life.

Methods: Participants were 375 children in Project Viva (48% female, 71% White).

Associations of Macronutrient Intake Determined by Point-of-Care Human Milk Analysis with Brain Development among very Preterm Infants.

Point-of-care human milk analysis is now feasible in the neonatal intensive care unit (NICU) and allows accurate measurement of macronutrient delivery. Higher macronutrient intakes over this period may promote brain growth and development. In a prospective, observational study of 55 infants born at <32 weeks’ gestation, we used a mid-infrared spectroscopy-based human milk analyzer to measure the macronutrient content in repeated samples of human milk over the NICU hospitalization.

Associations of Maternal Milk Feeding With Neurodevelopmental Outcomes at 7 Years of Age in Former Preterm Infants.

Importance: Maternal milk feeding may have unique long-term neurodevelopmental benefits in very preterm infants.

Objective: To examine the extent to which maternal milk feeding after very preterm birth is associated with cognitive, academic, and behavioral outcomes at school age.

Design, Setting, And Participants: This prospective cohort study assessed 586 infants born at less than 33 weeks' gestation at 5 Australian perinatal centers and enrolled in the Docosahexaenoic Acid for Improvement of Neurodevelopmental Outcomes study (January 1, 2001, to December 31, 2005) who were evaluated at a corrected age of 7 years.

Quantitation of Exosomes and Their MicroRNA Cargos in Frozen Human Milk.

We assessed feasibility of analyzing exosomes and microRNA cargos in frozen human milk as a pre-requisite for epidemiological studies of milk exosomes. We collected milk from five mother-preterm infant dyads at 3 time points during postnatal hospital care for storage at -80°C. We purified exosomes by ultracentrifugation, probed marker proteins using immunoblots, assessed size and counts with a nanoparticle tracker, and quantified three microRNAs with quantitative PCR.

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

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. 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.

Intestinal Inflammation is Significantly Associated With Length Faltering in Preterm Infants at Neonatal Intensive Care Unit Discharge.

Objective: The aim of the study was to assess intestinal inflammatory measures, urinary intestinal fatty acid-binding protein (IFABP), and fecal calprotectin (FC) by gestational age (GA) and postmenstrual age (PMA) and determine the association between intestinal inflammation and growth in preterm infants from birth to hospital discharge. We hypothesized that intestinal inflammation is associated with adverse growth in preterm infants.

Methods: We assayed repeated measures of IFABP and FC in 72 hospitalized preterm infants (<34 weeks' gestation).

Human Milk and Preterm Infant Brain Development: A Narrative Review.

Purpose: To review and synthesize the literature on human milk and structural brain development and injury in preterm infants, focusing on the application of quantitative brain magnetic resonance imaging (MRI) in this field.

Methods: For this narrative review, we searched PubMed for articles published from 1990 to 2021 that reported observational or interventional studies of maternal milk or donor milk in relation to brain development and/or injury in preterm infants assessed with quantitative MRI at term equivalent age. Studies were characterized with respect to key aspects of study design, milk exposure definition, and MRI outcomes.